Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

Q91WA6

- SHRPN_MOUSE

UniProt

Q91WA6 - SHRPN_MOUSE

(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Protein

Sharpin

Gene

Sharpin

Organism
Mus musculus (Mouse)
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.4 Publications

Regions

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

GO - Molecular functioni

  1. polyubiquitin binding Source: UniProtKB
  2. zinc ion binding Source: InterPro

GO - Biological processi

  1. apoptotic nuclear changes Source: MGI
  2. brain development Source: Ensembl
  3. epidermis development Source: MGI
  4. keratinization Source: MGI
  5. mitochondrion organization Source: MGI
  6. negative regulation of inflammatory response Source: UniProtKB
  7. positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  8. protein homooligomerization Source: Ensembl
  9. protein linear polyubiquitination Source: UniProtKB
  10. regulation of CD40 signaling pathway Source: UniProtKB
  11. 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
Shank-interacting protein-like 1
Short name:
mSIPL1
Gene namesi
Name:Sharpin
Synonyms:Cpdm, Sipl1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 15

Organism-specific databases

MGIiMGI:1913331. Sharpin.

Subcellular locationi

Cytoplasmcytosol By similarity. Cell junctionsynapse By similarity
Note: Enriched at synaptic sites in mature neurons where it colocalizes with SHANK1.By similarity

GO - Cellular componenti

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

Keywords - Cellular componenti

Cell junction, Cytoplasm, Synapse

Pathology & Biotechi

Involvement in diseasei

Defects in Sharpin are the cause of chronic proliferative dermatitis (cpdm). Cpdm is a spontaneous mutation causing a chronic proliferative dermatitis phenotype, which is characterized histologically by severe inflammation, eosinophilic dermatitis and defects in secondary lymphoid organ development. Mice also display lower total and cortical bone mineral content and bone mineral density, trabecular and cortical bone volume, and trabecular number. TNF-alpha-induced NF-kappa-B activation is attenuated due to inability of the LUBAC complex to mediate linear ubiquitination.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 380380SharpinPRO_0000280635Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei163 – 1631PhosphoserineBy similarity
Modified residuei307 – 3071PhosphoserineBy similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ91WA6.
PaxDbiQ91WA6.
PRIDEiQ91WA6.

PTM databases

PhosphoSiteiQ91WA6.

Expressioni

Tissue specificityi

Highly expressed in thymus and spleen. Present at high level in splenic B- and T-cells (at protein level).1 Publication

Gene expression databases

BgeeiQ91WA6.
CleanExiMM_SHARPIN.
ExpressionAtlasiQ91WA6. baseline and differential.
GenevestigatoriQ91WA6.

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).1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
Eya1P977674EBI-646097,EBI-1368503
Eya2O085752EBI-646097,EBI-986503

Protein-protein interaction databases

BioGridi222977. 23 interactions.
DIPiDIP-49461N.
IntActiQ91WA6. 3 interactions.

Structurei

3D structure databases

ProteinModelPortaliQ91WA6.
SMRiQ91WA6. Positions 19-119, 212-299.
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-associationBy similarityAdd
BLAST
Regioni172 – 305134Interaction with SHANK1By similarityAdd
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.
InParanoidiQ91WA6.
OMAiHELQPPP.
OrthoDBiEOG7T7GTX.
PhylomeDBiQ91WA6.
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]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: Q91WA6) [UniParc]FASTAAdd to Basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSPPAGGAAV AADPASPVVL LAVHAAVRPL GAGQDAEAQP RKLQLIADPE
60 70 80 90 100
RPGRFRLGLL GTEPGAVSLE WPLEAICYTV RGPNQHELQP PPGGPGTFSV
110 120 130 140 150
HFLDPEEAQQ WAALVRDATA EGQNGSGSPA PAPAPAMCPI SPPCSSMAQI
160 170 180 190 200
PKATQPEVDL PQSSGNFKKE ELATRLSQAI AGGDEKAAAQ VAAVLAQHHV
210 220 230 240 250
ALNVQLMEAW FPPGPIRLQV TVEDATSVLS SSSSAHVSLK IHPHCSIAAL
260 270 280 290 300
QDQVFSEFGF PPAVQRWVIG RCLCMPERSL ASYGVSQDGD PAFLYLLSAP
310 320 330 340 350
REVSGQSLQN SKMDRKLGLF PQSLGLPHDL QPSSSSLPSP SQPGWSCPSC
360 370 380
TFINASNRPG CEMCSTQRPC AWDPLAAAST
Length:380
Mass (Da):39,852
Last modified:December 1, 2001 - v1
Checksum:iC7E4B8F40F6D8F05
GO
Isoform 2 (identifier: Q91WA6-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     306-380: Missing.

Note: No experimental confirmation available.

Show »
Length:305
Mass (Da):31,864
Checksum:i6428AD468FC5BEF6
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti131 – 1311P → Q in BAC53796. (PubMed:12753155)Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei306 – 38075Missing in isoform 2. 1 PublicationVSP_023839Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AB052763 mRNA. Translation: BAC53796.1.
BC016203 mRNA. Translation: AAH16203.1.
BC055758 mRNA. Translation: AAH55758.1.
CCDSiCCDS37121.1. [Q91WA6-1]
RefSeqiNP_079616.2. NM_025340.2. [Q91WA6-1]
UniGeneiMm.41463.

Genome annotation databases

EnsembliENSMUST00000023211; ENSMUSP00000023211; ENSMUSG00000022552. [Q91WA6-1]
GeneIDi106025.
KEGGimmu:106025.
UCSCiuc007wju.2. mouse. [Q91WA6-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AB052763 mRNA. Translation: BAC53796.1 .
BC016203 mRNA. Translation: AAH16203.1 .
BC055758 mRNA. Translation: AAH55758.1 .
CCDSi CCDS37121.1. [Q91WA6-1 ]
RefSeqi NP_079616.2. NM_025340.2. [Q91WA6-1 ]
UniGenei Mm.41463.

3D structure databases

ProteinModelPortali Q91WA6.
SMRi Q91WA6. Positions 19-119, 212-299.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 222977. 23 interactions.
DIPi DIP-49461N.
IntActi Q91WA6. 3 interactions.

PTM databases

PhosphoSitei Q91WA6.

Proteomic databases

MaxQBi Q91WA6.
PaxDbi Q91WA6.
PRIDEi Q91WA6.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000023211 ; ENSMUSP00000023211 ; ENSMUSG00000022552 . [Q91WA6-1 ]
GeneIDi 106025.
KEGGi mmu:106025.
UCSCi uc007wju.2. mouse. [Q91WA6-1 ]

Organism-specific databases

CTDi 81858.
MGIi MGI:1913331. Sharpin.

Phylogenomic databases

eggNOGi NOG278522.
GeneTreei ENSGT00530000063620.
HOGENOMi HOG000095521.
HOVERGENi HBG093954.
InParanoidi Q91WA6.
OMAi HELQPPP.
OrthoDBi EOG7T7GTX.
PhylomeDBi Q91WA6.
TreeFami TF323486.

Miscellaneous databases

NextBioi 358020.
PROi Q91WA6.
SOURCEi Search...

Gene expression databases

Bgeei Q91WA6.
CleanExi MM_SHARPIN.
ExpressionAtlasi Q91WA6. baseline and differential.
Genevestigatori Q91WA6.

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. "Novel human and mouse genes encoding a shank-interacting protein and its upregulation in gastric fundus of W/WV mouse."
    Daigo Y., Takayama I., Ward S.M., Sanders K.M., Fujino M.A.
    J. Gastroenterol. Hepatol. 18:712-718(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  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] (ISOFORMS 1 AND 2).
    Strain: C57BL/6.
    Tissue: Brain and Eye.
  3. "Spontaneous mutations in the mouse Sharpin gene result in multiorgan inflammation, immune system dysregulation and dermatitis."
    Seymour R.E., Hasham M.G., Cox G.A., Shultz L.D., Hogenesch H., Roopenian D.C., Sundberg J.P.
    Genes Immun. 8:416-421(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INVOLVEMENT IN CPDM.
  4. "Anti-IL5 decreases the number of eosinophils but not the severity of dermatitis in Sharpin-deficient mice."
    Renninger M.L., Seymour R.E., Whiteley L.O., Sundberg J.P., Hogenesch H.
    Exp. Dermatol. 19:252-258(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: INVOLVEMENT IN CPDM.
  5. "Sipl1 and Rbck1 are novel Eya1-binding proteins with a role in craniofacial development."
    Landgraf K., Bollig F., Trowe M.O., Besenbeck B., Ebert C., Kruspe D., Kispert A., Hanel F., Englert C.
    Mol. Cell. Biol. 30:5764-5775(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH EYA1 AND EYA2.
  6. "Loss-of-function of SHARPIN causes an osteopenic phenotype in mice."
    Xia T., Liang Y., Ma J., Li M., Gong M., Yu X.
    Endocrine 39:104-112(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: INVOLVEMENT IN CPDM.
  7. "Inhibition of NF-kappaB signaling retards eosinophilic dermatitis in SHARPIN-deficient mice."
    Liang Y., Seymour R.E., Sundberg J.P.
    J. Invest. Dermatol. 131:141-149(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: INVOLVEMENT IN CPDM.
  8. Cited for: FUNCTION, INVOLVEMENT IN CPDM.
  9. "SHARPIN is a component of the NF-kappaB-activating linear ubiquitin chain assembly complex."
    Tokunaga F., Nakagawa T., Nakahara M., Saeki Y., Taniguchi M., Sakata S., Tanaka K., Nakano H., Iwai K.
    Nature 471:633-636(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INVOLVEMENT IN CPDM, TISSUE SPECIFICITY.
  10. Cited for: FUNCTION, INVOLVEMENT IN CPDM.

Entry informationi

Entry nameiSHRPN_MOUSE
AccessioniPrimary (citable) accession number: Q91WA6
Secondary accession number(s): Q7TNT3, Q8CHL3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 20, 2007
Last sequence update: December 1, 2001
Last modified: October 29, 2014
This is version 92 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3