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Q61838 (A2M_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 118. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Alpha-2-macroglobulin

Short name=Alpha-2-M
Alternative name(s):
Pregnancy zone protein
Gene names
Name:A2m
Synonyms:Pzp
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1495 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Subcellular location

Secreted.

Tissue specificity

Highest expression in liver, medium expression in ovary, heart and stomach. Low expression in lung, kidney and uterus. Protein found in plasma. Ref.5

Developmental stage

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

Sequence similarities

Belongs to the protease inhibitor I39 (alpha-2-macroglobulin) family. [View classification]

Sequence caution

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2424 Potential
Chain25 – 14951471Alpha-2-macroglobulin
PRO_0000338413
Chain25 – 12391215Alpha-2-macroglobulin 165 kDa subunit
PRO_0000000056
Chain1240 – 1495256Alpha-2-macroglobulin 35 kDa subunit
PRO_0000000057

Regions

Region686 – 74459Bait region

Amino acid modifications

Glycosylation551N-linked (GlcNAc...) Potential
Glycosylation1571N-linked (GlcNAc...) Ref.6 Ref.7
Glycosylation3821N-linked (GlcNAc...) Potential
Glycosylation4051N-linked (GlcNAc...) Ref.6
Glycosylation4121N-linked (GlcNAc...) Ref.6
Glycosylation5681N-linked (GlcNAc...) Ref.7
Glycosylation8811N-linked (GlcNAc...) Ref.7
Glycosylation9421N-linked (GlcNAc...) Potential
Glycosylation10031N-linked (GlcNAc...) Ref.6 Ref.7
Glycosylation13851N-linked (GlcNAc...) Ref.6 Ref.7
Glycosylation14431N-linked (GlcNAc...) Ref.6 Ref.7
Disulfide bond48 ↔ 86 By similarity
Disulfide bond249 ↔ 298 By similarity
Disulfide bond267 ↔ 286 By similarity
Disulfide bond277Interchain (with C-430) By similarity
Disulfide bond430Interchain (with C-277) By similarity
Disulfide bond469 ↔ 562 By similarity
Disulfide bond594 ↔ 783 By similarity
Disulfide bond642 ↔ 689 By similarity
Disulfide bond833 ↔ 861 By similarity
Disulfide bond859 ↔ 895 By similarity
Disulfide bond933 ↔ 1339 By similarity
Disulfide bond1092 ↔ 1140 By similarity
Cross-link984 ↔ 987Isoglutamyl cysteine thioester (Cys-Gln) By similarity

Experimental info

Sequence conflict431V → I in AAA39508. Ref.1
Sequence conflict431V → I in AAH57983. Ref.3
Sequence conflict431V → I in AAA87890. Ref.4
Sequence conflict911I → V in AAA87890. Ref.4
Sequence conflict142 – 1443VKF → GII in AAA87890. Ref.4
Sequence conflict160 – 1612FP → VS in AAA87890. Ref.4
Sequence conflict2871E → A in AAA39508. Ref.1
Sequence conflict3001R → S in AAA39508. Ref.1
Sequence conflict3111R → S in AAA39508. Ref.1
Sequence conflict4911D → T in AAA39508. Ref.1
Sequence conflict5051F → G in AAA39508. Ref.1
Sequence conflict5411I → V in AAH57983. Ref.3
Sequence conflict7921L → S in AAA39508. Ref.1
Sequence conflict8841A → R in AAA39508. Ref.1
Sequence conflict890 – 8923QSP → ESQ in AAA39508. Ref.1
Sequence conflict9431W → S in AAA39508. Ref.1
Sequence conflict11331A → V in AAH57983. Ref.3
Sequence conflict1263 – 12686HGGFSS → DGGLLL in AAA39508. Ref.1
Sequence conflict12841A → S in AAA39508. Ref.1
Sequence conflict1298 – 12992IE → SR in AAA39508. Ref.1
Sequence conflict13751G → E in AAA39508. Ref.1
Sequence conflict14171K → R in AAA39508. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q61838 [UniParc].

Last modified June 28, 2011. Version 3.
Checksum: 5D060D6C639DF3BC

FASTA1,495165,853
        10         20         30         40         50         60 
MRRNQLPTPA FLLLFLLLPR DATTATAKPQ YVVLVPSEVY SGVPEKACVS LNHVNETVML 

        70         80         90        100        110        120 
SLTLEYAMQQ TKLLTDQAVD KDSFYCSPFT ISGSPLPYTF ITVEIKGPTQ RFIKKKSIQI 

       130        140        150        160        170        180 
IKAESPVFVQ TDKPIYKPGQ IVKFRVVSVD ISFRPLNETF PVVYIETPKR NRIFQWQNIH 

       190        200        210        220        230        240 
LAGGLHQLSF PLSVEPALGI YKVVVQKDSG KKIEHSFEVK EYVLPKFEVI IKMQKTMAFL 

       250        260        270        280        290        300 
EEELPITACG VYTYGKPVPG LVTLRVCRKY SRYRSTCHNQ NSMSICEEFS QQADDKGCFR 

       310        320        330        340        350        360 
QVVKTKVFQL RQKGHDMKIE VEAKIKEEGT GIELTGIGSC EIANALSKLK FTKVNTNYRP 

       370        380        390        400        410        420 
GLPFSGQVLL VDEKGKPIPN KNITSVVSPL GYLSIFTTDE HGLANISIDT SNFTAPFLRV 

       430        440        450        460        470        480 
VVTYKQNHVC YDNWWLDEFH TQADHSATLV FSPSQSYIQL ELVFGTLACG QTQEIRIHYL 

       490        500        510        520        530        540 
LNEDIMKNEK DLTFYYLIKA RGSIFNLGSH VLSLEQGNMK GVFSLPIQVE PGMAPEAQLL 

       550        560        570        580        590        600 
IYAILPNEEL VADAQNFEIE KCFANKVNLS FPSAQSLPAS DTHLKVKAAP LSLCALTAVD 

       610        620        630        640        650        660 
QSVLLLKPEA KLSPQSIYNL LPGKTVQGAF FGVPVYKDHE NCISGEDITH NGIVYTPKHS 

       670        680        690        700        710        720 
LGDNDAHSIF QSVGINIFTN SKIHKPRFCQ EFQHYPAMGG VAPQALAVAA SGPGSSFRAM 

       730        740        750        760        770        780 
GVPMMGLDYS DEINQVVEVR ETVRKYFPET WIWDLVPLDV SGDGELAVKV PDTITEWKAS 

       790        800        810        820        830        840 
AFCLSGTTGL GLSSTISLQA FQPFFLELTL PYSVVRGEAF TLKATVLNYM SHCIQIRVDL 

       850        860        870        880        890        900 
EISPDFLAVP VGGHENSHCI CGNERKTVSW AVTPKSLGEV NFTATAEALQ SPELCGNKLT 

       910        920        930        940        950        960 
EVPALVHKDT VVKSVIVEPE GIEKEQTYNT LLCPQDTELQ DNWSLELPPN VVEGSARATH 

       970        980        990       1000       1010       1020 
SVLGDILGSA MQNLQNLLQM PYGCGEQNMV LFVPNIYVLN YLNETQQLTE AIKSKAINYL 

      1030       1040       1050       1060       1070       1080 
ISGYQRQLNY QHSDGSYSTF GNHGGGNTPG NTWLTAFVLK AFAQAQSHIF IEKTHITNAF 

      1090       1100       1110       1120       1130       1140 
NWLSMKQKEN GCFQQSGYLL NNAMKGGVDD EVTLSAYITI ALLEMPLPVT HSAVRNALFC 

      1150       1160       1170       1180       1190       1200 
LETAWASISQ SQESHVYTKA LLAYAFALAG NKAKRSELLE SLNKDAVKEE DSLHWQRPGD 

      1210       1220       1230       1240       1250       1260 
VQKVKALSFY QPRAPSAEVE MTAYVLLAYL TSESSRPTRD LSSSDLSTAS KIVKWISKQQ 

      1270       1280       1290       1300       1310       1320 
NSHGGFSSTQ DTVVALQALS KYGAATFTRS QKEVLVTIES SGTFSKTFHV NSGNRLLLQE 

      1330       1340       1350       1360       1370       1380 
VRLPDLPGNY VTKGSGSGCV YLQTSLKYNI LPVADGKAPF ALQVNTLPLN FDKAGDHRTF 

      1390       1400       1410       1420       1430       1440 
QIRINVSYTG ERPSSNMVIV DVKMVSGFIP MKPSVKKLQD QPNIQRTEVN TNHVLIYIEK 

      1450       1460       1470       1480       1490 
LTNQTLGFSF AVEQDIPVKN LKPAPIKVYD YYETDEFTVE EYSAPFSDGS EQGNA 

« Hide

References

« Hide 'large scale' references
[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]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M93264 mRNA. Translation: AAA39508.1. Frameshift.
AC123060 Genomic DNA. No translation available.
BC057983 mRNA. Translation: AAH57983.1.
U06977 Genomic DNA. Translation: AAA87890.1.
PIRS27001.
RefSeqNP_031402.3. NM_007376.4.
UniGeneMm.260144.

3D structure databases

ProteinModelPortalQ61838.
SMRQ61838. Positions 124-225, 1357-1486.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid197897. 1 interaction.
IntActQ61838. 6 interactions.
MINTMINT-1846187.

PTM databases

PhosphoSiteQ61838.

Proteomic databases

PaxDbQ61838.
PRIDEQ61838.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000112132; ENSMUSP00000107760; ENSMUSG00000030359.
GeneID11287.
KEGGmmu:11287.
UCSCuc009eef.1. mouse.

Organism-specific databases

CTD5858.
MGIMGI:87854. Pzp.

Phylogenomic databases

eggNOGCOG2373.
GeneTreeENSGT00740000115177.
HOGENOMHOG000220939.
HOVERGENHBG000039.

Gene expression databases

BgeeQ61838.
CleanExMM_A2M.
MM_PZP.
GenevestigatorQ61838.

Family and domain databases

Gene3D1.50.10.20. 1 hit.
2.60.40.690. 1 hit.
InterProIPR009048. 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]
PfamPF00207. 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]
SUPFAMSSF48239. SSF48239. 1 hit.
SSF49410. SSF49410. 1 hit.
SSF81296. SSF81296. 1 hit.
PROSITEPS00477. ALPHA_2_MACROGLOBULIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio278574.
SOURCESearch...

Entry information

Entry nameA2M_MOUSE
AccessionPrimary (citable) accession number: Q61838
Secondary accession number(s): E9QPW0, Q60628, Q6PEM2
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: June 28, 2011
Last modified: April 16, 2014
This is version 118 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot