OTULIN
entrez
90268
canonical
uniprot
Q96BN8
canonical
ensembl
ENSG00000154124
resolver
ensp
ENSP00000284274
resolver
ensp
ENSP00000520900
resolver
ensp
ENSP00000625737
resolver
enst
ENST00000284274
resolver
enst
ENST00000850613
resolver
genesymbol
OTULIN
resolver
genesymbol_syn
FAM105B
resolver
hgnc
HGNC:25118
resolver
uniprot
D3DTD3
resolver
uniprot
Q8NAS0
resolver
uniprot
Q96IA3
resolver
uniprot_entry
OTUL_HUMAN
resolver
uniprot_sec
D3DTD3
resolver
uniprot_sec
Q8NAS0
resolver
uniprot_sec
Q96IA3
resolver
amino_acid_sequence
MSRGTMPQPEAWPGASCAETPAREAAATARDGGKAAASGQPRPEMQCPAEHEEDMYRAADEIEKEKELLIHERGASEPRLSVAPEMDIMDYCKKEWRGNTQKATCMKMGYEEVSQKFTSIRRVRGDNYCALRATLFQAMSQAVGLPPWLQDPELMLLPEKLISKYNWIKQWKLGLKFDGKNEDLVDKIKESLTLLRKKWAGLAEMRTAEARQIACDELFTNEAEEYSLYEAVKFLMLNRAIELYNDKEKGKEVPFFSVLLFARDTSNDPGQLLRNHLNQVGHTGGLEQVEMFLLAYAVRHTIQVYRLSKYNTEEFITVYPTDPPKDWPVVTLIAEDDRHYNIPVRVCEETSL
uniprot
proteins
disease_involvement
DISEASE: Autoinflammation, panniculitis, and dermatosis syndrome, autosomal recessive (AIPDSB) [MIM:617099]: An autosomal recessive autoinflammatory disorder characterized by neonatal-onset of fever, neutrophilic dermatitis, panniculitis, painful joints, failure to thrive. Patients do not exhibit overt primary immunodeficiency. {ECO:0000269|PubMed:27523608, ECO:0000269|PubMed:27559085, ECO:0000269|PubMed:30804083, ECO:0000269|PubMed:35170849}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Autoinflammation, panniculitis, and dermatosis syndrome, autosomal dominant (AIPDSA) [MIM:621030]: An autosomal dominant disorder characterized by the onset of autoinflammatory features in infancy, including fever, aseptic skin lesions, panniculitis, and poor wound healing. Patients do not exhibit signs of immunodeficiency. {ECO:0000269|PubMed:38630025, ECO:0000269|PubMed:38652464}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Immunodeficiency 107, susceptibility to invasive Staphylococcus aureus infection (IMD107) [MIM:619986]: An autosomal dominant immunologic disorder characterized by increased susceptibility to invasive and severe Staphylococcus aureus infection, causing life-threatening skin or pulmonary necrosis. Clinically, penetrance is incomplete and expressivity is variable. {ECO:0000269|PubMed:35587511}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry. OTULIN haploinsufficiency underlies life-threatening staphylococcal disease by disrupting cell-intrinsic immunity to alpha-toxin in non-leukocytic cells. {ECO:0000269|PubMed:35587511}.
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:23746843, PubMed:23806334, PubMed:23827681, PubMed:24726323, PubMed:24726327, PubMed:26997266, PubMed:27523608, PubMed:27559085, PubMed:28919039, PubMed:30804083, PubMed:35170849, PubMed:35587511, PubMed:38630025, PubMed:38652464). 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 (PubMed:23746843, PubMed:23806334). 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:26670046). 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 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 (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:24726327, ECO:0000269|PubMed:26670046, ECO:0000269|PubMed:26997266, ECO:0000269|PubMed:27523608, ECO:0000269|PubMed:27559085, ECO:0000269|PubMed:28919039, ECO:0000269|PubMed:30804083, ECO:0000269|PubMed:35170849, ECO:0000269|PubMed:35587511, ECO:0000269|PubMed:38630025, ECO:0000269|PubMed:38652464}.
uniprot
proteins
mass_dalton
40263
uniprot
proteins
mutagenesis
MUTAGEN 54; /note="D->A: Reduced interaction with RNF31."; /evidence="ECO:0000269|PubMed:24726323"; MUTAGEN 55; /note="M->D: Abolished interaction with RNF31."; /evidence="ECO:0000269|PubMed:24726323"; MUTAGEN 56; /note="Y->A,D: Abolished interaction with RNF31."; /evidence="ECO:0000269|PubMed:24726323, ECO:0000269|PubMed:24726327, ECO:0000269|PubMed:27458237"; MUTAGEN 56; /note="Y->E,F,W: Strongly reduced interaction with RNF31."; /evidence="ECO:0000269|PubMed:24726323, ECO:0000269|PubMed:24726327"; MUTAGEN 91; /note="Y->F: Results in strong reduction of kcat while not affecting KM."; /evidence="ECO:0000269|PubMed:23746843"; MUTAGEN 96; /note="W->A: Decreased activity toward linear ubiquitin."; /evidence="ECO:0000269|PubMed:23746843, ECO:0000269|PubMed:23806334"; MUTAGEN 100..102; /note="TQK->AAA: Decreased activity toward linear ubiquitin."; /evidence="ECO:0000269|PubMed:23746843"; MUTAGEN 129; /note="C->A: Abolishes deubiquitinase activity."; /evidence="ECO:0000269|PubMed:23708998, ECO:0000269|PubMed:23746843, ECO:0000269|PubMed:23806334, ECO:0000269|PubMed:24726327, ECO:0000269|PubMed:28919039"; MUTAGEN 254; /note="P->S: Severely decreased NF-kappa-B inhibition and increased NF-kappa-B signaling."; /evidence="ECO:0000269|PubMed:35587511"; MUTAGEN 259; /note="L->E: Decreased affinity for linear diubiquitin."; /evidence="ECO:0000269|PubMed:23746843"; MUTAGEN 314; /note="E->R: Decreased affinity for linear diubiquitin."; /evidence="ECO:0000269|PubMed:23746843"; MUTAGEN 336; /note="D->A: Stabilizes H-339 in the active conformation, generating a more reactive enzyme."; /evidence="ECO:0000269|PubMed:23746843"; MUTAGEN 339; /note="H->A: Impaired deubiquitinase activity."; /evidence="ECO:0000269|PubMed:23746843"; MUTAGEN 341; /note="N->A: Abolishes deubiquitinase activity."; /evidence="ECO:0000269|PubMed:23746843"; MUTAGEN 341; /note="N->D: Stabilizes H-339 in the active conformation, generating a more reactive enzyme. Severely decreased NF-kappa-B inhibition and increased NF-kappa-B signaling."; /evidence="ECO:0000269|PubMed:23746843, ECO:0000269|PubMed:35587511
uniprot
proteins
post_translational_modification
PTM: Ubiquitinated. {ECO:0000269|PubMed:23746843}.; PTM: Acetylated. {ECO:0000269|PubMed:23746843}.; PTM: Phosphorylated (PubMed:23746843, PubMed:24726323, PubMed:24726327). Phosphorylation at Tyr-56 prevents interaction with RNF31; dephosphorylation promotes interaction with RNF31 and the LUBAC complex (PubMed:24726323, PubMed:24726327). {ECO:0000269|PubMed:23746843, ECO:0000269|PubMed:24726323, ECO:0000269|PubMed:24726327}.
uniprot
proteins
protein_family
Otulin subfamily
uniprot
proteins
protein_family
Peptidase C65 family
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15372022
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
23708998
uniprot
proteins
pubmed
23746843
uniprot
proteins
pubmed
23806334
uniprot
proteins
pubmed
23827681
uniprot
proteins
pubmed
24726323
uniprot
proteins
pubmed
24726327
uniprot
proteins
pubmed
26670046
uniprot
proteins
pubmed
26997266
uniprot
proteins
pubmed
27458237
uniprot
proteins
pubmed
27523608
uniprot
proteins
pubmed
27559085
uniprot
proteins
pubmed
28919039
uniprot
proteins
pubmed
30804083
uniprot
proteins
pubmed
35170849
uniprot
proteins
pubmed
35587511
uniprot
proteins
pubmed
38630025
uniprot
proteins
pubmed
38652464
uniprot
proteins
sequence_length
352
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:23746843}.
uniprot
proteins