ID   SHRPN_RAT               Reviewed;         381 AA.
AC   Q9EQL9;
DT   20-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2001, sequence version 1.
DT   27-MAR-2024, entry version 141.
DE   RecName: Full=Sharpin;
DE   AltName: Full=Shank-associated RH domain-interacting protein;
GN   Name=Sharpin;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], SUBUNIT, INTERACTION WITH SHANK1, SUBCELLULAR
RP   LOCATION, AND TISSUE SPECIFICITY.
RC   STRAIN=Sprague-Dawley; TISSUE=Brain;
RX   PubMed=11178875; DOI=10.1006/mcne.2000.0940;
RA   Lim S., Sala C., Yoon J., Park S., Kuroda S., Sheng M., Kim E.;
RT   "Sharpin, a novel postsynaptic density protein that directly interacts with
RT   the shank family of proteins.";
RL   Mol. Cell. Neurosci. 17:385-397(2001).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Heart;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [3]
RP   INTERACTION WITH SHANK3.
RX   PubMed=23897824; DOI=10.1074/jbc.m112.424747;
RA   Mameza M.G., Dvoretskova E., Bamann M., Hoenck H.H., Gueler T.,
RA   Boeckers T.M., Schoen M., Verpelli C., Sala C., Barsukov I., Dityatev A.,
RA   Kreienkamp H.J.;
RT   "SHANK3 gene mutations associated with autism facilitate ligand binding to
RT   the Shank3 ankyrin repeat region.";
RL   J. Biol. Chem. 288:26697-26708(2013).
CC   -!- FUNCTION: Component of the LUBAC complex which conjugates linear
CC       polyubiquitin chains in a head-to-tail manner to substrates and plays a
CC       key role in NF-kappa-B activation and regulation of inflammation. LUBAC
CC       conjugates linear polyubiquitin to IKBKG and RIPK1 and is involved in
CC       activation of the canonical NF-kappa-B and the JNK signaling pathways.
CC       Linear ubiquitination mediated by the LUBAC complex interferes with
CC       TNF-induced cell death and thereby prevents inflammation. LUBAC is
CC       recruited to the TNF-R1 signaling complex (TNF-RSC) following
CC       polyubiquitination of TNF-RSC components by BIRC2 and/or BIRC3 and to
CC       conjugate linear polyubiquitin to IKBKG and possibly other components
CC       contributing to the stability of the complex. The LUBAC complex is also
CC       involved in innate immunity by conjugating linear polyubiquitin chains
CC       at the surface of bacteria invading the cytosol to form the ubiquitin
CC       coat surrounding bacteria. LUBAC is not able to initiate formation of
CC       the bacterial ubiquitin coat, and can only promote formation of linear
CC       polyubiquitins on pre-existing ubiquitin. The bacterial ubiquitin coat
CC       acts as an 'eat-me' signal for xenophagy and promotes NF-kappa-B
CC       activation. Together with OTULIN, the LUBAC complex regulates the
CC       canonical Wnt signaling during angiogenesis.
CC       {ECO:0000250|UniProtKB:Q9H0F6}.
CC   -!- PATHWAY: Protein modification; protein ubiquitination.
CC       {ECO:0000250|UniProtKB:Q9H0F6}.
CC   -!- SUBUNIT: Monomer and homodimer (PubMed:11178875). Component of the
CC       LUBAC complex (linear ubiquitin chain assembly complex) which consists
CC       of SHARPIN, RBCK1 and RNF31 (By similarity). LUBAC has a MW of
CC       approximately 600 kDa suggesting a heteromultimeric assembly of its
CC       subunits (By similarity). Associates with the TNF-R1 signaling complex
CC       (TNF-RSC) in a stimulation-dependent manner (By similarity). Interacts
CC       with EYA1, EYA2, SHANK1 and SHANK3 (via ANK repeats) (PubMed:11178875,
CC       PubMed:23897824). {ECO:0000250|UniProtKB:Q9H0F6,
CC       ECO:0000269|PubMed:11178875, ECO:0000269|PubMed:23897824}.
CC   -!- INTERACTION:
CC       Q9EQL9; Q9WV48: Shank1; NbExp=7; IntAct=EBI-1394695, EBI-80909;
CC       Q9EQL9; Q9EQL9: Sharpin; NbExp=2; IntAct=EBI-1394695, EBI-1394695;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11178875}. Synapse
CC       {ECO:0000269|PubMed:11178875}. Note=Enriched at synaptic sites in
CC       mature neurons where it colocalizes with SHANK1.
CC       {ECO:0000269|PubMed:11178875}.
CC   -!- TISSUE SPECIFICITY: Expressed in brain, spleen, lung, heart, skeletal
CC       muscle, kidney and testis (at protein level). Expressed in heart and
CC       testis. {ECO:0000269|PubMed:11178875}.
CC   -!- DOMAIN: The Ubiquitin-like domain is required for the interaction with
CC       RNF31. {ECO:0000250}.
CC   -!- DOMAIN: The RanBP2-type zinc fingers mediate the specific interaction
CC       with ubiquitin. Binds preferentially linear polyubiquitin chains and
CC       'Lys-63'-linked polyubiquitin chains over 'Lys-48'-linked polyubiquitin
CC       chains. Also binds monoubiquitin (By similarity). {ECO:0000250}.
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DR   EMBL; AF203906; AAG43482.1; -; mRNA.
DR   EMBL; BC083553; AAH83553.1; -; mRNA.
DR   RefSeq; NP_112415.1; NM_031153.2.
DR   AlphaFoldDB; Q9EQL9; -.
DR   SMR; Q9EQL9; -.
DR   BioGRID; 249689; 3.
DR   CORUM; Q9EQL9; -.
DR   IntAct; Q9EQL9; 5.
DR   STRING; 10116.ENSRNOP00000018032; -.
DR   PhosphoSitePlus; Q9EQL9; -.
DR   jPOST; Q9EQL9; -.
DR   PaxDb; 10116-ENSRNOP00000018032; -.
DR   Ensembl; ENSRNOT00000018031.5; ENSRNOP00000018032.3; ENSRNOG00000012812.5.
DR   Ensembl; ENSRNOT00055045068; ENSRNOP00055036965; ENSRNOG00055026109.
DR   Ensembl; ENSRNOT00060042396; ENSRNOP00060035131; ENSRNOG00060024484.
DR   Ensembl; ENSRNOT00065002204; ENSRNOP00065001547; ENSRNOG00065001639.
DR   Ensembl; ENSRNOT00065015871; ENSRNOP00065011999; ENSRNOG00065009872.
DR   GeneID; 81859; -.
DR   KEGG; rno:81859; -.
DR   UCSC; RGD:631353; rat.
DR   AGR; RGD:631353; -.
DR   CTD; 81858; -.
DR   RGD; 631353; Sharpin.
DR   eggNOG; KOG1815; Eukaryota.
DR   GeneTree; ENSGT00940000161574; -.
DR   HOGENOM; CLU_014998_0_1_1; -.
DR   InParanoid; Q9EQL9; -.
DR   OMA; SCTFINV; -.
DR   OrthoDB; 2903477at2759; -.
DR   PhylomeDB; Q9EQL9; -.
DR   TreeFam; TF323486; -.
DR   Reactome; R-RNO-5357786; TNFR1-induced proapoptotic signaling.
DR   Reactome; R-RNO-5357905; Regulation of TNFR1 signaling.
DR   Reactome; R-RNO-5357956; TNFR1-induced NF-kappa-B signaling pathway.
DR   UniPathway; UPA00143; -.
DR   PRO; PR:Q9EQL9; -.
DR   Proteomes; UP000002494; Chromosome 7.
DR   Bgee; ENSRNOG00000012812; Expressed in testis and 20 other cell types or tissues.
DR   GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR   GO; GO:0030425; C:dendrite; IDA:RGD.
DR   GO; GO:0071797; C:LUBAC complex; ISS:UniProtKB.
DR   GO; GO:0045202; C:synapse; IEA:UniProtKB-SubCell.
DR   GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0031593; F:polyubiquitin modification-dependent protein binding; ISS:UniProtKB.
DR   GO; GO:0044877; F:protein-containing complex binding; IPI:RGD.
DR   GO; GO:0030674; F:protein-macromolecule adaptor activity; ISO:RGD.
DR   GO; GO:0043130; F:ubiquitin binding; IBA:GO_Central.
DR   GO; GO:0004842; F:ubiquitin-protein transferase activity; IBA:GO_Central.
DR   GO; GO:0030262; P:apoptotic nuclear changes; ISO:RGD.
DR   GO; GO:0042742; P:defense response to bacterium; ISS:UniProtKB.
DR   GO; GO:0008544; P:epidermis development; ISO:RGD.
DR   GO; GO:0031424; P:keratinization; ISO:RGD.
DR   GO; GO:0007005; P:mitochondrion organization; ISO:RGD.
DR   GO; GO:0050728; P:negative regulation of inflammatory response; ISS:UniProtKB.
DR   GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; ISS:UniProtKB.
DR   GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR   GO; GO:0097039; P:protein linear polyubiquitination; ISS:UniProtKB.
DR   GO; GO:2000348; P:regulation of CD40 signaling pathway; ISS:UniProtKB.
DR   GO; GO:0010803; P:regulation of tumor necrosis factor-mediated signaling pathway; ISS:UniProtKB.
DR   CDD; cd01799; Ubl_HOIL1; 1.
DR   Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1.
DR   Gene3D; 2.30.30.380; Zn-finger domain of Sec23/24; 1.
DR   InterPro; IPR011993; PH-like_dom_sf.
DR   InterPro; IPR031912; Sharpin_PH.
DR   InterPro; IPR029071; Ubiquitin-like_domsf.
DR   InterPro; IPR001876; Znf_RanBP2.
DR   InterPro; IPR036443; Znf_RanBP2_sf.
DR   PANTHER; PTHR22770:SF43; SHARPIN; 1.
DR   PANTHER; PTHR22770; UBIQUITIN CONJUGATING ENZYME 7 INTERACTING PROTEIN-RELATED; 1.
DR   Pfam; PF16764; Sharpin_PH; 1.
DR   SMART; SM00547; ZnF_RBZ; 1.
DR   SUPFAM; SSF90209; Ran binding protein zinc finger-like; 1.
DR   SUPFAM; SSF54236; Ubiquitin-like; 1.
DR   PROSITE; PS01358; ZF_RANBP2_1; 1.
DR   PROSITE; PS50199; ZF_RANBP2_2; 1.
DR   Genevisible; Q9EQL9; RN.
PE   1: Evidence at protein level;
KW   Cytoplasm; Metal-binding; Phosphoprotein; Reference proteome; Synapse;
KW   Ubl conjugation pathway; Zinc; Zinc-finger.
FT   CHAIN           1..381
FT                   /note="Sharpin"
FT                   /id="PRO_0000280636"
FT   DOMAIN          216..285
FT                   /note="Ubiquitin-like"
FT   ZN_FING         342..371
FT                   /note="RanBP2-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00322"
FT   REGION          1..177
FT                   /note="Self-association"
FT                   /evidence="ECO:0000269|PubMed:11178875"
FT   REGION          121..153
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          172..305
FT                   /note="Interaction with SHANK1"
FT                   /evidence="ECO:0000269|PubMed:11178875"
FT   MOD_RES         307
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9H0F6"
SQ   SEQUENCE   381 AA;  40287 MW;  8D9A7D7D23665567 CRC64;
     MSPPAGGAAA AADPASPVVL LAVQAAVRLL GAGHEDEAQL RKLQLKADPE RPGRFRLGLL
     GIEPGAVSLE WPLESICYTI RGPNQHELQP PPGGPGTFSV HFLNSEEAQQ WAALVRDATA
     EGQNGNDSTA PVPTPAMCPT SPPCSSVTPT PKATQPEMDL PQGSGNLKKE ELATHLAQAI
     AGGDEKAAAQ VAAILAQHHV ALNVQLLEAW FPRGPIRLQV TVEDATSVLS SSSSAHVSLQ
     IHPHCSIAAL QEQVFSEFGF PPAVQRWVIG RCLCMPERSL ASYGVSQDGD PAFLYLLSAP
     REVSGHSPQH SKMDRKLGCL FPQSLELPHN LQASSSSLPS PPQPGWSCPS CTFINASNRP
     GCEMCSTQRP CAWDPLTATS T
//