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Q61838

- A2M_MOUSE

UniProt

Q61838 - A2M_MOUSE

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Protein

Alpha-2-macroglobulin

Gene

A2m

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein 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

  1. endopeptidase inhibitor activity Source: MGI
  2. serine-type endopeptidase inhibitor activity Source: UniProtKB-KW

GO - Biological processi

  1. embryo implantation Source: MGI
  2. negative regulation of endopeptidase activity Source: GOC
Complete GO annotation...

Keywords - Molecular functioni

Protease inhibitor, Serine protease inhibitor

Protein family/group databases

MEROPSiI39.003.

Names & Taxonomyi

Protein namesi
Recommended name:
Alpha-2-macroglobulin
Short name:
Alpha-2-M
Alternative name(s):
Pregnancy zone protein
Cleaved into the following 2 chains:
Gene namesi
Name:A2m
Synonyms:Pzp
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 6

Organism-specific databases

MGIiMGI:87854. Pzp.

Subcellular locationi

GO - Cellular componenti

  1. extracellular region Source: MGI
  2. extracellular space Source: InterPro
Complete GO annotation...

Keywords - Cellular componenti

Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2424Sequence AnalysisAdd
BLAST
Chaini25 – 14951471Alpha-2-macroglobulinPRO_0000338413Add
BLAST
Chaini25 – 12391215Alpha-2-macroglobulin 165 kDa subunitPRO_0000000056Add
BLAST
Chaini1240 – 1495256Alpha-2-macroglobulin 35 kDa subunitPRO_0000000057Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi48 ↔ 86By similarity
Glycosylationi55 – 551N-linked (GlcNAc...)Sequence Analysis
Glycosylationi157 – 1571N-linked (GlcNAc...)2 Publications
Disulfide bondi249 ↔ 298By similarity
Disulfide bondi267 ↔ 286By similarity
Disulfide bondi277 – 277Interchain (with C-430)By similarity
Glycosylationi382 – 3821N-linked (GlcNAc...)Sequence Analysis
Glycosylationi405 – 4051N-linked (GlcNAc...)1 Publication
Glycosylationi412 – 4121N-linked (GlcNAc...)1 Publication
Disulfide bondi430 – 430Interchain (with C-277)By similarity
Disulfide bondi469 ↔ 562By similarity
Glycosylationi568 – 5681N-linked (GlcNAc...)1 Publication
Disulfide bondi594 ↔ 783By similarity
Disulfide bondi642 ↔ 689By similarity
Disulfide bondi833 ↔ 861By similarity
Disulfide bondi859 ↔ 895By similarity
Glycosylationi881 – 8811N-linked (GlcNAc...)1 Publication
Disulfide bondi933 ↔ 1339By similarity
Glycosylationi942 – 9421N-linked (GlcNAc...)Sequence Analysis
Cross-linki984 ↔ 987Isoglutamyl cysteine thioester (Cys-Gln)By similarity
Glycosylationi1003 – 10031N-linked (GlcNAc...)2 Publications
Disulfide bondi1092 ↔ 1140By similarity
Glycosylationi1385 – 13851N-linked (GlcNAc...)2 Publications
Glycosylationi1443 – 14431N-linked (GlcNAc...)2 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein, Thioester bond

Proteomic databases

MaxQBiQ61838.
PaxDbiQ61838.
PRIDEiQ61838.

PTM databases

PhosphoSiteiQ61838.

Expressioni

Tissue specificityi

Highest expression in liver, medium expression in ovary, heart and stomach. Low expression in lung, kidney and uterus. Protein found in plasma.1 Publication

Developmental stagei

Contrary to the rat protein, which is an acute phase protein, this protein is always present at high levels in circulation.

Gene expression databases

BgeeiQ61838.
CleanExiMM_A2M.
MM_PZP.
ExpressionAtlasiQ61838. baseline and differential.
GenevestigatoriQ61838.

Interactioni

Protein-protein interaction databases

BioGridi197897. 2 interactions.
IntActiQ61838. 6 interactions.
MINTiMINT-1846187.

Structurei

3D structure databases

ProteinModelPortaliQ61838.
SMRiQ61838. Positions 124-225, 1357-1486.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni686 – 74459Bait regionAdd
BLAST

Sequence similaritiesi

Keywords - Domaini

Bait region, Signal

Phylogenomic databases

eggNOGiCOG2373.
GeneTreeiENSGT00760000118982.
HOGENOMiHOG000220939.
HOVERGENiHBG000039.
InParanoidiQ61838.

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.

Q61838-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MRRNQLPTPA FLLLFLLLPR DATTATAKPQ YVVLVPSEVY SGVPEKACVS
60 70 80 90 100
LNHVNETVML SLTLEYAMQQ TKLLTDQAVD KDSFYCSPFT ISGSPLPYTF
110 120 130 140 150
ITVEIKGPTQ RFIKKKSIQI IKAESPVFVQ TDKPIYKPGQ IVKFRVVSVD
160 170 180 190 200
ISFRPLNETF PVVYIETPKR NRIFQWQNIH LAGGLHQLSF PLSVEPALGI
210 220 230 240 250
YKVVVQKDSG KKIEHSFEVK EYVLPKFEVI IKMQKTMAFL EEELPITACG
260 270 280 290 300
VYTYGKPVPG LVTLRVCRKY SRYRSTCHNQ NSMSICEEFS QQADDKGCFR
310 320 330 340 350
QVVKTKVFQL RQKGHDMKIE VEAKIKEEGT GIELTGIGSC EIANALSKLK
360 370 380 390 400
FTKVNTNYRP GLPFSGQVLL VDEKGKPIPN KNITSVVSPL GYLSIFTTDE
410 420 430 440 450
HGLANISIDT SNFTAPFLRV VVTYKQNHVC YDNWWLDEFH TQADHSATLV
460 470 480 490 500
FSPSQSYIQL ELVFGTLACG QTQEIRIHYL LNEDIMKNEK DLTFYYLIKA
510 520 530 540 550
RGSIFNLGSH VLSLEQGNMK GVFSLPIQVE PGMAPEAQLL IYAILPNEEL
560 570 580 590 600
VADAQNFEIE KCFANKVNLS FPSAQSLPAS DTHLKVKAAP LSLCALTAVD
610 620 630 640 650
QSVLLLKPEA KLSPQSIYNL LPGKTVQGAF FGVPVYKDHE NCISGEDITH
660 670 680 690 700
NGIVYTPKHS LGDNDAHSIF QSVGINIFTN SKIHKPRFCQ EFQHYPAMGG
710 720 730 740 750
VAPQALAVAA SGPGSSFRAM GVPMMGLDYS DEINQVVEVR ETVRKYFPET
760 770 780 790 800
WIWDLVPLDV SGDGELAVKV PDTITEWKAS AFCLSGTTGL GLSSTISLQA
810 820 830 840 850
FQPFFLELTL PYSVVRGEAF TLKATVLNYM SHCIQIRVDL EISPDFLAVP
860 870 880 890 900
VGGHENSHCI CGNERKTVSW AVTPKSLGEV NFTATAEALQ SPELCGNKLT
910 920 930 940 950
EVPALVHKDT VVKSVIVEPE GIEKEQTYNT LLCPQDTELQ DNWSLELPPN
960 970 980 990 1000
VVEGSARATH SVLGDILGSA MQNLQNLLQM PYGCGEQNMV LFVPNIYVLN
1010 1020 1030 1040 1050
YLNETQQLTE AIKSKAINYL ISGYQRQLNY QHSDGSYSTF GNHGGGNTPG
1060 1070 1080 1090 1100
NTWLTAFVLK AFAQAQSHIF IEKTHITNAF NWLSMKQKEN GCFQQSGYLL
1110 1120 1130 1140 1150
NNAMKGGVDD EVTLSAYITI ALLEMPLPVT HSAVRNALFC LETAWASISQ
1160 1170 1180 1190 1200
SQESHVYTKA LLAYAFALAG NKAKRSELLE SLNKDAVKEE DSLHWQRPGD
1210 1220 1230 1240 1250
VQKVKALSFY QPRAPSAEVE MTAYVLLAYL TSESSRPTRD LSSSDLSTAS
1260 1270 1280 1290 1300
KIVKWISKQQ NSHGGFSSTQ DTVVALQALS KYGAATFTRS QKEVLVTIES
1310 1320 1330 1340 1350
SGTFSKTFHV NSGNRLLLQE VRLPDLPGNY VTKGSGSGCV YLQTSLKYNI
1360 1370 1380 1390 1400
LPVADGKAPF ALQVNTLPLN FDKAGDHRTF QIRINVSYTG ERPSSNMVIV
1410 1420 1430 1440 1450
DVKMVSGFIP MKPSVKKLQD QPNIQRTEVN TNHVLIYIEK LTNQTLGFSF
1460 1470 1480 1490
AVEQDIPVKN LKPAPIKVYD YYETDEFTVE EYSAPFSDGS EQGNA
Length:1,495
Mass (Da):165,853
Last modified:June 28, 2011 - v3
Checksum:i5D060D6C639DF3BC
GO

Sequence cautioni

The sequence AAA39508.1 differs from that shown. Reason: Frameshift at positions 41 and 47.

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti43 – 431V → I in AAA39508. (PubMed:1280217)Curated
Sequence conflicti43 – 431V → I in AAH57983. (PubMed:15489334)Curated
Sequence conflicti43 – 431V → I in AAA87890. (PubMed:7528166)Curated
Sequence conflicti91 – 911I → V in AAA87890. (PubMed:7528166)Curated
Sequence conflicti142 – 1443VKF → GII in AAA87890. (PubMed:7528166)Curated
Sequence conflicti160 – 1612FP → VS in AAA87890. (PubMed:7528166)Curated
Sequence conflicti287 – 2871E → A in AAA39508. (PubMed:1280217)Curated
Sequence conflicti300 – 3001R → S in AAA39508. (PubMed:1280217)Curated
Sequence conflicti311 – 3111R → S in AAA39508. (PubMed:1280217)Curated
Sequence conflicti491 – 4911D → T in AAA39508. (PubMed:1280217)Curated
Sequence conflicti505 – 5051F → G in AAA39508. (PubMed:1280217)Curated
Sequence conflicti541 – 5411I → V in AAH57983. (PubMed:15489334)Curated
Sequence conflicti792 – 7921L → S in AAA39508. (PubMed:1280217)Curated
Sequence conflicti884 – 8841A → R in AAA39508. (PubMed:1280217)Curated
Sequence conflicti890 – 8923QSP → ESQ in AAA39508. (PubMed:1280217)Curated
Sequence conflicti943 – 9431W → S in AAA39508. (PubMed:1280217)Curated
Sequence conflicti1133 – 11331A → V in AAH57983. (PubMed:15489334)Curated
Sequence conflicti1263 – 12686HGGFSS → DGGLLL in AAA39508. (PubMed:1280217)Curated
Sequence conflicti1284 – 12841A → S in AAA39508. (PubMed:1280217)Curated
Sequence conflicti1298 – 12992IE → SR in AAA39508. (PubMed:1280217)Curated
Sequence conflicti1375 – 13751G → E in AAA39508. (PubMed:1280217)Curated
Sequence conflicti1417 – 14171K → R in AAA39508. (PubMed:1280217)Curated

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M93264 mRNA. Translation: AAA39508.1. Frameshift.
AC123060 Genomic DNA. No translation available.
BC057983 mRNA. Translation: AAH57983.1.
U06977 Genomic DNA. Translation: AAA87890.1.
CCDSiCCDS39650.1.
PIRiS27001.
RefSeqiNP_031402.3. NM_007376.4.
UniGeneiMm.260144.

Genome annotation databases

EnsembliENSMUST00000112132; ENSMUSP00000107760; ENSMUSG00000030359.
GeneIDi11287.
KEGGimmu:11287.
UCSCiuc009eef.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M93264 mRNA. Translation: AAA39508.1 . Frameshift.
AC123060 Genomic DNA. No translation available.
BC057983 mRNA. Translation: AAH57983.1 .
U06977 Genomic DNA. Translation: AAA87890.1 .
CCDSi CCDS39650.1.
PIRi S27001.
RefSeqi NP_031402.3. NM_007376.4.
UniGenei Mm.260144.

3D structure databases

ProteinModelPortali Q61838.
SMRi Q61838. Positions 124-225, 1357-1486.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 197897. 2 interactions.
IntActi Q61838. 6 interactions.
MINTi MINT-1846187.

Protein family/group databases

MEROPSi I39.003.

PTM databases

PhosphoSitei Q61838.

Proteomic databases

MaxQBi Q61838.
PaxDbi Q61838.
PRIDEi Q61838.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000112132 ; ENSMUSP00000107760 ; ENSMUSG00000030359 .
GeneIDi 11287.
KEGGi mmu:11287.
UCSCi uc009eef.1. mouse.

Organism-specific databases

CTDi 5858.
MGIi MGI:87854. Pzp.

Phylogenomic databases

eggNOGi COG2373.
GeneTreei ENSGT00760000118982.
HOGENOMi HOG000220939.
HOVERGENi HBG000039.
InParanoidi Q61838.

Miscellaneous databases

NextBioi 278574.
SOURCEi Search...

Gene expression databases

Bgeei Q61838.
CleanExi MM_A2M.
MM_PZP.
ExpressionAtlasi Q61838. baseline and differential.
Genevestigatori Q61838.

Family and domain databases

Gene3Di 1.50.10.20. 1 hit.
2.60.40.690. 1 hit.
InterProi IPR009048. 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 ]
Pfami PF00207. 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 ]
SUPFAMi SSF48239. SSF48239. 1 hit.
SSF49410. SSF49410. 1 hit.
SSF81296. SSF81296. 1 hit.
PROSITEi PS00477. ALPHA_2_MACROGLOBULIN. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "The primary sequence and the subunit structure of mouse alpha-2-macroglobulin, deduced from protein sequencing of the isolated subunits and from molecular cloning of the cDNA."
    van Leuven F., Torrekens S., Overbergh L., Lorent K., de Strooper B., van den Berghe H.
    Eur. J. Biochem. 210:319-327(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 25-44 AND 1240-1259.
    Tissue: Liver.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  3. "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].
    Strain: FVB/N.
    Tissue: Liver.
  4. "Molecular cloning of the mouse gene coding for alpha 2-macroglobulin and targeting of the gene in embryonic stem cells."
    Umans L., Serneels L., Hilliker C., Stas L., Overbergh L., de Strooper B., van Leuven F., van den Berghe H.
    Genomics 22:519-529(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-161.
    Strain: 129/J.
  5. "Characterization of a murine alpha 2 macroglobulin gene expressed in reproductive and cardiovascular tissue."
    He H., McCartney D.J., Wei Q., Esadeg S., Zhang J., Foster R.A., Hayes M.A., Tayade C., Van Leuven F., Croy B.A.
    Biol. Reprod. 72:266-275(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
    Strain: C57BL/6.
    Tissue: Placenta.
  6. "Proteome-wide characterization of N-glycosylation events by diagonal chromatography."
    Ghesquiere B., Van Damme J., Martens L., Vandekerckhove J., Gevaert K.
    J. Proteome Res. 5:2438-2447(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-157; ASN-405; ASN-412; ASN-1003; ASN-1385 AND ASN-1443.
    Strain: C57BL/6.
    Tissue: Plasma.
  7. "Enhanced analysis of the mouse plasma proteome using cysteine-containing tryptic glycopeptides."
    Bernhard O.K., Kapp E.A., Simpson R.J.
    J. Proteome Res. 6:987-995(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-157; ASN-568; ASN-881; ASN-1003; ASN-1385 AND ASN-1443.
    Strain: C57BL/6.
    Tissue: Plasma.

Entry informationi

Entry nameiA2M_MOUSE
AccessioniPrimary (citable) accession number: Q61838
Secondary accession number(s): E9QPW0, Q60628, Q6PEM2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: June 28, 2011
Last modified: October 29, 2014
This is version 123 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3