ID RN170_HUMAN Reviewed; 258 AA. AC Q96K19; D3DSY6; E9PIL4; Q7Z483; Q86YC0; Q8IXR7; Q8N2B5; Q8N5G9; Q8NG30; AC Q9H0V6; DT 20-MAR-2007, integrated into UniProtKB/Swiss-Prot. DT 20-MAR-2007, sequence version 2. DT 10-JUN-2026, entry version 168. DE RecName: Full=E3 ubiquitin-protein ligase RNF170; DE EC=2.3.2.27 {ECO:0000269|PubMed:31076723}; DE AltName: Full=Putative LAG1-interacting protein; DE AltName: Full=RING finger protein 170; DE AltName: Full=RING-type E3 ubiquitin transferase RNF170 {ECO:0000305}; GN Name=RNF170; 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 [LARGE SCALE MRNA] (ISOFORMS 1 AND 4). RC TISSUE=Amygdala, and Placenta; 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 [2] 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 [3] 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2; 3; 5 AND 6). RC TISSUE=Brain, Lung, Pancreas, and Placenta; 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-167 (ISOFORM 1). RC TISSUE=Brain; 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 [6] RP NUCLEOTIDE SEQUENCE [MRNA] OF 140-258 (ISOFORM 1). RC TISSUE=Fetal brain; RA Pan H., Xu Z.G., Huo K.K., Li Y.Y.; RT "Interactors of a human homolog of yeast LAG1 gene."; RL Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases. RN [7] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [8] RP FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY, AND INTERACTION WITH RP ERLIN1/ERLIN2 COMPLEX AND ITPR1. RX PubMed=21610068; DOI=10.1074/jbc.m111.251983; RA Lu J.P., Wang Y., Sliter D.A., Pearce M.M., Wojcikiewicz R.J.; RT "RNF170 protein, an endoplasmic reticulum membrane ubiquitin ligase, RT mediates inositol 1,4,5-trisphosphate receptor ubiquitination and RT degradation."; RL J. Biol. Chem. 286:24426-24433(2011). RN [9] RP INTERACTION WITH HUMAN CYTOMEGALOVIRUS PROTEIN NEC2/UL50 (MICROBIAL RP INFECTION). RX PubMed=29743376; DOI=10.1128/jvi.00462-18; RA Lee M.K., Kim Y.J., Kim Y.E., Han T.H., Milbradt J., Marschall M., RA Ahn J.H.; RT "Transmembrane Protein pUL50 of Human Cytomegalovirus Inhibits ISGylation RT by Downregulating UBE1L."; RL J. Virol. 92:0-0(2018). RN [10] RP FUNCTION, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF RP CYS-102 AND HIS-104. RX PubMed=31076723; DOI=10.1038/s41423-019-0236-y; RA Song X., Liu S., Wang W., Ma Z., Cao X., Jiang M.; RT "E3 ubiquitin ligase RNF170 inhibits innate immune responses by targeting RT and degrading TLR3 in murine cells."; RL Cell. Mol. Immunol. 17:865-874(2020). RN [11] RP VARIANT SNAX1 CYS-199, AND TISSUE SPECIFICITY. RX PubMed=21115467; DOI=10.1093/brain/awq329; RA Valdmanis P.N., Dupre N., Lachance M., Stochmanski S.J., Belzil V.V., RA Dion P.A., Thiffault I., Brais B., Weston L., Saint-Amant L., Samuels M.E., RA Rouleau G.A.; RT "A mutation in the RNF170 gene causes autosomal dominant sensory ataxia."; RL Brain 134:602-607(2011). RN [12] RP VARIANT SPG85 ARG-102, AND INVOLVEMENT IN SPG85. RX PubMed=31636353; DOI=10.1038/s41467-019-12620-9; RA Wagner M., Osborn D.P.S., Gehweiler I., Nagel M., Ulmer U., Bakhtiari S., RA Amouri R., Boostani R., Hentati F., Hockley M.M., Hoelbling B., RA Schwarzmayr T., Karimiani E.G., Kernstock C., Maroofian R., RA Mueller-Felber W., Ozkan E., Padilla-Lopez S., Reich S., Reichbauer J., RA Darvish H., Shahmohammadibeni N., Tafakhori A., Vill K., Zuchner S., RA Kruer M.C., Winkelmann J., Jamshidi Y., Schuele R.; RT "Bi-allelic variants in RNF170 are associated with hereditary spastic RT paraplegia."; RL Nat. Commun. 10:4790-4790(2019). RN [13] RP VARIANT SPG85 114-TYR--ARG-258 DEL, AND INVOLVEMENT IN SPG85. RX PubMed=33165979; DOI=10.1002/mds.28371; RA de Sainte Agathe J.M., Mercier S., Mahe J.Y., Pereon Y., Buratti J., RA Tissier L., Kol B., Said S.A., Leguern E., Banneau G., Stevanin G.; RT "RNF170-related hereditary spastic paraplegia: confirmation by a novel RT mutation."; RL Mov. Disord. 36:771-774(2021). RN [14] RP VARIANT SPG85 TRP-107. RX PubMed=35041108; DOI=10.1007/s10048-022-00685-6; RA Chouery E., Mehawej C., Megarbane A.; RT "A novel homozygous variant in RNF170 causes hereditary spastic paraplegia: RT a case report and review of the literature."; RL Neurogenetics 23:85-90(2022). CC -!- FUNCTION: E3 ubiquitin-protein ligase that plays an essential role in CC stimulus-induced inositol 1,4,5-trisphosphate receptor type 1 (ITPR1) CC ubiquitination and degradation via the endoplasmic reticulum-associated CC degradation (ERAD) pathway. Also involved in ITPR1 turnover in resting CC cells. Selectively inhibits the TLR3-triggered innate immune response CC by promoting the 'Lys-48'-linked polyubiquitination and degradation of CC TLR3 (PubMed:31076723). {ECO:0000269|PubMed:21610068, CC ECO:0000269|PubMed:31076723}. CC -!- CATALYTIC ACTIVITY: CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L- CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.; CC EC=2.3.2.27; Evidence={ECO:0000269|PubMed:31076723}; CC -!- PATHWAY: Protein modification; protein ubiquitination. CC -!- SUBUNIT: (Microbial infection) Interacts with human cytomegalovirus CC protein NEC2/UL50; this interaction promotes of UBA7 ubiquitination and CC subsequent proteasomal degradation. {ECO:0000269|PubMed:29743376}. CC -!- SUBUNIT: Constitutively associated with the ERLIN1/ERLIN 2 complex. CC Interacts with activated ITPR1. {ECO:0000269|PubMed:21610068}. CC -!- INTERACTION: CC Q96K19; P60900: PSMA6; NbExp=3; IntAct=EBI-2130336, EBI-357793; CC Q96K19-5; Q96LL9: DNAJC30; NbExp=3; IntAct=EBI-12055631, EBI-8639143; CC Q96K19-5; B0YJ81: HACD1; NbExp=3; IntAct=EBI-12055631, EBI-12051643; CC Q96K19-5; Q8IY26: PLPP6; NbExp=3; IntAct=EBI-12055631, EBI-11721828; CC Q96K19-5; O43765: SGTA; NbExp=3; IntAct=EBI-12055631, EBI-347996; CC Q96K19-5; Q96EQ0: SGTB; NbExp=3; IntAct=EBI-12055631, EBI-744081; CC Q96K19-5; Q8TB61: SLC35B2; NbExp=3; IntAct=EBI-12055631, EBI-1054782; CC Q96K19-5; Q5SQN1: SNAP47; NbExp=3; IntAct=EBI-12055631, EBI-10244848; CC Q96K19-5; Q14849: STARD3; NbExp=3; IntAct=EBI-12055631, EBI-9819324; CC Q96K19-5; Q9BVC6: TMEM109; NbExp=3; IntAct=EBI-12055631, EBI-1057733; CC Q96K19-5; Q5BJF2: TMEM97; NbExp=3; IntAct=EBI-12055631, EBI-12111910; CC Q96K19-5; O00526: UPK2; NbExp=3; IntAct=EBI-12055631, EBI-10179682; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000269|PubMed:21610068, ECO:0000269|PubMed:31076723}; Multi-pass CC membrane protein {ECO:0000269|PubMed:21610068}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=6; CC Name=1; CC IsoId=Q96K19-1; Sequence=Displayed; CC Name=2; CC IsoId=Q96K19-2; Sequence=VSP_023856; CC Name=3; CC IsoId=Q96K19-3; Sequence=VSP_023855, VSP_023857; CC Name=4; CC IsoId=Q96K19-4; Sequence=VSP_023851, VSP_023852; CC Name=5; CC IsoId=Q96K19-5; Sequence=VSP_023853, VSP_023854; CC Name=6; CC IsoId=Q96K19-6; Sequence=VSP_044556; CC -!- TISSUE SPECIFICITY: Expressed in the spinal cord. CC {ECO:0000269|PubMed:21115467}. CC -!- DISEASE: Ataxia, sensory, 1, autosomal dominant (SNAX1) [MIM:608984]: A CC rare disease characterized by progressive ataxia caused by degeneration CC of the posterior columns of the spinal cord. Affected individuals have CC a reduced ability to feel pain, temperature and vibration, particularly CC in the hands and feet. Their most prominent feature is an ataxic gait CC resulting from a severe loss of proprioception. Thus, patients rely on CC visual cues for maintaining proper body posture, such that they are CC unable to remain upright if their eyes are closed (Romberg sign). CC {ECO:0000269|PubMed:21115467}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Spastic paraplegia 85, autosomal recessive (SPG85) CC [MIM:619686]: A form of spastic paraplegia, a neurodegenerative CC disorder characterized by a slow, gradual, progressive weakness and CC spasticity of the lower limbs. Rate of progression and the severity of CC symptoms are quite variable. Initial symptoms may include difficulty CC with balance, weakness and stiffness in the legs, muscle spasms, and CC dragging the toes when walking. In some forms of the disorder, bladder CC symptoms (such as incontinence) may appear, or the weakness and CC stiffness may spread to other parts of the body. SPG85 is an autosomal CC recessive form characterized by onset of motor symptoms in the first CC few years of life. Patients may have upper limb involvement and CC demonstrate axonal polyneuropathy. Additional features include optic CC atrophy, dysarthria, dysphagia, ataxia, and urinary incontinence. Brain CC imaging may show cerebellar atrophy. {ECO:0000269|PubMed:31636353, CC ECO:0000269|PubMed:33165979, ECO:0000269|PubMed:35041108}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SEQUENCE CAUTION: CC Sequence=AAH39461.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAH44566.1; Type=Erroneous initiation; Note=Extended N-terminus.; 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; AK027748; BAB55340.1; -; mRNA. DR EMBL; AK090864; BAC03534.1; -; mRNA. DR EMBL; AC009634; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC087533; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471080; EAW63201.1; -; Genomic_DNA. DR EMBL; CH471080; EAW63203.1; -; Genomic_DNA. DR EMBL; BC013422; AAH13422.1; -; mRNA. DR EMBL; BC032393; AAH32393.1; -; mRNA. DR EMBL; BC039461; AAH39461.1; ALT_INIT; mRNA. DR EMBL; BC044566; AAH44566.1; ALT_INIT; mRNA. DR EMBL; BC058289; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; AL136620; CAB66555.1; -; mRNA. DR EMBL; AF209504; AAM92891.1; -; mRNA. DR CCDS; CCDS55229.1; -. [Q96K19-6] DR CCDS; CCDS55230.1; -. [Q96K19-3] DR CCDS; CCDS6138.1; -. [Q96K19-1] DR RefSeq; NP_001153695.1; NM_001160223.2. [Q96K19-1] DR RefSeq; NP_001153696.1; NM_001160224.2. [Q96K19-3] DR RefSeq; NP_001153697.1; NM_001160225.2. [Q96K19-6] DR RefSeq; NP_112216.3; NM_030954.3. [Q96K19-1] DR RefSeq; XP_006716467.1; XM_006716404.3. [Q96K19-1] DR RefSeq; XP_011542968.1; XM_011544666.4. [Q96K19-1] DR RefSeq; XP_016869370.1; XM_017013881.2. [Q96K19-1] DR RefSeq; XP_047278235.1; XM_047422279.1. [Q96K19-1] DR RefSeq; XP_047278238.1; XM_047422282.1. [Q96K19-6] DR RefSeq; XP_054217282.1; XM_054361307.1. [Q96K19-1] DR RefSeq; XP_054217283.1; XM_054361308.1. [Q96K19-1] DR RefSeq; XP_054217284.1; XM_054361309.1. [Q96K19-1] DR RefSeq; XP_054217288.1; XM_054361313.1. [Q96K19-6] DR AlphaFoldDB; Q96K19; -. DR SMR; Q96K19; -. DR BioGRID; 123583; 82. DR CORUM; Q96K19; -. DR FunCoup; Q96K19; 948. DR IntAct; Q96K19; 53. DR MINT; Q96K19; -. DR NDEx; IQUERY-CP-RNF170; 1 NDEx IQuery Curated Pathway. DR STRING; 9606.ENSP00000445725; -. DR iPTMnet; Q96K19; -. DR PhosphoSitePlus; Q96K19; -. DR BioMuta; RNF170; -. DR DMDM; 134035027; -. DR jPOST; Q96K19; -. DR MassIVE; Q96K19; -. DR PaxDb; 9606-ENSP00000445725; -. DR PeptideAtlas; Q96K19; -. DR ProteomicsDB; 20847; -. DR ProteomicsDB; 77025; -. [Q96K19-1] DR ProteomicsDB; 77026; -. [Q96K19-2] DR ProteomicsDB; 77027; -. [Q96K19-3] DR ProteomicsDB; 77028; -. [Q96K19-4] DR ProteomicsDB; 77029; -. [Q96K19-5] DR Pumba; Q96K19; -. DR Antibodypedia; 24165; 119 antibodies from 24 providers. DR DNASU; 81790; -. DR Ensembl; ENST00000240159.8; ENSP00000240159.4; ENSG00000120925.17. [Q96K19-5] DR Ensembl; ENST00000319073.5; ENSP00000325969.5; ENSG00000120925.17. [Q96K19-5] DR Ensembl; ENST00000319104.7; ENSP00000326138.3; ENSG00000120925.17. [Q96K19-3] DR Ensembl; ENST00000526349.5; ENSP00000435782.1; ENSG00000120925.17. [Q96K19-6] DR Ensembl; ENST00000527424.6; ENSP00000434797.1; ENSG00000120925.17. [Q96K19-1] DR Ensembl; ENST00000534961.5; ENSP00000445725.1; ENSG00000120925.17. [Q96K19-1] DR Ensembl; ENST00000862754.1; ENSP00000532813.1; ENSG00000120925.17. [Q96K19-1] DR Ensembl; ENST00000862755.1; ENSP00000532814.1; ENSG00000120925.17. [Q96K19-1] DR Ensembl; ENST00000862758.1; ENSP00000532817.1; ENSG00000120925.17. [Q96K19-1] DR Ensembl; ENST00000862760.1; ENSP00000532819.1; ENSG00000120925.17. [Q96K19-1] DR Ensembl; ENST00000862761.1; ENSP00000532820.1; ENSG00000120925.17. [Q96K19-1] DR Ensembl; ENST00000862762.1; ENSP00000532821.1; ENSG00000120925.17. [Q96K19-1] DR Ensembl; ENST00000862763.1; ENSP00000532822.1; ENSG00000120925.17. [Q96K19-1] DR Ensembl; ENST00000913384.1; ENSP00000583443.1; ENSG00000120925.17. [Q96K19-1] DR Ensembl; ENST00000969234.1; ENSP00000639293.1; ENSG00000120925.17. [Q96K19-1] DR Ensembl; ENST00000969235.1; ENSP00000639294.1; ENSG00000120925.17. [Q96K19-1] DR GeneID; 81790; -. DR KEGG; hsa:81790; -. DR MANE-Select; ENST00000527424.6; ENSP00000434797.1; NM_030954.4; NP_112216.3. DR UCSC; uc003xpm.4; human. [Q96K19-1] DR AGR; HGNC:25358; -. DR ClinPGx; PA134922560; -. DR CTD; 81790; -. DR DisGeNET; 81790; -. DR GeneCards; RNF170; -. DR HGNC; HGNC:25358; RNF170. DR HPA; ENSG00000120925; Low tissue specificity. DR MalaCards; RNF170; -. DR MIM; 608984; phenotype. DR MIM; 614649; gene. DR MIM; 619686; phenotype. DR OpenTargets; ENSG00000120925; -. DR Orphanet; 631082; Autosomal recessive spastic paraplegia type 85. DR VEuPathDB; HostDB:ENSG00000120925; -. DR eggNOG; KOG2164; Eukaryota. DR GeneTree; ENSGT00390000017123; -. DR HOGENOM; CLU_1365859_0_0_1; -. DR InParanoid; Q96K19; -. DR OMA; CRQEEQN; -. DR OrthoDB; 9049620at2759; -. DR PAN-GO; Q96K19; 0 GO annotations based on evolutionary models. DR PhylomeDB; Q96K19; -. DR PathwayCommons; Q96K19; -. DR SignaLink; Q96K19; -. DR SIGNOR; Q96K19; -. DR UniPathway; UPA00143; -. DR Agora; ENSG00000120925; -. DR BioGRID-ORCS; 81790; 6 hits in 1193 CRISPR screens. DR ChiTaRS; RNF170; human. DR GenomeRNAi; 81790; -. DR Pharos; Q96K19; Tbio. DR PRO; PR:Q96K19; -. DR Proteomes; UP000005640; Chromosome 8. DR RNAct; Q96K19; protein. DR Bgee; ENSG00000120925; Expressed in lateral nuclear group of thalamus and 200 other cell types or tissues. DR ExpressionAtlas; Q96K19; baseline and differential. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProt. DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:UniProt. DR GO; GO:0008270; F:zinc ion binding; IEA:UniProtKB-KW. DR GO; GO:0034140; P:negative regulation of toll-like receptor 3 signaling pathway; IDA:UniProt. DR GO; GO:0070936; P:protein K48-linked ubiquitination; IDA:UniProt. DR CDD; cd16553; RING-HC_RNF170; 1. DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1. DR InterPro; IPR010652; DUF1232. DR InterPro; IPR038896; RNF170. DR InterPro; IPR027370; Znf-RING_euk. DR InterPro; IPR001841; Znf_RING. DR InterPro; IPR013083; Znf_RING/FYVE/PHD. DR InterPro; IPR017907; Znf_RING_CS. DR PANTHER; PTHR22894:SF1; E3 UBIQUITIN-PROTEIN LIGASE RNF170; 1. DR PANTHER; PTHR22894; RING-TYPE DOMAIN-CONTAINING PROTEIN; 1. DR Pfam; PF06803; DUF1232; 1. DR Pfam; PF13445; zf-RING_UBOX; 1. DR SMART; SM00184; RING; 1. DR SUPFAM; SSF57850; RING/U-box; 1. DR PROSITE; PS00518; ZF_RING_1; 1. DR PROSITE; PS50089; ZF_RING_2; 1. PE 1: Evidence at protein level; KW Alternative splicing; Disease variant; Endoplasmic reticulum; KW Hereditary spastic paraplegia; Host-virus interaction; Membrane; KW Metal-binding; Neurodegeneration; Proteomics identification; KW Reference proteome; Transferase; Transmembrane; Transmembrane helix; KW Ubl conjugation pathway; Zinc; Zinc-finger. FT CHAIN 1..258 FT /note="E3 ubiquitin-protein ligase RNF170" FT /id="PRO_0000280700" FT TOPO_DOM 1..24 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 25..45 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 46..201 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 202..222 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 223 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 224..244 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 245..258 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT ZN_FING 87..130 FT /note="RING-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175" FT VAR_SEQ 1..96 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_023851" FT VAR_SEQ 1..84 FT /note="Missing (in isoform 6)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_044556" FT VAR_SEQ 97..132 FT /note="PVETNCGHLFCGACIIAYWRYGSWLGAISCPICRQT -> MHLLPLDSSSTL FT TCTVPSACTKPPSRWRPTVDIFFV (in isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_023852" FT VAR_SEQ 109..116 FT /note="ACIIAYWR -> NLTPNSIW (in isoform 5)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_023853" FT VAR_SEQ 117..258 FT /note="Missing (in isoform 5)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_023854" FT VAR_SEQ 133..200 FT /note="VTLLLTVFGEDDQSQDVLRLHQDINDYNRRFSGQPRSIMERIMDLPTLLRHA FT FREMFSVGGLFWMFRI -> GSSEKSSRASEQTHQEAVACLDTQNSPACTVGCRSGPQH FT IPHDRMLPSASPRLCFTLLDCVSILWFSG (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_023855" FT VAR_SEQ 170..258 FT /note="IMERIMDLPTLLRHAFREMFSVGGLFWMFRIRIILCLMGAFFYLISPLDFVP FT EALFGILGFLDDFFVIFLLLIYISIMYREVITQRLTR -> VSNAKACSKLEEDTFLLF FT CKVRFTNKYSLTMRNLGQAQWLAPIVLALWEAKAGGSLEPRSLRPALET (in FT isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_023856" FT VAR_SEQ 201..258 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_023857" FT VARIANT 102 FT /note="C -> R (in SPG85)" FT /evidence="ECO:0000269|PubMed:31636353" FT /id="VAR_086712" FT VARIANT 107 FT /note="C -> W (in SPG85)" FT /evidence="ECO:0000269|PubMed:35041108" FT /id="VAR_086713" FT VARIANT 114..258 FT /note="Missing (in SPG85)" FT /evidence="ECO:0000269|PubMed:33165979" FT /id="VAR_086714" FT VARIANT 199 FT /note="R -> C (in SNAX1; dbSNP:rs397514478)" FT /evidence="ECO:0000269|PubMed:21115467" FT /id="VAR_068219" FT MUTAGEN 102 FT /note="C->S: Complete loss of E3 ligase activity; when FT associated with A-104." FT /evidence="ECO:0000269|PubMed:31076723" FT MUTAGEN 104 FT /note="H->A: Complete loss of E3 ligase activity; when FT associated with S-102." FT /evidence="ECO:0000269|PubMed:31076723" FT CONFLICT 9 FT /note="Q -> H (in Ref. 1; BAB55340)" FT /evidence="ECO:0000305" FT CONFLICT 74 FT /note="P -> T (in Ref. 4; AAH44566)" FT /evidence="ECO:0000305" FT CONFLICT 97 FT /note="P -> Q (in Ref. 4; AAH44566)" FT /evidence="ECO:0000305" SQ SEQUENCE 258 AA; 29815 MW; D87C0B0C121AFD76 CRC64; MAKYQGEVQS LKLDDDSVIE GVSDQVLVAV VVSFALIATL VYALFRNVHQ NIHPENQELV RVLREQLQTE QDAPAATRQQ FYTDMYCPIC LHQASFPVET NCGHLFCGAC IIAYWRYGSW LGAISCPICR QTVTLLLTVF GEDDQSQDVL RLHQDINDYN RRFSGQPRSI MERIMDLPTL LRHAFREMFS VGGLFWMFRI RIILCLMGAF FYLISPLDFV PEALFGILGF LDDFFVIFLL LIYISIMYRE VITQRLTR //