SHRPN_HUMAN
ID SHRPN_HUMAN Reviewed; 387 AA.
AC Q9H0F6; A6NEG3; C0L3L2; D3DWL3; Q8IXF5; Q8IXF6; Q8N2E7; Q8TB25; Q9BUE4;
DT 20-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Sharpin {ECO:0000303|PubMed:20179993};
DE AltName: Full=Shank-associated RH domain-interacting protein;
DE AltName: Full=Shank-interacting protein-like 1;
DE Short=hSIPL1;
GN Name=SHARPIN {ECO:0000303|PubMed:20179993}; Synonyms=SIPL1;
GN ORFNames=PSEC0216;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX PubMed=12753155; DOI=10.1046/j.1440-1746.2003.03046.x;
RA Daigo Y., Takayama I., Ward S.M., Sanders K.M., Fujino M.A.;
RT "Novel human and mouse genes encoding a shank-interacting protein and its
RT upregulation in gastric fundus of W/WV mouse.";
RL J. Gastroenterol. Hepatol. 18:712-718(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=20179993; DOI=10.1007/s11010-010-0413-x;
RA Jung J., Kim J.M., Park B., Cheon Y., Lee B., Choo S.H., Koh S.S.,
RA Lee S.J.;
RT "Newly identified tumor-associated role of human Sharpin.";
RL Mol. Cell. Biochem. 340:161-167(2010).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Testis;
RX PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and analysis of
RT 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Embryo;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M.,
RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B.,
RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA Platzer M., Shimizu N., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Pancreas, Prostate, and Uterus;
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 [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-165, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-312, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE LUBAC COMPLEX,
RP FUNCTION, DOMAIN RANBP2-TYPE, DOMAIN UBIQUITIN-LIKE, UBIQUITIN-BINDING, AND
RP MUTAGENESIS OF CYS-354; CYS-357; CYS-368 AND CYS-371.
RX PubMed=21455173; DOI=10.1038/nature09816;
RA Gerlach B., Cordier S.M., Schmukle A.C., Emmerich C.H., Rieser E.,
RA Haas T.L., Webb A.I., Rickard J.A., Anderton H., Wong W.W., Nachbur U.,
RA Gangoda L., Warnken U., Purcell A.W., Silke J., Walczak H.;
RT "Linear ubiquitination prevents inflammation and regulates immune
RT signalling.";
RL Nature 471:591-596(2011).
RN [11]
RP IDENTIFICATION IN THE LUBAC COMPLEX, FUNCTION, AND DOMAIN UBIQUITIN-LIKE.
RX PubMed=21455180; DOI=10.1038/nature09815;
RA Tokunaga F., Nakagawa T., Nakahara M., Saeki Y., Taniguchi M., Sakata S.,
RA Tanaka K., Nakano H., Iwai K.;
RT "SHARPIN is a component of the NF-kappaB-activating linear ubiquitin chain
RT assembly complex.";
RL Nature 471:633-636(2011).
RN [12]
RP IDENTIFICATION IN THE LUBAC COMPLEX, FUNCTION, DOMAIN RANBP2-TYPE, DOMAIN
RP UBIQUITIN-LIKE, UBIQUITIN-BINDING, AND MUTAGENESIS OF ILE-272 AND
RP 358-THR-PHE-359.
RX PubMed=21455181; DOI=10.1038/nature09814;
RA Ikeda F., Deribe Y.L., Skanland S.S., Stieglitz B., Grabbe C.,
RA Franz-Wachtel M., van Wijk S.J., Goswami P., Nagy V., Terzic J.,
RA Tokunaga F., Androulidaki A., Nakagawa T., Pasparakis M., Iwai K.,
RA Sundberg J.P., Schaefer L., Rittinger K., Macek B., Dikic I.;
RT "SHARPIN forms a linear ubiquitin ligase complex regulating NF-kappaB
RT activity and apoptosis.";
RL Nature 471:637-641(2011).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-165 AND SER-312, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1-127, MUTAGENESIS OF VAL-114, AND
RP SUBUNIT.
RX PubMed=22549881; DOI=10.1074/jbc.m112.359547;
RA Stieglitz B., Haire L.F., Dikic I., Rittinger K.;
RT "Structural analysis of SHARPIN, a subunit of a large multi-protein E3
RT ubiquitin ligase, reveals a novel dimerization function for the pleckstrin
RT homology superfold.";
RL J. Biol. Chem. 287:20823-20829(2012).
RN [15]
RP FUNCTION.
RX PubMed=23708998; DOI=10.1038/nature12296;
RA Rivkin E., Almeida S.M., Ceccarelli D.F., Juang Y.C., Maclean T.A.,
RA Srikumar T., Huang H., Dunham W.H., Fukumura R., Xie G., Gondo Y.,
RA Raught B., Gingras A.C., Sicheri F., Cordes S.P.;
RT "The linear ubiquitin-specific deubiquitinase gumby regulates
RT angiogenesis.";
RL Nature 498:318-324(2013).
RN [16]
RP FUNCTION, IDENTIFICATION IN THE LUBAC COMPLEX, AND PATHWAY.
RX PubMed=28481331; DOI=10.1038/nmicrobiol.2017.63;
RA Noad J., von der Malsburg A., Pathe C., Michel M.A., Komander D.,
RA Randow F.;
RT "LUBAC-synthesized linear ubiquitin chains restrict cytosol-invading
RT bacteria by activating autophagy and NF-kappaB.";
RL Nat. Microbiol. 2:17063-17063(2017).
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
CC (PubMed:21455173, PubMed:21455180, PubMed:21455181). LUBAC conjugates
CC linear polyubiquitin to IKBKG and RIPK1 and is involved in activation
CC of the canonical NF-kappa-B and the JNK signaling pathways
CC (PubMed:21455173, PubMed:21455180, PubMed:21455181). Linear
CC ubiquitination mediated by the LUBAC complex interferes with TNF-
CC induced cell death and thereby prevents inflammation (PubMed:21455173,
CC PubMed:21455180, PubMed:21455181). LUBAC is recruited to the TNF-R1
CC signaling complex (TNF-RSC) following polyubiquitination of TNF-RSC
CC components by BIRC2 and/or BIRC3 and to conjugate linear polyubiquitin
CC to IKBKG and possibly other components contributing to the stability of
CC the complex (PubMed:21455173, PubMed:21455180, PubMed:21455181). The
CC LUBAC complex is also involved in innate immunity by conjugating linear
CC polyubiquitin chains at the surface of bacteria invading the cytosol to
CC form the ubiquitin coat surrounding bacteria (PubMed:28481331). LUBAC
CC is not able to initiate formation of the bacterial ubiquitin coat, and
CC can only promote formation of linear polyubiquitins on pre-existing
CC ubiquitin (PubMed:28481331). The bacterial ubiquitin coat acts as an
CC 'eat-me' signal for xenophagy and promotes NF-kappa-B activation
CC (PubMed:28481331). Together with OTULIN, the LUBAC complex regulates
CC the canonical Wnt signaling during angiogenesis (PubMed:23708998).
CC {ECO:0000269|PubMed:21455173, ECO:0000269|PubMed:21455180,
CC ECO:0000269|PubMed:21455181, ECO:0000269|PubMed:23708998,
CC ECO:0000269|PubMed:28481331}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:28481331}.
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 (PubMed:21455173, PubMed:21455180,
CC PubMed:21455181, PubMed:22549881, PubMed:28481331). LUBAC has a MW of
CC approximately 600 kDa suggesting a heteromultimeric assembly of its
CC subunits (PubMed:21455173, PubMed:21455180, PubMed:21455181,
CC PubMed:22549881). Associates with the TNF-R1 signaling complex (TNF-
CC RSC) in a stimulation-dependent manner (PubMed:21455173,
CC PubMed:21455180, PubMed:21455181, PubMed:22549881). Interacts with
CC EYA1, EYA2, SHANK1 and SHANK3 (via ANK repeats) (By similarity).
CC {ECO:0000250|UniProtKB:Q9EQL9, ECO:0000269|PubMed:21455173,
CC ECO:0000269|PubMed:21455180, ECO:0000269|PubMed:21455181,
CC ECO:0000269|PubMed:22549881, ECO:0000269|PubMed:28481331}.
CC -!- INTERACTION:
CC Q9H0F6; Q9Y6K9: IKBKG; NbExp=14; IntAct=EBI-3942966, EBI-81279;
CC Q9H0F6; P17301: ITGA2; NbExp=5; IntAct=EBI-3942966, EBI-702960;
CC Q9H0F6; P08648: ITGA5; NbExp=4; IntAct=EBI-3942966, EBI-1382311;
CC Q9H0F6; Q9UDY8: MALT1; NbExp=2; IntAct=EBI-3942966, EBI-1047372;
CC Q9H0F6; Q9BYM8: RBCK1; NbExp=26; IntAct=EBI-3942966, EBI-2340624;
CC Q9H0F6; Q96EP0: RNF31; NbExp=32; IntAct=EBI-3942966, EBI-948111;
CC Q9H0F6-2; Q3LI66: KRTAP6-2; NbExp=3; IntAct=EBI-9843813, EBI-11962084;
CC Q9H0F6-2; Q8IUC3: KRTAP7-1; NbExp=3; IntAct=EBI-9843813, EBI-18394498;
CC Q9H0F6-2; Q15645: TRIP13; NbExp=3; IntAct=EBI-9843813, EBI-358993;
CC Q9H0F6-2; Q70EL1-9: USP54; NbExp=3; IntAct=EBI-9843813, EBI-11975223;
CC Q9H0F6-2; A0A0C4DGF1: ZBTB32; NbExp=3; IntAct=EBI-9843813, EBI-10188476;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:20179993}.
CC Synapse {ECO:0000250|UniProtKB:Q9EQL9}. Note=Enriched at synaptic sites
CC in mature neurons where it colocalizes with SHANK1.
CC {ECO:0000250|UniProtKB:Q9EQL9}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9H0F6-1; Sequence=Displayed;
CC Name=2; Synonyms=hSIPL1A;
CC IsoId=Q9H0F6-2; Sequence=VSP_023837, VSP_023838;
CC -!- TISSUE SPECIFICITY: Highly expressed in skeletal muscle and placenta
CC and at lower levels in brain, heart, colon without mucosa, thymus,
CC spleen, kidney, liver, small intestine, lung and peripheral blood
CC leukocytes. Up-regulated in various tumor tissues such as kidney,
CC liver, ovary and pancreas tumors. {ECO:0000269|PubMed:20179993}.
CC -!- DOMAIN: The Ubiquitin-like domain is required for the interaction with
CC RNF31. {ECO:0000269|PubMed:21455181}.
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:0000269|PubMed:21455181}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC11666.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAC53797.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAC53798.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing.; Evidence={ECO:0000305};
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DR EMBL; AB052764; BAC53797.1; ALT_FRAME; mRNA.
DR EMBL; AB052765; BAC53798.1; ALT_SEQ; mRNA.
DR EMBL; FJ655995; ACN38058.1; -; mRNA.
DR EMBL; AL136816; CAB66750.1; -; mRNA.
DR EMBL; AK075518; BAC11666.1; ALT_FRAME; mRNA.
DR EMBL; AC104592; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471162; EAW82152.1; -; Genomic_DNA.
DR EMBL; CH471162; EAW82153.1; -; Genomic_DNA.
DR EMBL; CH471162; EAW82150.1; -; Genomic_DNA.
DR EMBL; CH471162; EAW82151.1; -; Genomic_DNA.
DR EMBL; BC002688; AAH02688.2; -; mRNA.
DR EMBL; BC025244; AAH25244.1; -; mRNA.
DR EMBL; BC034028; AAH34028.1; -; mRNA.
DR CCDS; CCDS43777.1; -. [Q9H0F6-1]
DR RefSeq; NP_112236.3; NM_030974.3. [Q9H0F6-1]
DR RefSeq; XP_016869377.1; XM_017013888.1. [Q9H0F6-2]
DR PDB; 4EMO; X-ray; 2.00 A; A/B/C/D=1-127.
DR PDB; 5X0W; X-ray; 3.00 A; B/D/F/H=206-309.
DR PDBsum; 4EMO; -.
DR PDBsum; 5X0W; -.
DR AlphaFoldDB; Q9H0F6; -.
DR SMR; Q9H0F6; -.
DR BioGRID; 123608; 177.
DR ComplexPortal; CPX-1877; LUBAC ubiquitin ligase complex.
DR CORUM; Q9H0F6; -.
DR DIP; DIP-57842N; -.
DR IntAct; Q9H0F6; 68.
DR MINT; Q9H0F6; -.
DR STRING; 9606.ENSP00000381698; -.
DR BindingDB; Q9H0F6; -.
DR ChEMBL; CHEMBL4296109; -.
DR iPTMnet; Q9H0F6; -.
DR PhosphoSitePlus; Q9H0F6; -.
DR BioMuta; SHARPIN; -.
DR DMDM; 74733523; -.
DR EPD; Q9H0F6; -.
DR jPOST; Q9H0F6; -.
DR MassIVE; Q9H0F6; -.
DR MaxQB; Q9H0F6; -.
DR PaxDb; Q9H0F6; -.
DR PeptideAtlas; Q9H0F6; -.
DR PRIDE; Q9H0F6; -.
DR ProteomicsDB; 80272; -. [Q9H0F6-1]
DR ProteomicsDB; 80273; -. [Q9H0F6-2]
DR Antibodypedia; 7700; 272 antibodies from 30 providers.
DR DNASU; 81858; -.
DR Ensembl; ENST00000359551.6; ENSP00000352551.6; ENSG00000179526.17. [Q9H0F6-2]
DR Ensembl; ENST00000398712.7; ENSP00000381698.2; ENSG00000179526.17. [Q9H0F6-1]
DR GeneID; 81858; -.
DR KEGG; hsa:81858; -.
DR MANE-Select; ENST00000398712.7; ENSP00000381698.2; NM_030974.4; NP_112236.3.
DR UCSC; uc003zba.4; human. [Q9H0F6-1]
DR CTD; 81858; -.
DR DisGeNET; 81858; -.
DR GeneCards; SHARPIN; -.
DR HGNC; HGNC:25321; SHARPIN.
DR HPA; ENSG00000179526; Low tissue specificity.
DR MIM; 611885; gene.
DR neXtProt; NX_Q9H0F6; -.
DR OpenTargets; ENSG00000179526; -.
DR PharmGKB; PA142670925; -.
DR VEuPathDB; HostDB:ENSG00000179526; -.
DR eggNOG; KOG1815; Eukaryota.
DR GeneTree; ENSGT00940000161574; -.
DR HOGENOM; CLU_014998_0_1_1; -.
DR InParanoid; Q9H0F6; -.
DR OMA; TQQTEWA; -.
DR PhylomeDB; Q9H0F6; -.
DR TreeFam; TF323486; -.
DR PathwayCommons; Q9H0F6; -.
DR Reactome; R-HSA-5357905; Regulation of TNFR1 signaling.
DR Reactome; R-HSA-5357956; TNFR1-induced NFkappaB signaling pathway.
DR Reactome; R-HSA-6794361; Neurexins and neuroligins.
DR SignaLink; Q9H0F6; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 81858; 16 hits in 1080 CRISPR screens.
DR ChiTaRS; SHARPIN; human.
DR GenomeRNAi; 81858; -.
DR Pharos; Q9H0F6; Tbio.
DR PRO; PR:Q9H0F6; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q9H0F6; protein.
DR Bgee; ENSG00000179526; Expressed in right testis and 172 other tissues.
DR ExpressionAtlas; Q9H0F6; baseline and differential.
DR Genevisible; Q9H0F6; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0030425; C:dendrite; IEA:Ensembl.
DR GO; GO:0071797; C:LUBAC complex; IDA:UniProtKB.
DR GO; GO:0014069; C:postsynaptic density; IEA:Ensembl.
DR GO; GO:0000151; C:ubiquitin ligase complex; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0031593; F:polyubiquitin modification-dependent protein binding; IDA:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
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; IEA:Ensembl.
DR GO; GO:0007420; P:brain development; IEA:Ensembl.
DR GO; GO:0042742; P:defense response to bacterium; IDA:UniProtKB.
DR GO; GO:0031424; P:keratinization; IEA:Ensembl.
DR GO; GO:0007005; P:mitochondrion organization; IEA:Ensembl.
DR GO; GO:0050728; P:negative regulation of inflammatory response; ISS:UniProtKB.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IDA:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR GO; GO:0097039; P:protein linear polyubiquitination; IDA:UniProtKB.
DR GO; GO:2000348; P:regulation of CD40 signaling pathway; IDA:UniProtKB.
DR GO; GO:0010803; P:regulation of tumor necrosis factor-mediated signaling pathway; IDA:UniProtKB.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR026261; RBCK1/SHARPIN.
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; PTHR22770:SF43; 1.
DR Pfam; PF16764; Sharpin_PH; 1.
DR SMART; SM00547; ZnF_RBZ; 1.
DR SUPFAM; SSF54236; SSF54236; 1.
DR SUPFAM; SSF90209; SSF90209; 1.
DR PROSITE; PS01358; ZF_RANBP2_1; 1.
DR PROSITE; PS50199; ZF_RANBP2_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytoplasm; Metal-binding;
KW Phosphoprotein; Reference proteome; Synapse; Ubl conjugation pathway; Zinc;
KW Zinc-finger.
FT CHAIN 1..387
FT /note="Sharpin"
FT /id="PRO_0000280634"
FT DOMAIN 219..288
FT /note="Ubiquitin-like"
FT ZN_FING 348..377
FT /note="RanBP2-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00322"
FT REGION 1..180
FT /note="Self-association"
FT /evidence="ECO:0000250|UniProtKB:Q9EQL9"
FT REGION 122..169
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 175..310
FT /note="Interaction with SHANK1"
FT /evidence="ECO:0000250|UniProtKB:Q9EQL9"
FT REGION 305..349
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 138..163
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 330..344
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 165
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 312
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT VAR_SEQ 309..326
FT /note="TGPSPQHPQKMDGELGRL -> QLVLSFLHLHQCPRPPWL (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:12753155,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_023837"
FT VAR_SEQ 327..387
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12753155,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_023838"
FT VARIANT 282
FT /note="S -> T (in dbSNP:rs11541804)"
FT /id="VAR_047799"
FT VARIANT 294
FT /note="P -> S (in dbSNP:rs34674752)"
FT /id="VAR_047800"
FT VARIANT 311
FT /note="P -> R (in dbSNP:rs35844464)"
FT /id="VAR_047801"
FT MUTAGEN 114
FT /note="V->D: Abolishes homodimerization."
FT /evidence="ECO:0000269|PubMed:22549881"
FT MUTAGEN 272
FT /note="I->A: Abolishes interaction with RNF31 and ability
FT to mediate linear polyubiquitination."
FT /evidence="ECO:0000269|PubMed:21455181"
FT MUTAGEN 354
FT /note="C->S: Abolishes binding to ubiquitin without
FT affecting interaction with RNF31; when associated with S-
FT 357."
FT /evidence="ECO:0000269|PubMed:21455173"
FT MUTAGEN 357
FT /note="C->S: Abolishes binding to ubiquitin without
FT affecting interaction with RNF31; when associated with S-
FT 354."
FT /evidence="ECO:0000269|PubMed:21455173"
FT MUTAGEN 358..359
FT /note="TF->LV: Abolishes binding to ubiquitin and ability
FT to mediate linear polyubiquitination."
FT /evidence="ECO:0000269|PubMed:21455181"
FT MUTAGEN 368
FT /note="C->S: Abolishes binding to ubiquitin without
FT affecting interaction with RNF31; when associated with S-
FT 371."
FT /evidence="ECO:0000269|PubMed:21455173"
FT MUTAGEN 371
FT /note="C->S: Abolishes binding to ubiquitin without
FT affecting interaction with RNF31; when associated with S-
FT 368."
FT /evidence="ECO:0000269|PubMed:21455173"
FT CONFLICT 238
FT /note="A -> P (in Ref. 6; AAH02688)"
FT /evidence="ECO:0000305"
FT CONFLICT 243
FT /note="Q -> R (in Ref. 3; BAC11666)"
FT /evidence="ECO:0000305"
FT CONFLICT 257
FT /note="V -> A (in Ref. 6; AAH02688)"
FT /evidence="ECO:0000305"
FT TURN 3..5
FT /evidence="ECO:0007829|PDB:4EMO"
FT STRAND 7..11
FT /evidence="ECO:0007829|PDB:4EMO"
FT HELIX 12..15
FT /evidence="ECO:0007829|PDB:4EMO"
FT STRAND 20..30
FT /evidence="ECO:0007829|PDB:4EMO"
FT HELIX 31..33
FT /evidence="ECO:0007829|PDB:4EMO"
FT STRAND 40..48
FT /evidence="ECO:0007829|PDB:4EMO"
FT STRAND 56..60
FT /evidence="ECO:0007829|PDB:4EMO"
FT STRAND 70..73
FT /evidence="ECO:0007829|PDB:4EMO"
FT HELIX 74..76
FT /evidence="ECO:0007829|PDB:4EMO"
FT STRAND 77..83
FT /evidence="ECO:0007829|PDB:4EMO"
FT STRAND 86..90
FT /evidence="ECO:0007829|PDB:4EMO"
FT STRAND 99..105
FT /evidence="ECO:0007829|PDB:4EMO"
FT HELIX 106..119
FT /evidence="ECO:0007829|PDB:4EMO"
FT STRAND 219..226
FT /evidence="ECO:0007829|PDB:5X0W"
FT STRAND 239..244
FT /evidence="ECO:0007829|PDB:5X0W"
FT HELIX 250..261
FT /evidence="ECO:0007829|PDB:5X0W"
FT HELIX 265..267
FT /evidence="ECO:0007829|PDB:5X0W"
FT STRAND 268..271
FT /evidence="ECO:0007829|PDB:5X0W"
FT HELIX 283..285
FT /evidence="ECO:0007829|PDB:5X0W"
FT STRAND 293..299
FT /evidence="ECO:0007829|PDB:5X0W"
SQ SEQUENCE 387 AA; 39949 MW; 33EE4BF66936AB60 CRC64;
MAPPAGGAAA AASDLGSAAV LLAVHAAVRP LGAGPDAEAQ LRRLQLSADP ERPGRFRLEL
LGAGPGAVNL EWPLESVSYT IRGPTQHELQ PPPGGPGTLS LHFLNPQEAQ RWAVLVRGAT
VEGQNGSKSN SPPALGPEAC PVSLPSPPEA STLKGPPPEA DLPRSPGNLT EREELAGSLA
RAIAGGDEKG AAQVAAVLAQ HRVALSVQLQ EACFPPGPIR LQVTLEDAAS AASAASSAHV
ALQVHPHCTV AALQEQVFSE LGFPPAVQRW VIGRCLCVPE RSLASYGVRQ DGDPAFLYLL
SAPREAPATG PSPQHPQKMD GELGRLFPPS LGLPPGPQPA ASSLPSPLQP SWSCPSCTFI
NAPDRPGCEM CSTQRPCTWD PLAAAST
