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

Gene ID: 2, updated on 6-Aug-2014
Official Symbol
A2Mprovided by HGNC
Official Full Name
alpha-2-macroglobulinprovided by HGNC
Primary source
HGNC:7
See related
Ensembl:ENSG00000175899; HPRD:00072; 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
Alpha-2-macroglobulin is a protease inhibitor and cytokine transporter. It inhibits many proteases, including trypsin, thrombin and collagenase. A2M is implicated in Alzheimer disease (AD) due to its ability to mediate the clearance and degradation of A-beta, the major component of beta-amyloid deposits. [provided by RefSeq, Jul 2008]
Location:
12p13.31
Exon count:
36
Annotation release Status Assembly Chr Location
106 current GRCh38 (GCF_000001405.26) 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 subfamily G, member 1 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 B-cell translocation gene 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 Protein 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, organism-specific biosystem (from REACTOME)
    Intrinsic Pathway, 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
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 TAS
Traceable Author Statement
more info
 
blood coagulation, intrinsic pathway TAS
Traceable Author Statement
more info
 
extracellular matrix disassembly TAS
Traceable Author Statement
more info
 
extracellular matrix organization 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 IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of endopeptidase activity IEA
Inferred from Electronic Annotation
more info
 
platelet activation TAS
Traceable Author Statement
more info
 
platelet degranulation TAS
Traceable Author Statement
more info
 
regulation of small GTPase mediated signal transduction TAS
Traceable Author Statement
more info
 
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
 
cytosol TAS
Traceable Author Statement
more info
 
extracellular region NAS
Non-traceable Author Statement
more info
PubMed 
extracellular region TAS
Traceable Author Statement
more info
 
extracellular vesicular exosome IDA
Inferred from Direct Assay
more info
 
platelet alpha granule lumen TAS
Traceable Author Statement
more info
 
Preferred Names
alpha-2-macroglobulin
Names
alpha-2-macroglobulin
alpha-2-M
C3 and PZP-like alpha-2-macroglobulin domain-containing protein 5

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 

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

mRNA and Protein(s)

  1. NM_000014.4NP_000005.2  alpha-2-macroglobulin precursor

    See proteins identical to NP_000005.2

    Status: REVIEWED

    Source sequence(s)
    BC026246, BC040071, BX504041, BX647329
    Consensus CDS
    CCDS44827.1
    UniProtKB/Swiss-Prot
    P01023
    Related
    ENSP00000323929, OTTHUMP00000196829, ENST00000318602, OTTHUMT00000317233
    Conserved Domains (8) summary
    COG2373
    Location:1241071
    Blast Score: 228
    COG2373; Large extracellular alpha-helical protein [General function prediction only]
    cd02897
    Location:9581264
    Blast Score: 1228
    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
    Blast Score: 352
    A2M; Alpha-2-macroglobulin family
    pfam01835
    Location:129221
    Blast Score: 268
    A2M_N; MG2 domain
    pfam07677
    Location:13761463
    Blast Score: 331
    A2M_recep; A-macroglobulin receptor
    pfam07678
    Location:10101266
    Blast Score: 948
    A2M_comp; A-macroglobulin complement component
    pfam07703
    Location:459607
    Blast Score: 340
    A2M_N_2; Alpha-2-macroglobulin family N-terminal region
    pfam11974
    Location:23110
    Blast Score: 144
    MG1; Alpha-2-macroglobulin MG1 domain

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 106

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

Reference GRCh38 Primary Assembly

Genomic

  1. NC_000012.12 

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

mRNA and Protein(s)

  1. XM_006719056.1XP_006719119.1  

    Conserved Domains (8) summary
    COG2373
    Location:1241071
    Blast Score: 228
    COG2373; Large extracellular alpha-helical protein [General function prediction only]
    cd02897
    Location:9581264
    Blast Score: 1227
    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
    Blast Score: 353
    A2M; Alpha-2-macroglobulin family
    pfam01835
    Location:129221
    Blast Score: 269
    A2M_N; MG2 domain
    pfam07677
    Location:13761463
    Blast Score: 332
    A2M_recep; A-macroglobulin receptor
    pfam07678
    Location:10101266
    Blast Score: 948
    A2M_comp; A-macroglobulin complement component
    pfam07703
    Location:459607
    Blast Score: 340
    A2M_N_2; Alpha-2-macroglobulin family N-terminal region
    pfam11974
    Location:23110
    Blast Score: 144
    MG1; Alpha-2-macroglobulin MG1 domain

Alternate HuRef

Genomic

  1. AC_000144.1 

    Range
    9000837..9049088
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.1

Genomic

  1. NC_018923.2 

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