ID A2MG_HUMAN Reviewed; 1474 AA. AC P01023; Q13677; Q59F47; Q5QTS0; Q68DN2; Q6PIY3; Q6PN97; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 05-OCT-2010, sequence version 3. DT 13-FEB-2019, entry version 215. DE RecName: Full=Alpha-2-macroglobulin; DE Short=Alpha-2-M; DE AltName: Full=C3 and PZP-like alpha-2-macroglobulin domain-containing protein 5; DE Flags: Precursor; GN Name=A2M; Synonyms=CPAMD5; ORFNames=FWP007; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS ASP-639 AND VAL-1000. RX PubMed=2581245; DOI=10.1073/pnas.82.8.2282; RA Kan C.-C., Solomon E., Belt K.T., Chain A.C., Hiorns L.R., Fey G.H.; RT "Nucleotide sequence of cDNA encoding human alpha 2-macroglobulin and RT assignment of the chromosomal locus."; RL Proc. Natl. Acad. Sci. U.S.A. 82:2282-2286(1985). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS ASP-639 AND VAL-1000. RC TISSUE=Prostate; RX PubMed=15611997; DOI=10.1002/pros.20183; RA Lin V.K., Wang S.-Y., Boetticher N.C., Vazquez D.V., Saboorian H., RA McConnell J.D., Roehrborn C.G.; RT "Alpha(2) macroglobulin, a PSA-binding protein, is expressed in human RT prostate stroma."; RL Prostate 63:299-308(2005). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ASP-639. RC TISSUE=Spleen; RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., RA Ohara O., Nagase T., Kikuno R.F.; RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS ASP-639 AND RP VAL-1000. RC TISSUE=Liver; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16541075; DOI=10.1038/nature04569; RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., RA Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., RA Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., RA Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., RA Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., RA Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., RA Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., RA Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., RA Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., RA Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., RA Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., RA Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., RA Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., RA Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., RA Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., RA Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., RA Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., RA Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., RA Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., RA Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., RA Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., RA Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., RA Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., RA Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., RA Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., RA Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., RA Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., RA Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., RA Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., RA Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., RA Kucherlapati R., Weinstock G., Gibbs R.A.; RT "The finished DNA sequence of human chromosome 12."; RL Nature 440:346-351(2006). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS ASP-639 AND RP VAL-1000. RC TISSUE=Skin; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-29. RC TISSUE=Placenta; RX PubMed=1374237; DOI=10.1016/0006-291X(92)90631-T; RA Matthijs G., Devriendt K., Cassiman J.-J., van den Berghe H., RA Marynen P.; RT "Structure of the human alpha-2 macroglobulin gene and its promotor."; RL Biochem. Biophys. Res. Commun. 184:596-603(1992). RN [8] RP PROTEIN SEQUENCE OF 24-1474, SUBUNIT, SUBCELLULAR LOCATION, TISSUE RP SPECIFICITY, AND DISULFIDE BONDS. RX PubMed=6203908; RA Sottrup-Jensen L., Stepanik T.M., Kristensen T., Wierzbicki D.M., RA Jones C.M., Loenblad P.B., Magnusson S., Petersen T.E.; RT "Primary structure of human alpha 2-macroglobulin. V. The complete RT structure."; RL J. Biol. Chem. 259:8318-8327(1984). RN [9] RP ERRATUM. RA Sottrup-Jensen L., Stepanik T.M., Kristensen T., Wierzbicki D.M., RA Jones C.M., Loenblad P.B., Magnusson S., Petersen T.E.; RL J. Biol. Chem. 260:6500-6500(1985). RN [10] RP PROTEIN SEQUENCE OF 273-286 AND 426-436, AND DISULFIDE BONDS. RX PubMed=2430963; RA Jensen P.E.H., Sottrup-Jensen L.; RT "Primary structure of human alpha 2-macroglobulin. Complete disulfide RT bridge assignment and localization of two interchain bridges in the RT dimeric proteinase binding unit."; RL J. Biol. Chem. 261:15863-15869(1986). RN [11] RP PROTEIN SEQUENCE OF 672-747. RX PubMed=1692292; DOI=10.1016/0014-5793(90)80226-9; RA Marynen P., Devriendt K., van den Berghe H., Cassiman J.-J.; RT "A genetic polymorphism in a functional domain of human pregnancy zone RT protein: the bait region. Genomic structure of the bait domains of RT human pregnancy zone protein and alpha 2 macroglobulin."; RL FEBS Lett. 262:349-352(1990). RN [12] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 672-746, AND VARIANT TYR-972. RX PubMed=1370808; DOI=10.1007/BF00197266; RA Poller W., Faber J.-P., Klobeck G., Olek K.; RT "Cloning of the human alpha 2-macroglobulin gene and detection of RT mutations in two functional domains: the bait region and the RT thiolester site."; RL Hum. Genet. 88:313-319(1992). RN [13] RP NUCLEOTIDE SEQUENCE [MRNA] OF 832-1474. RC TISSUE=Liver; RX PubMed=2408344; DOI=10.1007/BF01534685; RA Bell G.I., Rall L.B., Sanchez-Pescador R., Merryweather J.P., RA Scott J., Eddy R.L., Shows T.B.; RT "Human alpha 2-macroglobulin gene is located on chromosome 12."; RL Somat. Cell Mol. Genet. 11:285-289(1985). RN [14] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1208-1474. RC TISSUE=Aorta; RA Liu B., Zhao B., Wang X.Y., Xu Y.Y., Liu Y.Q., Song L., Ye J., RA Sheng H., Gao Y., Zhang C.L., Wei Y.J., Zhang J., Song L., Jiang Y.X., RA Zhao Z.W., Ding J.F., Liu L.S., Gao R.L., Wu Q.Y., Qiang B.Q., RA Yuan J.G., Liew C.C., Zhao M.S., Hui R.T.; RL Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases. RN [15] RP INHIBITORY SITE. RX PubMed=6167263; DOI=10.1016/S0006-291X(81)80055-1; RA Hall P.K., Nelles L.P., Travis J., Roberts R.C.; RT "Proteolytic cleavage sites on alpha 2-macroglobulin resulting in RT proteinase binding are different for trypsin and Staphylococcus aureus RT V-8 proteinase."; RL Biochem. Biophys. Res. Commun. 100:8-16(1981). RN [16] RP INHIBITORY SITE. RX PubMed=6165619; DOI=10.1016/0014-5793(81)80197-4; RA Sottrup-Jensen L., Loenblad P.B., Stepanik T.M., Petersen T.E., RA Magnusson S., Joernvall H.; RT "Primary structure of the 'bait' region for proteinases in alpha 2- RT macroglobulin. Nature of the complex."; RL FEBS Lett. 127:167-173(1981). RN [17] RP INHIBITORY SITE. RX PubMed=6172288; DOI=10.1016/0014-5793(81)80804-6; RA Mortensen S.B., Sottrup-Jensen L., Hansen H.F., Petersen T.E., RA Magnusson S.; RT "Primary and secondary cleavage sites in the bait region of alpha 2- RT macroglobulin."; RL FEBS Lett. 135:295-300(1981). RN [18] RP INHIBITORY SITE. RX PubMed=6195065; RA Virca G.D., Salvesen G.S., Travis J.; RT "Human neutrophil elastase and cathepsin G cleavage sites in the bait RT region of alpha 2-macroglobulin. Proposed structural limits of the RT bait region."; RL Hoppe-Seyler's Z. Physiol. Chem. 364:1297-1302(1983). RN [19] RP GLYCOSYLATION AT ASN-991. RX PubMed=12754519; DOI=10.1038/nbt827; RA Zhang H., Li X.-J., Martin D.B., Aebersold R.; RT "Identification and quantification of N-linked glycoproteins using RT hydrazide chemistry, stable isotope labeling and mass spectrometry."; RL Nat. Biotechnol. 21:660-666(2003). RN [20] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-869 AND ASN-1424. RC TISSUE=Plasma; RX PubMed=14760718; DOI=10.1002/pmic.200300556; RA Bunkenborg J., Pilch B.J., Podtelejnikov A.V., Wisniewski J.R.; RT "Screening for N-glycosylated proteins by liquid chromatography mass RT spectrometry."; RL Proteomics 4:454-465(2004). RN [21] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-55; ASN-247; ASN-396; RP ASN-410; ASN-869; ASN-991 AND ASN-1424. RC TISSUE=Plasma; RX PubMed=16335952; DOI=10.1021/pr0502065; RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., RA Moore R.J., Smith R.D.; RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction, RT hydrazide chemistry, and mass spectrometry."; RL J. Proteome Res. 4:2070-2080(2005). RN [22] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-396; ASN-991 AND ASN-1424. RC TISSUE=Liver; RX PubMed=19159218; DOI=10.1021/pr8008012; RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.; RT "Glycoproteomics analysis of human liver tissue by combination of RT multiple enzyme digestion and hydrazide chemistry."; RL J. Proteome Res. 8:651-661(2009). RN [23] RP GLYCOSYLATION AT ASN-55 AND ASN-1424. RX PubMed=19139490; DOI=10.1074/mcp.M800504-MCP200; RA Jia W., Lu Z., Fu Y., Wang H.P., Wang L.H., Chi H., Yuan Z.F., RA Zheng Z.B., Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y., RA Zhang Y.K., Deng Y.L., Ying W.T., He S.M., Qian X.H.; RT "A strategy for precise and large scale identification of core RT fucosylated glycoproteins."; RL Mol. Cell. Proteomics 8:913-923(2009). RN [24] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [25] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [26] RP STRUCTURE BY NMR OF 1337-1474. RX PubMed=9865955; DOI=10.1002/pro.5560071214; RA Huang W., Dolmer K., Liao X., Gettins P.G.W.; RT "Localization of basic residues required for receptor binding to the RT single alpha-helix of the receptor binding domain of human alpha2- RT macroglobulin."; RL Protein Sci. 7:2602-2612(1998). RN [27] RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 126-227, AND DOMAIN RP STRUCTURE. RX PubMed=17608619; DOI=10.1042/BJ20070764; RA Doan N., Gettins P.G.W.; RT "Human alpha2-macroglobulin is composed of multiple domains, as RT predicted by homology with complement component C3."; RL Biochem. J. 407:23-30(2007). RN [28] RP VARIANT VAL-1000. RX PubMed=1707161; DOI=10.1093/nar/19.1.198-a; RA Poller W., Faber J.-P., Olek K.; RT "Sequence polymorphism in the human alpha2-macroglobulin (A2M) gene."; RL Nucleic Acids Res. 19:198-198(1991). CC -!- FUNCTION: Is able to inhibit all four classes of proteinases by a CC unique 'trapping' mechanism. This protein has a peptide stretch, CC called the 'bait region' which contains specific cleavage sites CC for different proteinases. When a proteinase cleaves the bait CC region, a conformational change is induced in the protein which CC traps the proteinase. The entrapped enzyme remains active against CC low molecular weight substrates (activity against high molecular CC weight substrates is greatly reduced). Following cleavage in the CC bait region, a thioester bond is hydrolyzed and mediates the CC covalent binding of the protein to the proteinase. CC -!- SUBUNIT: Homotetramer; disulfide-linked. CC {ECO:0000269|PubMed:2430963, ECO:0000269|PubMed:6203908}. CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:6203908}. CC -!- TISSUE SPECIFICITY: Secreted in plasma. CC {ECO:0000269|PubMed:6203908}. CC -!- DEVELOPMENTAL STAGE: Unlike the rat protein, which is an acute CC phase protein, this protein is always in circulation at high CC levels. CC -!- SIMILARITY: Belongs to the protease inhibitor I39 (alpha-2- CC macroglobulin) family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAT02228.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305}; CC Sequence=BAD92851.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Wikipedia; Note=Alpha-2 macroglobulin entry; CC URL="https://en.wikipedia.org/wiki/Alpha_2-macroglobulin"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC ----------------------------------------------------------------------- DR EMBL; M11313; AAA51551.1; -; mRNA. DR EMBL; AY591530; AAT02228.1; ALT_INIT; mRNA. DR EMBL; AB209614; BAD92851.1; ALT_INIT; mRNA. DR EMBL; CR749334; CAH18188.1; -; mRNA. DR EMBL; AC007436; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC026246; AAH26246.1; -; mRNA. DR EMBL; BC040071; AAH40071.1; -; mRNA. DR EMBL; Z11711; CAA77774.1; -; Genomic_DNA. DR EMBL; X68728; CAA48670.1; -; Genomic_DNA. DR EMBL; X68729; CAA48670.1; JOINED; Genomic_DNA. DR EMBL; M36501; AAA51552.1; -; mRNA. DR EMBL; AF109189; AAQ13498.1; -; mRNA. DR CCDS; CCDS44827.1; -. DR PIR; A94033; MAHU. DR RefSeq; NP_000005.2; NM_000014.5. DR RefSeq; NP_001334352.1; NM_001347423.1. DR RefSeq; NP_001334353.1; NM_001347424.1. DR RefSeq; NP_001334354.1; NM_001347425.1. DR UniGene; Hs.212838; -. DR UniGene; Hs.88556; -. DR PDB; 1BV8; NMR; -; A=1337-1474. DR PDB; 2P9R; X-ray; 2.30 A; A/B=126-227. DR PDB; 4ACQ; X-ray; 4.30 A; A/B/C/D=24-1474. DR PDBsum; 1BV8; -. DR PDBsum; 2P9R; -. DR PDBsum; 4ACQ; -. DR ProteinModelPortal; P01023; -. DR SMR; P01023; -. DR BioGrid; 106524; 109. DR CORUM; P01023; -. DR DIP; DIP-1118N; -. DR IntAct; P01023; 105. DR MINT; P01023; -. DR STRING; 9606.ENSP00000323929; -. DR DrugBank; DB00626; Bacitracin. DR DrugBank; DB00102; Becaplermin. DR DrugBank; DB08888; Ocriplasmin. DR MEROPS; I39.001; -. DR MoonDB; P01023; Predicted. DR CarbonylDB; P01023; -. DR GlyConnect; 730; -. DR iPTMnet; P01023; -. DR PhosphoSitePlus; P01023; -. DR SwissPalm; P01023; -. DR BioMuta; A2M; -. DR DMDM; 308153640; -. DR DOSAC-COBS-2DPAGE; P01023; -. DR SWISS-2DPAGE; P01023; -. DR EPD; P01023; -. DR jPOST; P01023; -. DR MaxQB; P01023; -. DR PaxDb; P01023; -. DR PeptideAtlas; P01023; -. DR PRIDE; P01023; -. DR ProteomicsDB; 51307; -. DR Ensembl; ENST00000318602; ENSP00000323929; ENSG00000175899. DR GeneID; 2; -. DR KEGG; hsa:2; -. DR UCSC; uc001qvk.2; human. DR CTD; 2; -. DR DisGeNET; 2; -. DR EuPathDB; HostDB:ENSG00000175899.14; -. DR GeneCards; A2M; -. DR H-InvDB; HIX0026392; -. DR HGNC; HGNC:7; A2M. DR HPA; CAB017621; -. DR HPA; HPA002265; -. DR MalaCards; A2M; -. DR MIM; 103950; gene. DR neXtProt; NX_P01023; -. DR OpenTargets; ENSG00000175899; -. DR PharmGKB; PA24357; -. DR eggNOG; KOG1366; Eukaryota. DR eggNOG; ENOG410XRED; LUCA. DR GeneTree; ENSGT00940000154904; -. DR HOVERGEN; HBG000039; -. DR InParanoid; P01023; -. DR KO; K03910; -. DR OMA; TKIFQMK; -. DR OrthoDB; 100680at2759; -. DR PhylomeDB; P01023; -. DR TreeFam; TF313285; -. DR Reactome; R-HSA-114608; Platelet degranulation. DR Reactome; R-HSA-140837; Intrinsic Pathway of Fibrin Clot Formation. DR Reactome; R-HSA-1474228; Degradation of the extracellular matrix. DR Reactome; R-HSA-194840; Rho GTPase cycle. DR Reactome; R-HSA-8963896; HDL assembly. DR ChiTaRS; A2M; human. DR EvolutionaryTrace; P01023; -. DR GenomeRNAi; 2; -. DR PRO; PR:P01023; -. DR Proteomes; UP000005640; Chromosome 12. DR Bgee; ENSG00000175899; Expressed in 235 organ(s), highest expression level in lung. DR ExpressionAtlas; P01023; baseline and differential. DR Genevisible; P01023; HS. DR GO; GO:0072562; C:blood microparticle; HDA:UniProtKB. DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0031093; C:platelet alpha granule lumen; TAS:Reactome. DR GO; GO:0048306; F:calcium-dependent protein binding; IPI:AgBase. DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB. DR GO; GO:0019838; F:growth factor binding; IDA:UniProtKB. DR GO; GO:0005096; F:GTPase activator activity; TAS:Reactome. DR GO; GO:0019966; F:interleukin-1 binding; IDA:UniProtKB. DR GO; GO:0019959; F:interleukin-8 binding; IPI:UniProtKB. DR GO; GO:0002020; F:protease binding; IPI:BHF-UCL. DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IDA:UniProtKB. DR GO; GO:0005102; F:signaling receptor binding; IMP:AgBase. DR GO; GO:0043120; F:tumor necrosis factor binding; IDA:UniProtKB. DR GO; GO:0007597; P:blood coagulation, intrinsic pathway; TAS:Reactome. DR GO; GO:0022617; P:extracellular matrix disassembly; TAS:Reactome. DR GO; GO:0001869; P:negative regulation of complement activation, lectin pathway; IDA:UniProtKB. DR GO; GO:0002576; P:platelet degranulation; TAS:Reactome. DR GO; GO:0051056; P:regulation of small GTPase mediated signal transduction; TAS:Reactome. DR GO; GO:0048863; P:stem cell differentiation; IEA:Ensembl. DR Gene3D; 2.60.40.10; -; 2. DR Gene3D; 2.60.40.690; -; 1. DR InterPro; IPR009048; A-macroglobulin_rcpt-bd. DR InterPro; IPR036595; A-macroglobulin_rcpt-bd_sf. DR InterPro; IPR011625; A2M_N_BRD. DR InterPro; IPR011626; Alpha-macroglobulin_TED. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR014756; Ig_E-set. DR InterPro; IPR001599; Macroglobln_a2. DR InterPro; IPR019742; MacrogloblnA2_CS. DR InterPro; IPR002890; MG2. DR InterPro; IPR008930; Terpenoid_cyclase/PrenylTrfase. DR InterPro; IPR010916; TonB_box_CS. DR Pfam; PF00207; A2M; 1. DR Pfam; PF07703; A2M_BRD; 1. DR Pfam; PF07677; A2M_recep; 1. DR Pfam; PF01835; MG2; 1. DR Pfam; PF07678; TED_complement; 1. DR SMART; SM01360; A2M; 1. DR SMART; SM01359; A2M_N_2; 1. DR SMART; SM01361; A2M_recep; 1. DR SUPFAM; SSF48239; SSF48239; 1. DR SUPFAM; SSF49410; SSF49410; 1. DR SUPFAM; SSF81296; SSF81296; 1. DR PROSITE; PS00477; ALPHA_2_MACROGLOBULIN; 1. PE 1: Evidence at protein level; KW 3D-structure; Bait region; Complete proteome; KW Direct protein sequencing; Disulfide bond; Glycoprotein; KW Isopeptide bond; Polymorphism; Protease inhibitor; Reference proteome; KW Secreted; Serine protease inhibitor; Signal; Thioester bond. FT SIGNAL 1 23 {ECO:0000269|PubMed:6203908}. FT CHAIN 24 1474 Alpha-2-macroglobulin. FT {ECO:0000269|PubMed:6203908}. FT /FTId=PRO_0000000055. FT REGION 690 728 Bait region. FT REGION 704 709 Inhibitory. FT REGION 719 723 Inhibitory. FT REGION 730 735 Inhibitory. FT CARBOHYD 55 55 N-linked (GlcNAc...) (complex) FT asparagine. {ECO:0000269|PubMed:16335952, FT ECO:0000269|PubMed:19139490}. FT CARBOHYD 70 70 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:6203908}. FT CARBOHYD 247 247 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:16335952, FT ECO:0000269|PubMed:6203908}. FT CARBOHYD 396 396 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:16335952, FT ECO:0000269|PubMed:19159218, FT ECO:0000269|PubMed:6203908}. FT CARBOHYD 410 410 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:16335952, FT ECO:0000269|PubMed:6203908}. FT CARBOHYD 869 869 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:14760718, FT ECO:0000269|PubMed:16335952}. FT CARBOHYD 991 991 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:12754519, FT ECO:0000269|PubMed:16335952, FT ECO:0000269|PubMed:19159218, FT ECO:0000269|PubMed:6203908}. FT CARBOHYD 1424 1424 N-linked (GlcNAc...) (complex) FT asparagine. {ECO:0000269|PubMed:14760718, FT ECO:0000269|PubMed:16335952, FT ECO:0000269|PubMed:19139490, FT ECO:0000269|PubMed:19159218}. FT DISULFID 48 86 {ECO:0000269|PubMed:6203908}. FT DISULFID 251 299 {ECO:0000269|PubMed:6203908}. FT DISULFID 269 287 {ECO:0000269|PubMed:6203908}. FT DISULFID 278 278 Interchain (with C-431). FT {ECO:0000269|PubMed:2430963}. FT DISULFID 431 431 Interchain (with C-278). FT {ECO:0000269|PubMed:2430963}. FT DISULFID 470 563 {ECO:0000269|PubMed:2430963}. FT DISULFID 595 771 {ECO:0000269|PubMed:2430963, FT ECO:0000269|PubMed:6203908}. FT DISULFID 642 689 {ECO:0000269|PubMed:6203908}. FT DISULFID 821 849 {ECO:0000269|PubMed:6203908}. FT DISULFID 847 883 {ECO:0000269|PubMed:6203908}. FT DISULFID 921 1321 {ECO:0000269|PubMed:6203908}. FT DISULFID 1079 1127 {ECO:0000269|PubMed:6203908}. FT DISULFID 1352 1467 {ECO:0000269|PubMed:6203908}. FT CROSSLNK 693 693 Isoglutamyl lysine isopeptide (Gln-Lys) FT (interchain with K-? in other proteins). FT {ECO:0000255}. FT CROSSLNK 694 694 Isoglutamyl lysine isopeptide (Gln-Lys) FT (interchain with K-? in other proteins). FT {ECO:0000255}. FT CROSSLNK 972 975 Isoglutamyl cysteine thioester (Cys-Gln). FT {ECO:0000269|PubMed:6203908}. FT VARIANT 639 639 N -> D (in dbSNP:rs226405). FT {ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:15611997, FT ECO:0000269|PubMed:17974005, FT ECO:0000269|PubMed:2581245, FT ECO:0000269|Ref.3}. FT /FTId=VAR_026820. FT VARIANT 704 704 R -> H (in dbSNP:rs1800434). FT /FTId=VAR_000012. FT VARIANT 815 815 L -> Q (in dbSNP:rs3180392). FT /FTId=VAR_026821. FT VARIANT 972 972 C -> Y (probably interferes with the FT activity; dbSNP:rs1800433). FT {ECO:0000269|PubMed:1370808}. FT /FTId=VAR_000013. FT VARIANT 1000 1000 I -> V (in dbSNP:rs669). FT {ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:15611997, FT ECO:0000269|PubMed:1707161, FT ECO:0000269|PubMed:17974005, FT ECO:0000269|PubMed:2581245}. FT /FTId=VAR_000014. FT CONFLICT 63 63 Missing (in Ref. 8; AA sequence). FT {ECO:0000305}. FT CONFLICT 82 82 D -> V (in Ref. 3; AAT02228). FT {ECO:0000305}. FT CONFLICT 350 353 LSFV -> ACCS (in Ref. 6; AAH26246). FT {ECO:0000305}. FT CONFLICT 563 563 C -> E (in Ref. 8; AA sequence). FT {ECO:0000305}. FT CONFLICT 844 844 A -> V (in Ref. 4; BAD92851). FT {ECO:0000305}. FT CONFLICT 872 872 V -> M (in Ref. 5; CAH18188). FT {ECO:0000305}. FT CONFLICT 1148 1148 A -> D (in Ref. 13; AAA51552). FT {ECO:0000305}. FT CONFLICT 1195 1195 H -> D (in Ref. 13; AAA51552). FT {ECO:0000305}. FT STRAND 128 134 {ECO:0000244|PDB:2P9R}. FT STRAND 136 138 {ECO:0000244|PDB:2P9R}. FT STRAND 143 151 {ECO:0000244|PDB:2P9R}. FT HELIX 153 155 {ECO:0000244|PDB:2P9R}. FT STRAND 161 168 {ECO:0000244|PDB:2P9R}. FT STRAND 174 182 {ECO:0000244|PDB:2P9R}. FT STRAND 187 193 {ECO:0000244|PDB:2P9R}. FT STRAND 201 208 {ECO:0000244|PDB:2P9R}. FT STRAND 214 221 {ECO:0000244|PDB:2P9R}. FT STRAND 1341 1347 {ECO:0000244|PDB:1BV8}. FT HELIX 1355 1359 {ECO:0000244|PDB:1BV8}. FT STRAND 1360 1369 {ECO:0000244|PDB:1BV8}. FT STRAND 1379 1384 {ECO:0000244|PDB:1BV8}. FT STRAND 1389 1391 {ECO:0000244|PDB:1BV8}. FT HELIX 1393 1400 {ECO:0000244|PDB:1BV8}. FT TURN 1401 1403 {ECO:0000244|PDB:1BV8}. FT STRAND 1407 1410 {ECO:0000244|PDB:1BV8}. FT STRAND 1412 1419 {ECO:0000244|PDB:1BV8}. FT STRAND 1427 1434 {ECO:0000244|PDB:1BV8}. FT STRAND 1445 1450 {ECO:0000244|PDB:1BV8}. FT STRAND 1454 1456 {ECO:0000244|PDB:1BV8}. FT STRAND 1459 1463 {ECO:0000244|PDB:1BV8}. SQ SEQUENCE 1474 AA; 163291 MW; 0A46DF09EFD3CF40 CRC64; MGKNKLLHPS LVLLLLVLLP TDASVSGKPQ YMVLVPSLLH TETTEKGCVL LSYLNETVTV SASLESVRGN RSLFTDLEAE NDVLHCVAFA VPKSSSNEEV MFLTVQVKGP TQEFKKRTTV MVKNEDSLVF VQTDKSIYKP GQTVKFRVVS MDENFHPLNE LIPLVYIQDP KGNRIAQWQS FQLEGGLKQF SFPLSSEPFQ GSYKVVVQKK SGGRTEHPFT VEEFVLPKFE VQVTVPKIIT ILEEEMNVSV CGLYTYGKPV PGHVTVSICR KYSDASDCHG EDSQAFCEKF SGQLNSHGCF YQQVKTKVFQ LKRKEYEMKL HTEAQIQEEG TVVELTGRQS SEITRTITKL SFVKVDSHFR QGIPFFGQVR LVDGKGVPIP NKVIFIRGNE ANYYSNATTD EHGLVQFSIN TTNVMGTSLT VRVNYKDRSP CYGYQWVSEE HEEAHHTAYL VFSPSKSFVH LEPMSHELPC GHTQTVQAHY ILNGGTLLGL KKLSFYYLIM AKGGIVRTGT HGLLVKQEDM KGHFSISIPV KSDIAPVARL LIYAVLPTGD VIGDSAKYDV ENCLANKVDL SFSPSQSLPA SHAHLRVTAA PQSVCALRAV DQSVLLMKPD AELSASSVYN LLPEKDLTGF PGPLNDQDNE DCINRHNVYI NGITYTPVSS TNEKDMYSFL EDMGLKAFTN SKIRKPKMCP QLQQYEMHGP EGLRVGFYES DVMGRGHARL VHVEEPHTET VRKYFPETWI WDLVVVNSAG VAEVGVTVPD TITEWKAGAF CLSEDAGLGI SSTASLRAFQ PFFVELTMPY SVIRGEAFTL KATVLNYLPK CIRVSVQLEA SPAFLAVPVE KEQAPHCICA NGRQTVSWAV TPKSLGNVNF TVSAEALESQ ELCGTEVPSV PEHGRKDTVI KPLLVEPEGL EKETTFNSLL CPSGGEVSEE LSLKLPPNVV EESARASVSV LGDILGSAMQ NTQNLLQMPY GCGEQNMVLF APNIYVLDYL NETQQLTPEI KSKAIGYLNT GYQRQLNYKH YDGSYSTFGE RYGRNQGNTW LTAFVLKTFA QARAYIFIDE AHITQALIWL SQRQKDNGCF RSSGSLLNNA IKGGVEDEVT LSAYITIALL EIPLTVTHPV VRNALFCLES AWKTAQEGDH GSHVYTKALL AYAFALAGNQ DKRKEVLKSL NEEAVKKDNS VHWERPQKPK APVGHFYEPQ APSAEVEMTS YVLLAYLTAQ PAPTSEDLTS ATNIVKWITK QQNAQGGFSS TQDTVVALHA LSKYGAATFT RTGKAAQVTI QSSGTFSSKF QVDNNNRLLL QQVSLPELPG EYSMKVTGEG CVYLQTSLKY NILPEKEEFP FALGVQTLPQ TCDEPKAHTS FQISLSVSYT GSRSASNMAI VDVKMVSGFI PLKPTVKMLE RSNHVSRTEV SSNHVLIYLD KVSNQTLSLF FTVLQDVPVR DLKPAIVKVY DYYETDEFAI AEYNAPCSKD LGNA //