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Protein

Sharpin

Gene

Sharpin

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri342 – 37130RanBP2-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  1. identical protein binding Source: IntAct
  2. polyubiquitin binding Source: UniProtKB
  3. protein complex binding Source: RGD
  4. zinc ion binding Source: InterPro

GO - Biological processi

  1. apoptotic nuclear changes Source: Ensembl
  2. brain development Source: RGD
  3. keratinization Source: Ensembl
  4. mitochondrion organization Source: Ensembl
  5. negative regulation of inflammatory response Source: UniProtKB
  6. positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  7. protein homooligomerization Source: RGD
  8. protein linear polyubiquitination Source: UniProtKB
  9. regulation of CD40 signaling pathway Source: UniProtKB
  10. regulation of tumor necrosis factor-mediated signaling pathway Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

Ubl conjugation pathway

Keywords - Ligandi

Metal-binding, Zinc

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494 Componenti: Chromosome 7

Organism-specific databases

RGDi631353. Sharpin.

Subcellular locationi

Cytoplasm 1 Publication. Cell junctionsynapse 1 Publication
Note: Enriched at synaptic sites in mature neurons where it colocalizes with SHANK1.

GO - Cellular componenti

  1. cell junction Source: UniProtKB-KW
  2. cytosol Source: UniProtKB
  3. dendrite Source: RGD
  4. LUBAC complex Source: UniProtKB
  5. postsynaptic density Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cytoplasm, Synapse

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 381381SharpinPRO_0000280636Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei307 – 3071PhosphoserineBy similarity

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

GenevestigatoriQ9EQL9.

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 approximative 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

WithEntry#Exp.IntActNotes
itself2EBI-1394695,EBI-1394695
Shank1Q9WV487EBI-1394695,EBI-80909

Protein-protein interaction databases

BioGridi249689. 1 interaction.
IntActiQ9EQL9. 5 interactions.
STRINGi10116.ENSRNOP00000018032.

Structurei

3D structure databases

ProteinModelPortaliQ9EQL9.
SMRiQ9EQL9. Positions 341-375.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini216 – 28570Ubiquitin-likeAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 177177Self-associationAdd
BLAST
Regioni172 – 305134Interaction with SHANK1Add
BLAST

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

Sequence similaritiesi

Contains 1 RanBP2-type zinc finger.PROSITE-ProRule annotation
Contains 1 ubiquitin-like domain.Curated

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri342 – 37130RanBP2-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiNOG278522.
GeneTreeiENSGT00530000063620.
HOGENOMiHOG000095521.
HOVERGENiHBG093954.
InParanoidiQ9EQL9.
OMAiHELQPPP.
OrthoDBiEOG7T7GTX.
PhylomeDBiQ9EQL9.
TreeFamiTF323486.

Family and domain databases

InterProiIPR026168. SHARPIN.
IPR029071. Ubiquitin-rel_dom.
IPR001876. Znf_RanBP2.
[Graphical view]
PANTHERiPTHR22770:SF31. PTHR22770:SF31. 1 hit.
PfamiPF00641. zf-RanBP. 1 hit.
[Graphical view]
SMARTiSM00547. ZnF_RBZ. 1 hit.
[Graphical view]
SUPFAMiSSF54236. SSF54236. 1 hit.
PROSITEiPS01358. ZF_RANBP2_1. 1 hit.
PS50199. ZF_RANBP2_2. 1 hit.
[Graphical view]

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.

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliQ9EQL9.
SMRiQ9EQL9. Positions 341-375.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi249689. 1 interaction.
IntActiQ9EQL9. 5 interactions.
STRINGi10116.ENSRNOP00000018032.

Proteomic databases

PaxDbiQ9EQL9.
PRIDEiQ9EQL9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi81858.
RGDi631353. Sharpin.

Phylogenomic databases

eggNOGiNOG278522.
GeneTreeiENSGT00530000063620.
HOGENOMiHOG000095521.
HOVERGENiHBG093954.
InParanoidiQ9EQL9.
OMAiHELQPPP.
OrthoDBiEOG7T7GTX.
PhylomeDBiQ9EQL9.
TreeFamiTF323486.

Miscellaneous databases

NextBioi615783.
PROiQ9EQL9.

Gene expression databases

GenevestigatoriQ9EQL9.

Family and domain databases

InterProiIPR026168. SHARPIN.
IPR029071. Ubiquitin-rel_dom.
IPR001876. Znf_RanBP2.
[Graphical view]
PANTHERiPTHR22770:SF31. PTHR22770:SF31. 1 hit.
PfamiPF00641. zf-RanBP. 1 hit.
[Graphical view]
SMARTiSM00547. ZnF_RBZ. 1 hit.
[Graphical view]
SUPFAMiSSF54236. SSF54236. 1 hit.
PROSITEiPS01358. ZF_RANBP2_1. 1 hit.
PS50199. ZF_RANBP2_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Sharpin, a novel postsynaptic density protein that directly interacts with the shank family of proteins."
    Lim S., Sala C., Yoon J., Park S., Kuroda S., Sheng M., Kim E.
    Mol. Cell. Neurosci. 17:385-397(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBUNIT, INTERACTION WITH SHANK1, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
    Strain: Sprague-Dawley.
    Tissue: Brain.
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Heart.
  3. "SHANK3 gene mutations associated with autism facilitate ligand binding to the Shank3 ankyrin repeat region."
    Mameza M.G., Dvoretskova E., Bamann M., Hoenck H.H., Gueler T., Boeckers T.M., Schoen M., Verpelli C., Sala C., Barsukov I., Dityatev A., Kreienkamp H.J.
    J. Biol. Chem. 288:26697-26708(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SHANK3.

Entry informationi

Entry nameiSHRPN_RAT
AccessioniPrimary (citable) accession number: Q9EQL9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 20, 2007
Last sequence update: March 1, 2001
Last modified: March 4, 2015
This is version 85 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.