ZN304_HUMAN
ID ZN304_HUMAN Reviewed; 659 AA.
AC Q9HCX3;
DT 19-SEP-2002, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 2.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=Zinc finger protein 304 {ECO:0000312|HGNC:HGNC:13505};
DE AltName: Full=KRAB-containing zinc finger protein {ECO:0000303|PubMed:12051768};
GN Name=ZNF304 {ECO:0000312|HGNC:HGNC:13505};
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], VARIANT GLU-367, AND TISSUE SPECIFICITY.
RC TISSUE=Thymus;
RX PubMed=12051768; DOI=10.1016/s0006-291x(02)00344-3;
RA Sabater L., Ashhab Y., Caro P., Kolkowski E.C., Pujol-Borrell R.,
RA Dominguez O.;
RT "Identification of a KRAB-containing zinc finger protein, ZNF304, by AU-
RT motif-directed display method and initial characterization in lymphocyte
RT activation.";
RL Biochem. Biophys. Res. Commun. 293:1066-1072(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [3]
RP FUNCTION, INTERACTION WITH USP28, POSSIBLE IDENTIFICATION IN A COREPRESSOR
RP COMPLEX, CHROMATIN-BINDING, DEUBIQUITINATION BY USP28, TISSUE SPECIFICITY,
RP AND INDUCTION.
RX PubMed=24623306; DOI=10.7554/elife.02313;
RA Serra R.W., Fang M., Park S.M., Hutchinson L., Green M.R.;
RT "A KRAS-directed transcriptional silencing pathway that mediates the CpG
RT island methylator phenotype.";
RL Elife 3:E02313-E02313(2014).
RN [4]
RP FUNCTION, DNA-BINDING, AND TISSUE SPECIFICITY.
RX PubMed=26081979; DOI=10.1038/ncomms8351;
RA Aslan B., Monroig P., Hsu M.C., Pena G.A., Rodriguez-Aguayo C.,
RA Gonzalez-Villasana V., Rupaimoole R., Nagaraja A.S., Mangala S., Han H.D.,
RA Yuca E., Wu S.Y., Ivan C., Moss T.J., Ram P.T., Wang H., Gol-Chambers A.,
RA Ozkayar O., Kanlikilicer P., Fuentes-Mattei E., Kahraman N., Pradeep S.,
RA Ozpolat B., Tucker S., Hung M.C., Baggerly K., Bartholomeusz G., Calin G.,
RA Sood A.K., Lopez-Berestein G.;
RT "The ZNF304-integrin axis protects against anoikis in cancer.";
RL Nat. Commun. 6:7351-7351(2015).
CC -!- FUNCTION: Acts as transcriptional regulator and plays a role in gene
CC silencing (PubMed:24623306, PubMed:26081979). Probably forms a
CC corepressor complex required for activated KRAS-mediated promoter
CC hypermethylation and transcriptional silencing of several tumor
CC suppressor genes (TSGs) or other tumor-related genes in colorectal
CC cancer (CRC) cells (PubMed:24623306). Also required to maintain a
CC transcriptionally repressive state of genes in undifferentiated
CC embryonic stem cells (ESCs) by inducing trimethylation of 'Lys-27' of
CC histone H3 (H3K27me3) (PubMed:24623306) in a Polycomb group (PcG)
CC complexes-dependent manner. Associates at promoter regions of TSGs and
CC mediates the recruitment of the corepressor complex containing the
CC scaffolding protein TRIM28, methyltransferase DNMT1 and histone
CC methyltransferase SETDB1 and/or the PcG complexes at those sites
CC (PubMed:24623306). Transcription factor involved in the metastatic
CC cascade process by inducing cell migration and proliferation and gain
CC resistance to anoikis of ovarian carcinoma (OC) cells via integrin-
CC mediated signaling pathways (PubMed:26081979). Associates with the
CC ITGB1 promoter and positively regulates beta-1 integrin transcription
CC expression (PubMed:26081979). Promotes angiogenesis (PubMed:26081979).
CC Promotes tumor growth (PubMed:24623306, PubMed:26081979).
CC {ECO:0000269|PubMed:24623306, ECO:0000269|PubMed:26081979}.
CC -!- SUBUNIT: Probably part of a corepressor complex containing ZNF304,
CC TRIM28, SETDB1 and DNMT1; leading to promoter hypermethylation and
CC transcriptional silencing (PubMed:24623306). Probably associates with
CC Polycomb group (PcG) complexes; leading to trimethylation of 'Lys-27'
CC of histone H3 (H3K27me3) (PubMed:24623306). Interacts with USP28
CC (PubMed:24623306). {ECO:0000269|PubMed:24623306}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305|PubMed:24623306}.
CC Note=Associates with chromatin (PubMed:24623306).
CC {ECO:0000269|PubMed:24623306}.
CC -!- TISSUE SPECIFICITY: Expressed in undifferentiated embryonic stem cells
CC (ESCs) (PubMed:24623306). Expressed strongly in colorectal cancers
CC cells (CRCs) (PubMed:24623306). Expressed strongly in ovarian carcinoma
CC (OC) tumor cell lines compared to non-transformed ovarian epithelial
CC cells (at protein level) (PubMed:26081979). Expressed in lymphoid
CC tissues, thyroid, adrenal gland, prostate, pancreas and skeletal
CC muscles (PubMed:12051768). {ECO:0000269|PubMed:12051768,
CC ECO:0000269|PubMed:24623306, ECO:0000269|PubMed:26081979}.
CC -!- INDUCTION: Down-regulated during embryonic stem cells (ESCs)
CC differentiation by retinoic acid treatment (PubMed:24623306).
CC {ECO:0000269|PubMed:24623306}.
CC -!- PTM: Deubiquitinated by USP28; the deubiquitination leads to the
CC stabilization of ZNF304 from proteolytic degradation (PubMed:24623306).
CC {ECO:0000269|PubMed:24623306}.
CC -!- SIMILARITY: Belongs to the krueppel C2H2-type zinc-finger protein
CC family. {ECO:0000305}.
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DR EMBL; AJ276316; CAC06610.1; -; mRNA.
DR EMBL; AC005261; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS12950.1; -.
DR RefSeq; NP_065708.2; NM_020657.3.
DR AlphaFoldDB; Q9HCX3; -.
DR SMR; Q9HCX3; -.
DR BioGRID; 121493; 4.
DR CORUM; Q9HCX3; -.
DR IntAct; Q9HCX3; 2.
DR STRING; 9606.ENSP00000375586; -.
DR GlyGen; Q9HCX3; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9HCX3; -.
DR PhosphoSitePlus; Q9HCX3; -.
DR BioMuta; ZNF304; -.
DR DMDM; 296453049; -.
DR MassIVE; Q9HCX3; -.
DR MaxQB; Q9HCX3; -.
DR PaxDb; Q9HCX3; -.
DR PeptideAtlas; Q9HCX3; -.
DR PRIDE; Q9HCX3; -.
DR ProteomicsDB; 81804; -.
DR Antibodypedia; 46525; 20 antibodies from 12 providers.
DR DNASU; 57343; -.
DR Ensembl; ENST00000282286.6; ENSP00000282286.4; ENSG00000131845.15.
DR Ensembl; ENST00000391705.7; ENSP00000375586.3; ENSG00000131845.15.
DR GeneID; 57343; -.
DR KEGG; hsa:57343; -.
DR MANE-Select; ENST00000282286.6; ENSP00000282286.4; NM_020657.4; NP_065708.2.
DR UCSC; uc010ygw.3; human.
DR CTD; 57343; -.
DR DisGeNET; 57343; -.
DR GeneCards; ZNF304; -.
DR HGNC; HGNC:13505; ZNF304.
DR HPA; ENSG00000131845; Low tissue specificity.
DR MIM; 613840; gene.
DR neXtProt; NX_Q9HCX3; -.
DR OpenTargets; ENSG00000131845; -.
DR PharmGKB; PA37791; -.
DR VEuPathDB; HostDB:ENSG00000131845; -.
DR eggNOG; KOG1721; Eukaryota.
DR GeneTree; ENSGT00940000161016; -.
DR HOGENOM; CLU_002678_44_5_1; -.
DR InParanoid; Q9HCX3; -.
DR OMA; KPHECNS; -.
DR PhylomeDB; Q9HCX3; -.
DR TreeFam; TF339848; -.
DR PathwayCommons; Q9HCX3; -.
DR Reactome; R-HSA-212436; Generic Transcription Pathway.
DR SignaLink; Q9HCX3; -.
DR SIGNOR; Q9HCX3; -.
DR BioGRID-ORCS; 57343; 10 hits in 1101 CRISPR screens.
DR GenomeRNAi; 57343; -.
DR Pharos; Q9HCX3; Tbio.
DR PRO; PR:Q9HCX3; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q9HCX3; protein.
DR Bgee; ENSG00000131845; Expressed in secondary oocyte and 181 other tissues.
DR ExpressionAtlas; Q9HCX3; baseline and differential.
DR Genevisible; Q9HCX3; HS.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:1990841; F:promoter-specific chromatin binding; IDA:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; IMP:UniProtKB.
DR GO; GO:2000811; P:negative regulation of anoikis; IMP:UniProtKB.
DR GO; GO:0035562; P:negative regulation of chromatin binding; IMP:UniProtKB.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IMP:UniProtKB.
DR GO; GO:0030335; P:positive regulation of cell migration; IMP:UniProtKB.
DR GO; GO:0090309; P:positive regulation of DNA methylation-dependent heterochromatin assembly; IMP:UniProtKB.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IMP:UniProtKB.
DR GO; GO:1902466; P:positive regulation of histone H3-K27 trimethylation; IMP:UniProtKB.
DR GO; GO:1900114; P:positive regulation of histone H3-K9 trimethylation; IMP:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0007265; P:Ras protein signal transduction; IMP:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR CDD; cd07765; KRAB_A-box; 1.
DR InterPro; IPR001909; KRAB.
DR InterPro; IPR036051; KRAB_dom_sf.
DR InterPro; IPR036236; Znf_C2H2_sf.
DR InterPro; IPR013087; Znf_C2H2_type.
DR Pfam; PF01352; KRAB; 1.
DR Pfam; PF00096; zf-C2H2; 11.
DR SMART; SM00349; KRAB; 1.
DR SMART; SM00355; ZnF_C2H2; 16.
DR SUPFAM; SSF109640; SSF109640; 1.
DR SUPFAM; SSF57667; SSF57667; 10.
DR PROSITE; PS50805; KRAB; 1.
DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 16.
DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 15.
PE 1: Evidence at protein level;
KW Activator; Angiogenesis; Chromatin regulator; DNA-binding; Metal-binding;
KW Nucleus; Reference proteome; Repeat; Transcription;
KW Transcription regulation; Zinc; Zinc-finger.
FT CHAIN 1..659
FT /note="Zinc finger protein 304"
FT /id="PRO_0000047523"
FT DOMAIN 14..88
FT /note="KRAB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00119"
FT ZN_FING 89..111
FT /note="C2H2-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 115..139
FT /note="C2H2-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 251..273
FT /note="C2H2-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 279..301
FT /note="C2H2-type 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 307..329
FT /note="C2H2-type 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 335..357
FT /note="C2H2-type 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 363..385
FT /note="C2H2-type 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 391..413
FT /note="C2H2-type 8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 419..441
FT /note="C2H2-type 9"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 447..469
FT /note="C2H2-type 10"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 475..497
FT /note="C2H2-type 11"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 503..525
FT /note="C2H2-type 12"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 531..553
FT /note="C2H2-type 13"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 559..581
FT /note="C2H2-type 14"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 587..609
FT /note="C2H2-type 15"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 615..637
FT /note="C2H2-type 16"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT VARIANT 121
FT /note="L -> P (in dbSNP:rs862708)"
FT /id="VAR_019979"
FT VARIANT 367
FT /note="K -> E (in dbSNP:rs862709)"
FT /evidence="ECO:0000269|PubMed:12051768"
FT /id="VAR_033563"
FT CONFLICT 323
FT /note="V -> A (in Ref. 1; CAC06610)"
FT /evidence="ECO:0000305"
FT CONFLICT 334
FT /note="S -> P (in Ref. 1; CAC06610)"
FT /evidence="ECO:0000305"
FT CONFLICT 445
FT /note="R -> S (in Ref. 1; CAC06610)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 659 AA; 75047 MW; 11B5263F41DB2704 CRC64;
MAAAVLMDRV QSCVTFEDVF VYFSREEWEL LEEAQRFLYR DVMLENFALV ATLGFWCEAE
HEAPSEQSVS VEGVSQVRTA ESGLFQKAHP CEMCDPLLKD ILHLAEHQGS HLTQKLCTRG
LCRRRFSFSA NFYQHQKQHN GENCFRGDDG GASFVKSCTV HMLGRSFTCR EEGMDLPDSS
GLFQHQTTYN RVSPCRRTEC MESFPHSSSL RQHQGDYDGQ MLFSCGDEGK AFLDTFTLLD
SQMTHAEVRP FRCLPCGNVF KEKSALINHR KIHSGEISHV CKECGKAFIH LHHLKMHQKF
HTGKRHYTCS ECGKAFSRKD TLVQHQRVHT GERSYDCSEC GKAYSRSSHL VQHQRIHTGE
RPYKCNKCGK AFSRKDTLVQ HQRFHTGERP YECSECGKFF SQSSHLIEHW RIHTGARPYE
CIECGKFFSH NSSLIKHRRV HTGARSYVCS KCGKAFGCKD TLVQHQIIHT GARPYECSEC
GKAFSRKDTL VQHQKIHTGE RPYECGECGK FFSHSSNLIV HQRIHTGAKP YECNECGKCF
SHNSSLILHQ RVHTGARPYV CSECGKAYIS SSHLVQHKKV HTGARPYECS ECGKFFSRNS
GLILHQRVHT GEKPYVCSEC GKAYSRSSHL VRHQKAHTGE RAHECNSFGG PLAASLKLV
