SHARPIN
entrez
81858
canonical
uniprot
Q9H0F6
canonical
ensembl
ENSG00000179526
resolver
ensp
ENSP00000381698
resolver
ensp
ENSP00000546528
resolver
ensp
ENSP00000546536
resolver
ensp
ENSP00000652148
resolver
genesymbol
SHARPIN
resolver
genesymbol_syn
SIPL1
resolver
hgnc
HGNC:25321
resolver
uniprot
A6NEG3
resolver
uniprot
C0L3L2
resolver
uniprot
D3DWL3
resolver
uniprot
Q6PJD5
resolver
uniprot
Q8IXF5
resolver
uniprot
Q8IXF6
resolver
uniprot
Q8N2E7
resolver
uniprot
Q8TB25
resolver
uniprot
Q9BUE4
resolver
uniprot_entry
Q6PJD5_HUMAN
resolver
uniprot_entry
SHRPN_HUMAN
resolver
uniprot_sec
A6NEG3
resolver
uniprot_sec
C0L3L2
resolver
uniprot_sec
D3DWL3
resolver
uniprot_sec
Q8IXF5
resolver
uniprot_sec
Q8IXF6
resolver
uniprot_sec
Q8N2E7
resolver
uniprot_sec
Q8TB25
resolver
uniprot_sec
Q9BUE4
resolver
amino_acid_sequence
MAPPAGGAAAAASDLGSAAVLLAVHAAVRPLGAGPDAEAQLRRLQLSADPERPGRFRLELLGAGPGAVNLEWPLESVSYTIRGPTQHELQPPPGGPGTLSLHFLNPQEAQRWAVLVRGATVEGQNGSKSNSPPALGPEACPVSLPSPPEASTLKGPPPEADLPRSPGNLTEREELAGSLARAIAGGDEKGAAQVAAVLAQHRVALSVQLQEACFPPGPIRLQVTLEDAASAASAASSAHVALQVHPHCTVAALQEQVFSELGFPPAVQRWVIGRCLCVPERSLASYGVRQDGDPAFLYLLSAPREAPATGPSPQHPQKMDGELGRLFPPSLGLPPGPQPAASSLPSPLQPSWSCPSCTFINAPDRPGCEMCSTQRPCTWDPLAAAST
uniprot
proteins
disease_involvement
DISEASE: Autoinflammation with episodic fever and immune dysregulation (AIFID) [MIM:620795]: An autosomal recessive disorder characterized by recurrent fever and autoinflammation with onset in infancy or early childhood. Variable clinical manifestations include lymphadenopathy, hepatosplenomegaly, gastrointestinal inflammation, polyarthritis and joint inflammation, parotitis, and immune dysregulation. {ECO:0000269|PubMed:38609546}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: Component of the LUBAC complex which conjugates linear polyubiquitin chains in a head-to-tail manner to substrates and plays a key role in NF-kappa-B activation and regulation of inflammation (PubMed:21455173, PubMed:21455180, PubMed:21455181). LUBAC conjugates linear polyubiquitin to IKBKG and RIPK1 and is involved in activation of the canonical NF-kappa-B and the JNK signaling pathways (PubMed:21455173, PubMed:21455180, PubMed:21455181). Linear ubiquitination mediated by the LUBAC complex interferes with TNF-induced cell death and thereby prevents inflammation (PubMed:21455173, PubMed:21455180, PubMed:21455181). LUBAC is recruited to the TNF-R1 signaling complex (TNF-RSC) following polyubiquitination of TNF-RSC components by BIRC2 and/or BIRC3 and to conjugate linear polyubiquitin to IKBKG and possibly other components contributing to the stability of the complex (PubMed:21455173, PubMed:21455180, PubMed:21455181). The LUBAC complex is also involved in innate immunity by conjugating linear polyubiquitin chains at the surface of bacteria invading the cytosol to form the ubiquitin coat surrounding bacteria (PubMed:28481331). LUBAC is not able to initiate formation of the bacterial ubiquitin coat, and can only promote formation of linear polyubiquitins on pre-existing ubiquitin (PubMed:28481331). The bacterial ubiquitin coat acts as an 'eat-me' signal for xenophagy and promotes NF-kappa-B activation (PubMed:28481331). Together with OTULIN, the LUBAC complex regulates the canonical Wnt signaling during angiogenesis (PubMed:23708998). {ECO:0000269|PubMed:21455173, ECO:0000269|PubMed:21455180, ECO:0000269|PubMed:21455181, ECO:0000269|PubMed:23708998, ECO:0000269|PubMed:28481331}.
uniprot
proteins
mass_dalton
39949
uniprot
proteins
mutagenesis
MUTAGEN 114; /note="V->D: Abolishes homodimerization."; /evidence="ECO:0000269|PubMed:22549881"; MUTAGEN 272; /note="I->A: Abolishes interaction with RNF31 and ability to mediate linear polyubiquitination."; /evidence="ECO:0000269|PubMed:21455181"; MUTAGEN 354; /note="C->S: Abolishes binding to ubiquitin without affecting interaction with RNF31; when associated with S-357."; /evidence="ECO:0000269|PubMed:21455173"; MUTAGEN 357; /note="C->S: Abolishes binding to ubiquitin without affecting interaction with RNF31; when associated with S-354."; /evidence="ECO:0000269|PubMed:21455173"; MUTAGEN 358..359; /note="TF->LV: Abolishes binding to ubiquitin and ability to mediate linear polyubiquitination."; /evidence="ECO:0000269|PubMed:21455181"; MUTAGEN 368; /note="C->S: Abolishes binding to ubiquitin without affecting interaction with RNF31; when associated with S-371."; /evidence="ECO:0000269|PubMed:21455173"; MUTAGEN 371; /note="C->S: Abolishes binding to ubiquitin without affecting interaction with RNF31; when associated with S-368."; /evidence="ECO:0000269|PubMed:21455173
uniprot
proteins
pathway_participation
PATHWAY: Protein modification; protein ubiquitination. {ECO:0000269|PubMed:28481331}.
uniprot
proteins
pubmed
11230166
uniprot
proteins
pubmed
12753155
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16421571
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20179993
uniprot
proteins
pubmed
21455173
uniprot
proteins
pubmed
21455180
uniprot
proteins
pubmed
21455181
uniprot
proteins
pubmed
22549881
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23708998
uniprot
proteins
pubmed
28481331
uniprot
proteins
pubmed
38609546
uniprot
proteins
sequence_length
387
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:20179993}. Synapse {ECO:0000250|UniProtKB:Q9EQL9}. Note=Enriched at synaptic sites in mature neurons where it colocalizes with SHANK1. {ECO:0000250|UniProtKB:Q9EQL9}.
uniprot
proteins