Otulin
entrez
432940
canonical
uniprot
Q3UCV8
canonical
ensembl
ENSMUSG00000046034
resolver
ensp
ENSMUSP00000057893
resolver
ensp
ENSMUSP00000247926
resolver
enst
ENSMUST00000059662
resolver
genesymbol
Otulin
resolver
genesymbol_syn
Fam105b
resolver
genesymbol_syn
Gum
resolver
uniprot
Q3UY59
resolver
uniprot
Q5M8N1
resolver
uniprot
Q8R027
resolver
uniprot_entry
OTUL_MOUSE
resolver
uniprot_sec
Q3UY59
resolver
uniprot_sec
Q5M8N1
resolver
uniprot_sec
Q8R027
resolver
amino_acid_sequence
MSRGTMPQPGAWPGASCAETPAREAGAAARDGGKVTAGAQPRAATRCPAEHEEDMYRAADEIEKEKELLIHERGISEPRLSVAPEMDIMDYCKKEWRGNTQKATCMKKGYEEVSQKFTSIRRVRGDNYCALRATLFQAMSQLAELPPWLQDLELILLPEKLINKYTWIKQWKLGLKFDGKSEDLVEKIKESLALLRKKWVSLAAMKTAEARQTACDELFTNEEEEYSLYEAVKFLMLNRAIELYDDKEKGKEVPFFSVLLFARDTSNDPEQLLRNHLNQVGHTGGLEQVEMFLLAYAVRHSIRVYRLSKYNTEEFITVYPTDPPKDWPMVTLIAEDDRHYNIPVRVCEETSV
uniprot
proteins
ec_number
3.4.19.12
uniprot
proteins
function
FUNCTION: 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:27523608, PubMed:29950720). 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 regulating the activity of the LUBAC complex (By similarity). OTULIN function is mainly restricted to homeostasis of the LUBAC complex: acts by removing 'Met-1'-linked autoubiquitination of the LUBAC complex, thereby preventing inactivation of the LUBAC complex (PubMed:29950720). Acts as a key negative regulator of inflammation by restricting spontaneous inflammation and maintaining immune homeostasis (PubMed:27523608, PubMed:29950720). In myeloid cell, required to prevent unwarranted secretion of cytokines leading to inflammation and autoimmunity by restricting linear polyubiquitin formation (PubMed:27523608). Plays a role in innate immune response by restricting linear polyubiquitin formation on LUBAC complex in response to NOD2 stimulation, probably to limit NOD2-dependent pro-inflammatory signaling (By similarity). {ECO:0000250|UniProtKB:Q96BN8, ECO:0000269|PubMed:23708998, ECO:0000269|PubMed:27523608, ECO:0000269|PubMed:29950720}.
uniprot
proteins
mass_dalton
40320
uniprot
proteins
mutagenesis
MUTAGEN 96; /note="W->R: In Gum(W96R) mutant; defects in embryonic angiogenesis. Embryos appear normal before 11.5 dpc but die between 12.5 dpc-14 dpc, probably due to defects in organization of branching vascular networks in the head and trunk."; /evidence="ECO:0000269|PubMed:23708998"; MUTAGEN 129; /note="C->A,S: Abolishes deubiquitinase activity without affecting interaction with RNF31. Lethality at midgestation in knockin mice caused by inactivation of the LUBAC complex, leading to cell death mediated by TNFR1 and RIPK1."; /evidence="ECO:0000269|PubMed:23708998, ECO:0000269|PubMed:29950720"; MUTAGEN 336; /note="D->E: In Gum(D366E) mutant; defects in embryonic angiogenesis. Weaker mutant compared to Gum(W96R) mutant."; /evidence="ECO:0000269|PubMed:23708998"; MUTAGEN 349..352; /note="ETSV->AAAA: Does not affect interaction with RNF31."; /evidence="ECO:0000269|PubMed:23708998
uniprot
proteins
post_translational_modification
PTM: Ubiquitinated. {ECO:0000250|UniProtKB:Q96BN8}.; PTM: Acetylated. {ECO:0000250|UniProtKB:Q96BN8}.; PTM: Phosphorylated. Phosphorylation at Tyr-56 prevents interaction with RNF31; dephosphorylation promotes interaction with RNF31 and the LUBAC complex. {ECO:0000250|UniProtKB:Q96BN8}.
uniprot
proteins
protein_family
Otulin subfamily
uniprot
proteins
protein_family
Peptidase C65 family
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
19468303
uniprot
proteins
pubmed
23708998
uniprot
proteins
pubmed
27523608
uniprot
proteins
pubmed
29950720
uniprot
proteins
sequence_length
352
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:23708998}.
uniprot
proteins