Free for academic non-profit institutions. Other users need a Commercial license
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]
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 Lipoprotein metabolism and Formation of Fibrin Clot (Clotting Cascade). Gene Ontology (GO) annotations related to this gene include signaling receptor binding and serine-type endopeptidase inhibitor activity. An important paralog of this gene is PZP.
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0002020 | protease binding | IPI | 18485748 |
GO:0004866 | endopeptidase inhibitor activity | IEA,IBA | 21873635 |
GO:0004867 | serine-type endopeptidase inhibitor activity | IEA,IDA | 12538697 |
GO:0005102 | signaling receptor binding | IMP | 15226301 |
GO:0005515 | protein binding | IPI | 6698368 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005576 | extracellular region | TAS | -- |
GO:0005615 | extracellular space | IBA | 21873635 |
GO:0005829 | cytosol | TAS | -- |
GO:0031093 | platelet alpha granule lumen | TAS | -- |
GO:0062023 | colocalizes_with collagen-containing extracellular matrix | HDA | 28327460 |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | Response to elevated platelet cytosolic Ca2+ |
.44
|
|
2 | Formation of Fibrin Clot (Clotting Cascade) | ||
3 | Lipoprotein metabolism | ||
4 | Complement and coagulation cascades | ||
5 | Sertoli-Sertoli Cell Junction Dynamics |
Germ Cell-Sertoli Cell Junction Dynamics
.38
|
Sertoli-Sertoli Cell Junction Dynamics
.38
|
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 | -- |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Bacitracin | Approved, Vet_approved | Pharma | Target, inhibitor | 43 | ||
Becaplermin | Approved, Investigational | Pharma | Target | 24 | ||
Cisplatin | Approved | Pharma | Target | Inhibits DNA synthesis,chemotherapy drug, Potent pro-apoptotic anticancer agent; activates caspase-3, Platinum | 3412 | |
Copper | Approved, Investigational | Pharma | Carrier, binder | 249 | ||
Mangafodipir | Approved, Investigational, Withdrawn | Pharma | Carrier, binder | 0 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs |
---|
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: |
This gene was present in the common ancestor of animals.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | A2M 30 31 |
|
OneToOne | |
Dog (Canis familiaris) |
Mammalia | A2M 30 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | A2M 30 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | A2m 30 |
|
||
Mouse (Mus musculus) |
Mammalia | A2m 30 17 31 |
|
OneToOne | |
Oppossum (Monodelphis domestica) |
Mammalia | -- 31 |
|
OneToMany | |
Platypus (Ornithorhynchus anatinus) |
Mammalia | -- 31 |
|
ManyToMany | |
-- 31 |
|
ManyToMany | |||
-- 31 |
|
ManyToMany | |||
Chicken (Gallus gallus) |
Aves | -- 31 |
|
ManyToMany | |
A2M 30 |
|
||||
-- 31 |
|
ManyToMany | |||
-- 31 |
|
ManyToMany | |||
Lizard (Anolis carolinensis) |
Reptilia | -- 31 |
|
ManyToMany | |
-- 31 |
|
ManyToMany | |||
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | a2m 30 |
|
||
Zebrafish (Danio rerio) |
Actinopterygii | LOC100006925 30 |
|
||
Rainbow Trout (Oncorhynchus mykiss) |
Actinopterygii | Omy.10981 30 |
|
||
Fruit Fly (Drosophila melanogaster) |
Insecta | TepII 32 |
|
|
SNP ID | Clinical significance and condition | Chr 12 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
18173 | Benign: ALPHA-2-MACROGLOBULIN POLYMORPHISM | 9,093,579(-) | TCTATGGTGAGTGAGG | SPLICE_ACCEPTOR_VARIANT,SPLICE_DONOR_VARIANT | |
711716 | Likely Benign: not provided | 9,079,271(-) | C/T | MISSENSE_VARIANT | |
713107 | Benign: not provided | 9,074,556(-) | C/T | ||
714506 | Benign: not provided | 9,090,420(-) | C/T | SYNONYMOUS_VARIANT | |
714548 | Likely Benign: not provided | 9,107,581(-) | G/A | SYNONYMOUS_VARIANT |
Disorder | Aliases | PubMed IDs |
---|---|---|
alzheimer disease |
|
|
alpha-2-macroglobulin deficiency |
|
|
mastitis |
|
|
anterior segment dysgenesis |
|
|
subendocardial myocardial infarction |
|
|