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Protein

Sharpin

Gene

Sharpin

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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. LUBAC conjugates linear polyubiquitin to IKBKG and RIPK1 and is involved in activation of the canonical NF-kappa-B and the JNK signaling pathways. Linear ubiquitination mediated by the LUBAC complex interferes with TNF-induced cell death and thereby prevents inflammation. LUBAC is proposed to be 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. Together with FAM105B/otulin, the LUBAC complex regulates the canonical Wnt signaling during angiogenesis (By similarity).By similarity

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri342 – 371RanBP2-typePROSITE-ProRule annotationAdd BLAST30

GO - Molecular functioni

GO - Biological processi

Keywordsi

Biological processUbl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-RNO-5357905 Regulation of TNFR1 signaling
R-RNO-5357956 TNFR1-induced NFkappaB signaling pathway

Names & Taxonomyi

Protein namesi
Recommended name:
Sharpin
Alternative name(s):
Shank-associated RH domain-interacting protein
Gene namesi
Name:Sharpin
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 7

Organism-specific databases

RGDi631353 Sharpin

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell junction, Cytoplasm, Synapse

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002806361 – 381SharpinAdd BLAST381

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei307PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ9EQL9
PRIDEiQ9EQL9

Expressioni

Tissue specificityi

Expressed in brain, spleen, lung, heart, skeletal muscle, kidney and testis (at protein level). Expressed in heart and testis.1 Publication

Gene expression databases

BgeeiENSRNOG00000012812
GenevisibleiQ9EQL9 RN

Interactioni

Subunit structurei

Monomer and homodimer. Component of the LUBAC complex (linear ubiquitin chain assembly complex) which consists of SHARPIN, RBCK1 and RNF31. LUBAC has a MW of approximately 600 kDa suggesting a heteromultimeric assembly of its subunits. Associates with the TNF-R1 signaling complex (TNF-RSC) in a stimulation-dependent manner. Interacts with EYA1, EYA2, SHANK1 and SHANK3 (via ANK repeats).2 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi249689, 3 interactors
CORUMiQ9EQL9
IntActiQ9EQL9, 5 interactors
STRINGi10116.ENSRNOP00000018032

Structurei

3D structure databases

ProteinModelPortaliQ9EQL9
SMRiQ9EQL9
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini216 – 285Ubiquitin-likeAdd BLAST70

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 177Self-associationAdd BLAST177
Regioni172 – 305Interaction with SHANK11 PublicationAdd BLAST134

Domaini

The Ubiquitin-like domain is required for the interaction with RNF31.By similarity
The RanBP2-type zinc fingers mediate the specific interaction with ubiquitin. Binds preferentially linear polyubiquitin chains and 'Lys-63'-linked polyubiquitin chains over 'Lys-48'-linked polyubiquitin chains. Also binds monoubiquitin (By similarity).By similarity

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri342 – 371RanBP2-typePROSITE-ProRule annotationAdd BLAST30

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG1815 Eukaryota
ENOG410XP9Y LUCA
GeneTreeiENSGT00530000063620
HOGENOMiHOG000095521
HOVERGENiHBG093954
InParanoidiQ9EQL9
KOiK20894
OMAiCEMCSTQ
OrthoDBiEOG091G0GY5
PhylomeDBiQ9EQL9
TreeFamiTF323486

Family and domain databases

Gene3Di2.30.29.30, 1 hit
InterProiView protein in InterPro
IPR011993 PH-like_dom_sf
IPR026168 SHARPIN
IPR031912 Sharpin_PH
IPR029071 Ubiquitin-like_domsf
IPR001876 Znf_RanBP2
IPR036443 Znf_RanBP2_sf
PANTHERiPTHR22770:SF36 PTHR22770:SF36, 1 hit
PfamiView protein in Pfam
PF16764 Sharpin_PH, 1 hit
SMARTiView protein in SMART
SM00547 ZnF_RBZ, 1 hit
SUPFAMiSSF54236 SSF54236, 1 hit
SSF90209 SSF90209, 1 hit
PROSITEiView protein in PROSITE
PS01358 ZF_RANBP2_1, 1 hit
PS50199 ZF_RANBP2_2, 1 hit

Sequencei

Sequence statusi: Complete.

Q9EQL9-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSPPAGGAAA AADPASPVVL LAVQAAVRLL GAGHEDEAQL RKLQLKADPE
60 70 80 90 100
RPGRFRLGLL GIEPGAVSLE WPLESICYTI RGPNQHELQP PPGGPGTFSV
110 120 130 140 150
HFLNSEEAQQ WAALVRDATA EGQNGNDSTA PVPTPAMCPT SPPCSSVTPT
160 170 180 190 200
PKATQPEMDL PQGSGNLKKE ELATHLAQAI AGGDEKAAAQ VAAILAQHHV
210 220 230 240 250
ALNVQLLEAW FPRGPIRLQV TVEDATSVLS SSSSAHVSLQ IHPHCSIAAL
260 270 280 290 300
QEQVFSEFGF PPAVQRWVIG RCLCMPERSL ASYGVSQDGD PAFLYLLSAP
310 320 330 340 350
REVSGHSPQH SKMDRKLGCL FPQSLELPHN LQASSSSLPS PPQPGWSCPS
360 370 380
CTFINASNRP GCEMCSTQRP CAWDPLTATS T
Length:381
Mass (Da):40,287
Last modified:March 1, 2001 - v1
Checksum:i8D9A7D7D23665567
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF203906 mRNA Translation: AAG43482.1
BC083553 mRNA Translation: AAH83553.1
RefSeqiNP_112415.1, NM_031153.2
UniGeneiRn.38393

Genome annotation databases

EnsembliENSRNOT00000018031; ENSRNOP00000018032; ENSRNOG00000012812
GeneIDi81859
KEGGirno:81859
UCSCiRGD:631353 rat

Similar proteinsi

Entry informationi

Entry nameiSHRPN_RAT
AccessioniPrimary (citable) accession number: Q9EQL9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 20, 2007
Last sequence update: March 1, 2001
Last modified: May 23, 2018
This is version 111 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
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Main funding by: National Institutes of Health