ZN703_HUMAN
ID ZN703_HUMAN Reviewed; 590 AA.
AC Q9H7S9; Q5XG76;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Zinc finger protein 703;
DE AltName: Full=Zinc finger elbow-related proline domain protein 1;
GN Name=ZNF703; Synonyms=ZEPPO1, ZPO1;
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=Placenta;
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 GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M.,
RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B.,
RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA Platzer M., Shimizu N., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=PNS, and Skin;
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 [4]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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 [5]
RP FUNCTION, INVOLVEMENT IN LUMINAL B BREAST CANCER, SUBCELLULAR LOCATION,
RP INTERACTION WITH DCAF7; HSPD1 AND PHB2, AND INDUCTION BY 17-BETA-ESTRADIOL.
RX PubMed=21328542; DOI=10.1002/emmm.201100121;
RA Sircoulomb F., Nicolas N., Ferrari A., Finetti P., Bekhouche I.,
RA Rousselet E., Lonigro A., Adelaide J., Baudelet E., Esteyries S.,
RA Wicinski J., Audebert S., Charafe-Jauffret E., Jacquemier J., Lopez M.,
RA Borg J.P., Sotiriou C., Popovici C., Bertucci F., Birnbaum D.,
RA Chaffanet M., Ginestier C.;
RT "ZNF703 gene amplification at 8p12 specifies luminal B breast cancer.";
RL EMBO Mol. Med. 3:153-166(2011).
RN [6]
RP FUNCTION, INVOLVEMENT IN LUMINAL B BREAST CANCER, AND SUBCELLULAR LOCATION.
RX PubMed=21337521; DOI=10.1002/emmm.201100122;
RA Holland D.G., Burleigh A., Git A., Goldgraben M.A., Perez-Mancera P.A.,
RA Chin S.F., Hurtado A., Bruna A., Ali H.R., Greenwood W., Dunning M.J.,
RA Samarajiwa S., Menon S., Rueda O.M., Lynch A.G., McKinney S., Ellis I.O.,
RA Eaves C.J., Carroll J.S., Curtis C., Aparicio S., Caldas C.;
RT "ZNF703 is a common Luminal B breast cancer oncogene that differentially
RT regulates luminal and basal progenitors in human mammary epithelium.";
RL EMBO Mol. Med. 3:167-180(2011).
RN [7]
RP TISSUE SPECIFICITY.
RX PubMed=21317240; DOI=10.1101/gad.1998111;
RA Slorach E.M., Chou J., Werb Z.;
RT "Zeppo1 is a novel metastasis promoter that represses E-cadherin expression
RT and regulates p120-catenin isoform expression and localization.";
RL Genes Dev. 25:471-484(2011).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-252, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
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).
CC -!- FUNCTION: Transcriptional corepressor which does not bind directly to
CC DNA and may regulate transcription through recruitment of histone
CC deacetylases to gene promoters. Regulates cell adhesion, migration and
CC proliferation. May be required for segmental gene expression during
CC hindbrain development. {ECO:0000269|PubMed:21328542,
CC ECO:0000269|PubMed:21337521}.
CC -!- SUBUNIT: Interacts with TLE4; increases transcriptional repression (By
CC similarity). Interacts with DCAF7 and PHB2. May interact with HSPD1.
CC {ECO:0000250, ECO:0000269|PubMed:21328542}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:21328542,
CC ECO:0000269|PubMed:21337521}. Cytoplasm {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in mammary epithelium.
CC {ECO:0000269|PubMed:21317240}.
CC -!- INDUCTION: Up-regulated by 17-beta-estradiol.
CC {ECO:0000269|PubMed:21328542}.
CC -!- DISEASE: Note=Luminal B breast cancers are the clinically more
CC aggressive estrogen receptor-positive tumors. Amplification of a distal
CC 8p12 locus occurs in around one third of the cases and ZNF703 is the
CC single gene within the minimal amplicon. Amplification of the gene
CC correlates with its protein expression in tumor cells. ZNF703 is a
CC classical breast cancer oncogene since it is able to transform non-
CC malignant cells and increase cellular proliferation.
CC -!- SIMILARITY: Belongs to the Elbow/Noc family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH84581.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing.; Evidence={ECO:0000305};
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DR EMBL; AK024361; BAB14897.1; -; mRNA.
DR EMBL; AC137579; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC032534; AAH32534.1; -; mRNA.
DR EMBL; BC084581; AAH84581.1; ALT_SEQ; mRNA.
DR CCDS; CCDS6094.1; -.
DR RefSeq; NP_079345.1; NM_025069.2.
DR AlphaFoldDB; Q9H7S9; -.
DR BioGRID; 123134; 79.
DR IntAct; Q9H7S9; 49.
DR MINT; Q9H7S9; -.
DR STRING; 9606.ENSP00000332325; -.
DR iPTMnet; Q9H7S9; -.
DR PhosphoSitePlus; Q9H7S9; -.
DR BioMuta; ZNF703; -.
DR DMDM; 74761508; -.
DR jPOST; Q9H7S9; -.
DR MassIVE; Q9H7S9; -.
DR MaxQB; Q9H7S9; -.
DR PaxDb; Q9H7S9; -.
DR PeptideAtlas; Q9H7S9; -.
DR PRIDE; Q9H7S9; -.
DR ProteomicsDB; 81143; -.
DR Antibodypedia; 10770; 306 antibodies from 32 providers.
DR DNASU; 80139; -.
DR Ensembl; ENST00000331569.6; ENSP00000332325.4; ENSG00000183779.7.
DR GeneID; 80139; -.
DR KEGG; hsa:80139; -.
DR MANE-Select; ENST00000331569.6; ENSP00000332325.4; NM_025069.3; NP_079345.1.
DR UCSC; uc003xjy.2; human.
DR CTD; 80139; -.
DR DisGeNET; 80139; -.
DR GeneCards; ZNF703; -.
DR HGNC; HGNC:25883; ZNF703.
DR HPA; ENSG00000183779; Tissue enhanced (skeletal).
DR neXtProt; NX_Q9H7S9; -.
DR OpenTargets; ENSG00000183779; -.
DR PharmGKB; PA142670500; -.
DR VEuPathDB; HostDB:ENSG00000183779; -.
DR eggNOG; ENOG502QV57; Eukaryota.
DR GeneTree; ENSGT00390000014618; -.
DR HOGENOM; CLU_035082_1_0_1; -.
DR InParanoid; Q9H7S9; -.
DR OMA; CKDPYCQ; -.
DR OrthoDB; 1163882at2759; -.
DR PhylomeDB; Q9H7S9; -.
DR TreeFam; TF324968; -.
DR PathwayCommons; Q9H7S9; -.
DR Reactome; R-HSA-212436; Generic Transcription Pathway.
DR SignaLink; Q9H7S9; -.
DR BioGRID-ORCS; 80139; 10 hits in 1091 CRISPR screens.
DR ChiTaRS; ZNF703; human.
DR GenomeRNAi; 80139; -.
DR Pharos; Q9H7S9; Tbio.
DR PRO; PR:Q9H7S9; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q9H7S9; protein.
DR Bgee; ENSG00000183779; Expressed in upper arm skin and 172 other tissues.
DR Genevisible; Q9H7S9; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0016363; C:nuclear matrix; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
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:0034333; P:adherens junction assembly; ISS:UniProtKB.
DR GO; GO:0071392; P:cellular response to estradiol stimulus; IDA:UniProtKB.
DR GO; GO:0060644; P:mammary gland epithelial cell differentiation; IDA:UniProtKB.
DR GO; GO:0034111; P:negative regulation of homotypic cell-cell adhesion; ISS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0030335; P:positive regulation of cell migration; ISS:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:UniProtKB.
DR GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; ISS:UniProtKB.
DR GO; GO:0033601; P:positive regulation of mammary gland epithelial cell proliferation; IDA:UniProtKB.
DR GO; GO:0060828; P:regulation of canonical Wnt signaling pathway; ISS:UniProtKB.
DR GO; GO:0051726; P:regulation of cell cycle; IDA:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0017015; P:regulation of transforming growth factor beta receptor signaling pathway; IDA:UniProtKB.
DR InterPro; IPR022129; Tscrpt_rep_NocA-like.
DR InterPro; IPR013087; Znf_C2H2_type.
DR Pfam; PF12402; nlz1; 1.
DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cytoplasm; Metal-binding; Methylation; Nucleus;
KW Phosphoprotein; Reference proteome; Repressor; Transcription;
KW Transcription regulation; Zinc; Zinc-finger.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330"
FT CHAIN 2..590
FT /note="Zinc finger protein 703"
FT /id="PRO_0000047702"
FT ZN_FING 456..484
FT /note="C2H2-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 1..43
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 96..293
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 341..366
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..19
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 165..189
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 208..223
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:19413330"
FT MOD_RES 252
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 580
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:P0CL69"
SQ SEQUENCE 590 AA; 58222 MW; 713243279114EF46 CRC64;
MSDSPAGSNP RTPESSGSGS GGGGKRPAVP AAVSLLPPAD PLRQANRLPI RVLKMLSAHT
GHLLHPEYLQ PLSSTPVSPI ELDAKKSPLA LLAQTCSQIG KPDPPPSSKL NSVAAAANGL
GAEKDPGRSA PGAASAAAAL KQLGDSPAED KSSFKPYSKG SGGGDSRKDS GSSSVSSTSS
SSSSSPGDKA GFRVPSAACP PFPPHGAPVS ASSSSSSPGG SRGGSPHHSD CKNGGGVGGG
ELDKKDQEPK PSPEPAAVSR GGGGEPGAHG GAESGASGRK SEPPSALVGA GHVAPVSPYK
PGHSVFPLPP SSIGYHGSIV GAYAGYPSQF VPGLDPSKSG LVGGQLSGGL GLPPGKPPSS
SPLTGASPPS FLQGLCRDPY CLGGYHGASH LGGSSCSTCS AHDPAGPSLK AGGYPLVYPG
HPLQPAALSS SAAQAALPGH PLYTYGFMLQ NEPLPHSCNW VAASGPCDKR FATSEELLSH
LRTHTALPGA EKLLAAYPGA SGLGSAAAAA AAAASCHLHL PPPAAPGSPG SLSLRNPHTL
GLSRYHPYGK SHLSTAGGLA VPSLPTAGPY YSPYALYGQR LASASALGYQ
