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

    Gene ID: 2, updated on 2-Nov-2024

    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; AllianceGenome:HGNC:7
    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
    Try the new Gene table
    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
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (9067708..9116229, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (9049893..9098416, complement)
    RS_2024_09 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 ATAC-STARR-seq lymphoblastoid silent region 4221 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4222 Neighboring gene long intergenic non-protein coding RNA 612 Neighboring gene A2M antisense RNA 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5939 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 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

    Clone Names

    • DKFZp779B086

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables brain-derived neurotrophic factor binding IEA
    Inferred from Electronic Annotation
    more info
     
    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
     
    enables endopeptidase inhibitor activity IDA
    Inferred from Direct Assay
    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 identical protein binding IEA
    Inferred from Electronic Annotation
    more info
     
    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 nerve growth factor binding IEA
    Inferred from Electronic Annotation
    more info
     
    enables protease binding IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    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 
    Process Evidence Code Pubs
    involved_in acute inflammatory response to antigenic stimulus IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in acute-phase response IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in embryonic liver development IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in luteinization IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in negative regulation of complement activation, lectin pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in negative regulation of peptidase activity IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in response to carbon dioxide IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in response to glucocorticoid IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in response to nutrient IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in response to prostaglandin E IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in 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)

    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_000014.6 → NP_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
      UniProtKB/Swiss-Prot
      P01023, Q13677, Q59F47, Q5QTS0, Q68DN2, Q6PIY3, Q6PN97
      Related
      ENSP00000323929.8, ENST00000318602.12
      Conserved Domains (7) summary
      cd02897
      Location:958 → 1264
      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:738 → 828
      A2M; Alpha-2-macroglobulin family
      pfam01835
      Location:129 → 221
      A2M_N; MG2 domain
      pfam07677
      Location:1376 → 1463
      A2M_recep; A-macroglobulin receptor
      pfam07703
      Location:459 → 607
      A2M_N_2; Alpha-2-macroglobulin family N-terminal region
      pfam17789
      Location:350 → 445
      MG4; Macroglobulin domain MG4
      pfam17791
      Location:223 → 313
      MG3; Macroglobulin domain MG3
    2. NM_001347423.2 → NP_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
      UniProtKB/Swiss-Prot
      P01023, Q13677, Q59F47, Q5QTS0, Q68DN2, Q6PIY3, Q6PN97
      Conserved Domains (7) summary
      cd02897
      Location:958 → 1264
      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:738 → 828
      A2M; Alpha-2-macroglobulin family
      pfam01835
      Location:129 → 221
      A2M_N; MG2 domain
      pfam07677
      Location:1376 → 1463
      A2M_recep; A-macroglobulin receptor
      pfam07703
      Location:459 → 607
      A2M_N_2; Alpha-2-macroglobulin family N-terminal region
      pfam17789
      Location:350 → 445
      MG4; Macroglobulin domain MG4
      pfam17791
      Location:223 → 313
      MG3; Macroglobulin domain MG3
    3. NM_001347424.2 → NP_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:858 → 1164
      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:638 → 728
      A2M; Alpha-2-macroglobulin family
      pfam07677
      Location:1276 → 1363
      A2M_recep; A-macroglobulin receptor
      pfam17789
      Location:250 → 345
      MG4; Macroglobulin domain MG4
      pfam17791
      Location:123 → 210
      MG3; Macroglobulin domain MG3
      pfam01835
      Location:29 → 121
      A2M_N; MG2 domain
      pfam07703
      Location:359 → 507
      A2M_N_2; Alpha-2-macroglobulin family N-terminal region
    4. NM_001347425.2 → NP_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:808 → 1114
      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:588 → 678
      A2M; Alpha-2-macroglobulin family
      pfam07677
      Location:1226 → 1313
      A2M_recep; A-macroglobulin receptor
      pfam17789
      Location:200 → 295
      MG4; Macroglobulin domain MG4
      pfam17791
      Location:73 → 160
      MG3; Macroglobulin domain MG3
      pfam01835
      Location:1 → 71
      A2M_N; MG2 domain
      pfam07703
      Location:309 → 457
      A2M_N_2; Alpha-2-macroglobulin family N-terminal region

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000012.12 Reference GRCh38.p14 Primary Assembly

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

    mRNA and Protein(s)

    1. XM_006719056.4 → XP_006719119.1  alpha-2-macroglobulin isoform X1

      Conserved Domains (7) summary
      COG2373
      Location:124 → 1071
      YfaS; Uncharacterized conserved protein YfaS, alpha-2-macroglobulin family [General function prediction only]
      cd02897
      Location:958 → 1264
      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:738 → 828
      A2M; Alpha-2-macroglobulin family
      pfam01835
      Location:129 → 221
      A2M_N; MG2 domain
      pfam07677
      Location:1376 → 1463
      A2M_recep; A-macroglobulin receptor
      pfam07678
      Location:1010 → 1266
      A2M_comp; A-macroglobulin complement component
      pfam07703
      Location:461 → 606
      A2M_N_2; Alpha-2-macroglobulin family N-terminal region

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060936.1 Alternate T2T-CHM13v2.0

      Range
      9049893..9098416 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054371391.1 → XP_054227366.1  alpha-2-macroglobulin isoform X1