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Protein

Alpha-2-macroglobulin

Gene

A2m

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Is able to inhibit all four classes of proteinases by a unique 'trapping' mechanism. This protein has a peptide stretch, called the 'bait region' which contains specific cleavage sites for different proteinases. When a proteinase cleaves the bait region, a conformational change is induced in the protein which traps the proteinase. The entrapped enzyme remains active against low molecular weight substrates (activity against high molecular weight substrates is greatly reduced). Following cleavage in the bait region a thioester bond is hydrolyzed and mediates the covalent binding of the protein to the proteinase.

GO - Molecular functioni

  • endopeptidase inhibitor activity Source: RGD
  • peptidase inhibitor activity Source: RGD
  • serine-type endopeptidase inhibitor activity Source: UniProtKB-KW

GO - Biological processi

  • acute-phase response Source: RGD
  • inflammatory response Source: RGD
  • negative regulation of endopeptidase activity Source: RGD
  • response to carbon dioxide Source: RGD
  • response to glucocorticoid Source: RGD
  • response to nutrient Source: RGD
  • response to wounding Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Protease inhibitor, Serine protease inhibitor

Keywords - Biological processi

Acute phase

Enzyme and pathway databases

ReactomeiREACT_288006. Platelet degranulation.
REACT_298574. Rho GTPase cycle.
REACT_319794. Degradation of the extracellular matrix.
REACT_343460. Intrinsic Pathway of Fibrin Clot Formation.
REACT_346849. HDL-mediated lipid transport.

Protein family/group databases

MEROPSiI39.001.

Names & Taxonomyi

Protein namesi
Recommended name:
Alpha-2-macroglobulin
Short name:
Alpha-2-M
Gene namesi
Name:A2m
Synonyms:A2m1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494 Componenti: Chromosome 4

Organism-specific databases

RGDi2004. A2m.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2727Add
BLAST
Chaini28 – 14721445Alpha-2-macroglobulinPRO_0000000058Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi52 ↔ 90By similarity
Glycosylationi59 – 591N-linked (GlcNAc...)Sequence Analysis
Glycosylationi74 – 741N-linked (GlcNAc...)Sequence Analysis
Glycosylationi250 – 2501N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi254 ↔ 302By similarity
Disulfide bondi272 ↔ 290By similarity
Disulfide bondi281 – 281Interchain (with C-434)By similarity
Glycosylationi399 – 3991N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi434 – 434Interchain (with C-281)By similarity
Disulfide bondi473 ↔ 566By similarity
Disulfide bondi598 ↔ 769By similarity
Disulfide bondi647 ↔ 694By similarity
Glycosylationi651 – 6511N-linked (GlcNAc...)Sequence Analysis
Glycosylationi772 – 7721N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi819 ↔ 847By similarity
Disulfide bondi845 ↔ 881By similarity
Glycosylationi867 – 8671N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi919 ↔ 1319By similarity
Cross-linki970 ↔ 973Isoglutamyl cysteine thioester (Cys-Gln)By similarity
Glycosylationi989 – 9891N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi1077 ↔ 1125By similarity
Disulfide bondi1350 ↔ 1465By similarity
Glycosylationi1364 – 13641N-linked (GlcNAc...)Sequence Analysis
Glycosylationi1422 – 14221N-linked (GlcNAc...)Sequence Analysis
Glycosylationi1426 – 14261N-linked (GlcNAc...)Sequence Analysis

Keywords - PTMi

Disulfide bond, Glycoprotein, Thioester bond

Proteomic databases

PaxDbiP06238.
PRIDEiP06238.

Expressioni

Tissue specificityi

Highest constitutive expression in ovary. Low level in testis, uterus and non-acute phase liver. Protein found in plasma.1 Publication

Inductioni

By inflammatory stimulus in liver. The level of this protein increases during acute phase, then decreases again.1 Publication

Gene expression databases

GenevisibleiP06238. RN.

Interactioni

Subunit structurei

Homotetramer; disulfide-linked.

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000019346.

Structurei

3D structure databases

ProteinModelPortaliP06238.
SMRiP06238. Positions 129-230, 1336-1472.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni620 – 750131Bait regionAdd
BLAST

Sequence similaritiesi

Keywords - Domaini

Bait region, Signal

Phylogenomic databases

eggNOGiCOG2373.
GeneTreeiENSGT00760000118982.
HOGENOMiHOG000220939.
HOVERGENiHBG000039.
InParanoidiP06238.
KOiK03910.
OMAiHCICGNG.
OrthoDBiEOG7DJSKB.
PhylomeDBiP06238.
TreeFamiTF313285.

Family and domain databases

Gene3Di1.50.10.20. 1 hit.
2.60.40.690. 1 hit.
InterProiIPR009048. A-macroglobulin_rcpt-bd.
IPR011626. A2M_comp.
IPR002890. A2M_N.
IPR011625. A2M_N_2.
IPR014756. Ig_E-set.
IPR001599. Macroglobln_a2.
IPR019742. MacrogloblnA2_CS.
IPR019565. MacrogloblnA2_thiol-ester-bond.
IPR008930. Terpenoid_cyclase/PrenylTrfase.
[Graphical view]
PfamiPF00207. A2M. 1 hit.
PF07678. A2M_comp. 1 hit.
PF01835. A2M_N. 1 hit.
PF07703. A2M_N_2. 1 hit.
PF07677. A2M_recep. 1 hit.
PF10569. Thiol-ester_cl. 1 hit.
[Graphical view]
SUPFAMiSSF48239. SSF48239. 1 hit.
SSF49410. SSF49410. 1 hit.
SSF81296. SSF81296. 1 hit.
PROSITEiPS00477. ALPHA_2_MACROGLOBULIN. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P06238-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGKHRLRSLA LLPLLLRLLL LLLPTDASAP QKPIYMVMVP SLLHAGTPEK
60 70 80 90 100
ACFLFSHLNE TVAVRVSLES VRGNQSLFTD LVVDKDLFHC TSFTVPQSSS
110 120 130 140 150
DEVMFFTVQV KGATHEFRRR STVLVKKKES LVFAQTDKPI YKPGQTVRFR
160 170 180 190 200
VVSLDESFHP LNELIPLLYI QDPKNNRIAQ WQNFNLEGGL KQLSFPLSSE
210 220 230 240 250
PTQGSYKVVI RTESGRTVEH PFSVEEFVLP KFEVRVTVPE TITILEEEMN
260 270 280 290 300
VSVCGIYTYG KPVPGRVTVN ICRKYSNPSN CFGEESVAFC EKLSQQLDGR
310 320 330 340 350
GCFSQLVKTK SFQLKRQEYE MQLDVHAKIQ EEGTGVEETG KGLTKITRTI
360 370 380 390 400
TKLSFVNVDS HFRQGIPFVG QVLLVDGRGT PIPYETIFIG ADEANLYINT
410 420 430 440 450
TTDKHGLARF SINTDDIMGT SLTVRAKYKD SNACYGFRWL TEENVEAWHT
460 470 480 490 500
AYAVFSPSRS FLHLESLPDK LRCDQTLEVQ AHYILNGEAM QELKELVFYY
510 520 530 540 550
LMMAKGGIVR AGTHVLPLKQ GQMRGHFSIL ISMETDLAPV ARLVLYAILP
560 570 580 590 600
NGEVVGDTAK YEIENCLANK VDLVFRPNSG LPATRALLSV MASPQSLCGL
610 620 630 640 650
RAVDQSVLLM KPETELSASL IYDLLPVKDL TGFPQGADQR EEDTNGCVKQ
660 670 680 690 700
NDTYINGILY SPVQNTNEED MYGFLKDMGL KVFTNSNIRK PKVCERLRDN
710 720 730 740 750
KGIPAAYHLV SQSHMDAFLE SSESPTETRR SYFPETWIWD LVVVDSAGVA
760 770 780 790 800
EVEVTVPDTI TEWKAGAFCL SNDTGLGLSP VVQFQAFQPF FVELTMPYSV
810 820 830 840 850
IRGEAFTLKA TVLNYLPTCI RVAVQLEASP DFLAAPEEKE QRSHCICMNQ
860 870 880 890 900
RHTASWAVIP KSLGNVNFTV SAEALNSKEL CGNEVPVVPE QGKKDTIIKS
910 920 930 940 950
LLVEPEGLEN EVTFNSLLCP MGAEVSELIA LKLPSDVVEE SARASVTVLG
960 970 980 990 1000
DILGSAMQNT QDLLKMPYGC GEQNMVLFAP NIYVLDYLNE TQQLTQEIKT
1010 1020 1030 1040 1050
KAIAYLNTGY QRQLNYKHRD GSYSTFGDKP GRNHANTWLT AFVLKSFAQA
1060 1070 1080 1090 1100
RKYIFIDEVH ITQALLWLSQ QQKDNGCFRS SGSLLNNAMK GGVEDEVTLS
1110 1120 1130 1140 1150
AYITIALLEM SLPVTHPVVR NALFCLDTAW KSARGGAGGS HVYTKALLAY
1160 1170 1180 1190 1200
AFALAGNQDT KKEILKSLDE EAVKEEDSVH WTRPQKPSVS VALWYQPQAP
1210 1220 1230 1240 1250
SAEVEMTAYV LLAYLTTEPA PTQEDLTAAM LIVKWLTKQQ NSHGGFSSTQ
1260 1270 1280 1290 1300
DTVVALHALS KYGSATFTRA KKAAQVTIHS SGTFSTKFQV NNNNQLLLQR
1310 1320 1330 1340 1350
VTLPTVPGDY TVKVTGEGCV YLQTSLKYSV LPREEEFPFT VVVQTLPGTC
1360 1370 1380 1390 1400
EDPKAHTSFQ ISLNISYTGS RSESNMAIAD VKMVSGFIPL KPTVKMLERS
1410 1420 1430 1440 1450
VHVSRTEVSN NHVLIYLDKV SNQTVNLSFT VQQDIPIRDL KPAVVKVYDY
1460 1470
YEKDEFAVAK YSAPCSTDYG NA
Length:1,472
Mass (Da):163,785
Last modified:December 12, 2006 - v2
Checksum:iBFD63B8A4F6A2632
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti23 – 231L → V in CAA32164 (PubMed:2466233).Curated
Sequence conflicti72 – 721R → H in AAA40636 (PubMed:2432068).Curated
Sequence conflicti72 – 721R → H in CAA32164 (PubMed:2466233).Curated
Sequence conflicti103 – 1031V → L in AAA40636 (PubMed:2432068).Curated
Sequence conflicti103 – 1031V → L in CAA32164 (PubMed:2466233).Curated
Sequence conflicti120 – 1201R → Q in AAA40636 (PubMed:2432068).Curated
Sequence conflicti120 – 1201R → Q in CAA32164 (PubMed:2466233).Curated
Sequence conflicti490 – 4901M → L in AAA40638 (PubMed:2414291).Curated
Sequence conflicti1025 – 10251T → A in AAA40636 (PubMed:2432068).Curated
Sequence conflicti1192 – 11921A → G in AAA40636 (PubMed:2432068).Curated
Sequence conflicti1200 – 12001P → T in AAA40636 (PubMed:2432068).Curated
Sequence conflicti1279 – 12791H → R in AAA40636 (PubMed:2432068).Curated
Sequence conflicti1340 – 13401T → A in AAA40636 (PubMed:2432068).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J02635 mRNA. Translation: AAA40636.1.
BC098922 mRNA. Translation: AAH98922.1.
X13983, X13984, X13985 Genomic DNA. Translation: CAA32164.1.
M11792 mRNA. Translation: AAA40637.1.
M11793 mRNA. Translation: AAA40638.1.
PIRiA26122.
RefSeqiNP_036620.2. NM_012488.2.
XP_003749876.1. XM_003749828.2.
UniGeneiRn.225884.

Genome annotation databases

EnsembliENSRNOT00000019346; ENSRNOP00000019346; ENSRNOG00000028896.
ENSRNOT00000075799; ENSRNOP00000066130; ENSRNOG00000045772.
GeneIDi100911545.
24153.
KEGGirno:100911545.
rno:24153.
UCSCiRGD:2004. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J02635 mRNA. Translation: AAA40636.1.
BC098922 mRNA. Translation: AAH98922.1.
X13983, X13984, X13985 Genomic DNA. Translation: CAA32164.1.
M11792 mRNA. Translation: AAA40637.1.
M11793 mRNA. Translation: AAA40638.1.
PIRiA26122.
RefSeqiNP_036620.2. NM_012488.2.
XP_003749876.1. XM_003749828.2.
UniGeneiRn.225884.

3D structure databases

ProteinModelPortaliP06238.
SMRiP06238. Positions 129-230, 1336-1472.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000019346.

Protein family/group databases

MEROPSiI39.001.

Proteomic databases

PaxDbiP06238.
PRIDEiP06238.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000019346; ENSRNOP00000019346; ENSRNOG00000028896.
ENSRNOT00000075799; ENSRNOP00000066130; ENSRNOG00000045772.
GeneIDi100911545.
24153.
KEGGirno:100911545.
rno:24153.
UCSCiRGD:2004. rat.

Organism-specific databases

CTDi2.
RGDi2004. A2m.

Phylogenomic databases

eggNOGiCOG2373.
GeneTreeiENSGT00760000118982.
HOGENOMiHOG000220939.
HOVERGENiHBG000039.
InParanoidiP06238.
KOiK03910.
OMAiHCICGNG.
OrthoDBiEOG7DJSKB.
PhylomeDBiP06238.
TreeFamiTF313285.

Enzyme and pathway databases

ReactomeiREACT_288006. Platelet degranulation.
REACT_298574. Rho GTPase cycle.
REACT_319794. Degradation of the extracellular matrix.
REACT_343460. Intrinsic Pathway of Fibrin Clot Formation.
REACT_346849. HDL-mediated lipid transport.

Miscellaneous databases

NextBioi602439.
PROiP06238.

Gene expression databases

GenevisibleiP06238. RN.

Family and domain databases

Gene3Di1.50.10.20. 1 hit.
2.60.40.690. 1 hit.
InterProiIPR009048. A-macroglobulin_rcpt-bd.
IPR011626. A2M_comp.
IPR002890. A2M_N.
IPR011625. A2M_N_2.
IPR014756. Ig_E-set.
IPR001599. Macroglobln_a2.
IPR019742. MacrogloblnA2_CS.
IPR019565. MacrogloblnA2_thiol-ester-bond.
IPR008930. Terpenoid_cyclase/PrenylTrfase.
[Graphical view]
PfamiPF00207. A2M. 1 hit.
PF07678. A2M_comp. 1 hit.
PF01835. A2M_N. 1 hit.
PF07703. A2M_N_2. 1 hit.
PF07677. A2M_recep. 1 hit.
PF10569. Thiol-ester_cl. 1 hit.
[Graphical view]
SUPFAMiSSF48239. SSF48239. 1 hit.
SSF49410. SSF49410. 1 hit.
SSF81296. SSF81296. 1 hit.
PROSITEiPS00477. ALPHA_2_MACROGLOBULIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Sequence of rat liver alpha 2-macroglobulin and acute phase control of its messenger RNA."
    Gehring M.R., Shiels B.R., Northemann W., de Bruijn M.H.L., Kan C.-C., Chain A.C., Noonan D.J., Fey G.H.
    J. Biol. Chem. 262:446-454(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], INDUCTION.
    Tissue: Liver.
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Placenta.
  3. "Identification of the promoter sequences involved in the interleukin-6 dependent expression of the rat alpha 2-macroglobulin gene."
    Kunz D., Zimmermann R., Heisig M., Heinrich P.C.
    Nucleic Acids Res. 17:1121-1138(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-164.
    Strain: Wistar.
    Tissue: Liver.
  4. "Molecular cloning of DNA complementary to rat alpha 2-macroglobulin mRNA."
    Hayashida K., Okubo H., Noguchi M., Yoshida H., Kangawa K., Matsuo H., Sakaki Y.
    J. Biol. Chem. 260:14224-14229(1985) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 178-227 AND 420-526.
  5. "Sequence of rat alpha 1-macroglobulin, a broad-range proteinase inhibitor from the alpha-macroglobulin-complement family."
    Eggertsen G., Hudson G., Shiels B., Reed D., Fey G.H.
    Mol. Biol. Med. 8:287-302(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
    Strain: Fischer 344.
    Tissue: Liver.

Entry informationi

Entry nameiA2MG_RAT
AccessioniPrimary (citable) accession number: P06238
Secondary accession number(s): Q4FZY3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: December 12, 2006
Last modified: July 22, 2015
This is version 129 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.