A2MG_MOUSE
ID A2MG_MOUSE Reviewed; 1474 AA.
AC Q6GQT1; E9QMQ7; Q811S0;
DT 09-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=Alpha-2-macroglobulin-P;
DE AltName: Full=Alpha-2-macroglobulin;
DE Flags: Precursor;
GN Name=A2m {ECO:0000312|MGI:MGI:2449119};
GN Synonyms=A2mp {ECO:0000312|EMBL:AAO25741.1};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAO25741.1}
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:AAO25741.1};
RC TISSUE=Placenta {ECO:0000312|EMBL:AAO25741.1};
RX PubMed=15355875; DOI=10.1095/biolreprod.104.029835;
RA He H., McCartney D.J., Wei Q., Esadeg S., Zhang J., Foster R.A.,
RA Hayes M.A., Tayade C., Van Leuven F., Croy B.A.;
RT "Characterization of a murine alpha 2 macroglobulin gene expressed in
RT reproductive and cardiovascular tissue.";
RL Biol. Reprod. 72:266-275(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3] {ECO:0000312|EMBL:AAH72642.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:AAH72642.1};
RC TISSUE=Brain {ECO:0000312|EMBL:AAH72642.1};
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).
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|UniProtKB:P01023}.
CC -!- SUBUNIT: Homotetramer; disulfide-linked.
CC {ECO:0000250|UniProtKB:P01023}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in uterus, mesometrial lymphoid aggregate
CC and mammary tissue during pregnancy. Expressed in ovary, testis and
CC kidney. Low level expression in heart. Not expressed in liver.
CC {ECO:0000269|PubMed:15355875}.
CC -!- DEVELOPMENTAL STAGE: Expressed in uterus of pregnant females during
CC decidualization from 6 dpc with highest level around 10 dpc declining
CC throughout the rest of the pregnancy. {ECO:0000269|PubMed:15355875}.
CC -!- SIMILARITY: Belongs to the protease inhibitor I39 (alpha-2-
CC macroglobulin) family. {ECO:0000255}.
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DR EMBL; AY185125; AAO25741.1; -; mRNA.
DR EMBL; AC153581; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC072642; AAH72642.1; -; mRNA.
DR CCDS; CCDS39617.1; -.
DR RefSeq; NP_783327.2; NM_175628.3.
DR AlphaFoldDB; Q6GQT1; -.
DR SMR; Q6GQT1; -.
DR BioGRID; 231245; 7.
DR IntAct; Q6GQT1; 1.
DR MINT; Q6GQT1; -.
DR STRING; 10090.ENSMUSP00000032203; -.
DR MEROPS; I39.004; -.
DR GlyGen; Q6GQT1; 9 sites.
DR iPTMnet; Q6GQT1; -.
DR PhosphoSitePlus; Q6GQT1; -.
DR CPTAC; non-CPTAC-3311; -.
DR CPTAC; non-CPTAC-3384; -.
DR jPOST; Q6GQT1; -.
DR MaxQB; Q6GQT1; -.
DR PaxDb; Q6GQT1; -.
DR PeptideAtlas; Q6GQT1; -.
DR PRIDE; Q6GQT1; -.
DR ProteomicsDB; 286006; -.
DR Antibodypedia; 859; 939 antibodies from 41 providers.
DR DNASU; 232345; -.
DR Ensembl; ENSMUST00000032203; ENSMUSP00000032203; ENSMUSG00000030111.
DR GeneID; 232345; -.
DR KEGG; mmu:232345; -.
DR UCSC; uc009doq.1; mouse.
DR CTD; 2; -.
DR MGI; MGI:2449119; A2m.
DR VEuPathDB; HostDB:ENSMUSG00000030111; -.
DR eggNOG; KOG1366; Eukaryota.
DR GeneTree; ENSGT00940000154904; -.
DR HOGENOM; CLU_001634_0_1_1; -.
DR InParanoid; Q6GQT1; -.
DR OMA; CFGEESQ; -.
DR OrthoDB; 354230at2759; -.
DR PhylomeDB; Q6GQT1; -.
DR TreeFam; TF313285; -.
DR Reactome; R-MMU-114608; Platelet degranulation.
DR Reactome; R-MMU-140837; Intrinsic Pathway of Fibrin Clot Formation.
DR Reactome; R-MMU-1474228; Degradation of the extracellular matrix.
DR Reactome; R-MMU-8963896; HDL assembly.
DR BioGRID-ORCS; 232345; 3 hits in 73 CRISPR screens.
DR ChiTaRS; A2m; mouse.
DR PRO; PR:Q6GQT1; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q6GQT1; protein.
DR Bgee; ENSMUSG00000030111; Expressed in gastrula and 144 other tissues.
DR ExpressionAtlas; Q6GQT1; baseline and differential.
DR Genevisible; Q6GQT1; MM.
DR GO; GO:0005615; C:extracellular space; ISO:MGI.
DR GO; GO:0048403; F:brain-derived neurotrophic factor binding; ISO:MGI.
DR GO; GO:0048306; F:calcium-dependent protein binding; ISO:MGI.
DR GO; GO:0004866; F:endopeptidase inhibitor activity; ISO:MGI.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0019838; F:growth factor binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0019966; F:interleukin-1 binding; ISO:MGI.
DR GO; GO:0019959; F:interleukin-8 binding; ISO:MGI.
DR GO; GO:0048406; F:nerve growth factor binding; ISO:MGI.
DR GO; GO:0030414; F:peptidase inhibitor activity; TAS:MGI.
DR GO; GO:0002020; F:protease binding; ISO:MGI.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; ISO:MGI.
DR GO; GO:0005102; F:signaling receptor binding; ISO:MGI.
DR GO; GO:0043120; F:tumor necrosis factor binding; ISO:MGI.
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:0007565; P:female pregnancy; IEA:UniProtKB-KW.
DR GO; GO:0001553; P:luteinization; IEA:Ensembl.
DR GO; GO:0001869; P:negative regulation of complement activation, lectin pathway; ISO:MGI.
DR GO; GO:0010951; P:negative regulation of endopeptidase activity; ISO:MGI.
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; IDA:MGI.
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 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 2: Evidence at transcript level;
KW Bait region; Disulfide bond; Glycoprotein; Pregnancy; Protease inhibitor;
KW Reference proteome; Secreted; Serine protease inhibitor; Signal;
KW Thioester bond.
FT SIGNAL 1..32
FT /evidence="ECO:0000255"
FT CHAIN 33..1474
FT /note="Alpha-2-macroglobulin-P"
FT /evidence="ECO:0000255"
FT /id="PRO_0000271402"
FT REGION 623..752
FT /note="Bait region"
FT /evidence="ECO:0000250|UniProtKB:P01023"
FT CARBOHYD 62
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 77
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 253
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 402
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 654
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 774
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 869
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 991
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1366
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 55..93
FT /evidence="ECO:0000250|UniProtKB:P01023"
FT DISULFID 257..305
FT /evidence="ECO:0000250|UniProtKB:P01023"
FT DISULFID 275..293
FT /evidence="ECO:0000250|UniProtKB:P01023"
FT DISULFID 284
FT /note="Interchain (with C-437)"
FT /evidence="ECO:0000250|UniProtKB:P01023"
FT DISULFID 437
FT /note="Interchain (with C-284)"
FT /evidence="ECO:0000250|UniProtKB:P01023"
FT DISULFID 476..569
FT /evidence="ECO:0000250|UniProtKB:P01023"
FT DISULFID 601..771
FT /evidence="ECO:0000250|UniProtKB:P01023"
FT DISULFID 650..697
FT /evidence="ECO:0000250|UniProtKB:P01023"
FT DISULFID 821..849
FT /evidence="ECO:0000250|UniProtKB:P01023"
FT DISULFID 847..883
FT /evidence="ECO:0000250|UniProtKB:P01023"
FT DISULFID 921..1321
FT /evidence="ECO:0000250|UniProtKB:P01023"
FT DISULFID 1079..1127
FT /evidence="ECO:0000250|UniProtKB:P01023"
FT DISULFID 1352..1467
FT /evidence="ECO:0000250|UniProtKB:P01023"
FT CROSSLNK 972..975
FT /note="Isoglutamyl cysteine thioester (Cys-Gln)"
FT /evidence="ECO:0000250|UniProtKB:P01023"
FT CONFLICT 366
FT /note="R -> G (in Ref. 1; AAO25741)"
FT /evidence="ECO:0000305"
FT CONFLICT 452
FT /note="H -> R (in Ref. 1; AAO25741)"
FT /evidence="ECO:0000305"
FT CONFLICT 659..666
FT /note="NGILYSPV -> RNPVLPR (in Ref. 1; AAO25741)"
FT /evidence="ECO:0000305"
FT CONFLICT 799
FT /note="P -> A (in Ref. 3; AAH72642)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1474 AA; 164353 MW; 996A152EC0899F99 CRC64;
MGKRWLPSLA LLPLPPPLLL LLLLLLPTNA SAPQKPIYMV MVPSLLHAGT PEKGCLLFNH
LNETVTVKVS MESVRGNQSL FTDLVVDKDL FHCASFIVPQ SSSNEVMFLT VQVKGPTHEF
RRRSTVLIKT KESLVFAQTD KPIYKPGQMV RFRVVSLDEN FHPLNELIPL LYIQDSKKNR
IAQWQNFRLE GGLKQLSFPL SSEPTQGSYK VVIRTESGRT VEHPFSVKEF VLPKFEVKVA
VPETITILEE EMNVSVCGIY TYGKPVPGHV TVNICRKYSN PSSCFGEESL AFCEKFSQQL
DGRGCFSQLV KTKSFQLKRQ EYEMQLDVNA KIQEEGTGVE ETGKGLTKIT RTITKLSFVN
VDTHFRQGIP FVGQVLLVDG RGTPIPYEMI FIGADEANQN INTTTDKNGL ARFSINTDDI
MGTSLTVRAK YKDSNVCYGF RWLTEENVEA WHTANAVFSP SRSFVHLESL PYKLRCEQTL
AVQAHYILND EAVLERKELV FYYLMMAKGG IVRAGTHVLP VTQGHKKGHF SILISMETDL
APVARLVLYT ILPNGEVVGD TVKYEIEKCL ANKVDLVFHP NIGLPATRAF LSVMASPQSL
CGLRAVDQSV LLTKPEAELS ASLVYDLLPV KDLTGFPKGV NQQEEDTNGC LKQNDTYING
ILYSPVQNTN EEDMYGFLKD MGLKVFTNLN IRKPKVCERL GVNKIPAAYH LVSQGHMDAF
LESSESPTET TRSYFPETWI WDLVIVDSTG VAEMEVTVPD TITEWKAGAF CLSNDTGLGL
SPVIDFQAFQ PFFVDLTMPY SVIRGEAFTL KATVLNYLQT CIRVGVQLEA SPDFLATPEE
KEQKSHCICM NERHTMSWAV IPKSLGNVNF TVSAEALDSK ELCRNEVPVV PERGKKDTII
KSLLVEPEGL ENEVTFNSLL CPTGAEVSEQ ISLKLPSDVV EESARASVTV LGDILGSAMQ
NTQDLLKMPY GCGEQNMVLF APNIYVLDYL NETEQLTQEI KTKAITYLNT GYQRQLNYKH
RDGSYSTFGD KPGRSHANTW LTAFVLKSFA QARRYIFIDE SHITQALTWL SQQQKDNGCF
RSSGSLLNNA MKGGVEDEVT LSAYITIALL EMSLPVTHPV VRNALFCLDT AWKSARRGAS
GNHVYTKALL AYAFALAGNQ DTKKEILKSL DEEAVKEDNS VHWTRAQKPR VPADLWYQPQ
APSAEVEMTA YVLLAYLTTE LVPTREDLTA AMLIVKWLTK QQNSHGGFSS TQDTVVALHA
LSKYGAATFT RAKKAAHVTI QSSGAFYTKF QVNNDNQLLL QRVTLPTVPG DYTAKVAGEG
CVYLQTSLKY SVLPREKEFP FALVVQTLPG TCEDLKAHTT FQISLNISYI GSRSDSNMAI
ADVKMVSGFI PLKPTVKMLE RSVHVSRTEV SNNHVLIYLD KVSNQMLTLF FMVQQDIPVR
DLKPAIVKVY DYYEKDEFAV AKYSAPCSAG YGNA
