UBR7_HUMAN
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 03-AUG-2022, entry version 159.
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};
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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; 76.
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; Q8N806; -.
DR PeptideAtlas; Q8N806; -.
DR PRIDE; Q8N806; -.
DR ProteomicsDB; 72353; -.
DR Antibodypedia; 29; 196 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 CTD; 55148; -.
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; GQPYFCR; -.
DR OrthoDB; 1428122at2759; -.
DR PhylomeDB; Q8N806; -.
DR TreeFam; TF105941; -.
DR PathwayCommons; Q8N806; -.
DR SignaLink; Q8N806; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 55148; 11 hits in 1109 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 105 other tissues.
DR ExpressionAtlas; Q8N806; baseline and differential.
DR Genevisible; Q8N806; HS.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IEA:InterPro.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR040204; UBR7.
DR InterPro; IPR011011; Znf_FYVE_PHD.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR003126; Znf_UBR.
DR PANTHER; PTHR13513; PTHR13513; 1.
DR Pfam; PF02207; zf-UBR; 1.
DR SMART; SM00396; ZnF_UBR1; 1.
DR SUPFAM; SSF57903; SSF57903; 1.
DR PROSITE; PS51157; ZF_UBR; 1.
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; unknown pathological
FT 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
