ZN445_HUMAN
ID ZN445_HUMAN Reviewed; 1031 AA.
AC P59923; Q3MJD1;
DT 10-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 10-OCT-2003, sequence version 1.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Zinc finger protein 445 {ECO:0000305};
DE Short=ZFP445 {ECO:0000303|PubMed:30602440};
DE AltName: Full=Zinc finger protein 168;
DE AltName: Full=Zinc finger protein with KRAB and SCAN domains 15;
GN Name=ZNF445 {ECO:0000312|HGNC:HGNC:21018};
GN Synonyms=ZFP445 {ECO:0000303|PubMed:30602440}, ZKSCAN15, ZNF168;
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].
RA Shan Y.X., Luo K.T., Guo Z.K., Tang W.W., Ye G.M., Yu L., Huang C.Q.;
RT "Cloning and characterization of a novel zinc finger protein.";
RL Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [3]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-938, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25218447; DOI=10.1038/nsmb.2890;
RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M.,
RA Vertegaal A.C.;
RT "Uncovering global SUMOylation signaling networks in a site-specific
RT manner.";
RL Nat. Struct. Mol. Biol. 21:927-936(2014).
RN [4]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-28, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25114211; DOI=10.1073/pnas.1413825111;
RA Impens F., Radoshevich L., Cossart P., Ribet D.;
RT "Mapping of SUMO sites and analysis of SUMOylation changes induced by
RT external stimuli.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:12432-12437(2014).
RN [5]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-938, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25755297; DOI=10.1074/mcp.o114.044792;
RA Xiao Z., Chang J.G., Hendriks I.A., Sigurdsson J.O., Olsen J.V.,
RA Vertegaal A.C.;
RT "System-wide analysis of SUMOylation dynamics in response to replication
RT stress reveals novel small ubiquitin-like modified target proteins and
RT acceptor lysines relevant for genome stability.";
RL Mol. Cell. Proteomics 14:1419-1434(2015).
RN [6]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-317; LYS-374; LYS-375; LYS-399;
RP LYS-567; LYS-654; LYS-736; LYS-758; LYS-938; LYS-956 AND LYS-975, 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 [7]
RP FUNCTION, DEVELOPMENTAL STAGE, AND SUBCELLULAR LOCATION.
RX PubMed=30602440; DOI=10.1101/gad.320069.118;
RA Takahashi N., Coluccio A., Thorball C.W., Planet E., Shi H., Offner S.,
RA Turelli P., Imbeault M., Ferguson-Smith A.C., Trono D.;
RT "ZNF445 is a primary regulator of genomic imprinting.";
RL Genes Dev. 33:49-54(2019).
CC -!- FUNCTION: Transcription regulator required to maintain maternal and
CC paternal gene imprinting, a process by which gene expression is
CC restricted in a parent of origin-specific manner by epigenetic
CC modification of genomic DNA and chromatin, including DNA methylation.
CC Acts by controlling DNA methylation during the earliest multicellular
CC stages of development at multiple imprinting control regions (ICRs)
CC (PubMed:30602440). Acts together with ZFP57, but seems to be the major
CC factor in human early embryonic imprinting maintenance. In contrast, in
CC mice, ZFP57 plays the predominant role in imprinting maintenance
CC (PubMed:30602440). {ECO:0000269|PubMed:30602440}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:30602440}. Note=Binds
CC various differentially methylated regions (DMR).
CC {ECO:0000269|PubMed:30602440}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the oocyte, expression is maintained
CC at least until blastocyst stage. {ECO:0000269|PubMed:30602440}.
CC -!- SIMILARITY: Belongs to the krueppel C2H2-type zinc-finger protein
CC family. {ECO:0000305}.
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DR EMBL; AY262260; AAP36990.1; -; mRNA.
DR EMBL; AY295873; AAP50258.1; -; mRNA.
DR EMBL; BC101486; AAI01487.1; -; mRNA.
DR CCDS; CCDS2713.1; -.
DR RefSeq; NP_852466.1; NM_181489.5.
DR RefSeq; XP_005265159.1; XM_005265102.2.
DR RefSeq; XP_011531976.1; XM_011533674.2.
DR AlphaFoldDB; P59923; -.
DR SMR; P59923; -.
DR BioGRID; 131672; 57.
DR IntAct; P59923; 21.
DR MINT; P59923; -.
DR STRING; 9606.ENSP00000413073; -.
DR iPTMnet; P59923; -.
DR PhosphoSitePlus; P59923; -.
DR BioMuta; ZNF445; -.
DR DMDM; 45593854; -.
DR EPD; P59923; -.
DR jPOST; P59923; -.
DR MassIVE; P59923; -.
DR MaxQB; P59923; -.
DR PaxDb; P59923; -.
DR PeptideAtlas; P59923; -.
DR PRIDE; P59923; -.
DR ProteomicsDB; 57172; -.
DR Antibodypedia; 29430; 48 antibodies from 13 providers.
DR DNASU; 353274; -.
DR Ensembl; ENST00000396077.8; ENSP00000379387.2; ENSG00000185219.18.
DR Ensembl; ENST00000425708.6; ENSP00000413073.2; ENSG00000185219.18.
DR Ensembl; ENST00000634579.1; ENSP00000489139.1; ENSG00000283034.2.
DR Ensembl; ENST00000635479.2; ENSP00000489368.1; ENSG00000283034.2.
DR GeneID; 353274; -.
DR KEGG; hsa:353274; -.
DR MANE-Select; ENST00000396077.8; ENSP00000379387.2; NM_181489.6; NP_852466.1.
DR UCSC; uc003cnf.3; human.
DR CTD; 353274; -.
DR GeneCards; ZNF445; -.
DR HGNC; HGNC:21018; ZNF445.
DR HPA; ENSG00000185219; Low tissue specificity.
DR MIM; 619508; gene.
DR neXtProt; NX_P59923; -.
DR OpenTargets; ENSG00000185219; -.
DR PharmGKB; PA134904986; -.
DR VEuPathDB; HostDB:ENSG00000185219; -.
DR eggNOG; KOG1721; Eukaryota.
DR GeneTree; ENSGT00900000141186; -.
DR HOGENOM; CLU_002678_23_0_1; -.
DR InParanoid; P59923; -.
DR OMA; CHKCNIC; -.
DR OrthoDB; 1318335at2759; -.
DR PhylomeDB; P59923; -.
DR TreeFam; TF350827; -.
DR PathwayCommons; P59923; -.
DR Reactome; R-HSA-212436; Generic Transcription Pathway.
DR SignaLink; P59923; -.
DR BioGRID-ORCS; 353274; 23 hits in 1111 CRISPR screens.
DR ChiTaRS; ZNF445; human.
DR GenomeRNAi; 353274; -.
DR Pharos; P59923; Tdark.
DR PRO; PR:P59923; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; P59923; protein.
DR Bgee; ENSG00000185219; Expressed in cortical plate and 110 other tissues.
DR ExpressionAtlas; P59923; baseline and differential.
DR Genevisible; P59923; HS.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0010385; F:double-stranded methylated DNA binding; IDA:UniProtKB.
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:0010216; P:maintenance of DNA methylation; IMP:UniProtKB.
DR GO; GO:2000653; P:regulation of genetic imprinting; 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 CDD; cd07936; SCAN; 1.
DR Gene3D; 1.10.4020.10; -; 1.
DR InterPro; IPR001909; KRAB.
DR InterPro; IPR036051; KRAB_dom_sf.
DR InterPro; IPR003309; SCAN_dom.
DR InterPro; IPR038269; SCAN_sf.
DR InterPro; IPR036236; Znf_C2H2_sf.
DR InterPro; IPR013087; Znf_C2H2_type.
DR Pfam; PF01352; KRAB; 1.
DR Pfam; PF02023; SCAN; 1.
DR Pfam; PF00096; zf-C2H2; 11.
DR SMART; SM00349; KRAB; 1.
DR SMART; SM00431; SCAN; 1.
DR SMART; SM00355; ZnF_C2H2; 14.
DR SUPFAM; SSF109640; SSF109640; 1.
DR SUPFAM; SSF57667; SSF57667; 9.
DR PROSITE; PS50805; KRAB; 1.
DR PROSITE; PS50804; SCAN_BOX; 1.
DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 14.
DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 14.
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..1031
FT /note="Zinc finger protein 445"
FT /id="PRO_0000047594"
FT DOMAIN 55..137
FT /note="SCAN box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00187"
FT DOMAIN 234..304
FT /note="KRAB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00119"
FT ZN_FING 485..507
FT /note="C2H2-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 513..535
FT /note="C2H2-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 541..563
FT /note="C2H2-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 597..619
FT /note="C2H2-type 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 625..647
FT /note="C2H2-type 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 681..703
FT /note="C2H2-type 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 709..731
FT /note="C2H2-type 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 762..784
FT /note="C2H2-type 8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 790..812
FT /note="C2H2-type 9"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 840..862
FT /note="C2H2-type 10"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 868..890
FT /note="C2H2-type 11"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 896..918
FT /note="C2H2-type 12"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 978..1000
FT /note="C2H2-type 13"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 1006..1028
FT /note="C2H2-type 14"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 1..43
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 911..939
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 21..36
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CROSSLNK 28
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1)"
FT /evidence="ECO:0007744|PubMed:25114211"
FT CROSSLNK 317
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 374
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 375
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 399
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 567
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 654
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 736
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 758
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 938
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25218447,
FT ECO:0007744|PubMed:25755297, ECO:0007744|PubMed:28112733"
FT CROSSLNK 956
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 975
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VARIANT 428
FT /note="Y -> C (in dbSNP:rs11710965)"
FT /id="VAR_052832"
SQ SEQUENCE 1031 AA; 118963 MW; 39C288802894006E CRC64;
MPPGRWHAAY PAQAQSSRER GRLQTVKKEE EDESYTPVQA ARPQTLNRPG QELFRQLFRQ
LRYHESSGPL ETLSRLRELC RWWLRPDVLS KAQILELLVL EQFLSILPGE LRVWVQLHNP
ESGEEAVALL EELQRDLDGT SWRDPGPAQS PDVHWMGTGA LRSAQIWSLA SPLRSSSALG
DHLEPPYEIE ARDFLAGQSD TPAAQMPALF PREGCPGDQV TPTRSLTAQL QETMTFKDVE
VTFSQDEWGW LDSAQRNLYR DVMLENYRNM ASLVGPFTKP ALISWLEARE PWGLNMQAAQ
PKGNPVAAPT GDDLQSKTNK FILNQEPLEE AETLAVSSGC PATSVSEGIG LRESFQQKSR
QKDQCENPIQ VRVKKEETNF SHRTGKDSEV SGSNSLDLKH VTYLRVSGRK ESLKHGCGKH
FRMSSHHYDY KKYGKGLRHM IGGFSLHQRI HSGLKGNKKD VCGKDFSLSS HHQRGQSLHT
VGVSFKCSDC GRTFSHSSHL AYHQRLHTQE KAFKCRVCGK AFRWSSNCAR HEKIHTGVKP
YKCDLCEKAF RRLSAYRLHR ETHAKKKFLE LNQYRAALTY SSGFDHHLGD QSGEKLFDCS
QCRKSFHCKS YVLEHQRIHT QEKPYKCTKC RKTFRWRSNF TRHMRLHEEE KFYKQDECRE
GFRQSPDCSQ PQGAPAVEKT FLCQQCGKTF TRKKTLVDHQ RIHTGEKPYQ CSDCGKDFAY
RSAFIVHKKK HAMKRKPEGG PSFSQDTVFQ VPQSSHSKEE PYKCSQCGKA FRNHSFLLIH
QRVHTGEKPY KCRECGKAFR WSSNLYRHQR IHSLQKQYDC HESEKTPNVE PKILTGEKRF
WCQECGKTFT RKRTLLDHKG IHSGEKRYKC NLCGKSYDRN YRLVNHQRIH STERPFKCQW
CGKEFIGRHT LSSHQRKHTR AAQAERSPPA RSSSQDTKLR LQKLKPSEEM PLEDCKEACS
QSSRLTGLQD ISIGKKCHKC SICGKTFNKS SQLISHKRFH TRERPFKCSK CGKTFRWSSN
LARHMKNHIR D
