======= A2M =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: A2M
  * **<color #00a2e8>Official Name</color>**: alpha-2-macroglobulin
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=2|2]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/P01023|P01023]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=A2M&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20A2M|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/103950|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  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]. 
  * **<color #00a2e8>UniProt Summary</color>**:  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.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|Thiol-ester cl|
|A2M|
|A2M recep|
|A2M N 2|
|A2M comp|
|A2M N|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|regulation of complement activation, lectin pathway|
|negative regulation of complement activation, lectin pathway|
|tumor necrosis factor binding|
|interleukin-8 binding|
|interleukin-1 binding|
|negative regulation of complement activation|
|negative regulation of humoral immune response|
|blood coagulation, intrinsic pathway|
|blood coagulation, fibrin clot formation|
|protein activation cascade|
|growth factor binding|
|endopeptidase inhibitor activity|
|negative regulation of innate immune response|
|calcium-dependent protein binding|
|extracellular matrix disassembly|
|platelet alpha granule lumen|
|negative regulation of response to biotic stimulus|
|serine-type endopeptidase inhibitor activity|
|protease binding|
|regulation of complement activation|
|negative regulation of immune effector process|
|platelet degranulation|
|regulation of humoral immune response|
|blood microparticle|
|negative regulation of immune response|
|stem cell differentiation|
|negative regulation of defense response|
|negative regulation of multi-organism process|
|negative regulation of endopeptidase activity|
|negative regulation of peptidase activity|
|blood coagulation|
|coagulation|
|hemostasis|
|signaling receptor binding|
|extracellular matrix organization|
|regulation of small GTPase mediated signal transduction|
|enzyme binding|
|negative regulation of proteolysis|
|collagen-containing extracellular matrix|
|negative regulation of response to external stimulus|
|extracellular structure organization|
|cellular component disassembly|
|regulation of endopeptidase activity|
|negative regulation of immune system process|
|regulation of peptidase activity|
|regulation of innate immune response|
|negative regulation of hydrolase activity|
|regulation of immune effector process|
|wound healing|
|regulation of body fluid levels|
|regulation of response to biotic stimulus|
|response to wounding|
|regulated exocytosis|
|regulation of proteolysis|
|regulation of defense response|
|regulation of multi-organism process|
|negative regulation of catalytic activity|
|exocytosis|
|secretion by cell|
|negative regulation of cellular protein metabolic process|
|export from cell|
|regulation of response to external stimulus|
|negative regulation of protein metabolic process|
|secretion|
|negative regulation of molecular function|
|regulation of immune response|
|regulation of hydrolase activity|
|regulation of response to stress|
|extracellular space|
|negative regulation of response to stimulus|
|regulation of immune system process|
|regulation of intracellular signal transduction|
|extracellular region|
|vesicle-mediated transport|
</modal>
\\

 === CRISPR Data ===
<button type='default' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='default' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
No hits were found.
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
No correlation found to any other genes in chemogenomics.
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 0/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/26|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/16|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/16|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 8277
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 1.18 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='A2M Expression in NALM6 Cells: 1.18'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>