ZNF93_HUMAN
ID ZNF93_HUMAN Reviewed; 620 AA.
AC P35789; A6NMY2; B9EGT2; Q8N8Q4; Q9H9X5; Q9Y2N8;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 10-JAN-2006, sequence version 4.
DT 03-AUG-2022, entry version 192.
DE RecName: Full=Zinc finger protein 93;
DE AltName: Full=Zinc finger protein 505;
DE AltName: Full=Zinc finger protein HTF34;
GN Name=ZNF93; Synonyms=ZNF505;
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] (ISOFORM 2), NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 307-620 (ISOFORM 3), AND VARIANT TYR-93.
RC TISSUE=Teratocarcinoma;
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=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 NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain, and Testis;
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 [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 5-195.
RX PubMed=2023909; DOI=10.1073/pnas.88.9.3608;
RA Bellefroid E.J., Poncelet D.A., Lecocq P.J., Revelant O., Martial J.A.;
RT "The evolutionarily conserved Kruppel-associated box domain defines a
RT subfamily of eukaryotic multifingered proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:3608-3612(1991).
RN [6]
RP RESISTANCE TO ET-743 AND PM00104 ANTITUMORS.
RX PubMed=19742314; DOI=10.1371/journal.pone.0006967;
RA Duan Z., Choy E., Harmon D., Yang C., Ryu K., Schwab J., Mankin H.,
RA Hornicek F.J.;
RT "ZNF93 increases resistance to ET-743 (Trabectedin; Yondelis) and PM00104
RT (Zalypsis) in human cancer cell lines.";
RL PLoS ONE 4:E6967-E6967(2009).
RN [7]
RP FUNCTION.
RX PubMed=25274305; DOI=10.1038/nature13760;
RA Jacobs F.M., Greenberg D., Nguyen N., Haeussler M., Ewing A.D., Katzman S.,
RA Paten B., Salama S.R., Haussler D.;
RT "An evolutionary arms race between KRAB zinc-finger genes ZNF91/93 and
RT SVA/L1 retrotransposons.";
RL Nature 516:242-245(2014).
CC -!- FUNCTION: Transcription factor specifically required to repress long
CC interspersed nuclear element 1 (L1) retrotransposons: recognizes and
CC binds L1 sequences and repress their expression by recruiting a
CC repressive complex containing TRIM28/KAP1 (PubMed:25274305). Not able
CC to repress expression of all subtypes of L1 elements. Binds to the 5'
CC end of L1PA4, L1PA5 and L1PA6 subtypes, and some L1PA3 subtypes. Does
CC not bind to L1PA7 or older subtypes nor at the most recently evolved
CC L1PA2 and L1Hs. 50% of L1PA3 elements have lost the ZNF93-binding site,
CC explaining why ZNF93 is not able to repress their expression
CC (PubMed:25274305). {ECO:0000269|PubMed:25274305}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P35789-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P35789-2; Sequence=VSP_016988;
CC Name=3;
CC IsoId=P35789-3; Sequence=VSP_016989;
CC -!- DEVELOPMENTAL STAGE: Expressed early during embryonic development.
CC -!- MISCELLANEOUS: ZNF93 is only present in primates and evolved to repress
CC the primate L1 lineage until 12.5 million years. Evolution stopped when
CC the L1PA3-subfamily of retrotransposons, that escape repression by
CC ZNF93 through the removal of the ZNF93-binding site, appeared
CC (PubMed:25274305). {ECO:0000269|PubMed:25274305}.
CC -!- MISCELLANEOUS: Confers resistance to ET-743 (trabectedin, Yondelis) and
CC PM00104 (Zalypsis), 2 marine derived compounds with antitumor activity
CC in cancer cell lines. {ECO:0000305|PubMed:19742314}.
CC -!- SIMILARITY: Belongs to the krueppel C2H2-type zinc-finger protein
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD22981.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=BAB14093.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AK022550; BAB14093.1; ALT_INIT; mRNA.
DR EMBL; AK096342; BAC04764.1; -; mRNA.
DR EMBL; AC007204; AAD22981.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AC011477; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471106; EAW84866.1; -; Genomic_DNA.
DR EMBL; BC136718; AAI36719.1; -; mRNA.
DR EMBL; BC136719; AAI36720.1; -; mRNA.
DR EMBL; M61873; AAA83548.1; -; Genomic_DNA.
DR CCDS; CCDS32973.1; -. [P35789-1]
DR PIR; H39384; H39384.
DR RefSeq; NP_112495.2; NM_031218.3. [P35789-1]
DR AlphaFoldDB; P35789; -.
DR SMR; P35789; -.
DR BioGRID; 123631; 3.
DR IntAct; P35789; 2.
DR STRING; 9606.ENSP00000342002; -.
DR iPTMnet; P35789; -.
DR PhosphoSitePlus; P35789; -.
DR BioMuta; ZNF93; -.
DR DMDM; 85681872; -.
DR EPD; P35789; -.
DR jPOST; P35789; -.
DR MassIVE; P35789; -.
DR MaxQB; P35789; -.
DR PaxDb; P35789; -.
DR PeptideAtlas; P35789; -.
DR PRIDE; P35789; -.
DR ProteomicsDB; 55151; -. [P35789-1]
DR ProteomicsDB; 55152; -. [P35789-2]
DR ProteomicsDB; 55153; -. [P35789-3]
DR Antibodypedia; 56725; 121 antibodies from 15 providers.
DR DNASU; 81931; -.
DR Ensembl; ENST00000343769.6; ENSP00000342002.4; ENSG00000184635.16. [P35789-1]
DR GeneID; 81931; -.
DR KEGG; hsa:81931; -.
DR MANE-Select; ENST00000343769.6; ENSP00000342002.4; NM_031218.4; NP_112495.2.
DR UCSC; uc002non.4; human. [P35789-1]
DR CTD; 81931; -.
DR DisGeNET; 81931; -.
DR GeneCards; ZNF93; -.
DR HGNC; HGNC:13169; ZNF93.
DR HPA; ENSG00000184635; Low tissue specificity.
DR MIM; 603975; gene.
DR neXtProt; NX_P35789; -.
DR OpenTargets; ENSG00000184635; -.
DR PharmGKB; PA37741; -.
DR VEuPathDB; HostDB:ENSG00000184635; -.
DR eggNOG; KOG1721; Eukaryota.
DR GeneTree; ENSGT00940000162960; -.
DR HOGENOM; CLU_002678_0_2_1; -.
DR InParanoid; P35789; -.
DR OMA; HEFIHMG; -.
DR PhylomeDB; P35789; -.
DR TreeFam; TF342117; -.
DR PathwayCommons; P35789; -.
DR SignaLink; P35789; -.
DR BioGRID-ORCS; 81931; 17 hits in 1065 CRISPR screens.
DR ChiTaRS; ZNF93; human.
DR GenomeRNAi; 81931; -.
DR Pharos; P35789; Tbio.
DR PRO; PR:P35789; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; P35789; protein.
DR Bgee; ENSG00000184635; Expressed in secondary oocyte and 160 other tissues.
DR ExpressionAtlas; P35789; baseline and differential.
DR Genevisible; P35789; HS.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; NAS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0070895; P:negative regulation of transposon integration; IDA: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; 14.
DR SMART; SM00349; KRAB; 1.
DR SMART; SM00355; ZnF_C2H2; 17.
DR SUPFAM; SSF109640; SSF109640; 1.
DR SUPFAM; SSF57667; SSF57667; 9.
DR PROSITE; PS50805; KRAB; 1.
DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 16.
DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 17.
PE 2: Evidence at transcript level;
KW Alternative splicing; DNA-binding; Metal-binding; Nucleus;
KW Reference proteome; Repeat; Repressor; Transcription;
KW Transcription regulation; Zinc; Zinc-finger.
FT CHAIN 1..620
FT /note="Zinc finger protein 93"
FT /id="PRO_0000047402"
FT DOMAIN 4..75
FT /note="KRAB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00119"
FT ZN_FING 145..167
FT /note="C2H2-type 1; degenerate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 173..195
FT /note="C2H2-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 201..223
FT /note="C2H2-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 229..251
FT /note="C2H2-type 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 257..279
FT /note="C2H2-type 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 285..307
FT /note="C2H2-type 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 313..335
FT /note="C2H2-type 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 341..363
FT /note="C2H2-type 8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 369..391
FT /note="C2H2-type 9"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 397..419
FT /note="C2H2-type 10"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 425..447
FT /note="C2H2-type 11"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 453..475
FT /note="C2H2-type 12"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 481..503
FT /note="C2H2-type 13"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 509..531
FT /note="C2H2-type 14"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 537..559
FT /note="C2H2-type 15"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 565..587
FT /note="C2H2-type 16"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 593..615
FT /note="C2H2-type 17"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT VAR_SEQ 391..418
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_016988"
FT VAR_SEQ 499..582
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_016989"
FT VARIANT 93
FT /note="D -> Y (in dbSNP:rs12151060)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_052768"
FT CONFLICT 75
FT /note="S -> SGP (in Ref. 5; AAA83548)"
FT /evidence="ECO:0000305"
FT CONFLICT 89
FT /note="Q -> H (in Ref. 5; AAA83548)"
FT /evidence="ECO:0000305"
FT CONFLICT 119
FT /note="S -> R (in Ref. 5; AAA83548)"
FT /evidence="ECO:0000305"
FT CONFLICT 136
FT /note="C -> S (in Ref. 5; AAA83548)"
FT /evidence="ECO:0000305"
FT CONFLICT 153
FT /note="V -> D (in Ref. 5; AAA83548)"
FT /evidence="ECO:0000305"
FT CONFLICT 337
FT /note="G -> E (in Ref. 1; BAC04764)"
FT /evidence="ECO:0000305"
FT CONFLICT 597
FT /note="K -> E (in Ref. 1; BAC04764)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 620 AA; 70971 MW; 722A49B2EA82801A CRC64;
MGPLQFRDVA IEFSLEEWHC LDTAQRNLYR NVMLENYSNL VFLGIVVSKP DLIAHLEQGK
KPLTMKRHEM VANPSVICSH FAQDLWPEQN IKDSFQKVIL RRYEKRGHGN LQLIKRCESV
DECKVHTGGY NGLNQCSTTT QSKVFQCDKY GKVFHKFSNS NRHNIRHTEK KPFKCIECGK
AFNQFSTLIT HKKIHTGEKP YICEECGKAF KYSSALNTHK RIHTGEKPYK CDKCDKAFIA
SSTLSKHEII HTGKKPYKCE ECGKAFNQSS TLTKHKKIHT GEKPYKCEEC GKAFNQSSTL
TKHKKIHTGE KPYVCEECGK AFKYSRILTT HKRIHTGEKP YKCNKCGKAF IASSTLSRHE
FIHMGKKHYK CEECGKAFIW SSVLTRHKRV HTGEKPYKCE ECGKAFKYSS TLSSHKRSHT
GEKPYKCEEC GKAFVASSTL SKHEIIHTGK KPYKCEECGK AFNQSSSLTK HKKIHTGEKP
YKCEECGKAF NQSSSLTKHK KIHTGEKPYK CEECGKAFNQ SSTLIKHKKI HTREKPYKCE
ECGKAFHLST HLTTHKILHT GEKPYRCREC GKAFNHSATL SSHKKIHSGE KPYECDKCGK
AFISPSSLSR HEIIHTGEKP
