Protein: Alpha-2-macroglobulin (Alpha-2-M) (C3 and PZP-like alpha-2-macroglobulin domain-containing protein 5) (P01023)
Organism: Homo sapiens (Human)
Function: Is able to inhibit all four classes of proteinases by a unique 'trapping' mechanism. This protein has a peptide stretch, called the 'bait region' which contains specific cleavage sites for different proteinases. When a proteinase cleaves the bait region, a conformational change is induced in the protein which traps the proteinase. The entrapped enzyme remains active against low molecular weight substrates (activity against high molecular weight substrates is greatly reduced). Following cleavage in the bait region, a thioester bond is hydrolyzed and mediates the covalent binding of the protein to the proteinase.
Subcellular location: Secreted {ECO:0000269|PubMed:6203908}.
Sequence: MGKNKLLHPSLVLLLLVLLPTDASVSGKPQYMVLVPSLLHTETTEKGCVLLSYLNETVTVSASLESVRGNRSLFTDLEAENDVLHCVAFAVPKSSSNEEVMFLTVQVKGPTQEFKKRTTVMVKNEDSLVFVQTDKSIYKPGQTVKFRVVSMDENFHPLNELIPLVYIQDPKGNRIAQWQSFQLEGGLKQFSFPLSSEPFQGSYKVVVQKKSGGRTEHPFTVEEFVLPKFEVQVTVPKIITILEEEMNVSVCGLYTYGKPVPGHVTVSICRKYSDASDCHGEDSQAFCEKFSGQLNSHGCFYQQVKTKVFQLKRKEYEMKLHTEAQIQEEGTVVELTGRQSSEITRTITKLSFVKVDSHFRQGIPFFGQVRLVDGKGVPIPNKVIFIRGNEANYYSNATTDEHGLVQFSINTTNVMGTSLTVRVNYKDRSPCYGYQWVSEEHEEAHHTAYLVFSPSKSFVHLEPMSHELPCGHTQTVQAHYILNGGTLLGLKKLSFYYLIMAKGGIVRTGTHGLLVKQEDMKGHFSISIPVKSDIAPVARLLIYAVLPTGDVIGDSAKYDVENCLANKVDLSFSPSQSLPASHAHLRVTAAPQSVCALRAVDQSVLLMKPDAELSASSVYNLLPEKDLTGFPGPLNDQDNEDCINRHNVYINGITYTPVSSTNEKDMYSFLEDMGLKAFTNSKIRKPKMCPQLQQYEMHGPEGLRVGFYESDVMGRGHARLVHVEEPHTETVRKYFPETWIWDLVVVNSAGVAEVGVTVPDTITEWKAGAFCLSEDAGLGISSTASLRAFQPFFVELTMPYSVIRGEAFTLKATVLNYLPKCIRVSVQLEASPAFLAVPVEKEQAPHCICANGRQTVSWAVTPKSLGNVNFTVSAEALESQELCGTEVPSVPEHGRKDTVIKPLLVEPEGLEKETTFNSLLCPSGGEVSEELSLKLPPNVVEESARASVSVLGDILGSAMQNTQNLLQMPYGCGEQNMVLFAPNIYVLDYLNETQQLTPEIKSKAIGYLNTGYQRQLNYKHYDGSYSTFGERYGRNQGNTWLTAFVLKTFAQARAYIFIDEAHITQALIWLSQRQKDNGCFRSSGSLLNNAIKGGVEDEVTLSAYITIALLEIPLTVTHPVVRNALFCLESAWKTAQEGDHGSHVYTKALLAYAFALAGNQDKRKEVLKSLNEEAVKKDNSVHWERPQKPKAPVGHFYEPQAPSAEVEMTSYVLLAYLTAQPAPTSEDLTSATNIVKWITKQQNAQGGFSSTQDTVVALHALSKYGAATFTRTGKAAQVTIQSSGTFSSKFQVDNNNRLLLQQVSLPELPGEYSMKVTGEGCVYLQTSLKYNILPEKEEFPFALGVQTLPQTCDEPKAHTSFQISLSVSYTGSRSASNMAIVDVKMVSGFIPLKPTVKMLERSNHVSRTEVSSNHVLIYLDKVSNQTLSLFFTVLQDVPVRDLKPAIVKVYDYYETDEFAIAEYNAPCSKDLGNA
InterPro domains: - IPR008930: Terpenoid cyclases/protein prenyltransferase alpha-alpha toroid (homologous_superfamily) [958-1267]
- IPR050473: Alpha-2-macroglobulin/Complement system (family) [11-1472]
- IPR009048: Alpha-macroglobulin, receptor-binding (domain) [1375-1464]
- IPR041813: Alpha-2-macroglobulin, TED domain (domain) [958-1264]
- IPR036595: Alpha-macroglobulin, receptor-binding domain superfamily (homologous_superfamily) [1337-1474]
- IPR041555: Macroglobulin domain MG3 (domain) [223-312]
- IPR013783: Immunoglobulin-like fold (homologous_superfamily) [352-906]
- IPR001599: Alpha-2-macroglobulin (domain) [738-828]
- IPR011626: Alpha-macroglobulin-like, TED domain (domain) [948-1264]
- IPR010916: TonB box, conserved site (conserved_site) [1-63]
- IPR019742: Alpha-2-macroglobulin, conserved site (conserved_site) [969-977]
- IPR011625: Alpha-2-macroglobulin, bait region domain (domain) [459-607]
- IPR014756: Immunoglobulin E-set (homologous_superfamily) [786-906]
- IPR002890: Macroglobulin domain (domain) [129-221]
- IPR047565: Alpha-macroglobulin-like, thiol-ester bond-forming region (conserved_site) [961-990]
- IPR040839: Macroglobulin domain MG4 (domain) [350-445]
Interaction partners: - Apolipoprotein A-I
- Prolow-density lipoprotein receptor-related protein 1
- Haptoglobin
- Kallikrein-4
- Interleukin-1 beta
- Albumin
- Alpha-1-antitrypsin
- Apolipoprotein E
- Endoplasmic reticulum chaperone BiP
- Alpha-2-antiplasmin
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0098772 (molecular function regulator activity), GO:0030234 (enzyme regulator activity), GO:0140678 (molecular function inhibitor activity), GO:0061134 (peptidase regulator activity), GO:0004857 (enzyme inhibitor activity), GO:0061135 (endopeptidase regulator activity), GO:0030414 (peptidase inhibitor activity), GO:0004866 (endopeptidase inhibitor activity)
Biological Process (BP): GO:0008150 (biological process), GO:0000003 (reproduction), GO:0032501 (multicellular organismal process), GO:0022414 (reproductive process), GO:0044706 (multi-multicellular organism process), GO:0044703 (multi-organism reproductive process), GO:0007565 (female pregnancy)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0072562 (blood microparticle), GO:0043226 (organelle), GO:0030312 (external encapsulating structure), GO:0005615 (extracellular space), GO:0071944 (cell periphery), GO:0005576 (extracellular region), GO:0031012 (extracellular matrix), GO:0070062 (extracellular exosome), GO:0043227 (membrane-bounded organelle), GO:0043230 (extracellular organelle), GO:0065010 (extracellular membrane-bounded organelle), GO:0062023 (collagen-containing extracellular matrix), GO:0031982 (vesicle), GO:1903561 (extracellular vesicle)