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 27-MAR-2024, entry version 173. 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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 EMDB; EMD-11054; -. DR SMR; Q9H0F6; -. DR BioGRID; 123608; 185. DR ComplexPortal; CPX-1877; LUBAC ubiquitin ligase complex. DR CORUM; Q9H0F6; -. DR DIP; DIP-57842N; -. DR IntAct; Q9H0F6; 69. 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; 9606-ENSP00000381698; -. DR PeptideAtlas; Q9H0F6; -. DR ProteomicsDB; 80272; -. [Q9H0F6-1] DR ProteomicsDB; 80273; -. [Q9H0F6-2] DR Pumba; Q9H0F6; -. DR Antibodypedia; 7700; 309 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 AGR; HGNC:25321; -. 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; CIQQEKG; -. DR OrthoDB; 2903477at2759; -. DR PhylomeDB; Q9H0F6; -. DR TreeFam; TF323486; -. DR PathwayCommons; Q9H0F6; -. DR Reactome; R-HSA-5357786; TNFR1-induced proapoptotic signaling. DR Reactome; R-HSA-5357905; Regulation of TNFR1 signaling. DR Reactome; R-HSA-5357956; TNFR1-induced NF-kappa-B signaling pathway. DR Reactome; R-HSA-6794361; Neurexins and neuroligins. DR SignaLink; Q9H0F6; -. DR UniPathway; UPA00143; -. DR BioGRID-ORCS; 81858; 19 hits in 1159 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 174 other cell types or tissues. DR ExpressionAtlas; Q9H0F6; baseline and differential. 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:0045202; C:synapse; IEA:UniProtKB-SubCell. 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:0030674; F:protein-macromolecule adaptor activity; 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: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 canonical NF-kappaB signal transduction; 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 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. DR Genevisible; Q9H0F6; HS. 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 FT S-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 FT S-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 FT S-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 FT S-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 //