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

    Gene ID: 2, updated on 12-Nov-2017
    Official Symbol
    A2Mprovided by HGNC
    Official Full Name
    alpha-2-macroglobulinprovided by HGNC
    Primary source
    HGNC:HGNC:7
    See related
    Ensembl:ENSG00000175899 MIM:103950; Vega:OTTHUMG00000150267
    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]
    Orthologs
    Location:
    12p13.31
    Exon count:
    36
    Annotation release Status Assembly Chr Location
    108 current GRCh38.p7 (GCF_000001405.33) 12 NC_000012.12 (9067708..9115962, 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 voltage dependent anion channel 2 pseudogene 2 Neighboring gene long intergenic non-protein coding RNA 612 Neighboring gene A2M antisense RNA 1 (head to head) Neighboring gene keratin 17 pseudogene 8 Neighboring gene BTG anti-proliferation factor 1 pseudogene 1

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    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

    • Complement and Coagulation Cascades, organism-specific biosystem (from WikiPathways)
      Complement and Coagulation Cascades, organism-specific biosystemBlood coagulation is a series of coordinated and calcium-dependent proenzyme-to-serine protease conversions likely to be localized on the surfaces of activated cells in vivo. It culminates in the for...
    • Complement and coagulation cascades, organism-specific biosystem (from KEGG)
      Complement and coagulation cascades, organism-specific biosystemThe complement system is a proteolytic cascade in blood plasma and a mediator of innate immunity, a nonspecific defense mechanism against pathogens. There are three pathways of complement activation:...
    • Complement and coagulation cascades, conserved biosystem (from KEGG)
      Complement and coagulation cascades, conserved biosystemThe complement system is a proteolytic cascade in blood plasma and a mediator of innate immunity, a nonspecific defense mechanism against pathogens. There are three pathways of complement activation:...
    • Degradation of the extracellular matrix, organism-specific biosystem (from REACTOME)
      Degradation of the extracellular matrix, organism-specific biosystemMatrix metalloproteinases (MMPs), previously referred to as matrixins because of their role in degradation of the extracellular matrix (ECM), are zinc and calcium dependent proteases belonging to the...
    • Extracellular matrix organization, organism-specific biosystem (from REACTOME)
      Extracellular matrix organization, organism-specific biosystemThe extracellular matrix is a component of all mammalian tissues, a network consisting largely of the fibrous proteins collagen, elastin and associated-microfibrils, fibronectin and laminins embedded...
    • Formation of Fibrin Clot (Clotting Cascade), organism-specific biosystem (from REACTOME)
      Formation of Fibrin Clot (Clotting Cascade), organism-specific biosystemThe formation of a fibrin clot at the site of an injury to the wall of a normal blood vessel is an essential part of the process to stop blood loss after vascular injury. The reactions that lead to ...
    • HDL-mediated lipid transport, organism-specific biosystem (from REACTOME)
      HDL-mediated lipid transport, organism-specific biosystemHDL particles play a central role in the reverse transport of cholesterol, the process by which cholesterol in tissues other than the liver is returned to the liver for conversion to bile salts and e...
    • Hemostasis, organism-specific biosystem (from REACTOME)
      Hemostasis, organism-specific biosystemHemostasis is a physiological response that culminates in the arrest of bleeding from an injured vessel. Under normal conditions the vascular endothelium supports vasodilation, inhibits platelet adhe...
    • IL6-mediated signaling events, organism-specific biosystem (from Pathway Interaction Database)
      IL6-mediated signaling events, organism-specific biosystem
      IL6-mediated signaling events
    • Intrinsic Pathway of Fibrin Clot Formation, organism-specific biosystem (from REACTOME)
      Intrinsic Pathway of Fibrin Clot Formation, organism-specific biosystemThe intrinsic pathway of blood clotting connects interactions among kininogen (high molecular weight kininogen, HK), prekallikrein (PK), and factor XII to the activation of clotting factor X by a ser...
    • Lipid digestion, mobilization, and transport, organism-specific biosystem (from REACTOME)
      Lipid digestion, mobilization, and transport, organism-specific biosystemProcesses annotated here include the digestion of dietary lipids, sterol uptake, the formation and turnover of lipoproteins (chylomicrons, VLDL, LDL, and HDL), and the mobilization of fatty acids thr...
    • Lipoprotein metabolism, organism-specific biosystem (from REACTOME)
      Lipoprotein metabolism, organism-specific biosystemBecause of their hydrophobicity, lipids are found in the extracellular spaces of the human body primarily in the form of lipoprotein complexes. Chylomicrons form in the small intestine and transport ...
    • Metabolism, organism-specific biosystem (from REACTOME)
      Metabolism, organism-specific biosystemMetabolic processes in human cells generate energy through the oxidation of molecules consumed in the diet and mediate the synthesis of diverse essential molecules not taken in the diet as well as th...
    • Metabolism of lipids and lipoproteins, organism-specific biosystem (from REACTOME)
      Metabolism of lipids and lipoproteins, organism-specific biosystemLipids are hydrophobic but otherwise chemically diverse molecules that play a wide variety of roles in human biology. They include ketone bodies, fatty acids, triacylglycerols, phospholipids and sphi...
    • Platelet activation, signaling and aggregation, organism-specific biosystem (from REACTOME)
      Platelet activation, signaling and aggregation, organism-specific biosystemPlatelet activation begins with the initial binding of adhesive ligands and of the excitatory platelet agonists (released or generated at the sites of vascular trauma) to cognate receptors on the pla...
    • Platelet degranulation, organism-specific biosystem (from REACTOME)
      Platelet degranulation, organism-specific biosystemPlatelets function as exocytotic cells, secreting a plethora of effector molecules at sites of vascular injury. Platelets contain a number of distinguishable storage granules including alpha granules...
    • Response to elevated platelet cytosolic Ca2+, organism-specific biosystem (from REACTOME)
      Response to elevated platelet cytosolic Ca2+, organism-specific biosystemActivation of phospholipase C enzymes results in the generation of second messengers of the phosphatidylinositol pathway. The events resulting from this pathway are a rise in intracellular calcium an...
    • Rho GTPase cycle, organism-specific biosystem (from REACTOME)
      Rho GTPase cycle, organism-specific biosystemThe cycling of Rho GTPases is tightly controlled by three classes of protein. These are (1) guanine nucleotide dissociation inhibitors or GDIs, which maintain Rho proteins in an inactive state in the...
    • Signal Transduction, organism-specific biosystem (from REACTOME)
      Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
    • Signaling by Rho GTPases, organism-specific biosystem (from REACTOME)
      Signaling by Rho GTPases, organism-specific biosystemThe Rho family of small guanine nucleotide binding proteins is one of five generally recognized branches of the Ras superfamily. Like most Ras superfamily members, typical Rho proteins function as bi...
    Products Interactant Other Gene Complex Source Pubs Description

    Markers

    Homology

    Clone Names

    • DKFZp779B086

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    GTPase activator activity TAS
    Traceable Author Statement
    more info
     
    calcium-dependent protein binding IPI
    Inferred from Physical Interaction
    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 IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    receptor binding IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    serine-type endopeptidase inhibitor activity IDA
    Inferred from Direct Assay
    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
     
    positive regulation of GTPase activity IEA
    Inferred from Electronic Annotation
    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
     
    Component Evidence Code Pubs
    blood microparticle IDA
    Inferred from Direct Assay
    more info
    PubMed 
    cytosol TAS
    Traceable Author Statement
    more info
     
    extracellular exosome IDA
    Inferred from Direct Assay
    more info
    PubMed 
    extracellular region NAS
    Non-traceable Author Statement
    more info
    PubMed 
    extracellular region TAS
    Traceable Author Statement
    more info
     
    platelet alpha granule lumen TAS
    Traceable Author Statement
    more info
     
    Preferred Names
    alpha-2-macroglobulin
    Names
    C3 and PZP-like alpha-2-macroglobulin domain-containing protein 5
    alpha-2-M

    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
      5001..53255
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_000014.5NP_000005.2  alpha-2-macroglobulin isoform a precursor

      See identical proteins and their annotated locations for NP_000005.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (a). Both variants 1 and 2 encode isoform a.
      Source sequence(s)
      AB209614, BC040071, DC334781, DC402196
      Consensus CDS
      CCDS44827.1
      UniProtKB/Swiss-Prot
      P01023
      Related
      ENSP00000323929.7, OTTHUMP00000196829, ENST00000318602.11, OTTHUMT00000317233
      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
    2. NM_001347423.1NP_001334352.1  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)
      AB209614, BC040071, DC334781
      UniProtKB/Swiss-Prot
      P01023
    3. NM_001347424.1NP_001334353.1  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)
      AB209614, AC007436, BC040071, DB288732, DC334781, DC402196
      UniProtKB/Swiss-Prot
      P01023
    4. NM_001347425.1NP_001334354.1  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)
      AK307832, BC040071, DC334781, DC402196
      UniProtKB/Swiss-Prot
      P01023

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 108 details...Open this link in a new tab

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

    Reference GRCh38.p7 Primary Assembly

    Genomic

    1. NC_000012.12 Reference GRCh38.p7 Primary Assembly

      Range
      9067708..9115962 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_006719056.2XP_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

    Alternate CHM1_1.1

    Genomic

    1. NC_018923.2 Alternate CHM1_1.1

      Range
      9189284..9237532 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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