ID   ZFP57_HUMAN             Reviewed;         452 AA.
AC   Q9NU63; B0S894; B0V254; B2RXJ7; Q5SSB1;
DT   26-JUN-2007, integrated into UniProtKB/Swiss-Prot.
DT   26-JUN-2007, sequence version 2.
DT   27-MAR-2024, entry version 172.
DE   RecName: Full=Zinc finger protein 57 homolog {ECO:0000305};
DE            Short=Zfp-57;
DE   AltName: Full=Zinc finger protein 698;
GN   Name=ZFP57 {ECO:0000312|HGNC:HGNC:18791}; Synonyms=C6orf40, ZNF698;
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 GENOMIC DNA], AND VARIANT VAL-284.
RX   PubMed=14574404; DOI=10.1038/nature02055;
RA   Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA   Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA   Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA   Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA   Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA   Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA   Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA   Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA   Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA   Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA   French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA   Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA   Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA   Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA   Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA   Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA   Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA   Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA   Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA   Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA   Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA   Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA   Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA   Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA   Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA   Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA   West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA   Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA   Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA   Rogers J., Beck S.;
RT   "The DNA sequence and analysis of human chromosome 6.";
RL   Nature 425:805-811(2003).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
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   FUNCTION, AND DEVELOPMENTAL STAGE.
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).
RN   [4]
RP   VARIANTS TNDM1 HIS-166; ASN-193 AND ASP-374, AND FUNCTION.
RX   PubMed=18622393; DOI=10.1038/ng.187;
RA   Mackay D.J.G., Callaway J.L.A., Marks S.M., White H.E., Acerini C.L.,
RA   Boonen S.E., Dayanikli P., Firth H.V., Goodship J.A., Haemers A.P.,
RA   Hahnemann J.M.D., Kordonouri O., Masoud A.F., Oestergaard E., Storr J.,
RA   Ellard S., Hattersley A.T., Robinson D.O., Temple I.K.;
RT   "Hypomethylation of multiple imprinted loci in individuals with transient
RT   neonatal diabetes is associated with mutations in ZFP57.";
RL   Nat. Genet. 40:949-951(2008).
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:18622393, PubMed:30602440). Acts together with ZNF445, but
CC       ZNF445 seems to be the major factor in human early embryonic imprinting
CC       maintenance. In contrast, in mice, ZFP57 plays the predominant role in
CC       imprinting maintenance (PubMed:30602440). Required for the
CC       establishment of maternal methylation imprints at SNRPN locus. Acts as
CC       a transcriptional repressor in Schwann cells. Binds to a 5'-TGCCGC-3'
CC       consensus sequence and recognizes the methylated CpG within this
CC       element (By similarity). {ECO:0000250|UniProtKB:Q8C6P8,
CC       ECO:0000269|PubMed:18622393, ECO:0000269|PubMed:30602440}.
CC   -!- INTERACTION:
CC       Q9NU63-3; Q96Q77: CIB3; NbExp=3; IntAct=EBI-12879708, EBI-10292696;
CC       Q9NU63-3; Q92997: DVL3; NbExp=3; IntAct=EBI-12879708, EBI-739789;
CC       Q9NU63-3; P50402: EMD; NbExp=3; IntAct=EBI-12879708, EBI-489887;
CC       Q9NU63-3; Q63ZY3: KANK2; NbExp=3; IntAct=EBI-12879708, EBI-2556193;
CC       Q9NU63-3; Q13064: MKRN3; NbExp=3; IntAct=EBI-12879708, EBI-2340269;
CC       Q9NU63-3; P40692: MLH1; NbExp=3; IntAct=EBI-12879708, EBI-744248;
CC       Q9NU63-3; O15160: POLR1C; NbExp=3; IntAct=EBI-12879708, EBI-1055079;
CC       Q9NU63-3; Q5VVQ6: YOD1; NbExp=3; IntAct=EBI-12879708, EBI-2510804;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:30602440}. Note=Binds
CC       various differentially methylated regions (DMR).
CC       {ECO:0000269|PubMed:30602440}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=Q9NU63-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q9NU63-2; Sequence=VSP_026329, VSP_026330;
CC       Name=3;
CC         IsoId=Q9NU63-3; Sequence=VSP_036659, VSP_026330;
CC   -!- DEVELOPMENTAL STAGE: In contrast to mice, transcripts are undetectable
CC       in the oocyte and during the earliest stages of embryonic development,
CC       increasing only after zygotic genome activation.
CC       {ECO:0000269|PubMed:30602440}.
CC   -!- DOMAIN: The KRAB domain is required for function as transcriptional
CC       repressor. {ECO:0000250|UniProtKB:Q8C6P8}.
CC   -!- DOMAIN: Zinc fingers 3 and 4 mediate recognition of the target element,
CC       ZF3 interacting with the 5' half (TGC) and ZF4 interacting with the 3'
CC       half (CGC). {ECO:0000250|UniProtKB:Q8C6P8}.
CC   -!- DISEASE: Diabetes mellitus, transient neonatal, 1 (TNDM1) [MIM:601410]:
CC       An autosomal dominant form of diabetes mellitus defined by the onset of
CC       mild-to-severe hyperglycemia within the first month of life. In about
CC       half of the neonates, diabetes is transient and resolves at a median
CC       age of 3 months, whereas the rest have a permanent form of diabetes.
CC       {ECO:0000269|PubMed:18622393}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the krueppel C2H2-type zinc-finger protein
CC       family. ZFP57 subfamily. {ECO:0000305}.
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DR   EMBL; AL050328; CAB89275.2; -; Genomic_DNA.
DR   EMBL; AL645936; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL669813; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL929591; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BX120002; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BX927250; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CR388408; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CR759766; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CR936483; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC157878; AAI57879.1; -; mRNA.
DR   CCDS; CCDS43436.2; -. [Q9NU63-3]
DR   RefSeq; NP_001103279.2; NM_001109809.2. [Q9NU63-3]
DR   AlphaFoldDB; Q9NU63; -.
DR   SMR; Q9NU63; -.
DR   BioGRID; 131375; 14.
DR   IntAct; Q9NU63; 9.
DR   MINT; Q9NU63; -.
DR   STRING; 9606.ENSP00000418259; -.
DR   iPTMnet; Q9NU63; -.
DR   PhosphoSitePlus; Q9NU63; -.
DR   BioMuta; ZFP57; -.
DR   DMDM; 150416327; -.
DR   EPD; Q9NU63; -.
DR   MassIVE; Q9NU63; -.
DR   MaxQB; Q9NU63; -.
DR   PeptideAtlas; Q9NU63; -.
DR   ProteomicsDB; 82655; -. [Q9NU63-1]
DR   ProteomicsDB; 82656; -. [Q9NU63-2]
DR   ProteomicsDB; 82657; -. [Q9NU63-3]
DR   Antibodypedia; 26080; 231 antibodies from 20 providers.
DR   DNASU; 346171; -.
DR   Ensembl; ENST00000376883.2; ENSP00000366080.2; ENSG00000204644.10. [Q9NU63-3]
DR   Ensembl; ENST00000383628.6; ENSP00000373124.2; ENSG00000206510.9. [Q9NU63-2]
DR   Ensembl; ENST00000416974.5; ENSP00000396462.1; ENSG00000223858.7. [Q9NU63-2]
DR   Ensembl; ENST00000435906.5; ENSP00000412932.1; ENSG00000226858.7. [Q9NU63-2]
DR   Ensembl; ENST00000437216.5; ENSP00000398086.1; ENSG00000223852.7. [Q9NU63-2]
DR   Ensembl; ENST00000446005.5; ENSP00000394222.1; ENSG00000234669.7. [Q9NU63-2]
DR   Ensembl; ENST00000448114.5; ENSP00000409118.1; ENSG00000232099.7. [Q9NU63-2]
DR   Ensembl; ENST00000547542.2; ENSP00000447492.2; ENSG00000223852.7. [Q9NU63-1]
DR   Ensembl; ENST00000547911.2; ENSP00000449556.2; ENSG00000234669.7. [Q9NU63-1]
DR   Ensembl; ENST00000548001.2; ENSP00000446541.2; ENSG00000232099.7. [Q9NU63-1]
DR   Ensembl; ENST00000548337.1; ENSP00000449407.1; ENSG00000232099.7. [Q9NU63-3]
DR   Ensembl; ENST00000548574.1; ENSP00000446798.1; ENSG00000223852.7. [Q9NU63-3]
DR   Ensembl; ENST00000548769.1; ENSP00000448351.1; ENSG00000206510.9. [Q9NU63-3]
DR   Ensembl; ENST00000549167.1; ENSP00000449230.1; ENSG00000226858.7. [Q9NU63-3]
DR   Ensembl; ENST00000549501.2; ENSP00000447698.2; ENSG00000226858.7. [Q9NU63-1]
DR   Ensembl; ENST00000552809.1; ENSP00000450279.1; ENSG00000223858.7. [Q9NU63-3]
DR   Ensembl; ENST00000552898.2; ENSP00000450397.2; ENSG00000223858.7. [Q9NU63-1]
DR   Ensembl; ENST00000552987.2; ENSP00000448634.2; ENSG00000206510.9. [Q9NU63-1]
DR   Ensembl; ENST00000553137.1; ENSP00000447495.1; ENSG00000234669.7. [Q9NU63-3]
DR   GeneID; 346171; -.
DR   KEGG; hsa:346171; -.
DR   MANE-Select; ENST00000376883.2; ENSP00000366080.2; NM_001109809.5; NP_001103279.2. [Q9NU63-3]
DR   UCSC; uc011dlw.2; human. [Q9NU63-1]
DR   AGR; HGNC:18791; -.
DR   CTD; 346171; -.
DR   DisGeNET; 346171; -.
DR   GeneCards; ZFP57; -.
DR   GeneReviews; ZFP57; -.
DR   HGNC; HGNC:18791; ZFP57.
DR   HPA; ENSG00000204644; Group enriched (brain, heart muscle).
DR   MalaCards; ZFP57; -.
DR   MIM; 601410; phenotype.
DR   MIM; 612192; gene.
DR   neXtProt; NX_Q9NU63; -.
DR   OpenTargets; ENSG00000204644; -.
DR   Orphanet; 99886; Transient neonatal diabetes mellitus.
DR   PharmGKB; PA134937821; -.
DR   VEuPathDB; HostDB:ENSG00000204644; -.
DR   GeneTree; ENSGT00390000002599; -.
DR   HOGENOM; CLU_002678_0_7_1; -.
DR   InParanoid; Q9NU63; -.
DR   OMA; HQQTHWR; -.
DR   OrthoDB; 5265384at2759; -.
DR   PhylomeDB; Q9NU63; -.
DR   TreeFam; TF337947; -.
DR   PathwayCommons; Q9NU63; -.
DR   SignaLink; Q9NU63; -.
DR   BioGRID-ORCS; 346171; 31 hits in 1164 CRISPR screens.
DR   GeneWiki; ZFP57; -.
DR   GenomeRNAi; 346171; -.
DR   Pharos; Q9NU63; Tbio.
DR   PRO; PR:Q9NU63; -.
DR   Proteomes; UP000005640; Chromosome 6.
DR   RNAct; Q9NU63; Protein.
DR   Bgee; ENSG00000204644; Expressed in primordial germ cell in gonad and 86 other cell types or tissues.
DR   ExpressionAtlas; Q9NU63; baseline and differential.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0003682; F:chromatin binding; IDA:UniProtKB.
DR   GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IBA:GO_Central.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR   GO; GO:0141068; P:autosome genomic imprinting; IMP:UniProtKB.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   CDD; cd07765; KRAB_A-box; 1.
DR   Gene3D; 6.10.140.140; -; 1.
DR   Gene3D; 3.30.160.60; Classic Zinc Finger; 6.
DR   InterPro; IPR001909; KRAB.
DR   InterPro; IPR036051; KRAB_dom_sf.
DR   InterPro; IPR036236; Znf_C2H2_sf.
DR   InterPro; IPR013087; Znf_C2H2_type.
DR   PANTHER; PTHR23232; KRAB DOMAIN C2H2 ZINC FINGER; 1.
DR   PANTHER; PTHR23232:SF90; KRAB DOMAIN-CONTAINING PROTEIN; 1.
DR   Pfam; PF01352; KRAB; 1.
DR   Pfam; PF00096; zf-C2H2; 6.
DR   SMART; SM00349; KRAB; 1.
DR   SMART; SM00355; ZnF_C2H2; 7.
DR   SUPFAM; SSF57667; beta-beta-alpha zinc fingers; 4.
DR   SUPFAM; SSF109640; KRAB domain (Kruppel-associated box); 1.
DR   PROSITE; PS50805; KRAB; 1.
DR   PROSITE; PS00028; ZINC_FINGER_C2H2_1; 6.
DR   PROSITE; PS50157; ZINC_FINGER_C2H2_2; 7.
DR   Genevisible; Q9NU63; HS.
PE   1: Evidence at protein level;
KW   Alternative splicing; Developmental protein; Diabetes mellitus;
KW   Disease variant; DNA-binding; Metal-binding; Nucleus; Reference proteome;
KW   Repeat; Repressor; Transcription; Transcription regulation; Zinc;
KW   Zinc-finger.
FT   CHAIN           1..452
FT                   /note="Zinc finger protein 57 homolog"
FT                   /id="PRO_0000291964"
FT   DOMAIN          16..88
FT                   /note="KRAB"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00119"
FT   ZN_FING         91..113
FT                   /note="C2H2-type 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT   ZN_FING         119..141
FT                   /note="C2H2-type 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT   ZN_FING         147..169
FT                   /note="C2H2-type 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT   ZN_FING         175..197
FT                   /note="C2H2-type 4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT   ZN_FING         300..322
FT                   /note="C2H2-type 5"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT   ZN_FING         328..350
FT                   /note="C2H2-type 6"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT   ZN_FING         356..378
FT                   /note="C2H2-type 7; degenerate"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT   REGION          410..452
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   SITE            185
FT                   /note="Crucial for 5-methylcytosine recognition"
FT                   /evidence="ECO:0000250"
FT   VAR_SEQ         1..13
FT                   /note="MAAGEPRSLLFFQ -> MFEQLKPIEPRDCWREARVKK (in isoform
FT                   2)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_026329"
FT   VAR_SEQ         1..13
FT                   /note="MAAGEPRSLLFFQ -> MFEQLKPIEPVQKTLPWVGEVAATLQEAMKRDCWR
FT                   EARVKK (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_036659"
FT   VAR_SEQ         78
FT                   /note="E -> EFVHLPNTEGLSEGKKKELREQHPSLRDEGTSDDKVFLACRGAGQCP
FT                   LSAPAGTMDR (in isoform 2 and isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_026330"
FT   VARIANT         114
FT                   /note="N -> S (in dbSNP:rs9461544)"
FT                   /id="VAR_032902"
FT   VARIANT         166
FT                   /note="R -> H (in TNDM1; dbSNP:rs199589695)"
FT                   /evidence="ECO:0000269|PubMed:18622393"
FT                   /id="VAR_054771"
FT   VARIANT         193
FT                   /note="H -> N (in TNDM1; dbSNP:rs78378398)"
FT                   /evidence="ECO:0000269|PubMed:18622393"
FT                   /id="VAR_054772"
FT   VARIANT         284
FT                   /note="D -> V (in dbSNP:rs2535241)"
FT                   /evidence="ECO:0000269|PubMed:14574404"
FT                   /id="VAR_032903"
FT   VARIANT         374
FT                   /note="H -> D (in TNDM1; dbSNP:rs79020217)"
FT                   /evidence="ECO:0000269|PubMed:18622393"
FT                   /id="VAR_054773"
FT   CONFLICT        151
FT                   /note="L -> F (in Ref. 2; AAI57879)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   452 AA;  51919 MW;  6B285B7FB9ABB3BA CRC64;
     MAAGEPRSLL FFQKPVTFED VAVNFTQEEW DCLDASQRVL YQDVMSETFK NLTSVARIFL
     HKPELITKLE QEEEQWRETR VLQASQAGPP FFCYTCGKCF SRRSYLYSHQ FVHNPKLTNS
     CSQCGKLFRS PKSLSYHRRM HLGERPFCCT LCDKTYCDAS GLSRHRRVHL GYRPHSCSVC
     GKSFRDQSEL KRHQKIHQNQ EPVDGNQECT LRIPGTQAEF QTPIARSQRS IQGLLDVNHA
     PVARSQEPIF RTEGPMAQNQ ASVLKNQAPV TRTQAPITGT LCQDARSNSH PVKPSRLNVF
     CCPHCSLTFS KKSYLSRHQK AHLTEPPNYC FHCSKSFSSF SRLVRHQQTH WKQKSYLCPI
     CDLSFGEKEG LMDHWRGYKG KDLCQSSHHK CRVILGQWLG FSHDVPTMAG EEWKHGGDQS
     PPRIHTPRRR GLREKACKGD KTKEAVSILK HK
//