A2MG_HUMAN
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 03-AUG-2022, entry version 234.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC 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 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., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA 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., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., 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., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., 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., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA 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 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 project:
RT 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., 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; DOI=10.1016/s0021-9258(17)39730-2;
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 OF 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.;
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; DOI=10.1016/s0021-9258(18)66643-8;
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 dimeric
RT 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 human
RT 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 mutations
RT in two functional domains: the bait region and the 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., Scott J.,
RA 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., Sheng H.,
RA Gao Y., Zhang C.L., Wei Y.J., Zhang J., Song L., Jiang Y.X., Zhao Z.W.,
RA Ding J.F., Liu L.S., Gao R.L., Wu Q.Y., Qiang B.Q., Yuan J.G., Liew C.C.,
RA 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 V-8
RT 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; DOI=10.1515/bchm2.1983.364.2.1297;
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 bait
RT 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; ASN-410;
RP 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., Moore R.J.,
RA 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 multiple
RT 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., Zheng Z.B.,
RA Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y., Zhang Y.K., Deng Y.L.,
RA Ying W.T., He S.M., Qian X.H.;
RT "A strategy for precise and large scale identification of core fucosylated
RT 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., Buerckstuemmer T.,
RA 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., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT 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 single
RT alpha-helix of the receptor binding domain of human alpha2-macroglobulin.";
RL Protein Sci. 7:2602-2612(1998).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 126-227, AND DOMAIN 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 predicted
RT 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, called
CC the 'bait region' which contains specific cleavage sites for different
CC proteinases. When a proteinase cleaves the bait region, a
CC conformational change is induced in the protein which traps the
CC proteinase. The entrapped enzyme remains active against low molecular
CC weight substrates (activity against high molecular weight substrates is
CC greatly reduced). Following cleavage in the bait region, a thioester
CC bond is hydrolyzed and mediates the covalent binding of the protein to
CC the proteinase.
CC -!- SUBUNIT: Homotetramer; disulfide-linked. {ECO:0000269|PubMed:2430963,
CC ECO:0000269|PubMed:6203908}.
CC -!- INTERACTION:
CC P01023; Q6PCB6: ABHD17C; NbExp=3; IntAct=EBI-640741, EBI-22011868;
CC P01023; P63010-2: AP2B1; NbExp=3; IntAct=EBI-640741, EBI-11529439;
CC P01023; Q9UII2: ATP5IF1; NbExp=3; IntAct=EBI-640741, EBI-718459;
CC P01023; Q8WUW1: BRK1; NbExp=3; IntAct=EBI-640741, EBI-2837444;
CC P01023; Q92478: CLEC2B; NbExp=3; IntAct=EBI-640741, EBI-13350535;
CC P01023; Q9UNS2: COPS3; NbExp=3; IntAct=EBI-640741, EBI-350590;
CC P01023; P04141: CSF2; NbExp=3; IntAct=EBI-640741, EBI-1809826;
CC P01023; P35222: CTNNB1; NbExp=3; IntAct=EBI-640741, EBI-491549;
CC P01023; Q7L576: CYFIP1; NbExp=3; IntAct=EBI-640741, EBI-1048143;
CC P01023; Q9NR90-2: DAZ3; NbExp=3; IntAct=EBI-640741, EBI-25830216;
CC P01023; Q9UHI6: DDX20; NbExp=3; IntAct=EBI-640741, EBI-347658;
CC P01023; Q9H147: DNTTIP1; NbExp=3; IntAct=EBI-640741, EBI-2795449;
CC P01023; O75616: ERAL1; NbExp=3; IntAct=EBI-640741, EBI-6393536;
CC P01023; Q9Y261-2: FOXA2; NbExp=3; IntAct=EBI-640741, EBI-25830360;
CC P01023; Q6PIV2: FOXR1; NbExp=3; IntAct=EBI-640741, EBI-10253815;
CC P01023; Q9ULV1: FZD4; NbExp=3; IntAct=EBI-640741, EBI-2466380;
CC P01023; P0C0S5: H2AZ1; NbExp=3; IntAct=EBI-640741, EBI-1199859;
CC P01023; P68431: H3C12; NbExp=3; IntAct=EBI-640741, EBI-79722;
CC P01023; P09017: HOXC4; NbExp=3; IntAct=EBI-640741, EBI-3923226;
CC P01023; Q6DN90-2: IQSEC1; NbExp=3; IntAct=EBI-640741, EBI-21911304;
CC P01023; Q92993: KAT5; NbExp=3; IntAct=EBI-640741, EBI-399080;
CC P01023; Q92993-2: KAT5; NbExp=3; IntAct=EBI-640741, EBI-20795332;
CC P01023; P60409: KRTAP10-7; NbExp=3; IntAct=EBI-640741, EBI-10172290;
CC P01023; Q8IUC2: KRTAP8-1; NbExp=3; IntAct=EBI-640741, EBI-10261141;
CC P01023; Q9UPM6: LHX6; NbExp=3; IntAct=EBI-640741, EBI-10258746;
CC P01023; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-640741, EBI-739832;
CC P01023; P07948: LYN; NbExp=3; IntAct=EBI-640741, EBI-79452;
CC P01023; Q8TDB4: MGARP; NbExp=3; IntAct=EBI-640741, EBI-4397720;
CC P01023; A4FUJ8: MKL1; NbExp=3; IntAct=EBI-640741, EBI-21250407;
CC P01023; P41218: MNDA; NbExp=3; IntAct=EBI-640741, EBI-2829677;
CC P01023; Q9Y605: MRFAP1; NbExp=3; IntAct=EBI-640741, EBI-995714;
CC P01023; Q96FW1: OTUB1; NbExp=3; IntAct=EBI-640741, EBI-1058491;
CC P01023; Q6GQQ9-2: OTUD7B; NbExp=3; IntAct=EBI-640741, EBI-25830200;
CC P01023; Q99497: PARK7; NbExp=3; IntAct=EBI-640741, EBI-1164361;
CC P01023; O75925: PIAS1; NbExp=3; IntAct=EBI-640741, EBI-629434;
CC P01023; P27986-2: PIK3R1; NbExp=3; IntAct=EBI-640741, EBI-9090282;
CC P01023; O75626-3: PRDM1; NbExp=3; IntAct=EBI-640741, EBI-25829882;
CC P01023; P57729: RAB38; NbExp=3; IntAct=EBI-640741, EBI-6552718;
CC P01023; Q9ULX5: RNF112; NbExp=3; IntAct=EBI-640741, EBI-25829984;
CC P01023; Q96D59: RNF183; NbExp=3; IntAct=EBI-640741, EBI-743938;
CC P01023; P04271: S100B; NbExp=3; IntAct=EBI-640741, EBI-458391;
CC P01023; Q16637-3: SMN2; NbExp=3; IntAct=EBI-640741, EBI-395447;
CC P01023; Q7Z6I5: SPATA12; NbExp=3; IntAct=EBI-640741, EBI-10696971;
CC P01023; Q9UNE7: STUB1; NbExp=3; IntAct=EBI-640741, EBI-357085;
CC P01023; O75558: STX11; NbExp=3; IntAct=EBI-640741, EBI-714135;
CC P01023; Q8N4C7: STX19; NbExp=3; IntAct=EBI-640741, EBI-8484990;
CC P01023; P43405-2: SYK; NbExp=3; IntAct=EBI-640741, EBI-25892332;
CC P01023; P28347-2: TEAD1; NbExp=3; IntAct=EBI-640741, EBI-12151837;
CC P01023; Q86WT6-2: TRIM69; NbExp=3; IntAct=EBI-640741, EBI-11525489;
CC P01023; Q8WVJ9: TWIST2; NbExp=3; IntAct=EBI-640741, EBI-1797313;
CC P01023; P10599: TXN; NbExp=3; IntAct=EBI-640741, EBI-594644;
CC P01023; Q9BVJ6: UTP14A; NbExp=3; IntAct=EBI-640741, EBI-473284;
CC P01023; Q9UBQ0-2: VPS29; NbExp=3; IntAct=EBI-640741, EBI-11141397;
CC P01023; Q96AX1: VPS33A; NbExp=3; IntAct=EBI-640741, EBI-2527283;
CC P01023; Q8N895: ZNF366; NbExp=3; IntAct=EBI-640741, EBI-2813661;
CC P01023; Q99KR7: Ppif; Xeno; NbExp=3; IntAct=EBI-640741, EBI-6455001;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:6203908}.
CC -!- TISSUE SPECIFICITY: Secreted in plasma. {ECO:0000269|PubMed:6203908}.
CC -!- DEVELOPMENTAL STAGE: Unlike the rat protein, which is an acute phase
CC protein, this protein is always in circulation at high 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=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAD92851.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Alpha-2 macroglobulin entry;
CC URL="https://en.wikipedia.org/wiki/Alpha_2-macroglobulin";
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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 PDB; 1BV8; NMR; -; A=1337-1474.
DR PDB; 2P9R; X-ray; 2.30 A; A/B=126-227.
DR PDB; 6TAV; X-ray; 4.20 A; A/B/C/D=1-1474.
DR PDB; 7O7M; EM; 6.60 A; A/B/C/D=1-1474.
DR PDB; 7O7N; EM; 7.30 A; A/B/C/D=1-1474.
DR PDB; 7O7O; EM; 4.80 A; A/B/C/D=1-1474.
DR PDB; 7O7P; EM; 4.60 A; A/B/C/D=1-1474.
DR PDB; 7O7Q; EM; 3.60 A; A/B/C/D=1-1474.
DR PDB; 7O7R; EM; 3.90 A; A/B/C/D=1-1474.
DR PDB; 7O7S; EM; 4.30 A; A/B/C/D=1-1474.
DR PDBsum; 1BV8; -.
DR PDBsum; 2P9R; -.
DR PDBsum; 6TAV; -.
DR PDBsum; 7O7M; -.
DR PDBsum; 7O7N; -.
DR PDBsum; 7O7O; -.
DR PDBsum; 7O7P; -.
DR PDBsum; 7O7Q; -.
DR PDBsum; 7O7R; -.
DR PDBsum; 7O7S; -.
DR AlphaFoldDB; P01023; -.
DR BMRB; P01023; -.
DR PCDDB; P01023; -.
DR SASBDB; P01023; -.
DR SMR; P01023; -.
DR BioGRID; 106524; 333.
DR CORUM; P01023; -.
DR DIP; DIP-1118N; -.
DR IntAct; P01023; 185.
DR MINT; P01023; -.
DR STRING; 9606.ENSP00000323929; -.
DR BindingDB; P01023; -.
DR ChEMBL; CHEMBL4295690; -.
DR DrugBank; DB00626; Bacitracin.
DR DrugBank; DB00102; Becaplermin.
DR DrugBank; DB00515; Cisplatin.
DR DrugBank; DB09130; Copper.
DR DrugBank; DB06796; Mangafodipir.
DR DrugBank; DB08888; Ocriplasmin.
DR DrugBank; DB12965; Silver.
DR DrugBank; DB01593; Zinc.
DR DrugBank; DB14487; Zinc acetate.
DR DrugBank; DB14533; Zinc chloride.
DR DrugBank; DB14548; Zinc sulfate, unspecified form.
DR MEROPS; I39.001; -.
DR MoonDB; P01023; Predicted.
DR CarbonylDB; P01023; -.
DR GlyConnect; 730; 47 N-Linked glycans (7 sites).
DR GlyGen; P01023; 15 sites, 72 N-linked glycans (7 sites), 3 O-linked glycans (7 sites).
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 CPTAC; non-CPTAC-1068; -.
DR EPD; P01023; -.
DR jPOST; P01023; -.
DR MassIVE; P01023; -.
DR MaxQB; P01023; -.
DR PaxDb; P01023; -.
DR PeptideAtlas; P01023; -.
DR PRIDE; P01023; -.
DR ProteomicsDB; 51307; -.
DR Antibodypedia; 859; 939 antibodies from 41 providers.
DR DNASU; 2; -.
DR Ensembl; ENST00000318602.12; ENSP00000323929.8; ENSG00000175899.15.
DR GeneID; 2; -.
DR KEGG; hsa:2; -.
DR MANE-Select; ENST00000318602.12; ENSP00000323929.8; NM_000014.6; NP_000005.3.
DR UCSC; uc001qvk.2; human.
DR CTD; 2; -.
DR DisGeNET; 2; -.
DR GeneCards; A2M; -.
DR HGNC; HGNC:7; A2M.
DR HPA; ENSG00000175899; Tissue enhanced (lung).
DR MalaCards; A2M; -.
DR MIM; 103950; gene.
DR neXtProt; NX_P01023; -.
DR OpenTargets; ENSG00000175899; -.
DR PharmGKB; PA24357; -.
DR VEuPathDB; HostDB:ENSG00000175899; -.
DR eggNOG; KOG1366; Eukaryota.
DR GeneTree; ENSGT00940000154904; -.
DR HOGENOM; CLU_001634_0_1_1; -.
DR InParanoid; P01023; -.
DR OMA; CFGEESQ; -.
DR OrthoDB; 354230at2759; -.
DR PhylomeDB; P01023; -.
DR TreeFam; TF313285; -.
DR PathwayCommons; P01023; -.
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-8963896; HDL assembly.
DR SignaLink; P01023; -.
DR SIGNOR; P01023; -.
DR BioGRID-ORCS; 2; 6 hits in 1068 CRISPR screens.
DR ChiTaRS; A2M; human.
DR EvolutionaryTrace; P01023; -.
DR GenomeRNAi; 2; -.
DR Pharos; P01023; Tbio.
DR PRO; PR:P01023; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; P01023; protein.
DR Bgee; ENSG00000175899; Expressed in lower lobe of lung and 201 other tissues.
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:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0031093; C:platelet alpha granule lumen; TAS:Reactome.
DR GO; GO:0048403; F:brain-derived neurotrophic factor binding; IEA:Ensembl.
DR GO; GO:0048306; F:calcium-dependent protein binding; IPI:AgBase.
DR GO; GO:0004866; F:endopeptidase inhibitor activity; IBA:GO_Central.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0019838; F:growth factor binding; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0019966; F:interleukin-1 binding; IDA:UniProtKB.
DR GO; GO:0019959; F:interleukin-8 binding; IPI:UniProtKB.
DR GO; GO:0048406; F:nerve growth factor binding; IEA:Ensembl.
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:0002438; P:acute inflammatory response to antigenic stimulus; IEA:Ensembl.
DR GO; GO:0006953; P:acute-phase response; IEA:Ensembl.
DR GO; GO:1990402; P:embryonic liver development; IEA:Ensembl.
DR GO; GO:0001553; P:luteinization; IEA:Ensembl.
DR GO; GO:0001869; P:negative regulation of complement activation, lectin pathway; IDA:UniProtKB.
DR GO; GO:0010037; P:response to carbon dioxide; IEA:Ensembl.
DR GO; GO:0051384; P:response to glucocorticoid; IEA:Ensembl.
DR GO; GO:0007584; P:response to nutrient; IEA:Ensembl.
DR GO; GO:0034695; P:response to prostaglandin E; IEA:Ensembl.
DR GO; GO:0048863; P:stem cell differentiation; IEA:Ensembl.
DR CDD; cd02897; A2M_2; 1.
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; IPR041813; A2M_TED.
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; IPR041555; MG3.
DR InterPro; IPR040839; MG4.
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; PF17791; MG3; 1.
DR Pfam; PF17789; MG4; 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; Direct protein sequencing; Disulfide bond;
KW Glycoprotein; Isopeptide bond; Protease inhibitor; Reference proteome;
KW Secreted; Serine protease inhibitor; Signal; Thioester bond.
FT SIGNAL 1..23
FT /evidence="ECO:0000269|PubMed:6203908"
FT CHAIN 24..1474
FT /note="Alpha-2-macroglobulin"
FT /evidence="ECO:0000269|PubMed:6203908"
FT /id="PRO_0000000055"
FT REGION 690..728
FT /note="Bait region"
FT REGION 704..709
FT /note="Inhibitory"
FT REGION 719..723
FT /note="Inhibitory"
FT REGION 730..735
FT /note="Inhibitory"
FT CARBOHYD 55
FT /note="N-linked (GlcNAc...) (complex) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952,
FT ECO:0000269|PubMed:19139490"
FT CARBOHYD 70
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:6203908"
FT CARBOHYD 247
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952,
FT ECO:0000269|PubMed:6203908"
FT CARBOHYD 396
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952,
FT ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:6203908"
FT CARBOHYD 410
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952,
FT ECO:0000269|PubMed:6203908"
FT CARBOHYD 869
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:14760718,
FT ECO:0000269|PubMed:16335952"
FT CARBOHYD 991
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:12754519,
FT ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:19159218,
FT ECO:0000269|PubMed:6203908"
FT CARBOHYD 1424
FT /note="N-linked (GlcNAc...) (complex) asparagine"
FT /evidence="ECO:0000269|PubMed:14760718,
FT ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:19139490,
FT ECO:0000269|PubMed:19159218"
FT DISULFID 48..86
FT /evidence="ECO:0000269|PubMed:6203908"
FT DISULFID 251..299
FT /evidence="ECO:0000269|PubMed:6203908"
FT DISULFID 269..287
FT /evidence="ECO:0000269|PubMed:6203908"
FT DISULFID 278
FT /note="Interchain (with C-431)"
FT /evidence="ECO:0000269|PubMed:2430963"
FT DISULFID 431
FT /note="Interchain (with C-278)"
FT /evidence="ECO:0000269|PubMed:2430963"
FT DISULFID 470..563
FT /evidence="ECO:0000269|PubMed:2430963"
FT DISULFID 595..771
FT /evidence="ECO:0000269|PubMed:2430963,
FT ECO:0000269|PubMed:6203908"
FT DISULFID 642..689
FT /evidence="ECO:0000269|PubMed:6203908"
FT DISULFID 821..849
FT /evidence="ECO:0000269|PubMed:6203908"
FT DISULFID 847..883
FT /evidence="ECO:0000269|PubMed:6203908"
FT DISULFID 921..1321
FT /evidence="ECO:0000269|PubMed:6203908"
FT DISULFID 1079..1127
FT /evidence="ECO:0000269|PubMed:6203908"
FT DISULFID 1352..1467
FT /evidence="ECO:0000269|PubMed:6203908"
FT CROSSLNK 693
FT /note="Isoglutamyl lysine isopeptide (Gln-Lys) (interchain
FT with K-? in other proteins)"
FT /evidence="ECO:0000255"
FT CROSSLNK 694
FT /note="Isoglutamyl lysine isopeptide (Gln-Lys) (interchain
FT with K-? in other proteins)"
FT /evidence="ECO:0000255"
FT CROSSLNK 972..975
FT /note="Isoglutamyl cysteine thioester (Cys-Gln)"
FT /evidence="ECO:0000269|PubMed:6203908"
FT VARIANT 639
FT /note="N -> D (in dbSNP:rs226405)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:15611997, ECO:0000269|PubMed:17974005,
FT ECO:0000269|PubMed:2581245, ECO:0000269|Ref.3"
FT /id="VAR_026820"
FT VARIANT 704
FT /note="R -> H (in dbSNP:rs1800434)"
FT /id="VAR_000012"
FT VARIANT 815
FT /note="L -> Q (in dbSNP:rs3180392)"
FT /id="VAR_026821"
FT VARIANT 972
FT /note="C -> Y (probably interferes with the activity;
FT dbSNP:rs1800433)"
FT /evidence="ECO:0000269|PubMed:1370808"
FT /id="VAR_000013"
FT VARIANT 1000
FT /note="I -> V (in dbSNP:rs669)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:15611997, ECO:0000269|PubMed:1707161,
FT ECO:0000269|PubMed:17974005, ECO:0000269|PubMed:2581245"
FT /id="VAR_000014"
FT CONFLICT 63
FT /note="Missing (in Ref. 8; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 82
FT /note="D -> V (in Ref. 3; AAT02228)"
FT /evidence="ECO:0000305"
FT CONFLICT 350..353
FT /note="LSFV -> ACCS (in Ref. 6; AAH26246)"
FT /evidence="ECO:0000305"
FT CONFLICT 563
FT /note="C -> E (in Ref. 8; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 844
FT /note="A -> V (in Ref. 4; BAD92851)"
FT /evidence="ECO:0000305"
FT CONFLICT 872
FT /note="V -> M (in Ref. 5; CAH18188)"
FT /evidence="ECO:0000305"
FT CONFLICT 1148
FT /note="A -> D (in Ref. 13; AAA51552)"
FT /evidence="ECO:0000305"
FT CONFLICT 1195
FT /note="H -> D (in Ref. 13; AAA51552)"
FT /evidence="ECO:0000305"
FT STRAND 128..134
FT /evidence="ECO:0007829|PDB:2P9R"
FT STRAND 136..138
FT /evidence="ECO:0007829|PDB:2P9R"
FT STRAND 143..151
FT /evidence="ECO:0007829|PDB:2P9R"
FT HELIX 153..155
FT /evidence="ECO:0007829|PDB:2P9R"
FT STRAND 161..168
FT /evidence="ECO:0007829|PDB:2P9R"
FT STRAND 174..182
FT /evidence="ECO:0007829|PDB:2P9R"
FT STRAND 187..193
FT /evidence="ECO:0007829|PDB:2P9R"
FT STRAND 201..208
FT /evidence="ECO:0007829|PDB:2P9R"
FT STRAND 214..221
FT /evidence="ECO:0007829|PDB:2P9R"
FT STRAND 1341..1347
FT /evidence="ECO:0007829|PDB:1BV8"
FT HELIX 1355..1359
FT /evidence="ECO:0007829|PDB:1BV8"
FT STRAND 1360..1369
FT /evidence="ECO:0007829|PDB:1BV8"
FT STRAND 1379..1384
FT /evidence="ECO:0007829|PDB:1BV8"
FT STRAND 1389..1391
FT /evidence="ECO:0007829|PDB:1BV8"
FT HELIX 1393..1400
FT /evidence="ECO:0007829|PDB:1BV8"
FT TURN 1401..1403
FT /evidence="ECO:0007829|PDB:1BV8"
FT STRAND 1407..1410
FT /evidence="ECO:0007829|PDB:1BV8"
FT STRAND 1412..1419
FT /evidence="ECO:0007829|PDB:1BV8"
FT STRAND 1427..1434
FT /evidence="ECO:0007829|PDB:1BV8"
FT STRAND 1445..1450
FT /evidence="ECO:0007829|PDB:1BV8"
FT STRAND 1454..1456
FT /evidence="ECO:0007829|PDB:1BV8"
FT STRAND 1459..1463
FT /evidence="ECO:0007829|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
