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Q9EQL9

- SHRPN_RAT

UniProt

Q9EQL9 - SHRPN_RAT

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Protein
Sharpin
Gene
Sharpin
Organism
Rattus norvegicus (Rat)
Status
Reviewed - 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.

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri342 – 37130RanBP2-type
Add
BLAST

GO - Molecular functioni

  1. identical protein binding Source: IntAct
  2. polyubiquitin binding Source: UniProtKB
  3. protein binding Source: IntAct
  4. protein complex binding Source: RGD
  5. 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: Chromosome 7

Organism-specific databases

RGDi631353. Sharpin.

Subcellular locationi

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

GO - Cellular componenti

  1. LUBAC complex Source: UniProtKB
  2. cell junction Source: UniProtKB-KW
  3. cytosol Source: UniProtKB
  4. dendrite Source: RGD
  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 – 381381Sharpin
PRO_0000280636Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei307 – 3071Phosphoserine By 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.

Family & Domainsi

Domains and Repeats

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

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 177177Self-association
Add
BLAST
Regioni172 – 305134Interaction with SHANK1
Add
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.

Sequence similaritiesi

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

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MSPPAGGAAA AADPASPVVL LAVQAAVRLL GAGHEDEAQL RKLQLKADPE    50
RPGRFRLGLL GIEPGAVSLE WPLESICYTI RGPNQHELQP PPGGPGTFSV 100
HFLNSEEAQQ WAALVRDATA EGQNGNDSTA PVPTPAMCPT SPPCSSVTPT 150
PKATQPEMDL PQGSGNLKKE ELATHLAQAI AGGDEKAAAQ VAAILAQHHV 200
ALNVQLLEAW FPRGPIRLQV TVEDATSVLS SSSSAHVSLQ IHPHCSIAAL 250
QEQVFSEFGF PPAVQRWVIG RCLCMPERSL ASYGVSQDGD PAFLYLLSAP 300
REVSGHSPQH SKMDRKLGCL FPQSLELPHN LQASSSSLPS PPQPGWSCPS 350
CTFINASNRP GCEMCSTQRP CAWDPLTATS T 381
Length:381
Mass (Da):40,287
Last modified:March 1, 2001 - v1
Checksum:i8D9A7D7D23665567
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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:
EMBL
GenBank
DDBJ
Links Updated
AF203906 mRNA. Translation: AAG43482.1 .
BC083553 mRNA. Translation: AAH83553.1 .
RefSeqi NP_112415.1. NM_031153.2.
UniGenei Rn.38393.

3D structure databases

ProteinModelPortali Q9EQL9.
SMRi Q9EQL9. Positions 341-375.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 249689. 1 interaction.
IntActi Q9EQL9. 5 interactions.
STRINGi 10116.ENSRNOP00000018032.

Proteomic databases

PaxDbi Q9EQL9.
PRIDEi Q9EQL9.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSRNOT00000018031 ; ENSRNOP00000018032 ; ENSRNOG00000012812 .
GeneIDi 81859.
KEGGi rno:81859.
UCSCi RGD:631353. rat.

Organism-specific databases

CTDi 81858.
RGDi 631353. Sharpin.

Phylogenomic databases

eggNOGi NOG278522.
GeneTreei ENSGT00530000063620.
HOGENOMi HOG000095521.
HOVERGENi HBG093954.
InParanoidi Q9EQL9.
OMAi HELQPPP.
OrthoDBi EOG7T7GTX.
PhylomeDBi Q9EQL9.
TreeFami TF323486.

Miscellaneous databases

NextBioi 615783.
PROi Q9EQL9.

Gene expression databases

Genevestigatori Q9EQL9.

Family and domain databases

InterProi IPR026168. SHARPIN.
IPR029071. Ubiquitin-rel_dom.
IPR001876. Znf_RanBP2.
[Graphical view ]
PANTHERi PTHR22770:SF31. PTHR22770:SF31. 1 hit.
Pfami PF00641. zf-RanBP. 1 hit.
[Graphical view ]
SMARTi SM00547. ZnF_RBZ. 1 hit.
[Graphical view ]
SUPFAMi SSF54236. SSF54236. 1 hit.
PROSITEi PS01358. ZF_RANBP2_1. 1 hit.
PS50199. ZF_RANBP2_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

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(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.

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: June 11, 2014
This is version 81 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

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