Human Gene A2M (ENST00000318602.12)
  Description: Homo sapiens alpha-2-macroglobulin (A2M), transcript variant 4, mRNA. (from RefSeq NM_001347425)
RefSeq Summary (NM_000014): 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].
Gencode Transcript: ENST00000318602.12
Gencode Gene: ENSG00000175899.15
Transcript (Including UTRs)
   Position: hg38 chr12:9,067,708-9,115,919 Size: 48,212 Total Exon Count: 36 Strand: -
Coding Region
   Position: hg38 chr12:9,067,823-9,115,849 Size: 48,027 Coding Exon Count: 36 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDRNA-Seq Expression
Microarray ExpressionRNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA Descriptions
PathwaysOther NamesMethods
Data last updated at UCSC: 2021-01-14 15:32:12

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr12:9,067,708-9,115,919)mRNA (may differ from genome)Protein (1474 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=Alpha-2-macroglobulin; Short=Alpha-2-M; AltName: Full=C3 and PZP-like alpha-2-macroglobulin domain-containing protein 5; Flags: Precursor;
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.
SUBUNIT: Homotetramer; disulfide-linked.
TISSUE SPECIFICITY: Secreted in plasma.
DEVELOPMENTAL STAGE: Contrary to the rat protein, which is an acute phase protein, this protein is always present at high levels in circulation.
SIMILARITY: Belongs to the protease inhibitor I39 (alpha-2- macroglobulin) family.
SEQUENCE CAUTION: Sequence=AAT02228.1; Type=Erroneous initiation; Note=Translation N-terminally shortened; Sequence=BAD92851.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
WEB RESOURCE: Name=Wikipedia; Note=Alpha-2 macroglobulin entry; URL="";

-  MalaCards Disease Associations
  MalaCards Gene Search: A2M
Diseases sorted by gene-association score: alzheimer disease* (295), alpha-2-macroglobulin deficiency* (169), subendocardial myocardial infarction (10), allergic urticaria (8), corticosteroid-binding globulin deficiency (6), argentine hemorrhagic fever (6), byssinosis (5), epileptic encephalopathy, early infantile, 36 (5), osteosclerotic myeloma (4)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 1311.03 RPKM in Lung
Total median expression: 7812.12 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -16.6070-0.237 Picture PostScript Text
3' UTR -34.50115-0.300 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR009048 - A-macroglobulin_rcpt-bd
IPR011626 - A2M_comp
IPR002890 - A2M_N
IPR011625 - A2M_N_2
IPR001599 - Macroglobln_a2
IPR019742 - MacrogloblnA2_CS
IPR019565 - MacrogloblnA2_thiol-ester-bond
IPR008930 - Terpenoid_cyclase/PrenylTrfase
IPR010916 - TonB_box_CS

Pfam Domains:
PF00207 - Alpha-2-macroglobulin family
PF07678 - A-macroglobulin complement component
PF01835 - MG2 domain
PF07703 - Alpha-2-macroglobulin family N-terminal region
PF07677 - A-macroglobulin receptor
PF10569 - Alpha-macro-globulin thiol-ester bond-forming region

Protein Data Bank (PDB) 3-D Structure
MuPIT help


- X-ray MuPIT

- X-ray

ModBase Predicted Comparative 3D Structure on P01023
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
Protein SequenceProtein Sequence    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0002020 protease binding
GO:0004866 endopeptidase inhibitor activity
GO:0004867 serine-type endopeptidase inhibitor activity
GO:0005096 GTPase activator activity
GO:0005102 receptor binding
GO:0005515 protein binding
GO:0019838 growth factor binding
GO:0019899 enzyme binding
GO:0019959 interleukin-8 binding
GO:0019966 interleukin-1 binding
GO:0030414 peptidase inhibitor activity
GO:0043120 tumor necrosis factor binding
GO:0048306 calcium-dependent protein binding

Biological Process:
GO:0001869 negative regulation of complement activation, lectin pathway
GO:0002576 platelet degranulation
GO:0007597 blood coagulation, intrinsic pathway
GO:0010466 negative regulation of peptidase activity
GO:0010951 negative regulation of endopeptidase activity
GO:0022617 extracellular matrix disassembly
GO:0043547 positive regulation of GTPase activity
GO:0048863 stem cell differentiation
GO:0051056 regulation of small GTPase mediated signal transduction

Cellular Component:
GO:0005576 extracellular region
GO:0005615 extracellular space
GO:0005829 cytosol
GO:0031093 platelet alpha granule lumen
GO:0070062 extracellular exosome
GO:0072562 blood microparticle

-  Descriptions from all associated GenBank mRNAs
  LP895858 - Sequence 722 from Patent EP3253886.
LF207372 - JP 2014500723-A/14875: Polycomb-Associated Non-Coding RNAs.
MA442949 - JP 2018138019-A/14875: Polycomb-Associated Non-Coding RNAs.
AF109189 - Homo sapiens FWP007 mRNA, complete cds.
AB209614 - Homo sapiens mRNA for alpha 2 macroglobulin variant, partial cds.
BC040071 - Homo sapiens alpha-2-macroglobulin, mRNA (cDNA clone MGC:47683 IMAGE:6056126), complete cds.
A21185 - H.sapiens mRNA for alpha 2-macroglobulin 690-730.
A21187 - H.sapiens mRNA for alpha 2-macroglobulin 690-740.
BC026246 - Homo sapiens alpha-2-macroglobulin, mRNA (cDNA clone IMAGE:4733707), complete cds.
BX647329 - Homo sapiens mRNA; cDNA DKFZp779L1515 (from clone DKFZp779L1515).
M36501 - Human alpha-2-macroglobulin mRNA, 3' end.
M11313 - Human alpha-2-macroglobulin mRNA, complete cds.
CR749334 - Homo sapiens mRNA; cDNA DKFZp779B086 (from clone DKFZp779B086).
AY591530 - Homo sapiens alpha 2 macroglobulin (A2M) mRNA, complete cds.
JD206138 - Sequence 187162 from Patent EP1572962.
AK307832 - Homo sapiens cDNA, FLJ97780.
JD434053 - Sequence 415077 from Patent EP1572962.
AK312482 - Homo sapiens cDNA, FLJ92841.
KJ896355 - Synthetic construct Homo sapiens clone ccsbBroadEn_05749 A2M gene, encodes complete protein.
KR710910 - Synthetic construct Homo sapiens clone CCSBHm_00018118 A2M (A2M) mRNA, encodes complete protein.
KR710911 - Synthetic construct Homo sapiens clone CCSBHm_00018119 A2M (A2M) mRNA, encodes complete protein.
AB384991 - Synthetic construct DNA, clone: pF1KB4815, Homo sapiens A2M gene for alpha-2-macroglobulin precursor, complete cds, without stop codon, in Flexi system.
LF365673 - JP 2014500723-A/173176: Polycomb-Associated Non-Coding RNAs.
MA601250 - JP 2018138019-A/173176: Polycomb-Associated Non-Coding RNAs.
LF365672 - JP 2014500723-A/173175: Polycomb-Associated Non-Coding RNAs.
MA601249 - JP 2018138019-A/173175: Polycomb-Associated Non-Coding RNAs.
LF365670 - JP 2014500723-A/173173: Polycomb-Associated Non-Coding RNAs.
MA601247 - JP 2018138019-A/173173: Polycomb-Associated Non-Coding RNAs.
LF365669 - JP 2014500723-A/173172: Polycomb-Associated Non-Coding RNAs.
MA601246 - JP 2018138019-A/173172: Polycomb-Associated Non-Coding RNAs.
LF365668 - JP 2014500723-A/173171: Polycomb-Associated Non-Coding RNAs.
MA601245 - JP 2018138019-A/173171: Polycomb-Associated Non-Coding RNAs.
LF365667 - JP 2014500723-A/173170: Polycomb-Associated Non-Coding RNAs.
MA601244 - JP 2018138019-A/173170: Polycomb-Associated Non-Coding RNAs.
LF365666 - JP 2014500723-A/173169: Polycomb-Associated Non-Coding RNAs.
MA601243 - JP 2018138019-A/173169: Polycomb-Associated Non-Coding RNAs.
LF365665 - JP 2014500723-A/173168: Polycomb-Associated Non-Coding RNAs.
MA601242 - JP 2018138019-A/173168: Polycomb-Associated Non-Coding RNAs.
LF365662 - JP 2014500723-A/173165: Polycomb-Associated Non-Coding RNAs.
MA601239 - JP 2018138019-A/173165: Polycomb-Associated Non-Coding RNAs.
LF365661 - JP 2014500723-A/173164: Polycomb-Associated Non-Coding RNAs.
MA601238 - JP 2018138019-A/173164: Polycomb-Associated Non-Coding RNAs.
JD150331 - Sequence 131355 from Patent EP1572962.
JD427079 - Sequence 408103 from Patent EP1572962.
JD527271 - Sequence 508295 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04610 - Complement and coagulation cascades

Reactome (by CSHL, EBI, and GO)

Protein P01023 (Reactome details) participates in the following event(s):

R-HSA-158340 kallikrein + alpha2-macroglobulin -> kallikrein:alpha2-macrogloulin
R-HSA-1454781 MMP1,3,13 (2, 7-12, 19) binding by Alpha-2 macroglubulin
R-HSA-481007 Exocytosis of platelet alpha granule contents
R-HSA-194922 GAPs inactivate Rho GTPase:GTP by hydrolysis
R-HSA-140837 Intrinsic Pathway of Fibrin Clot Formation
R-HSA-1474228 Degradation of the extracellular matrix
R-HSA-114608 Platelet degranulation
R-HSA-140877 Formation of Fibrin Clot (Clotting Cascade)
R-HSA-1474244 Extracellular matrix organization
R-HSA-76005 Response to elevated platelet cytosolic Ca2+
R-HSA-194840 Rho GTPase cycle
R-HSA-109582 Hemostasis
R-HSA-76002 Platelet activation, signaling and aggregation
R-HSA-194315 Signaling by Rho GTPases
R-HSA-162582 Signal Transduction

-  Other Names for This Gene
  Alternate Gene Symbols: A2MG_HUMAN, CPAMD5, ENST00000318602.1, ENST00000318602.10, ENST00000318602.11, ENST00000318602.2, ENST00000318602.3, ENST00000318602.4, ENST00000318602.5, ENST00000318602.6, ENST00000318602.7, ENST00000318602.8, ENST00000318602.9, FWP007, NM_001347425, P01023, Q13677, Q59F47, Q5QTS0, Q68DN2, Q6PIY3, Q6PN97, uc001qvk.1, uc001qvk.2, uc001qvk.3
UCSC ID: ENST00000318602.12
RefSeq Accession: NM_000014
Protein: P01023 (aka A2MG_HUMAN)
CCDS: CCDS44827.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.