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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 Degradation of the extracellular matrix and Sertoli-Sertoli Cell Junction Dynamics. 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.

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

Regulatory Elements for A2M Gene

Enhancers for A2M Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH12G009063 1 ENCODE 23.4 +51.5 51478 2.3 HNRNPUL1 ZFP64 ARID4B SIN3A DMAP1 ZNF2 ZNF48 YY1 GLIS2 FOS A2M A2M-AS1 KRT17P8 BTG1P1 LINC00612 VDAC2P2
GH12G009115 1 ENCODE 17.8 -0.3 -349 3.1 FOXA2 ATF1 MLX ZFP64 ARID4B DMAP1 ZNF48 YY1 PAF1 SP5 A2M KLRG1 PZP GC12M009115
GH12G009083 0.6 FANTOM5 23.6 +32.4 32435 0.7 ZNF680 CBX3 ZNF791 CBX5 RBFOX2 TRIM28 A2M LOC642846 KLRG1 GC12M009066
GH12G009131 1.3 ENCODE dbSUPER 10.2 -16.4 -16429 2.5 HNRNPUL1 FOXA2 PKNOX1 MLX CREB3L1 ZFP64 ARID4B DMAP1 YY1 SLC30A9 A2M BTG1P1 KRT17P8
GH12G009072 0.6 ENCODE 12 +43.1 43068 1.3 PAF1 MAX RAD21 YY1 JUND SSRP1 POLR2A ATF3 HNF4A RBFOX2 A2M-AS1 A2M GC12M009066
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around A2M on UCSC Golden Path with GeneCards custom track

Promoters for A2M Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000048585 1329 2201 FOXA2 ATF1 MLX ZFP64 ARID4B DMAP1 ZNF48 YY1 PAF1 SP5

Genomic Location for A2M Gene

Chromosome:
12
Start:
9,067,664 bp from pter
End:
9,116,229 bp from pter
Size:
48,566 bases
Orientation:
Minus strand

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 StructureGene Density

RefSeq DNA sequence for A2M Gene

Proteins for A2M Gene

  • 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

Post-translational modifications for A2M Gene

  • Glycosylation at posLast=5555, Asn70, posLast=247247, Asn396, Asn410, posLast=869869, posLast=991991, and Asn1424
  • Modification sites at PhosphoSitePlus

Antibody Products

  • R&D Systems Antibodies for A2M (alpha 2-Macroglobulin)

Protein Products

Assay Products

No data available for DME Specific Peptides for A2M Gene

Domains & Families for A2M Gene

Suggested Antigen Peptide Sequences for A2M Gene

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

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

CRISPR Products

miRNA for A2M Gene

Inhibitory RNA Products

Clone Products

  • Addgene plasmids for A2M
  • Applied Biological Materials Clones for A2M

No data available for Enzyme Numbers (IUBMB) , 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 IDA 20458337
genes like me logo Genes that share ontologies with A2M: view

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

(11) 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 40
Becaplermin Approved, Investigational Pharma Target 0
Ocriplasmin Approved Pharma Target, ligand 0
Enzymes Pharma 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

Unigene Clusters for A2M Gene

Alpha-2-macroglobulin:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

Clone Products

  • Addgene plasmids for A2M
  • Applied Biological Materials Clones 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

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE 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(2.3)
genes like me logo Genes that share expression patterns with A2M: view

Primer Products

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 34 35
  • 99.32 (n)
dog
(Canis familiaris)
Mammalia A2M 34 35
  • 84.75 (n)
cow
(Bos Taurus)
Mammalia A2M 34 35
  • 83.51 (n)
rat
(Rattus norvegicus)
Mammalia LOC100911545 34
  • 78.36 (n)
mouse
(Mus musculus)
Mammalia A2m 34 16 35
  • 78.19 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia -- 35
  • 60 (a)
ManyToMany
-- 35
  • 57 (a)
ManyToMany
-- 35
  • 42 (a)
ManyToMany
oppossum
(Monodelphis domestica)
Mammalia -- 35
  • 60 (a)
OneToMany
chicken
(Gallus gallus)
Aves -- 35
  • 65 (a)
ManyToMany
A2M 34
  • 64.21 (n)
-- 35
  • 58 (a)
ManyToMany
-- 35
  • 56 (a)
ManyToMany
lizard
(Anolis carolinensis)
Reptilia -- 35
  • 53 (a)
ManyToMany
-- 35
  • 53 (a)
ManyToMany
tropical clawed frog
(Silurana tropicalis)
Amphibia a2m 34
  • 57.27 (n)
zebrafish
(Danio rerio)
Actinopterygii LOC100006925 34
  • 53.89 (n)
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.10981 34
fruit fly
(Drosophila melanogaster)
Insecta TepII 36
  • 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

Sequence variations from dbSNP and Humsavar for A2M Gene

SNP ID Clin Chr 12 pos Sequence Context AA Info Type
rs1800433 Benign 9,079,755(-) TGGCT(A/G)TGGAG intron-variant, reference, missense
rs1800434 Benign 9,094,987(-) TCTAC(A/G)TGTAG intron-variant, reference, missense
rs1799759 other 9,093,582(-) ACTCA(-/ACCAT)GAGTC intron-variant
rs669 other 9,079,672(-) CAGAG(A/G)TCAAG intron-variant, reference, missense
rs1000046307 -- 9,080,657(+) ATACA(A/G)AGATA 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)

Relevant External Links for A2M Gene

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

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

Disorders for A2M Gene

MalaCards: The human disease database

(10) MalaCards diseases for A2M Gene - From: OMIM, GeneTests, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
alzheimer disease
  • alzheimer disease, late-onset
alpha-2-macroglobulin deficiency
  • alpha-2-macroglobulin
subendocardial myocardial infarction
allergic urticaria
emphysema due to aat deficiency
  • emphysema-cirrhosis, due to aat deficiency
- 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)

Relevant External Links for A2M

Genetic Association Database (GAD)
A2M
Human Genome Epidemiology (HuGE) Navigator
A2M
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
A2M
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. (Exp. Neurol. 2003) 3 22 46 64
  2. Alpha-2 macroglobulin is genetically associated with Alzheimer disease. (PMID: 9697696) Blacker D. … Tanzi R.E. (Nat. Genet. 1998) 2 3 46 64
  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. (Hum. Genet. 1992) 3 4 22 64
  4. Structure of the human alpha-2 macroglobulin gene and its promotor. (PMID: 1374237) Matthijs G. … Marynen P. (Biochem. Biophys. Res. Commun. 1992) 3 4 22 64
  5. Human alpha 2-macroglobulin gene is located on chromosome 12. (PMID: 2408344) Bell G.I. … Shows T.B. (Somat. Cell Mol. Genet. 1985) 2 3 4 64

Products for A2M Gene

  • Addgene plasmids for A2M

Sources for A2M Gene

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