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Conserved domains on  [gi|148664546|gb|EDK96962|]
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meprin 1 beta [Mus musculus]

Protein Classification

MAM and EGF_CA domain-containing protein( domain architecture ID 11620423)

protein containing domains ZnMc, MAM, MATH, and EGF_CA

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
ZnMc super family cl00064
Zinc-dependent metalloprotease. This super-family of metalloproteases contains two major ...
 30-256 9.75e-143

Zinc-dependent metalloprotease. This super-family of metalloproteases contains two major branches, the astacin-like proteases and the adamalysin/reprolysin-like proteases. Both branches have wide phylogenetic distribution, and contain sub-families, which are involved in vertebrate development and disease.


The actual alignment was detected with superfamily member cd04282:

Pssm-ID: 469599 [Multi-domain]  Cd Length: 230  Bit Score: 416.49  E-value: 9.75e-143
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546  30 DIDGGIDQDIFDINQGLGLDLFEGDIKLE-ANGKNSIIGDHKRWPHTIPYVLEDSLEMNAKGVILNAFERYRLKTCIDFK 108
Cdd:cd04282    3 DADEGIDQDIFEINLGAGLDLFEGDILLDeGQSRNGLIGDTYRWPFPIPYILDDSLDLNAKGVILKAFEMYRLKSCVDFK 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546 109 PWSGEANYISVFKGSGCWSSVGNIHaGKQELSIGTNCDRIATVQHEFLHALGFWHEQSRADRDDYVIIVWDRIQPGKEHN 188
Cdd:cd04282   83 PYEGESNYIFFFKGSGCWSMVGDQQ-GGQNLSIGAGCDYKATVEHEFLHALGFYHEQSRSDRDDYVKIWWDQILSGREHN 161

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 148664546 189 FNIYNDSVSDSLNVPYDYTSVMHYSKTAFQNG-TESTIVTRISEFEDVIGQRMDFSDYDLLKLNQLYNC 256
Cdd:cd04282  162 FNKYDDSFSTDLNTPYDYESVMHYSPFSFNKGaSEPTITTKIPEFNDIIGQRLDFSDIDLERLNRMYNC 230
MATH super family cl02446
MATH (meprin and TRAF-C homology) domain; an independent folding unit with an eight-stranded ...
 428-587 9.83e-94

MATH (meprin and TRAF-C homology) domain; an independent folding unit with an eight-stranded beta-sandwich structure found in meprins, TRAFs and other proteins. Meprins comprise a class of extracellular metalloproteases which are anchored to the membrane and are capable of cleaving growth factors, extracellular matrix proteins, and biologically active peptides. TRAF molecules serve as adapter proteins that link cell surface receptors of the Tumor Necrosis Factor and 1nterleukin-1/Toll-like families to downstream kinase cascades, which results in the activation of transcription factors and the regulation of cell survival, proliferation and stress responses in the immune and inflammatory systems. Other members include the ubiquitin ligases, TRIM37 and SPOP, and the ubiquitin-specific proteases, HAUSP and Ubp21p. A large number of uncharacterized members mostly from lineage-specific expansions in C. elegans and rice contain MATH and BTB domains, similar to SPOP. The MATH domain has been shown to bind peptide/protein substrates in TRAFs and HAUSP. It is possible that the MATH domain in other members of this superfamily also interacts with various protein substrates. The TRAF domain may also be involved in the trimerization of TRAFs. Based on homology, it is postulated that the MATH domain in meprins may be involved in its tetramer assembly and that the MATH domain, in general, may take part in diverse modular arrangements defined by adjacent multimerization domains.


The actual alignment was detected with superfamily member cd03782:

Pssm-ID: 445786  Cd Length: 167  Bit Score: 287.91  E-value: 9.83e-94
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546 428 CPHHIWHIQNFTQILG--GQDTSVYSPPFYSSKGYAFQIYMDL----RSSTNVGIYFHLISGANDDQLQWPCPWQQATMT 501
Cdd:cd03782    1 CPEHIWHIRNFTQLLAttPPNGKIYSPPFLSSTGYSFQVGLYLngtdDYPGNLAIYLHLTSGPNDDQLQWPCPWQQATMM 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546 502 LLDQNPDIRQRMFNQRSITTDPTMTS-DNGSYFWDRPSKVGVTDVFPNGTQFSRGIGYGTTVFITRERLKSREFIKGDDI 580
Cdd:cd03782   81 LLDQHPDIRQRMSNQRSVTTDPNMTStDSDEYFWDDPRKVGSEVTDTDGSTFYRGPGYGTSAFITHLRLRSRDFIKGDDV 160


                 ....*..
gi 148664546 581 YILLTVE 587
Cdd:cd03782  161 IFLLTME 167
MAM pfam00629
MAM domain, meprin/A5/mu; An extracellular domain found in many receptors. The MAM domain ...
 266-429 6.47e-53

MAM domain, meprin/A5/mu; An extracellular domain found in many receptors. The MAM domain along with the associated Ig domain in type IIB receptor protein tyrosine phosphatases forms a structural unit (termed MIg) with a seamless interdomain interface. It plays a major role in homodimerization of the phosphatase ectoprotein and in cell adhesion. MAM is a beta-sandwich consisting of two five-stranded antiparallel beta-sheets rotated away from each other by approx 25 degrees, and plays a similar role in meprin metalloproteinases.


:

Pssm-ID: 459878 [Multi-domain]  Cd Length: 159  Bit Score: 179.87  E-value: 6.47e-53
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546  266 CDFELENICGMIQSSGDSADWQRVS--QVLSGPESDHSkmgQCKDSGFFMHFNTSILNEGATAMLESRLLYPKRGFQCLE 343
Cdd:pfam00629   1 CDFEDGNLCGWTQDSSDDFDWERVSgpSVKTGPSSDHT---QGTGSGHFMYVDTSSGAPGQTARLLSPLLPPSRSPQCLR 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546  344 FYLYNSGSGNDQLNIYTREYTTGQQggvlTLQRQIKEVPIGSWQLHYVTLQV-TKKFRVVFEGLRGPGtSSGGLSIDDIN 422
Cdd:pfam00629  78 FWYHMSGSGVGTLRVYVRENGGTLD----TLLWSISGDQGPSWKEARVTLSSsTQPFQVVFEGIRGGG-SRGGIALDDIS 152


                  ....*..
gi 148664546  423 LSETRCP 429
Cdd:pfam00629 153 LSSGPCP 159
EGF_CA cd00054
Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular ...
 609-647 6.18e-06

Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the N-terminus of particular EGF-like domains; calcium-binding may be crucial for numerous protein-protein interactions. Six conserved core cysteines form three disulfide bridges as in non calcium-binding EGF domains, whose structures are very similar. EGF_CA can be found in tandem repeat arrangements.


:

Pssm-ID: 238011  Cd Length: 38  Bit Score: 43.39  E-value: 6.18e-06
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 148664546 609 NACSEV-VCQNGGICVVQDGRAECKCPAGedwwYMGKRCE 647
Cdd:cd00054    3 DECASGnPCQNGGTCVNTVGSYRCSCPPG----YTGRNCE 38
 
Name Accession Description Interval E-value
ZnMc_meprin cd04282
Zinc-dependent metalloprotease, meprin_like subfamily. Meprins are membrane-bound or secreted ...
 30-256 9.75e-143

Zinc-dependent metalloprotease, meprin_like subfamily. Meprins are membrane-bound or secreted extracellular proteases, which cleave a variety of targets, including peptides such as parathyroid hormone, gastrin, and cholecystokinin, cytokines such as osteopontin, and proteins such as collagen IV, fibronectin, casein and gelatin. Meprins may also be able to release proteins from the cell surface. Closely related meprin alpha- and beta-subunits form homo- and hetero-oligomers; these complexes are found on epithelial cells of the intestine, for example, and are also expressed in certain cancer cells.


Pssm-ID: 239809 [Multi-domain]  Cd Length: 230  Bit Score: 416.49  E-value: 9.75e-143
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546  30 DIDGGIDQDIFDINQGLGLDLFEGDIKLE-ANGKNSIIGDHKRWPHTIPYVLEDSLEMNAKGVILNAFERYRLKTCIDFK 108
Cdd:cd04282    3 DADEGIDQDIFEINLGAGLDLFEGDILLDeGQSRNGLIGDTYRWPFPIPYILDDSLDLNAKGVILKAFEMYRLKSCVDFK 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546 109 PWSGEANYISVFKGSGCWSSVGNIHaGKQELSIGTNCDRIATVQHEFLHALGFWHEQSRADRDDYVIIVWDRIQPGKEHN 188
Cdd:cd04282   83 PYEGESNYIFFFKGSGCWSMVGDQQ-GGQNLSIGAGCDYKATVEHEFLHALGFYHEQSRSDRDDYVKIWWDQILSGREHN 161

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 148664546 189 FNIYNDSVSDSLNVPYDYTSVMHYSKTAFQNG-TESTIVTRISEFEDVIGQRMDFSDYDLLKLNQLYNC 256
Cdd:cd04282  162 FNKYDDSFSTDLNTPYDYESVMHYSPFSFNKGaSEPTITTKIPEFNDIIGQRLDFSDIDLERLNRMYNC 230
MATH_Meprin_Beta cd03782
Meprin family, Beta subunit, MATH domain; Meprins are multidomain extracellular ...
 428-587 9.83e-94

Meprin family, Beta subunit, MATH domain; Meprins are multidomain extracellular metalloproteases capable of cleaving growth factors, cytokines, extracellular matrix proteins, and biologically active peptides. They are composed of two related subunits, alpha and beta, which form homo- or hetro-complexes where the basic unit is a disulfide-linked dimer. The beta subunit is a type I membrane protein, which forms homodimers or heterotetramers (alpha2beta2 or alpha3beta). Meprin beta shows preference for acidic residues at the P1 and P1' sites of its substrate. Among its best substrates are growth factors and chemokines such as gastrin and osteopontin. Both alpha and beta subunits contain a catalytic astacin (M12 family) protease domain followed by the adhesion or interaction domains MAM, MATH and AM. The MATH and MAM domains provide symmetrical intersubunit disulfide bonds necessary for the dimerization of meprin subunits. The MATH domain may also be required for folding of an activable zymogen.


Pssm-ID: 239751  Cd Length: 167  Bit Score: 287.91  E-value: 9.83e-94
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546 428 CPHHIWHIQNFTQILG--GQDTSVYSPPFYSSKGYAFQIYMDL----RSSTNVGIYFHLISGANDDQLQWPCPWQQATMT 501
Cdd:cd03782    1 CPEHIWHIRNFTQLLAttPPNGKIYSPPFLSSTGYSFQVGLYLngtdDYPGNLAIYLHLTSGPNDDQLQWPCPWQQATMM 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546 502 LLDQNPDIRQRMFNQRSITTDPTMTS-DNGSYFWDRPSKVGVTDVFPNGTQFSRGIGYGTTVFITRERLKSREFIKGDDI 580
Cdd:cd03782   81 LLDQHPDIRQRMSNQRSVTTDPNMTStDSDEYFWDDPRKVGSEVTDTDGSTFYRGPGYGTSAFITHLRLRSRDFIKGDDV 160


                 ....*..
gi 148664546 581 YILLTVE 587
Cdd:cd03782  161 IFLLTME 167
Astacin pfam01400
Astacin (Peptidase family M12A); The members of this family are enzymes that cleave peptides. ...
 70-258 1.07e-91

Astacin (Peptidase family M12A); The members of this family are enzymes that cleave peptides. These proteases require zinc for catalysis. Members of this family contain two conserved disulphide bridges, these are joined 1-4 and 2-3. Members of this family have an amino terminal propeptide which is cleaved to give the active protease domain. All other linked domains are found to the carboxyl terminus of this domain. This family includes: Astacin, a digestive enzyme from Crayfish. Meprin, a multiple domain membrane component that is constructed from a homologous alpha and beta chain. Proteins involved in morphogenesis such as Swiss:P13497, and Tolloid from drosophila.


Pssm-ID: 426242 [Multi-domain]  Cd Length: 192  Bit Score: 283.40  E-value: 1.07e-91
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546   70 KRWPHT-IPYVLEDSLEMNAKGVILNAFERYRLKTCIDFKPWSGEA--NYISVFKGSGCWSSVGNIHaGKQELSIGTNCD 146
Cdd:pfam01400   1 KKWPNGpIPYVIDGSLTGLARALIRQAMRHWENKTCIRFVERTPAPdnNYLFFFKGDGCYSYVGRVG-GRQPVSIGDGCD 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546  147 RIATVQHEFLHALGFWHEQSRADRDDYVIIVWDRIQPGKEHNFNIYNDSVSDSLNVPYDYTSVMHYSKTAF-QNGTESTI 225
Cdd:pfam01400  80 KFGIIVHELGHALGFFHEQSRPDRDDYVSINWDNIDPGQEGNFDKYDPSEVDSYGVPYDYGSIMHYGPNAFsKNGSLPTI 159

                         170       180       190
                  ....*....|....*....|....*....|...
gi 148664546  226 VTRISEFEDVIGQRMDFSDYDLLKLNQLYNCTS 258
Cdd:pfam01400 160 VPKDNDYQATIGQRVKLSFYDIKKINKLYKCPS 192
MAM pfam00629
MAM domain, meprin/A5/mu; An extracellular domain found in many receptors. The MAM domain ...
 266-429 6.47e-53

MAM domain, meprin/A5/mu; An extracellular domain found in many receptors. The MAM domain along with the associated Ig domain in type IIB receptor protein tyrosine phosphatases forms a structural unit (termed MIg) with a seamless interdomain interface. It plays a major role in homodimerization of the phosphatase ectoprotein and in cell adhesion. MAM is a beta-sandwich consisting of two five-stranded antiparallel beta-sheets rotated away from each other by approx 25 degrees, and plays a similar role in meprin metalloproteinases.


Pssm-ID: 459878 [Multi-domain]  Cd Length: 159  Bit Score: 179.87  E-value: 6.47e-53
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546  266 CDFELENICGMIQSSGDSADWQRVS--QVLSGPESDHSkmgQCKDSGFFMHFNTSILNEGATAMLESRLLYPKRGFQCLE 343
Cdd:pfam00629   1 CDFEDGNLCGWTQDSSDDFDWERVSgpSVKTGPSSDHT---QGTGSGHFMYVDTSSGAPGQTARLLSPLLPPSRSPQCLR 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546  344 FYLYNSGSGNDQLNIYTREYTTGQQggvlTLQRQIKEVPIGSWQLHYVTLQV-TKKFRVVFEGLRGPGtSSGGLSIDDIN 422
Cdd:pfam00629  78 FWYHMSGSGVGTLRVYVRENGGTLD----TLLWSISGDQGPSWKEARVTLSSsTQPFQVVFEGIRGGG-SRGGIALDDIS 152


                  ....*..
gi 148664546  423 LSETRCP 429
Cdd:pfam00629 153 LSSGPCP 159
MAM smart00137
Domain in meprin, A5, receptor protein tyrosine phosphatase mu (and others); Likely to have an ...
 261-428 9.46e-46

Domain in meprin, A5, receptor protein tyrosine phosphatase mu (and others); Likely to have an adhesive function. Mutations in the meprin MAM domain affect noncovalent associations within meprin oligomers. In receptor tyrosine phosphatase mu-like molecules the MAM domain is important for homophilic cell-cell interactions.


Pssm-ID: 214533 [Multi-domain]  Cd Length: 161  Bit Score: 160.20  E-value: 9.46e-46
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546   261 SFMDSCDFELENICGMIQSSGDSADWQRVSqvlSGPESDHSKMGQCKDSGFFMHFNTSILNEGATAMLESRLLYPKRGFQ 340
Cdd:smart00137   1 TSPGNCDFEEGSTCGWHQDSNDDGHWERVS---SATGIPGPNRDHTTGNGHFMFFETSSGAEGQTARLLSPPLYENRSTH 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546   341 CLEFYLYNSGSGNDQLNIYTREYTTGQQggvlTLQRQIKEVPIGSWQLHYVTLQ-VTKKFRVVFEGLRGPGtSSGGLSID 419
Cdd:smart00137  78 CLTFWYYMYGSGSGTLNVYVRENNGSQD----TLLWSRSGTQGGQWLQAEVALSsWPQPFQVVFEGTRGKG-HSGYIALD 152


                   ....*....
gi 148664546   420 DINLSETRC 428
Cdd:smart00137 153 DILLSNGPC 161
MAM cd06263
Meprin, A5 protein, and protein tyrosine phosphatase Mu (MAM) domain. MAM is an extracellular ...
 266-428 4.16e-41

Meprin, A5 protein, and protein tyrosine phosphatase Mu (MAM) domain. MAM is an extracellular domain which mediates protein-protein interactions and is found in a diverse set of proteins, many of which are known to function in cell adhesion. Members include: type IIB receptor protein tyrosine phosphatases (such as RPTPmu), meprins (plasma membrane metalloproteases), neuropilins (receptors of secreted semaphorins), and zonadhesins (sperm-specific membrane proteins which bind to the extracellular matrix of the egg). In meprin A and neuropilin-1 and -2, MAM is involved in homo-oligomerization. In RPTPmu, it has been associated with both homophilic adhesive (trans) interactions and lateral (cis) receptor oligomerization. In a GPI-anchored protein that is expressed in cells in the embryonic chicken spinal chord, MDGA1, the MAM domain has been linked to heterophilic interactions with axon-rich region.


Pssm-ID: 99706  Cd Length: 157  Bit Score: 147.14  E-value: 4.16e-41
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546 266 CDFElENICGMIQSSGDSADWQRVSQVlSGPESDHSKMGQCKDSGFFMHFNTSILNEGATAMLESRLLYPKRGFQCLEFY 345
Cdd:cd06263    1 CDFE-DGLCGWTQDSTDDFDWTRVSGS-TPSPGTPPDHTHGTGSGHYLYVESSSGREGQKARLLSPLLPPPRSSHCLSFW 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546 346 LYNSGSGNDQLNIYTREYTTGQQggvlTLQRQIKEVPIGSWQLHYVTLQ-VTKKFRVVFEGLRGPGtSSGGLSIDDINLS 424
Cdd:cd06263   79 YHMYGSGVGTLNVYVREEGGGLG----TLLWSASGGQGNQWQEAEVTLSaSSKPFQVVFEGVRGSG-SRGDIALDDISLS 153


                 ....
gi 148664546 425 ETRC 428
Cdd:cd06263  154 PGPC 157
ZnMc smart00235
Zinc-dependent metalloprotease; Neutral zinc metallopeptidases. This alignment represents a ...
 69-208 7.63e-40

Zinc-dependent metalloprotease; Neutral zinc metallopeptidases. This alignment represents a subset of known subfamilies. Highest similarity occurs in the HExxH zinc-binding site/ active site.


Pssm-ID: 214576 [Multi-domain]  Cd Length: 139  Bit Score: 142.87  E-value: 7.63e-40
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546    69 HKRWPH-TIPYVLEDS-LEMNAKGVILNAFERYRLKTCIDFKPWSGEA-NYISVFKG-SGCWSSVGNIHAGKQELSIGTN 144
Cdd:smart00235   2 SKKWPKgTVPYVIDSSsLSPEEREAIAKALAEWSDVTCIRFVERTGTAdIYISFGSGdSGCTLSHAGRPGGDQHLSLGNG 81

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 148664546   145 CDRIATVQHEFLHALGFWHEQSRADRDDYVIIVWDRIQpgkEHNFNIYNDsvsDSLNVPYDYTS 208
Cdd:smart00235  82 CINTGVAAHELGHALGLYHEQSRSDRDNYMYINYTNID---TRNFDLSED---DSLGIPYDYGS 139
EGF_CA cd00054
Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular ...
 609-647 6.18e-06

Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the N-terminus of particular EGF-like domains; calcium-binding may be crucial for numerous protein-protein interactions. Six conserved core cysteines form three disulfide bridges as in non calcium-binding EGF domains, whose structures are very similar. EGF_CA can be found in tandem repeat arrangements.


Pssm-ID: 238011  Cd Length: 38  Bit Score: 43.39  E-value: 6.18e-06
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 148664546 609 NACSEV-VCQNGGICVVQDGRAECKCPAGedwwYMGKRCE 647
Cdd:cd00054    3 DECASGnPCQNGGTCVNTVGSYRCSCPPG----YTGRNCE 38
MATH smart00061
meprin and TRAF homology;
433-512 1.56e-05

meprin and TRAF homology;


Pssm-ID: 214496 [Multi-domain]  Cd Length: 95  Bit Score: 43.83  E-value: 1.56e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546   433 WHIQNFTQILG-GQDTSVYSPPFYSSK-GYAFQIYmdlRSSTNVGIYFHLISGANDDqLQWPCpWQQATMTLLDQNPDIR 510
Cdd:smart00061   1 VLSHTFKNVSRlEEGESYFSPSEEHFNiPWRLKIY---RKNGFLSLYLHCEKEECDS-RKWSI-EAEFTLKLVSQNGKSL 75


                   ..
gi 148664546   511 QR 512
Cdd:smart00061  76 SK 77
EGF_CA smart00179
Calcium-binding EGF-like domain;
609-647 1.93e-04

Calcium-binding EGF-like domain;


Pssm-ID: 214542 [Multi-domain]  Cd Length: 39  Bit Score: 39.15  E-value: 1.93e-04
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 148664546   609 NACSEV-VCQNGGICVVQDGRAECKCPAGedwWYMGKRCE 647
Cdd:smart00179   3 DECASGnPCQNGGTCVNTVGSYRCECPPG---YTDGRNCE 39
hEGF pfam12661
Human growth factor-like EGF; hEGF, or human growth factor-like EGF, domains have six ...
 616-636 7.84e-04

Human growth factor-like EGF; hEGF, or human growth factor-like EGF, domains have six conserved residues disulfide-bonded into the characteriztic 'ababcc' pattern. They are involved in growth and proliferation of cells, in proteins of the Notch/Delta pathway, neurogulin and selectins. hEGFs are also found in mosaic proteins with four-disulfide laminin EGFs such as aggrecan and perlecan. The core fold of the EGF domain consists of two small beta-hairpins packed against each other. Two major structural variants have been identified based on the structural context of the C-terminal Cys residue of disulfide 'c' in the C-terminal hairpin: hEGFs and cEGFs. In hEGFs the C-terminal thiol resides in the beta-turn, resulting in shorter loop-lengths between the Cys residues of disulfide 'c', typically C[8-9]XC. These shorter loop-lengths are also typical of the four-disulfide EGF domains, laminin ad integrin. Tandem hEGF domains have six linking residues between terminal cysteines of adjacent domains. hEGF domains may or may not bind calcium in the linker region. hEGF domains with the consensus motif CXD4X[F,Y]XCXC are hydroxylated exclusively in the Asp residue.


Pssm-ID: 463660  Cd Length: 22  Bit Score: 37.31  E-value: 7.84e-04
                          10        20
                  ....*....|....*....|.
gi 148664546  616 CQNGGICVVQDGRAECKCPAG 636
Cdd:pfam12661   1 CQNGGTCVDGVNGYKCQCPPG 21
 
Name Accession Description Interval E-value
ZnMc_meprin cd04282
Zinc-dependent metalloprotease, meprin_like subfamily. Meprins are membrane-bound or secreted ...
 30-256 9.75e-143

Zinc-dependent metalloprotease, meprin_like subfamily. Meprins are membrane-bound or secreted extracellular proteases, which cleave a variety of targets, including peptides such as parathyroid hormone, gastrin, and cholecystokinin, cytokines such as osteopontin, and proteins such as collagen IV, fibronectin, casein and gelatin. Meprins may also be able to release proteins from the cell surface. Closely related meprin alpha- and beta-subunits form homo- and hetero-oligomers; these complexes are found on epithelial cells of the intestine, for example, and are also expressed in certain cancer cells.


Pssm-ID: 239809 [Multi-domain]  Cd Length: 230  Bit Score: 416.49  E-value: 9.75e-143
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546  30 DIDGGIDQDIFDINQGLGLDLFEGDIKLE-ANGKNSIIGDHKRWPHTIPYVLEDSLEMNAKGVILNAFERYRLKTCIDFK 108
Cdd:cd04282    3 DADEGIDQDIFEINLGAGLDLFEGDILLDeGQSRNGLIGDTYRWPFPIPYILDDSLDLNAKGVILKAFEMYRLKSCVDFK 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546 109 PWSGEANYISVFKGSGCWSSVGNIHaGKQELSIGTNCDRIATVQHEFLHALGFWHEQSRADRDDYVIIVWDRIQPGKEHN 188
Cdd:cd04282   83 PYEGESNYIFFFKGSGCWSMVGDQQ-GGQNLSIGAGCDYKATVEHEFLHALGFYHEQSRSDRDDYVKIWWDQILSGREHN 161

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 148664546 189 FNIYNDSVSDSLNVPYDYTSVMHYSKTAFQNG-TESTIVTRISEFEDVIGQRMDFSDYDLLKLNQLYNC 256
Cdd:cd04282  162 FNKYDDSFSTDLNTPYDYESVMHYSPFSFNKGaSEPTITTKIPEFNDIIGQRLDFSDIDLERLNRMYNC 230
MATH_Meprin_Beta cd03782
Meprin family, Beta subunit, MATH domain; Meprins are multidomain extracellular ...
 428-587 9.83e-94

Meprin family, Beta subunit, MATH domain; Meprins are multidomain extracellular metalloproteases capable of cleaving growth factors, cytokines, extracellular matrix proteins, and biologically active peptides. They are composed of two related subunits, alpha and beta, which form homo- or hetro-complexes where the basic unit is a disulfide-linked dimer. The beta subunit is a type I membrane protein, which forms homodimers or heterotetramers (alpha2beta2 or alpha3beta). Meprin beta shows preference for acidic residues at the P1 and P1' sites of its substrate. Among its best substrates are growth factors and chemokines such as gastrin and osteopontin. Both alpha and beta subunits contain a catalytic astacin (M12 family) protease domain followed by the adhesion or interaction domains MAM, MATH and AM. The MATH and MAM domains provide symmetrical intersubunit disulfide bonds necessary for the dimerization of meprin subunits. The MATH domain may also be required for folding of an activable zymogen.


Pssm-ID: 239751  Cd Length: 167  Bit Score: 287.91  E-value: 9.83e-94
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546 428 CPHHIWHIQNFTQILG--GQDTSVYSPPFYSSKGYAFQIYMDL----RSSTNVGIYFHLISGANDDQLQWPCPWQQATMT 501
Cdd:cd03782    1 CPEHIWHIRNFTQLLAttPPNGKIYSPPFLSSTGYSFQVGLYLngtdDYPGNLAIYLHLTSGPNDDQLQWPCPWQQATMM 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546 502 LLDQNPDIRQRMFNQRSITTDPTMTS-DNGSYFWDRPSKVGVTDVFPNGTQFSRGIGYGTTVFITRERLKSREFIKGDDI 580
Cdd:cd03782   81 LLDQHPDIRQRMSNQRSVTTDPNMTStDSDEYFWDDPRKVGSEVTDTDGSTFYRGPGYGTSAFITHLRLRSRDFIKGDDV 160


                 ....*..
gi 148664546 581 YILLTVE 587
Cdd:cd03782  161 IFLLTME 167
Astacin pfam01400
Astacin (Peptidase family M12A); The members of this family are enzymes that cleave peptides. ...
 70-258 1.07e-91

Astacin (Peptidase family M12A); The members of this family are enzymes that cleave peptides. These proteases require zinc for catalysis. Members of this family contain two conserved disulphide bridges, these are joined 1-4 and 2-3. Members of this family have an amino terminal propeptide which is cleaved to give the active protease domain. All other linked domains are found to the carboxyl terminus of this domain. This family includes: Astacin, a digestive enzyme from Crayfish. Meprin, a multiple domain membrane component that is constructed from a homologous alpha and beta chain. Proteins involved in morphogenesis such as Swiss:P13497, and Tolloid from drosophila.


Pssm-ID: 426242 [Multi-domain]  Cd Length: 192  Bit Score: 283.40  E-value: 1.07e-91
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546   70 KRWPHT-IPYVLEDSLEMNAKGVILNAFERYRLKTCIDFKPWSGEA--NYISVFKGSGCWSSVGNIHaGKQELSIGTNCD 146
Cdd:pfam01400   1 KKWPNGpIPYVIDGSLTGLARALIRQAMRHWENKTCIRFVERTPAPdnNYLFFFKGDGCYSYVGRVG-GRQPVSIGDGCD 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546  147 RIATVQHEFLHALGFWHEQSRADRDDYVIIVWDRIQPGKEHNFNIYNDSVSDSLNVPYDYTSVMHYSKTAF-QNGTESTI 225
Cdd:pfam01400  80 KFGIIVHELGHALGFFHEQSRPDRDDYVSINWDNIDPGQEGNFDKYDPSEVDSYGVPYDYGSIMHYGPNAFsKNGSLPTI 159

                         170       180       190
                  ....*....|....*....|....*....|...
gi 148664546  226 VTRISEFEDVIGQRMDFSDYDLLKLNQLYNCTS 258
Cdd:pfam01400 160 VPKDNDYQATIGQRVKLSFYDIKKINKLYKCPS 192
MATH_Meprin cd03771
Meprin family, MATH domain; Meprins are multidomain, highly glycosylated extracellular ...
 428-587 3.88e-87

Meprin family, MATH domain; Meprins are multidomain, highly glycosylated extracellular metalloproteases, which are either anchored to the membrane or secreted into extracellular spaces. They are expressed in renal and intestinal brush border membranes, leukocytes, and cancer cells, and are capable of cleaving growth factors, cytokines, extracellular matrix proteins, and biologically active peptides. Meprin proteases are composed of two related subunits, alpha and beta, which form homo- or hetro-complexes where the basic unit is a disulfide-linked dimer. Despite their similarity, the two subunits differ in their ability to self-associate, in proteolytic processing during biosynthesis and in substrate specificity. Both subunits are synthesized as membrane spanning proteins, however, the alpha subunit is cleaved during biosynthesis and loses its transmembrane domain. Meprin beta forms homodimers or heterotetramers while meprin alpha oligomerizes into large complexes containing 10-100 subunits. Both alpha and beta subunits contain a catalytic astacin (M12 family) protease domain followed by the adhesion or interaction domains MAM, MATH and AM. The MATH and MAM domains provide symmetrical intersubunit disulfide bonds necessary for the dimerization of meprin subunits. The MATH domain may also be required for folding of an activable zymogen.


Pssm-ID: 239740  Cd Length: 167  Bit Score: 270.42  E-value: 3.88e-87
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546 428 CPHHIWHIQNFTQIL--GGQDTSVYSPPFYSSKGYAFQIYMDLRS----STNVGIYFHLISGANDDQLQWPCPWQQATMT 501
Cdd:cd03771    1 CPEAVWRVRNFSQLLetTPKGTKIYSPRFYSPEGYAFQVGLYPNGtesyPGYTGLYFHLCSGENDDVLEWPCPNRQATMT 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546 502 LLDQNPDIRQRMFNQRSITTDPTMTS-DNGSYFWDRPSKVGVTDVFPNGTQFSRGIGYGTTVFITRERLKSREFIKGDDI 580
Cdd:cd03771   81 LLDQDPDIQQRMSNQRSFTTDPSMTSsDNGEYFWDRPSKVGSYDTDTNGCTCYRGPGYGWSTFISHSRLRRRDFLKGDDL 160


                 ....*..
gi 148664546 581 YILLTVE 587
Cdd:cd03771  161 IILLDFE 167
ZnMc_astacin_like cd04280
Zinc-dependent metalloprotease, astacin_like subfamily or peptidase family M12A, a group of ...
 75-254 4.97e-81

Zinc-dependent metalloprotease, astacin_like subfamily or peptidase family M12A, a group of zinc-dependent proteolytic enzymes with a HExxH zinc-binding site/active site. Members of this family may have an amino terminal propeptide, which is cleaved to yield the active protease domain, which is consequently always found at the N-terminus in multi-domain architectures. This family includes: astacin, a digestive enzyme from Crayfish; meprin, a multiple domain membrane component that is constructed from a homologous alpha and beta chain, proteins involved in (bone) morphogenesis, tolloid from drosophila, and the sea urchin SPAN protein, which may also play a role in development.


Pssm-ID: 239807 [Multi-domain]  Cd Length: 180  Bit Score: 255.19  E-value: 4.97e-81
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546  75 TIPYVLEDSLEMNAKGVILNAFERYRLKTCIDFKPWSGEANYISVFKGSGCWSSVGNIHaGKQELSIGTNCDRIATVQHE 154
Cdd:cd04280    3 TVPYVIDGSFDESDRSLILRAMREIESNTCIRFVPRTTEKDYIRIVKGSGCWSYVGRVG-GRQVVSLGSGCFSLGTIVHE 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546 155 FLHALGFWHEQSRADRDDYVIIVWDRIQPGKEHNFNIYNDSVSDSLNVPYDYTSVMHYSKTAFQNGTESTIVTRISEFED 234
Cdd:cd04280   82 LMHALGFYHEQSRPDRDDYVTINWENIQPGYEHNFDKYSPDTVTTYGVPYDYGSVMHYGPTAFSKNGKPTIVPKDPGYQI 161

                        170       180
                 ....*....|....*....|
gi 148664546 235 vIGQRMDFSDYDLLKLNQLY 254
Cdd:cd04280  162 -IGQREGLSFLDIKKINKMY 180
ZnMc_hatching_enzyme cd04283
Zinc-dependent metalloprotease, hatching enzyme-like subfamily. Hatching enzymes are secreted ...
 76-256 7.12e-63

Zinc-dependent metalloprotease, hatching enzyme-like subfamily. Hatching enzymes are secreted by teleost embryos to digest the egg envelope or chorion. In some teleosts, the hatching enzyme may be a system consisting of two evolutionary related metalloproteases, high choriolytic enzyme and low choriolytic enzyme (HCE and LCE), which may have different substrate specificities and cooperatively digest the chorion.


Pssm-ID: 239810 [Multi-domain]  Cd Length: 182  Bit Score: 207.11  E-value: 7.12e-63
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546  76 IPYVLEDSLEMNAKGVILNAFERYRLKTCIDFKPWSGEANYISVFKGSGCWSSVGNIhAGKQELSIGTN-CDRIATVQHE 154
Cdd:cd04283    6 VPYVISPQYSENERAVIEKAMQEFETLTCVRFVPRTTERDYLNIESRSGCWSYIGRQ-GGRQTVSLQKQgCMYKGIIQHE 84

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546 155 FLHALGFWHEQSRADRDDYVIIVWDRIQPGKEHNFNIYNdsvSDSLNVPYDYTSVMHYSKTAFQNGTESTIVTrISEFED 234
Cdd:cd04283   85 LLHALGFYHEQTRSDRDKYVRINWENIIPDQLYNFDKQD---TNNLGTPYDYSSVMHYGRYAFSINGKPTIVP-IPDPNV 160

                        170       180
                 ....*....|....*....|..
gi 148664546 235 VIGQRMDFSDYDLLKLNQLYNC 256
Cdd:cd04283  161 PIGQRQGMSNLDILRINKLYNC 182
MAM pfam00629
MAM domain, meprin/A5/mu; An extracellular domain found in many receptors. The MAM domain ...
 266-429 6.47e-53

MAM domain, meprin/A5/mu; An extracellular domain found in many receptors. The MAM domain along with the associated Ig domain in type IIB receptor protein tyrosine phosphatases forms a structural unit (termed MIg) with a seamless interdomain interface. It plays a major role in homodimerization of the phosphatase ectoprotein and in cell adhesion. MAM is a beta-sandwich consisting of two five-stranded antiparallel beta-sheets rotated away from each other by approx 25 degrees, and plays a similar role in meprin metalloproteinases.


Pssm-ID: 459878 [Multi-domain]  Cd Length: 159  Bit Score: 179.87  E-value: 6.47e-53
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546  266 CDFELENICGMIQSSGDSADWQRVS--QVLSGPESDHSkmgQCKDSGFFMHFNTSILNEGATAMLESRLLYPKRGFQCLE 343
Cdd:pfam00629   1 CDFEDGNLCGWTQDSSDDFDWERVSgpSVKTGPSSDHT---QGTGSGHFMYVDTSSGAPGQTARLLSPLLPPSRSPQCLR 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546  344 FYLYNSGSGNDQLNIYTREYTTGQQggvlTLQRQIKEVPIGSWQLHYVTLQV-TKKFRVVFEGLRGPGtSSGGLSIDDIN 422
Cdd:pfam00629  78 FWYHMSGSGVGTLRVYVRENGGTLD----TLLWSISGDQGPSWKEARVTLSSsTQPFQVVFEGIRGGG-SRGGIALDDIS 152


                  ....*..
gi 148664546  423 LSETRCP 429
Cdd:pfam00629 153 LSSGPCP 159
MAM smart00137
Domain in meprin, A5, receptor protein tyrosine phosphatase mu (and others); Likely to have an ...
 261-428 9.46e-46

Domain in meprin, A5, receptor protein tyrosine phosphatase mu (and others); Likely to have an adhesive function. Mutations in the meprin MAM domain affect noncovalent associations within meprin oligomers. In receptor tyrosine phosphatase mu-like molecules the MAM domain is important for homophilic cell-cell interactions.


Pssm-ID: 214533 [Multi-domain]  Cd Length: 161  Bit Score: 160.20  E-value: 9.46e-46
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546   261 SFMDSCDFELENICGMIQSSGDSADWQRVSqvlSGPESDHSKMGQCKDSGFFMHFNTSILNEGATAMLESRLLYPKRGFQ 340
Cdd:smart00137   1 TSPGNCDFEEGSTCGWHQDSNDDGHWERVS---SATGIPGPNRDHTTGNGHFMFFETSSGAEGQTARLLSPPLYENRSTH 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546   341 CLEFYLYNSGSGNDQLNIYTREYTTGQQggvlTLQRQIKEVPIGSWQLHYVTLQ-VTKKFRVVFEGLRGPGtSSGGLSID 419
Cdd:smart00137  78 CLTFWYYMYGSGSGTLNVYVRENNGSQD----TLLWSRSGTQGGQWLQAEVALSsWPQPFQVVFEGTRGKG-HSGYIALD 152


                   ....*....
gi 148664546   420 DINLSETRC 428
Cdd:smart00137 153 DILLSNGPC 161
ZnMc_BMP1_TLD cd04281
Zinc-dependent metalloprotease; BMP1/TLD-like subfamily. BMP1 (Bone morphogenetic protein 1) ...
 70-256 3.19e-44

Zinc-dependent metalloprotease; BMP1/TLD-like subfamily. BMP1 (Bone morphogenetic protein 1) and TLD (tolloid)-like metalloproteases play vital roles in extracellular matrix formation, by cleaving precursor proteins such as enzymes, structural proteins, and proteins involved in the mineralization of the extracellular matrix. The drosophila protein tolloid and its Xenopus homologue xolloid cleave and inactivate Sog and chordin, respectively, which are inhibitors of Dpp (the Drosophila decapentaplegic gene product) and its homologue BMP4, involved in dorso-ventral patterning.


Pssm-ID: 239808 [Multi-domain]  Cd Length: 200  Bit Score: 157.60  E-value: 3.19e-44
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546  70 KRWPH-TIPYVLEDSLEMNAKGVILNAFERYRLKTCIDFKPWSGEANYIsVF--KGSGCWSSVGNIHAGKQELSIGTNCD 146
Cdd:cd04281    8 RIWPGgVIPYVIDGNFTGSQRAMFKQAMRHWENFTCVTFVERTPEENYI-VFtyRPCGCCSYVGRRGNGPQAISIGKNCD 86

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546 147 RIATVQHEFLHALGFWHEQSRADRDDYVIIVWDRIQPGKEHNFNIYNDSVSDSLNVPYDYTSVMHYSKTAFQNGTE-STI 225
Cdd:cd04281   87 KFGIVVHELGHVIGFWHEHTRPDRDDHVTIIRENIQPGQEYNFLKMEPEEVDSLGEPYDFDSIMHYARNTFSRGMFlDTI 166

                        170       180       190
                 ....*....|....*....|....*....|...
gi 148664546 226 VTRISEFEDV--IGQRMDFSDYDLLKLNQLYNC 256
Cdd:cd04281  167 LPKRDPNGVRpeIGQRTRLSEGDIIQANKLYKC 199
MAM cd06263
Meprin, A5 protein, and protein tyrosine phosphatase Mu (MAM) domain. MAM is an extracellular ...
 266-428 4.16e-41

Meprin, A5 protein, and protein tyrosine phosphatase Mu (MAM) domain. MAM is an extracellular domain which mediates protein-protein interactions and is found in a diverse set of proteins, many of which are known to function in cell adhesion. Members include: type IIB receptor protein tyrosine phosphatases (such as RPTPmu), meprins (plasma membrane metalloproteases), neuropilins (receptors of secreted semaphorins), and zonadhesins (sperm-specific membrane proteins which bind to the extracellular matrix of the egg). In meprin A and neuropilin-1 and -2, MAM is involved in homo-oligomerization. In RPTPmu, it has been associated with both homophilic adhesive (trans) interactions and lateral (cis) receptor oligomerization. In a GPI-anchored protein that is expressed in cells in the embryonic chicken spinal chord, MDGA1, the MAM domain has been linked to heterophilic interactions with axon-rich region.


Pssm-ID: 99706  Cd Length: 157  Bit Score: 147.14  E-value: 4.16e-41
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546 266 CDFElENICGMIQSSGDSADWQRVSQVlSGPESDHSKMGQCKDSGFFMHFNTSILNEGATAMLESRLLYPKRGFQCLEFY 345
Cdd:cd06263    1 CDFE-DGLCGWTQDSTDDFDWTRVSGS-TPSPGTPPDHTHGTGSGHYLYVESSSGREGQKARLLSPLLPPPRSSHCLSFW 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546 346 LYNSGSGNDQLNIYTREYTTGQQggvlTLQRQIKEVPIGSWQLHYVTLQ-VTKKFRVVFEGLRGPGtSSGGLSIDDINLS 424
Cdd:cd06263   79 YHMYGSGVGTLNVYVREEGGGLG----TLLWSASGGQGNQWQEAEVTLSaSSKPFQVVFEGVRGSG-SRGDIALDDISLS 153


                 ....
gi 148664546 425 ETRC 428
Cdd:cd06263  154 PGPC 157
MATH_Meprin_Alpha cd03783
Meprin family, Alpha subunit, MATH domain; Meprins are multidomain extracellular ...
 428-587 1.88e-40

Meprin family, Alpha subunit, MATH domain; Meprins are multidomain extracellular metalloproteases capable of cleaving growth factors, cytokines, extracellular matrix proteins, and biologically active peptides. They are composed of two related subunits, alpha and beta, which form homo- or hetro-complexes where the basic unit is a disulfide-linked dimer. The alpha subunit is synthesized as a membrane spanning protein, however, it is cleaved during biosynthesis and loses its transmembrane domain. It oligomerizes into large complexes, containing 10-100 subunits (dimers that associate noncovalently), which are secreted as latent proteases and can move through extracellular spaces in a nondestructive manner. This allows delivery of the concentrated protease to sites containing activating enzymes, such as sites of inflammation, infection or cancerous growth. Meprin alpha shows preference for small or hydrophobic residues at the P1 and P1' sites of its substrate. Both alpha and beta subunits contain a catalytic astacin (M12 family) protease domain followed by the adhesion or interaction domains MAM, MATH and AM. The MATH and MAM domains provide symmetrical intersubunit disulfide bonds necessary for the dimerization of meprin subunits. The MATH domain may also be required for folding of an activable zymogen.


Pssm-ID: 239752  Cd Length: 167  Bit Score: 145.78  E-value: 1.88e-40
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546 428 CPHHIWHIQNFTQIL--GGQDTSVYSPPFYSSKGYAFQIYM------DLRSSTNVGIYFHLISGANDDQLQWPCPWQQAT 499
Cdd:cd03783    1 CPNAVWRVRNFSQILenTTKGDVLQSPRFYSPEGYGYGVSLyplsneSDYSGNYTGLYFHLCSGENDAVLEWPALNRQAI 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546 500 MTLLDQNPDIRQRMFNQRSITTDPTMTSD--NGSYFWDRPSKVGVTDVFPNgtqFSRGIGYGTTVFITRERLKSREFIKG 577
Cdd:cd03783   81 ITVLDQDPDVRLRMSSSRSFTTDKSQTSSaiNGTLRWDRPSRVGTYDTSCD---CFRGIDFGWSTFISHSQLRRRSFLKN 157

                        170
                 ....*....|
gi 148664546 578 DDIYILLTVE 587
Cdd:cd03783  158 DDLIIFVDFE 167
ZnMc smart00235
Zinc-dependent metalloprotease; Neutral zinc metallopeptidases. This alignment represents a ...
 69-208 7.63e-40

Zinc-dependent metalloprotease; Neutral zinc metallopeptidases. This alignment represents a subset of known subfamilies. Highest similarity occurs in the HExxH zinc-binding site/ active site.


Pssm-ID: 214576 [Multi-domain]  Cd Length: 139  Bit Score: 142.87  E-value: 7.63e-40
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546    69 HKRWPH-TIPYVLEDS-LEMNAKGVILNAFERYRLKTCIDFKPWSGEA-NYISVFKG-SGCWSSVGNIHAGKQELSIGTN 144
Cdd:smart00235   2 SKKWPKgTVPYVIDSSsLSPEEREAIAKALAEWSDVTCIRFVERTGTAdIYISFGSGdSGCTLSHAGRPGGDQHLSLGNG 81

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 148664546   145 CDRIATVQHEFLHALGFWHEQSRADRDDYVIIVWDRIQpgkEHNFNIYNDsvsDSLNVPYDYTS 208
Cdd:smart00235  82 CINTGVAAHELGHALGLYHEQSRSDRDNYMYINYTNID---TRNFDLSED---DSLGIPYDYGS 139
MATH_TRAF_C cd00270
Tumor Necrosis Factor Receptor (TNFR)-Associated Factor (TRAF) family, TRAF domain, C-terminal ...
 430-582 5.92e-23

Tumor Necrosis Factor Receptor (TNFR)-Associated Factor (TRAF) family, TRAF domain, C-terminal MATH subdomain; TRAF molecules serve as adapter proteins that link cell surface TNFRs and receptors of the interleukin-1/Toll-like family to downstream kinase signaling cascades which results in the activation of transcription factors and the regulation of cell survival, proliferation and stress responses in the immune and inflammatory systems. There are at least six mammalian and three Drosophila proteins containing TRAF domains. The mammalian TRAFs display varying expression profiles, indicating independent and cell type-specific regulation. They display distinct, as well as overlapping functions and interactions with receptors. Most TRAFs, except TRAF1, share N-terminal homology and contain a RING domain, multiple zinc finger domains, and a TRAF domain. TRAFs form homo- and heterotrimers through its TRAF domain. The TRAF domain can be divided into a more divergent N-terminal alpha helical region (TRAF-N), and a highly conserved C-terminal MATH subdomain (TRAF-C) with an eight-stranded beta-sandwich structure. TRAF-N mediates trimerization while TRAF-C interacts with receptors.


Pssm-ID: 238168  Cd Length: 149  Bit Score: 95.37  E-value: 5.92e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546 430 HHIWHIQNFTQIL----GGQDTSVYSPPFYSSK-GYAFQIYMDL-----RSSTNVGIYFHLISGANDDQLQWPCPwQQAT 499
Cdd:cd00270    2 VLIWKIKDYSRKLqeavAGSNTVLYSPPFYTSRyGYKLCLRLYLngdgtGKGTHLSLFVHVMKGEYDALLEWPFR-GKIT 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546 500 MTLLDQNPDirqrmfNQRSITTDPTMTSDNGSYFWDRPskvgvtdvfpngtQFSRGIGYGTTVFITRERLKSREFIKGDD 579
Cdd:cd00270   81 LTLLDQSDD------SKRKHITETFMPDPNSSAFQRPP-------------TGENNIGFGYPEFVPLEKLESRGYVKDDT 141


                 ...
gi 148664546 580 IYI 582
Cdd:cd00270  142 LFI 144
ZnMc cd00203
Zinc-dependent metalloprotease. This super-family of metalloproteases contains two major ...
 75-254 7.79e-18

Zinc-dependent metalloprotease. This super-family of metalloproteases contains two major branches, the astacin-like proteases and the adamalysin/reprolysin-like proteases. Both branches have wide phylogenetic distribution, and contain sub-families, which are involved in vertebrate development and disease.


Pssm-ID: 238124 [Multi-domain]  Cd Length: 167  Bit Score: 81.41  E-value: 7.79e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546  75 TIPYVLEDSLEM--------NAKGVILNAFERYRLKTCIDFKP--WSGEANYISVF-------KGSGCWSSVGNIH-AGK 136
Cdd:cd00203    2 VIPYVVVADDRDveeenlsaQIQSLILIAMQIWRDYLNIRFVLvgVEIDKADIAILvtrqdfdGGTGGWAYLGRVCdSLR 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546 137 QELSIGTNC----DRIATVQHEFLHALGFWHEQSRADRDDYViivwdriqpgkehnfniynDSVSDSLNVPYDYTSVMHY 212
Cdd:cd00203   82 GVGVLQDNQsgtkEGAQTIAHELGHALGFYHDHDRKDRDDYP-------------------TIDDTLNAEDDDYYSVMSY 142

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 148664546 213 SKTAFQngtestivtrisefedvIGQRMDFSDYDLLKLNQLY 254
Cdd:cd00203  143 TKGSFS-----------------DGQRKDFSQCDIDQINKLY 167
MATH_TRAF4 cd03781
Tumor Necrosis Factor Receptor (TNFR)-Associated Factor (TRAF) family, TRAF4 subfamily, TRAF ...
 432-587 5.60e-16

Tumor Necrosis Factor Receptor (TNFR)-Associated Factor (TRAF) family, TRAF4 subfamily, TRAF domain, C-terminal MATH subdomain; composed of proteins with similarity to human TRAF4, including the Drosophila protein DTRAF1. TRAF molecules serve as adapter proteins that link TNFRs and downstream kinase cascades resulting in the activation of transcription factors and the regulation of cell survival, proliferation and stress responses. TRAF4 is highly expressed during embryogenesis, especially in the central and peripheral nervous system. Studies using TRAF4-deficient mice show that TRAF4 is required for neurogenesis, as well as the development of the trachea and the axial skeleton. In addition, TRAF4 augments nuclear factor-kappaB activation triggered by GITR (glucocorticoid-induced TNFR), a receptor expressed in T-cells, B-cells and macrophages. It also participates in counteracting the signaling mediated by Toll-like receptors through its association with TRAF6 and TRIF. DTRAF1 plays a pivotal role in the development of eye imaginal discs and photosensory neuron arrays in Drosophila. TRAF4 contains a RING finger domain, seven zinc finger domains, and a TRAF domain. The TRAF domain can be divided into a more divergent N-terminal alpha helical region (TRAF-N), and a highly conserved C-terminal MATH subdomain (TRAF-C) with an eight-stranded beta-sandwich structure. TRAF-N mediates trimerization while TRAF-C interacts with receptors.


Pssm-ID: 239750  Cd Length: 154  Bit Score: 75.62  E-value: 5.60e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546 432 IWHIQNFTQIL----GGQDTSVYSPPFYSSK-GYAFQIYMDLRSS-----TNVGIYFHLISGANDDQLQWPCPWQqATMT 501
Cdd:cd03781    4 LWKITDYSRKLqeakGRDNLELFSPPFYTHRyGYKLQVSAFLNGNgsgegSHLSVYIRVLPGEYDNLLEWPFSHR-ITFT 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546 502 LLDQN-PDIRQRMFNQRSITTDPTMTSdngsyfWDRPSKVGVTDvfpngtqfsRGIGYGTTVFITRERLKSREFIKGDDI 580
Cdd:cd03781   83 LLDQSdPSLSKPQHITETFTPDPTWKN------FQKPSASRLDE---------STLGFGYPKFISHEDLKKRNYIKDDAI 147


                 ....*..
gi 148664546 581 YILLTVE 587
Cdd:cd03781  148 FLRASVE 154
ZnMc_MMP_like cd04268
Zinc-dependent metalloprotease, MMP_like subfamily. This group contains matrix ...
 75-254 6.58e-15

Zinc-dependent metalloprotease, MMP_like subfamily. This group contains matrix metalloproteinases (MMPs), serralysins, and the astacin_like family of proteases.


Pssm-ID: 239796 [Multi-domain]  Cd Length: 165  Bit Score: 72.91  E-value: 6.58e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546  75 TIPYVLEDSLEMNAKGVILNAFERYRLKTCIDFKP----WSGEANYISV---FKGSGCWSSVG-NIHAGKQELSIGTNCD 146
Cdd:cd04268    3 PITYYIDDSVPDKLRAAILDAIEAWNKAFAIGFKNandvDPADIRYSVIrwiPYNDGTWSYGPsQVDPLTGEILLARVYL 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546 147 -----------RIATVQHEFLHALGFWHEQSRADRDDYViivwdriqpgkehnfniyndsvsDSLNVPYDYTSVMHYSKT 215
Cdd:cd04268   83 yssfveysgarLRNTAEHELGHALGLRHNFAASDRDDNV-----------------------DLLAEKGDTSSVMDYAPS 139

                        170       180       190
                 ....*....|....*....|....*....|....*....
gi 148664546 216 AFQngtestivtriseFEDVIGQRMDFSDYDLLKLNQLY 254
Cdd:cd04268  140 NFS-------------IQLGDGQKYTIGPYDIAAIKKLY 165
MATH_TRAF3 cd03777
Tumor Necrosis Factor Receptor (TNFR)-Associated Factor (TRAF) family, TRAF3 subfamily, TRAF ...
 432-587 2.15e-11

Tumor Necrosis Factor Receptor (TNFR)-Associated Factor (TRAF) family, TRAF3 subfamily, TRAF domain; TRAF molecules serve as adapter proteins that link TNFRs and downstream kinase cascades resulting in the activation of transcription factors and the regulation of cell survival, proliferation and stress responses. TRAF3 was first described as a molecule that binds the cytoplasmic tail of CD40. However, it is not required for CD40 signaling. More recently, TRAF3 has been identified as a key regulator of type I interferon (IFN) production and the mammalian innate antiviral immunity. It mediates IFN responses in Toll-like receptor (TLR)-dependent as well as TLR-independent viral recognition pathways. It is also a key element in immunological homeostasis through its regulation of the anti-inflammatory cytokine interleukin-10. TRAF3 contains a RING finger domain, five zinc finger domains, and a TRAF domain. The TRAF domain can be divided into a more divergent N-terminal alpha helical region (TRAF-N), and a highly conserved C-terminal MATH subdomain (TRAF-C) with an eight-stranded beta-sandwich structure. TRAF-N mediates trimerization while TRAF-C interacts with receptors.


Pssm-ID: 239746  Cd Length: 186  Bit Score: 63.43  E-value: 2.15e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546 432 IWHIQNFT----QILGGQDTSVYSPPFYSSK-GYAF--QIYMD---LRSSTNVGIYFHLISGANDDQLQWPCPwQQATMT 501
Cdd:cd03777   42 IWKIRDYKrrkqEAVMGKTLSLYSQPFYTGYfGYKMcaRVYLNgdgMGKGTHLSLFFVIMRGEYDALLPWPFK-QKVTLM 120

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546 502 LLDQNPDIRQRmfnQRSITTDPTMTSdngsyfWDRPSKvgvtdvfpngtqfSRGIGYGTTVFITRERLKSREFIKGDDIY 581
Cdd:cd03777  121 LMDQGSSRRHL---GDAFKPDPNSSS------FKKPTG-------------EMNIASGCPVFVAQTVLENGTYIKDDTIF 178


                 ....*.
gi 148664546 582 ILLTVE 587
Cdd:cd03777  179 IKVIVD 184
MATH cd00121
MATH (meprin and TRAF-C homology) domain; an independent folding unit with an eight-stranded ...
 429-587 2.83e-11

MATH (meprin and TRAF-C homology) domain; an independent folding unit with an eight-stranded beta-sandwich structure found in meprins, TRAFs and other proteins. Meprins comprise a class of extracellular metalloproteases which are anchored to the membrane and are capable of cleaving growth factors, extracellular matrix proteins, and biologically active peptides. TRAF molecules serve as adapter proteins that link cell surface receptors of the Tumor Necrosis Factor and 1nterleukin-1/Toll-like families to downstream kinase cascades, which results in the activation of transcription factors and the regulation of cell survival, proliferation and stress responses in the immune and inflammatory systems. Other members include the ubiquitin ligases, TRIM37 and SPOP, and the ubiquitin-specific proteases, HAUSP and Ubp21p. A large number of uncharacterized members mostly from lineage-specific expansions in C. elegans and rice contain MATH and BTB domains, similar to SPOP. The MATH domain has been shown to bind peptide/protein substrates in TRAFs and HAUSP. It is possible that the MATH domain in other members of this superfamily also interacts with various protein substrates. The TRAF domain may also be involved in the trimerization of TRAFs. Based on homology, it is postulated that the MATH domain in meprins may be involved in its tetramer assembly and that the MATH domain, in general, may take part in diverse modular arrangements defined by adjacent multimerization domains.


Pssm-ID: 238068  Cd Length: 126  Bit Score: 61.24  E-value: 2.83e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546 429 PHHIWHIQNFTQILGgqdTSVYSPPFYSSkGYAFQIYM----DLRSSTNVGIYFHLISGANDDQlqWPCPWQQATMTLLD 504
Cdd:cd00121    1 GKHTWKIVNFSELEG---ESIYSPPFEVG-GYKWRIRIypngDGESGDYLSLYLELDKGESDLE--KWSVRAEFTLKLVN 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546 505 QNPDirqrmfnqrsittdptmtsdngsyfwdRPSKVGVTDVFPNgtqfSRGIGYGTTVFITRERLKSREFIKGDDIYILL 584
Cdd:cd00121   75 QNGG---------------------------KSLSKSFTHVFFS----EKGSGWGFPKFISWDDLEDSYYLVDDSLTIEV 123


                 ...
gi 148664546 585 TVE 587
Cdd:cd00121  124 EVK 126
MATH_TRAF6 cd03776
Tumor Necrosis Factor Receptor (TNFR)-Associated Factor (TRAF) family, TRAF6 subfamily, TRAF ...
 432-582 4.19e-10

Tumor Necrosis Factor Receptor (TNFR)-Associated Factor (TRAF) family, TRAF6 subfamily, TRAF domain, C-terminal MATH subdomain; composed of proteins with similarity to human TRAF6, including the Drosophila protein DTRAF2. TRAF molecules serve as adapter proteins that link TNFRs and downstream kinase cascades resulting in the activation of transcription factors and the regulation of cell survival, proliferation and stress responses. TRAF6 is the most divergent in its TRAF domain among the mammalian TRAFs. In addition to mediating TNFR family signaling, it is also an essential signaling molecule of the interleukin-1/Toll-like receptor superfamily. Whereas other TRAF molecules display similar and overlapping TNFR-binding specificities, TRAF6 binds completely different sites on receptors such as CD40 and RANK. TRAF6 serves as a molecular bridge between innate and adaptive immunity and plays a central role in osteoimmunology. DTRAF2, as an activator of nuclear factor-kappaB, plays a pivotal role in Drosophila development and innate immunity. TRAF6 contains a RING finger domain, five zinc finger domains, and a TRAF domain. The TRAF domain can be divided into a more divergent N-terminal alpha helical region (TRAF-N), and a highly conserved C-terminal MATH subdomain (TRAF-C) with an eight-stranded beta-sandwich structure. TRAF-N mediates trimerization while TRAF-C interacts with receptors.


Pssm-ID: 239745  Cd Length: 147  Bit Score: 58.49  E-value: 4.19e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546 432 IWHIQNFTQIL----GGQDTSVYSPPFYSSK-GYAFQIYMDL-----RSSTNVGIYFHLISGANDDQLQWPCpwqQATMT 501
Cdd:cd03776    4 VWKIKNFSNLRrsmeAGSPVVIHSPGFYTSPpGYKLCARLNLslpeaRCPNYISLFVHLMQGENDSHLDWPF---QGTIT 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546 502 L--LDQNPDIRqrmfNQRSIttdpTMTSDNGSYFwDRPskvgVTDVFPngtqfsRGIGYgtTVFITRERLKSREFIKGDD 579
Cdd:cd03776   81 LtlLDQSEPRQ----NIHET----MMSKPELLAF-QRP----TTDRNP------KGFGY--VEFAHIEDLLQRGFVKNDT 139


                 ...
gi 148664546 580 IYI 582
Cdd:cd03776  140 LLI 142
MATH_TRAF2 cd03778
Tumor Necrosis Factor Receptor (TNFR) Associated Factor (TRAF) family, TRAF2 subfamily, TRAF ...
 432-520 2.94e-08

Tumor Necrosis Factor Receptor (TNFR) Associated Factor (TRAF) family, TRAF2 subfamily, TRAF domain; TRAF molecules serve as adapter proteins that link TNFRs and downstream kinase cascades resulting in the activation of transcription factors and the regulation of cell survival, proliferation and stress responses. TRAF2 associates with the receptors TNFR-1, TNFR-2, RANK (which mediates differentiation and maturation of osteoclasts) and CD40 (which is important for the proliferation and activation of B cells), among others. It regulates distinct pathways that lead to the activation of nuclear factor-kappaB and Jun NH2-terminal kinases. TRAF2 also indirectly associates with death receptors through its interaction with TRADD (TNFR-associated death domain protein). It is involved in regulating oxidative stress or ROS-induced cell death and in the preconditioning of cells by sublethal stress for protection from subsequent injury. TRAF2 contains a RING finger domain, five zinc finger domains, and a TRAF domain. The TRAF domain can be divided into a more divergent N-terminal alpha helical region (TRAF-N), and a highly conserved C-terminal MATH subdomain (TRAF-C) with an eight-stranded beta-sandwich structure. TRAF-N mediates trimerization while TRAF-C interacts with receptors.


Pssm-ID: 239747  Cd Length: 164  Bit Score: 53.85  E-value: 2.94e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546 432 IWHIQNFTQ----ILGGQDTSVYSPPFYSSK-GY--AFQIYMDLRSS---TNVGIYFHLISGANDDQLQWPCPwQQATMT 501
Cdd:cd03778   22 IWKISDFARkrqeAVAGRIPAIFSPAFYTSRyGYkmCLRIYLNGDGTgrgTHLSLFFVVMKGPNDALLRWPFN-QKVTLM 100

                         90       100
                 ....*....|....*....|....*....
gi 148664546 502 LLDQN----------PDIRQRMFnQRSIT 520
Cdd:cd03778  101 LLDQNnrehvidafrPDVTSSSF-QRPVN 128
ZnMc_MMP_like_3 cd04327
Zinc-dependent metalloprotease; MMP_like sub-family 3. A group of bacterial and fungal ...
 70-213 7.66e-07

Zinc-dependent metalloprotease; MMP_like sub-family 3. A group of bacterial and fungal metalloproteinase domains similar to matrix metalloproteinases and astacin.


Pssm-ID: 239819 [Multi-domain]  Cd Length: 198  Bit Score: 50.07  E-value: 7.66e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546  70 KRWP--HTIPYVLEDSLEMNAKGVILNAFERYRLKTCIDFKpWSGEAN---YISVFKGSGCWSSVG----NIHAGKQ--- 137
Cdd:cd04327    1 KLWRngTVLRIAFLGGPDAFLKDKVRAAAREWLPYANLKFK-FVTDADadiRISFTPGDGYWSYVGtdalLIGADAPtmn 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546 138 ---ELSIGTNCDRIATVQHEFLHALGFWHEQSRADRDdyviIVWDR-------IQPG-------KEHN-FNIYNDsvSDS 199
Cdd:cd04327   80 lgwFTDDTPDPEFSRVVLHEFGHALGFIHEHQSPAAN----IPWDKeavyayfSGPPnwdretvINHNvFAKLDD--GDV 153

                        170
                 ....*....|....
gi 148664546 200 LNVPYDYTSVMHYS 213
Cdd:cd04327  154 AYSPYDPDSIMHYP 167
MATH_TRAF5 cd03780
Tumor Necrosis Factor Receptor (TNFR)-Associated Factor (TRAF) family, TRAF5 subfamily, TRAF ...
 432-527 8.36e-07

Tumor Necrosis Factor Receptor (TNFR)-Associated Factor (TRAF) family, TRAF5 subfamily, TRAF domain, C-terminal MATH subdomain; TRAF molecules serve as adapter proteins that link TNFRs and downstream kinase cascades resulting in the activation of transcription factors and the regulation of cell survival, proliferation and stress responses. TRAF5 was identified as an activator of nuclear factor-kappaB and a regulator of lymphotoxin-beta receptor and CD40 signaling. Its interaction with CD40 is indirect, involving hetero-oligomerization with TRAF3. In addition, TRAF5 has been shown to associate with other TNFRs including CD27, CD30, OX40 and GITR (glucocorticoid-induced TNFR). It plays a role in modulating Th2 immune responses (driven by OX40 costimulation) and T-cell activation (triggered by GITR). It is also involved in osteoclastogenesis. TRAF5 contains a RING finger domain, five zinc finger domains, and a TRAF domain. The TRAF domain can be divided into a more divergent N-terminal alpha helical region (TRAF-N), and a highly conserved C-terminal MATH subdomain (TRAF-C) with an eight-stranded beta-sandwich structure. TRAF-N mediates trimerization while TRAF-C interacts with receptors.


Pssm-ID: 239749 [Multi-domain]  Cd Length: 148  Bit Score: 49.25  E-value: 8.36e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546 432 IWHIQNFT----QILGGQDTSVYSPPFYSSK-GYAF--QIYMDLRSS---TNVGIYFHLISGANDDQLQWPCPwQQATMT 501
Cdd:cd03780    4 IWKVTDYKmkkkEAVDGHTVSIFSQPFYTSRcGYRLcaRAYLNGDGSgkgTHLSLYFVVMRGEFDSLLQWPFR-QRVTLM 82

                         90       100
                 ....*....|....*....|....*.
gi 148664546 502 LLDQNPDIRQRMfnqRSITTDPTMTS 527
Cdd:cd03780   83 LLDQSGKKNHIM---ETFKADPNSSS 105
EGF_CA cd00054
Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular ...
 609-647 6.18e-06

Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the N-terminus of particular EGF-like domains; calcium-binding may be crucial for numerous protein-protein interactions. Six conserved core cysteines form three disulfide bridges as in non calcium-binding EGF domains, whose structures are very similar. EGF_CA can be found in tandem repeat arrangements.


Pssm-ID: 238011  Cd Length: 38  Bit Score: 43.39  E-value: 6.18e-06
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 148664546 609 NACSEV-VCQNGGICVVQDGRAECKCPAGedwwYMGKRCE 647
Cdd:cd00054    3 DECASGnPCQNGGTCVNTVGSYRCSCPPG----YTGRNCE 38
MATH smart00061
meprin and TRAF homology;
433-512 1.56e-05

meprin and TRAF homology;


Pssm-ID: 214496 [Multi-domain]  Cd Length: 95  Bit Score: 43.83  E-value: 1.56e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546   433 WHIQNFTQILG-GQDTSVYSPPFYSSK-GYAFQIYmdlRSSTNVGIYFHLISGANDDqLQWPCpWQQATMTLLDQNPDIR 510
Cdd:smart00061   1 VLSHTFKNVSRlEEGESYFSPSEEHFNiPWRLKIY---RKNGFLSLYLHCEKEECDS-RKWSI-EAEFTLKLVSQNGKSL 75


                   ..
gi 148664546   511 QR 512
Cdd:smart00061  76 SK 77
MATH_TRAF1 cd03779
Tumor Necrosis Factor Receptor (TNFR) Associated Factor (TRAF) family, TRAF1 subfamily, TRAF ...
 432-516 1.19e-04

Tumor Necrosis Factor Receptor (TNFR) Associated Factor (TRAF) family, TRAF1 subfamily, TRAF domain, C-terminal MATH subdomain; TRAF molecules serve as adapter proteins that link TNFRs and downstream kinase cascades resulting in the activation of transcription factors and the regulation of cell survival, proliferation and stress responses. TRAF1 expression is the most restricted among the TRAFs. It is found exclusively in activated lymphocytes, dendritic cells and certain epithelia. TRAF1 associates, directly or indirectly through heterodimerization with TRAF2, with the TNFR family receptors TNFR-2, CD30, RANK, CD40 and LMP1, among others. It also binds the intracellular proteins TRADD, TANK, TRIP, RIP1, RIP2 and FLIP. TRAF1 is unique among the TRAFs in that it lacks a RING domain, which is critical for the activation of nuclear factor-kappaB and Jun NH2-terminal kinase. Studies on TRAF1-deficient mice suggest that TRAF1 has a negative regulatory role in TNFR-mediated signaling events. TRAF1 contains one zinc finger and one TRAF domain. The TRAF domain can be divided into a more divergent N-terminal alpha helical region (TRAF-N), and a highly conserved C-terminal MATH subdomain (TRAF-C) with an eight-stranded beta-sandwich structure. TRAF-N mediates trimerization while TRAF-C interacts with receptors.


Pssm-ID: 239748  Cd Length: 147  Bit Score: 42.96  E-value: 1.19e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148664546 432 IWHIQNFTQIL----GGQDTSVYSPPFYSSK-GY--AFQIYMD---LRSSTNVGIYFHLISGANDDQLQWPCPwQQATMT 501
Cdd:cd03779    4 LWKITDVSQKQressHGRDVSLCSPAFYTAKyGYkvCLRLYLNgdgAGKGTHISLFFVIMKGEYDALLPWPFR-HKVTFM 82

                         90       100
                 ....*....|....*....|....*
gi 148664546 502 LLDQN----------PDIRQRMFNQ 516
Cdd:cd03779   83 LLDQNnrehvidafrPDLSSASFQR 107
EGF_CA smart00179
Calcium-binding EGF-like domain;
609-647 1.93e-04

Calcium-binding EGF-like domain;


Pssm-ID: 214542 [Multi-domain]  Cd Length: 39  Bit Score: 39.15  E-value: 1.93e-04
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 148664546   609 NACSEV-VCQNGGICVVQDGRAECKCPAGedwWYMGKRCE 647
Cdd:smart00179   3 DECASGnPCQNGGTCVNTVGSYRCECPPG---YTDGRNCE 39
EGF cd00053
Epidermal growth factor domain, found in epidermal growth factor (EGF) presents in a large ...
 616-647 3.53e-04

Epidermal growth factor domain, found in epidermal growth factor (EGF) presents in a large number of proteins, mostly animal; the list of proteins currently known to contain one or more copies of an EGF-like pattern is large and varied; the functional significance of EGF-like domains in what appear to be unrelated proteins is not yet clear; a common feature is that these repeats are found in the extracellular domain of membrane-bound proteins or in proteins known to be secreted (exception: prostaglandin G/H synthase); the domain includes six cysteine residues which have been shown to be involved in disulfide bonds; the main structure is a two-stranded beta-sheet followed by a loop to a C-terminal short two-stranded sheet; Subdomains between the conserved cysteines vary in length; the region between the 5th and 6th cysteine contains two conserved glycines of which at least one is present in most EGF-like domains; a subset of these bind calcium.


Pssm-ID: 238010  Cd Length: 36  Bit Score: 38.61  E-value: 3.53e-04
                         10        20        30
                 ....*....|....*....|....*....|...
gi 148664546 616 CQNGGICVVQDGRAECKCPAGedwwYMG-KRCE 647
Cdd:cd00053    8 CSNGGTCVNTPGSYRCVCPPG----YTGdRSCE 36
hEGF pfam12661
Human growth factor-like EGF; hEGF, or human growth factor-like EGF, domains have six ...
 616-636 7.84e-04

Human growth factor-like EGF; hEGF, or human growth factor-like EGF, domains have six conserved residues disulfide-bonded into the characteriztic 'ababcc' pattern. They are involved in growth and proliferation of cells, in proteins of the Notch/Delta pathway, neurogulin and selectins. hEGFs are also found in mosaic proteins with four-disulfide laminin EGFs such as aggrecan and perlecan. The core fold of the EGF domain consists of two small beta-hairpins packed against each other. Two major structural variants have been identified based on the structural context of the C-terminal Cys residue of disulfide 'c' in the C-terminal hairpin: hEGFs and cEGFs. In hEGFs the C-terminal thiol resides in the beta-turn, resulting in shorter loop-lengths between the Cys residues of disulfide 'c', typically C[8-9]XC. These shorter loop-lengths are also typical of the four-disulfide EGF domains, laminin ad integrin. Tandem hEGF domains have six linking residues between terminal cysteines of adjacent domains. hEGF domains may or may not bind calcium in the linker region. hEGF domains with the consensus motif CXD4X[F,Y]XCXC are hydroxylated exclusively in the Asp residue.


Pssm-ID: 463660  Cd Length: 22  Bit Score: 37.31  E-value: 7.84e-04
                          10        20
                  ....*....|....*....|.
gi 148664546  616 CQNGGICVVQDGRAECKCPAG 636
Cdd:pfam12661   1 CQNGGTCVDGVNGYKCQCPPG 21
EGF_2 pfam07974
EGF-like domain; This family contains EGF domains found in a variety of extracellular proteins.
 615-646 1.72e-03

EGF-like domain; This family contains EGF domains found in a variety of extracellular proteins.


Pssm-ID: 400365  Cd Length: 26  Bit Score: 36.17  E-value: 1.72e-03
                          10        20        30
                  ....*....|....*....|....*....|..
gi 148664546  615 VCQNGGICVVQDGRaeCKCPAGedwwYMGKRC 646
Cdd:pfam07974   1 ICSGRGTCVNQCGK--CVCDSG----YQGATC 26
EGF pfam00008
EGF-like domain; There is no clear separation between noise and signal. pfam00053 is very ...
 611-636 3.32e-03

EGF-like domain; There is no clear separation between noise and signal. pfam00053 is very similar, but has 8 instead of 6 conserved cysteines. Includes some cytokine receptors. The EGF domain misses the N-terminus regions of the Ca2+ binding EGF domains (this is the main reason of discrepancy between swiss-prot domain start/end and Pfam). The family is hard to model due to many similar but different sub-types of EGF domains. Pfam certainly misses a number of EGF domains.


Pssm-ID: 394967  Cd Length: 31  Bit Score: 35.44  E-value: 3.32e-03
                          10        20
                  ....*....|....*....|....*.
gi 148664546  611 CSEVVCQNGGICVVQDGRAECKCPAG 636
Cdd:pfam00008   1 CAPNPCSNGGTCVDTPGGYTCICPEG 26
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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