ZN746_HUMAN
ID ZN746_HUMAN Reviewed; 644 AA.
AC Q6NUN9; A8K6Z9; Q6ZRF9;
DT 17-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Zinc finger protein 746 {ECO:0000305};
DE AltName: Full=Parkin-interacting substrate;
DE Short=PARIS;
GN Name=ZNF746 {ECO:0000312|HGNC:HGNC:21948}; Synonyms=PARIS;
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] (ISOFORMS 2 AND 3).
RC TISSUE=Prostate, and Testis;
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=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
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 FUNCTION, SUBCELLULAR LOCATION, UBIQUITINATION, AND MUTAGENESIS OF CYS-458;
RP HIS-471; CYS-518; HIS-528; CYS-543; HIS-560; CYS-571 AND HIS-584.
RX PubMed=21376232; DOI=10.1016/j.cell.2011.02.010;
RA Shin J.H., Ko H.S., Kang H., Lee Y., Lee Y.I., Pletinkova O.,
RA Troconso J.C., Dawson V.L., Dawson T.M.;
RT "PARIS (ZNF746) repression of PGC-1alpha contributes to neurodegeneration
RT in Parkinson's disease.";
RL Cell 144:689-702(2011).
RN [5]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-282 AND LYS-286, AND
RP 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).
RN [6]
RP FUNCTION, SUBUNIT, AND INTERACTION WITH TRIM28.
RX PubMed=31856708; DOI=10.1186/s12860-019-0243-y;
RA Al Chiblak M., Steinbeck F., Thiesen H.J., Lorenz P.;
RT "DUF3669, a 'domain of unknown function' within ZNF746 and ZNF777,
RT oligomerizes and contributes to transcriptional repression.";
RL BMC Mol. Cell Biol. 20:60-60(2019).
CC -!- FUNCTION: Transcription repressor that specifically binds to the 5'-
CC TATTTT[T/G]-3' consensus sequence on promoters and repress
CC transcription of PGC-1-alpha (PPARGC1A), thereby playing a role in
CC regulation of neuron death. {ECO:0000269|PubMed:21376232,
CC ECO:0000269|PubMed:31856708}.
CC -!- SUBUNIT: Homooligomer, heterooligomer with ZNF746 (PubMed:31856708).
CC Interacts (via C2H2-type zinc fingers) with PRKN (By similarity).
CC {ECO:0000250|UniProtKB:Q3U133, ECO:0000269|PubMed:31856708}.
CC -!- SUBUNIT: [Isoform 1]: Interacts with TRIM28.
CC {ECO:0000269|PubMed:31856708}.
CC -!- INTERACTION:
CC Q6NUN9; O60260: PRKN; NbExp=6; IntAct=EBI-3862525, EBI-716346;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:21376232}. Nucleus
CC {ECO:0000305|PubMed:21376232}. Note=Mainly localizes to the cytoplasm;
CC probably translocates to the nucleus to repress selected genes.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q6NUN9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6NUN9-2; Sequence=VSP_041053;
CC Name=3;
CC IsoId=Q6NUN9-3; Sequence=VSP_041052;
CC -!- PTM: Ubiquitinated by PRKN. 'Lys-48'-linked polyubiquitination by PRKN
CC leads to degradation by the proteasome and may play a key role in
CC regulation of neuron death. {ECO:0000269|PubMed:21376232}.
CC -!- MISCELLANEOUS: May act as a downstream effector of PRKN and contribute
CC to neurodegeneration in Parkinson disease cases caused by defects in
CC PRKN: its accumulation due to the absence of PRKN, followed by up-
CC regulation of PPARGC1A, could lead to the selective loss of dopamine
CC neurons in the substantia nigra. {ECO:0000305|PubMed:21376232}.
CC -!- SIMILARITY: Belongs to the krueppel C2H2-type zinc-finger protein
CC family. {ECO:0000305}.
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DR EMBL; AK128244; BAC87351.1; -; mRNA.
DR EMBL; AK291814; BAF84503.1; -; mRNA.
DR EMBL; AC073314; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC068505; AAH68505.1; -; mRNA.
DR CCDS; CCDS55180.1; -. [Q6NUN9-2]
DR CCDS; CCDS5897.1; -. [Q6NUN9-1]
DR RefSeq; NP_001156946.1; NM_001163474.1. [Q6NUN9-2]
DR RefSeq; NP_689770.3; NM_152557.4. [Q6NUN9-1]
DR AlphaFoldDB; Q6NUN9; -.
DR BioGRID; 127574; 319.
DR IntAct; Q6NUN9; 36.
DR MINT; Q6NUN9; -.
DR STRING; 9606.ENSP00000395007; -.
DR iPTMnet; Q6NUN9; -.
DR PhosphoSitePlus; Q6NUN9; -.
DR BioMuta; ZNF746; -.
DR DMDM; 74736828; -.
DR EPD; Q6NUN9; -.
DR jPOST; Q6NUN9; -.
DR MassIVE; Q6NUN9; -.
DR MaxQB; Q6NUN9; -.
DR PaxDb; Q6NUN9; -.
DR PeptideAtlas; Q6NUN9; -.
DR PRIDE; Q6NUN9; -.
DR ProteomicsDB; 66696; -. [Q6NUN9-1]
DR ProteomicsDB; 66697; -. [Q6NUN9-2]
DR ProteomicsDB; 66698; -. [Q6NUN9-3]
DR ABCD; Q6NUN9; 1 sequenced antibody.
DR Antibodypedia; 46329; 66 antibodies from 21 providers.
DR DNASU; 155061; -.
DR Ensembl; ENST00000340622.8; ENSP00000345140.3; ENSG00000181220.18. [Q6NUN9-1]
DR Ensembl; ENST00000685153.1; ENSP00000508891.1; ENSG00000181220.18. [Q6NUN9-2]
DR GeneID; 155061; -.
DR KEGG; hsa:155061; -.
DR UCSC; uc003wfw.3; human. [Q6NUN9-1]
DR CTD; 155061; -.
DR DisGeNET; 155061; -.
DR GeneCards; ZNF746; -.
DR HGNC; HGNC:21948; ZNF746.
DR HPA; ENSG00000181220; Low tissue specificity.
DR MIM; 613914; gene.
DR neXtProt; NX_Q6NUN9; -.
DR OpenTargets; ENSG00000181220; -.
DR PharmGKB; PA144596520; -.
DR VEuPathDB; HostDB:ENSG00000181220; -.
DR eggNOG; KOG1721; Eukaryota.
DR GeneTree; ENSGT00940000161747; -.
DR HOGENOM; CLU_002678_76_3_1; -.
DR InParanoid; Q6NUN9; -.
DR OrthoDB; 1318335at2759; -.
DR PhylomeDB; Q6NUN9; -.
DR TreeFam; TF337777; -.
DR PathwayCommons; Q6NUN9; -.
DR Reactome; R-HSA-212436; Generic Transcription Pathway.
DR SignaLink; Q6NUN9; -.
DR BioGRID-ORCS; 155061; 6 hits in 1097 CRISPR screens.
DR ChiTaRS; ZNF746; human.
DR GenomeRNAi; 155061; -.
DR Pharos; Q6NUN9; Tbio.
DR PRO; PR:Q6NUN9; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q6NUN9; protein.
DR Bgee; ENSG00000181220; Expressed in blood and 162 other tissues.
DR ExpressionAtlas; Q6NUN9; baseline and differential.
DR Genevisible; Q6NUN9; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IC:ParkinsonsUK-UCL.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:ParkinsonsUK-UCL.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:NTNU_SB.
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; IDA:NTNU_SB.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:ParkinsonsUK-UCL.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:1901216; P:positive regulation of neuron death; IDA:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:ParkinsonsUK-UCL.
DR GO; GO:0051291; P:protein heterooligomerization; IDA:UniProtKB.
DR GO; GO:0051260; P:protein homooligomerization; 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; 3.
DR SMART; SM00349; KRAB; 1.
DR SMART; SM00355; ZnF_C2H2; 4.
DR SUPFAM; SSF109640; SSF109640; 1.
DR SUPFAM; SSF57667; SSF57667; 3.
DR PROSITE; PS50805; KRAB; 1.
DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 3.
DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 4.
PE 1: Evidence at protein level;
KW Alternative splicing; Coiled coil; Cytoplasm; DNA-binding; Isopeptide bond;
KW Metal-binding; Nucleus; Reference proteome; Repeat; Repressor;
KW Transcription; Transcription regulation; Ubl conjugation; Zinc;
KW Zinc-finger.
FT CHAIN 1..644
FT /note="Zinc finger protein 746"
FT /id="PRO_0000253728"
FT DOMAIN 96..167
FT /note="KRAB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00119"
FT ZN_FING 453..478
FT /note="C2H2-type 1; degenerate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 510..532
FT /note="C2H2-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 538..560
FT /note="C2H2-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 566..588
FT /note="C2H2-type 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 153..176
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 324..370
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 472..503
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 581..623
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 16..92
FT /evidence="ECO:0000255"
FT COMPBIAS 598..614
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CROSSLNK 282
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 286
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 1..185
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_041052"
FT VAR_SEQ 279
FT /note="E -> EA (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_041053"
FT MUTAGEN 458
FT /note="C->A: No effect."
FT /evidence="ECO:0000269|PubMed:21376232"
FT MUTAGEN 471
FT /note="H->A: No effect."
FT /evidence="ECO:0000269|PubMed:21376232"
FT MUTAGEN 518
FT /note="C->A: No effect."
FT /evidence="ECO:0000269|PubMed:21376232"
FT MUTAGEN 528
FT /note="H->A: No effect."
FT /evidence="ECO:0000269|PubMed:21376232"
FT MUTAGEN 543
FT /note="C->A: No effect."
FT /evidence="ECO:0000269|PubMed:21376232"
FT MUTAGEN 560
FT /note="H->A: No effect."
FT /evidence="ECO:0000269|PubMed:21376232"
FT MUTAGEN 571
FT /note="C->A: Impairs DNA-binding and ability to repress
FT PGC-1-alpha (PPARGC1A)."
FT /evidence="ECO:0000269|PubMed:21376232"
FT MUTAGEN 584
FT /note="H->A: No effect."
FT /evidence="ECO:0000269|PubMed:21376232"
SQ SEQUENCE 644 AA; 69136 MW; 4F6723D2225D95AB CRC64;
MAEAVAAPIS PWTMAATIQA MERKIESQAA RLLSLEGRTG MAEKKLADCE KTAVEFGNQL
EGKWAVLGTL LQEYGLLQRR LENVENLLRN RNFWILRLPP GSKGESPKEW GKLEDWQKEL
YKHVMRGNYE TLVSLDYAIS KPEVLSQIEQ GKEPCNWRRP GPKIPDVPVD PSPGSGPPVP
APDLLMQIKQ EGELQLQEQQ ALGVEAWAAG QPDIGEEPWG LSQLDSGAGD ISTDATSGVH
SNFSTTIPPT SWQTDLPPHH PSSACSDGTL KLNTAASTED VKIVIKTEVQ EEEVVATPVH
PTDLEAHGTL FGPGQATRFF PSPAQEGAWE SQGSSFPSQD PVLGLREPAR PERDMGELSP
AVAQEETPPG DWLFGGVRWG WNFRCKPPVG LNPRTGPEGL PYSSPDNGEA ILDPSQAPRP
FNEPCKYPGR TKGFGHKPGL KKHPAAPPGG RPFTCATCGK SFQLQVSLSA HQRSCGAPDG
SGPGTGGGGS GSGGGGGGSG GGSARDGSAL RCGECGRCFT RPAHLIRHRM LHTGERPFPC
TECEKRFTER SKLIDHYRTH TGVRPFTCTV CGKSFIRKDH LRKHQRNHAA GAKTPARGQP
LPTPPAPPDP FKSPASKGPL ASTDLVTDWT CGLSVLGPTD GGDM
