======= FAM105B =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: OTULIN
  * **<color #00a2e8>Official Name</color>**: OTU deubiquitinase with linear linkage specificity
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=90268|90268]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/Q96BN8|Q96BN8]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=FAM105B&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20FAM105B|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/615712|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  This gene encodes a member of the peptidase C65 family of ubiquitin isopeptidases. Members of this family remove ubiquitin from proteins. The encoded enzyme specifically recognizes and removes M1(Met1)-linked, or linear, ubiquitin chains from protein substrates. Linear ubiquitin chains are known to regulate the NF-kappa B signaling pathway in the context of immunity and inflammation. Mutations in this gene cause a potentially fatal autoinflammatory syndrome in human patients. [provided by RefSeq, Sep 2016]. 
  * **<color #00a2e8>UniProt Summary</color>**:  Deubiquitinase that specifically removes linear ('Met- 1'-linked) polyubiquitin chains to substrates and acts as a regulator of angiogenesis and innate immune response (PubMed:23708998, PubMed:23746843, PubMed:23806334, PubMed:23827681, PubMed:27523608, PubMed:27559085, PubMed:24726323, PubMed:24726327). Associates with the LUBAC complex via direct interaction with RNF31 and counteracts its action by cleaving linear polyubiquitin chains to substrates (PubMed:23708998, PubMed:23746843, PubMed:23806334, PubMed:23827681, PubMed:24726323, PubMed:24726327). Required during angiogenesis, craniofacial and neuronal development by regulating the canonical Wnt signaling together with the LUBAC complex (PubMed:23708998). Acts as a negative regulator of NF- kappa-B by counteracting activity of the LUBAC complex (PubMed:23746843, PubMed:23806334). Required for homeostasis of the LUBAC complex by restricting autoubiquination of the LUBAC complex subunit RNF31 (PubMed:24726323). Some results have suggested that OTULIN function is restricted to homeostasis of the LUBAC complex, because it is not stably associated with TNF or NOD2 receptor signaling complexes (RSCs) (PubMed:26670046). However, further report have shown that it plays active roles in receptor signaling (PubMed:26997266, PubMed:27523608). Acts as a key negative regulator of inflammation by restricting spontaneous inflammation and maintaining immune homeostasis (PubMed:27523608). In myeloid cell, required to prevent unwarranted secretion of cytokines leading to inflammation and autoimmunity by restricting linear polyubiquitin formation (PubMed:27523608). Plays a key role in innate immune response by restricting linear polyubiquitin formation on RIPK2 in response to NOD2 stimulation, probably to limit NOD2-dependent proinflammatory signaling (PubMed:23806334). {ECO:0000269|PubMed:23708998, ECO:0000269|PubMed:23746843, ECO:0000269|PubMed:23806334, ECO:0000269|PubMed:23827681, ECO:0000269|PubMed:24726323, ECO:0000269|PubMed:26670046, ECO:0000269|PubMed:26997266, ECO:0000269|PubMed:27523608, ECO:0000269|PubMed:27559085}.

<button type='default' 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'>
No Pfam Domain information is available for this gene.
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|protein linear deubiquitination|
|LUBAC complex|
|nucleotide-binding oligomerization domain containing 2 signaling pathway|
|nucleotide-binding oligomerization domain containing signaling pathway|
|nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway|
|cysteine-type peptidase activity|
|cytoplasmic pattern recognition receptor signaling pathway|
|sprouting angiogenesis|
|regulation of tumor necrosis factor-mediated signaling pathway|
|negative regulation of NF-kappaB transcription factor activity|
|thiol-dependent ubiquitin-specific protease activity|
|pattern recognition receptor signaling pathway|
|negative regulation of inflammatory response|
|negative regulation of DNA-binding transcription factor activity|
|regulation of cytokine-mediated signaling pathway|
|intracellular receptor signaling pathway|
|regulation of response to cytokine stimulus|
|negative regulation of defense response|
|innate immune response-activating signal transduction|
|activation of innate immune response|
|protein deubiquitination|
|regulation of canonical Wnt signaling pathway|
|protein modification by small protein removal|
|angiogenesis|
|regulation of inflammatory response|
|positive regulation of innate immune response|
|Wnt signaling pathway|
|cell-cell signaling by wnt|
|regulation of Wnt signaling pathway|
|positive regulation of response to biotic stimulus|
|negative regulation of response to external stimulus|
|blood vessel morphogenesis|
|regulation of DNA-binding transcription factor activity|
|cell surface receptor signaling pathway involved in cell-cell signaling|
|regulation of innate immune response|
|positive regulation of defense response|
|blood vessel development|
|positive regulation of multi-organism process|
|vasculature development|
|cardiovascular system development|
|regulation of response to biotic stimulus|
|immune response-activating signal transduction|
|immune response-regulating signaling pathway|
|positive regulation of response to external stimulus|
|activation of immune response|
|tube morphogenesis|
|protein ubiquitination|
|regulation of defense response|
|innate immune response|
|protein modification by small protein conjugation|
|regulation of multi-organism process|
|tube development|
|positive regulation of immune response|
|circulatory system development|
|anatomical structure formation involved in morphogenesis|
|defense response to other organism|
|protein modification by small protein conjugation or removal|
|regulation of response to external stimulus|
|cell-cell signaling|
|negative regulation of molecular function|
|positive regulation of immune system process|
|regulation of immune response|
|proteolysis|
|response to other organism|
|response to external biotic stimulus|
|response to biotic stimulus|
|defense response|
|regulation of response to stress|
|negative regulation of response to stimulus|
|regulation of immune system process|
|intracellular signal transduction|
|immune response|
</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:exp36|TRAIL 50ng/ml R00 exp36]]|2.73|
|[[:results:exp35|TRAIL 5ng/ml R00 exp35]]|2.86|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:c:casp8|CASP8]]|0.443|
|[[:human genes:h:hgc6.3|HGC6.3]]|0.405|
</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>**: 9722
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 6.26 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='FAM105B Expression in NALM6 Cells: 6.26'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>