Seroatlas · Human Serome Atlas

A2M

Alpha-2-macroglobulin

Also known as: A2MG_HUMAN, CPAMD5, FWP007, S863-7

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: P01023
Gene: A2M
Ensembl: ENSG00000175899
Chromosome: 12
Canonical length: 1474 aa
Protein class: Cancer-related genes, Candidate cardiovascular disease genes, Plasma proteins, Predicted secreted proteins
Secretome location: Secreted to blood
Quaternary structure: Homotetramer

OverviewNCBI Gene

The protein encoded by this gene is a protease inhibitor and cytokine transporter. It uses a bait-and-trap mechanism to inhibit a broad spectrum of proteases, including trypsin, thrombin and collagenase. It can also inhibit inflammatory cytokines, and it thus disrupts inflammatory cascades. Mutations in this gene are a cause of alpha-2-macroglobulin deficiency. This gene is implicated in Alzheimer's disease (AD) due to its ability to mediate the clearance and degradation of A-beta, the major component of beta-amyloid deposits. A related pseudogene, which is also located on the p arm of chromosome 12, has been identified. [provided by RefSeq, Nov 2016]

Canonical amino-acid sequenceUniProt

1474 residues, UniProt reviewed canonical sequence.

>P01023|A2M
     1  MGKNKLLHPS LVLLLLVLLP TDASVSGKPQ YMVLVPSLLH TETTEKGCVL LSYLNETVTV
    61  SASLESVRGN RSLFTDLEAE NDVLHCVAFA VPKSSSNEEV MFLTVQVKGP TQEFKKRTTV
   121  MVKNEDSLVF VQTDKSIYKP GQTVKFRVVS MDENFHPLNE LIPLVYIQDP KGNRIAQWQS
   181  FQLEGGLKQF SFPLSSEPFQ GSYKVVVQKK SGGRTEHPFT VEEFVLPKFE VQVTVPKIIT
   241  ILEEEMNVSV CGLYTYGKPV PGHVTVSICR KYSDASDCHG EDSQAFCEKF SGQLNSHGCF
   301  YQQVKTKVFQ LKRKEYEMKL HTEAQIQEEG TVVELTGRQS SEITRTITKL SFVKVDSHFR
   361  QGIPFFGQVR LVDGKGVPIP NKVIFIRGNE ANYYSNATTD EHGLVQFSIN TTNVMGTSLT
   421  VRVNYKDRSP CYGYQWVSEE HEEAHHTAYL VFSPSKSFVH LEPMSHELPC GHTQTVQAHY
   481  ILNGGTLLGL KKLSFYYLIM AKGGIVRTGT HGLLVKQEDM KGHFSISIPV KSDIAPVARL
   541  LIYAVLPTGD VIGDSAKYDV ENCLANKVDL SFSPSQSLPA SHAHLRVTAA PQSVCALRAV
   601  DQSVLLMKPD AELSASSVYN LLPEKDLTGF PGPLNDQDNE DCINRHNVYI NGITYTPVSS
   661  TNEKDMYSFL EDMGLKAFTN SKIRKPKMCP QLQQYEMHGP EGLRVGFYES DVMGRGHARL
   721  VHVEEPHTET VRKYFPETWI WDLVVVNSAG VAEVGVTVPD TITEWKAGAF CLSEDAGLGI
   781  SSTASLRAFQ PFFVELTMPY SVIRGEAFTL KATVLNYLPK CIRVSVQLEA SPAFLAVPVE
   841  KEQAPHCICA NGRQTVSWAV TPKSLGNVNF TVSAEALESQ ELCGTEVPSV PEHGRKDTVI
   901  KPLLVEPEGL EKETTFNSLL CPSGGEVSEE LSLKLPPNVV EESARASVSV LGDILGSAMQ
   961  NTQNLLQMPY GCGEQNMVLF APNIYVLDYL NETQQLTPEI KSKAIGYLNT GYQRQLNYKH
  1021  YDGSYSTFGE RYGRNQGNTW LTAFVLKTFA QARAYIFIDE AHITQALIWL SQRQKDNGCF
  1081  RSSGSLLNNA IKGGVEDEVT LSAYITIALL EIPLTVTHPV VRNALFCLES AWKTAQEGDH
  1141  GSHVYTKALL AYAFALAGNQ DKRKEVLKSL NEEAVKKDNS VHWERPQKPK APVGHFYEPQ
  1201  APSAEVEMTS YVLLAYLTAQ PAPTSEDLTS ATNIVKWITK QQNAQGGFSS TQDTVVALHA
  1261  LSKYGAATFT RTGKAAQVTI QSSGTFSSKF QVDNNNRLLL QQVSLPELPG EYSMKVTGEG
  1321  CVYLQTSLKY NILPEKEEFP FALGVQTLPQ TCDEPKAHTS FQISLSVSYT GSRSASNMAI
  1381  VDVKMVSGFI PLKPTVKMLE RSNHVSRTEV SSNHVLIYLD KVSNQTLSLF FTVLQDVPVR
  1441  DLKPAIVKVY DYYETDEFAI AEYNAPCSKD LGNA

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against A2M can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability: Secreted
Secreted: Yes
Transmembrane segments: 0
Mean surface accessibility (rSASA): 0.26
Highest tissue expression: 1,684 nTPM

Expression across tissuesHPA

Tissue

lung: 1,684 nTPM
liver: 1,169 nTPM
blood vessel: 843 nTPM
urinary bladder: 791 nTPM
smooth muscle: 486 nTPM
gallbladder: 424 nTPM

Single-cell type

vascular endothelial cells: 1,020 nCPM
microglia: 849 nCPM
hepatocytes: 758 nCPM
vascular smooth muscle cells: 724 nCPM
retinal horizontal cells: 681 nCPM
pericytes: 657 nCPM

Immune cell

gdT-cell: 1.5 nTPM
MAIT T-cell: 0.8 nTPM
plasmacytoid DC: 0.5 nTPM
memory CD8 T-cell: 0.4 nTPM
naive CD8 T-cell: 0.2 nTPM
classical monocyte: 0.1 nTPM

Brain region

spinal cord: 225 nTPM
medulla oblongata: 215 nTPM
thalamus: 215 nTPM
pons: 214 nTPM
white matter: 206 nTPM
hypothalamus: 177 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about A2M.

Disease | ImmuneIEDB

Conditions an epitope on A2M was assayed in.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance): 0.54
gnomAD pLI: 0
gnomAD missense Z: 1.87
DepMap mean gene effect: 0.04
DepMap dependency class: none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads A2M as an antibody target. Whether an autoantibody or antibody against A2M could matter depends on whether native A2M is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

A2M is annotated as secreted, so native A2M circulates and is directly accessible to antibodies. Secreted and cell-surface proteins are the autoantibody targets most likely to act like drugs, blocking or depleting the native protein.

Annotation status

The present source text does not explicitly label A2M as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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