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 568921615 391 CNFDHGLCGWIREKDSDLHWETAR--------------DPAGGQYLTVSAAKAPGGKAARLVLRLGHLMhSGDLCLSFRH 456
Cdd:cd06263    1 CDFEDGLCGWTQDSTDDFDWTRVSgstpspgtppdhthGTGSGHYLYVESSSGREGQKARLLSPLLPPP-RSSHCLSFWY 79

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568921615 457 KVTGLHSGTLQVFVR-KHGTHGAALWGRNG--GHGWRQTQITLRGADVK-SVIFKGEKRRGHTGEIGLDDVSLKRGRC 530
Cdd:cd06263   80 HMYGSGVGTLNVYVReEGGGLGTLLWSASGgqGNQWQEAEVTLSASSKPfQVVFEGVRGSGSRGDIALDDISLSPGPC 157

Calcium-binding EGF domain;

                          10        20
                  ....*....|....*....|....*....
gi 568921615  138 DIDECATGRVSCPRFRQCVNTFGSYICKC 166
Cdd:pfam07645   1 DVDECATGTHNCPANTVCVNTIGSFECRC 29

Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of fold. The vWA domain, since its discovery, has drawn great interest because of its widespread occurrence and its involvement in a wide variety of important cellular functions. These include basal membrane formation, cell migration, cell differentiation, adhesion, haemostasis, signaling, chromosomal stability, malignant transformation and in immune defenses In integrins these domains form heterodimers while in vWF it forms multimers. There are different interaction surfaces of this domain as seen by the various molecules it complexes with. Ligand binding in most cases is mediated by the presence of a metal ion dependent adhesion site termed as the MIDAS motif that is a characteristic feature of most, if not all A domains.

                         10        20        30
                 ....*....|....*....|....*....|....*....
gi 568921615  56 CQHLNECGLKPRPCKHRCMNTFGSYKCYCLNGYMLLPDG 94
Cdd:cd01475  184 CVVPDLCATLSHVCQQVCISTPGSYLCACTEGYALLEDN 222

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 568921615 391 CNFDHGLCGWIREKDSDLHWETAR--------------DPAGGQYLTVSAAKAPGGKAARLVLRLGHLMhSGDLCLSFRH 456
Cdd:cd06263    1 CDFEDGLCGWTQDSTDDFDWTRVSgstpspgtppdhthGTGSGHYLYVESSSGREGQKARLLSPLLPPP-RSSHCLSFWY 79

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568921615 457 KVTGLHSGTLQVFVR-KHGTHGAALWGRNG--GHGWRQTQITLRGADVK-SVIFKGEKRRGHTGEIGLDDVSLKRGRC 530
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 568921615  391 CNFDHG-LCGWIREKDSDLHWE----------TARD----PAGGQYLTVSAAKAPGGKAARLvlrLGHLMH--SGDLCLS 453
Cdd:pfam00629   1 CDFEDGnLCGWTQDSSDDFDWErvsgpsvktgPSSDhtqgTGSGHFMYVDTSSGAPGQTARL---LSPLLPpsRSPQCLR 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568921615  454 FRHKVTGLHSGTLQVFVRKHGTH-GAALWGRNGGHG--WRQTQITL-RGADVKSVIFKGEKRRGHTGEIGLDDVSLKRGR 529
Cdd:pfam00629  78 FWYHMSGSGVGTLRVYVRENGGTlDTLLWSISGDQGpsWKEARVTLsSSTQPFQVVFEGIRGGGSRGGIALDDISLSSGP 157

                  .
gi 568921615  530 C 530
Cdd:pfam00629 158 C 158

Calcium-binding EGF-like domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 568921615   183 DIDECSLGqHQCSSYARCYNIHGSYKCQCRDGYEgDGLNCV 223
Cdd:smart00179   1 DIDECASG-NPCQNGGTCVNTVGSYRCECPPGYT-DGRNCE 39

Calcium-binding EGF domain;

                          10        20
                  ....*....|....*....|....*....
gi 568921615  138 DIDECATGRVSCPRFRQCVNTFGSYICKC 166
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 568921615  119 RCQCPsPGLQLAPDGRTCVDIDE 141
Cdd:pfam12662   1 TCSCP-PGYQLDPDGRTCVDIDE 22

VWA_Matrilin: In cartilaginous plate, extracellular matrix molecules mediate cell-matrix and matrix-matrix interactions thereby providing tissue integrity. Some members of the matrilin family are expressed specifically in developing cartilage rudiments. The matrilin family consists of at least four members. All the members of the matrilin family contain VWA domains, EGF-like domains and a heptad repeat coiled-coiled domain at the carboxy terminus which is responsible for the oligomerization of the matrilins. The VWA domains have been shown to be essential for matrilin network formation by interacting with matrix ligands.

                         10        20        30
                 ....*....|....*....|....*....|....*....
gi 568921615  56 CQHLNECGLKPRPCKHRCMNTFGSYKCYCLNGYMLLPDG 94
Cdd:cd01475  184 CVVPDLCATLSHVCQQVCISTPGSYLCACTEGYALLEDN 222

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 568921615 391 CNFDHGLCGWIREKDSDLHWETAR--------------DPAGGQYLTVSAAKAPGGKAARLVLRLGHLMhSGDLCLSFRH 456
Cdd:cd06263    1 CDFEDGLCGWTQDSTDDFDWTRVSgstpspgtppdhthGTGSGHYLYVESSSGREGQKARLLSPLLPPP-RSSHCLSFWY 79

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568921615 457 KVTGLHSGTLQVFVR-KHGTHGAALWGRNG--GHGWRQTQITLRGADVK-SVIFKGEKRRGHTGEIGLDDVSLKRGRC 530
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 568921615  391 CNFDHG-LCGWIREKDSDLHWE----------TARD----PAGGQYLTVSAAKAPGGKAARLvlrLGHLMH--SGDLCLS 453
Cdd:pfam00629   1 CDFEDGnLCGWTQDSSDDFDWErvsgpsvktgPSSDhtqgTGSGHFMYVDTSSGAPGQTARL---LSPLLPpsRSPQCLR 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568921615  454 FRHKVTGLHSGTLQVFVRKHGTH-GAALWGRNGGHG--WRQTQITL-RGADVKSVIFKGEKRRGHTGEIGLDDVSLKRGR 529
Cdd:pfam00629  78 FWYHMSGSGVGTLRVYVRENGGTlDTLLWSISGDQGpsWKEARVTLsSSTQPFQVVFEGIRGGGSRGGIALDDISLSSGP 157

                  .
gi 568921615  530 C 530
Cdd:pfam00629 158 C 158

Calcium-binding EGF-like domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 568921615   183 DIDECSLGqHQCSSYARCYNIHGSYKCQCRDGYEgDGLNCV 223
Cdd:smart00179   1 DIDECASG-NPCQNGGTCVNTVGSYRCECPPGYT-DGRNCE 39

Calcium-binding EGF domain;

                          10        20        30
                  ....*....|....*....|....*....|..
gi 568921615  183 DIDECSLGQHQCSSYARCYNIHGSYKCQCRDG 214
Cdd:pfam07645   1 DVDECATGTHNCPANTVCVNTIGSFECRCPDG 32

Calcium-binding EGF-like domain;

                           10        20        30
                   ....*....|....*....|....*....|...
gi 568921615   138 DIDECATGRVsCPRFRQCVNTFGSYICKCHTGF 170
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 568921615 138 DIDECATGRVsCPRFRQCVNTFGSYICKCHTGF 170
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 568921615 186 ECSLgQHQCSSYARCYNIHGSYKCQCRDGYEGDG 219
Cdd:cd00053    1 ECAA-SNPCSNGGTCVNTPGSYRCVCPPGYTGDR 33

Coagulation Factor Xa inhibitory site; This short domain on coagulation enzyme factor Xa is found to be the target for a potent inhibitor of coagulation, TAK-442.

                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 568921615   62 CGLKPRPCKHRCMNTFGSYKCYCLNGYMLLPDG-SC 96
Cdd:pfam14670   1 CSVNNGGCSHLCLNTPGGYTCSCPEGYELQDDGrTC 36