XIAP [The Human Chemical-Genetic Interaction Map Project]

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======= XIAP =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: XIAP
  * **<color #00a2e8>Official Name</color>**: X-linked inhibitor of apoptosis
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=331|331]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/P98170|P98170]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=XIAP&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20XIAP|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/300079|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  This gene encodes a protein that belongs to a family of apoptotic suppressor proteins. Members of this family share a conserved motif termed, baculovirus IAP repeat, which is necessary for their anti-apoptotic function. This protein functions through binding to tumor necrosis factor receptor-associated factors TRAF1 and TRAF2 and inhibits apoptosis induced by menadione, a potent inducer of free radicals, and interleukin 1-beta converting enzyme. This protein also inhibits at least two members of the caspase family of cell-death proteases, caspase-3 and caspase-7. Mutations in this gene are the cause of X-linked lymphoproliferative syndrome. Alternate splicing results in multiple transcript variants. Pseudogenes of this gene are found on chromosomes 2 and 11.[provided by RefSeq, Feb 2011]. 
  * **<color #00a2e8>UniProt Summary</color>**:  Multi-functional protein which regulates not only caspases and apoptosis, but also modulates inflammatory signaling and immunity, copper homeostasis, mitogenic kinase signaling, cell proliferation, as well as cell invasion and metastasis. Acts as a direct caspase inhibitor. Directly bind to the active site pocket of CASP3 and CASP7 and obstructs substrate entry. Inactivates CASP9 by keeping it in a monomeric, inactive state. Acts as an E3 ubiquitin-protein ligase regulating NF-kappa-B signaling and the target proteins for its E3 ubiquitin-protein ligase activity include: RIPK1, CASP3, CASP7, CASP8, CASP9, MAP3K2/MEKK2, DIABLO/SMAC, AIFM1, CCS and BIRC5/survivin. Ubiquitinion of CCS leads to enhancement of its chaperone activity toward its physiologic target, SOD1, rather than proteasomal degradation. Ubiquitinion of MAP3K2/MEKK2 and AIFM1 does not lead to proteasomal degradation. Plays a role in copper homeostasis by ubiquitinationg COMMD1 and promoting its proteasomal degradation. Can also function as E3 ubiquitin-protein ligase of the NEDD8 conjugation pathway, targeting effector caspases for neddylation and inactivation. Regulates the BMP signaling pathway and the SMAD and MAP3K7/TAK1 dependent pathways leading to NF-kappa-B and JNK activation. Acts as an important regulator of innate immune signaling via regulation of Nodlike receptors (NLRs). Protects cells from spontaneous formation of the ripoptosome, a large multi-protein complex that has the capability to kill cancer cells in a caspase-dependent and caspase-independent manner. Suppresses ripoptosome formation by ubiquitinating RIPK1 and CASP8. Acts as a positive regulator of Wnt signaling and ubiquitinates TLE1, TLE2, TLE3, TLE4 and AES. Ubiquitination of TLE3 results in inhibition of its interaction with TCF7L2/TCF4 thereby allowing efficient recruitment and binding of the transcriptional coactivator beta- catenin to TCF7L2/TCF4 that is required to initiate a Wnt-specific transcriptional program. {ECO:0000269|PubMed:11447297, ECO:0000269|PubMed:12121969, ECO:0000269|PubMed:14645242, ECO:0000269|PubMed:14685266, ECO:0000269|PubMed:17560374, ECO:0000269|PubMed:17967870, ECO:0000269|PubMed:19473982, ECO:0000269|PubMed:20154138, ECO:0000269|PubMed:21145488, ECO:0000269|PubMed:22103349, ECO:0000269|PubMed:22304967, ECO:0000269|PubMed:9230442}.

<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'>
|BIR|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|regulation of protein linear polyubiquitination|
|positive regulation of protein linear polyubiquitination|
|inhibition of cysteine-type endopeptidase activity involved in apoptotic process|
|regulation of nucleotide-binding oligomerization domain containing signaling pathway|
|positive regulation of protein polyubiquitination|
|zymogen inhibition|
|inhibition of cysteine-type endopeptidase activity|
|copper ion homeostasis|
|regulation of protein polyubiquitination|
|cysteine-type endopeptidase inhibitor activity involved in apoptotic process|
|negative regulation of protein processing|
|negative regulation of protein maturation|
|regulation of protein processing|
|regulation of protein maturation|
|negative regulation of cysteine-type endopeptidase activity involved in apoptotic process|
|regulation of BMP signaling pathway|
|negative regulation of cysteine-type endopeptidase activity|
|positive regulation of protein ubiquitination|
|transition metal ion homeostasis|
|positive regulation of protein modification by small protein conjugation or removal|
|positive regulation of canonical Wnt signaling pathway|
|positive regulation of Wnt signaling pathway|
|regulation of protein ubiquitination|
|regulation of cysteine-type endopeptidase activity involved in apoptotic process|
|ubiquitin protein ligase activity|
|regulation of protein modification by small protein conjugation or removal|
|regulation of transmembrane receptor protein serine/threonine kinase signaling pathway|
|regulation of cysteine-type endopeptidase activity|
|negative regulation of endopeptidase activity|
|ubiquitin-protein transferase activity|
|negative regulation of peptidase activity|
|regulation of cellular response to growth factor stimulus|
|regulation of canonical Wnt signaling pathway|
|regulation of inflammatory response|
|negative regulation of proteolysis|
|cell-cell signaling by wnt|
|Wnt signaling pathway|
|regulation of Wnt signaling pathway|
|regulation of endopeptidase activity|
|cell surface receptor signaling pathway involved in cell-cell signaling|
|regulation of peptidase activity|
|regulation of innate immune response|
|negative regulation of hydrolase activity|
|regulation of response to biotic stimulus|
|metal ion homeostasis|
|protein ubiquitination|
|cation homeostasis|
|inorganic ion homeostasis|
|regulation of proteolysis|
|regulation of defense response|
|protein modification by small protein conjugation|
|regulation of multi-organism process|
|cellular response to DNA damage stimulus|
|ion homeostasis|
|negative regulation of catalytic activity|
|negative regulation of apoptotic process|
|negative regulation of programmed cell death|
|apoptotic process|
|protein modification by small protein conjugation or removal|
|negative regulation of cell death|
|negative regulation of cellular protein metabolic process|
|programmed cell death|
|identical protein binding|
|cell death|
|regulation of response to external stimulus|
|negative regulation of protein metabolic process|
|chemical homeostasis|
|cell-cell signaling|
|negative regulation of molecular function|
|regulation of immune response|
|positive regulation of protein modification process|
|regulation of hydrolase activity|
|regulation of response to stress|
|regulation of apoptotic process|
|regulation of programmed cell death|
|positive regulation of cellular protein metabolic process|
|regulation of cell population proliferation|
|homeostatic process|
|positive regulation of signal transduction|
|regulation of immune system process|
|regulation of cell death|
|cellular response to stress|
|positive regulation of protein metabolic process|
|negative regulation of gene expression|
|positive regulation of cell communication|
|positive regulation of signaling|
|regulation of intracellular signal transduction|
|regulation of protein modification process|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='primary' 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'>
^Screen^Score^
|[[:results:exp35|TRAIL 5ng/ml R00 exp35]]|-3.64|
|[[:results:exp505|ML-792 0.2μM R08 exp505]]|-3.03|
|[[:results:exp36|TRAIL 50ng/ml R00 exp36]]|-2.71|
|[[:results:exp19|Etoposide 1μM R00 exp19]]|-2.51|
|[[:results:exp329|Hydroxyurea 100μM R07 exp329]]|-2.2|
|[[:results:exp459|Bleomycin 5μM R08 exp459]]|-2|
|[[:results:exp440|Aphidicolin 0.4μM R08 exp440]]|-1.88|
|[[:results:exp28|Pimelic-diphenylamide-106 5μM R00 exp28]]|-1.78|
|[[:results:exp468|CB-5083 0.4μM R08 exp468]]|-1.74|
|[[:results:exp15|Cycloheximide 0.2μM R00 exp15]]|1.78|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:s:smg7|SMG7]]|0.425|
|[[:human genes:a:atp13a1|ATP13A1]]|0.4|
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 0/683
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/26|
|bone|0/25|
|breast|0/30|
|central nervous system|0/49|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/11|
|fibroblast|0/1|
|gastric|0/14|
|kidney|0/18|
|liver|0/19|
|lung|0/72|
|lymphocyte|0/14|
|ovary|0/25|
|pancreas|0/22|
|peripheral nervous system|0/15|
|plasma cell|0/12|
|prostate|0/1|
|skin|0/20|
|soft tissue|0/7|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/28|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 13948
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 6.46 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='XIAP Expression in NALM6 Cells: 6.46'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>