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Protein

Alpha-2-macroglobulin

Gene

A2M

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

  • calcium-dependent protein binding Source: AgBase
  • enzyme binding Source: UniProtKB
  • growth factor binding Source: UniProtKB
  • GTPase activator activity Source: Reactome
  • interleukin-1 binding Source: UniProtKB
  • interleukin-8 binding Source: UniProtKB
  • protease binding Source: BHF-UCL
  • serine-type endopeptidase inhibitor activity Source: UniProtKB
  • signaling receptor binding Source: AgBase
  • tumor necrosis factor binding Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionProtease inhibitor, Serine protease inhibitor

Enzyme and pathway databases

ReactomeiR-HSA-114608 Platelet degranulation
R-HSA-140837 Intrinsic Pathway of Fibrin Clot Formation
R-HSA-1474228 Degradation of the extracellular matrix
R-HSA-194840 Rho GTPase cycle
R-HSA-8963896 HDL assembly

Protein family/group databases

MEROPSiI39.001
MoonDBiP01023 Predicted

Names & Taxonomyi

Protein namesi
Recommended name:
Alpha-2-macroglobulin
Short name:
Alpha-2-M
Alternative name(s):
C3 and PZP-like alpha-2-macroglobulin domain-containing protein 5
Gene namesi
Name:A2M
Synonyms:CPAMD5
ORF Names:FWP007
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

EuPathDBiHostDB:ENSG00000175899.14
HGNCiHGNC:7 A2M
MIMi103950 gene
neXtProtiNX_P01023

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi2
MalaCardsiA2M
OpenTargetsiENSG00000175899
PharmGKBiPA24357

Chemistry databases

DrugBankiDB00626 Bacitracin
DB00102 Becaplermin
DB08888 Ocriplasmin

Polymorphism and mutation databases

BioMutaiA2M
DMDMi308153640

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 231 PublicationAdd BLAST23
ChainiPRO_000000005524 – 1474Alpha-2-macroglobulin1 PublicationAdd BLAST1451

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi48 ↔ 861 Publication
Glycosylationi55N-linked (GlcNAc...) (complex) asparagine2 Publications1
Glycosylationi70N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi247N-linked (GlcNAc...) asparagine2 Publications1
Disulfide bondi251 ↔ 2991 Publication
Disulfide bondi269 ↔ 2871 Publication
Disulfide bondi278Interchain (with C-431)1 Publication
Glycosylationi396N-linked (GlcNAc...) asparagine3 Publications1
Glycosylationi410N-linked (GlcNAc...) asparagine2 Publications1
Disulfide bondi431Interchain (with C-278)1 Publication
Disulfide bondi470 ↔ 5631 Publication
Disulfide bondi595 ↔ 7712 Publications
Disulfide bondi642 ↔ 6891 Publication
Cross-linki693Isoglutamyl lysine isopeptide (Gln-Lys) (interchain with K-? in other proteins)Sequence analysis
Cross-linki694Isoglutamyl lysine isopeptide (Gln-Lys) (interchain with K-? in other proteins)Sequence analysis
Disulfide bondi821 ↔ 8491 Publication
Disulfide bondi847 ↔ 8831 Publication
Glycosylationi869N-linked (GlcNAc...) asparagine2 Publications1
Disulfide bondi921 ↔ 13211 Publication
Cross-linki972 ↔ 975Isoglutamyl cysteine thioester (Cys-Gln)1 Publication
Glycosylationi991N-linked (GlcNAc...) asparagine4 Publications1
Disulfide bondi1079 ↔ 11271 Publication
Disulfide bondi1352 ↔ 14671 Publication
Glycosylationi1424N-linked (GlcNAc...) (complex) asparagine4 Publications1

Keywords - PTMi

Disulfide bond, Glycoprotein, Isopeptide bond, Thioester bond

Proteomic databases

EPDiP01023
MaxQBiP01023
PaxDbiP01023
PeptideAtlasiP01023
PRIDEiP01023
ProteomicsDBi51307

2D gel databases

DOSAC-COBS-2DPAGEiP01023
SWISS-2DPAGEiP01023

PTM databases

CarbonylDBiP01023
GlyConnecti730
iPTMnetiP01023
PhosphoSitePlusiP01023

Expressioni

Tissue specificityi

Secreted in plasma.1 Publication

Developmental stagei

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

Gene expression databases

BgeeiENSG00000175899 Expressed in 235 organ(s), highest expression level in lung
CleanExiHS_A2M
ExpressionAtlasiP01023 baseline and differential
GenevisibleiP01023 HS

Organism-specific databases

HPAiCAB017621
HPA002265

Interactioni

Subunit structurei

Homotetramer; disulfide-linked.2 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi106524, 109 interactors
CORUMiP01023
DIPiDIP-1118N
IntActiP01023, 105 interactors
MINTiP01023
STRINGi9606.ENSP00000323929

Structurei

Secondary structure

11474
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP01023
SMRiP01023
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP01023

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni690 – 728Bait regionAdd BLAST39
Regioni704 – 709Inhibitory6
Regioni719 – 723Inhibitory5
Regioni730 – 735Inhibitory6

Sequence similaritiesi

Keywords - Domaini

Bait region, Signal

Phylogenomic databases

eggNOGiKOG1366 Eukaryota
ENOG410XRED LUCA
GeneTreeiENSGT00760000118982
HOVERGENiHBG000039
InParanoidiP01023
KOiK03910
OMAiTKIFQMK
OrthoDBiEOG091G00F5
PhylomeDBiP01023
TreeFamiTF313285

Family and domain databases

Gene3Di2.60.40.10, 2 hits
2.60.40.690, 1 hit
InterProiView protein in InterPro
IPR009048 A-macroglobulin_rcpt-bd
IPR036595 A-macroglobulin_rcpt-bd_sf
IPR011626 A2M_comp
IPR002890 A2M_N
IPR011625 A2M_N_2
IPR013783 Ig-like_fold
IPR014756 Ig_E-set
IPR001599 Macroglobln_a2
IPR019742 MacrogloblnA2_CS
IPR019565 MacrogloblnA2_thiol-ester-bond
IPR008930 Terpenoid_cyclase/PrenylTrfase
IPR010916 TonB_box_CS
PfamiView protein in Pfam
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
SMARTiView protein in SMART
SM01360 A2M, 1 hit
SM01359 A2M_N_2, 1 hit
SM01361 A2M_recep, 1 hit
SUPFAMiSSF48239 SSF48239, 1 hit
SSF49410 SSF49410, 1 hit
SSF81296 SSF81296, 1 hit
PROSITEiView protein in PROSITE
PS00477 ALPHA_2_MACROGLOBULIN, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 3 potential isoforms that are computationally mapped.Show allAlign All

P01023-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MGKNKLLHPS LVLLLLVLLP TDASVSGKPQ YMVLVPSLLH TETTEKGCVL
60 70 80 90 100
LSYLNETVTV SASLESVRGN RSLFTDLEAE NDVLHCVAFA VPKSSSNEEV
110 120 130 140 150
MFLTVQVKGP TQEFKKRTTV MVKNEDSLVF VQTDKSIYKP GQTVKFRVVS
160 170 180 190 200
MDENFHPLNE LIPLVYIQDP KGNRIAQWQS FQLEGGLKQF SFPLSSEPFQ
210 220 230 240 250
GSYKVVVQKK SGGRTEHPFT VEEFVLPKFE VQVTVPKIIT ILEEEMNVSV
260 270 280 290 300
CGLYTYGKPV PGHVTVSICR KYSDASDCHG EDSQAFCEKF SGQLNSHGCF
310 320 330 340 350
YQQVKTKVFQ LKRKEYEMKL HTEAQIQEEG TVVELTGRQS SEITRTITKL
360 370 380 390 400
SFVKVDSHFR QGIPFFGQVR LVDGKGVPIP NKVIFIRGNE ANYYSNATTD
410 420 430 440 450
EHGLVQFSIN TTNVMGTSLT VRVNYKDRSP CYGYQWVSEE HEEAHHTAYL
460 470 480 490 500
VFSPSKSFVH LEPMSHELPC GHTQTVQAHY ILNGGTLLGL KKLSFYYLIM
510 520 530 540 550
AKGGIVRTGT HGLLVKQEDM KGHFSISIPV KSDIAPVARL LIYAVLPTGD
560 570 580 590 600
VIGDSAKYDV ENCLANKVDL SFSPSQSLPA SHAHLRVTAA PQSVCALRAV
610 620 630 640 650
DQSVLLMKPD AELSASSVYN LLPEKDLTGF PGPLNDQDNE DCINRHNVYI
660 670 680 690 700
NGITYTPVSS TNEKDMYSFL EDMGLKAFTN SKIRKPKMCP QLQQYEMHGP
710 720 730 740 750
EGLRVGFYES DVMGRGHARL VHVEEPHTET VRKYFPETWI WDLVVVNSAG
760 770 780 790 800
VAEVGVTVPD TITEWKAGAF CLSEDAGLGI SSTASLRAFQ PFFVELTMPY
810 820 830 840 850
SVIRGEAFTL KATVLNYLPK CIRVSVQLEA SPAFLAVPVE KEQAPHCICA
860 870 880 890 900
NGRQTVSWAV TPKSLGNVNF TVSAEALESQ ELCGTEVPSV PEHGRKDTVI
910 920 930 940 950
KPLLVEPEGL EKETTFNSLL CPSGGEVSEE LSLKLPPNVV EESARASVSV
960 970 980 990 1000
LGDILGSAMQ NTQNLLQMPY GCGEQNMVLF APNIYVLDYL NETQQLTPEI
1010 1020 1030 1040 1050
KSKAIGYLNT GYQRQLNYKH YDGSYSTFGE RYGRNQGNTW LTAFVLKTFA
1060 1070 1080 1090 1100
QARAYIFIDE AHITQALIWL SQRQKDNGCF RSSGSLLNNA IKGGVEDEVT
1110 1120 1130 1140 1150
LSAYITIALL EIPLTVTHPV VRNALFCLES AWKTAQEGDH GSHVYTKALL
1160 1170 1180 1190 1200
AYAFALAGNQ DKRKEVLKSL NEEAVKKDNS VHWERPQKPK APVGHFYEPQ
1210 1220 1230 1240 1250
APSAEVEMTS YVLLAYLTAQ PAPTSEDLTS ATNIVKWITK QQNAQGGFSS
1260 1270 1280 1290 1300
TQDTVVALHA LSKYGAATFT RTGKAAQVTI QSSGTFSSKF QVDNNNRLLL
1310 1320 1330 1340 1350
QQVSLPELPG EYSMKVTGEG CVYLQTSLKY NILPEKEEFP FALGVQTLPQ
1360 1370 1380 1390 1400
TCDEPKAHTS FQISLSVSYT GSRSASNMAI VDVKMVSGFI PLKPTVKMLE
1410 1420 1430 1440 1450
RSNHVSRTEV SSNHVLIYLD KVSNQTLSLF FTVLQDVPVR DLKPAIVKVY
1460 1470
DYYETDEFAI AEYNAPCSKD LGNA
Length:1,474
Mass (Da):163,291
Last modified:October 5, 2010 - v3
Checksum:i0A46DF09EFD3CF40
GO

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F8W7L3F8W7L3_HUMAN
Alpha-2-macroglobulin
A2M
168Annotation score:
F5H1E8F5H1E8_HUMAN
Alpha-2-macroglobulin
A2M
90Annotation score:
H0YFH1H0YFH1_HUMAN
Alpha-2-macroglobulin
A2M
73Annotation score:

Sequence cautioni

The sequence AAT02228 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence BAD92851 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti63Missing AA sequence (PubMed:6203908).Curated1
Sequence conflicti82D → V in AAT02228 (Ref. 3) Curated1
Sequence conflicti350 – 353LSFV → ACCS in AAH26246 (PubMed:15489334).Curated4
Sequence conflicti563C → E AA sequence (PubMed:6203908).Curated1
Sequence conflicti844A → V in BAD92851 (PubMed:17974005).Curated1
Sequence conflicti872V → M in CAH18188 (PubMed:16541075).Curated1
Sequence conflicti1148A → D in AAA51552 (PubMed:2408344).Curated1
Sequence conflicti1195H → D in AAA51552 (PubMed:2408344).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_026820639N → D5 PublicationsCorresponds to variant dbSNP:rs226405Ensembl.1
Natural variantiVAR_000012704R → H. Corresponds to variant dbSNP:rs1800434EnsemblClinVar.1
Natural variantiVAR_026821815L → Q. Corresponds to variant dbSNP:rs3180392Ensembl.1
Natural variantiVAR_000013972C → Y Probably interferes with the activity. 1 PublicationCorresponds to variant dbSNP:rs1800433EnsemblClinVar.1
Natural variantiVAR_0000141000I → V5 PublicationsCorresponds to variant dbSNP:rs669EnsemblClinVar.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M11313 mRNA Translation: AAA51551.1
AY591530 mRNA Translation: AAT02228.1 Different initiation.
AB209614 mRNA Translation: BAD92851.1 Different initiation.
CR749334 mRNA Translation: CAH18188.1
AC007436 Genomic DNA No translation available.
BC026246 mRNA Translation: AAH26246.1
BC040071 mRNA Translation: AAH40071.1
Z11711 Genomic DNA Translation: CAA77774.1
X68728, X68729 Genomic DNA Translation: CAA48670.1
M36501 mRNA Translation: AAA51552.1
AF109189 mRNA Translation: AAQ13498.1
CCDSiCCDS44827.1
PIRiA94033 MAHU
RefSeqiNP_000005.2, NM_000014.5
NP_001334352.1, NM_001347423.1
NP_001334353.1, NM_001347424.1
NP_001334354.1, NM_001347425.1
UniGeneiHs.212838
Hs.88556

Genome annotation databases

EnsembliENST00000318602; ENSP00000323929; ENSG00000175899
GeneIDi2
KEGGihsa:2
UCSCiuc001qvk.2 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

Wikipedia

Alpha-2 macroglobulin entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M11313 mRNA Translation: AAA51551.1
AY591530 mRNA Translation: AAT02228.1 Different initiation.
AB209614 mRNA Translation: BAD92851.1 Different initiation.
CR749334 mRNA Translation: CAH18188.1
AC007436 Genomic DNA No translation available.
BC026246 mRNA Translation: AAH26246.1
BC040071 mRNA Translation: AAH40071.1
Z11711 Genomic DNA Translation: CAA77774.1
X68728, X68729 Genomic DNA Translation: CAA48670.1
M36501 mRNA Translation: AAA51552.1
AF109189 mRNA Translation: AAQ13498.1
CCDSiCCDS44827.1
PIRiA94033 MAHU
RefSeqiNP_000005.2, NM_000014.5
NP_001334352.1, NM_001347423.1
NP_001334353.1, NM_001347424.1
NP_001334354.1, NM_001347425.1
UniGeneiHs.212838
Hs.88556

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1BV8NMR-A1337-1474[»]
2P9RX-ray2.30A/B126-227[»]
4ACQX-ray4.30A/B/C/D24-1474[»]
ProteinModelPortaliP01023
SMRiP01023
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106524, 109 interactors
CORUMiP01023
DIPiDIP-1118N
IntActiP01023, 105 interactors
MINTiP01023
STRINGi9606.ENSP00000323929

Chemistry databases

DrugBankiDB00626 Bacitracin
DB00102 Becaplermin
DB08888 Ocriplasmin

Protein family/group databases

MEROPSiI39.001
MoonDBiP01023 Predicted

PTM databases

CarbonylDBiP01023
GlyConnecti730
iPTMnetiP01023
PhosphoSitePlusiP01023

Polymorphism and mutation databases

BioMutaiA2M
DMDMi308153640

2D gel databases

DOSAC-COBS-2DPAGEiP01023
SWISS-2DPAGEiP01023

Proteomic databases

EPDiP01023
MaxQBiP01023
PaxDbiP01023
PeptideAtlasiP01023
PRIDEiP01023
ProteomicsDBi51307

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000318602; ENSP00000323929; ENSG00000175899
GeneIDi2
KEGGihsa:2
UCSCiuc001qvk.2 human

Organism-specific databases

CTDi2
DisGeNETi2
EuPathDBiHostDB:ENSG00000175899.14
GeneCardsiA2M
H-InvDBiHIX0026392
HGNCiHGNC:7 A2M
HPAiCAB017621
HPA002265
MalaCardsiA2M
MIMi103950 gene
neXtProtiNX_P01023
OpenTargetsiENSG00000175899
PharmGKBiPA24357
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1366 Eukaryota
ENOG410XRED LUCA
GeneTreeiENSGT00760000118982
HOVERGENiHBG000039
InParanoidiP01023
KOiK03910
OMAiTKIFQMK
OrthoDBiEOG091G00F5
PhylomeDBiP01023
TreeFamiTF313285

Enzyme and pathway databases

ReactomeiR-HSA-114608 Platelet degranulation
R-HSA-140837 Intrinsic Pathway of Fibrin Clot Formation
R-HSA-1474228 Degradation of the extracellular matrix
R-HSA-194840 Rho GTPase cycle
R-HSA-8963896 HDL assembly

Miscellaneous databases

ChiTaRSiA2M human
EvolutionaryTraceiP01023
GenomeRNAii2
PROiPR:P01023
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000175899 Expressed in 235 organ(s), highest expression level in lung
CleanExiHS_A2M
ExpressionAtlasiP01023 baseline and differential
GenevisibleiP01023 HS

Family and domain databases

Gene3Di2.60.40.10, 2 hits
2.60.40.690, 1 hit
InterProiView protein in InterPro
IPR009048 A-macroglobulin_rcpt-bd
IPR036595 A-macroglobulin_rcpt-bd_sf
IPR011626 A2M_comp
IPR002890 A2M_N
IPR011625 A2M_N_2
IPR013783 Ig-like_fold
IPR014756 Ig_E-set
IPR001599 Macroglobln_a2
IPR019742 MacrogloblnA2_CS
IPR019565 MacrogloblnA2_thiol-ester-bond
IPR008930 Terpenoid_cyclase/PrenylTrfase
IPR010916 TonB_box_CS
PfamiView protein in Pfam
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
SMARTiView protein in SMART
SM01360 A2M, 1 hit
SM01359 A2M_N_2, 1 hit
SM01361 A2M_recep, 1 hit
SUPFAMiSSF48239 SSF48239, 1 hit
SSF49410 SSF49410, 1 hit
SSF81296 SSF81296, 1 hit
PROSITEiView protein in PROSITE
PS00477 ALPHA_2_MACROGLOBULIN, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiA2MG_HUMAN
AccessioniPrimary (citable) accession number: P01023
Secondary accession number(s): Q13677
, Q59F47, Q5QTS0, Q68DN2, Q6PIY3, Q6PN97
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: October 5, 2010
Last modified: November 7, 2018
This is version 212 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
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