P4HB [The Human Chemical-Genetic Interaction Map Project]

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======= P4HB =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: P4HB
  * **<color #00a2e8>Official Name</color>**: prolyl 4-hydroxylase subunit beta
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=5034|5034]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/P07237|P07237]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=P4HB&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20P4HB|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/176790|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  This gene encodes the beta subunit of prolyl 4-hydroxylase, a highly abundant multifunctional enzyme that belongs to the protein disulfide isomerase family. When present as a tetramer consisting of two alpha and two beta subunits, this enzyme is involved in hydroxylation of prolyl residues in preprocollagen. This enzyme is also a disulfide isomerase containing two thioredoxin domains that catalyze the formation, breakage and rearrangement of disulfide bonds. Other known functions include its ability to act as a chaperone that inhibits aggregation of misfolded proteins in a concentration-dependent manner, its ability to bind thyroid hormone, its role in both the influx and efflux of S-nitrosothiol-bound nitric oxide, and its function as a subunit of the microsomal triglyceride transfer protein complex. [provided by RefSeq, Jul 2008]. 
  * **<color #00a2e8>UniProt Summary</color>**:  This multifunctional protein catalyzes the formation, breakage and rearrangement of disulfide bonds. At the cell surface, seems to act as a reductase that cleaves disulfide bonds of proteins attached to the cell. May therefore cause structural modifications of exofacial proteins. Inside the cell, seems to form/rearrange disulfide bonds of nascent proteins. At high concentrations, functions as a chaperone that inhibits aggregation of misfolded proteins. At low concentrations, facilitates aggregation (anti-chaperone activity). May be involved with other chaperones in the structural modification of the TG precursor in hormone biogenesis. Also acts a structural subunit of various enzymes such as prolyl 4-hydroxylase and microsomal triacylglycerol transfer protein MTTP. Receptor for LGALS9; the interaction retains P4HB at the cell surface of Th2 T helper cells, increasing disulfide reductase activity at the plasma membrane, altering the plasma membrane redox state and enhancing cell migration (PubMed:21670307). {ECO:0000269|PubMed:10636893, ECO:0000269|PubMed:12485997, ECO:0000269|PubMed:21670307}.

<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'>
|Thioredoxin|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|procollagen-proline 4-dioxygenase complex|
|procollagen-proline 4-dioxygenase activity|
|peptidyl-proline hydroxylation to 4-hydroxy-L-proline|
|peptide disulfide oxidoreductase activity|
|interleukin-23-mediated signaling pathway|
|positive regulation of viral entry into host cell|
|chylomicron assembly|
|endoplasmic reticulum chaperone complex|
|very-low-density lipoprotein particle assembly|
|peptidyl-proline hydroxylation|
|4-hydroxyproline metabolic process|
|protein disulfide isomerase activity|
|protein hydroxylation|
|plasma lipoprotein particle assembly|
|regulation of oxidative stress-induced intrinsic apoptotic signaling pathway|
|response to interleukin-7|
|cellular response to interleukin-7|
|regulation of viral entry into host cell|
|protein-lipid complex assembly|
|plasma lipoprotein particle organization|
|interleukin-12-mediated signaling pathway|
|protein-lipid complex subunit organization|
|cellular response to interleukin-12|
|response to interleukin-12|
|peptidyl-proline modification|
|positive regulation of viral life cycle|
|regulation of oxidative stress-induced cell death|
|regulation of plasma lipoprotein particle levels|
|regulation of cellular response to oxidative stress|
|endoplasmic reticulum-Golgi intermediate compartment|
|cell redox homeostasis|
|regulation of response to oxidative stress|
|melanosome|
|positive regulation of viral process|
|integrin binding|
|regulation of viral life cycle|
|regulation of intrinsic apoptotic signaling pathway|
|cellular response to hypoxia|
|cellular modified amino acid metabolic process|
|cellular response to decreased oxygen levels|
|regulation of viral process|
|alpha-amino acid metabolic process|
|cellular response to oxygen levels|
|regulation of symbiosis, encompassing mutualism through parasitism|
|protein folding|
|response to endoplasmic reticulum stress|
|endoplasmic reticulum lumen|
|cellular amino acid metabolic process|
|response to hypoxia|
|enzyme binding|
|response to decreased oxygen levels|
|post-translational protein modification|
|response to oxygen levels|
|extracellular structure organization|
|external side of plasma membrane|
|regulation of apoptotic signaling pathway|
|focal adhesion|
|protein heterodimerization activity|
|positive regulation of multi-organism process|
|cytokine-mediated signaling pathway|
|regulation of cellular response to stress|
|regulation of multi-organism process|
|peptidyl-amino acid modification|
|cellular homeostasis|
|carboxylic acid metabolic process|
|oxidation-reduction process|
|oxoacid metabolic process|
|cellular response to cytokine stimulus|
|endoplasmic reticulum|
|organic acid metabolic process|
|response to cytokine|
|response to abiotic stimulus|
|RNA binding|
|regulation of response to stress|
|regulation of apoptotic process|
|protein-containing complex assembly|
|regulation of programmed cell death|
|homeostatic process|
|regulation of cell death|
|cellular response to stress|
|small molecule metabolic process|
|regulation of intracellular signal transduction|
|protein-containing complex subunit organization|
|extracellular region|
</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:exp407|Thapsigargin 0.005μM R07 exp407]]|-2.87|
|[[:results:exp335|Aminopterin 0.005μM R07 exp335]]|-2.23|
|[[:results:exp416|Tubacin 1.6μM R07 exp416]]|-2.02|
|[[:results:exp321|ABT-702 5μM plus Deferoxamine 11μM R07 exp321]]|-1.93|
|[[:results:exp180|Dynasore 10μM R04 exp180]]|-1.91|
|[[:results:exp175|3-Bromopyruvate 7μM R04 exp175]]|-1.88|
|[[:results:exp436|Dynasore 7μM R08 exp436]]|-1.87|
|[[:results:exp153|SGC2096 2.6μM R03 exp153]]|-1.7|
|[[:results:exp420|Tunicamycin 0.04 to 0.125μM  on day4 R07 exp420]]|1.73|
|[[:results:exp282|Fluvastatin 2.2μM R06 exp282]]|1.78|
|[[:results:exp21|MLN-4924 0.2μM R00 exp21]]|1.84|
|[[:results:exp212|Phenformin 20μM R05 exp212]]|1.85|
|[[:results:exp233|EPZ-5676 30μM R05 exp233]]|1.88|
|[[:results:exp418|Tunicamycin 0.04μM R07 exp418]]|1.88|
|[[:results:exp248|UM0131023 0.05μM R05 exp248]]|1.95|
|[[:results:exp400|Senexin-A 25μM R07 exp400]]|1.99|
|[[:results:exp419|Tunicamycin 0.04 to 0.075μM  on day4 R07 exp419]]|2|
|[[:results:exp274|Citral 50μM R06 exp274]]|2.01|
|[[:results:exp535|Trimetrexate 0.03μM R08 exp535]]|2.44|
|[[:results:exp492|iCRT14 30μM R08 exp492]]|2.63|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:k:kiaa0922|KIAA0922]]|0.527|
|[[:human genes:t:tmem39a|TMEM39A]]|0.457|
|[[:human genes:u:ufm1|UFM1]]|0.42|
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 0/726
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/25|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/15|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/14|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/7|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 5275
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 9.07 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='P4HB Expression in NALM6 Cells: 9.07'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>