ZFP57_HUMAN
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 03-AUG-2022, entry version 163.
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; 12.
DR IntAct; Q9NU63; 8.
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 PRIDE; Q9NU63; -.
DR ProteomicsDB; 82655; -. [Q9NU63-1]
DR ProteomicsDB; 82656; -. [Q9NU63-2]
DR ProteomicsDB; 82657; -. [Q9NU63-3]
DR Antibodypedia; 26080; 219 antibodies from 19 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 CTD; 346171; -.
DR DisGeNET; 346171; -.
DR GeneCards; ZFP57; -.
DR GeneReviews; ZFP57; -.
DR HGNC; HGNC:18791; ZFP57.
DR HPA; ENSG00000204644; Tissue enriched (heart).
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; 1551203at2759; -.
DR PhylomeDB; Q9NU63; -.
DR TreeFam; TF337947; -.
DR PathwayCommons; Q9NU63; -.
DR SignaLink; Q9NU63; -.
DR BioGRID-ORCS; 346171; 29 hits in 1087 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 C1 segment of cervical spinal cord and 84 other tissues.
DR ExpressionAtlas; Q9NU63; baseline and differential.
DR Genevisible; Q9NU63; HS.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
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:0043045; P:DNA methylation involved in embryo development; IMP:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006349; P:regulation of gene expression by genomic 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 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; 4.
DR SMART; SM00349; KRAB; 1.
DR SMART; SM00355; ZnF_C2H2; 7.
DR SUPFAM; SSF109640; SSF109640; 1.
DR SUPFAM; SSF57667; SSF57667; 4.
DR PROSITE; PS50805; KRAB; 1.
DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 6.
DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 7.
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
