Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(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)

Q91WA6

- SHRPN_MOUSE

UniProt

Q91WA6 - SHRPN_MOUSE

Protein

Sharpin

Gene

Sharpin

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 91 (01 Oct 2014)
      Sequence version 1 (01 Dec 2001)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    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. protein binding Source: IntAct
    3. 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

    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

    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

    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

    ArrayExpressiQ91WA6.
    BgeeiQ91WA6.
    CleanExiMM_SHARPIN.
    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: Q91WA6-1) [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

    MSPPAGGAAV AADPASPVVL LAVHAAVRPL GAGQDAEAQP RKLQLIADPE    50
    RPGRFRLGLL GTEPGAVSLE WPLEAICYTV RGPNQHELQP PPGGPGTFSV 100
    HFLDPEEAQQ WAALVRDATA EGQNGSGSPA PAPAPAMCPI SPPCSSMAQI 150
    PKATQPEVDL PQSSGNFKKE ELATRLSQAI AGGDEKAAAQ VAAVLAQHHV 200
    ALNVQLMEAW FPPGPIRLQV TVEDATSVLS SSSSAHVSLK IHPHCSIAAL 250
    QDQVFSEFGF PPAVQRWVIG RCLCMPERSL ASYGVSQDGD PAFLYLLSAP 300
    REVSGQSLQN SKMDRKLGLF PQSLGLPHDL QPSSSSLPSP SQPGWSCPSC 350
    TFINASNRPG CEMCSTQRPC AWDPLAAAST 380
    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

    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

    ArrayExpressi Q91WA6.
    Bgeei Q91WA6.
    CleanExi MM_SHARPIN.
    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

    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 1, 2014
    This is version 91 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