ZN516_HUMAN
ID ZN516_HUMAN Reviewed; 1163 AA.
AC Q92618;
DT 20-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 03-AUG-2022, entry version 179.
DE RecName: Full=Zinc finger protein 516 {ECO:0000312|HGNC:HGNC:28990};
GN Name=ZNF516 {ECO:0000312|HGNC:HGNC:28990};
GN Synonyms=KIAA0222 {ECO:0000312|EMBL:BAA13211.2};
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=Bone marrow;
RX PubMed=9039502; DOI=10.1093/dnares/3.5.321;
RA Nagase T., Seki N., Ishikawa K., Ohira M., Kawarabayasi Y., Ohara O.,
RA Tanaka A., Kotani H., Miyajima N., Nomura N.;
RT "Prediction of the coding sequences of unidentified human genes. VI. The
RT coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of
RT cDNA clones from cell line KG-1 and brain.";
RL DNA Res. 3:321-329(1996).
RN [2]
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 [3]
RP FUNCTION.
RX PubMed=23446422; DOI=10.1038/nature11935;
RA Burrell R.A., McClelland S.E., Endesfelder D., Groth P., Weller M.C.,
RA Shaikh N., Domingo E., Kanu N., Dewhurst S.M., Gronroos E., Chew S.K.,
RA Rowan A.J., Schenk A., Sheffer M., Howell M., Kschischo M., Behrens A.,
RA Helleday T., Bartek J., Tomlinson I.P., Swanton C.;
RT "Replication stress links structural and numerical cancer chromosomal
RT instability.";
RL Nature 494:492-496(2013).
RN [4]
RP INTERACTION WITH PRDM16.
RX PubMed=25578880; DOI=10.1016/j.molcel.2014.12.005;
RA Dempersmier J., Sambeat A., Gulyaeva O., Paul S.M., Hudak C.S.,
RA Raposo H.F., Kwan H.Y., Kang C., Wong R.H., Sul H.S.;
RT "Cold-inducible Zfp516 activates UCP1 transcription to promote browning of
RT white fat and development of brown fat.";
RL Mol. Cell 57:235-246(2015).
RN [5]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-643; LYS-681; LYS-1043 AND
RP LYS-1062, 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).
CC -!- FUNCTION: Transcriptional regulator that binds to the promoter and
CC activates the transcription of genes promoting brown adipose tissue
CC (BAT) differentiation. Among brown adipose tissue-specific genes, binds
CC the proximal region of the promoter of the UCP1 gene to activate its
CC transcription and thereby regulate thermogenesis (By similarity). May
CC also play a role in the cellular response to replication stress
CC (PubMed:23446422). {ECO:0000250|UniProtKB:Q7TSH3,
CC ECO:0000269|PubMed:23446422}.
CC -!- SUBUNIT: Interacts with PRDM16; the interaction is direct and may play
CC a role in the transcription of brown adipose tissue-specific genes
CC (PubMed:25578880). Interacts with PWWP2B (By similarity). Interacts
CC with HDAC1; this interaction is enhanced in the presence of PWWP2B (By
CC similarity). {ECO:0000250|UniProtKB:Q7TSH3,
CC ECO:0000269|PubMed:25578880}.
CC -!- INTERACTION:
CC Q92618; Q13363: CTBP1; NbExp=14; IntAct=EBI-2799490, EBI-908846;
CC Q92618; P56545: CTBP2; NbExp=6; IntAct=EBI-2799490, EBI-741533;
CC Q92618; Q13547: HDAC1; NbExp=8; IntAct=EBI-2799490, EBI-301834;
CC Q92618; Q92769: HDAC2; NbExp=6; IntAct=EBI-2799490, EBI-301821;
CC Q92618; O60341: KDM1A; NbExp=6; IntAct=EBI-2799490, EBI-710124;
CC Q92618; Q9UKL0: RCOR1; NbExp=6; IntAct=EBI-2799490, EBI-926563;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q7TSH3}.
CC -!- SIMILARITY: Belongs to the krueppel C2H2-type zinc-finger protein
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA13211.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; D86975; BAA13211.2; ALT_INIT; mRNA.
DR CCDS; CCDS74234.1; -.
DR RefSeq; NP_055458.1; NM_014643.3.
DR RefSeq; XP_011524571.1; XM_011526269.1.
DR RefSeq; XP_011524572.1; XM_011526270.2.
DR RefSeq; XP_011524573.1; XM_011526271.2.
DR RefSeq; XP_011524574.1; XM_011526272.2.
DR RefSeq; XP_011524575.1; XM_011526273.2.
DR RefSeq; XP_011524576.1; XM_011526274.2.
DR RefSeq; XP_011524577.1; XM_011526275.2.
DR RefSeq; XP_016881586.1; XM_017026097.1.
DR AlphaFoldDB; Q92618; -.
DR BioGRID; 115016; 36.
DR CORUM; Q92618; -.
DR IntAct; Q92618; 34.
DR MINT; Q92618; -.
DR STRING; 9606.ENSP00000394757; -.
DR iPTMnet; Q92618; -.
DR MetOSite; Q92618; -.
DR PhosphoSitePlus; Q92618; -.
DR BioMuta; ZNF516; -.
DR DMDM; 14548318; -.
DR EPD; Q92618; -.
DR jPOST; Q92618; -.
DR MassIVE; Q92618; -.
DR MaxQB; Q92618; -.
DR PaxDb; Q92618; -.
DR PeptideAtlas; Q92618; -.
DR PRIDE; Q92618; -.
DR ProteomicsDB; 75371; -.
DR Antibodypedia; 5767; 70 antibodies from 16 providers.
DR DNASU; 9658; -.
DR Ensembl; ENST00000443185.7; ENSP00000394757.2; ENSG00000101493.11.
DR GeneID; 9658; -.
DR KEGG; hsa:9658; -.
DR MANE-Select; ENST00000443185.7; ENSP00000394757.2; NM_014643.4; NP_055458.1.
DR UCSC; uc032hhr.2; human.
DR CTD; 9658; -.
DR DisGeNET; 9658; -.
DR GeneCards; ZNF516; -.
DR HGNC; HGNC:28990; ZNF516.
DR HPA; ENSG00000101493; Low tissue specificity.
DR MIM; 615114; gene.
DR neXtProt; NX_Q92618; -.
DR OpenTargets; ENSG00000101493; -.
DR PharmGKB; PA134992707; -.
DR VEuPathDB; HostDB:ENSG00000101493; -.
DR eggNOG; KOG1721; Eukaryota.
DR GeneTree; ENSGT00940000160839; -.
DR HOGENOM; CLU_009481_0_0_1; -.
DR InParanoid; Q92618; -.
DR OMA; KLNHTHE; -.
DR OrthoDB; 1318335at2759; -.
DR PhylomeDB; Q92618; -.
DR TreeFam; TF332241; -.
DR PathwayCommons; Q92618; -.
DR SignaLink; Q92618; -.
DR BioGRID-ORCS; 9658; 9 hits in 334 CRISPR screens.
DR ChiTaRS; ZNF516; human.
DR GenomeRNAi; 9658; -.
DR Pharos; Q92618; Tbio.
DR PRO; PR:Q92618; -.
DR Proteomes; UP000005640; Chromosome 18.
DR RNAct; Q92618; protein.
DR Bgee; ENSG00000101493; Expressed in stromal cell of endometrium and 155 other tissues.
DR ExpressionAtlas; Q92618; baseline and differential.
DR Genevisible; Q92618; HS.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0000987; F:cis-regulatory region sequence-specific DNA binding; ISS:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; IEA:Ensembl.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0060612; P:adipose tissue development; ISS:UniProtKB.
DR GO; GO:0050873; P:brown fat cell differentiation; ISS:UniProtKB.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IBA:GO_Central.
DR GO; GO:0009409; P:response to cold; IEA:Ensembl.
DR InterPro; IPR036236; Znf_C2H2_sf.
DR InterPro; IPR013087; Znf_C2H2_type.
DR Pfam; PF00096; zf-C2H2; 4.
DR SMART; SM00355; ZnF_C2H2; 10.
DR SUPFAM; SSF57667; SSF57667; 4.
DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 7.
DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 7.
PE 1: Evidence at protein level;
KW DNA-binding; Isopeptide bond; Metal-binding; Nucleus; Reference proteome;
KW Repeat; Transcription; Transcription regulation; Ubl conjugation; Zinc;
KW Zinc-finger.
FT CHAIN 1..1163
FT /note="Zinc finger protein 516"
FT /id="PRO_0000047634"
FT ZN_FING 34..56
FT /note="C2H2-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 62..84
FT /note="C2H2-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 174..197
FT /note="C2H2-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 200..223
FT /note="C2H2-type 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 248..270
FT /note="C2H2-type 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 276..298
FT /note="C2H2-type 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 335..357
FT /note="C2H2-type 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 515..537
FT /note="C2H2-type 8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 760..783
FT /note="C2H2-type 9; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 1098..1120
FT /note="C2H2-type 10"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 1..431
FT /note="Mediates promoter DNA-binding and activation of
FT transcription"
FT /evidence="ECO:0000250|UniProtKB:Q7TSH3"
FT REGION 1..26
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 460..512
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 533..667
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 679..730
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 838..1007
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1126..1163
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 540..556
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 560..576
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 612..629
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 707..723
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 842..856
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 927..941
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 988..1003
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1131..1163
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CROSSLNK 643
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 681
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 1043
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 1062
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VARIANT 4
FT /note="N -> S (in dbSNP:rs3752097)"
FT /id="VAR_052852"
FT VARIANT 239
FT /note="G -> S (in dbSNP:rs12961584)"
FT /id="VAR_052853"
SQ SEQUENCE 1163 AA; 124289 MW; 9D6DDDE2D70236A4 CRC64;
MDRNREAEME LRRGPSPTRA GRGHEVDGDK ATCHTCCICG KSFPFQSSLS QHMRKHTGEK
PYKCPYCDHR ASQKGNLKIH IRSHRTGTLI QGHEPEAGEA PLGEMRASEG LDACASPTKS
ASACNRLLNG ASQADGARVL NGASQADSGR VLLRSSKKGA EGSACAPGEA KAAVQCSFCK
SQFERKKDLE LHVHQAHKPF KCRLCSYATL REESLLSHIE RDHITAQGPG SGEACVENGK
PELSPGEFPC EVCGQAFSQT WFLKAHMKKH RGSFDHGCHI CGRRFKEPWF LKNHMKAHGP
KTGSKNRPKS ELDPIATINN VVQEEVIVAG LSLYEVCAKC GNLFTNLDSL NAHNAIHRRV
EASRTRAPAE EGAEGPSDTK QFFLQCLNLR PSAAGDSCPG TQAGRRVAEL DPVNSYQAWQ
LATRGKVAEP AEYLKYGAWD EALAGDVAFD KDRREYVLVS QEKRKREQDA PAAQGPPRKR
ASGPGDPAPA GHLDPRSAAR PNRRAAATTG QGKSSECFEC GKIFRTYHQM VLHSRVHRRA
RRERDSDGDR AARARCGSLS EGDSASQPSS PGSACAAADS PGSGLADEAA EDSGEEGAPE
PAPGGQPRRC CFSEEVTSTE LSSGDQSHKM GDNASERDTG ESKAGIAASV SILENSSRET
SRRQEQHRFS MDLKMPAFHP KQEVPVPGDG VEFPSSTGAE GQTGHPAEKL SDLHNKEHSG
GGKRALAPDL MPLDLSARST RDDPSNKETA SSLQAALVVH PCPYCSHKTY YPEVLWMHKR
IWHRVSCNSV APPWIQPNGY KSIRSNLVFL SRSGRTGPPP ALGGKECQPL LLARFTRTQV
PGGMPGSKSG SSPLGVVTKA ASMPKNKESH SGGPCALWAP GPDGYRQTKP CHGQEPHGAA
TQGPLAKPRQ EASSKPVPAP GGGGFSRSAT PTPTVIARAG AQPSANSKPV EKFGVPPAGA
GFAPTNKHSA PDSLKAKFSA QPQGPPPAKG EGGAPPLPPR EPPSKAAQEL RTLATCAAGS
RGDAALQAQP GVAGAPPVLH SIKQEPVAEG HEKRLDILNI FKTYIPKDFA TLYQGWGVSG
PGLEHRGTLR TQARPGEFVC IECGKSFHQP GHLRAHMRAH SVVFESDGPR GSEVHTTSAD
APKQGRDHSN TGTVQTVPLR KGT
