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

Gene ID: 2, updated on 14-Nov-2024

Summary

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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
all
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Genomic context

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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

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • 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

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Related articles in PubMed

  1. HK2 Proximal Tubule Epithelial Cells Synthesize and Secrete Plasma Proteins Predominantly Through the Apical Surface. Zhao KW, et al. J Cell Biochem, 2017 Apr. PMID 27862254
  2. A Pro-Nerve Growth Factor (proNGF) and NGF Binding Protein, α2-Macroglobulin, Differentially Regulates p75 and TrkA Receptors and Is Relevant to Neurodegeneration Ex Vivo and In Vivo. Barcelona PF, et al. Mol Cell Biol, 2015 Oct. PMID 26217017, Free PMC Article
  3. Pharmacogenetic Study on the Impact of Rivastigmine Concerning Genetic Variants of A2M and IL-6 Genes on Iranian Alzheimer's Patients. Zamani M, et al. Mol Neurobiol, 2016 Sep. PMID 26289409
  4. Alpha-2-macroglobulin loaded microcapsules enhance human leukocyte functions and innate immune response. Federici Canova D, et al. J Control Release, 2015 Nov 10. PMID 26385167, Free PMC Article
  5. Protease activation of alpha2-macroglobulin modulates a chaperone-like action with broad specificity. French K, et al. Biochemistry, 2008 Jan 29. PMID 18171086

See all (318) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Alpha-2-Macroglobulin Is a Novel Anticancer Agent.
    Title: Alpha-2-Macroglobulin Is a Novel Anticancer Agent.
  2. CCCTC-binding factor suppresses alpha-2-macroglobulin transcription to improve vascular endothelial cell functions in lower extremity arteriosclerosis obliterans.
    Title: CCCTC-binding factor suppresses alpha-2-macroglobulin transcription to improve vascular endothelial cell functions in lower extremity arteriosclerosis obliterans.
  3. Tandem Mass Tag-Labeled Quantitative Proteome Analyses Identify C1R and A2M as Novel Serum Biomarkers in Pregnant Women with Obstructive Sleep Apnea.
    Title: Tandem Mass Tag-Labeled Quantitative Proteome Analyses Identify C1R and A2M as Novel Serum Biomarkers in Pregnant Women with Obstructive Sleep Apnea.
  4. [Pathogenetic role of multifunctional protein alpha-2-macroglobulin and its activity in tears and serum in age-related macular degeneration and proliferative diabetic retinopathy].
    Title: [Pathogenetic role of multifunctional protein alpha-2-macroglobulin and its activity in tears and serum in age-related macular degeneration and proliferative diabetic retinopathy].
  5. Alpha-2 macroglobulin activity in SARS-CoV-2 induced infection and in the post-COVID-19 period.
    Title: Alpha-2 macroglobulin activity in SARS-CoV-2 induced infection and in the post-COVID-19 period.
  6. Alpha-2-macroglobulin prevents platelet aggregation induced by brain-derived neurotrophic factor.
    Title: Alpha-2-macroglobulin prevents platelet aggregation induced by brain-derived neurotrophic factor.
  7. Alpha-2-Macroglobulin (A2M) and Dopamine Receptor D2 (DRD2) expression analysis and Influence of Separation from Parents in Childhood on the Suicide and Self-injury Behavior and Psychological Adjustment in Adolescence.
    Title: Alpha-2-Macroglobulin (A2M) and Dopamine Receptor D2 (DRD2) expression analysis and Influence of Separation from Parents in Childhood on the Suicide and Self-injury Behavior and Psychological Adjustment in Adolescence.
  8. Alpha-2-macroglobulin is involved in the occurrence of early-onset pre-eclampsia via its negative impact on uterine spiral artery remodeling and placental angiogenesis.
    Title: Alpha-2-macroglobulin is involved in the occurrence of early-onset pre-eclampsia via its negative impact on uterine spiral artery remodeling and placental angiogenesis.
  9. LincRNA00612 inhibits apoptosis and inflammation in LPS-induced BEAS-2B cells via enhancing interaction between p-STAT3 and A2M promoter.
    Title: LincRNA00612 inhibits apoptosis and inflammation in LPS-induced BEAS-2B cells via enhancing interaction between p-STAT3 and A2M promoter.
  10. A2M inhibits inflammatory mediators of chondrocytes by blocking IL-1beta/NF-kappaB pathway.
    Title: A2M inhibits inflammatory mediators of chondrocytes by blocking IL-1β/NF-κB pathway.
Submit: New GeneRIF Correction See all GeneRIFs (129)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See Variation Viewer (GRCh37.p13)

HIV-1 interactions

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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

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

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 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
  
Component Evidence Code Pubs
located_in blood microparticle HDA PubMed 
colocalizes_with collagen-containing extracellular matrix HDA PubMed 
located_in collagen-containing extracellular matrix HDA PubMed 
located_in extracellular exosome HDA PubMed 
located_in extracellular region NAS
Non-traceable Author Statement
more info
 PubMed 
located_in extracellular region TAS
Traceable Author Statement
more info
  
is_active_in extracellular space IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in platelet alpha granule lumen TAS
Traceable Author Statement
more info
  

General protein information

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

NCBI Reference Sequences (RefSeq)

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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

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P01023.3 GenPept UniProtKB/Swiss-Prot:P01023

Gene LinkOut

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