Ankyrin repeat and sterile alpha motif (SAM) domain-containing (Anks) protein family Phosphotyrosine-binding (PTB) domain; Both AIDA-1b (AbetaPP intracellular domain-associated protein 1b) and Odin (also known as ankyrin repeat and sterile alpha motif domain-containing 1A; ANKS1A) belong to the Anks protein family. Both of these family members interacts with the EphA8 receptor. Ank members consists of ankyrin repeats, a SAM domain and a C-terminal PTB domain which is crucial for interaction with the juxtamembrane (JM) region of EphA8. PTB domains are classified into three groups, namely, phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains of which the Anks PTB is a member. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the Dab-like subgroup.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024386160 743 QNWQHQPEKLIFESCGYEANYLGSMLIKDLRGTESTQDACAKMRKSTEHMKKIPTIILSITYKGVKFIDASNKNVIAEHE 822
Cdd:cd01274     1 TQWRHSPEKLITGSVNYEAHYLGSTEIKELRGTESTKKAIQKLKKSTREMKKIPTIILSISYKGVKFIDATTKNLICEHE 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2024386160 823 IRNISCAAQDPEDLCTFAYITKDLQTSHHYCHVFSTVDVNLTYEIILTLGQAFEVAYQLALQAQR 887
Cdd:cd01274    81 IRNISCACQDPEDLNTFAYITKDLKTDHHYCHVFCVLTVDLATEIILTLGQAFEVAYQLALRAQK 145

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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2024386160 585 DGNSQPSVPAWLDSLGLQDYIQSFLSSGYSSIDTVKNLWELEIVNVLKVNLLGHRKRIIASLADR 649
Cdd:cd09500     1 DGNSPASVSEWLDSIGLGDYIETFLKHGYTSMERVKRIWEVELTNVLEINKLGHRKRILASLADR 65

Ankyrin repeat and sterile alpha motif (SAM) domain-containing (Anks) protein family Phosphotyrosine-binding (PTB) domain; Both AIDA-1b (AbetaPP intracellular domain-associated protein 1b) and Odin (also known as ankyrin repeat and sterile alpha motif domain-containing 1A; ANKS1A) belong to the Anks protein family. Both of these family members interacts with the EphA8 receptor. Ank members consists of ankyrin repeats, a SAM domain and a C-terminal PTB domain which is crucial for interaction with the juxtamembrane (JM) region of EphA8. PTB domains are classified into three groups, namely, phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains of which the Anks PTB is a member. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the Dab-like subgroup.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024386160 743 QNWQHQPEKLIFESCGYEANYLGSMLIKDLRGTESTQDACAKMRKSTEHMKKIPTIILSITYKGVKFIDASNKNVIAEHE 822
Cdd:cd01274     1 TQWRHSPEKLITGSVNYEAHYLGSTEIKELRGTESTKKAIQKLKKSTREMKKIPTIILSISYKGVKFIDATTKNLICEHE 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2024386160 823 IRNISCAAQDPEDLCTFAYITKDLQTSHHYCHVFSTVDVNLTYEIILTLGQAFEVAYQLALQAQR 887
Cdd:cd01274    81 IRNISCACQDPEDLNTFAYITKDLKTDHHYCHVFCVLTVDLATEIILTLGQAFEVAYQLALRAQK 145

Phosphotyrosine-binding domain, phosphotyrosine-interaction (PI) domain; PTB/PI domain structure similar to those of pleckstrin homology (PH) and IRS-1-like PTB domains.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024386160  755 ESCGYEANYLGSMLIKDLRGTESTQDACAKMRKS-TEHMKKIPTIILSITYKGVKFIDASNKNVIAEHEIRNISCAAQDP 833
Cdd:smart00462   2 SGVSFRVKYLGSVEVPEARGLQVVQEAIRKLRAAqGSEKKEPQKVILSISSRGVKLIDEDTKAVLHEHPLRRISFCAVGP 81

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024386160  834 EDLCTFAYITKDLQTSHHYCHVFSTVDVNltYEIILTLGQAFEVAYQLALQAQR 887
Cdd:smart00462  82 DDLDVFGYIARDPGSSRFACHVFRCEKAA--EDIALAIGQAFQLAYELKLKARS 133

Ankyrin repeat [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024386160   2 RNNKFETPLDLAALYGRLEVVKMLLNAHPNLLSCNTKKHTPLHLAARNGHKTVVHVLLDAGMDSNYQTEKG-SALHEAAL 80
Cdd:COG0666   116 RDKDGETPLHLAAYNGNLEIVKLLLEAGADVNAQDNDGNTPLHLAAANGNLEIVKLLLEAGADVNARDNDGeTPLHLAAE 195

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2024386160  81 FGKTDVVQILLAAGIDVNIKDNRGLTALDIVRElpsQKSQHIAALIEDYTTGKKSAKAAEKTAQ 144
Cdd:COG0666   196 NGHLEIVKLLLEAGADVNAKDNDGKTALDLAAE---NGNLEIVKLLLEAGADLNAKDKDGLTAL 256

Phosphotyrosine interaction domain (PTB/PID);

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024386160 759 YEANYLGSM-------LIKDLRgTESTQDA--CAKM------RKSTEHMKKIPTIILSITYKGVKFIDASNKNVIAEHEI 823
Cdd:pfam00640   1 FAVRYLGSVevpeeraPDKNTR-MQQAREAirRVKAakinkiRGLSGETGPGTKVDLFISTDGLKLLNPDTQELIHDHPL 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 2024386160 824 RNIS-CAAQDPEDLCTFAYITKDLQTSHHYCHVFSTVDvnLTYEIILTLGQAFEVA 878
Cdd:pfam00640  80 VSISfCADGDPDLMRYFAYIARDKATNKFACHVFESED--GAQDIAQSIGQAFALA 133

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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2024386160 585 DGNSQPSVPAWLDSLGLQDYIQSFlSSGYSSIDTVKNLWELEIVNvLKVNLLGHRKRIIASL 646
Cdd:pfam00536   1 DGWSVEDVGEWLESIGLGQYIDSF-RAGYIDGDALLQLTEDDLLK-LGVTLLGHRKKILYAI 60

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.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2024386160  585 DGNSQPSVPAWLDSLGLQDYIQSFLSSGYSSIDTVkNLWELEIVNVLKVNLLGHRKRIIASL 646
Cdd:smart00454   2 SQWSPESVADWLESIGLEQYADNFRKNGIDGALLL-LLTSEEDLKELGITKLGHRKKILKAI 62

Transient Receptor Potential channel, Vanilloid subfamily (TRPV), types 5 and 6; TRPV5 and TRPV6 (TRPV5/6) are two homologous members within the vanilloid subfamily of the transient receptor potential (TRP) family. TRPV5 and TRPV6 show only 30-40% homology with other members of the TRP family and have unique properties that differentiates them from other TRP channels. They mediate calcium uptake in epithelia and their expression is dramatically increased in numerous types of cancer. The structure of TRPV5/6 shows the typical topology features of all TRP family members, such as six transmembrane regions, a short hydrophobic stretch between transmembrane segments 5 and 6, which is predicted to form the Ca2+ pore, and large intracellular N- and C-terminal domains. The N-terminal domain of TRPV5/6 contains three ankyrin repeats. This structural element is present in several proteins and plays a role in protein-protein interactions. The N- and C-terminal tails of TRPV5/6 each contain an internal PDZ motif which can function as part of a molecular scaffold via interaction with PDZ-domain containing proteins. A major difference between the properties of TRPV5 and TRPV6 is in their tissue distribution: TRPV5 is predominantly expressed in the distal convoluted tubules (DCT) and connecting tubules (CNT) of the kidney, with limited expression in extrarenal tissues. In contrast, TRPV6 has a broader expression pattern such as expression in the intestine, kidney, placenta, epididymis, exocrine tissues, and a few other tissues.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024386160   7 ETPLDLAALYGRLEVVKMLLNAHPNLL-----SCNTKKHTPLHLAARNGHKTVVHVLLDAGMDSNYQTEKGSA------- 74
Cdd:cd22192    52 ETALHVAALYDNLEAAVVLMEAAPELVnepmtSDLYQGETALHIAVVNQNLNLVRELIARGADVVSPRATGTFfrpgpkn 131

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 2024386160  75 --------LHEAALFGKTDVVQILLAAGIDVNIKDNRGLTALDIVRELPSQK 118
Cdd:cd22192   132 liyygehpLSFAACVGNEEIVRLLIEHGADIRAQDSLGNTVLHILVLQPNKT 183

Ankyrin repeat and sterile alpha motif (SAM) domain-containing (Anks) protein family Phosphotyrosine-binding (PTB) domain; Both AIDA-1b (AbetaPP intracellular domain-associated protein 1b) and Odin (also known as ankyrin repeat and sterile alpha motif domain-containing 1A; ANKS1A) belong to the Anks protein family. Both of these family members interacts with the EphA8 receptor. Ank members consists of ankyrin repeats, a SAM domain and a C-terminal PTB domain which is crucial for interaction with the juxtamembrane (JM) region of EphA8. PTB domains are classified into three groups, namely, phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains of which the Anks PTB is a member. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the Dab-like subgroup.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024386160 743 QNWQHQPEKLIFESCGYEANYLGSMLIKDLRGTESTQDACAKMRKSTEHMKKIPTIILSITYKGVKFIDASNKNVIAEHE 822
Cdd:cd01274     1 TQWRHSPEKLITGSVNYEAHYLGSTEIKELRGTESTKKAIQKLKKSTREMKKIPTIILSISYKGVKFIDATTKNLICEHE 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2024386160 823 IRNISCAAQDPEDLCTFAYITKDLQTSHHYCHVFSTVDVNLTYEIILTLGQAFEVAYQLALQAQR 887
Cdd:cd01274    81 IRNISCACQDPEDLNTFAYITKDLKTDHHYCHVFCVLTVDLATEIILTLGQAFEVAYQLALRAQK 145

Phosphotyrosine-binding domain, phosphotyrosine-interaction (PI) domain; PTB/PI domain structure similar to those of pleckstrin homology (PH) and IRS-1-like PTB domains.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024386160  755 ESCGYEANYLGSMLIKDLRGTESTQDACAKMRKS-TEHMKKIPTIILSITYKGVKFIDASNKNVIAEHEIRNISCAAQDP 833
Cdd:smart00462   2 SGVSFRVKYLGSVEVPEARGLQVVQEAIRKLRAAqGSEKKEPQKVILSISSRGVKLIDEDTKAVLHEHPLRRISFCAVGP 81

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2024386160  834 EDLCTFAYITKDLQTSHHYCHVFSTVDVNltYEIILTLGQAFEVAYQLALQAQR 887
Cdd:smart00462  82 DDLDVFGYIARDPGSSRFACHVFRCEKAA--EDIALAIGQAFQLAYELKLKARS 133

Ankyrin repeat [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024386160   2 RNNKFETPLDLAALYGRLEVVKMLLNAHPNLLSCNTKKHTPLHLAARNGHKTVVHVLLDAGMDSNYQTEKG-SALHEAAL 80
Cdd:COG0666   116 RDKDGETPLHLAAYNGNLEIVKLLLEAGADVNAQDNDGNTPLHLAAANGNLEIVKLLLEAGADVNARDNDGeTPLHLAAE 195

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2024386160  81 FGKTDVVQILLAAGIDVNIKDNRGLTALDIVRElpsQKSQHIAALIEDYTTGKKSAKAAEKTAQ 144
Cdd:COG0666   196 NGHLEIVKLLLEAGADVNAKDNDGKTALDLAAE---NGNLEIVKLLLEAGADLNAKDKDGLTAL 256

Phosphotyrosine-binding (PTB) PH-like fold; PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to bind peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024386160 757 CGYEANYLGSMLIKDLRGTESTQDACAKMRKSTEHMKKIPT-IILSITYKGVKFIDASNKNVIAEHEIRNISCAAQDPED 835
Cdd:cd00934     1 ASFQVKYLGSVEVGSSRGVDVVEEALKALAAALKSSKRKPGpVLLEVSSKGVKLLDLDTKELLLRHPLHRISYCGRDPDN 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 2024386160 836 LCTFAYITKDLQTSHHYCHVFSTVDVNLTYEIILTLGQAF 875
Cdd:cd00934    81 PNVFAFIAGEEGGSGFRCHVFQCEDEEEAEEILQAIGQAF 120

Ankyrin repeat [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024386160   3 NNKFETPLDLAALYGRLEVVKMLLNAHPNLLSCNTKKHTPLHLAARNGHKTVVHVLLDAGMDSNYQTEKG-SALHEAALF 81
Cdd:COG0666    51 DALGALLLLAAALAGDLLVALLLLAAGADINAKDDGGNTLLHAAARNGDLEIVKLLLEAGADVNARDKDGeTPLHLAAYN 130

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 2024386160  82 GKTDVVQILLAAGIDVNIKDNRGLTAL---------DIVREL 114
Cdd:COG0666   131 GNLEIVKLLLEAGADVNAQDNDGNTPLhlaaangnlEIVKLL 172

Cell death protein 6 homolog (CED-6/GULP1) Phosphotyrosine-binding (PTB) domain; CED6 (also known as GULP1: engulfment adaptor PTB domain containing 1) is an adaptor protein involved in the specific recognition and engulfment of apoptotic cells. CED6 has been shown to interact with the cytoplasmic tail of another protein involved in the engulfment of apoptotic cells, CED1. CED6 has a C-terminal PTB domain, which can bind to NPXY motifs. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the Dab-like subgroup.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024386160 747 HQPEKLIFESCGYEANYLGSMLIKDLRGTESTQDACAKMrKSTEHMK-----KIPTIILSITYKGVKFIDASNKNVIAEH 821
Cdd:cd01273     2 HPPEALIKGHVAYLVKFLGCTEVEQPKGTEVVKEAIRKL-KFARQLKksegaKLPKVELQISIDGVKIQDPKTKVIMHQF 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2024386160 822 EIRNISCAAQDPEDLCTFAYITKDLQTSHHYCHVFstVDVNLTYEIILTLGQAFEVAYQLALQ 884
Cdd:cd01273    81 PLHRISFCADDKTDKRIFSFIAKDSESEKHLCFVF--DSEKLAEEITLTIGQAFDLAYRRFLE 141

Tyrosine-specific kinase/HM-motif TK (TM/HMTK) Phosphotyrosine-binding (PTB) PH-like fold; TK kinases catalyzes the transfer of the terminal phosphate of ATP to a specific tyrosine residue on its target protein. TK kinases play significant roles in development and cell division. Tyrosine-protein kinases can be divided into two subfamilies: receptor tyrosine kinases, which have an intracellular tyrosine kinase domain, a transmembrane domain and an extracellular ligand-binding domain; and non-receptor (cytoplasmic) tyrosine kinases, which are soluble, cytoplasmic kinases. In HMTK the conserved His-Arg-Asp sequence within the catalytic loop is replaced by a His-Met sequence. TM/HMTK have are 2-3 N-terminal PTB domains. PTB domains in TKs are thought to function analogously to the membrane targeting (PH, myristoylation) and pTyr binding (SH2) domains of Src subgroup kinases. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the Dab-like subgroup.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024386160 759 YEANYLGSMLIKDLRGTESTQDACAKMRksteHMKKIPT-IILSITYKGVKFIDASNKNVIAEHEIRNISCAAQDPEDLC 837
Cdd:cd13161     4 FEAKYLGSVPVKEPKGNDVVMAAVKRLK----DLKLKPKpVVLVVSSEGIRVVERLTGEVLTNVPIKDISFVTVDPKDKK 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 2024386160 838 TFAYITKDLQTSHHYCHVFSTVDVNltYEIILTLGQAFEVAYQ 880
Cdd:cd13161    80 LFAFISHDPRLGRITCHVFRCKRGA--QEICDTIAEAFKAAAE 120

Ankyrin repeat [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024386160   2 RNNKFETPLDLAALYGRLEVVKMLLNAHPNLLSCNTKKHTPLHLAARNGHKTVVHVLLDAGMDSNYQTEKG-SALHEAAL 80
Cdd:COG0666   182 RDNDGETPLHLAAENGHLEIVKLLLEAGADVNAKDNDGKTALDLAAENGNLEIVKLLLEAGADLNAKDKDGlTALLLAAA 261

                          90       100
                  ....*....|....*....|....*...
gi 2024386160  81 FGKTDVVQILLAAGIDVNIKDNRGLTAL 108
Cdd:COG0666   262 AGAALIVKLLLLALLLLAAALLDLLTLL 289

Low Density Lipoprotein Receptor Adaptor Protein 1 (LDLRAP1) in mammals and similar proteins Phosphotyrosine-binding (PTB) PH-like fold; The null mutations in the LDL receptor adaptor protein 1 (LDLRAP1) gene, which serves as an adaptor for LDLR endocytosis in the liver, causes autosomal recessive hypercholesterolemia (ARH). LDLRAP1 contains a single PTB domain. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd contains mammals, insects, and sponges.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024386160 759 YEANYLGSMLIKDLRGTESTQDACA---KMRKSTEhmKKIPTIILSITYKGVKFIDASNKNVIAEHEIRNIS-CAAqDPE 834
Cdd:cd13159     5 FYLKYLGSTLVEKPKGEGATAEAVKtiiAMAKASG--KKLQKVTLTVSPKGIKVTDSATNETILEVSIYRISyCTA-DAN 81

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 2024386160 835 DLCTFAYITKDLQTSHHYCHVFSTVDVNLTYEIILTLGQAFE 876
Cdd:cd13159    82 HDKVFAFIATNQDNEKLECHAFLCAKRKMAQAVTLTVAQAFN 123

Ankyrin repeat [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024386160   3 NNKFETPLDLAALYGRLEVVKMLLNAHPNLLSCNTKKHTPLHLAARNGHKTVVHVLLDAGMDSNYQTEKG-SALHEAALF 81
Cdd:COG0666    18 LLLLALLLLAAALLLLLLLLLLLLLALLALALADALGALLLLAAALAGDLLVALLLLAAGADINAKDDGGnTLLHAAARN 97

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 2024386160  82 GKTDVVQILLAAGIDVNIKDNRGLTAL---------DIVREL 114
Cdd:COG0666    98 GDLEIVKLLLEAGADVNARDKDGETPLhlaayngnlEIVKLL 139

Numb Phosphotyrosine-binding (PTB) domain; Numb is a membrane associated adaptor protein which plays critical roles in cell fate determination. Numb proteins are involved in control of asymmetric cell division and cell fate choice, endocytosis, cell adhesion, cell migration, ubiquitination of specific substrates and a number of signaling pathways (Notch, Hedgehog, p53). Mutations in Numb plays a critical role in disease (cancer). Numb has an N-terminal PTB domain and a C-terminal NumbF domain. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the Dab-like subgroup.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024386160 743 QNWQHQPEKLIFESCGYEANYLGSMLIKDLRGTESTQDACAKMRKSTehmKKIPTIILSITYKGVKFIDASNKNVIAEHE 822
Cdd:cd01268     1 HQWQADEEAVRSGTCSFPVKYLGCVEVGESRGMQVCEEALKKLKASR---KKPVRAVLWVSGDGLRVVDEKTKGLIVDQT 77

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 2024386160 823 IRNISCAAQDPEDLCTFAYITKDLQTSHHYCHVFSTVD 860
Cdd:cd01268    78 IEKVSFCAPDRNHERAFSYICRDGTTRRWMCHCFLAVK 115

SAM domain (Sterile alpha motif);

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2024386160 516 QSVGEWLESIGLQQYESKLLLNGFDDVRFLgcNVMEDQDLRDIGIGDPQHRRKLLQAARSL 576
Cdd:pfam07647   7 ESVADWLRSIGLEQYTDNFRDQGITGAELL--LRLTLEDLKRLGITSVGHRRKILKKIQEL 65

Tensin-related Phosphotyrosine-binding (PTB) domain; Tensin plays critical roles in renal function, muscle regeneration, and cell migration. It binds to actin filaments and interacts with the cytoplasmic tails of beta-integrin via its PTB domain, allowing tensin to link actin filaments to integrin receptors. Tensin functions as a platform for assembly and disassembly of signaling complexes at focal adhesions by recruiting tyrosine-phosphorylated signaling molecules, and also by providing interaction sites for other proteins. In addition to its PTB domain, it contains a C-terminal SH2 domain. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024386160 761 ANYLGSMLIKDLrgteSTQDACAKMRKSTEHMKKIPT----IILSITYKGVKFIDASNKNVIAEHEIRNISCAAQDPEDl 836
Cdd:cd13157     6 AQYIGSFPVSGL----DVADRADSVRKQLESLKESGSrgrpVILSVSLSGIKICSEDGKVVLMAHALRRVSYSTCRPAH- 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 2024386160 837 CTFAYITKDLQ--TSHHYCHVFSTVDVNLTYEIILTLGQAFEVAY 879
Cdd:cd13157    81 AQFAFVARNPGgpTNRQYCHVFVTRSPREAQELNLLLCRAFQLAY 125

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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 2024386160 518 VGEWLESIGLQQYESKLLLNGFDDVRFlgCNVMEDQDLRDIGIGDPQHRRKLLQAARSL 576
Cdd:cd09527     5 VYDWLRTLQLEQYAEKFVDNGYDDLEV--CKQIGDPDLDAIGVMNPAHRKRILEAVRRL 61

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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024386160 516 QSVGEWLESIGLQQYESKLLLNGFDDVRFLgcNVMEDQDLRDIGIGDPQHRRKLLQAARS 575
Cdd:cd09493     3 KTVEELLERINLQEHTSTLLLNGYETLEDF--KDLKESHLNELNITDPEHRAKLLTAAEL 60

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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 2024386160 595 WLDSLGLQDYIQSFLSSGYSSIDTVKNL-WE-LEivnVLKVNLLGHRKRII 643
Cdd:cd09498    13 WLSLLGLPQYHKVLVENGYDSIDFVTDLtWEdLQ---DIGITKLGHQKKLM 60

SAM domain (Sterile alpha motif);

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2024386160 588 SQPSVPAWLDSLGLQDYIQSFLSSGYSSIDTVKNLwELEIVNVLKVNLLGHRKRIIASLAD 648
Cdd:pfam07647   5 SLESVADWLRSIGLEQYTDNFRDQGITGAELLLRL-TLEDLKRLGITSVGHRRKILKKIQE 64

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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2024386160 585 DGNSQPSVPAWLDSLGLQDYIQSFLSSGYSSIDTVKNLWELEIVNvLKVNLLGHRKRIIASL 646
Cdd:cd09543     1 EGVPFRTVAEWLESIKMQQYTEHFMAAGYNSIDKVLQMTQEDIKH-IGVRLPGHQKRIAYSI 61

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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 2024386160 591 SVPAWLDSLGLQDYIQSFLSSGYSSIDTVKNLwELEIVNVLKVNLLGHRKRIIASLAD 648
Cdd:cd09546     5 SVGEWLEAIKMGRYTEIFMENGYSSMDAVAQV-TLEDLRRLGVTLVGHQKKIMNSIQE 61

Carboxyl-terminal PDZ ligand of neuronal nitric oxide synthase protein (CAPON) Phosphotyrosine-binding (PTB) domain; CAPON (also known as Nitric oxide synthase 1 adaptor protein, NOS1AP, encodes a cytosolic protein that binds to the signaling molecule, neuronal NOS (nNOS). It contains a N-terminal PTB domain that binds to the small monomeric G protein, Dexras1 and a C-terminal PDZ-binding domain that mediates interactions with nNOS. Included in this cd are C. elegan proteins dystrobrevin, DYB-1, which controls neurotransmitter release and muscle Ca(2+) transients by localizing BK channels and DYstrophin-like phenotype and CAPON related,DYC-1, which is functionally related to dystrophin homolog, DYS-1. Mutations in the dystrophin gene causes Duchenne muscular dystrophy. DYS-1 shares sequence similarity, including key motifs, with their mammalian counterparts. These CAPON-like proteins all have a single PTB domain. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the Dab-like subgroup.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024386160 759 YEANYLGSMLIKdlRGTeSTQDACAKMR------KSTEHMKKIPTIILSITykGVKFI-----------DASNKNVIAEH 821
Cdd:cd01270    31 FQAKYIGSLEVP--RPS-SRVEIVAAMRriryefKAKNIKKKKVTITVSVD--GVKVVlrkkkkkkgwtWDESKLLLMQH 105

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2024386160 822 EIRNISCAAQDPEDLCTFAYITKDLQTSHHYCHVFSTVDVNLTYEIILTLGQAFEVAYQLALQAQRAKPPGAAA 895
Cdd:cd01270   106 PIYRIFYVSHDSQDLKIFSYIARDGSSNVFKCNVFKSKKKSQAMRIVRTIGQAFEVCHKLSLQHMQGNADDEAE 179

Disabled (Dab) Phosphotyrosine-binding domain; Dab is a cystosolic adaptor protein, which binds to the cytoplasmic tails of lipoprotein receptors, such as ApoER2 and VLDLR, via its PTB domain. The dab PTB domain has a preference for unphosphorylated tyrosine within an NPxY motif. Additionally, the Dab PTB domain, which is structurally similar to PH domains, binds to phosphatidlyinositol phosphate 4,5 bisphosphate in a manner characteristic of phosphoinositide binding PH domains. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the Dab-like subgroup.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024386160 759 YEANYLGSMLIKDLRGTESTQDACAKM----RKSTEHMKKIptiILSITYKGVKFIDASNKNVIAEHEIRNISCAAQDPE 834
Cdd:cd01215    18 FKAKLIGIDEVPAARGDKMCQDAMMKLkgavKAAGEHKQRI---WLNISLEGIKILDEKTGALLHHHPVHKISFIARDTT 94

                          90
                  ....*....|....*...
gi 2024386160 835 DLCTFAYITKdLQTSHHY 852
Cdd:cd01215    95 DNRAFGYVCG-LDGGHRF 111

ankyrin repeat protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024386160   8 TPLDLAALYGRLEVVKMLLN--AHPNLLSCNtkKHTPLHLAARNGHKTVVHVLLDAGMDSNYQTEKG--SALHEAALFGK 83
Cdd:PHA02875  137 SPLHLAVMMGDIKGIELLIDhkACLDIEDCC--GCTPLIIAMAKGDIAICKMLLDSGANIDYFGKNGcvAALCYAIENNK 214

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 2024386160  84 TDVVQILLAAGIDVNIK---DNRGLTALDIVRELPSQ-KSQHIAALIED 128
Cdd:PHA02875  215 IDIVRLFIKRGADCNIMfmiEGEECTILDMICNMCTNlESEAIDALIAD 263

Transient Receptor Potential channel, Vanilloid subfamily (TRPV), types 5 and 6; TRPV5 and TRPV6 (TRPV5/6) are two homologous members within the vanilloid subfamily of the transient receptor potential (TRP) family. TRPV5 and TRPV6 show only 30-40% homology with other members of the TRP family and have unique properties that differentiates them from other TRP channels. They mediate calcium uptake in epithelia and their expression is dramatically increased in numerous types of cancer. The structure of TRPV5/6 shows the typical topology features of all TRP family members, such as six transmembrane regions, a short hydrophobic stretch between transmembrane segments 5 and 6, which is predicted to form the Ca2+ pore, and large intracellular N- and C-terminal domains. The N-terminal domain of TRPV5/6 contains three ankyrin repeats. This structural element is present in several proteins and plays a role in protein-protein interactions. The N- and C-terminal tails of TRPV5/6 each contain an internal PDZ motif which can function as part of a molecular scaffold via interaction with PDZ-domain containing proteins. A major difference between the properties of TRPV5 and TRPV6 is in their tissue distribution: TRPV5 is predominantly expressed in the distal convoluted tubules (DCT) and connecting tubules (CNT) of the kidney, with limited expression in extrarenal tissues. In contrast, TRPV6 has a broader expression pattern such as expression in the intestine, kidney, placenta, epididymis, exocrine tissues, and a few other tissues.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024386160   7 ETPLDLAALYGRLEVVKMLLNAHPNLL-----SCNTKKHTPLHLAARNGHKTVVHVLLDAGMDSNYQTEKGSA------- 74
Cdd:cd22192    52 ETALHVAALYDNLEAAVVLMEAAPELVnepmtSDLYQGETALHIAVVNQNLNLVRELIARGADVVSPRATGTFfrpgpkn 131

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 2024386160  75 --------LHEAALFGKTDVVQILLAAGIDVNIKDNRGLTALDIVRELPSQK 118
Cdd:cd22192   132 liyygehpLSFAACVGNEEIVRLLIEHGADIRAQDSLGNTVLHILVLQPNKT 183