ID UBR7_HUMAN Reviewed; 425 AA. AC Q8N806; Q86U21; Q86UA9; Q96BY0; Q9NVV6; DT 24-OCT-2003, integrated into UniProtKB/Swiss-Prot. DT 24-OCT-2003, sequence version 2. DT 27-MAR-2024, entry version 168. DE RecName: Full=Putative E3 ubiquitin-protein ligase UBR7; DE EC=2.3.2.27; DE AltName: Full=N-recognin-7; DE AltName: Full=RING-type E3 ubiquitin transferase UBR7; GN Name=UBR7; Synonyms=C14orf130; 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]. RC TISSUE=Teratocarcinoma, and Testis; 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 MRNA]. RC TISSUE=Leiomyosarcoma, and Retinoblastoma; 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 [LARGE SCALE MRNA] OF 3-425. RC TISSUE=Neuroblastoma; RA Li W.B., Gruber C., Jessee J., Polayes D.; RT "Full-length cDNA libraries and normalization."; RL Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases. RN [4] 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 [5] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-354, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=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 [6] RP TISSUE SPECIFICITY. RX PubMed=24664117; DOI=10.1007/s00441-014-1808-x; RA Zimmerman S.W., Yi Y.J., Sutovsky M., van Leeuwen F.W., Conant G., RA Sutovsky P.; RT "Identification and characterization of RING-finger ubiquitin ligase UBR7 RT in mammalian spermatozoa."; RL Cell Tissue Res. 356:261-278(2014). RN [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-264, 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 [8] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-225; LYS-252; LYS-274 AND RP LYS-398, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=28112733; DOI=10.1038/nsmb.3366; RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C., RA Nielsen M.L.; RT "Site-specific mapping of the human SUMO proteome reveals co-modification RT with phosphorylation."; RL Nat. Struct. Mol. Biol. 24:325-336(2017). RN [9] RP INVOLVEMENT IN LICAS, AND VARIANTS LICAS 13-GLU--SER-425 DEL AND SER-305. RX PubMed=33340455; DOI=10.1016/j.ajhg.2020.11.018; RA Li C., Beauregard-Lacroix E., Kondratev C., Rousseau J., Heo A.J., Neas K., RA Graham B.H., Rosenfeld J.A., Bacino C.A., Wagner M., Wenzel M., RA Al Mutairi F., Al Deiab H., Gleeson J.G., Stanley V., Zaki M.S., Kwon Y.T., RA Leroux M.R., Campeau P.M.; RT "UBR7 functions with UBR5 in the Notch signaling pathway and is involved in RT a neurodevelopmental syndrome with epilepsy, ptosis, and hypothyroidism."; RL Am. J. Hum. Genet. 108:134-147(2021). 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. CC {ECO:0000250}. 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 -!- TISSUE SPECIFICITY: Expressed in sperm (at protein level). CC {ECO:0000269|PubMed:24664117}. CC -!- DISEASE: Li-Campeau syndrome (LICAS) [MIM:619189]: An autosomal CC recessive neurodevelopmental disorder characterized by global CC developmental delay, intellectual disability, epilepsy, ptosis, CC hypothyroidism, and variable cardiac and genital anomalies. Additional CC features may include seizures, short stature, hypotonia, and brain CC imaging anomalies, such as cortical atrophy. CC {ECO:0000269|PubMed:33340455}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SEQUENCE CAUTION: CC Sequence=AAH15046.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=AAH51819.4; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=BAA91639.1; 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; AK001345; BAA91639.1; ALT_INIT; mRNA. DR EMBL; AK097477; BAC05069.1; -; mRNA. DR EMBL; BC015046; AAH15046.1; ALT_INIT; mRNA. DR EMBL; BC051819; AAH51819.4; ALT_INIT; mRNA. DR EMBL; BX248249; CAD62577.1; -; mRNA. DR CCDS; CCDS9909.1; -. DR RefSeq; NP_786924.2; NM_175748.3. DR AlphaFoldDB; Q8N806; -. DR BioGRID; 120451; 93. DR IntAct; Q8N806; 13. DR MINT; Q8N806; -. DR STRING; 9606.ENSP00000013070; -. DR GlyGen; Q8N806; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q8N806; -. DR PhosphoSitePlus; Q8N806; -. DR BioMuta; UBR7; -. DR DMDM; 37999713; -. DR EPD; Q8N806; -. DR jPOST; Q8N806; -. DR MassIVE; Q8N806; -. DR MaxQB; Q8N806; -. DR PaxDb; 9606-ENSP00000013070; -. DR PeptideAtlas; Q8N806; -. DR ProteomicsDB; 72353; -. DR Pumba; Q8N806; -. DR Antibodypedia; 29; 222 antibodies from 25 providers. DR DNASU; 55148; -. DR Ensembl; ENST00000013070.11; ENSP00000013070.6; ENSG00000012963.15. DR Ensembl; ENST00000619583.3; ENSP00000483908.1; ENSG00000278787.4. DR GeneID; 55148; -. DR KEGG; hsa:55148; -. DR MANE-Select; ENST00000013070.11; ENSP00000013070.6; NM_175748.4; NP_786924.2. DR UCSC; uc001ybm.4; human. DR AGR; HGNC:20344; -. DR DisGeNET; 55148; -. DR GeneCards; UBR7; -. DR HGNC; HGNC:20344; UBR7. DR HPA; ENSG00000012963; Low tissue specificity. DR MalaCards; UBR7; -. DR MIM; 613816; gene. DR MIM; 619189; phenotype. DR neXtProt; NX_Q8N806; -. DR OpenTargets; ENSG00000012963; -. DR Orphanet; 528084; Non-specific syndromic intellectual disability. DR PharmGKB; PA162408298; -. DR VEuPathDB; HostDB:ENSG00000012963; -. DR eggNOG; KOG2752; Eukaryota. DR GeneTree; ENSGT00390000017610; -. DR HOGENOM; CLU_025221_0_0_1; -. DR InParanoid; Q8N806; -. DR OMA; GAMVYNH; -. DR OrthoDB; 11436at2759; -. DR PhylomeDB; Q8N806; -. DR TreeFam; TF105941; -. DR PathwayCommons; Q8N806; -. DR SignaLink; Q8N806; -. DR UniPathway; UPA00143; -. DR BioGRID-ORCS; 55148; 13 hits in 1188 CRISPR screens. DR ChiTaRS; UBR7; human. DR GenomeRNAi; 55148; -. DR Pharos; Q8N806; Tbio. DR PRO; PR:Q8N806; -. DR Proteomes; UP000005640; Chromosome 14. DR RNAct; Q8N806; Protein. DR Bgee; ENSG00000012963; Expressed in left testis and 107 other cell types or tissues. DR ExpressionAtlas; Q8N806; baseline and differential. DR GO; GO:0061630; F:ubiquitin protein ligase activity; IEA:InterPro. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway. DR CDD; cd15542; PHD_UBR7; 1. DR CDD; cd19677; UBR-box_UBR7; 1. DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1. DR InterPro; IPR040204; UBR7. DR InterPro; IPR047506; UBR7-like_UBR-box. DR InterPro; IPR011011; Znf_FYVE_PHD. DR InterPro; IPR013083; Znf_RING/FYVE/PHD. DR InterPro; IPR003126; Znf_UBR. DR PANTHER; PTHR13513; E3 UBIQUITIN-PROTEIN LIGASE UBR7; 1. DR PANTHER; PTHR13513:SF9; E3 UBIQUITIN-PROTEIN LIGASE UBR7-RELATED; 1. DR Pfam; PF02207; zf-UBR; 1. DR SMART; SM00396; ZnF_UBR1; 1. DR SUPFAM; SSF57903; FYVE/PHD zinc finger; 1. DR PROSITE; PS51157; ZF_UBR; 1. DR Genevisible; Q8N806; HS. PE 1: Evidence at protein level; KW Disease variant; Intellectual disability; Isopeptide bond; Metal-binding; KW Phosphoprotein; Reference proteome; Transferase; Ubl conjugation; KW Ubl conjugation pathway; Zinc; Zinc-finger. FT CHAIN 1..425 FT /note="Putative E3 ubiquitin-protein ligase UBR7" FT /id="PRO_0000089932" FT ZN_FING 44..116 FT /note="UBR-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00508" FT ZN_FING 132..188 FT /note="PHD-type; atypical" FT REGION 225..246 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 264 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 354 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT CROSSLNK 225 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 252 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 274 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 398 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT VARIANT 13..425 FT /note="Missing (in LICAS; no UBR7 protein detected in FT patient cells)" FT /evidence="ECO:0000269|PubMed:33340455" FT /id="VAR_085255" FT VARIANT 305 FT /note="W -> S (in LICAS; uncertain significance)" FT /evidence="ECO:0000269|PubMed:33340455" FT /id="VAR_085256" FT CONFLICT 41 FT /note="S -> G (in Ref. 1; BAC05069)" FT /evidence="ECO:0000305" FT CONFLICT 170 FT /note="I -> T (in Ref. 1; BAA91639)" FT /evidence="ECO:0000305" FT CONFLICT 179 FT /note="E -> K (in Ref. 1; BAC05069)" FT /evidence="ECO:0000305" FT CONFLICT 344 FT /note="K -> R (in Ref. 1; BAC05069)" FT /evidence="ECO:0000305" SQ SEQUENCE 425 AA; 47999 MW; 6FFE5795E6737BE5 CRC64; MAGAEGAAGR QSELEPVVSL VDVLEEDEEL ENEACAVLGG SDSEKCSYSQ GSVKRQALYA CSTCTPEGEE PAGICLACSY ECHGSHKLFE LYTKRNFRCD CGNSKFKNLE CKLLPDKAKV NSGNKYNDNF FGLYCICKRP YPDPEDEIPD EMIQCVVCED WFHGRHLGAI PPESGDFQEM VCQACMKRCS FLWAYAAQLA VTKISTEDDG LVRNIDGIGD QEVIKPENGE HQDSTLKEDV PEQGKDDVRE VKVEQNSEPC AGSSSESDLQ TVFKNESLNA ESKSGCKLQE LKAKQLIKKD TATYWPLNWR SKLCTCQDCM KMYGDLDVLF LTDEYDTVLA YENKGKIAQA TDRSDPLMDT LSSMNRVQQV ELICEYNDLK TELKDYLKRF ADEGTVVKRE DIQQFFEEFQ SKKRRRVDGM QYYCS //