ID UBR1_HUMAN Reviewed; 1749 AA. AC Q8IWV7; O60708; O75492; Q14D45; Q68DN9; Q8IWY6; Q96JY4; DT 16-AUG-2005, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2003, sequence version 1. DT 27-MAR-2024, entry version 172. DE RecName: Full=E3 ubiquitin-protein ligase UBR1; DE EC=2.3.2.27; DE AltName: Full=N-recognin-1; DE AltName: Full=RING-type E3 ubiquitin transferase UBR1; DE AltName: Full=Ubiquitin-protein ligase E3-alpha-1; DE AltName: Full=Ubiquitin-protein ligase E3-alpha-I; GN Name=UBR1; 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 1), TISSUE SPECIFICITY, AND FUNCTION. RX PubMed=15548684; DOI=10.1158/0008-5472.can-04-2102; RA Kwak K.S., Zhou X., Solomon V., Baracos V.E., Davis J., Bannon A.W., RA Boyle W.J., Lacey D.L., Han H.Q.; RT "Regulation of protein catabolism by muscle-specific and cytokine-inducible RT ubiquitin ligase E3alpha-II during cancer cachexia."; RL Cancer Res. 64:8193-8198(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; 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 NUCLEOTIDE SEQUENCE [MRNA] OF 18-1727 (ISOFORM 1). RC TISSUE=Erythroid cell; RX PubMed=12434312; DOI=10.1086/344781; RA Dgany O., Avidan N., Delaunay J., Krasnov T., Shalmon L., Shalev H., RA Eidelitz-Markus T., Kapelushnik J., Cattan D., Pariente A., Tulliez M., RA Cretien A., Schischmanoff P.-O., Iolascon A., Fibach E., Koren A., RA Roessler J., Le Merrer M., Yaniv I., Zaizov R., Ben-Asher E., Olender T., RA Lancet D., Beckmann J.S., Tamary H.; RT "Congenital dyserythropoietic anemia type I is caused by mutations in RT codanin-1."; RL Am. J. Hum. Genet. 71:1467-1474(2002). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 166-1014 (ISOFORM 1). RC TISSUE=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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 656-1749 (ISOFORM 2). RC TISSUE=Heart; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 702-1034 (ISOFORM 1), AND RP TISSUE SPECIFICITY. RX PubMed=9653112; DOI=10.1073/pnas.95.14.7898; RA Kwon Y.T., Reiss Y., Fried V.A., Hershko A., Yoon J.K., Gonda D.K., RA Sangan P., Copeland N.G., Jenkins N.A., Varshavsky A.; RT "The mouse and human genes encoding the recognition component of the N-end RT rule pathway."; RL Proc. Natl. Acad. Sci. U.S.A. 95:7898-7903(1998). RN [7] RP INTERACTION WITH RECQL4, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=15317757; DOI=10.1093/hmg/ddh269; RA Yin J., Kwon Y.T., Varshavsky A., Wang W.; RT "RECQL4, mutated in the Rothmund-Thomson and RAPADILINO syndromes, RT interacts with ubiquitin ligases UBR1 and UBR2 of the N-end rule pathway."; RL Hum. Mol. Genet. 13:2421-2430(2004). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1179, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic kidney; RX PubMed=17525332; DOI=10.1126/science.1140321; RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., RA Gygi S.P., Elledge S.J.; RT "ATM and ATR substrate analysis reveals extensive protein networks RT responsive to DNA damage."; RL Science 316:1160-1166(2007). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-21, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [10] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE SCALE RP ANALYSIS] AT THR-21, CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE RP ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200; RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., RA Mann M., Daub H.; RT "Large-scale proteomics analysis of the human kinome."; RL Mol. Cell. Proteomics 8:1751-1764(2009). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-21, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [12] RP FUNCTION. RX PubMed=20298436; DOI=10.1111/j.1365-2443.2010.01385.x; RA Kume K., Iizumi Y., Shimada M., Ito Y., Kishi T., Yamaguchi Y., Handa H.; RT "Role of N-end rule ubiquitin ligases UBR1 and UBR2 in regulating the RT leucine-mTOR signaling pathway."; RL Genes Cells 15:339-349(2010). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-21, AND IDENTIFICATION BY RP 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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-21, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [15] RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 98-167 ALONE AND IN COMPLEX WITH RP N-END RULE PEPTIDE, UBR-TYPE ZINC-FINGER, FUNCTION, AND VARIANT JB5 RP ARG-136. RX PubMed=20835242; DOI=10.1038/nsmb.1894; RA Matta-Camacho E., Kozlov G., Li F.F., Gehring K.; RT "Structural basis of substrate recognition and specificity in the N-end RT rule pathway."; RL Nat. Struct. Mol. Biol. 17:1182-1187(2010). RN [16] RP VARIANTS JBS ARG-136 AND SER-1279, FUNCTION, DISEASE, TISSUE SPECIFICITY, RP SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE. RX PubMed=16311597; DOI=10.1038/ng1681; RA Zenker M., Mayerle J., Lerch M.M., Tagariello A., Zerres K., Durie P.R., RA Beier M., Hulskamp G., Guzman C., Rehder H., Beemer F.A., Hamel B.C.J., RA Vanlieferinghen P., Gershoni-Baruch R., Vieira M.W., Dumic M., RA Auslender R., Gil-da-Silva-Lopes V.L., Steinlicht S., Rauh M., Shalev S.A., RA Thiel C., Winterpacht A., Kwon Y.T., Varshavsky A., Reis A.; RT "Deficiency of UBR1, a ubiquitin ligase of the N-end rule pathway, causes RT pancreatic dysfunction, malformations and mental retardation (Johanson- RT Blizzard syndrome)."; RL Nat. Genet. 37:1345-1350(2005). RN [17] RP VARIANTS JBS LEU-122; ARG-136 AND GLU-1102, AND CHARACTERIZATION OF RP VARIANTS JBS LEU-122; ARG-136 AND GLU-1102. RX PubMed=21931868; DOI=10.1371/journal.pone.0024925; RA Hwang C.S., Sukalo M., Batygin O., Addor M.C., Brunner H., Aytes A.P., RA Mayerle J., Song H.K., Varshavsky A., Zenker M.; RT "Ubiquitin ligases of the N-end rule pathway: assessment of mutations in RT UBR1 that cause the Johanson-Blizzard syndrome."; RL PLoS ONE 6:E24925-E24925(2011). RN [18] RP VARIANT JBS PRO-700. RX PubMed=22072859; DOI=10.3748/wjg.v17.i37.4247; RA Almashraki N., Abdulnabee M.Z., Sukalo M., Alrajoudi A., Sharafadeen I., RA Zenker M.; RT "Johanson-Blizzard syndrome."; RL World J. Gastroenterol. 17:4247-4250(2011). RN [19] RP VARIANTS JBS LEU-122; PHE-127; ARG-136; ARG-166; ARG-217; ARG-286; PRO-317; RP 389-ALA--PHE-392 DEL; ASP-563; VAL-660 DEL; PRO-700; CYS-754; HIS-754; RP GLU-1102; GLY-1242; SER-1279; LEU-1426; PHE-1427; PRO-1431 AND ARG-1661. RX PubMed=24599544; DOI=10.1002/humu.22538; RA Sukalo M., Fiedler A., Guzman C., Spranger S., Addor M.C., McHeik J.N., RA Oltra Benavent M., Cobben J.M., Gillis L.A., Shealy A.G., Deshpande C., RA Bozorgmehr B., Everman D.B., Stattin E.L., Liebelt J., Keller K.M., RA Bertola D.R., van Karnebeek C.D., Bergmann C., Liu Z., Dueker G., RA Rezaei N., Alkuraya F.S., Ogur G., Alrajoudi A., Venegas-Vega C.A., RA Verbeek N.E., Richmond E.J., Kirbiyik O., Ranganath P., Singh A., RA Godbole K., Ali F.A., Alves C., Mayerle J., Lerch M.M., Witt H., Zenker M.; RT "Mutations in the human UBR1 gene and the associated phenotypic spectrum."; RL Hum. Mutat. 35:521-531(2014). RN [20] RP VARIANT JBS ARG-427. RX PubMed=26149651; DOI=10.1016/j.gene.2015.06.082; RA Atik T., Karakoyun M., Sukalo M., Zenker M., Ozkinay F., Aydogdu S.; RT "Two novel UBR1 gene mutations in a patient with Johanson Blizzard RT Syndrome: A mild phenotype without mental retardation."; RL Gene 570:153-155(2015). CC -!- FUNCTION: E3 ubiquitin-protein ligase which is a component of the N-end CC rule pathway. Recognizes and binds to proteins bearing specific N- CC terminal residues that are destabilizing according to the N-end rule, CC leading to their ubiquitination and subsequent degradation. May be CC involved in pancreatic homeostasis. Binds leucine and is a negative CC regulator of the leucine-mTOR signaling pathway, thereby controlling CC cell growth. {ECO:0000269|PubMed:15548684, ECO:0000269|PubMed:16311597, CC ECO:0000269|PubMed:20298436, ECO:0000269|PubMed:20835242}. 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; CC -!- PATHWAY: Protein modification; protein ubiquitination. CC -!- SUBUNIT: Interacts with RECQL4. {ECO:0000269|PubMed:15317757, CC ECO:0000269|PubMed:20835242}. CC -!- INTERACTION: CC Q8IWV7; P07686: HEXB; NbExp=3; IntAct=EBI-711736, EBI-7133736; CC Q8IWV7; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-711736, EBI-5235340; CC Q8IWV7; P02766: TTR; NbExp=3; IntAct=EBI-711736, EBI-711909; CC Q8IWV7; P63146: UBE2B; NbExp=2; IntAct=EBI-711736, EBI-712629; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:16311597}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q8IWV7-1; Sequence=Displayed; CC Name=2; CC IsoId=Q8IWV7-2; Sequence=VSP_015164, VSP_015165; CC -!- TISSUE SPECIFICITY: Broadly expressed, with highest levels in skeletal CC muscle, kidney and pancreas. Present in acinar cells of the pancreas CC (at protein level). {ECO:0000269|PubMed:15548684, CC ECO:0000269|PubMed:16311597, ECO:0000269|PubMed:9653112}. CC -!- DEVELOPMENTAL STAGE: Expressed in fetal pancreas. CC {ECO:0000269|PubMed:16311597}. CC -!- DOMAIN: The RING-H2 zinc finger is an atypical RING finger with a His CC ligand in place of the fourth Cys of the classical motif. CC -!- DOMAIN: The UBR-type zinc finger forms a pocket that mediates CC recognition of type 1 N-degrons. It exhibits preference for Arginine in CC first position, has poor affinity for histidine, and doesn't bind CC acetylated peptides. CC -!- DISEASE: Johanson-Blizzard syndrome (JBS) [MIM:243800]: This disorder CC includes congenital exocrine pancreatic insufficiency, multiple CC malformations such as nasal wing aplasia, and intellectual disability. CC Pancreas of individuals with JBS do not express UBR1 and show CC intrauterine-onset destructive pancreatitis. CC {ECO:0000269|PubMed:16311597, ECO:0000269|PubMed:21931868, CC ECO:0000269|PubMed:22072859, ECO:0000269|PubMed:24599544, CC ECO:0000269|PubMed:26149651}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the UBR1 family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAB55380.1; Type=Erroneous initiation; 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; AY061886; AAL32103.1; -; mRNA. DR EMBL; BC113505; AAI13506.1; -; mRNA. DR EMBL; BC113507; AAI13508.1; -; mRNA. DR EMBL; AF525401; AAO14997.1; -; mRNA. DR EMBL; AK027803; BAB55380.1; ALT_INIT; mRNA. DR EMBL; CR749326; CAH18181.1; -; mRNA. DR EMBL; AF061556; AAC39845.1; -; mRNA. DR EMBL; AH006181; AAC23677.1; -; Genomic_DNA. DR CCDS; CCDS10091.1; -. [Q8IWV7-1] DR RefSeq; NP_777576.1; NM_174916.2. [Q8IWV7-1] DR PDB; 3NY1; X-ray; 2.08 A; A/B=97-168. DR PDB; 5TDC; X-ray; 1.61 A; A/C=98-168. DR PDBsum; 3NY1; -. DR PDBsum; 5TDC; -. DR AlphaFoldDB; Q8IWV7; -. DR SMR; Q8IWV7; -. DR BioGRID; 128238; 203. DR DIP; DIP-47033N; -. DR IntAct; Q8IWV7; 71. DR MINT; Q8IWV7; -. DR STRING; 9606.ENSP00000290650; -. DR GlyCosmos; Q8IWV7; 1 site, 1 glycan. DR GlyGen; Q8IWV7; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q8IWV7; -. DR MetOSite; Q8IWV7; -. DR PhosphoSitePlus; Q8IWV7; -. DR BioMuta; UBR1; -. DR DMDM; 73622071; -. DR EPD; Q8IWV7; -. DR jPOST; Q8IWV7; -. DR MassIVE; Q8IWV7; -. DR MaxQB; Q8IWV7; -. DR PaxDb; 9606-ENSP00000290650; -. DR PeptideAtlas; Q8IWV7; -. DR ProteomicsDB; 70907; -. [Q8IWV7-1] DR ProteomicsDB; 70908; -. [Q8IWV7-2] DR Pumba; Q8IWV7; -. DR Antibodypedia; 23750; 223 antibodies from 28 providers. DR DNASU; 197131; -. DR Ensembl; ENST00000290650.9; ENSP00000290650.4; ENSG00000159459.12. [Q8IWV7-1] DR GeneID; 197131; -. DR KEGG; hsa:197131; -. DR MANE-Select; ENST00000290650.9; ENSP00000290650.4; NM_174916.3; NP_777576.1. DR UCSC; uc001zqq.4; human. [Q8IWV7-1] DR AGR; HGNC:16808; -. DR DisGeNET; 197131; -. DR GeneCards; UBR1; -. DR GeneReviews; UBR1; -. DR HGNC; HGNC:16808; UBR1. DR HPA; ENSG00000159459; Low tissue specificity. DR MalaCards; UBR1; -. DR MIM; 243800; phenotype. DR MIM; 605981; gene. DR neXtProt; NX_Q8IWV7; -. DR OpenTargets; ENSG00000159459; -. DR Orphanet; 2315; Johanson-Blizzard syndrome. DR PharmGKB; PA38187; -. DR VEuPathDB; HostDB:ENSG00000159459; -. DR eggNOG; KOG1140; Eukaryota. DR GeneTree; ENSGT00950000183075; -. DR HOGENOM; CLU_001801_2_0_1; -. DR InParanoid; Q8IWV7; -. DR OMA; TWMKLLA; -. DR OrthoDB; 51389at2759; -. DR PhylomeDB; Q8IWV7; -. DR TreeFam; TF323875; -. DR BioCyc; MetaCyc:ENSG00000159459-MONOMER; -. DR BRENDA; 3.4.17.20; 2681. DR PathwayCommons; Q8IWV7; -. DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation. DR SignaLink; Q8IWV7; -. DR SIGNOR; Q8IWV7; -. DR UniPathway; UPA00143; -. DR BioGRID-ORCS; 197131; 11 hits in 1196 CRISPR screens. DR ChiTaRS; UBR1; human. DR EvolutionaryTrace; Q8IWV7; -. DR GeneWiki; UBR1; -. DR GenomeRNAi; 197131; -. DR Pharos; Q8IWV7; Tbio. DR PRO; PR:Q8IWV7; -. DR Proteomes; UP000005640; Chromosome 15. DR RNAct; Q8IWV7; Protein. DR Bgee; ENSG00000159459; Expressed in epithelial cell of pancreas and 197 other cell types or tissues. DR ExpressionAtlas; Q8IWV7; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell. DR GO; GO:0000502; C:proteasome complex; IEA:Ensembl. DR GO; GO:0000151; C:ubiquitin ligase complex; IBA:GO_Central. DR GO; GO:0070728; F:leucine binding; IDA:UniProtKB. DR GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0071233; P:cellular response to leucine; IDA:UniProtKB. DR GO; GO:0032007; P:negative regulation of TOR signaling; IMP:UniProtKB. DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central. DR GO; GO:0071596; P:ubiquitin-dependent protein catabolic process via the N-end rule pathway; IBA:GO_Central. DR CDD; cd19678; UBR-box_UBR1; 1. DR Gene3D; 2.10.110.30; -; 1. DR Gene3D; 3.30.1390.10; -; 1. DR Gene3D; 1.10.10.2670; E3 ubiquitin-protein ligase; 1. DR InterPro; IPR003769; ClpS_core. DR InterPro; IPR042065; E3_ELL-like. DR InterPro; IPR044046; E3_ligase_UBR-like_C. DR InterPro; IPR014719; Ribosomal_bL12_C/ClpS-like. DR InterPro; IPR047507; UBR-box_UBR1. DR InterPro; IPR039164; UBR1-like. DR InterPro; IPR036390; WH_DNA-bd_sf. DR InterPro; IPR003126; Znf_UBR. DR PANTHER; PTHR21497:SF27; E3 UBIQUITIN-PROTEIN LIGASE UBR1; 1. DR PANTHER; PTHR21497; UBIQUITIN LIGASE E3 ALPHA-RELATED; 1. DR Pfam; PF02617; ClpS; 1. DR Pfam; PF18995; PRT6_C; 1. DR Pfam; PF02207; zf-UBR; 1. DR SMART; SM00396; ZnF_UBR1; 1. DR SUPFAM; SSF54736; ClpS-like; 1. DR SUPFAM; SSF46785; Winged helix' DNA-binding domain; 1. DR PROSITE; PS51157; ZF_UBR; 1. DR Genevisible; Q8IWV7; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Cytoplasm; KW Disease variant; Metal-binding; Phosphoprotein; Reference proteome; KW Transferase; Ubl conjugation pathway; Zinc; Zinc-finger. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:19369195" FT CHAIN 2..1749 FT /note="E3 ubiquitin-protein ligase UBR1" FT /id="PRO_0000056136" FT ZN_FING 97..168 FT /note="UBR-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00508" FT ZN_FING 1098..1201 FT /note="RING-type; atypical" FT REGION 842..868 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 842..861 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0007744|PubMed:19369195" FT MOD_RES 21 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT MOD_RES 1179 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17525332" FT VAR_SEQ 795..803 FT /note="NNETGLENV -> TRCIRPWSL (in isoform 2)" FT /evidence="ECO:0000303|PubMed:17974005" FT /id="VSP_015164" FT VAR_SEQ 804..1749 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:17974005" FT /id="VSP_015165" FT VARIANT 122 FT /note="V -> L (in JBS; decreased, but detectable activity FT in a yeast-based assay)" FT /evidence="ECO:0000269|PubMed:21931868, FT ECO:0000269|PubMed:24599544" FT /id="VAR_075179" FT VARIANT 127 FT /note="C -> F (in JBS)" FT /evidence="ECO:0000269|PubMed:24599544" FT /id="VAR_075180" FT VARIANT 136 FT /note="H -> R (in JBS; prevents proper folding of the FT UBR-type zinc finger; may decrease protein stability; loss FT of activity in a yeast-based assay; dbSNP:rs119477054)" FT /evidence="ECO:0000269|PubMed:16311597, FT ECO:0000269|PubMed:20835242, ECO:0000269|PubMed:21931868, FT ECO:0000269|PubMed:24599544" FT /id="VAR_024741" FT VARIANT 166 FT /note="H -> R (in JBS)" FT /evidence="ECO:0000269|PubMed:24599544" FT /id="VAR_075181" FT VARIANT 217 FT /note="L -> R (in JBS)" FT /evidence="ECO:0000269|PubMed:24599544" FT /id="VAR_075182" FT VARIANT 286 FT /note="I -> R (in JBS)" FT /evidence="ECO:0000269|PubMed:24599544" FT /id="VAR_075183" FT VARIANT 317 FT /note="L -> P (in JBS)" FT /evidence="ECO:0000269|PubMed:24599544" FT /id="VAR_075184" FT VARIANT 389..392 FT /note="Missing (in JBS)" FT /evidence="ECO:0000269|PubMed:24599544" FT /id="VAR_075185" FT VARIANT 427 FT /note="L -> R (in JBS; uncertain significance; FT dbSNP:rs1158249054)" FT /evidence="ECO:0000269|PubMed:26149651" FT /id="VAR_075186" FT VARIANT 563 FT /note="A -> D (in JBS; dbSNP:rs768686147)" FT /evidence="ECO:0000269|PubMed:24599544" FT /id="VAR_075187" FT VARIANT 596 FT /note="K -> M (in dbSNP:rs34568456)" FT /id="VAR_034467" FT VARIANT 660 FT /note="Missing (in JBS)" FT /evidence="ECO:0000269|PubMed:24599544" FT /id="VAR_075188" FT VARIANT 700 FT /note="S -> P (in JBS)" FT /evidence="ECO:0000269|PubMed:22072859, FT ECO:0000269|PubMed:24599544" FT /id="VAR_075189" FT VARIANT 754 FT /note="R -> C (in JBS; dbSNP:rs1388367359)" FT /evidence="ECO:0000269|PubMed:24599544" FT /id="VAR_075190" FT VARIANT 754 FT /note="R -> H (in JBS; dbSNP:rs1567131023)" FT /evidence="ECO:0000269|PubMed:24599544" FT /id="VAR_075191" FT VARIANT 899 FT /note="I -> V (in dbSNP:rs35069201)" FT /id="VAR_052116" FT VARIANT 1102 FT /note="Q -> E (in JBS; strong decrease in activity in a FT yeast-based assay)" FT /evidence="ECO:0000269|PubMed:21931868, FT ECO:0000269|PubMed:24599544" FT /id="VAR_075192" FT VARIANT 1242 FT /note="R -> G (in JBS; dbSNP:rs1235541565)" FT /evidence="ECO:0000269|PubMed:24599544" FT /id="VAR_075193" FT VARIANT 1279 FT /note="G -> S (in JBS)" FT /evidence="ECO:0000269|PubMed:16311597, FT ECO:0000269|PubMed:24599544" FT /id="VAR_024742" FT VARIANT 1426 FT /note="P -> L (in JBS)" FT /evidence="ECO:0000269|PubMed:24599544" FT /id="VAR_075194" FT VARIANT 1427 FT /note="S -> F (in JBS; dbSNP:rs1480939799)" FT /evidence="ECO:0000269|PubMed:24599544" FT /id="VAR_075195" FT VARIANT 1431 FT /note="S -> P (in JBS; dbSNP:rs140972409)" FT /evidence="ECO:0000269|PubMed:24599544" FT /id="VAR_075196" FT VARIANT 1548 FT /note="T -> A (in dbSNP:rs3917223)" FT /id="VAR_061822" FT VARIANT 1661 FT /note="G -> R (in JBS)" FT /evidence="ECO:0000269|PubMed:24599544" FT /id="VAR_075197" FT CONFLICT 201 FT /note="V -> A (in Ref. 4)" FT /evidence="ECO:0000305" FT CONFLICT 900 FT /note="D -> N (in Ref. 6; AAC39845)" FT /evidence="ECO:0000305" FT CONFLICT 973 FT /note="D -> T (in Ref. 3; AAO14997)" FT /evidence="ECO:0000305" FT CONFLICT 993 FT /note="C -> S (in Ref. 6; AAC23677)" FT /evidence="ECO:0000305" FT CONFLICT 1710..1719 FT /note="LSRERYRKLH -> FLVSGTEAP (in Ref. 3)" FT /evidence="ECO:0000305" FT CONFLICT 1722 FT /note="W -> R (in Ref. 3)" FT /evidence="ECO:0000305" FT STRAND 108..112 FT /evidence="ECO:0007829|PDB:5TDC" FT TURN 113..115 FT /evidence="ECO:0007829|PDB:5TDC" FT STRAND 116..118 FT /evidence="ECO:0007829|PDB:5TDC" FT HELIX 125..129 FT /evidence="ECO:0007829|PDB:5TDC" FT HELIX 132..135 FT /evidence="ECO:0007829|PDB:5TDC" FT STRAND 138..142 FT /evidence="ECO:0007829|PDB:5TDC" FT TURN 154..156 FT /evidence="ECO:0007829|PDB:5TDC" FT STRAND 157..159 FT /evidence="ECO:0007829|PDB:5TDC" FT TURN 164..166 FT /evidence="ECO:0007829|PDB:5TDC" SQ SEQUENCE 1749 AA; 200211 MW; 3AE0E1A749884971 CRC64; MADEEAGGTE RMEISAELPQ TPQRLASWWD QQVDFYTAFL HHLAQLVPEI YFAEMDPDLE KQEESVQMSI FTPLEWYLFG EDPDICLEKL KHSGAFQLCG RVFKSGETTY SCRDCAIDPT CVLCMDCFQD SVHKNHRYKM HTSTGGGFCD CGDTEAWKTG PFCVNHEPGR AGTIKENSRC PLNEEVIVQA RKIFPSVIKY VVEMTIWEEE KELPPELQIR EKNERYYCVL FNDEHHSYDH VIYSLQRALD CELAEAQLHT TAIDKEGRRA VKAGAYAACQ EAKEDIKSHS ENVSQHPLHV EVLHSEIMAH QKFALRLGSW MNKIMSYSSD FRQIFCQACL REEPDSENPC LISRLMLWDA KLYKGARKIL HELIFSSFFM EMEYKKLFAM EFVKYYKQLQ KEYISDDHDR SISITALSVQ MFTVPTLARH LIEEQNVISV ITETLLEVLP EYLDRNNKFN FQGYSQDKLG RVYAVICDLK YILISKPTIW TERLRMQFLE GFRSFLKILT CMQGMEEIRR QVGQHIEVDP DWEAAIAIQM QLKNILLMFQ EWCACDEELL LVAYKECHKA VMRCSTSFIS SSKTVVQSCG HSLETKSYRV SEDLVSIHLP LSRTLAGLHV RLSRLGAVSR LHEFVSFEDF QVEVLVEYPL RCLVLVAQVV AEMWRRNGLS LISQVFYYQD VKCREEMYDK DIIMLQIGAS LMDPNKFLLL VLQRYELAEA FNKTISTKDQ DLIKQYNTLI EEMLQVLIYI VGERYVPGVG NVTKEEVTMR EIIHLLCIEP MPHSAIAKNL PENENNETGL ENVINKVATF KKPGVSGHGV YELKDESLKD FNMYFYHYSK TQHSKAEHMQ KKRRKQENKD EALPPPPPPE FCPAFSKVIN LLNCDIMMYI LRTVFERAID TDSNLWTEGM LQMAFHILAL GLLEEKQQLQ KAPEEEVTFD FYHKASRLGS SAMNIQMLLE KLKGIPQLEG QKDMITWILQ MFDTVKRLRE KSCLIVATTS GSESIKNDEI THDKEKAERK RKAEAARLHR QKIMAQMSAL QKNFIETHKL MYDNTSEMPG KEDSIMEEES TPAVSDYSRI ALGPKRGPSV TEKEVLTCIL CQEEQEVKIE NNAMVLSACV QKSTALTQHR GKPIELSGEA LDPLFMDPDL AYGTYTGSCG HVMHAVCWQK YFEAVQLSSQ QRIHVDLFDL ESGEYLCPLC KSLCNTVIPI IPLQPQKINS ENADALAQLL TLARWIQTVL ARISGYNIRH AKGENPIPIF FNQGMGDSTL EFHSILSFGV ESSIKYSNSI KEMVILFATT IYRIGLKVPP DERDPRVPML TWSTCAFTIQ AIENLLGDEG KPLFGALQNR QHNGLKALMQ FAVAQRITCP QVLIQKHLVR LLSVVLPNIK SEDTPCLLSI DLFHVLVGAV LAFPSLYWDD PVDLQPSSVS SSYNHLYLFH LITMAHMLQI LLTVDTGLPL AQVQEDSEEA HSASSFFAEI SQYTSGSIGC DIPGWYLWVS LKNGITPYLR CAALFFHYLL GVTPPEELHT NSAEGEYSAL CSYLSLPTNL FLLFQEYWDT VRPLLQRWCA DPALLNCLKQ KNTVVRYPRK RNSLIELPDD YSCLLNQASH FRCPRSADDE RKHPVLCLFC GAILCSQNIC CQEIVNGEEV GACIFHALHC GAGVCIFLKI RECRVVLVEG KARGCAYPAP YLDEYGETDP GLKRGNPLHL SRERYRKLHL VWQQHCIIEE IARSQETNQM LFGFNWQLL //