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A2M alpha-2-macroglobulin [ Homo sapiens (human) ]

Gene ID: 2, updated on 1-Aug-2020

Summary

Official Symbol
A2Mprovided by HGNC
Official Full Name
alpha-2-macroglobulinprovided by HGNC
Primary source
HGNC:HGNC:7
See related
Ensembl:ENSG00000175899 MIM:103950
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
A2MD; CPAMD5; FWP007; S863-7
Summary
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]
Expression
Broad expression in lung (RPKM 732.0), urinary bladder (RPKM 374.7) and 21 other tissues See more
Orthologs

Genomic context

See A2M in Genome Data Viewer
Location:
12p13.31
Exon count:
37
Annotation release Status Assembly Chr Location
109.20200522 current GRCh38.p13 (GCF_000001405.39) 12 NC_000012.12 (9067708..9116229, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (9220304..9268558, complement)

Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene killer cell lectin like receptor G1 Neighboring gene VDAC2 pseudogene 2 Neighboring gene long intergenic non-protein coding RNA 612 Neighboring gene A2M antisense RNA 1 Neighboring gene keratin 17 pseudogene 8 Neighboring gene BTG anti-proliferation factor 1 pseudogene 1

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

HIV-1 interactions

Protein interactions

Protein Gene Interaction Pubs
Envelope transmembrane glycoprotein gp41 env A synthetic peptide corresponding to the immunosuppressive domain (amino acids 574-592) of HIV-1 gp41 downregulates the expression of alpha-2-macroglobulin (A2M) in peptide-treated PBMCs PubMed
Tat tat Binding of HIV-1 Tat to LRP inhibits neuronal binding, uptake and degradation of physiological ligands for LRP, including alpha2-macroglobulin, apolipoprotein E4, amyloid precursor and amyloid beta-protein PubMed
retropepsin gag-pol The cleavage site of alpha 2-Macroglobulin by HIV-1 protease is the Phe684-Tyr685 bond PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Clone Names

  • DKFZp779B086

Gene Ontology Provided by GOA

Function Evidence Code Pubs
calcium-dependent protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
endopeptidase inhibitor activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
enzyme binding IPI
Inferred from Physical Interaction
more info
PubMed 
growth factor binding IDA
Inferred from Direct Assay
more info
PubMed 
interleukin-1 binding IDA
Inferred from Direct Assay
more info
PubMed 
interleukin-8 binding IPI
Inferred from Physical Interaction
more info
PubMed 
protease binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
protease binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
serine-type endopeptidase inhibitor activity IDA
Inferred from Direct Assay
more info
PubMed 
signaling receptor binding IMP
Inferred from Mutant Phenotype
more info
PubMed 
tumor necrosis factor binding IDA
Inferred from Direct Assay
more info
PubMed 
Process Evidence Code Pubs
blood coagulation, intrinsic pathway TAS
Traceable Author Statement
more info
 
extracellular matrix disassembly TAS
Traceable Author Statement
more info
 
negative regulation of complement activation, lectin pathway IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of endopeptidase activity IEA
Inferred from Electronic Annotation
more info
 
platelet degranulation TAS
Traceable Author Statement
more info
 
regulation of small GTPase mediated signal transduction TAS
Traceable Author Statement
more info
 
stem cell differentiation IEA
Inferred from Electronic Annotation
more info
 

General protein information

Preferred Names
alpha-2-macroglobulin
Names
C3 and PZP-like alpha-2-macroglobulin domain-containing protein 5
alpha-2-M

NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_011717.1 RefSeqGene

    Range
    4734..53255
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_000014.6NP_000005.3  alpha-2-macroglobulin isoform a precursor

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longest isoform (a). Both variants 1 and 2 encode isoform a.
    Source sequence(s)
    AC007436
    Consensus CDS
    CCDS44827.1
    Related
    ENSP00000323929.7, ENST00000318602.11
  2. NM_001347423.2NP_001334352.2  alpha-2-macroglobulin isoform a precursor

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) splices out a region of the 5' UTR, compared to variant 1. Both variants 1 and 2 encode the same isoform (a).
    Source sequence(s)
    AC007436
    Consensus CDS
    CCDS44827.1
  3. NM_001347424.2NP_001334353.2  alpha-2-macroglobulin isoform b

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) contains an alternate splice site in the 5' region, and it thus differs in its 5' UTR and initiates translation from a downstream in-frame start codon, compared to variant 1. The encoded isoform (b) is shorter at the N-terminus, compared to isoform a.
    Source sequence(s)
    AC007436
  4. NM_001347425.2NP_001334354.2  alpha-2-macroglobulin isoform c

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) lacks an exon in the 5' region, and it thus differs in its 5' UTR and initiates translation from a downstream in-frame start codon, compared to variant 1. The encoded isoform (c) is shorter at the N-terminus, compared to isoform a.
    Source sequence(s)
    AC007436

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109.20200522

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000012.12 Reference GRCh38.p13 Primary Assembly

    Range
    9067708..9116229 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_006719056.3XP_006719119.1  alpha-2-macroglobulin isoform X1

    Conserved Domains (7) summary
    COG2373
    Location:1241071
    YfaS; Uncharacterized conserved protein YfaS, alpha-2-macroglobulin family [General function prediction only]
    cd02897
    Location:9581264
    A2M_2; Proteins similar to alpha2-macroglobulin (alpha (2)-M). This group also contains the pregnancy zone protein (PZP). Alpha(2)-M and PZP are broadly specific proteinase inhibitors. Alpha (2)-M is a major carrier protein in serum. The structural thioester ...
    pfam00207
    Location:738828
    A2M; Alpha-2-macroglobulin family
    pfam01835
    Location:129221
    A2M_N; MG2 domain
    pfam07677
    Location:13761463
    A2M_recep; A-macroglobulin receptor
    pfam07678
    Location:10101266
    A2M_comp; A-macroglobulin complement component
    pfam07703
    Location:461606
    A2M_N_2; Alpha-2-macroglobulin family N-terminal region
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