ZNRF2_HUMAN
ID ZNRF2_HUMAN Reviewed; 242 AA.
AC Q8NHG8;
DT 20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=E3 ubiquitin-protein ligase ZNRF2;
DE EC=2.3.2.27;
DE AltName: Full=Protein Ells2;
DE AltName: Full=RING finger protein 202;
DE AltName: Full=RING-type E3 ubiquitin transferase ZNRF2;
DE AltName: Full=Zinc/RING finger protein 2;
GN Name=ZNRF2; Synonyms=RNF202;
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], FUNCTION, MYRISTOYLATION AT GLY-2, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=14561866; DOI=10.1523/jneurosci.23-28-09385.2003;
RA Araki T., Milbrandt J.;
RT "ZNRF proteins constitute a family of presynaptic E3 ubiquitin ligases.";
RL J. Neurosci. 23:9385-9394(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Ovary;
RA Guo J.H., Yu L.;
RL Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-135, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [4]
RP INTERACTION WITH UBE2N.
RX PubMed=16215985; DOI=10.1002/jcb.20587;
RA Plans V., Scheper J., Soler M., Loukili N., Okano Y., Thomson T.M.;
RT "The RING finger protein RNF8 recruits UBC13 for lysine 63-based self
RT polyubiquitylation.";
RL J. Cell. Biochem. 97:572-582(2006).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-82 AND SER-151, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-82; SER-113 AND SER-116, AND
RP IDENTIFICATION BY 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 [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-82 AND SER-135, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-82 AND SER-135, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-82; SER-135 AND SER-193, AND
RP IDENTIFICATION BY 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 [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-82; SER-89 AND SER-135, AND
RP IDENTIFICATION BY 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).
CC -!- FUNCTION: May play a role in the establishment and maintenance of
CC neuronal transmission and plasticity via its ubiquitin ligase activity.
CC E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating
CC enzyme in the form of a thioester and then directly transfer the
CC ubiquitin to targeted substrates. {ECO:0000269|PubMed:14561866}.
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 UBE2N. {ECO:0000269|PubMed:16215985}.
CC -!- SUBCELLULAR LOCATION: Endosome membrane {ECO:0000269|PubMed:14561866};
CC Peripheral membrane protein {ECO:0000269|PubMed:14561866}. Lysosome
CC membrane {ECO:0000269|PubMed:14561866}; Peripheral membrane protein
CC {ECO:0000269|PubMed:14561866}. Presynaptic cell membrane
CC {ECO:0000269|PubMed:14561866}; Peripheral membrane protein
CC {ECO:0000269|PubMed:14561866}.
CC -!- TISSUE SPECIFICITY: Highly expressed in the brain, with higher
CC expression during development than in adult. Expressed also in mammary
CC glands, testis, colon and kidney. {ECO:0000269|PubMed:14561866}.
CC -!- DOMAIN: The RING-type zinc finger domain is required for E3 ligase
CC activity. {ECO:0000250}.
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DR EMBL; AF513707; AAQ08115.1; -; mRNA.
DR EMBL; AF527533; AAM88868.1; -; mRNA.
DR CCDS; CCDS5426.1; -.
DR RefSeq; NP_667339.1; NM_147128.3.
DR AlphaFoldDB; Q8NHG8; -.
DR SMR; Q8NHG8; -.
DR BioGRID; 128825; 54.
DR IntAct; Q8NHG8; 5.
DR MINT; Q8NHG8; -.
DR STRING; 9606.ENSP00000323879; -.
DR iPTMnet; Q8NHG8; -.
DR PhosphoSitePlus; Q8NHG8; -.
DR BioMuta; ZNRF2; -.
DR DMDM; 74762595; -.
DR EPD; Q8NHG8; -.
DR jPOST; Q8NHG8; -.
DR MassIVE; Q8NHG8; -.
DR MaxQB; Q8NHG8; -.
DR PaxDb; Q8NHG8; -.
DR PeptideAtlas; Q8NHG8; -.
DR PRIDE; Q8NHG8; -.
DR ProteomicsDB; 73707; -.
DR Antibodypedia; 35132; 121 antibodies from 25 providers.
DR DNASU; 223082; -.
DR Ensembl; ENST00000323037.5; ENSP00000323879.4; ENSG00000180233.11.
DR GeneID; 223082; -.
DR KEGG; hsa:223082; -.
DR MANE-Select; ENST00000323037.5; ENSP00000323879.4; NM_147128.4; NP_667339.1.
DR UCSC; uc003tat.3; human.
DR CTD; 223082; -.
DR DisGeNET; 223082; -.
DR GeneCards; ZNRF2; -.
DR HGNC; HGNC:22316; ZNRF2.
DR HPA; ENSG00000180233; Low tissue specificity.
DR MIM; 612061; gene.
DR neXtProt; NX_Q8NHG8; -.
DR OpenTargets; ENSG00000180233; -.
DR PharmGKB; PA134961488; -.
DR VEuPathDB; HostDB:ENSG00000180233; -.
DR eggNOG; KOG0801; Eukaryota.
DR GeneTree; ENSGT00940000159017; -.
DR HOGENOM; CLU_062700_2_0_1; -.
DR InParanoid; Q8NHG8; -.
DR OMA; SEEMDLH; -.
DR OrthoDB; 1256682at2759; -.
DR PhylomeDB; Q8NHG8; -.
DR TreeFam; TF317681; -.
DR PathwayCommons; Q8NHG8; -.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; Q8NHG8; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 223082; 12 hits in 1083 CRISPR screens.
DR ChiTaRS; ZNRF2; human.
DR GenomeRNAi; 223082; -.
DR Pharos; Q8NHG8; Tbio.
DR PRO; PR:Q8NHG8; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q8NHG8; protein.
DR Bgee; ENSG00000180233; Expressed in buccal mucosa cell and 152 other tissues.
DR ExpressionAtlas; Q8NHG8; baseline and differential.
DR Genevisible; Q8NHG8; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0042995; C:cell projection; IEA:UniProtKB-KW.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IDA:MGI.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0001650; C:fibrillar center; IDA:HPA.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0042734; C:presynaptic membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0032991; C:protein-containing complex; IDA:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:MGI.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR GO; GO:0070936; P:protein K48-linked ubiquitination; IBA:GO_Central.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR Pfam; PF13639; zf-RING_2; 1.
DR SMART; SM00184; RING; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cell projection; Endosome; Lipoprotein; Lysosome; Membrane;
KW Metal-binding; Myristate; Phosphoprotein; Reference proteome; Synapse;
KW Transferase; Ubl conjugation pathway; Zinc; Zinc-finger.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000305"
FT CHAIN 2..242
FT /note="E3 ubiquitin-protein ligase ZNRF2"
FT /id="PRO_0000277803"
FT ZN_FING 199..240
FT /note="RING-type; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 1..141
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 18..33
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 95..120
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 21
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q71FD5"
FT MOD_RES 25
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q71FD5"
FT MOD_RES 82
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 89
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 113
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 116
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 135
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 145
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q71FD5"
FT MOD_RES 151
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 193
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000305|PubMed:14561866"
SQ SEQUENCE 242 AA; 24115 MW; D02776578A1E9E55 CRC64;
MGAKQSGPAA ANGRTRAYSG SDLPSSSSGG ANGTAGGGGG ARAAAAGRFP AQVPSAHQPS
ASGGAAAAAA APAAPAAPRS RSLGGAVGSV ASGARAAQSP FSIPNSSSGP YGSQDSVHSS
PEDGGGGRDR PVGGSPGGPR LVIGSLPAHL SPHMFGGFKC PVCSKFVSSD EMDLHLVMCL
TKPRITYNED VLSKDAGECA ICLEELQQGD TIARLPCLCI YHKGCIDEWF EVNRSCPEHP
SD
