A2MG_RAT
ID A2MG_RAT Reviewed; 1472 AA.
AC P06238; Q4FZY3;
DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT 12-DEC-2006, sequence version 2.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=Alpha-2-macroglobulin;
DE Short=Alpha-2-M;
DE Flags: Precursor;
GN Name=A2m; Synonyms=A2m1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND INDUCTION.
RC TISSUE=Liver;
RX PubMed=2432068; DOI=10.1016/s0021-9258(19)75947-x;
RA Gehring M.R., Shiels B.R., Northemann W., de Bruijn M.H.L., Kan C.-C.,
RA Chain A.C., Noonan D.J., Fey G.H.;
RT "Sequence of rat liver alpha 2-macroglobulin and acute phase control of its
RT messenger RNA.";
RL J. Biol. Chem. 262:446-454(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
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 [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-164.
RC STRAIN=Wistar; TISSUE=Liver;
RX PubMed=2466233; DOI=10.1093/nar/17.3.1121;
RA Kunz D., Zimmermann R., Heisig M., Heinrich P.C.;
RT "Identification of the promoter sequences involved in the interleukin-6
RT dependent expression of the rat alpha 2-macroglobulin gene.";
RL Nucleic Acids Res. 17:1121-1138(1989).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 178-227 AND 420-526.
RX PubMed=2414291; DOI=10.1016/s0021-9258(17)38706-9;
RA Hayashida K., Okubo H., Noguchi M., Yoshida H., Kangawa K., Matsuo H.,
RA Sakaki Y.;
RT "Molecular cloning of DNA complementary to rat alpha 2-macroglobulin
RT mRNA.";
RL J. Biol. Chem. 260:14224-14229(1985).
RN [5]
RP TISSUE SPECIFICITY.
RC STRAIN=Fischer 344; TISSUE=Liver;
RX PubMed=1725450;
RA Eggertsen G., Hudson G., Shiels B., Reed D., Fey G.H.;
RT "Sequence of rat alpha 1-macroglobulin, a broad-range proteinase inhibitor
RT from the alpha-macroglobulin-complement family.";
RL Mol. Biol. Med. 8:287-302(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.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Highest constitutive expression in ovary. Low level
CC in testis, uterus and non-acute phase liver. Protein found in plasma.
CC {ECO:0000269|PubMed:1725450}.
CC -!- INDUCTION: By inflammatory stimulus in liver. The level of this protein
CC increases during acute phase, then decreases again.
CC {ECO:0000269|PubMed:2432068}.
CC -!- SIMILARITY: Belongs to the protease inhibitor I39 (alpha-2-
CC macroglobulin) family. {ECO:0000305}.
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DR EMBL; J02635; AAA40636.1; -; mRNA.
DR EMBL; BC098922; AAH98922.1; -; mRNA.
DR EMBL; X13983; CAA32164.1; -; Genomic_DNA.
DR EMBL; X13984; CAA32164.1; JOINED; Genomic_DNA.
DR EMBL; X13985; CAA32164.1; JOINED; Genomic_DNA.
DR EMBL; M11792; AAA40637.1; -; mRNA.
DR EMBL; M11793; AAA40638.1; -; mRNA.
DR PIR; A26122; A26122.
DR RefSeq; NP_036620.2; NM_012488.2.
DR RefSeq; XP_003749876.1; XM_003749828.2.
DR AlphaFoldDB; P06238; -.
DR SMR; P06238; -.
DR BioGRID; 246347; 1.
DR IntAct; P06238; 1.
DR MINT; P06238; -.
DR STRING; 10116.ENSRNOP00000019346; -.
DR MEROPS; I39.004; -.
DR GlyGen; P06238; 11 sites.
DR jPOST; P06238; -.
DR PaxDb; P06238; -.
DR PRIDE; P06238; -.
DR Ensembl; ENSRNOT00000019346; ENSRNOP00000019346; ENSRNOG00000028896.
DR GeneID; 24153; -.
DR KEGG; rno:24153; -.
DR UCSC; RGD:2004; rat.
DR CTD; 2; -.
DR RGD; 2004; A2m.
DR eggNOG; KOG1366; Eukaryota.
DR GeneTree; ENSGT00940000154904; -.
DR HOGENOM; CLU_001634_0_1_1; -.
DR InParanoid; P06238; -.
DR OMA; CFGEESQ; -.
DR OrthoDB; 354230at2759; -.
DR PhylomeDB; P06238; -.
DR TreeFam; TF313285; -.
DR Reactome; R-RNO-114608; Platelet degranulation.
DR Reactome; R-RNO-140837; Intrinsic Pathway of Fibrin Clot Formation.
DR Reactome; R-RNO-1474228; Degradation of the extracellular matrix.
DR Reactome; R-RNO-8963896; HDL assembly.
DR PRO; PR:P06238; -.
DR Proteomes; UP000002494; Chromosome 4.
DR Bgee; ENSRNOG00000028896; Expressed in ovary and 14 other tissues.
DR Genevisible; P06238; RN.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0048403; F:brain-derived neurotrophic factor binding; IDA:RGD.
DR GO; GO:0048306; F:calcium-dependent protein binding; ISO:RGD.
DR GO; GO:0004866; F:endopeptidase inhibitor activity; IDA:RGD.
DR GO; GO:0019899; F:enzyme binding; ISO:RGD.
DR GO; GO:0019838; F:growth factor binding; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; IPI:RGD.
DR GO; GO:0019966; F:interleukin-1 binding; ISO:RGD.
DR GO; GO:0019959; F:interleukin-8 binding; ISO:RGD.
DR GO; GO:0048406; F:nerve growth factor binding; IDA:RGD.
DR GO; GO:0002020; F:protease binding; ISO:RGD.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; ISO:RGD.
DR GO; GO:0005102; F:signaling receptor binding; ISO:RGD.
DR GO; GO:0043120; F:tumor necrosis factor binding; ISO:RGD.
DR GO; GO:0002438; P:acute inflammatory response to antigenic stimulus; IEP:RGD.
DR GO; GO:0006953; P:acute-phase response; IEP:RGD.
DR GO; GO:1990402; P:embryonic liver development; IEP:RGD.
DR GO; GO:0001553; P:luteinization; IEP:RGD.
DR GO; GO:0001869; P:negative regulation of complement activation, lectin pathway; ISO:RGD.
DR GO; GO:0010951; P:negative regulation of endopeptidase activity; IDA:RGD.
DR GO; GO:0010037; P:response to carbon dioxide; IEP:RGD.
DR GO; GO:0051384; P:response to glucocorticoid; IEP:RGD.
DR GO; GO:0007584; P:response to nutrient; IEP:RGD.
DR GO; GO:0034695; P:response to prostaglandin E; IEP:RGD.
DR GO; GO:0009611; P:response to wounding; TAS:RGD.
DR GO; GO:0048863; P:stem cell differentiation; ISO:RGD.
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 Acute phase; Bait region; Disulfide bond; Glycoprotein; Protease inhibitor;
KW Reference proteome; Secreted; Serine protease inhibitor; Signal;
KW Thioester bond.
FT SIGNAL 1..27
FT CHAIN 28..1472
FT /note="Alpha-2-macroglobulin"
FT /id="PRO_0000000058"
FT REGION 620..750
FT /note="Bait region"
FT CARBOHYD 59
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 74
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 250
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 399
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 651
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 772
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 867
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 989
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1364
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1422
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1426
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 52..90
FT /evidence="ECO:0000250|UniProtKB:P01023"
FT DISULFID 254..302
FT /evidence="ECO:0000250|UniProtKB:P01023"
FT DISULFID 272..290
FT /evidence="ECO:0000250|UniProtKB:P01023"
FT DISULFID 281
FT /note="Interchain (with C-434)"
FT /evidence="ECO:0000250|UniProtKB:P01023"
FT DISULFID 434
FT /note="Interchain (with C-281)"
FT /evidence="ECO:0000250|UniProtKB:P01023"
FT DISULFID 473..566
FT /evidence="ECO:0000250|UniProtKB:P01023"
FT DISULFID 598..769
FT /evidence="ECO:0000250|UniProtKB:P01023"
FT DISULFID 647..694
FT /evidence="ECO:0000250|UniProtKB:P01023"
FT DISULFID 819..847
FT /evidence="ECO:0000250|UniProtKB:P01023"
FT DISULFID 845..881
FT /evidence="ECO:0000250|UniProtKB:P01023"
FT DISULFID 919..1319
FT /evidence="ECO:0000250|UniProtKB:P01023"
FT DISULFID 1077..1125
FT /evidence="ECO:0000250|UniProtKB:P01023"
FT DISULFID 1350..1465
FT /evidence="ECO:0000250|UniProtKB:P01023"
FT CROSSLNK 970..973
FT /note="Isoglutamyl cysteine thioester (Cys-Gln)"
FT /evidence="ECO:0000250"
FT CONFLICT 23
FT /note="L -> V (in Ref. 3; CAA32164)"
FT /evidence="ECO:0000305"
FT CONFLICT 72
FT /note="R -> H (in Ref. 1; AAA40636 and 3; CAA32164)"
FT /evidence="ECO:0000305"
FT CONFLICT 103
FT /note="V -> L (in Ref. 1; AAA40636 and 3; CAA32164)"
FT /evidence="ECO:0000305"
FT CONFLICT 120
FT /note="R -> Q (in Ref. 1; AAA40636 and 3; CAA32164)"
FT /evidence="ECO:0000305"
FT CONFLICT 490
FT /note="M -> L (in Ref. 4; AAA40638)"
FT /evidence="ECO:0000305"
FT CONFLICT 1025
FT /note="T -> A (in Ref. 1; AAA40636)"
FT /evidence="ECO:0000305"
FT CONFLICT 1192
FT /note="A -> G (in Ref. 1; AAA40636)"
FT /evidence="ECO:0000305"
FT CONFLICT 1200
FT /note="P -> T (in Ref. 1; AAA40636)"
FT /evidence="ECO:0000305"
FT CONFLICT 1279
FT /note="H -> R (in Ref. 1; AAA40636)"
FT /evidence="ECO:0000305"
FT CONFLICT 1340
FT /note="T -> A (in Ref. 1; AAA40636)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1472 AA; 163785 MW; BFD63B8A4F6A2632 CRC64;
MGKHRLRSLA LLPLLLRLLL LLLPTDASAP QKPIYMVMVP SLLHAGTPEK ACFLFSHLNE
TVAVRVSLES VRGNQSLFTD LVVDKDLFHC TSFTVPQSSS DEVMFFTVQV KGATHEFRRR
STVLVKKKES LVFAQTDKPI YKPGQTVRFR VVSLDESFHP LNELIPLLYI QDPKNNRIAQ
WQNFNLEGGL KQLSFPLSSE PTQGSYKVVI RTESGRTVEH PFSVEEFVLP KFEVRVTVPE
TITILEEEMN VSVCGIYTYG KPVPGRVTVN ICRKYSNPSN CFGEESVAFC EKLSQQLDGR
GCFSQLVKTK SFQLKRQEYE MQLDVHAKIQ EEGTGVEETG KGLTKITRTI TKLSFVNVDS
HFRQGIPFVG QVLLVDGRGT PIPYETIFIG ADEANLYINT TTDKHGLARF SINTDDIMGT
SLTVRAKYKD SNACYGFRWL TEENVEAWHT AYAVFSPSRS FLHLESLPDK LRCDQTLEVQ
AHYILNGEAM QELKELVFYY LMMAKGGIVR AGTHVLPLKQ GQMRGHFSIL ISMETDLAPV
ARLVLYAILP NGEVVGDTAK YEIENCLANK VDLVFRPNSG LPATRALLSV MASPQSLCGL
RAVDQSVLLM KPETELSASL IYDLLPVKDL TGFPQGADQR EEDTNGCVKQ NDTYINGILY
SPVQNTNEED MYGFLKDMGL KVFTNSNIRK PKVCERLRDN KGIPAAYHLV SQSHMDAFLE
SSESPTETRR SYFPETWIWD LVVVDSAGVA EVEVTVPDTI TEWKAGAFCL SNDTGLGLSP
VVQFQAFQPF FVELTMPYSV IRGEAFTLKA TVLNYLPTCI RVAVQLEASP DFLAAPEEKE
QRSHCICMNQ RHTASWAVIP KSLGNVNFTV SAEALNSKEL CGNEVPVVPE QGKKDTIIKS
LLVEPEGLEN EVTFNSLLCP MGAEVSELIA LKLPSDVVEE SARASVTVLG DILGSAMQNT
QDLLKMPYGC GEQNMVLFAP NIYVLDYLNE TQQLTQEIKT KAIAYLNTGY QRQLNYKHRD
GSYSTFGDKP GRNHANTWLT AFVLKSFAQA RKYIFIDEVH ITQALLWLSQ QQKDNGCFRS
SGSLLNNAMK GGVEDEVTLS AYITIALLEM SLPVTHPVVR NALFCLDTAW KSARGGAGGS
HVYTKALLAY AFALAGNQDT KKEILKSLDE EAVKEEDSVH WTRPQKPSVS VALWYQPQAP
SAEVEMTAYV LLAYLTTEPA PTQEDLTAAM LIVKWLTKQQ NSHGGFSSTQ DTVVALHALS
KYGSATFTRA KKAAQVTIHS SGTFSTKFQV NNNNQLLLQR VTLPTVPGDY TVKVTGEGCV
YLQTSLKYSV LPREEEFPFT VVVQTLPGTC EDPKAHTSFQ ISLNISYTGS RSESNMAIAD
VKMVSGFIPL KPTVKMLERS VHVSRTEVSN NHVLIYLDKV SNQTVNLSFT VQQDIPIRDL
KPAVVKVYDY YEKDEFAVAK YSAPCSTDYG NA
