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

    Gene ID: 2, updated on 9-Oct-2021

    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
    NEW
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    Try the new Transcript table

    Genomic context

    See A2M in Genome Data Viewer
    Location:
    12p13.31
    Exon count:
    37
    Annotation release Status Assembly Chr Location
    109.20210514 current GRCh38.p13 (GCF_000001405.39) 12 NC_000012.12 (9067708..9116229, complement)
    105.20201022 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (9220304..9268825, 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
    enables calcium-dependent protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables endopeptidase inhibitor activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    enables enzyme binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables growth factor binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables interleukin-1 binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables interleukin-8 binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protease binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    enables protease binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables serine-type endopeptidase inhibitor activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables signaling receptor binding IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    enables tumor necrosis factor binding IDA
    Inferred from Direct Assay
    more info
    PubMed 

    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)

    NEW Try the new Transcript table

    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_011717.2 RefSeqGene

      Range
      5044..53255
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_591

    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
      ENSP00000323929.8, ENST00000318602.12
      Conserved Domains (7) summary
      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
      pfam07703
      Location:459607
      A2M_N_2; Alpha-2-macroglobulin family N-terminal region
      pfam17789
      Location:350445
      MG4; Macroglobulin domain MG4
      pfam17791
      Location:223313
      MG3; Macroglobulin domain MG3
    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
      Conserved Domains (7) summary
      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
      pfam07703
      Location:459607
      A2M_N_2; Alpha-2-macroglobulin family N-terminal region
      pfam17789
      Location:350445
      MG4; Macroglobulin domain MG4
      pfam17791
      Location:223313
      MG3; Macroglobulin domain MG3
    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
      Conserved Domains (7) summary
      cd02897
      Location:8581164
      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:638728
      A2M; Alpha-2-macroglobulin family
      pfam07677
      Location:12761363
      A2M_recep; A-macroglobulin receptor
      pfam17789
      Location:250345
      MG4; Macroglobulin domain MG4
      pfam17791
      Location:123210
      MG3; Macroglobulin domain MG3
      pfam01835
      Location:29121
      A2M_N; MG2 domain
      pfam07703
      Location:359507
      A2M_N_2; Alpha-2-macroglobulin family N-terminal region
    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
      Conserved Domains (7) summary
      cd02897
      Location:8081114
      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:588678
      A2M; Alpha-2-macroglobulin family
      pfam07677
      Location:12261313
      A2M_recep; A-macroglobulin receptor
      pfam17789
      Location:200295
      MG4; Macroglobulin domain MG4
      pfam17791
      Location:73160
      MG3; Macroglobulin domain MG3
      pfam01835
      Location:171
      A2M_N; MG2 domain
      pfam07703
      Location:309457
      A2M_N_2; Alpha-2-macroglobulin family N-terminal region

    RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20210514

    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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