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Q9EQL9

- SHRPN_RAT

UniProt

Q9EQL9 - SHRPN_RAT

Protein

Sharpin

Gene

Sharpin

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 82 (01 Oct 2014)
      Sequence version 1 (01 Mar 2001)
      Previous versions | rss
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    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 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

    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 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

    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

    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

    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: October 1, 2014
    This is version 82 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