ID SHRPN_BOVIN Reviewed; 409 AA.
AC E1BDF2;
DT 31-MAY-2011, integrated into UniProtKB/Swiss-Prot.
DT 02-NOV-2010, sequence version 1.
DT 24-JAN-2024, entry version 78.
DE RecName: Full=Sharpin;
DE AltName: Full=Shank-associated RH domain-interacting protein;
GN Name=SHARPIN;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=19390049; DOI=10.1126/science.1169588;
RG The bovine genome sequencing and analysis consortium;
RT "The genome sequence of taurine cattle: a window to ruminant biology and
RT evolution.";
RL Science 324:522-528(2009).
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 (By similarity). Component of the LUBAC
CC complex (linear ubiquitin chain assembly complex) which consists of
CC 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) (By similarity).
CC {ECO:0000250|UniProtKB:Q9EQL9, ECO:0000250|UniProtKB:Q9H0F6}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q9H0F6}. Synapse {ECO:0000250|UniProtKB:Q9EQL9}.
CC Note=Enriched at synaptic sites in mature neurons where it colocalizes
CC with SHANK1. {ECO:0000250|UniProtKB:Q9EQL9}.
CC -!- DOMAIN: The Ubiquitin-like domain is required for the interaction with
CC RNF31. {ECO:0000250|UniProtKB:Q9H0F6}.
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. {ECO:0000250|UniProtKB:Q9H0F6}.
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DR EMBL; AAFC03035445; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_001103236.1; NM_001109766.1.
DR AlphaFoldDB; E1BDF2; -.
DR SMR; E1BDF2; -.
DR STRING; 9913.ENSBTAP00000046530; -.
DR PaxDb; 9913-ENSBTAP00000046530; -.
DR Ensembl; ENSBTAT00000049670.3; ENSBTAP00000046530.2; ENSBTAG00000012235.5.
DR GeneID; 512499; -.
DR KEGG; bta:512499; -.
DR CTD; 81858; -.
DR VEuPathDB; HostDB:ENSBTAG00000012235; -.
DR VGNC; VGNC:34587; SHARPIN.
DR eggNOG; KOG1815; Eukaryota.
DR GeneTree; ENSGT00940000161574; -.
DR HOGENOM; CLU_014998_0_1_1; -.
DR InParanoid; E1BDF2; -.
DR OMA; CIQQEKG; -.
DR TreeFam; TF323486; -.
DR Reactome; R-BTA-5357786; TNFR1-induced proapoptotic signaling.
DR Reactome; R-BTA-5357905; Regulation of TNFR1 signaling.
DR Reactome; R-BTA-5357956; TNFR1-induced NF-kappa-B signaling pathway.
DR UniPathway; UPA00143; -.
DR Proteomes; UP000009136; Chromosome 14.
DR Bgee; ENSBTAG00000012235; Expressed in laryngeal cartilage and 107 other cell types or tissues.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0071797; C:LUBAC complex; ISS:UniProtKB.
DR GO; GO:0045202; C:synapse; IEA:UniProtKB-SubCell.
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:0043130; F:ubiquitin binding; IBA:GO_Central.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IBA:GO_Central.
DR GO; GO:0042742; P:defense response to bacterium; ISS:UniProtKB.
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; cd13305; PH_SHARPIN; 1.
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.
PE 3: Inferred from homology;
KW Cytoplasm; Metal-binding; Phosphoprotein; Reference proteome; Synapse;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..409
FT /note="Sharpin"
FT /id="PRO_0000409513"
FT DOMAIN 217..280
FT /note="Ubiquitin-like"
FT ZN_FING 338..367
FT /note="RanBP2-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00322"
FT REGION 1..178
FT /note="Self-association"
FT /evidence="ECO:0000250|UniProtKB:Q9EQL9"
FT REGION 121..164
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 173..300
FT /note="Interaction with SHANK1"
FT /evidence="ECO:0000250|UniProtKB:Q9EQL9"
FT REGION 315..337
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 384..409
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 135..158
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 322..337
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 163
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H0F6"
FT MOD_RES 302
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H0F6"
SQ SEQUENCE 409 AA; 43394 MW; 982E3C33A2D41D0D CRC64;
MAPPAGGTAA GSDPGSAAVL LAVHVAVRPL GAGLDVAAQP RRLQLSADPE RPGRFRLEML
GAGPGAVILE WPLESVSYTV RGPCQHELQP PPGGPGTLSL HFANPQEAQR WAALVRDATV
EGQNGSDSLP PALGPETRPV SPPSPLEVPT PKAPKPKVDL PWSPGDLMEK EELAGRLTRA
VEGGDEKGAA QAAAILAQRH VALRVQLQEA YFPPGPIRLQ VTVEDAASSA HVSLQVHPHC
TIRALQEQVF SEFGFPPAVQ RWVIGRCLCV PEHSLAFYGV QRDGDPAFLY LLSAPREAPG
RSPQRPQKVD GELGRLFPQS LGLPPTPQPT SSSLPSPLQP GWPCPSCTFI NAPSRPGCEM
CSTQRPCAWD PLPTASIQQL PKVTRREDGP SLPGPRSLDP LLNLSGNLC
//
