A2MG_BOVIN
ID A2MG_BOVIN Reviewed; 1510 AA.
AC Q7SIH1; A8E647;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 20-APR-2010, sequence version 2.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=Alpha-2-macroglobulin;
DE Short=Alpha-2-M;
DE Flags: Precursor;
GN Name=A2M;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Fetal liver;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (SEP-2007) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 1375-1504, PARTIAL PROTEIN
RP SEQUENCE, DISULFIDE BOND, AND GLYCOSYLATION AT ASN-1440.
RX PubMed=9634697; DOI=10.1016/s0969-2126(98)00061-6;
RA Jenner L., Husted L., Thirup S., Sottrup-Jensen L., Nyborg J.;
RT "Crystal structure of the receptor-binding domain of alpha 2-
RT macroglobulin.";
RL Structure 6:595-604(1998).
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 (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Homotetramer; disulfide-linked. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Plasma.
CC -!- SIMILARITY: Belongs to the protease inhibitor I39 (alpha-2-
CC macroglobulin) family. {ECO:0000305}.
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DR EMBL; BC153840; AAI53841.1; -; mRNA.
DR RefSeq; NP_001103265.1; NM_001109795.1.
DR PDB; 1AYO; X-ray; 1.90 A; A/B=1375-1504.
DR PDBsum; 1AYO; -.
DR AlphaFoldDB; Q7SIH1; -.
DR SMR; Q7SIH1; -.
DR STRING; 9913.ENSBTAP00000006167; -.
DR MEROPS; I39.001; -.
DR iPTMnet; Q7SIH1; -.
DR PaxDb; Q7SIH1; -.
DR PeptideAtlas; Q7SIH1; -.
DR PRIDE; Q7SIH1; -.
DR GeneID; 513856; -.
DR KEGG; bta:513856; -.
DR CTD; 2; -.
DR eggNOG; KOG1366; Eukaryota.
DR HOGENOM; CLU_001634_0_1_1; -.
DR InParanoid; Q7SIH1; -.
DR OrthoDB; 354230at2759; -.
DR TreeFam; TF313285; -.
DR EvolutionaryTrace; Q7SIH1; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0004866; F:endopeptidase inhibitor activity; IBA:GO_Central.
DR GO; GO:0002020; F:protease binding; IPI:UniProtKB.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IEA:UniProtKB-KW.
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; Direct protein sequencing; Disulfide bond; Glycoprotein;
KW Protease inhibitor; Reference proteome; Secreted;
KW Serine protease inhibitor; Signal; Thioester bond.
FT SIGNAL 1..23
FT CHAIN 24..1510
FT /note="Alpha-2-macroglobulin"
FT /id="PRO_0000093790"
FT REGION 692..730
FT /note="Bait region"
FT /evidence="ECO:0000250"
FT REGION 706..711
FT /note="Inhibitory"
FT /evidence="ECO:0000250"
FT REGION 721..725
FT /note="Inhibitory"
FT /evidence="ECO:0000250"
FT REGION 732..737
FT /note="Inhibitory"
FT /evidence="ECO:0000250"
FT CARBOHYD 55
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 70
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 870
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1028
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1440
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:9634697"
FT CARBOHYD 1460
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250"
FT DISULFID 48..86
FT /evidence="ECO:0000250|UniProtKB:P01023"
FT DISULFID 251..299
FT /evidence="ECO:0000250|UniProtKB:P01023"
FT DISULFID 269..287
FT /evidence="ECO:0000250|UniProtKB:P01023"
FT DISULFID 278
FT /note="Interchain (with C-431)"
FT /evidence="ECO:0000250|UniProtKB:P01023"
FT DISULFID 431
FT /note="Interchain (with C-278)"
FT /evidence="ECO:0000250|UniProtKB:P01023"
FT DISULFID 470..563
FT /evidence="ECO:0000250|UniProtKB:P01023"
FT DISULFID 595..773
FT /evidence="ECO:0000250|UniProtKB:P01023"
FT DISULFID 644..691
FT /evidence="ECO:0000250|UniProtKB:P01023"
FT DISULFID 823..850
FT /evidence="ECO:0000250|UniProtKB:P01023"
FT DISULFID 848..884
FT /evidence="ECO:0000250|UniProtKB:P01023"
FT DISULFID 922..1358
FT /evidence="ECO:0000250|UniProtKB:P01023"
FT DISULFID 1116..1164
FT /evidence="ECO:0000250|UniProtKB:P01023"
FT DISULFID 1389..1503
FT /evidence="ECO:0000269|PubMed:9634697"
FT CROSSLNK 1009..1012
FT /note="Isoglutamyl cysteine thioester (Cys-Gln)"
FT /evidence="ECO:0000250"
FT STRAND 1377..1388
FT /evidence="ECO:0007829|PDB:1AYO"
FT HELIX 1392..1395
FT /evidence="ECO:0007829|PDB:1AYO"
FT STRAND 1397..1406
FT /evidence="ECO:0007829|PDB:1AYO"
FT STRAND 1408..1421
FT /evidence="ECO:0007829|PDB:1AYO"
FT STRAND 1426..1428
FT /evidence="ECO:0007829|PDB:1AYO"
FT HELIX 1430..1434
FT /evidence="ECO:0007829|PDB:1AYO"
FT STRAND 1438..1447
FT /evidence="ECO:0007829|PDB:1AYO"
FT STRAND 1450..1456
FT /evidence="ECO:0007829|PDB:1AYO"
FT STRAND 1463..1473
FT /evidence="ECO:0007829|PDB:1AYO"
FT STRAND 1481..1489
FT /evidence="ECO:0007829|PDB:1AYO"
FT STRAND 1494..1499
FT /evidence="ECO:0007829|PDB:1AYO"
SQ SEQUENCE 1510 AA; 167576 MW; 93928C5436E0E20F CRC64;
MGKNKLLYPS LTLLLLLLLP TDASVSGKPQ YMVLVPSLLH TETPEKGCLL LSHLNETVTV
SASLESVREN RSLFTDVVAE KDLFHCVSFT LPRSPTSQEV MFLTIQVKGP TQEFKKRTTV
LVKNEESLVF VQTDKPIYKP EQTVKFRIVL LDESFHPLNE LVPLVYVEDP KGNRIAQWQN
LEVENGLQQL TFPLSSEPFQ GSYKVVVQKG SGGTAEHPFT VEEFVLPKFE VQVRMPKIIT
ILEEEVQVSV CGLYTYGKPV PGRVTMNMCR KYRNPSNCYG EESNAVCEKF SGELNNEGCF
SQQVNTKIFQ LKRQEFEMKI EVEAKIQEEG TEVELTGKGA TEITTTITKL SFVTVDSNLR
RGIPFTGKVL LVDGKGVPMP NKVIFITANE ANHNSNTTTD EHGLAQFSIT TTKIKGTSLS
IRVKYKDHSP CYGYQWLSEE HQDAYHSANL VFSRSNSFVY LEPLPRELPC GKTQTVQAHY
VLKGQVLKDL KELVFYYLIM AKGGIVRSGT HTLPVEQGDM QGHFSMSVPV ESDIAPVARL
LIYAILPDGE VVGDSARYEI EHCLANKVGL NFSPGQSFPA SQAHLRVTAS PQSLCALRAV
DQSVLLMRPE AELSAATVYN LLPVKDLSSF PSSVNQQEED NEDCISHDNV YINGIMYFPV
SNTNEKDMYS FLQDMGLKAF TNSKIHKPKI CPQPEEHRIQ HHTLLASPVR AEMGRNRDFV
HFDDTSEPPT ETVRKYFPET WIWDLVVVSS SGVHEVEVTV PDTITEWKAG ALCLSRDTGL
GLSPTASLRV FQPFFVELTM PYSVIRGEAF TLKATVLNYL PKCIRVSVQL EASPAFLAVP
EKEQETYCIC GNGRQTVSWA VTPKSLGNVN FTVSAEAVES QELCGSEVPV VPEHGRKDTI
IKPLLVEPEG LEKEVIFNSL LCPSVDFVFL GAEDGGQVLR HFPPAAATDT AADAHDPARP
GAKVSESLSL KLPPNVVEES ARASFSVLGD ILGSAMRNTQ NLLQMPYGCG EQNMARFAPN
IYVLDYLNET QQLTAELKSK AILYLNTGYQ RQLLYKHFDG SYSTFGEHRG NSEGNTWLTA
FVLKSFAQAR GYIFIDEAHI TEALTWLAQK QKSNGCFRST GTLLNNAIKG GVDDEVTLSA
YITIALLEMP LPVTHPVVRN ALFCLDSAWK SAKEGSQGSH VYTKALLAYA FALAGNQERR
TEVLTSLYEE AVKEDNTIHW TRPQKPRLLT EDIYQPRAPS AEVEMTAYVI LAHVTAQPAP
NPEDLKRATS IVKWISKQQN CQGGFSSTQD TVVALHALSR YGAATFTSAR KAAQVTIQSS
GTFSTKFQVE NSNRLLLQQV SLPEVPGEYS MSVTGEGCVY LQTSLKYNIL PKKDEFPFAL
EVQTLPQTCD GPKAHTSFQI SLSVSYIGSR PASNMAIVDV KMVSGFIPLK PTVKMLERSN
VSRTEVSNNH VLIYLDKVTN ETLTLTFTVL QDIPVRDLKP AIVKVYDYYE TDEFAVAEYS
APCSKDIGNA
