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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 560879463 318 CNFDHGLCGWIREKDSDLHWETAR--------------DPAGGQYLTVSAAKAPGGKAARLVLRLGHLMhSGDLCLSFRH 383
Cdd:cd06263    1 CDFEDGLCGWTQDSTDDFDWTRVSgstpspgtppdhthGTGSGHYLYVESSSGREGQKARLLSPLLPPP-RSSHCLSFWY 79

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 560879463 384 KVTGLHSGTLQVFVR-KHGTHGAALWGRNG--GHGWRQTQITLRGADVK-SVIFKGEKRRGHTGEIGLDDVSLKRGRC 457
Cdd:cd06263   80 HMYGSGVGTLNVYVReEGGGLGTLLWSASGgqGNQWQEAEVTLSASSKPfQVVFEGVRGSGSRGDIALDDISLSPGPC 157

Calcium-binding EGF domain;

                          10        20
                  ....*....|....*....|....*....
gi 560879463   65 DIDECATGRVSCPRFRQCVNTFGSYICKC 93
Cdd:pfam07645   1 DVDECATGTHNCPANTVCVNTIGSFECRC 29

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 560879463 318 CNFDHGLCGWIREKDSDLHWETAR--------------DPAGGQYLTVSAAKAPGGKAARLVLRLGHLMhSGDLCLSFRH 383
Cdd:cd06263    1 CDFEDGLCGWTQDSTDDFDWTRVSgstpspgtppdhthGTGSGHYLYVESSSGREGQKARLLSPLLPPP-RSSHCLSFWY 79

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 560879463 384 KVTGLHSGTLQVFVR-KHGTHGAALWGRNG--GHGWRQTQITLRGADVK-SVIFKGEKRRGHTGEIGLDDVSLKRGRC 457
Cdd:cd06263   80 HMYGSGVGTLNVYVReEGGGLGTLLWSASGgqGNQWQEAEVTLSASSKPfQVVFEGVRGSGSRGDIALDDISLSPGPC 157

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 560879463  318 CNFDHG-LCGWIREKDSDLHWE----------TARD----PAGGQYLTVSAAKAPGGKAARLvlrLGHLMH--SGDLCLS 380
Cdd:pfam00629   1 CDFEDGnLCGWTQDSSDDFDWErvsgpsvktgPSSDhtqgTGSGHFMYVDTSSGAPGQTARL---LSPLLPpsRSPQCLR 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 560879463  381 FRHKVTGLHSGTLQVFVRKHGTH-GAALWGRNGGHG--WRQTQITL-RGADVKSVIFKGEKRRGHTGEIGLDDVSLKRGR 456
Cdd:pfam00629  78 FWYHMSGSGVGTLRVYVRENGGTlDTLLWSISGDQGpsWKEARVTLsSSTQPFQVVFEGIRGGGSRGGIALDDISLSSGP 157

                  .
gi 560879463  457 C 457
Cdd:pfam00629 158 C 158

Calcium-binding EGF-like domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 560879463   110 DIDECSLGqHQCSSYARCYNIHGSYKCQCRDGYEgDGLNCV 150
Cdd:smart00179   1 DIDECASG-NPCQNGGTCVNTVGSYRCECPPGYT-DGRNCE 39

Calcium-binding EGF domain;

                          10        20
                  ....*....|....*....|....*....
gi 560879463   65 DIDECATGRVSCPRFRQCVNTFGSYICKC 93
Cdd:pfam07645   1 DVDECATGTHNCPANTVCVNTIGSFECRC 29

Complement Clr-like EGF-like; cEGF, or complement Clr-like EGF, domains have six conserved cysteine residues disulfide-bonded into the characteriztic pattern 'ababcc'. They are found in blood coagulation proteins such as fibrillin, Clr and Cls, thrombomodulin, and the LDL receptor. 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 cysteine residue of disulfide 'c' in the C-terminal hairpin: hEGFs and cEGFs. In cEGFs the C-terminal thiol resides on the C-terminal beta-sheet, resulting in long loop-lengths between the cysteine residues of disulfide 'c', typically C[10+]XC. These longer loop-lengths may have arisen by selective cysteine loss from a four-disulfide EGF template such as laminin or integrin. Tandem cEGF domains have five linking residues between terminal cysteines of adjacent domains. cEGF domains may or may not bind calcium in the linker region. cEGF domains with the consensus motif CXN4X[F,Y]XCXC are hydroxylated exclusively on the asparagine residue.

                          10        20
                  ....*....|....*....|...
gi 560879463   46 RCQCPsPGLQLAPDGRTCVDIDE 68
Cdd:pfam12662   1 TCSCP-PGYQLDPDGRTCVDIDE 22

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 560879463 318 CNFDHGLCGWIREKDSDLHWETAR--------------DPAGGQYLTVSAAKAPGGKAARLVLRLGHLMhSGDLCLSFRH 383
Cdd:cd06263    1 CDFEDGLCGWTQDSTDDFDWTRVSgstpspgtppdhthGTGSGHYLYVESSSGREGQKARLLSPLLPPP-RSSHCLSFWY 79

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 560879463 384 KVTGLHSGTLQVFVR-KHGTHGAALWGRNG--GHGWRQTQITLRGADVK-SVIFKGEKRRGHTGEIGLDDVSLKRGRC 457
Cdd:cd06263   80 HMYGSGVGTLNVYVReEGGGLGTLLWSASGgqGNQWQEAEVTLSASSKPfQVVFEGVRGSGSRGDIALDDISLSPGPC 157

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 560879463  318 CNFDHG-LCGWIREKDSDLHWE----------TARD----PAGGQYLTVSAAKAPGGKAARLvlrLGHLMH--SGDLCLS 380
Cdd:pfam00629   1 CDFEDGnLCGWTQDSSDDFDWErvsgpsvktgPSSDhtqgTGSGHFMYVDTSSGAPGQTARL---LSPLLPpsRSPQCLR 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 560879463  381 FRHKVTGLHSGTLQVFVRKHGTH-GAALWGRNGGHG--WRQTQITL-RGADVKSVIFKGEKRRGHTGEIGLDDVSLKRGR 456
Cdd:pfam00629  78 FWYHMSGSGVGTLRVYVRENGGTlDTLLWSISGDQGpsWKEARVTLsSSTQPFQVVFEGIRGGGSRGGIALDDISLSSGP 157

                  .
gi 560879463  457 C 457
Cdd:pfam00629 158 C 158

Calcium-binding EGF-like domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 560879463   110 DIDECSLGqHQCSSYARCYNIHGSYKCQCRDGYEgDGLNCV 150
Cdd:smart00179   1 DIDECASG-NPCQNGGTCVNTVGSYRCECPPGYT-DGRNCE 39

Calcium-binding EGF domain;

                          10        20        30
                  ....*....|....*....|....*....|..
gi 560879463  110 DIDECSLGQHQCSSYARCYNIHGSYKCQCRDG 141
Cdd:pfam07645   1 DVDECATGTHNCPANTVCVNTIGSFECRCPDG 32

Calcium-binding EGF-like domain;

                           10        20        30
                   ....*....|....*....|....*....|...
gi 560879463    65 DIDECATGRVsCPRFRQCVNTFGSYICKCHTGF 97
Cdd:smart00179   1 DIDECASGNP-CQNGGTCVNTVGSYRCECPPGY 32

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.

                         10        20        30
                 ....*....|....*....|....*....|...
gi 560879463  65 DIDECATGRVsCPRFRQCVNTFGSYICKCHTGF 97
Cdd:cd00054    1 DIDECASGNP-CQNGGTCVNTVGSYRCSCPPGY 32

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.

                         10        20        30
                 ....*....|....*....|....*....|....
gi 560879463 113 ECSLgQHQCSSYARCYNIHGSYKCQCRDGYEGDG 146
Cdd:cd00053    1 ECAA-SNPCSNGGTCVNTPGSYRCVCPPGYTGDR 33