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A2M Gene(Protein Coding)

Alpha-2-Macroglobulin

GCID:
GC12M009067
GIFtS:
55
Genes Participants
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Aliases for A2M Gene

Aliases for A2M Gene

  • Alpha-2-Macroglobulin 2 3 3 5
  • C3 And PZP-Like Alpha-2-Macroglobulin Domain-Containing Protein 5 3 4
  • Alpha-2-M 3 4
  • CPAMD5 3 4
  • FWP007 3
  • S863-7 3
  • A2MD 3

External Ids for A2M Gene

Previous GeneCards Identifiers for A2M Gene

  • GC12M008928
  • GC12M009368
  • GC12M009120
  • GC12M009111
  • GC12M009103
  • GC12M009220
  • GC12M009001

Summaries for A2M Gene

Entrez Gene Summary for A2M Gene

  • 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]

GeneCards Summary for A2M Gene

A2M (Alpha-2-Macroglobulin) is a Protein Coding gene. Diseases associated with A2M include Alzheimer Disease and Alpha-2-Macroglobulin Deficiency. Among its related pathways are Complement and coagulation cascades and Response to elevated platelet cytosolic Ca2+. Gene Ontology (GO) annotations related to this gene include receptor binding and serine-type endopeptidase inhibitor activity. An important paralog of this gene is PZP.

UniProtKB/Swiss-Prot for A2M Gene

  • Is able to inhibit all four classes of proteinases by a unique trapping mechanism. This protein has a peptide stretch, called the bait region which contains specific cleavage sites for different proteinases. When a proteinase cleaves the bait region, a conformational change is induced in the protein which traps the proteinase. The entrapped enzyme remains active against low molecular weight substrates (activity against high molecular weight substrates is greatly reduced). Following cleavage in the bait region, a thioester bond is hydrolyzed and mediates the covalent binding of the protein to the proteinase.

Additional gene information for A2M Gene

No data available for CIViC summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for A2M Gene

Genomics for A2M Gene

Products:

  1. Regulatory Element

GeneHancer (GH) Regulatory Elements for A2M Gene

Promoters and enhancers for A2M Gene
GeneHancer (GH) Identifier GH Type GH
Score		 GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites		 Gene Targets
GH12I009113 Promoter/Enhancer 1.9 EPDnew Ensembl ENCODE 567.8 +0.3 257 4.3 FOXA2 MLX ZFP64 ARID4B DMAP1 ZNF48 ETS1 YY1 ATF7 PAF1 A2M KLRG1 PZP GC12M009115 GC12M009066
GH12I009063 Promoter/Enhancer 1.4 Ensembl ENCODE 23.4 +51.5 51477 2.3 ZFP64 ARID4B SIN3A DMAP1 ZNF2 ZNF48 YY1 GLIS2 PAF1 RXRA A2M-AS1 LINC00612 A2M KRT17P8 BTG1P1 VDAC2P2
GH12I009131 Enhancer 1.2 ENCODE dbSUPER 10.2 -16.4 -16429 2.5 FOXA2 MLX ARID4B DMAP1 ETS1 YY1 TCF12 SLC30A9 ATF7 RXRA A2M BTG1P1 KRT17P8 GC12M009133
GH12I009083 Enhancer 0.4 FANTOM5 23.6 +32.4 32434 0.7 ZNF791 SETDB1 A2M LOC642846 KLRG1 GC12M009066
GH12I009072 Enhancer 0.6 ENCODE 12 +43.1 43067 1.3 PAF1 FOXA2 RXRA MAX RAD21 YY1 SSRP1 JUND POLR2A ATF3 A2M-AS1 A2M GC12M009066
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around A2M on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the A2M gene promoter:

Genomic Locations for A2M Gene

Genomic Locations for A2M Gene
chr12:9,067,664-9,116,229
(GRCh38/hg38)
Size:
48,566 bases
Orientation:
Minus strand
chr12:9,220,260-9,268,825
(GRCh37/hg19)

Genomic View for A2M Gene

Genes around A2M on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
A2M Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for A2M Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for A2M Gene

Proteins for A2M Gene

Products:

  1. Antibody
  2. Protein
  3. Assay

  • Protein details for A2M Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P01023-A2MG_HUMAN
    Recommended name:
    Alpha-2-macroglobulin
    Protein Accession:
    P01023
    Secondary Accessions:
    • Q13677
    • Q59F47
    • Q5QTS0
    • Q68DN2
    • Q6PIY3
    • Q6PN97

    Protein attributes for A2M Gene

    Size:
    1474 amino acids
    Molecular mass:
    163291 Da
    Quaternary structure:
    • Homotetramer; disulfide-linked.
    SequenceCaution:
    • Sequence=AAT02228.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305}; Sequence=BAD92851.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for A2M Gene

neXtProt entry for A2M Gene

Protein Expression for A2M Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Post-translational modifications for A2M Gene

  • Glycosylation at Asn55, posLast=7070, posLast=247247, Asn396, Asn410, Asn869, Asn991, and posLast=14241424
  • Modification sites at PhosphoSitePlus

Other Protein References for A2M Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for A2M Gene

Domains & Families for A2M Gene

Gene Families for A2M Gene

HGNC:
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Candidate cardiovascular disease genes
  • Plasma proteins
  • Predicted secreted proteins

Protein Domains for A2M Gene

InterPro:
Blocks:
ProtoNet:

Suggested Antigen Peptide Sequences for A2M Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

P01023

UniProtKB/Swiss-Prot:

A2MG_HUMAN :
  • Belongs to the protease inhibitor I39 (alpha-2-macroglobulin) family.
Family:
  • Belongs to the protease inhibitor I39 (alpha-2-macroglobulin) family.
genes like me logo Genes that share domains with A2M: view

Function for A2M Gene

Products:

  1. Animal Model
  2. CRISPR
  3. miRNA
  4. Inhibitory RNA
  5. Clone
  6. Cell Line

Molecular function for A2M Gene

GENATLAS Biochemistry:
macroglobulin,alpha-2- (protease inhibitor),may be implicated in susceptibility to Alzheimer disease (AD5)
UniProtKB/Swiss-Prot Function:
Is able to inhibit all four classes of proteinases by a unique trapping mechanism. This protein has a peptide stretch, called the bait region which contains specific cleavage sites for different proteinases. When a proteinase cleaves the bait region, a conformational change is induced in the protein which traps the proteinase. The entrapped enzyme remains active against low molecular weight substrates (activity against high molecular weight substrates is greatly reduced). Following cleavage in the bait region, a thioester bond is hydrolyzed and mediates the covalent binding of the protein to the proteinase.

Gene Ontology (GO) - Molecular Function for A2M Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002020 protease binding IPI 18485748
GO:0004866 endopeptidase inhibitor activity IEA --
GO:0004867 serine-type endopeptidase inhibitor activity IEA,IDA 12538697
GO:0005096 GTPase activator activity TAS --
GO:0005102 receptor binding IMP 15226301
genes like me logo Genes that share ontologies with A2M: view
genes like me logo Genes that share phenotypes with A2M: view

Human Phenotype Ontology for A2M Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Model Products

miRNA for A2M Gene

miRTarBase miRNAs that target A2M

Clone Products

  • Addgene plasmids for A2M

No data available for Enzyme Numbers (IUBMB) , Phenotypes From GWAS Catalog , Animal Models , Transcription Factor Targets and HOMER Transcription for A2M Gene

Localization for A2M Gene

Subcellular locations from UniProtKB/Swiss-Prot for A2M Gene

Secreted.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for A2M gene
Compartment Confidence
extracellular 5
cytosol 5
plasma membrane 2
nucleus 2
lysosome 2
endoplasmic reticulum 1
golgi apparatus 1
endosome 1

Gene Ontology (GO) - Cellular Components for A2M Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS --
GO:0005615 extracellular space IEA --
GO:0005829 cytosol TAS --
GO:0031093 platelet alpha granule lumen TAS --
GO:0070062 extracellular exosome HDA,IDA 20458337
genes like me logo Genes that share ontologies with A2M: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for A2M Gene

Pathways & Interactions for A2M Gene

genes like me logo Genes that share pathways with A2M: view

Gene Ontology (GO) - Biological Process for A2M Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001869 negative regulation of complement activation, lectin pathway IDA 12538697
GO:0002576 platelet degranulation TAS --
GO:0007597 blood coagulation, intrinsic pathway TAS --
GO:0010466 negative regulation of peptidase activity IEA --
GO:0010951 negative regulation of endopeptidase activity IEA --
genes like me logo Genes that share ontologies with A2M: view

No data available for SIGNOR curated interactions for A2M Gene

Drugs & Compounds for A2M Gene

Products:

  1. Drug

(15) Drugs for A2M Gene - From: DrugBank, PharmGKB, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Bacitracin Approved, Vet_approved Pharma Target, inhibitor 42
Becaplermin Approved, Investigational Pharma Target 0
Cisplatin Approved Pharma Target Inhibits DNA synthesis,chemotherapy drug, Potent pro-apoptotic anticancer agent; activates caspase-3, Platinum 2906
Copper Approved, Investigational Pharma Carrier, binder 202
Mangafodipir Approved, Investigational, Withdrawn Pharma Carrier, binder 0

(3) Additional Compounds for A2M Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with A2M: view

Transcripts for A2M Gene

Products:

  1. CRISPR
  2. miRNA
  3. Inhibitory RNA
  4. Clone

mRNA/cDNA for A2M Gene

(5) REFSEQ mRNAs :
(10) Additional mRNA sequences :
(1603) Selected AceView cDNA sequences:
(13) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for A2M Gene

Alpha-2-macroglobulin:
Representative Sequences:

Clone Products

  • Addgene plasmids for A2M

Alternative Splicing Database (ASD) splice patterns (SP) for A2M Gene

ExUns: 1 ^ 2a · 2b · 2c · 2d · 2e ^ 3a · 3b ^ 4 ^ 5a · 5b ^ 6a · 6b ^ 7 ^ 8 ^ 9a · 9b ^ 10a · 10b ^ 11a · 11b ^ 12a · 12b ^ 13a · 13b ^ 14a ·
SP1: - - - - - - - - - - - - - - - - - - -
SP2:
SP3:
SP4:
SP5:
SP6: - -
SP7: - - - - -
SP8:
SP9: - - - - - - - - - - - - - - - - -
SP10:
SP11:
SP12: -
SP13:
SP14:

ExUns: 14b ^ 15a · 15b ^ 16 ^ 17a · 17b ^ 18a · 18b ^ 19 ^ 20a · 20b · 20c ^ 21a · 21b ^ 22 ^ 23 ^ 24a · 24b ^ 25 ^ 26 ^ 27a · 27b ^ 28a · 28b ^ 29 ^ 30 ^
SP1: - - - - - - - - - - - - -
SP2:
SP3:
SP4:
SP5:
SP6:
SP7:
SP8:
SP9: - - - - - - - - - - - - - - - - - - - - -
SP10:
SP11:
SP12:
SP13:
SP14:

ExUns: 31 ^ 32 ^ 33 ^ 34 ^ 35 ^ 36 ^ 37 ^ 38 ^ 39 ^ 40
SP1:
SP2:
SP3:
SP4:
SP5:
SP6:
SP7:
SP8:
SP9:
SP10:
SP11:
SP12:
SP13:
SP14:

Relevant External Links for A2M Gene

GeneLoc Exon Structure for
A2M
ECgene alternative splicing isoforms for
A2M

Expression for A2M Gene

Products:

  1. Primer
  2. Gene Expression Assay

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for A2M Gene

mRNA expression in normal human tissues for A2M Gene
mRNA expression by GTEx for A2M GenemRNA expression by BioGPS for A2M Gene

mRNA differential expression in normal tissues according to GTEx for A2M Gene

This gene is overexpressed in Lung (x7.4) and Liver (x4.6).

Protein differential expression in normal tissues from HIPED for A2M Gene

This gene is overexpressed in Synovial fluid (27.9) and Plasma (17.5).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for A2M Gene



Protein tissue co-expression partners for A2M Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of A2M Gene:

A2M

SOURCE GeneReport for Unigene cluster for A2M Gene:

Hs.212838

mRNA Expression by UniProt/SwissProt for A2M Gene:

P01023-A2MG_HUMAN
Tissue specificity: Secreted in plasma.

Evidence on tissue expression from TISSUES for A2M Gene

  • Liver(5)
  • Nervous system(4.9)
  • Lung(4.8)
  • Skin(4.8)
  • Intestine(4.7)
  • Spleen(4.6)
  • Bone marrow(4.2)
  • Heart(3.8)
  • Eye(3.7)
  • Kidney(3.7)
  • Muscle(3.7)
  • Gall bladder(3.5)
  • Stomach(3.4)
  • Blood(3.2)
  • Pancreas(3.2)
  • Adrenal gland(2)
genes like me logo Genes that share expression patterns with A2M: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and Phenotype-based relationships between genes and organs from Gene ORGANizer for A2M Gene

Orthologs for A2M Gene

This gene was present in the common ancestor of animals.

Orthologs for A2M Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
 Mammalia A2M 33 34
  • 99.32 (n)
dog
(Canis familiaris)
 Mammalia A2M 33 34
  • 84.75 (n)
cow
(Bos Taurus)
 Mammalia A2M 33 34
  • 83.51 (n)
rat
(Rattus norvegicus)
 Mammalia LOC100911545 33
  • 78.36 (n)
mouse
(Mus musculus)
 Mammalia A2m 33 16 34
  • 78.19 (n)
oppossum
(Monodelphis domestica)
 Mammalia -- 34
  • 60 (a)
 OneToMany
platypus
(Ornithorhynchus anatinus)
 Mammalia -- 34
  • 60 (a)
 ManyToMany
-- 34
  • 57 (a)
 ManyToMany
-- 34
  • 42 (a)
 ManyToMany
chicken
(Gallus gallus)
 Aves -- 34
  • 65 (a)
 ManyToMany
A2M 33
  • 64.21 (n)
-- 34
  • 58 (a)
 ManyToMany
-- 34
  • 56 (a)
 ManyToMany
lizard
(Anolis carolinensis)
 Reptilia -- 34
  • 53 (a)
 ManyToMany
-- 34
  • 53 (a)
 ManyToMany
tropical clawed frog
(Silurana tropicalis)
 Amphibia a2m 33
  • 57.27 (n)
zebrafish
(Danio rerio)
 Actinopterygii LOC100006925 33
  • 53.89 (n)
rainbow trout
(Oncorhynchus mykiss)
 Actinopterygii Omy.10981 33
fruit fly
(Drosophila melanogaster)
 Insecta TepII 35
  • 29 (a)
Species where no ortholog for A2M was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for A2M Gene

ENSEMBL:
Gene Tree for A2M (if available)
TreeFam:
Gene Tree for A2M (if available)

Paralogs for A2M Gene

Paralogs for A2M Gene

(5) SIMAP similar genes for A2M Gene using alignment to 7 proteins:

genes like me logo Genes that share paralogs with A2M: view

Variants for A2M Gene

Products:

  1. SNP Genotyping and Copy Number Assay

Sequence variations from dbSNP and Humsavar for A2M Gene

SNP ID Clin Chr 12 pos Variation AA Info Type
rs1800433 benign, ALPHA-2-MACROGLOBULIN POLYMORPHISM 9,079,755(-) C/T coding_sequence_variant, missense_variant
rs1800434 benign, ALPHA-2-MACROGLOBULIN POLYMORPHISM 9,094,987(-) C/T coding_sequence_variant, missense_variant
rs669 benign, risk-factor, ALPHA-2-MACROGLOBULIN POLYMORPHISM, Alzheimer disease, susceptibility to 9,079,672(-) T/C coding_sequence_variant, missense_variant
rs1000046307 -- 9,080,657(-) A/G intron_variant
rs1000078744 -- 9,080,338(-) G/A intron_variant

Structural Variations from Database of Genomic Variants (DGV) for A2M Gene

Variant ID Type Subtype PubMed ID
nsv1051530 CNV gain 25217958
nsv527404 CNV gain 19592680
nsv832327 CNV loss 17160897

Variation tolerance for A2M Gene

Residual Variation Intolerance Score: 31.9% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 8.07; 84.40% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for A2M Gene

Human Gene Mutation Database (HGMD)
A2M
SNPedia medical, phenotypic, and genealogical associations of SNPs for
A2M

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for A2M Gene

Disorders for A2M Gene

MalaCards: The human disease database

(8) MalaCards diseases for A2M Gene - From: HGMD, OMIM, GTR, DISEASES, Novoseek, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search A2M in MalaCards View complete list of genes associated with diseases

Genatlas disease for A2M Gene

emphysema with lung destruction II (macroglobulin,alpha-2- deficiency)

Additional Disease Information for A2M

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with A2M: view

No data available for UniProtKB/Swiss-Prot for A2M Gene

Publications for A2M Gene

  1. Human alpha2-macroglobulin: genotype-phenotype relation. (PMID: 14637088) Birkenmeier G … Reichenbach A (Experimental neurology 2003) 3 22 44 58
  2. Alpha-2 macroglobulin is genetically associated with Alzheimer disease. (PMID: 9697696) Blacker D … Tanzi RE (Nature genetics 1998) 2 3 44 58
  3. Cloning of the human alpha 2-macroglobulin gene and detection of mutations in two functional domains: the bait region and the thiolester site. (PMID: 1370808) Poller W … Olek K (Human genetics 1992) 3 4 22 58
  4. Structure of the human alpha-2 macroglobulin gene and its promotor. (PMID: 1374237) Matthijs G … Marynen P (Biochemical and biophysical research communications 1992) 3 4 22 58
  5. Human alpha 2-macroglobulin gene is located on chromosome 12. (PMID: 2408344) Bell GI … Shows TB (Somatic cell and molecular genetics 1985) 2 3 4 58

Products for A2M Gene

  • Addgene plasmids for A2M

Sources for A2M Gene

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