Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q9EQL9 (SHRPN_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 81. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Sharpin
Alternative name(s):
Shank-associated RH domain-interacting protein
Gene names
Name:Sharpin
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length381 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. 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.

Subunit structure

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). Ref.1 Ref.3

Subcellular location

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

Tissue specificity

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

Domain

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.

Sequence similarities

Contains 1 RanBP2-type zinc finger.

Contains 1 ubiquitin-like domain.

Ontologies

Keywords
   Biological processUbl conjugation pathway
   Cellular componentCell junction
Cytoplasm
Synapse
   DomainZinc-finger
   LigandMetal-binding
Zinc
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processapoptotic nuclear changes

Inferred from electronic annotation. Source: Ensembl

brain development

Inferred from expression pattern Ref.1. Source: RGD

keratinization

Inferred from electronic annotation. Source: Ensembl

mitochondrion organization

Inferred from electronic annotation. Source: Ensembl

negative regulation of inflammatory response

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of I-kappaB kinase/NF-kappaB signaling

Inferred from sequence or structural similarity. Source: UniProtKB

protein homooligomerization

Inferred from direct assay Ref.1. Source: RGD

protein linear polyubiquitination

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of CD40 signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of tumor necrosis factor-mediated signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentLUBAC complex

Inferred from sequence or structural similarity. Source: UniProtKB

cell junction

Inferred from electronic annotation. Source: UniProtKB-KW

cytosol

Inferred from sequence or structural similarity. Source: UniProtKB

dendrite

Inferred from direct assay Ref.1. Source: RGD

postsynaptic density

Inferred from direct assay Ref.1. Source: RGD

   Molecular_functionidentical protein binding

Inferred from physical interaction Ref.1. Source: IntAct

polyubiquitin binding

Inferred from sequence or structural similarity. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.1. Source: IntAct

protein complex binding

Inferred from physical interaction Ref.1. Source: RGD

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

itself2EBI-1394695,EBI-1394695
Shank1Q9WV487EBI-1394695,EBI-80909

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 381381Sharpin
PRO_0000280636

Regions

Domain216 – 28570Ubiquitin-like
Zinc finger342 – 37130RanBP2-type
Region1 – 177177Self-association
Region172 – 305134Interaction with SHANK1

Amino acid modifications

Modified residue3071Phosphoserine By similarity

Sequences

Sequence LengthMass (Da)Tools
Q9EQL9 [UniParc].

Last modified March 1, 2001. Version 1.
Checksum: 8D9A7D7D23665567

FASTA38140,287
        10         20         30         40         50         60 
MSPPAGGAAA AADPASPVVL LAVQAAVRLL GAGHEDEAQL RKLQLKADPE RPGRFRLGLL 

        70         80         90        100        110        120 
GIEPGAVSLE WPLESICYTI RGPNQHELQP PPGGPGTFSV HFLNSEEAQQ WAALVRDATA 

       130        140        150        160        170        180 
EGQNGNDSTA PVPTPAMCPT SPPCSSVTPT PKATQPEMDL PQGSGNLKKE ELATHLAQAI 

       190        200        210        220        230        240 
AGGDEKAAAQ VAAILAQHHV ALNVQLLEAW FPRGPIRLQV TVEDATSVLS SSSSAHVSLQ 

       250        260        270        280        290        300 
IHPHCSIAAL QEQVFSEFGF PPAVQRWVIG RCLCMPERSL ASYGVSQDGD PAFLYLLSAP 

       310        320        330        340        350        360 
REVSGHSPQH SKMDRKLGCL FPQSLELPHN LQASSSSLPS PPQPGWSCPS CTFINASNRP 

       370        380 
GCEMCSTQRP CAWDPLTATS T 

« Hide

References

« Hide 'large scale' references
[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(2001) [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(2004) [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(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SHANK3.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF203906 mRNA. Translation: AAG43482.1.
BC083553 mRNA. Translation: AAH83553.1.
RefSeqNP_112415.1. NM_031153.2.
UniGeneRn.38393.

3D structure databases

ProteinModelPortalQ9EQL9.
SMRQ9EQL9. Positions 341-375.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid249689. 1 interaction.
IntActQ9EQL9. 5 interactions.
STRING10116.ENSRNOP00000018032.

Proteomic databases

PaxDbQ9EQL9.
PRIDEQ9EQL9.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000018031; ENSRNOP00000018032; ENSRNOG00000012812.
GeneID81859.
KEGGrno:81859.
UCSCRGD:631353. rat.

Organism-specific databases

CTD81858.
RGD631353. Sharpin.

Phylogenomic databases

eggNOGNOG278522.
GeneTreeENSGT00530000063620.
HOGENOMHOG000095521.
HOVERGENHBG093954.
InParanoidQ9EQL9.
OMAHELQPPP.
OrthoDBEOG7T7GTX.
PhylomeDBQ9EQL9.
TreeFamTF323486.

Gene expression databases

GenevestigatorQ9EQL9.

Family and domain databases

InterProIPR026168. SHARPIN.
IPR029071. Ubiquitin-rel_dom.
IPR001876. Znf_RanBP2.
[Graphical view]
PANTHERPTHR22770:SF31. PTHR22770:SF31. 1 hit.
PfamPF00641. zf-RanBP. 1 hit.
[Graphical view]
SMARTSM00547. ZnF_RBZ. 1 hit.
[Graphical view]
SUPFAMSSF54236. SSF54236. 1 hit.
PROSITEPS01358. ZF_RANBP2_1. 1 hit.
PS50199. ZF_RANBP2_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio615783.
PROQ9EQL9.

Entry information

Entry nameSHRPN_RAT
AccessionPrimary (citable) accession number: Q9EQL9
Entry history
Integrated into UniProtKB/Swiss-Prot: March 20, 2007
Last sequence update: March 1, 2001
Last modified: June 11, 2014
This is version 81 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families