NCBI Home Page NCBI Site Search page NCBI Guide that lists and describes the NCBI resources
Conserved domains on  [gi|831296835|ref|XP_012680221|]
View 

PREDICTED: SAM and SH3 domain-containing protein 1 isoform X2 [Clupea harengus]

Protein Classification

Graphical summary

 Zoom to residue level

show extra options »

Show site features     Horizontal zoom: ×

List of domain hits

Name Accession Description Interval E-value
SH3_SASH1 cd11967
Src homology 3 domain of SAM And SH3 Domain Containing Protein 1; SASH1 is a potential tumor ...
675-731 3.61e-34

Src homology 3 domain of SAM And SH3 Domain Containing Protein 1; SASH1 is a potential tumor suppressor in breast and colon cancer. Its decreased expression is associated with aggressive tumor growth, metastasis, and poor prognosis. It is widely expressed in normal tissues (except lymphocytes and dendritic cells) and is localized in the nucleus and the cytoplasm. SASH1 interacts with the oncoprotein cortactin and is important in cell migration and adhesion. It is a member of the SLY family of proteins, which are adaptor proteins containing a central conserved region with a bipartite nuclear localization signal (NLS) as well as SAM (sterile alpha motif) and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


:

Pssm-ID: 212900  Cd Length: 57  Bit Score: 124.77  E-value: 3.61e-34
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 831296835  675 GRARVHTDFTPSPYDSDSLKLKRGDVIDIISKPPMGTWMGLLNNKVGTFKFIYVDVL 731
Cdd:cd11967     1 GRARVHTDFTPSPYDTDSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTFKFIYVDVL 57
SAM_Samd5 cd09527
SAM domain of Samd5 subfamily; SAM (sterile alpha motif) domain of Samd5 subfamily is a ...
5-67 8.95e-33

SAM domain of Samd5 subfamily; SAM (sterile alpha motif) domain of Samd5 subfamily is a putative protein-protein interaction domain. Proteins of this subfamily have a SAM domain at the N-terminus. SAM is a widespread domain in signaling and regulatory proteins. In many cases SAM mediates dimerization/oligomerization. The exact function of proteins belonging to this subfamily is unknown.


:

Pssm-ID: 188926  Cd Length: 63  Bit Score: 121.01  E-value: 8.95e-33
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 831296835    5 GPNIVYEWLRTLQLVQYTEAFMDNGYDDLEVCKQIGEPDLDAIGVFVPHHRQRIYDAVQRLRD 67
Cdd:cd09527     1 CSNIVYDWLRTLQLEQYAEKFVDNGYDDLEVCKQIGDPDLDAIGVMNPAHRKRILEAVRRLKE 63
SLY super family cl13866
Lymphocyte signaling adaptor protein; This domain family is found in eukaryotes, and is ...
555-673 4.59e-29

Lymphocyte signaling adaptor protein; This domain family is found in eukaryotes, and is typically between 144 and 156 amino acids in length. The family is found in association with pfam07647, pfam07653. There is a conserved LGKK sequence motif. SLY contains a Src homology 3 domain and a sterile alpha motif, suggesting that it functions as a signaling adaptor protein in lymphocytes.


The actual alignment was detected with superfamily member pfam12485:

Pssm-ID: 315207  Cd Length: 156  Bit Score: 113.99  E-value: 4.59e-29
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 831296835   555 YREVIKSPSTSRISLGKKVKSVKETMRKRISKKYSSSLSEQSSPDGTPVSPQSPQQECEP----LEKPKLKAGGSVESLR 630
Cdd:pfam12485   39 GPEEAGKPSSSGGSLGKKWRAISRTMRKKMGKKYIKALSEEGGEDGEEGSPSPPSPDDPPdgdsLEKVSLKASDSEESLY 118
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 831296835   631 SSLSGQSSMSGqTVSTTDSSASNRESVKSEegedEEPPYRGPF 673
Cdd:pfam12485  119 SPLSGQSSSSS-GVTSPSSGTSNRDSLRLE----EEPPYTGPF 156
SAM_superfamily super family cl15755
SAM (Sterile alpha motif ); SAM (Sterile Alpha Motif) domain is a module consisting of ...
756-818 1.73e-25

SAM (Sterile alpha motif ); SAM (Sterile Alpha Motif) domain is a module consisting of approximately 70 amino acids. This domain is found in the Fungi/Metazoa group and in a restricted number of bacteria. Proteins with SAM domains are represented by a wide variety of domain architectures and have different intracellular localization, including nucleus, cytoplasm and membranes. SAM domains have diverse functions. They can interact with proteins, RNAs and membrane lipids, contain site of phosphorylation and/or kinase docking site, and play a role in protein homo and hetero dimerization/oligomerization in processes ranging from signal transduction to regulation of transcription. Mutations in SAM domains have been linked to several diseases.


The actual alignment was detected with superfamily member cd09559:

Pssm-ID: 353976  Cd Length: 66  Bit Score: 100.48  E-value: 1.73e-25
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 831296835  756 ASVQELLERINLKELMPTFLFNGYEDLDTFKLLEEEDLDELNIKDPQHRAVLLTAVELLQEYD 818
Cdd:cd09559     4 KSVEDLLDRINLKEHMPTFLFNGYEDLDTFKLLEEEDLDELNIRDPEHRAVLLTAVELLQEYD 66
SAM_superfamily super family cl15755
SAM (Sterile alpha motif ); SAM (Sterile Alpha Motif) domain is a module consisting of ...
1246-1312 9.64e-18

SAM (Sterile alpha motif ); SAM (Sterile Alpha Motif) domain is a module consisting of approximately 70 amino acids. This domain is found in the Fungi/Metazoa group and in a restricted number of bacteria. Proteins with SAM domains are represented by a wide variety of domain architectures and have different intracellular localization, including nucleus, cytoplasm and membranes. SAM domains have diverse functions. They can interact with proteins, RNAs and membrane lipids, contain site of phosphorylation and/or kinase docking site, and play a role in protein homo and hetero dimerization/oligomerization in processes ranging from signal transduction to regulation of transcription. Mutations in SAM domains have been linked to several diseases.


The actual alignment was detected with superfamily member cd09492:

Pssm-ID: 353976  Cd Length: 70  Bit Score: 78.32  E-value: 9.64e-18
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 831296835 1246 PASPYRSVSVSDWLVSIGLPMYATPLASAGCDSLAGVRALTEERLRQAGVRQDGHLHWLLHEARLLS 1312
Cdd:cd09492     1 PVSPGHVSSVSDWLVSIGLPMYSPPLLEAGFSTLSRVSSLSETCLREAGITEERHIRKLLSAARLVS 67
PHA03247 super family cl33720
large tegument protein UL36; Provisional
897-1164 1.29e-03

large tegument protein UL36; Provisional


The actual alignment was detected with superfamily member PHA03247:

Pssm-ID: 223021 [Multi-domain]  Cd Length: 3151  Bit Score: 43.39  E-value: 1.29e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 831296835  897 RARKHPAKHFLFHPPIKALRGLGRGMRDARRcgvmmPTSRSCEMLDGPLEAPDGPRKRSQ-----SLGDLlwEQGFDQQQ 971
Cdd:PHA03247 2634 AANEPDPHPPPTVPPPERPRDDPAPGRVSRP-----RRARRLGRAAQASSPPQRPRRRAArptvgSLTSL--ADPPPPPP 2706
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 831296835  972 KPQRGAPPQEPG--AHEGPKNWKEERGGMPGAPAVPALPPRPAATTTATSPSSPlvsQNTLSPFRKSPPVSHDASFTspf 1049
Cdd:PHA03247 2707 TPEPAPHALVSAtpLPPGPAAARQASPALPAAPAPPAVPAGPATPGGPARPARP---PTTAGPPAPAPPAAPAAGPP--- 2780
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 831296835 1050 sspptspplRTLPKKAPVPPPVPVKKSRERLPNGLRPPPPAHLLPALPVKTCPSPLESTTVTPTPISPTLSPEELESGTP 1129
Cdd:PHA03247 2781 ---------RRLTRPAVASLSESRESLPSPWDPADPPAAVLAPAAALPPAASPAGPLPPPTSAQPTAPPPPPGPPPPSLP 2851
                         250       260       270
                  ....*....|....*....|....*....|....*....
gi 831296835 1130 P--SVPP--PWLSDLPESACPQIHGSRPMVALRRVSKLA 1164
Cdd:PHA03247 2852 LggSVAPggDVRRRPPSRSPAAKPAAPARPPVRRLARPA 2890
 
Name Accession Description Interval E-value
SH3_SASH1 cd11967
Src homology 3 domain of SAM And SH3 Domain Containing Protein 1; SASH1 is a potential tumor ...
675-731 3.61e-34

Src homology 3 domain of SAM And SH3 Domain Containing Protein 1; SASH1 is a potential tumor suppressor in breast and colon cancer. Its decreased expression is associated with aggressive tumor growth, metastasis, and poor prognosis. It is widely expressed in normal tissues (except lymphocytes and dendritic cells) and is localized in the nucleus and the cytoplasm. SASH1 interacts with the oncoprotein cortactin and is important in cell migration and adhesion. It is a member of the SLY family of proteins, which are adaptor proteins containing a central conserved region with a bipartite nuclear localization signal (NLS) as well as SAM (sterile alpha motif) and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212900  Cd Length: 57  Bit Score: 124.77  E-value: 3.61e-34
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 831296835  675 GRARVHTDFTPSPYDSDSLKLKRGDVIDIISKPPMGTWMGLLNNKVGTFKFIYVDVL 731
Cdd:cd11967     1 GRARVHTDFTPSPYDTDSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTFKFIYVDVL 57
SAM_Samd5 cd09527
SAM domain of Samd5 subfamily; SAM (sterile alpha motif) domain of Samd5 subfamily is a ...
5-67 8.95e-33

SAM domain of Samd5 subfamily; SAM (sterile alpha motif) domain of Samd5 subfamily is a putative protein-protein interaction domain. Proteins of this subfamily have a SAM domain at the N-terminus. SAM is a widespread domain in signaling and regulatory proteins. In many cases SAM mediates dimerization/oligomerization. The exact function of proteins belonging to this subfamily is unknown.


Pssm-ID: 188926  Cd Length: 63  Bit Score: 121.01  E-value: 8.95e-33
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 831296835    5 GPNIVYEWLRTLQLVQYTEAFMDNGYDDLEVCKQIGEPDLDAIGVFVPHHRQRIYDAVQRLRD 67
Cdd:cd09527     1 CSNIVYDWLRTLQLEQYAEKFVDNGYDDLEVCKQIGDPDLDAIGVMNPAHRKRILEAVRRLKE 63
SLY pfam12485
Lymphocyte signaling adaptor protein; This domain family is found in eukaryotes, and is ...
555-673 4.59e-29

Lymphocyte signaling adaptor protein; This domain family is found in eukaryotes, and is typically between 144 and 156 amino acids in length. The family is found in association with pfam07647, pfam07653. There is a conserved LGKK sequence motif. SLY contains a Src homology 3 domain and a sterile alpha motif, suggesting that it functions as a signaling adaptor protein in lymphocytes.


Pssm-ID: 315207  Cd Length: 156  Bit Score: 113.99  E-value: 4.59e-29
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 831296835   555 YREVIKSPSTSRISLGKKVKSVKETMRKRISKKYSSSLSEQSSPDGTPVSPQSPQQECEP----LEKPKLKAGGSVESLR 630
Cdd:pfam12485   39 GPEEAGKPSSSGGSLGKKWRAISRTMRKKMGKKYIKALSEEGGEDGEEGSPSPPSPDDPPdgdsLEKVSLKASDSEESLY 118
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 831296835   631 SSLSGQSSMSGqTVSTTDSSASNRESVKSEegedEEPPYRGPF 673
Cdd:pfam12485  119 SPLSGQSSSSS-GVTSPSSGTSNRDSLRLE----EEPPYTGPF 156
SAM_SASH1_repeat1 cd09559
SAM domain of SASH1 proteins, repeat 1; SAM (sterile alpha motif) repeat 1 of SASH1 proteins ...
756-818 1.73e-25

SAM domain of SASH1 proteins, repeat 1; SAM (sterile alpha motif) repeat 1 of SASH1 proteins is a predicted protein-protein interaction domain. Members of this subfamily are putative adaptor proteins. They appear to mediate signal transduction. SASH1 can bind 14-3-3 proteins in response to IGF1/phosphatidylinositol 3-kinase signaling. SASH1 was found upregulated in different tissues including thymus, placenta, lungs and downregulated in some breast tumors, liver metastases and colon cancers, relative to corresponding normal tissues. SASH1 is a potential candidate for a tumor suppressor gene in breast cancers. At the same time, downregulation of SASH1 in colon cancer is associated with metastasis and a poor prognosis.


Pssm-ID: 188958  Cd Length: 66  Bit Score: 100.48  E-value: 1.73e-25
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 831296835  756 ASVQELLERINLKELMPTFLFNGYEDLDTFKLLEEEDLDELNIKDPQHRAVLLTAVELLQEYD 818
Cdd:cd09559     4 KSVEDLLDRINLKEHMPTFLFNGYEDLDTFKLLEEEDLDELNIRDPEHRAVLLTAVELLQEYD 66
SAM_SASH1_repeat2 cd09492
SAM domain of SASH1 proteins, repeat 2; SAM (sterile alpha motif) repeat 2 of SASH1 proteins ...
1246-1312 9.64e-18

SAM domain of SASH1 proteins, repeat 2; SAM (sterile alpha motif) repeat 2 of SASH1 proteins is a protein-protein interaction domain. Members of this subfamily are putative adaptor proteins. They appear to mediate signal transduction. SASH1 can bind 14-3-3 proteins in response to IGF1/phosphatidylinositol 3-kinase signaling. SASH1 was found upregulated in different tissues including thymus, placenta, lungs and downregulated in some breast tumors, liver metastases and colon cancers if compare to corresponding normal tissues. SASH1 is a potential candidate for a tumor suppressor gene in breast cancers. At the same time, downregulation of SASH1 in colon cancer is associated with metastasis and a poor prognosis.


Pssm-ID: 188891  Cd Length: 70  Bit Score: 78.32  E-value: 9.64e-18
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 831296835 1246 PASPYRSVSVSDWLVSIGLPMYATPLASAGCDSLAGVRALTEERLRQAGVRQDGHLHWLLHEARLLS 1312
Cdd:cd09492     1 PVSPGHVSSVSDWLVSIGLPMYSPPLLEAGFSTLSRVSSLSETCLREAGITEERHIRKLLSAARLVS 67
SAM_1 pfam00536
SAM domain (Sterile alpha motif); It has been suggested that SAM is an evolutionarily ...
6-66 1.26e-11

SAM domain (Sterile alpha motif); It has been suggested that SAM is an evolutionarily conserved protein binding domain that is involved in the regulation of numerous developmental processes in diverse eukaryotes. The SAM domain can potentially function as a protein interaction module through its ability to homo- and heterooligomerise with other SAM domains.


Pssm-ID: 334133  Cd Length: 64  Bit Score: 60.73  E-value: 1.26e-11
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 831296835     6 PNIVYEWLRTLQLVQYTEAFMdNGYDDLEVCKQIGEPDLDAIGVFVPHHRQRIYDAVQRLR 66
Cdd:pfam00536    5 VEDVGEWLESIGLGQYIDLFR-AGYIDGDTLLLLTEDDLMKLGVTLLGHRKKILYSIQGLK 64
SAM smart00454
Sterile alpha motif; Widespread domain in signalling and nuclear proteins. In EPH-related ...
6-67 4.05e-10

Sterile alpha motif; Widespread domain in signalling and nuclear proteins. In EPH-related tyrosine kinases, appears to mediate cell-cell initiated signal transduction via the binding of SH2-containing proteins to a conserved tyrosine that is phosphorylated. In many cases mediates homodimerisation.


Pssm-ID: 197735  Cd Length: 68  Bit Score: 56.92  E-value: 4.05e-10
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 831296835      6 PNIVYEWLRTLQLVQYTEAFMDNGYDDLEVCKQIGEPDLDAIGVFVPHHRQRIYDAVQRLRD 67
Cdd:smart00454    6 PESVADWLESIGLEQYADNFRKNGIDGALLLLLTSEEDLKELGITKLGHRKKILKAIQKLKE 67
SAM smart00454
Sterile alpha motif; Widespread domain in signalling and nuclear proteins. In EPH-related ...
1254-1311 4.95e-05

Sterile alpha motif; Widespread domain in signalling and nuclear proteins. In EPH-related tyrosine kinases, appears to mediate cell-cell initiated signal transduction via the binding of SH2-containing proteins to a conserved tyrosine that is phosphorylated. In many cases mediates homodimerisation.


Pssm-ID: 197735  Cd Length: 68  Bit Score: 42.28  E-value: 4.95e-05
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*...
gi 831296835   1254 SVSDWLVSIGLPMYATPLASAGCDSLAGVRALTEERLRQAGVRQDGHLHWLLHEARLL 1311
Cdd:smart00454    8 SVADWLESIGLEQYADNFRKNGIDGALLLLLTSEEDLKELGITKLGHRKKILKAIQKL 65
SH3 smart00326
Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ...
674-728 1.37e-04

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.


Pssm-ID: 214620  Cd Length: 56  Bit Score: 40.60  E-value: 1.37e-04
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*.
gi 831296835    674 CGRARVHTDFTPSpyDSDSLKLKRGDVIDIISKPPMGTWMG-LLNNKVGTFKFIYV 728
Cdd:smart00326    2 GPQVRALYDYTAQ--DPDELSFKKGDIITVLEKSDDGWWKGrLGRGKEGLFPSNYV 55
SH3_2 pfam07653
Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in ...
676-728 9.03e-04

Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organisation. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.


Pssm-ID: 336757  Cd Length: 52  Bit Score: 38.21  E-value: 9.03e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 831296835   676 RARVHTDFTPspYDSDSLKLKRGDVIDIISKPPMGTWMGLLNNKVGTFKFIYV 728
Cdd:pfam07653    1 YIRAIFDYVG--TDPTELSLKKGDVIKVIDKDSDGWWEGETGGRRGLVPSSAV 51
SAM smart00454
Sterile alpha motif; Widespread domain in signalling and nuclear proteins. In EPH-related ...
757-817 1.23e-03

Sterile alpha motif; Widespread domain in signalling and nuclear proteins. In EPH-related tyrosine kinases, appears to mediate cell-cell initiated signal transduction via the binding of SH2-containing proteins to a conserved tyrosine that is phosphorylated. In many cases mediates homodimerisation.


Pssm-ID: 197735  Cd Length: 68  Bit Score: 38.43  E-value: 1.23e-03
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 831296835    757 SVQELLERINLKELMPTFLFNGYEDLDTFKLLEEEDLDELNIKDPQHRAVLLTAVELLQEY 817
Cdd:smart00454    8 SVADWLESIGLEQYADNFRKNGIDGALLLLLTSEEDLKELGITKLGHRKKILKAIQKLKEQ 68
PHA03247 PHA03247
large tegument protein UL36; Provisional
897-1164 1.29e-03

large tegument protein UL36; Provisional


Pssm-ID: 223021 [Multi-domain]  Cd Length: 3151  Bit Score: 43.39  E-value: 1.29e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 831296835  897 RARKHPAKHFLFHPPIKALRGLGRGMRDARRcgvmmPTSRSCEMLDGPLEAPDGPRKRSQ-----SLGDLlwEQGFDQQQ 971
Cdd:PHA03247 2634 AANEPDPHPPPTVPPPERPRDDPAPGRVSRP-----RRARRLGRAAQASSPPQRPRRRAArptvgSLTSL--ADPPPPPP 2706
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 831296835  972 KPQRGAPPQEPG--AHEGPKNWKEERGGMPGAPAVPALPPRPAATTTATSPSSPlvsQNTLSPFRKSPPVSHDASFTspf 1049
Cdd:PHA03247 2707 TPEPAPHALVSAtpLPPGPAAARQASPALPAAPAPPAVPAGPATPGGPARPARP---PTTAGPPAPAPPAAPAAGPP--- 2780
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 831296835 1050 sspptspplRTLPKKAPVPPPVPVKKSRERLPNGLRPPPPAHLLPALPVKTCPSPLESTTVTPTPISPTLSPEELESGTP 1129
Cdd:PHA03247 2781 ---------RRLTRPAVASLSESRESLPSPWDPADPPAAVLAPAAALPPAASPAGPLPPPTSAQPTAPPPPPGPPPPSLP 2851
                         250       260       270
                  ....*....|....*....|....*....|....*....
gi 831296835 1130 P--SVPP--PWLSDLPESACPQIHGSRPMVALRRVSKLA 1164
Cdd:PHA03247 2852 LggSVAPggDVRRRPPSRSPAAKPAAPARPPVRRLARPA 2890
SAM_1 pfam00536
SAM domain (Sterile alpha motif); It has been suggested that SAM is an evolutionarily ...
1254-1311 2.15e-03

SAM domain (Sterile alpha motif); It has been suggested that SAM is an evolutionarily conserved protein binding domain that is involved in the regulation of numerous developmental processes in diverse eukaryotes. The SAM domain can potentially function as a protein interaction module through its ability to homo- and heterooligomerise with other SAM domains.


Pssm-ID: 334133  Cd Length: 64  Bit Score: 37.62  E-value: 2.15e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 831296835  1254 SVSDWLVSIGLPMYAtPLASAGCDSLAGVRALTEERLRQAGVRQDGHLHWLLHEARLL 1311
Cdd:pfam00536    7 DVGEWLESIGLGQYI-DLFRAGYIDGDTLLLLTEDDLMKLGVTLLGHRKKILYSIQGL 63
DUF4654 pfam15547
Domain of unknown function (DUF4654); This family of proteins is found in eukaryotes. Proteins ...
977-1039 3.55e-03

Domain of unknown function (DUF4654); This family of proteins is found in eukaryotes. Proteins in this family are typically between 145 and 169 amino acids in length. There is a conserved IDC sequence motif.


Pssm-ID: 317881  Cd Length: 137  Bit Score: 39.02  E-value: 3.55e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 831296835   977 APPQEPGAHEGP-------------KNW-----KEERGGMPGAPAVPALPPRPAATTTATSPSSPLVSQNtlSPFRKSPP 1038
Cdd:pfam15547   30 APPRAPSPNRGPvtppmktyivfcgENQphltqEAPLGGGCLAQARGTLPPCRGTVAPASSPVSPLCPQE--APEAKGSP 107

                   .
gi 831296835  1039 V 1039
Cdd:pfam15547  108 L 108
 
Name Accession Description Interval E-value
SH3_SASH1 cd11967
Src homology 3 domain of SAM And SH3 Domain Containing Protein 1; SASH1 is a potential tumor ...
675-731 3.61e-34

Src homology 3 domain of SAM And SH3 Domain Containing Protein 1; SASH1 is a potential tumor suppressor in breast and colon cancer. Its decreased expression is associated with aggressive tumor growth, metastasis, and poor prognosis. It is widely expressed in normal tissues (except lymphocytes and dendritic cells) and is localized in the nucleus and the cytoplasm. SASH1 interacts with the oncoprotein cortactin and is important in cell migration and adhesion. It is a member of the SLY family of proteins, which are adaptor proteins containing a central conserved region with a bipartite nuclear localization signal (NLS) as well as SAM (sterile alpha motif) and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212900  Cd Length: 57  Bit Score: 124.77  E-value: 3.61e-34
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 831296835  675 GRARVHTDFTPSPYDSDSLKLKRGDVIDIISKPPMGTWMGLLNNKVGTFKFIYVDVL 731
Cdd:cd11967     1 GRARVHTDFTPSPYDTDSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTFKFIYVDVL 57
SAM_Samd5 cd09527
SAM domain of Samd5 subfamily; SAM (sterile alpha motif) domain of Samd5 subfamily is a ...
5-67 8.95e-33

SAM domain of Samd5 subfamily; SAM (sterile alpha motif) domain of Samd5 subfamily is a putative protein-protein interaction domain. Proteins of this subfamily have a SAM domain at the N-terminus. SAM is a widespread domain in signaling and regulatory proteins. In many cases SAM mediates dimerization/oligomerization. The exact function of proteins belonging to this subfamily is unknown.


Pssm-ID: 188926  Cd Length: 63  Bit Score: 121.01  E-value: 8.95e-33
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 831296835    5 GPNIVYEWLRTLQLVQYTEAFMDNGYDDLEVCKQIGEPDLDAIGVFVPHHRQRIYDAVQRLRD 67
Cdd:cd09527     1 CSNIVYDWLRTLQLEQYAEKFVDNGYDDLEVCKQIGDPDLDAIGVMNPAHRKRILEAVRRLKE 63
SH3_SASH3 cd11968
Src homology 3 domain of Sam And SH3 Domain Containing Protein 3; SASH3, also called SLY/SLY1 ...
675-730 3.17e-32

Src homology 3 domain of Sam And SH3 Domain Containing Protein 3; SASH3, also called SLY/SLY1 (SH3-domain containing protein expressed in lymphocytes), is expressed exclusively in lymhocytes and is essential in the full activation of adaptive immunity. It is involved in the signaling of T cell receptors. It was the first described member of the SLY family of proteins, which are adaptor proteins containing a central conserved region with a bipartite nuclear localization signal (NLS) as well as SAM (sterile alpha motif) and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212901  Cd Length: 56  Bit Score: 119.21  E-value: 3.17e-32
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 831296835  675 GRARVHTDFTPSPYDSDSLKLKRGDVIDIISKPPMGTWMGLLNNKVGTFKFIYVDV 730
Cdd:cd11968     1 GRARVHTDFIPSPYDGDSLKLQKGDIIQIIEKPPVGTWTGLLNNKVGTFKFIYVDV 56
SH3_SASH_like cd11822
Src homology 3 domain of SAM And SH3 Domain Containing Proteins; This subfamily, also called ...
676-727 2.01e-31

Src homology 3 domain of SAM And SH3 Domain Containing Proteins; This subfamily, also called the SLY family, is composed of SAM And SH3 Domain Containing Protein 1 (SASH1), SASH2, SASH3, and similar proteins. These are adaptor proteins containing a central conserved region with a bipartite nuclear localization signal (NLS) as wells as SAM (sterile alpha motif) and SH3 domains. SASH1 is a potential tumor suppressor in breast and colon cancer. It is widely expressed in normal tissues (except lymphocytes and dendritic cells) and is localized in the nucleus and the cytoplasm. SASH1 interacts with the oncoprotein cortactin and is important in cell migration and adhesion. SASH2 (also called SAMSN-1, SLY2, HACS1 or NASH1) and SASH3 (also called SLY/SLY1) are expressed mainly in hematopoietic cells, although SASH2 is also found in endothelial cells as well as myeloid leukemias and myeloma. SASH2 was found to be differentially expressed in malignant haematopoietic cells and in colorectal tumors, and is a potential tumor suppressor in lung cancer. SASH3 is essential in the full activation of adaptive immunity and is involved in the signaling of T cell receptors. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212756  Cd Length: 52  Bit Score: 116.92  E-value: 2.01e-31
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 831296835  676 RARVHTDFTPSPYDSDSLKLKRGDVIDIISKPPMGTWMGLLNNKVGTFKFIY 727
Cdd:cd11822     1 RAKVHTDFTPSPYDTDSLKLKKGDIIDIINKPPMGIWTGMLNNKVGNFKFIY 52
SLY pfam12485
Lymphocyte signaling adaptor protein; This domain family is found in eukaryotes, and is ...
555-673 4.59e-29

Lymphocyte signaling adaptor protein; This domain family is found in eukaryotes, and is typically between 144 and 156 amino acids in length. The family is found in association with pfam07647, pfam07653. There is a conserved LGKK sequence motif. SLY contains a Src homology 3 domain and a sterile alpha motif, suggesting that it functions as a signaling adaptor protein in lymphocytes.


Pssm-ID: 315207  Cd Length: 156  Bit Score: 113.99  E-value: 4.59e-29
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 831296835   555 YREVIKSPSTSRISLGKKVKSVKETMRKRISKKYSSSLSEQSSPDGTPVSPQSPQQECEP----LEKPKLKAGGSVESLR 630
Cdd:pfam12485   39 GPEEAGKPSSSGGSLGKKWRAISRTMRKKMGKKYIKALSEEGGEDGEEGSPSPPSPDDPPdgdsLEKVSLKASDSEESLY 118
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 831296835   631 SSLSGQSSMSGqTVSTTDSSASNRESVKSEegedEEPPYRGPF 673
Cdd:pfam12485  119 SPLSGQSSSSS-GVTSPSSGTSNRDSLRLE----EEPPYTGPF 156
SAM_SASH1_repeat1 cd09559
SAM domain of SASH1 proteins, repeat 1; SAM (sterile alpha motif) repeat 1 of SASH1 proteins ...
756-818 1.73e-25

SAM domain of SASH1 proteins, repeat 1; SAM (sterile alpha motif) repeat 1 of SASH1 proteins is a predicted protein-protein interaction domain. Members of this subfamily are putative adaptor proteins. They appear to mediate signal transduction. SASH1 can bind 14-3-3 proteins in response to IGF1/phosphatidylinositol 3-kinase signaling. SASH1 was found upregulated in different tissues including thymus, placenta, lungs and downregulated in some breast tumors, liver metastases and colon cancers, relative to corresponding normal tissues. SASH1 is a potential candidate for a tumor suppressor gene in breast cancers. At the same time, downregulation of SASH1 in colon cancer is associated with metastasis and a poor prognosis.


Pssm-ID: 188958  Cd Length: 66  Bit Score: 100.48  E-value: 1.73e-25
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 831296835  756 ASVQELLERINLKELMPTFLFNGYEDLDTFKLLEEEDLDELNIKDPQHRAVLLTAVELLQEYD 818
Cdd:cd09559     4 KSVEDLLDRINLKEHMPTFLFNGYEDLDTFKLLEEEDLDELNIRDPEHRAVLLTAVELLQEYD 66
SAM_SASH-like cd09493
SAM (Sterile alpha motif ), SASH1-like; SAM (sterile alpha motif) domain of SASH1-like ...
757-813 3.50e-20

SAM (Sterile alpha motif ), SASH1-like; SAM (sterile alpha motif) domain of SASH1-like proteins is a protein-protein interaction domain. Members of this subfamily are putative adaptor proteins. They appear to mediate signal transduction. Proteins of this subfamily are known to be involved in preventing DN thymocytes from premature initiation of programmed cell death and in B cells activation and differentiation. They have been found downregulated in some breast tumors, liver metastases and colon cancers if compare to corresponding normal tissues.


Pssm-ID: 188892  Cd Length: 60  Bit Score: 85.25  E-value: 3.50e-20
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 831296835  757 SVQELLERINLKELMPTFLFNGYEDLDTFKLLEEEDLDELNIKDPQHRAVLLTAVEL 813
Cdd:cd09493     4 TVEELLERINLQEHTSTLLLNGYETLEDFKDLKESHLNELNITDPEHRAKLLTAAEL 60
SAM_SASH1_repeat2 cd09492
SAM domain of SASH1 proteins, repeat 2; SAM (sterile alpha motif) repeat 2 of SASH1 proteins ...
1246-1312 9.64e-18

SAM domain of SASH1 proteins, repeat 2; SAM (sterile alpha motif) repeat 2 of SASH1 proteins is a protein-protein interaction domain. Members of this subfamily are putative adaptor proteins. They appear to mediate signal transduction. SASH1 can bind 14-3-3 proteins in response to IGF1/phosphatidylinositol 3-kinase signaling. SASH1 was found upregulated in different tissues including thymus, placenta, lungs and downregulated in some breast tumors, liver metastases and colon cancers if compare to corresponding normal tissues. SASH1 is a potential candidate for a tumor suppressor gene in breast cancers. At the same time, downregulation of SASH1 in colon cancer is associated with metastasis and a poor prognosis.


Pssm-ID: 188891  Cd Length: 70  Bit Score: 78.32  E-value: 9.64e-18
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 831296835 1246 PASPYRSVSVSDWLVSIGLPMYATPLASAGCDSLAGVRALTEERLRQAGVRQDGHLHWLLHEARLLS 1312
Cdd:cd09492     1 PVSPGHVSSVSDWLVSIGLPMYSPPLLEAGFSTLSRVSSLSETCLREAGITEERHIRKLLSAARLVS 67
SAM_SASH3 cd09560
SAM domain of SASH3 subfamily; SAM (sterile alpha motif) domain of SAHS3 (also known as SLY) ...
757-818 1.42e-13

SAM domain of SASH3 subfamily; SAM (sterile alpha motif) domain of SAHS3 (also known as SLY) proteins is a predicted protein-protein interaction domain. Members of this subfamily are putative signaling/adaptor proteins. In addition to SAM, they contain SLY and SH3 domains. They appear to mediate signal transduction in lymphoid tissues. Murine SASH3 is involved in preventing DN thymocytes from premature initiation of programmed cell death and in mTOR (mammalian target of rapamycin) activation via signal integration of the Notch receptor and preTCR (T cell receptor) pathways.


Pssm-ID: 188959  Cd Length: 68  Bit Score: 66.65  E-value: 1.42e-13
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 831296835  757 SVQELLERINLKELMPTFLFNGYEDLDTFKLLEEEDLDELNIKDPQHRAVLLTAVELLQEYD 818
Cdd:cd09560     7 TLHELLERIGLEEHTSTLLLNGYQTLEDFKELRETHLNELNIMDPQHRAKLLTAAELLLDYD 68
SAM_Ship2 cd09491
SAM domain of Ship2 lipid phosphatase proteins; SAM (sterile alpha motif) domain of Ship2 ...
5-63 2.37e-12

SAM domain of Ship2 lipid phosphatase proteins; SAM (sterile alpha motif) domain of Ship2 subfamily is a protein-protein interaction domain. Ship2 proteins are lipid phosphatases (Phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase 2) containing an N-terminal SH2 domain, a central phosphatase domain and a C-terminal SAM domain. Ship2 is involved in a number of PI3K signaling pathways. For example, it plays a role in regulation of the actin cytoskeleton remodeling, in insulin signaling pathways, and in EphA2 receptor endocytosis. SAM domain of Ship2 can interact with SAM domain of other proteins in these pathways, thus participating in signal transduction. In particular, SAM of Ship2 is known to form heterodimers with SAM domain of Eph-A2 receptor tyrosine kinase during receptor endocytosis as well as with SAM domain of PI3K effector protein Arap3 in the actin cytoskeleton signaling network. Since Ship2 plays a role in negatively regulating insulin signaling, it has been suggested that inhibition of its expression or function may contribute in treating type 2 diabetes and obesity-induced insulin resistance.


Pssm-ID: 188890  Cd Length: 63  Bit Score: 62.92  E-value: 2.37e-12
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 831296835    5 GPNIVYEWLRTLQLVQYTEAFMDNGYDDLEVCKQIGEPDLDAIGVFVPHHRQRIYDAVQ 63
Cdd:cd09491     4 WPKTVSEWLMNLGLQQYEEGLMHNGWDSLEFLSDITEEDLEEAGVTNPAHKRRLLDSLQ 62
SAM_1 pfam00536
SAM domain (Sterile alpha motif); It has been suggested that SAM is an evolutionarily ...
6-66 1.26e-11

SAM domain (Sterile alpha motif); It has been suggested that SAM is an evolutionarily conserved protein binding domain that is involved in the regulation of numerous developmental processes in diverse eukaryotes. The SAM domain can potentially function as a protein interaction module through its ability to homo- and heterooligomerise with other SAM domains.


Pssm-ID: 334133  Cd Length: 64  Bit Score: 60.73  E-value: 1.26e-11
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 831296835     6 PNIVYEWLRTLQLVQYTEAFMdNGYDDLEVCKQIGEPDLDAIGVFVPHHRQRIYDAVQRLR 66
Cdd:pfam00536    5 VEDVGEWLESIGLGQYIDLFR-AGYIDGDTLLLLTEDDLMKLGVTLLGHRKKILYSIQGLK 64
SAM_SAMSN1 cd09561
SAM domain of SAMSN1 subfamily; SAM (sterile alpha motif) domain of SAMSN1 (also known as ...
757-816 2.32e-10

SAM domain of SAMSN1 subfamily; SAM (sterile alpha motif) domain of SAMSN1 (also known as HACS1 or NASH1) proteins is a predicted protein-protein interaction domain. Members of this group are putative signaling/adaptor proteins. They appear to mediate signal transduction in lymphoid tissues. Murine HACS1 protein likely plays a role in B cell activation and differentiation. Potential binding partners of HACS1 are SLAM, DEC205 and PIR-B receptors and also some unidentified tyrosine-phosphorylated proteins. Proteins of this group were found preferentially expressed in normal hematopietic tissues and in some malignancies including lymphoma, myeloid leukemia and myeloma.


Pssm-ID: 188960  Cd Length: 66  Bit Score: 57.57  E-value: 2.32e-10
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 831296835  757 SVQELLERINLKELMPTFLFNGYEDLDTFKLLEEEDLDELNIKDPQHRAVLLTAVELLQE 816
Cdd:cd09561     7 TLQELLERIHLQEYTSTLLLNGYETLEDLKDLKESHLIELNITDPEDRARLLSAAENLLD 66
SAM smart00454
Sterile alpha motif; Widespread domain in signalling and nuclear proteins. In EPH-related ...
6-67 4.05e-10

Sterile alpha motif; Widespread domain in signalling and nuclear proteins. In EPH-related tyrosine kinases, appears to mediate cell-cell initiated signal transduction via the binding of SH2-containing proteins to a conserved tyrosine that is phosphorylated. In many cases mediates homodimerisation.


Pssm-ID: 197735  Cd Length: 68  Bit Score: 56.92  E-value: 4.05e-10
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 831296835      6 PNIVYEWLRTLQLVQYTEAFMDNGYDDLEVCKQIGEPDLDAIGVFVPHHRQRIYDAVQRLRD 67
Cdd:smart00454    6 PESVADWLESIGLEQYADNFRKNGIDGALLLLLTSEEDLKELGITKLGHRKKILKAIQKLKE 67
SAM_superfamily cd09487
SAM (Sterile alpha motif ); SAM (Sterile Alpha Motif) domain is a module consisting of ...
9-64 4.52e-10

SAM (Sterile alpha motif ); SAM (Sterile Alpha Motif) domain is a module consisting of approximately 70 amino acids. This domain is found in the Fungi/Metazoa group and in a restricted number of bacteria. Proteins with SAM domains are represented by a wide variety of domain architectures and have different intracellular localization, including nucleus, cytoplasm and membranes. SAM domains have diverse functions. They can interact with proteins, RNAs and membrane lipids, contain site of phosphorylation and/or kinase docking site, and play a role in protein homo and hetero dimerization/oligomerization in processes ranging from signal transduction to regulation of transcription. Mutations in SAM domains have been linked to several diseases.


Pssm-ID: 188886  Cd Length: 56  Bit Score: 56.09  E-value: 4.52e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 831296835    9 VYEWLRTLQLVQYTEAFMDNgYDDLEVCKQIGEPDLDAIGVFVPHHRQRIYDAVQR 64
Cdd:cd09487     2 VAEWLESLGLEQYADLFRKN-EIDGDALLLLTDEDLKELGITSPGHRKKILRAIQR 56
SAM_caskin1,2_repeat1 cd09497
SAM domain of caskin protein repeat 1; SAM (sterile alpha motif) domain repeat 1 of caskin1,2 ...
8-66 4.56e-10

SAM domain of caskin protein repeat 1; SAM (sterile alpha motif) domain repeat 1 of caskin1,2 proteins is a protein-protein interaction domain. Caskin has two tandem SAM domains. Caskin protein is known to interact with membrane-associated guanylate kinase CASK, and apparently may play a role in neural development, synaptic protein targeting, and regulation of gene expression.


Pssm-ID: 188896  Cd Length: 66  Bit Score: 56.50  E-value: 4.56e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 831296835    8 IVYEWLRTLQLVQYTEAFMDNGYDDLEVCKQIGEpDLDAIGVFVPHHRQRIYDAVQRLR 66
Cdd:cd09497     6 AIFDWLREFGLEEYTPNFIKAGYDLPTISRMTPE-DLTAIGITKPGHRKKLKSEIAQLQ 63
SAM_AIDA1AB-like_repeat1 cd09499
SAM domain of AIDA1AB-like proteins, repeat 1; SAM (sterile alpha motif) domain repeat 1 of ...
9-65 1.35e-09

SAM domain of AIDA1AB-like proteins, repeat 1; SAM (sterile alpha motif) domain repeat 1 of AIDA1AB-like proteins is a protein-protein interaction domain. AIDA1AB-like proteins have two tandem SAM domains. They may form an intramolecular head-to-tail homodimer. One of two basic motifs of the nuclear localization signal (NLS) is located within helix 5 of SAM2 (motif HKRK). This signal plays a role in decoupling of SAM2 from SAM1, thus facilitating translocation of this type proteins into the nucleus. SAM1 domain has a potential phosphorylation site for CMGC group of serine/threonine kinases. SAM domains of the AIDA1-like subfamily can directly bind ubiquitin and participate in regulating the degradation of ubiquitinated EphA receptors, particularly EPH-A8 receptor. Additionally AIDA1AB-like proteins may participate in the regulation of nucleoplasmic coilin protein interactions.


Pssm-ID: 188898  Cd Length: 67  Bit Score: 55.38  E-value: 1.35e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 831296835    9 VYEWLRTLQLVQYTEAFMDNGYDDLE--VCKQIGEPDLDAIGVFVPHHRQRIYDAVQRL 65
Cdd:cd09499     5 VGQWLESIGLPQYESKLLLNGFDDVDflGSGVMEDQDLKEIGITDEQHRQIILQAARSL 63
SH3_CRK_C cd11759
C-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins; CRK adaptor ...
676-730 2.44e-09

C-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins; CRK adaptor proteins consists of SH2 and SH3 domains, which bind tyrosine-phosphorylated peptides and proline-rich motifs, respectively. They function downstream of protein tyrosine kinases in many signaling pathways started by various extracellular signals, including growth and differentiation factors. Cellular CRK (c-CRK) contains a single SH2 domain, followed by N-terminal and C-terminal SH3 domains. It is involved in the regulation of many cellular processes including cell growth, motility, adhesion, and apoptosis. CRK has been implicated in the malignancy of various human cancers. The C-terminal SH3 domain of CRK has not been shown to bind any target protein; it acts as a negative regulator of CRK function by stabilizing a structure that inhibits the access by target proteins to the N-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212693  Cd Length: 57  Bit Score: 54.03  E-value: 2.44e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 831296835  676 RARVHTDFTPSPYDSDSLKLKRGDVIDIISKPPMGTWMGLLNNKVGTFKFIYVDV 730
Cdd:cd11759     3 YARVIQKRVPNAYDKTALALEVGDLVKVTKINVSGQWEGELNGKVGHFPFTHVEL 57
SAM_EPH-A5 cd09546
SAM domain of EPH-A5 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
9-66 2.50e-09

SAM domain of EPH-A5 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A5 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A5 receptors and appears to mediate cell-cell initiated signal transduction. Eph-A5 gene is almost exclusively expressed in the nervous system. Murine EPH-A5 receptors participate in axon guidance during embryogenesis and play a role in the adult synaptic plasticity, particularly in neuron-target interactions in multiple neural circuits. Additionally EPH-A5 receptors and its ligand ephrin A5 regulate dopaminergic axon outgrowth and influence the formation of the midbrain dopaminergic pathways. EphA5 gene expression was found decreased in a few different breast cancer cell lines, thus it might be a potential molecular marker for breast cancer carcinogenesis and progression.


Pssm-ID: 188945  Cd Length: 66  Bit Score: 54.55  E-value: 2.50e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 831296835    9 VYEWLRTLQLVQYTEAFMDNGYDDLEVCKQIGEPDLDAIGVFVPHHRQRIYDAVQRLR 66
Cdd:cd09546     6 VGEWLEAIKMGRYTEIFMENGYSSMDAVAQVTLEDLRRLGVTLVGHQKKIMNSIQEMR 63
SAM_2 pfam07647
SAM domain (Sterile alpha motif);
11-66 1.27e-08

SAM domain (Sterile alpha motif);


Pssm-ID: 336753  Cd Length: 66  Bit Score: 52.27  E-value: 1.27e-08
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 831296835    11 EWLRTLQLVQYTEAFMDNGYDDLEVCKQIGEPDLDAIGVFVPHHRQRIYDAVQRLR 66
Cdd:pfam07647   11 EWLRSIGLEQYKDNFTDQGITGAELLLRLTEEDLKRLGITSVGHRKKILKKIQELK 66
SAM_EPH-A2 cd09543
SAM domain of EPH-A2 family of tyrosine kinase receptors; SAM (sterile alpha motif) domain of ...
9-68 1.16e-07

SAM domain of EPH-A2 family of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A2 subfamily of receptor tyrosine kinases is a C-terminal protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A2 receptors and appears to mediate cell-cell initiated signal transduction. For example, SAM domain of EPH-A2 receptors interacts with SAM domain of Ship2 proteins (SH2 containing phosphoinositide 5-phosphotase-2) forming heterodimers; such recruitment of Ship2 by EPH-A2 attenuates the positive signal for receptor endocytosis. Eph-A2 is found overexpressed in many types of human cancer, including breast, prostate, lung and colon cancer. High level of expression could induce cancer progression by a variety of mechanisms and could be used as a novel tag for cancer immunotherapy. EPH-A2 receptors are attractive targets for drag design.


Pssm-ID: 188942  Cd Length: 70  Bit Score: 49.83  E-value: 1.16e-07
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 831296835    9 VYEWLRTLQLVQYTEAFMDNGYDDLEVCKQIGEPDLDAIGVFVPHHRQRIYDAVQRLRDE 68
Cdd:cd09543     8 VAEWLESIKMQQYTEHFMAAGYNSIDKVLQMTQEDIKHIGVRLPGHQKRIAYSILGLKEQ 67
SAM_Arap1,2,3 cd09490
SAM domain of Arap1,2,3 (angiotensin receptor-associated protein); SAM (sterile alpha motif) ...
9-64 1.72e-07

SAM domain of Arap1,2,3 (angiotensin receptor-associated protein); SAM (sterile alpha motif) domain of Arap1,2,3 subfamily proteins (angiotensin receptor-associated) is a protein-protein interaction domain. Arap1,2,3 proteins are phosphatidylinositol-3,4,5-trisphosphate-dependent GTPase-activating proteins. They are involved in phosphatidylinositol-3 kinase (PI3K) signaling pathways. In addition to SAM domain, Arap1,2,3 proteins contain ArfGap, PH-like, RhoGAP and UBQ domains. SAM domain of Arap3 protein was shown to interact with SAM domain of Ship2 phosphatidylinositol-trisphosphate phosphatase proteins. Such interaction apparently plays a role in inhibition of PI3K regulated pathways since Ship2 converts PI(3,4,5)P3 into PI(3,4)P2. Proteins of this subfamily participate in regulation of signaling and trafficking associated with a number of different receptors (including EGFR, TRAIL-R1/DR4, TRAIL-R2/DR5) in normal and cancer cells; they are involved in regulation of actin cytoskeleton remodeling, cell spreading and formation of lamellipodia.


Pssm-ID: 188889  Cd Length: 63  Bit Score: 49.22  E-value: 1.72e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 831296835    9 VYEWLRTLQLVQYTEAFMDNGYDDLEVCKQIGEPDLDAIGVFVPHHRQRIYDAVQR 64
Cdd:cd09490     6 IAEWLASIHLEQYLDLFREHGYVTATDCQGINDSRLKQIGISPTGHRRRILKQLPI 61
SAM_AIDA1AB-like_repeat2 cd09500
SAM domain of AIDA1AB-like proteins, repeat 2; SAM (sterile alpha motif) domain repeat 2 of ...
4-58 2.88e-07

SAM domain of AIDA1AB-like proteins, repeat 2; SAM (sterile alpha motif) domain repeat 2 of AIDA1AB-like proteins is a protein-protein interaction domain. AIDA1AB-like proteins have two tandem SAM domains. They may form an intramolecular head-to-tail homodimer. One of two basic motifs of the nuclear localization signal (NLS) is located within helix 5 of the SAM2 (motif HKRK). This signal plays a role in decoupling of SAM2 from SAM1, thus facilitating translocation of this type proteins into the nucleus. SAM domains of the AIDA1AB-like subfamily can directly bind ubiquitin and participate in regulating the degradation of ubiquitinated EphA receptors, particularly EPH-A8 receptor. Additionally AIDA1AB-like proteins may participate in the regulation of nucleoplasmic coilin protein interactions.


Pssm-ID: 188899  Cd Length: 65  Bit Score: 48.46  E-value: 2.88e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 831296835    4 GGPNIVYEWLRTLQLVQYTEAFMDNGYDDLEVCKQIGEPDLDAI-GVFVPHHRQRI 58
Cdd:cd09500     3 NSPASVSEWLDSIGLGDYIETFLKHGYTSMERVKRIWEVELTNVlEINKLGHRKRI 58
SAM_EPH-R cd09488
SAM domain of EPH family of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH ...
9-65 2.99e-07

SAM domain of EPH family of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH (erythropoietin-producing hepatocyte) family of receptor tyrosine kinases is a C-terminal signal transduction module located in the cytoplasmic region of these receptors. SAM appears to mediate cell-cell initiated signal transduction via binding proteins to a conserved tyrosine that is phosphorylated. In some cases the SAM domain mediates homodimerization/oligomerization and plays a role in the clustering process necessary for signaling. EPH kinases are the largest family of receptor tyrosine kinases. They are classified into two groups based on their abilities to bind ephrin-A and ephrin-B ligands. The EPH receptors are involved in regulation of cell movement, shape, and attachment during embryonic development; they control cell-cell interactions in the vascular, nervous, epithelial, and immune systems, and in many tumors. They are potential molecular markers for cancer diagnostics and potential targets for cancer therapy.


Pssm-ID: 188887  Cd Length: 61  Bit Score: 48.38  E-value: 2.99e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 831296835    9 VYEWLRTLQLVQYTEAFMDNGYDDLEVCKQIGEPDLDAIGVFVPHHRQRIYDAVQRL 65
Cdd:cd09488     5 VGEWLESIKMGRYKENFTAAGYTSLDAVAQMTAEDLTRLGVTLVGHQKKILNSIQAL 61
SAM_caskin1,2_repeat2 cd09498
SAM domain of caskin protein repeat 2; SAM (sterile alpha motif) domain repeat 2 of caskin1,2 ...
6-67 3.12e-07

SAM domain of caskin protein repeat 2; SAM (sterile alpha motif) domain repeat 2 of caskin1,2 proteins is a protein-protein interaction domain. Caskin has two tandem SAM domains. Caskin protein is known to interact with membrane-associated guanylate kinase CASK, and may play a role in neural development, synaptic protein targeting, and regulation of gene expression.


Pssm-ID: 188897  Cd Length: 71  Bit Score: 48.83  E-value: 3.12e-07
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 831296835    6 PNIVYEWLRTLQLVQYTEAFMDNGYDDLEVCKQIGEPDLDAIGVFVPHHRQRIYDAVQRLRD 67
Cdd:cd09498     7 PNDLLEWLSLLGLPQYHKVLVENGYDSIDFVTDLTWEDLQDIGITKLGHQKKLMLAIKKLKD 68
SH3_CD2AP-like_2 cd11874
Second Src Homology 3 domain (SH3B) of CD2-associated protein and similar proteins; This ...
676-723 3.58e-07

Second Src Homology 3 domain (SH3B) of CD2-associated protein and similar proteins; This subfamily is composed of the second SH3 domain (SH3B) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3B of both proteins have been shown to bind to Cbl. In the case of CD2AP, its SH3B binds to Cbl at a site distinct from the c-Cbl/SH3A binding site. The CIN85 SH3B also binds ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212807  Cd Length: 53  Bit Score: 48.10  E-value: 3.58e-07
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 831296835  676 RARVhtDFTPSPYDSDSLKLKRGDVIDIISKPPMGTWMGLLNNKVGTF 723
Cdd:cd11874     1 RCKV--LFSYTPQNEDELELKVGDTIEVLGEVEEGWWEGKLNGKVGVF 46
SAM_EPH-B1 cd09551
SAM domain of EPH-B1 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
9-66 1.03e-06

SAM domain of EPH-B1 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-B1 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH- B1 receptors. In human vascular endothelial cells it appears to mediate cell-cell initiated signal transduction via the binding of the adaptor protein GRB10 (growth factor) through its SH2 domain to a conserved tyrosine that is phosphorylated. EPH-B1 receptors play a role in neurogenesis, in particular in regulation of proliferation and migration of neural progenitors in the hippocampus and in corneal neovascularization; they are involved in converting the crossed retinal projection to ipsilateral retinal projection. They may be potential targets in angiogenesis-related disorders.


Pssm-ID: 188950  Cd Length: 68  Bit Score: 47.34  E-value: 1.03e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 831296835    9 VYEWLRTLQLVQYTEAFMDNGYDDLEVCKQIGEPDLDAIGVFVPHHRQRIYDAVQRLR 66
Cdd:cd09551     9 VEDWLSAIKMSQYRDNFLSSGFTSLQLVAQMTSEDLLRIGVTLAGHQKKILNSIQSMR 66
SAM_EPH-B4 cd09554
SAM domain of EPH-B4 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
9-70 1.21e-06

SAM domain of EPH-B4 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-B4 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-B4 receptors and appears to mediate cell-cell initiated signal transduction. EPH-B4 protein kinase performs kinase-dependent and kinase-independent functions. These receptors play a role in the regular vascular system development during embryogenesis. They were found overexpressed in a variety of cancers, including carcinoma of the head and neck, ovarian cancer, bladder cancer, and downregulated in bone myeloma. Thus, EphB4 is a potential biomarker and a target for drug design.


Pssm-ID: 188953  Cd Length: 67  Bit Score: 46.78  E-value: 1.21e-06
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 831296835    9 VYEWLRTLQLVQYTEAFMDNGYDDLEVCKQIGEPDLDAIGVFVPHHRQRIYDAVQRLRDEDK 70
Cdd:cd09554     6 VGEWLRAIKMERYEDSFLQAGFTTFQLVSQISTEDLLRMGVTLAGHQKKILSSIQAMGIQNK 67
SAM_SASH1_repeat1 cd09559
SAM domain of SASH1 proteins, repeat 1; SAM (sterile alpha motif) repeat 1 of SASH1 proteins ...
6-69 1.70e-06

SAM domain of SASH1 proteins, repeat 1; SAM (sterile alpha motif) repeat 1 of SASH1 proteins is a predicted protein-protein interaction domain. Members of this subfamily are putative adaptor proteins. They appear to mediate signal transduction. SASH1 can bind 14-3-3 proteins in response to IGF1/phosphatidylinositol 3-kinase signaling. SASH1 was found upregulated in different tissues including thymus, placenta, lungs and downregulated in some breast tumors, liver metastases and colon cancers, relative to corresponding normal tissues. SASH1 is a potential candidate for a tumor suppressor gene in breast cancers. At the same time, downregulation of SASH1 in colon cancer is associated with metastasis and a poor prognosis.


Pssm-ID: 188958  Cd Length: 66  Bit Score: 46.55  E-value: 1.70e-06
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 831296835    6 PNIVYEWLRTLQLVQYTEAFMDNGYDDLEVCKQIGEPDLDAIGVFVPHHRQRIYDAVQRLRDED 69
Cdd:cd09559     3 PKSVEDLLDRINLKEHMPTFLFNGYEDLDTFKLLEEEDLDELNIRDPEHRAVLLTAVELLQEYD 66
SAM_Ship2 cd09491
SAM domain of Ship2 lipid phosphatase proteins; SAM (sterile alpha motif) domain of Ship2 ...
1254-1305 3.10e-06

SAM domain of Ship2 lipid phosphatase proteins; SAM (sterile alpha motif) domain of Ship2 subfamily is a protein-protein interaction domain. Ship2 proteins are lipid phosphatases (Phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase 2) containing an N-terminal SH2 domain, a central phosphatase domain and a C-terminal SAM domain. Ship2 is involved in a number of PI3K signaling pathways. For example, it plays a role in regulation of the actin cytoskeleton remodeling, in insulin signaling pathways, and in EphA2 receptor endocytosis. SAM domain of Ship2 can interact with SAM domain of other proteins in these pathways, thus participating in signal transduction. In particular, SAM of Ship2 is known to form heterodimers with SAM domain of Eph-A2 receptor tyrosine kinase during receptor endocytosis as well as with SAM domain of PI3K effector protein Arap3 in the actin cytoskeleton signaling network. Since Ship2 plays a role in negatively regulating insulin signaling, it has been suggested that inhibition of its expression or function may contribute in treating type 2 diabetes and obesity-induced insulin resistance.


Pssm-ID: 188890  Cd Length: 63  Bit Score: 45.59  E-value: 3.10e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 831296835 1254 SVSDWLVSIGLPMYATPLASAGCDSLAGVRALTEERLRQAGVRQDGHLHWLL 1305
Cdd:cd09491     7 TVSEWLMNLGLQQYEEGLMHNGWDSLEFLSDITEEDLEEAGVTNPAHKRRLL 58
SAM_EPH-A1 cd09542
SAM domain of EPH-A1 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
1249-1313 3.34e-06

SAM domain of EPH-A1 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A1 subfamily of the receptor tyrosine kinases is a C-terminal protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A1 receptors and appears to mediate cell-cell initiated signal transduction. Activation of these receptors leads to inhibition of cell spreading and migration in a RhoA-ROCK-dependent manner. EPH-A1 receptors are known to bind ILK (integrin-linked kinase) which is the mediator of interactions between integrin and the actin cytoskeleton. However SAM is not sufficient for this interaction; it rather plays an ancillary role. SAM domains of Eph-A1 receptors do not form homo/hetero dimers/oligomers. EphA1 gene was found expressed widely in differentiated epithelial cells. In a number of different malignant tumors EphA1 genes are downregulated. In breast carcinoma the downregulation is associated with invasive behavior of the cell.


Pssm-ID: 188941  Cd Length: 63  Bit Score: 45.38  E-value: 3.34e-06
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 831296835 1249 PYRSVSvsDWLVSIGLPMYATPLASAGCDSLAGVRALTEERLRQAGVRQDGhlhwllHEARLLSS 1313
Cdd:cd09542     3 PYRSVS--EWLESIRMKRYILHFRSAGLDTMECVLELTAEDLTQMGITLPG------HQKRILCS 59
SH3 cd00174
Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction ...
676-727 3.38e-06

Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction domains that bind proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. Thus, they are referred to as proline-recognition domains (PRDs). SH3 domains are less selective and show more diverse specificity compared to other PRDs. They have been shown to bind peptide sequences that lack the PxxP motif; examples include the PxxDY motif of Eps8 and the RKxxYxxY sequence in SKAP55. SH3 domain containing proteins play versatile and diverse roles in the cell, including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies, among others. Many members of this superfamily are adaptor proteins that associate with a number of protein partners, facilitating complex formation and signal transduction.


Pssm-ID: 212690  Cd Length: 51  Bit Score: 45.15  E-value: 3.38e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 831296835  676 RARVHTDFTPSpyDSDSLKLKRGDVIDIISKPPMGTWMG-LLNNKVGTFKFIY 727
Cdd:cd00174     1 YARALYDYEAQ--DDDELSFKKGDIITVLEKDDDGWWEGeLNGGREGLFPANY 51
SAM_EPH-B2 cd09552
SAM domain of EPH-B2 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
7-66 8.93e-06

SAM domain of EPH-B2 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-B2 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-B2 receptors and appears to mediate cell-cell initiated signal transduction. SAM domains of this subfamily form homodimers/oligomers (in head-to-head/tail-to-tail orientation); apparently such clustering is necessary for signaling. EPH-B2 receptor is involved in regulation of synaptic function; it is needed for normal vestibular function, proper formation of anterior commissure, control of cell positioning, and ordered migration in the intestinal epithelium. EPH-B2 plays a tumor suppressor role in colorectal cancer. It was found to be downregulated in gastric cancer and thus may be a negative biomarker for it.


Pssm-ID: 188951  Cd Length: 71  Bit Score: 44.61  E-value: 8.93e-06
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 831296835    7 NIVYEWLRTLQLVQYTEAFMDNGYDDLEVCKQIGEPDLDAIGVFVPHHRQRIYDAVQRLR 66
Cdd:cd09552     7 STVDEWLDAIKMGQYKESFANAGFTSFDVVSQMTMEDILRVGVTLAGHQKKILNSIQVMR 66
SH3_CIN85_2 cd12055
Second Src Homology 3 domain (SH3B) of Cbl-interacting protein of 85 kDa; CIN85, also called ...
678-723 1.10e-05

Second Src Homology 3 domain (SH3B) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the second SH3 domain (SH3B) of CIN85. SH3B has been shown to bind Cbl proline-rich peptides and ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212988  Cd Length: 53  Bit Score: 43.83  E-value: 1.10e-05
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 831296835  678 RVHTDFTPSPYDSDSLKLKRGDVIDIISKPPMGTWMGLLNNKVGTF 723
Cdd:cd12055     1 RCQVAFSYLPQNEDELELKVGDIIEVVGEVEEGWWEGVLNGKTGMF 46
SAM_EPH-A2 cd09543
SAM domain of EPH-A2 family of tyrosine kinase receptors; SAM (sterile alpha motif) domain of ...
1249-1300 1.75e-05

SAM domain of EPH-A2 family of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A2 subfamily of receptor tyrosine kinases is a C-terminal protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A2 receptors and appears to mediate cell-cell initiated signal transduction. For example, SAM domain of EPH-A2 receptors interacts with SAM domain of Ship2 proteins (SH2 containing phosphoinositide 5-phosphotase-2) forming heterodimers; such recruitment of Ship2 by EPH-A2 attenuates the positive signal for receptor endocytosis. Eph-A2 is found overexpressed in many types of human cancer, including breast, prostate, lung and colon cancer. High level of expression could induce cancer progression by a variety of mechanisms and could be used as a novel tag for cancer immunotherapy. EPH-A2 receptors are attractive targets for drag design.


Pssm-ID: 188942  Cd Length: 70  Bit Score: 43.67  E-value: 1.75e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 831296835 1249 PYRSVSvsDWLVSIGLPMYATPLASAGCDSLAGVRALTEERLRQAGVRQDGH 1300
Cdd:cd09543     4 PFRTVA--EWLESIKMQQYTEHFMAAGYNSIDKVLQMTQEDIKHIGVRLPGH 53
SH3_MyoIe_If_like cd11827
Src homology 3 domain of Myosins Ie, If, and similar proteins; Myosins Ie (MyoIe) and If ...
687-729 2.19e-05

Src homology 3 domain of Myosins Ie, If, and similar proteins; Myosins Ie (MyoIe) and If (MyoIf) are nonmuscle, unconventional, long tailed, class I myosins containing an N-terminal motor domain and a myosin tail with TH1, TH2, and SH3 domains. MyoIe interacts with the endocytic proteins, dynamin and synaptojanin-1, through its SH3 domain; it may play a role in clathrin-dependent endocytosis. In the kidney, MyoIe is critical for podocyte function and normal glomerular filtration. Mutations in MyoIe is associated with focal segmental glomerulosclerosis, a disease characterized by massive proteinuria and progression to end-stage kidney disease. MyoIf is predominantly expressed in the immune system; it plays a role in immune cell motility and innate immunity. Mutations in MyoIf may be associated with the loss of hearing. The MyoIf gene has also been found to be fused to the MLL (Mixed lineage leukemia) gene in infant acute myeloid leukemias (AML). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212761  Cd Length: 53  Bit Score: 42.79  E-value: 2.19e-05
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 831296835  687 PYDSDSLKLKRGDVIDIISKPPMGTWMGLLNNKVGTFKFIYVD 729
Cdd:cd11827    10 AQDTDELSFNEGDIIEILKEDPSGWWTGRLRGKEGLFPGNYVE 52
SH3_Nostrin cd11823
Src homology 3 domain of Nitric Oxide Synthase TRaffic INducer; Nostrin is expressed in ...
682-730 2.89e-05

Src homology 3 domain of Nitric Oxide Synthase TRaffic INducer; Nostrin is expressed in endothelial and epithelial cells and is involved in the regulation, trafficking and targeting of endothelial NOS (eNOS). It facilitates the endocytosis of eNOS by coordinating the functions of dynamin and the Wiskott-Aldrich syndrome protein (WASP). Increased expression of Nostrin may be correlated to preeclampsia. Nostrin contains an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212757  Cd Length: 53  Bit Score: 42.71  E-value: 2.89e-05
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 831296835  682 DFTPSPYDSdsLKLKRGDVIDIISKPPMGTWMGLLNNKVGTFKFIYVDV 730
Cdd:cd11823     7 SYTANREDE--LSLQPGDIIEVHEKQDDGWWLGELNGKKGIFPATYVEE 53
SAM_EPH-A4 cd09545
SAM domain of EPH-A4 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
9-66 3.29e-05

SAM domain of EPH-A4 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A4 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A4 receptors and appears to mediate cell-cell initiated signal transduction. SAM domains of EPH-A4 receptors can form homodimers. EPH-A4 receptors bind ligands such as erphirin A1, A4, A5. They are known to interact with a number of different proteins, including meltrin beta metalloprotease, Cdk5, and EFS2alpha, however SAM domain doesn't participate in these interactions. EPH-A4 receptors are involved in regulation of corticospinal tract formation, in pathway controlling voluntary movements, in formation of motor neurons, and in axon guidance (SAM domain is not required for axon guidance or for EPH-A4 kinase signaling). In Xenopus embryos EPH-A4 induces loss of cell adhesion, ventro-lateral protrusions, and severely expanded posterior structures. Mutations in SAM domain conserved tyrosine (Y928F) enhance the ability of EPH-A4 to induce these phenotypes, thus supporting the idea that the SAM domain may negatively regulate some aspects of EPH-A4 activity. EphA4 gene was found overexpressed in a number of different cancers including human gastric cancer, colorectal cancer, and pancreatic ductal adenocarcinoma. It is likely to be a promising molecular target for the cancer therapy.


Pssm-ID: 188944  Cd Length: 71  Bit Score: 43.02  E-value: 3.29e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 831296835    9 VYEWLRTLQLVQYTEAFMDNGYDDLEVCKQIGEPDLDAIGVFVPHHRQRIYDAVQRLR 66
Cdd:cd09545     6 VDDWLQAIKMERYKDNFTAAGYTTLEAVVHMNQDDLARIGISAIAHQNKILSSVQGMR 63
SAM_EPH-A6 cd09547
SAM domain of EPH-A6 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
9-66 3.35e-05

SAM domain of EPH-A6 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A6 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A6 receptors and appears to mediate cell-cell initiated signal transduction. Eph-A6 gene is preferentially expressed in the nervous system. EPH-A6 receptors are involved in primate retina vascular and axon guidance, and in neural circuits responsible for learning and memory. EphA6 gene was significantly down regulated in colorectal cancer and in malignant melanomas. It is a potential molecular marker for these cancers.


Pssm-ID: 188946  Cd Length: 64  Bit Score: 42.57  E-value: 3.35e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 831296835    9 VYEWLRTLQLVQYTEAFMDNGYDDLEVCKQIGEPDLDAIGVFVPHHRQRIYDAVQRLR 66
Cdd:cd09547     6 VSDWLDSIKMGQYKNNFMAAGFTTLDMVSRMTIDDIRRIGVTLIGHQRRIVSSIQTLR 63
SH3_CD2AP-like_3 cd11875
Third Src Homology 3 domain (SH3C) of CD2-associated protein and similar proteins; This ...
676-723 3.40e-05

Third Src Homology 3 domain (SH3C) of CD2-associated protein and similar proteins; This subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212808  Cd Length: 55  Bit Score: 42.34  E-value: 3.40e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 831296835  676 RARVHTDFTPSpyDSDSLKLKRGDVIDIISK--PPMGTWMGLLNNKVGTF 723
Cdd:cd11875     1 KARVLFDYEAE--NEDELTLREGDIVTILSKdcEDKGWWKGELNGKRGVF 48
SAM_EPH-B3 cd09553
SAM domain of EPH-B3 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
9-66 3.59e-05

SAM domain of EPH-B3 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-B3 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-B3 receptors and appears to mediate cell-cell initiated signal transduction. EPH-B3 receptor protein kinase performs kinase-dependent and kinase-independent functions. It is known to be involved in thymus morphogenesis, in regulation of cell adhesion and migration. Also EphB3 controls cell positioning and ordered migration in the intestinal epithelium and plays a role in the regulation of adult retinal ganglion cell axon plasticity after optic nerve injury. In some experimental models overexpression of EphB3 enhances cell/cell contacts and suppresses colon tumor growth.


Pssm-ID: 188952  Cd Length: 69  Bit Score: 42.71  E-value: 3.59e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 831296835    9 VYEWLRTLQLVQYTEAFMDNGYDDLEVCKQIGEPDLDAIGVFVPHHRQRIYDAVQRLR 66
Cdd:cd09553     9 VGDWLDAIKMGRYKENFVSAGFASFDLVAQMTAEDLLRIGVTLAGHQKKILSSIQDMR 66
SH3_GRB2_like_C cd11805
C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related ...
676-728 4.33e-05

C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins; This family includes the adaptor protein GRB2 and related proteins including Drosophila melanogaster Downstream of receptor kinase (DRK), Caenorhabditis elegans Sex muscle abnormal protein 5 (Sem-5), GRB2-related adaptor protein (GRAP), GRAP2, and similar proteins. Family members contain an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. GRB2/Sem-5/DRK is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. GRAP2 plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. GRAP acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. The C-terminal SH3 domains (SH3c) of GRB2 and GRAP2 have been shown to bind to classical PxxP motif ligands, as well as to non-classical motifs. GRB2 SH3c binds Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, while the SH3c of GRAP2 binds to the phosphatase-like protein HD-PTP via a RxxxxK motif. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212739  Cd Length: 53  Bit Score: 41.84  E-value: 4.33e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 831296835  676 RARVHTDFTPSpyDSDSLKLKRGDVIDIISKPPMGTWMGLLNNKVGTFKFIYV 728
Cdd:cd11805     1 RVQALYDFNPQ--EPGELEFRRGDIITVLDSSDPDWWKGELRGRVGIFPANYV 51
SH3_CD2AP_2 cd12054
Second Src Homology 3 domain (SH3B) of CD2-associated protein; CD2AP, also called CMS (Cas ...
687-731 4.45e-05

Second Src Homology 3 domain (SH3B) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the second SH3 domain (SH3B) of CD2AP. SH3B binds to c-Cbl in a site (TPSSRPLR is the core binding motif) distinct from the c-Cbl/SH3A binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212987  Cd Length: 55  Bit Score: 42.26  E-value: 4.45e-05
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 831296835  687 PYDSDSLKLKRGDVIDIISKPPMGTWMGLLNNKVGTFKFIYVDVL 731
Cdd:cd12054    11 PQNEDELELKVGDIIDINEEVEEGWWSGTLNGKSGLFPSNFVKEL 55
SAM smart00454
Sterile alpha motif; Widespread domain in signalling and nuclear proteins. In EPH-related ...
1254-1311 4.95e-05

Sterile alpha motif; Widespread domain in signalling and nuclear proteins. In EPH-related tyrosine kinases, appears to mediate cell-cell initiated signal transduction via the binding of SH2-containing proteins to a conserved tyrosine that is phosphorylated. In many cases mediates homodimerisation.


Pssm-ID: 197735  Cd Length: 68  Bit Score: 42.28  E-value: 4.95e-05
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*...
gi 831296835   1254 SVSDWLVSIGLPMYATPLASAGCDSLAGVRALTEERLRQAGVRQDGHLHWLLHEARLL 1311
Cdd:smart00454    8 SVADWLESIGLEQYADNFRKNGIDGALLLLLTSEEDLKELGITKLGHRKKILKAIQKL 65
SAM_SASH-like cd09493
SAM (Sterile alpha motif ), SASH1-like; SAM (sterile alpha motif) domain of SASH1-like ...
6-63 1.19e-04

SAM (Sterile alpha motif ), SASH1-like; SAM (sterile alpha motif) domain of SASH1-like proteins is a protein-protein interaction domain. Members of this subfamily are putative adaptor proteins. They appear to mediate signal transduction. Proteins of this subfamily are known to be involved in preventing DN thymocytes from premature initiation of programmed cell death and in B cells activation and differentiation. They have been found downregulated in some breast tumors, liver metastases and colon cancers if compare to corresponding normal tissues.


Pssm-ID: 188892  Cd Length: 60  Bit Score: 40.95  E-value: 1.19e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 831296835    6 PNIVYEWLRTLQLVQYTEAFMDNGYDDLEVCKQIGEPDLDAIGVFVPHHRQRIYDAVQ 63
Cdd:cd09493     2 PKTVEELLERINLQEHTSTLLLNGYETLEDFKDLKESHLNELNITDPEHRAKLLTAAE 59
SH3 smart00326
Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ...
674-728 1.37e-04

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.


Pssm-ID: 214620  Cd Length: 56  Bit Score: 40.60  E-value: 1.37e-04
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*.
gi 831296835    674 CGRARVHTDFTPSpyDSDSLKLKRGDVIDIISKPPMGTWMG-LLNNKVGTFKFIYV 728
Cdd:smart00326    2 GPQVRALYDYTAQ--DPDELSFKKGDIITVLEKSDDGWWKGrLGRGKEGLFPSNYV 55
SAM_EPH-A1 cd09542
SAM domain of EPH-A1 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
9-63 1.66e-04

SAM domain of EPH-A1 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A1 subfamily of the receptor tyrosine kinases is a C-terminal protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A1 receptors and appears to mediate cell-cell initiated signal transduction. Activation of these receptors leads to inhibition of cell spreading and migration in a RhoA-ROCK-dependent manner. EPH-A1 receptors are known to bind ILK (integrin-linked kinase) which is the mediator of interactions between integrin and the actin cytoskeleton. However SAM is not sufficient for this interaction; it rather plays an ancillary role. SAM domains of Eph-A1 receptors do not form homo/hetero dimers/oligomers. EphA1 gene was found expressed widely in differentiated epithelial cells. In a number of different malignant tumors EphA1 genes are downregulated. In breast carcinoma the downregulation is associated with invasive behavior of the cell.


Pssm-ID: 188941  Cd Length: 63  Bit Score: 40.76  E-value: 1.66e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 831296835    9 VYEWLRTLQLVQYTEAFMDNGYDDLEVCKQIGEPDLDAIGVFVPHHRQRIYDAVQ 63
Cdd:cd09542     7 VSEWLESIRMKRYILHFRSAGLDTMECVLELTAEDLTQMGITLPGHQKRILCSIQ 61
SAM_SASH3 cd09560
SAM domain of SASH3 subfamily; SAM (sterile alpha motif) domain of SAHS3 (also known as SLY) ...
6-69 2.33e-04

SAM domain of SASH3 subfamily; SAM (sterile alpha motif) domain of SAHS3 (also known as SLY) proteins is a predicted protein-protein interaction domain. Members of this subfamily are putative signaling/adaptor proteins. In addition to SAM, they contain SLY and SH3 domains. They appear to mediate signal transduction in lymphoid tissues. Murine SASH3 is involved in preventing DN thymocytes from premature initiation of programmed cell death and in mTOR (mammalian target of rapamycin) activation via signal integration of the Notch receptor and preTCR (T cell receptor) pathways.


Pssm-ID: 188959  Cd Length: 68  Bit Score: 40.46  E-value: 2.33e-04
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 831296835    6 PNIVYEWLRTLQLVQYTEAFMDNGYDDLEVCKQIGEPDLDAIGVFVPHHRQRIYDAVQRLRDED 69
Cdd:cd09560     5 PKTLHELLERIGLEEHTSTLLLNGYQTLEDFKELRETHLNELNIMDPQHRAKLLTAAELLLDYD 68
SH3_Sdc25 cd11883
Src Homology 3 domain of Sdc25/Cdc25 guanine nucleotide exchange factors; This subfamily is ...
678-724 3.36e-04

Src Homology 3 domain of Sdc25/Cdc25 guanine nucleotide exchange factors; This subfamily is composed of the Saccharomyces cerevisiae guanine nucleotide exchange factors (GEFs) Sdc25 and Cdc25, and similar proteins. These GEFs regulate Ras by stimulating the GDP/GTP exchange on Ras. Cdc25 is involved in the Ras/PKA pathway that plays an important role in the regulation of metabolism, stress responses, and proliferation, depending on available nutrients and conditions. Proteins in this subfamily contain an N-terminal SH3 domain as well as REM (Ras exchanger motif) and RasGEF domains at the C-terminus. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.


Pssm-ID: 212816  Cd Length: 55  Bit Score: 39.57  E-value: 3.36e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 831296835  678 RVHTDFTPSpyDSDSLKLKRGDVIDIISKPPMGTWMGLLNNKVGTFK 724
Cdd:cd11883     3 VALYDFTPK--SKNQLSFKAGDIIYVLNKDPSGWWDGVIISSSGKVK 47
SAM_caskin1,2_repeat2 cd09498
SAM domain of caskin protein repeat 2; SAM (sterile alpha motif) domain repeat 2 of caskin1,2 ...
1246-1301 3.39e-04

SAM domain of caskin protein repeat 2; SAM (sterile alpha motif) domain repeat 2 of caskin1,2 proteins is a protein-protein interaction domain. Caskin has two tandem SAM domains. Caskin protein is known to interact with membrane-associated guanylate kinase CASK, and may play a role in neural development, synaptic protein targeting, and regulation of gene expression.


Pssm-ID: 188897  Cd Length: 71  Bit Score: 39.97  E-value: 3.39e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 831296835 1246 PASPYRSVSVSDWLVSIGLPMYATPLASAGCDSLAGVRALTEERLRQAGVRQDGHL 1301
Cdd:cd09498     1 WLPDYPPNDLLEWLSLLGLPQYHKVLVENGYDSIDFVTDLTWEDLQDIGITKLGHQ 56
SH3_D21-like cd12142
Src Homology 3 domain of SH3 domain-containing protein 21 (SH3D21) and similar proteins; ...
683-723 7.39e-04

Src Homology 3 domain of SH3 domain-containing protein 21 (SH3D21) and similar proteins; N-terminal SH3 domain of the uncharacterized protein SH3 domain-containing protein 21, and similar uncharacterized domains, it belongs to the CD2AP-like_3 subfamily of proteins. The CD2AP-like_3 subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 213018  Cd Length: 55  Bit Score: 38.60  E-value: 7.39e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 831296835  683 FTPSPYDSDSLKLKRGDVIDIISKPP--MGTWMGLLNNKVGTF 723
Cdd:cd12142     6 FDYNPVAPDELALKKGDVIEVISKETedEGWWEGELNGRRGFF 48
SH3_2 pfam07653
Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in ...
676-728 9.03e-04

Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organisation. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.


Pssm-ID: 336757  Cd Length: 52  Bit Score: 38.21  E-value: 9.03e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 831296835   676 RARVHTDFTPspYDSDSLKLKRGDVIDIISKPPMGTWMGLLNNKVGTFKFIYV 728
Cdd:pfam07653    1 YIRAIFDYVG--TDPTELSLKKGDVIKVIDKDSDGWWEGETGGRRGLVPSSAV 51
SH3_Ysc84p_like cd11842
Src homology 3 domain of Ysc84p and similar fungal proteins; This family is composed of the ...
676-730 9.08e-04

Src homology 3 domain of Ysc84p and similar fungal proteins; This family is composed of the Saccharomyces cerevisiae proteins, Ysc84p (also called LAS17-binding protein 4, Lsb4p) and Lsb3p, and similar fungal proteins. They contain an N-terminal SYLF domain (also called DUF500) and a C-terminal SH3 domain. Ysc84p localizes to actin patches and plays an important in actin polymerization during endocytosis. The N-terminal domain of both Ysc84p and Lsb3p can bind and bundle actin filaments. A study of the yeast SH3 domain interactome predicts that the SH3 domains of Lsb3p and Lsb4p may function as molecular hubs for the assembly of endocytic complexes. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212776  Cd Length: 55  Bit Score: 38.56  E-value: 9.08e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 831296835  676 RARVHTDFTPSpyDSDSLKLKRGDVIDIISKPPMGT--WMGLLNNKVGTFKFIYVDV 730
Cdd:cd11842     1 KAVALYDFAGE--QPGDLAFQKGDIITILKKSDSQNdwWTGRIGGREGIFPANYVEL 55
SAM_Shank1,2,3 cd09506
SAM domain of Shank1,2,3 family proteins; SAM (sterile alpha motif) domain of Shank1,2,3 ...
9-65 1.17e-03

SAM domain of Shank1,2,3 family proteins; SAM (sterile alpha motif) domain of Shank1,2,3 family proteins is a protein-protein interaction domain. Shank1,2,3 proteins are scaffold proteins that are known to interact with a variety of cytoplasmic and membrane proteins. SAM domains of the Shank1,2,3 family are prone to homooligomerization. They are highly enriched in the postsynaptic density, acting as scaffolds to organize assembly of postsynaptic proteins. SAM domains of Shank3 proteins can form large sheets of helical fibers. Shank genes show distinct patterns of expression, in rat Shank1 mRNA is found almost exclusively in brain, Shank2 in brain, kidney and liver, and Shank3 in heart, brain and spleen.


Pssm-ID: 188905  Cd Length: 66  Bit Score: 38.45  E-value: 1.17e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 831296835    9 VYEWLRTLQLVQYTEAFMDNGYDDLEVcKQIGEPDLDAIGVFVPHHRQRIYDAVQRL 65
Cdd:cd09506    10 VGDWLESLNLGEHRERFMDNEIDGSHL-PNLDKEDLTELGVTRVGHRMNIERALKKL 65
SAM smart00454
Sterile alpha motif; Widespread domain in signalling and nuclear proteins. In EPH-related ...
757-817 1.23e-03

Sterile alpha motif; Widespread domain in signalling and nuclear proteins. In EPH-related tyrosine kinases, appears to mediate cell-cell initiated signal transduction via the binding of SH2-containing proteins to a conserved tyrosine that is phosphorylated. In many cases mediates homodimerisation.


Pssm-ID: 197735  Cd Length: 68  Bit Score: 38.43  E-value: 1.23e-03
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 831296835    757 SVQELLERINLKELMPTFLFNGYEDLDTFKLLEEEDLDELNIKDPQHRAVLLTAVELLQEY 817
Cdd:smart00454    8 SVADWLESIGLEQYADNFRKNGIDGALLLLLTSEEDLKELGITKLGHRKKILKAIQKLKEQ 68
PHA03247 PHA03247
large tegument protein UL36; Provisional
897-1164 1.29e-03

large tegument protein UL36; Provisional


Pssm-ID: 223021 [Multi-domain]  Cd Length: 3151  Bit Score: 43.39  E-value: 1.29e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 831296835  897 RARKHPAKHFLFHPPIKALRGLGRGMRDARRcgvmmPTSRSCEMLDGPLEAPDGPRKRSQ-----SLGDLlwEQGFDQQQ 971
Cdd:PHA03247 2634 AANEPDPHPPPTVPPPERPRDDPAPGRVSRP-----RRARRLGRAAQASSPPQRPRRRAArptvgSLTSL--ADPPPPPP 2706
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 831296835  972 KPQRGAPPQEPG--AHEGPKNWKEERGGMPGAPAVPALPPRPAATTTATSPSSPlvsQNTLSPFRKSPPVSHDASFTspf 1049
Cdd:PHA03247 2707 TPEPAPHALVSAtpLPPGPAAARQASPALPAAPAPPAVPAGPATPGGPARPARP---PTTAGPPAPAPPAAPAAGPP--- 2780
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 831296835 1050 sspptspplRTLPKKAPVPPPVPVKKSRERLPNGLRPPPPAHLLPALPVKTCPSPLESTTVTPTPISPTLSPEELESGTP 1129
Cdd:PHA03247 2781 ---------RRLTRPAVASLSESRESLPSPWDPADPPAAVLAPAAALPPAASPAGPLPPPTSAQPTAPPPPPGPPPPSLP 2851
                         250       260       270
                  ....*....|....*....|....*....|....*....
gi 831296835 1130 P--SVPP--PWLSDLPESACPQIHGSRPMVALRRVSKLA 1164
Cdd:PHA03247 2852 LggSVAPggDVRRRPPSRSPAAKPAAPARPPVRRLARPA 2890
SAM_EPH-A10 cd09549
SAM domain of EPH-A10 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
7-66 1.32e-03

SAM domain of EPH-A10 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A10 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A10 receptors and appears to mediate cell-cell initiated signal transduction. It was found preferentially expressed in the testis. EphA10 may be involved in the pathogenesis and development of prostate carcinoma and lymphocytic leukemia. It is a potential molecular marker and/or therapy target for these types of cancers.


Pssm-ID: 188948  Cd Length: 70  Bit Score: 38.31  E-value: 1.32e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 831296835    7 NIVYEWLRTLQLVQYTEAFMDNGYDDLEVCKQIGEPDLDAIGVFVPHHRQRIYDAVQRLR 66
Cdd:cd09549     8 GSVGEWLEALDLCRYKDNFAAAGYGSLEAVARMTAQDVLSLGITSLEHQELLLAGIQALR 67
SAM_SAMSN1 cd09561
SAM domain of SAMSN1 subfamily; SAM (sterile alpha motif) domain of SAMSN1 (also known as ...
6-67 1.32e-03

SAM domain of SAMSN1 subfamily; SAM (sterile alpha motif) domain of SAMSN1 (also known as HACS1 or NASH1) proteins is a predicted protein-protein interaction domain. Members of this group are putative signaling/adaptor proteins. They appear to mediate signal transduction in lymphoid tissues. Murine HACS1 protein likely plays a role in B cell activation and differentiation. Potential binding partners of HACS1 are SLAM, DEC205 and PIR-B receptors and also some unidentified tyrosine-phosphorylated proteins. Proteins of this group were found preferentially expressed in normal hematopietic tissues and in some malignancies including lymphoma, myeloid leukemia and myeloma.


Pssm-ID: 188960  Cd Length: 66  Bit Score: 38.31  E-value: 1.32e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 831296835    6 PNIVYEWLRTLQLVQYTEAFMDNGYDDLEVCKQIGEPDLDAIGVFVPHHRQRIYDAVQRLRD 67
Cdd:cd09561     5 PKTLQELLERIHLQEYTSTLLLNGYETLEDLKDLKESHLIELNITDPEDRARLLSAAENLLD 66
SH3_Nck_2 cd11766
Second Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin ...
691-729 1.39e-03

Second Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212700  Cd Length: 53  Bit Score: 37.63  E-value: 1.39e-03
                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 831296835  691 DSLKLKRGDVIDIISKPPMGTWMGLLNNKVGTFKFIYVD 729
Cdd:cd11766    14 DELSLRKGDRVLVLEKSSDGWWRGECNGQVGWFPSNYVT 52
SH3_PIX cd11877
Src Homology 3 domain of Pak Interactive eXchange factors; PIX proteins are Rho guanine ...
689-728 1.78e-03

Src Homology 3 domain of Pak Interactive eXchange factors; PIX proteins are Rho guanine nucleotide exchange factors (GEFs), which activate small GTPases by exchanging bound GDP for free GTP. They act as GEFs for both Cdc42 and Rac 1, and have been implicated in cell motility, adhesion, neurite outgrowth, and cell polarity. Vertebrates contain two proteins from the PIX subfamily, alpha-PIX and beta-PIX. Alpha-PIX, also called ARHGEF6, is localized in dendritic spines where it regulates spine morphogenesis. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. Beta-PIX play roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212810  Cd Length: 53  Bit Score: 37.29  E-value: 1.78e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 831296835  689 DSDSLKLKRGDVIDIISKPPMGTWMGLLNNKVGTFKFIYV 728
Cdd:cd11877    12 NEDELSFDKGDIITVTQVVEGGWWEGTLNGKTGWFPSNYV 51
SAM_1 pfam00536
SAM domain (Sterile alpha motif); It has been suggested that SAM is an evolutionarily ...
1254-1311 2.15e-03

SAM domain (Sterile alpha motif); It has been suggested that SAM is an evolutionarily conserved protein binding domain that is involved in the regulation of numerous developmental processes in diverse eukaryotes. The SAM domain can potentially function as a protein interaction module through its ability to homo- and heterooligomerise with other SAM domains.


Pssm-ID: 334133  Cd Length: 64  Bit Score: 37.62  E-value: 2.15e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 831296835  1254 SVSDWLVSIGLPMYAtPLASAGCDSLAGVRALTEERLRQAGVRQDGHLHWLLHEARLL 1311
Cdd:pfam00536    7 DVGEWLESIGLGQYI-DLFRAGYIDGDTLLLLTEDDLMKLGVTLLGHRKKILYSIQGL 63
SH3_CIN85_3 cd12057
Third Src Homology 3 domain (SH3C) of Cbl-interacting protein of 85 kDa; CIN85, also called ...
687-731 2.43e-03

Third Src Homology 3 domain (SH3C) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CIN85. SH3C has been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212990  Cd Length: 56  Bit Score: 37.19  E-value: 2.43e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 831296835  687 PYDS---DSLKLKRGDVIDIISKP--PMGTWMGLLNNKVGTFKFIYVDVL 731
Cdd:cd12057     7 PYEAqneDELTIKEGDIVTLISKDciDAGWWEGELNGRRGVFPDNFVKLL 56
SH3_VAV1_2 cd11976
C-terminal (or second) Src homology 3 domain of VAV1 protein; VAV1 is expressed predominantly ...
677-729 2.44e-03

C-terminal (or second) Src homology 3 domain of VAV1 protein; VAV1 is expressed predominantly in the hematopoietic system and it plays an important role in the development and activation of B and T cells. It is activated by tyrosine phosphorylation to function as a guanine nucleotide exchange factor (GEF) for Rho GTPases following cell surface receptor activation, triggering various effects such as cytoskeletal reorganization, transcription regulation, cell cycle progression, and calcium mobilization. It also serves as a scaffold protein and has been shown to interact with Ku70, Socs1, Janus kinase 2, SIAH2, S100B, Abl gene, ZAP-70, SLP76, and Syk, among others. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The C-terminal SH3 domain of Vav1 interacts with a wide variety of proteins including cytoskeletal regulators (zyxin), RNA-binding proteins (Sam68), transcriptional regulators, viral proteins, and dynamin 2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212909  Cd Length: 54  Bit Score: 37.23  E-value: 2.44e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 831296835  677 ARVHTDFtpSPYDSDSLKLKRGDVIDIISKP-PMGTWMGLLNNKVGTFKFIYVD 729
Cdd:cd11976     2 AKARYDF--CARDRSELSLKEGDIIKILNKKgQQGWWRGEIYGRVGWFPANYVE 53
SAM_2 pfam07647
SAM domain (Sterile alpha motif);
1254-1311 2.97e-03

SAM domain (Sterile alpha motif);


Pssm-ID: 336753  Cd Length: 66  Bit Score: 37.25  E-value: 2.97e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 831296835  1254 SVSDWLVSIGLPMYATPLASAGCDSLAGVRALTEERLRQAGVRQDGHLHWLLHEARLL 1311
Cdd:pfam07647    8 SVAEWLRSIGLEQYKDNFTDQGITGAELLLRLTEEDLKRLGITSVGHRKKILKKIQEL 65
SH3_CD2AP-like_1 cd11873
First Src Homology 3 domain (SH3A) of CD2-associated protein and similar proteins; This ...
690-723 3.14e-03

First Src Homology 3 domain (SH3A) of CD2-associated protein and similar proteins; This subfamily is composed of the first SH3 domain (SH3A) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3A of both proteins bind to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic domain of the cell adhesion protein CD2. CIN85 SH3A binds to internal proline-rich motifs within the proline-rich region; this intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. CIN85 SH3A has also been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212806  Cd Length: 53  Bit Score: 36.86  E-value: 3.14e-03
                          10        20        30
                  ....*....|....*....|....*....|....
gi 831296835  690 SDSLKLKRGDVIDIISKPPMGTWMGLLNNKVGTF 723
Cdd:cd11873    13 PDELTLKVGDIITNVKKMEEGWWEGTLNGKRGMF 46
SAM_AIDA1AB-like_repeat1 cd09499
SAM domain of AIDA1AB-like proteins, repeat 1; SAM (sterile alpha motif) domain repeat 1 of ...
1254-1311 3.14e-03

SAM domain of AIDA1AB-like proteins, repeat 1; SAM (sterile alpha motif) domain repeat 1 of AIDA1AB-like proteins is a protein-protein interaction domain. AIDA1AB-like proteins have two tandem SAM domains. They may form an intramolecular head-to-tail homodimer. One of two basic motifs of the nuclear localization signal (NLS) is located within helix 5 of SAM2 (motif HKRK). This signal plays a role in decoupling of SAM2 from SAM1, thus facilitating translocation of this type proteins into the nucleus. SAM1 domain has a potential phosphorylation site for CMGC group of serine/threonine kinases. SAM domains of the AIDA1-like subfamily can directly bind ubiquitin and participate in regulating the degradation of ubiquitinated EphA receptors, particularly EPH-A8 receptor. Additionally AIDA1AB-like proteins may participate in the regulation of nucleoplasmic coilin protein interactions.


Pssm-ID: 188898  Cd Length: 67  Bit Score: 37.28  E-value: 3.14e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 831296835 1254 SVSDWLVSIGLPMYATPLASAGCDSL----AGVraLTEERLRQAGVRQDGHLHWLLHEARLL 1311
Cdd:cd09499     4 SVGQWLESIGLPQYESKLLLNGFDDVdflgSGV--MEDQDLKEIGITDEQHRQIILQAARSL 63
SH3_MLK1-3 cd12059
Src Homology 3 domain of Mixed Lineage Kinases 1, 2, and 3; MLKs 1, 2, and 3 are Serine ...
691-728 3.44e-03

Src Homology 3 domain of Mixed Lineage Kinases 1, 2, and 3; MLKs 1, 2, and 3 are Serine/Threonine Kinases (STKs), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. Little is known about the specific function of MLK1, also called MAP3K9. It is capable of activating the c-Jun N-terminal kinase pathway. Mice lacking both MLK1 and MLK2 are viable, fertile, and have normal life spans. MLK2, also called MAP3K10, is abundant in brain, skeletal muscle, and testis. It functions upstream of the MAPK, c-Jun N-terminal kinase. It binds hippocalcin, a calcium-sensor protein that protects neurons against calcium-induced cell death. Both MLK2 and hippocalcin may be associated with the pathogenesis of Parkinson's disease. MLK3, also called MAP3K11, is highly expressed in breast cancer cells and its signaling through c-Jun N-terminal kinase has been implicated in the migration, invasion, and malignancy of cancer cells. It also functions as a negative regulator of Inhibitor of Nuclear Factor-KappaB Kinase (IKK) and thus, impacts inflammation and immunity. MLKs contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212992  Cd Length: 58  Bit Score: 36.67  E-value: 3.44e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 831296835  691 DSLKLKRGDVIDIISKPPM-----GTWMGLLNNKVGTFKFIYV 728
Cdd:cd12059    14 DELTLRRGDRVEVLSKDSAvsgdeGWWTGKINDRVGIFPSNYV 56
DUF4654 pfam15547
Domain of unknown function (DUF4654); This family of proteins is found in eukaryotes. Proteins ...
977-1039 3.55e-03

Domain of unknown function (DUF4654); This family of proteins is found in eukaryotes. Proteins in this family are typically between 145 and 169 amino acids in length. There is a conserved IDC sequence motif.


Pssm-ID: 317881  Cd Length: 137  Bit Score: 39.02  E-value: 3.55e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 831296835   977 APPQEPGAHEGP-------------KNW-----KEERGGMPGAPAVPALPPRPAATTTATSPSSPLVSQNtlSPFRKSPP 1038
Cdd:pfam15547   30 APPRAPSPNRGPvtppmktyivfcgENQphltqEAPLGGGCLAQARGTLPPCRGTVAPASSPVSPLCPQE--APEAKGSP 107

                   .
gi 831296835  1039 V 1039
Cdd:pfam15547  108 L 108
SAM_EPH-R cd09488
SAM domain of EPH family of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH ...
1254-1300 4.02e-03

SAM domain of EPH family of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH (erythropoietin-producing hepatocyte) family of receptor tyrosine kinases is a C-terminal signal transduction module located in the cytoplasmic region of these receptors. SAM appears to mediate cell-cell initiated signal transduction via binding proteins to a conserved tyrosine that is phosphorylated. In some cases the SAM domain mediates homodimerization/oligomerization and plays a role in the clustering process necessary for signaling. EPH kinases are the largest family of receptor tyrosine kinases. They are classified into two groups based on their abilities to bind ephrin-A and ephrin-B ligands. The EPH receptors are involved in regulation of cell movement, shape, and attachment during embryonic development; they control cell-cell interactions in the vascular, nervous, epithelial, and immune systems, and in many tumors. They are potential molecular markers for cancer diagnostics and potential targets for cancer therapy.


Pssm-ID: 188887  Cd Length: 61  Bit Score: 36.82  E-value: 4.02e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 831296835 1254 SVSDWLVSIGLPMYATPLASAGCDSLAGVRALTEERLRQAGVRQDGH 1300
Cdd:cd09488     4 SVGEWLESIKMGRYKENFTAAGYTSLDAVAQMTAEDLTRLGVTLVGH 50
SAM_EPH-A7 cd09548
SAM domain of EPH-A7 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
9-66 4.93e-03

SAM domain of EPH-A7 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A7 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A7 receptors and appears to mediate cell-cell initiated signal transduction. EphA7 was found expressed in human embryonic stem (ES) cells, neural tissues, kidney vasculature. EphA7 knockout mice show decrease in cortical progenitor cell death at mid-neurogenesis and significant increase in cortical size. EphA7 may be involved in the pathogenesis and development of different cancers; in particular, EphA7 was found upregulated in glioblastoma and downregulated in colorectal cancer and gastric cancer. Thus, it is a potential molecular marker and/or therapy target for these types of cancers.


Pssm-ID: 188947  Cd Length: 70  Bit Score: 36.93  E-value: 4.93e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 831296835    9 VYEWLRTLQLVQYTEAFMDNGYDDLEVCKQIGEPDLDAIGVFVPHHRQRIYDAVQRLR 66
Cdd:cd09548    10 VGEWLEAIKMERYKDNFTAAGYNSLESVARMTIEDVMSLGITLVGHQKKIMSSIQTMR 67
SAM_EPH-A6 cd09547
SAM domain of EPH-A6 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
1253-1313 4.96e-03

SAM domain of EPH-A6 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A6 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A6 receptors and appears to mediate cell-cell initiated signal transduction. Eph-A6 gene is preferentially expressed in the nervous system. EPH-A6 receptors are involved in primate retina vascular and axon guidance, and in neural circuits responsible for learning and memory. EphA6 gene was significantly down regulated in colorectal cancer and in malignant melanomas. It is a potential molecular marker for these cancers.


Pssm-ID: 188946  Cd Length: 64  Bit Score: 36.79  E-value: 4.96e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 831296835 1253 VSVSDWLVSIGLPMYATPLASAGCDSLAGVRALTEERLRQAGVRQDGhlhwllHEARLLSS 1313
Cdd:cd09547     4 VTVSDWLDSIKMGQYKNNFMAAGFTTLDMVSRMTIDDIRRIGVTLIG------HQRRIVSS 58
SAM_CNK1,2,3-suppressor cd09511
SAM domain of CNK1,2,3-suppressor subfamily; SAM (sterile alpha motif) domain of CNK ...
6-66 6.48e-03

SAM domain of CNK1,2,3-suppressor subfamily; SAM (sterile alpha motif) domain of CNK (connector enhancer of kinase suppressor of ras (Ksr)) subfamily is a protein-protein interaction domain. CNK proteins are multidomain scaffold proteins containing a few protein-protein interaction domains and are required for connecting Rho and Ras signaling pathways. In Drosophila, the SAM domain of CNK is known to interact with the SAM domain of the aveugle protein, forming a heterodimer. Mutation of the SAM domain in human CNK1 abolishes the ability to cooperate with the Ras effector, supporting the idea that this interaction is necessary for proper Ras signal transduction.


Pssm-ID: 188910  Cd Length: 69  Bit Score: 36.50  E-value: 6.48e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 831296835    6 PNIVYEWLRTLQ--LVQYTEAFMD---NGYDDLEVCKQigepDLDAIGVFVPHHRQRIYDAVQRLR 66
Cdd:cd09511     6 PKQVTDWLKGLDdcLQQYIYTFERekvTGEQLLNLSPQ----DLENLGVTKIGHQELILEAVELLC 67
SAM_EPH-A8 cd09550
SAM domain of EPH-A8 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
9-66 7.43e-03

SAM domain of EPH-A8 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A8 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A8 receptors and appears to mediate cell-cell initiated signal transduction. EPH-A8 receptors are involved in ligand dependent (ephirin A2, A3, A5) regulation of cell adhesion and migration, and in ligand independent regulation of neurite outgrowth in neuronal cells. They perform signaling in kinase dependent and kinase independent manner. EPH-A8 receptors are known to interact with a number of different proteins including PI 3-kinase and AIDA1-like subfamily SAM repeat domain containing proteins. However other domains (not SAM) of EPH-A8 receptors are involved in these interactions.


Pssm-ID: 188949  Cd Length: 65  Bit Score: 36.00  E-value: 7.43e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 831296835    9 VYEWLRTLQLVQYTEAFMDNGYDDLEVCKQIGEPDLDAIGVFVPHHRQRIYDAVQRLR 66
Cdd:cd09550     5 VDDWLDSIKMGRYKDHFAAGGYSSLGMVMRMNIEDIRRLGITLMGHQKKILTSIQVMR 62
SAM_Arap1,2,3 cd09490
SAM domain of Arap1,2,3 (angiotensin receptor-associated protein); SAM (sterile alpha motif) ...
1253-1300 7.91e-03

SAM domain of Arap1,2,3 (angiotensin receptor-associated protein); SAM (sterile alpha motif) domain of Arap1,2,3 subfamily proteins (angiotensin receptor-associated) is a protein-protein interaction domain. Arap1,2,3 proteins are phosphatidylinositol-3,4,5-trisphosphate-dependent GTPase-activating proteins. They are involved in phosphatidylinositol-3 kinase (PI3K) signaling pathways. In addition to SAM domain, Arap1,2,3 proteins contain ArfGap, PH-like, RhoGAP and UBQ domains. SAM domain of Arap3 protein was shown to interact with SAM domain of Ship2 phosphatidylinositol-trisphosphate phosphatase proteins. Such interaction apparently plays a role in inhibition of PI3K regulated pathways since Ship2 converts PI(3,4,5)P3 into PI(3,4)P2. Proteins of this subfamily participate in regulation of signaling and trafficking associated with a number of different receptors (including EGFR, TRAIL-R1/DR4, TRAIL-R2/DR5) in normal and cancer cells; they are involved in regulation of actin cytoskeleton remodeling, cell spreading and formation of lamellipodia.


Pssm-ID: 188889  Cd Length: 63  Bit Score: 36.12  E-value: 7.91e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 831296835 1253 VSVSDWLVSIGLPMYATPLASAGCDSLAGVRALTEERLRQAGVRQDGH 1300
Cdd:cd09490     4 LDIAEWLASIHLEQYLDLFREHGYVTATDCQGINDSRLKQIGISPTGH 51
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.17
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
  • Marchler-Bauer A et al. (2015), "CDD: NCBI's conserved domain database.", Nucleic Acids Res.43(D)222-6.
  • Marchler-Bauer A et al. (2011), "CDD: a Conserved Domain Database for the functional annotation of proteins.", Nucleic Acids Res.39(D)225-9.
  • Marchler-Bauer A, Bryant SH (2004), "CD-Search: protein domain annotations on the fly.", Nucleic Acids Res.32(W)327-331.
Help | Disclaimer | Write to the Help Desk
NCBI | NLM | NIH