UBR1_HUMAN
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 03-AUG-2022, entry version 163.
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};
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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; 195.
DR DIP; DIP-47033N; -.
DR IntAct; Q8IWV7; 71.
DR MINT; Q8IWV7; -.
DR STRING; 9606.ENSP00000290650; -.
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; Q8IWV7; -.
DR PeptideAtlas; Q8IWV7; -.
DR PRIDE; Q8IWV7; -.
DR ProteomicsDB; 70907; -. [Q8IWV7-1]
DR ProteomicsDB; 70908; -. [Q8IWV7-2]
DR Antibodypedia; 23750; 204 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 CTD; 197131; -.
DR DisGeNET; 197131; -.
DR GeneCards; UBR1; -.
DR GeneReviews; UBR1; -.
DR HGNC; HGNC:16808; UBR1.
DR HPA; ENSG00000159459; Tissue enhanced (brain).
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; ATTVYRI; -.
DR OrthoDB; 81415at2759; -.
DR PhylomeDB; Q8IWV7; -.
DR TreeFam; TF323875; -.
DR BioCyc; MetaCyc:ENSG00000159459-MON; -.
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 1118 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 195 other tissues.
DR ExpressionAtlas; Q8IWV7; baseline and differential.
DR Genevisible; Q8IWV7; HS.
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 Gene3D; 1.10.10.2670; -; 1.
DR Gene3D; 3.30.1390.10; -; 1.
DR InterPro; IPR003769; ClpS_core.
DR InterPro; IPR042065; E3_ELL-like.
DR InterPro; IPR044046; E3_ligase_UBR-like_C.
DR InterPro; IPR014719; Ribosomal_L7/12_C/ClpS-like.
DR InterPro; IPR039164; UBR1-like.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR InterPro; IPR003126; Znf_UBR.
DR PANTHER; PTHR21497; PTHR21497; 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; SSF46785; SSF46785; 1.
DR SUPFAM; SSF54736; SSF54736; 1.
DR PROSITE; PS51157; ZF_UBR; 1.
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 UBR-
FT type zinc finger; may decrease protein stability; loss of
FT 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; unknown pathological 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
