ZC3H8_HUMAN
ID ZC3H8_HUMAN Reviewed; 291 AA.
AC Q8N5P1; Q9BZ75;
DT 10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2004, sequence version 2.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Zinc finger CCCH domain-containing protein 8;
GN Name=ZC3H8; Synonyms=ZC3HDC8;
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 Zhuang D.Z., Gunnarsson D., Toffia O., Lind M., Lundgren P., Selstam G.;
RT "Mammalian Ssb proteins related to ovarian development and
RT differentiation.";
RL Submitted (JAN-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skin;
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.
RX PubMed=12153508; DOI=10.1046/j.1365-2567.2002.01455.x;
RA Hwang E.S., Ho I.-C.;
RT "Regulation of thymocyte homeostasis by Fliz1.";
RL Immunology 106:464-469(2002).
RN [4]
RP FUNCTION.
RX PubMed=12077251; DOI=10.4049/jimmunol.169.1.248;
RA Hwang E.S., Choi A., Ho I.-C.;
RT "Transcriptional regulation of GATA-3 by an intronic regulatory region and
RT fetal liver zinc finger protein 1.";
RL J. Immunol. 169:248-253(2002).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-77, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-77, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-32, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-22; THR-32; SER-59 AND
RP SER-63, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [11]
RP FUNCTION, SUBCELLULAR LOCATION, IDENTIFICATION IN THE LEC COMPLEX, AND
RP INTERACTION WITH ICE1.
RX PubMed=23932780; DOI=10.1016/j.molcel.2013.07.003;
RA Hu D., Smith E.R., Garruss A.S., Mohaghegh N., Varberg J.M., Lin C.,
RA Jackson J., Gao X., Saraf A., Florens L., Washburn M.P., Eissenberg J.C.,
RA Shilatifard A.;
RT "The little elongation complex functions at initiation and elongation
RT phases of snRNA gene transcription.";
RL Mol. Cell 51:493-505(2013).
RN [12]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-43, AND IDENTIFICATION BY MASS
RP 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).
CC -!- FUNCTION: Acts as a transcriptional repressor of the GATA3 promoter.
CC Sequence-specific DNA-binding factor that binds to the 5'-AGGTCTC-3'
CC sequence within the negative cis-acting element intronic regulatory
CC region (IRR) of the GATA3 gene (By similarity). Component of the little
CC elongation complex (LEC), a complex required to regulate small nuclear
CC RNA (snRNA) gene transcription by RNA polymerase II and III
CC (PubMed:23932780). Induces thymocyte apoptosis when overexpressed,
CC which may indicate a role in regulation of thymocyte homeostasis.
CC {ECO:0000250, ECO:0000269|PubMed:12077251, ECO:0000269|PubMed:12153508,
CC ECO:0000269|PubMed:23932780}.
CC -!- SUBUNIT: Component of the little elongation complex (LEC), at least
CC composed of ELL (ELL, ELL2 or ELL3), ZC3H8, ICE1 and ICE2. Interacts
CC with ICE1 (via C-terminus domain). {ECO:0000269|PubMed:23932780}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:23932780}.
CC Note=Colocalizes with coilin in subnuclear cajal and histone locus
CC bodies. Translocates in the LEC complex to cajal and histone locus
CC bodies at snRNA genes in a ICE1-dependent manner. Associates to
CC transcriptionally active chromatin at snRNA genes.
CC -!- DOMAIN: The N-terminal region and all three C3H1-type zinc fingers are
CC necessary to induce transcriptional repression.
CC {ECO:0000269|PubMed:23932780}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH32001.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF334161; AAK13496.1; -; mRNA.
DR EMBL; BC032001; AAH32001.1; ALT_FRAME; mRNA.
DR CCDS; CCDS46392.1; -.
DR RefSeq; NP_115883.2; NM_032494.2.
DR AlphaFoldDB; Q8N5P1; -.
DR SMR; Q8N5P1; -.
DR BioGRID; 124116; 77.
DR IntAct; Q8N5P1; 25.
DR MINT; Q8N5P1; -.
DR STRING; 9606.ENSP00000386488; -.
DR GlyGen; Q8N5P1; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q8N5P1; -.
DR PhosphoSitePlus; Q8N5P1; -.
DR BioMuta; ZC3H8; -.
DR DMDM; 47117585; -.
DR EPD; Q8N5P1; -.
DR jPOST; Q8N5P1; -.
DR MassIVE; Q8N5P1; -.
DR MaxQB; Q8N5P1; -.
DR PaxDb; Q8N5P1; -.
DR PeptideAtlas; Q8N5P1; -.
DR PRIDE; Q8N5P1; -.
DR ProteomicsDB; 72080; -.
DR Antibodypedia; 47908; 257 antibodies from 30 providers.
DR DNASU; 84524; -.
DR Ensembl; ENST00000409573.7; ENSP00000386488.1; ENSG00000144161.14.
DR GeneID; 84524; -.
DR KEGG; hsa:84524; -.
DR MANE-Select; ENST00000409573.7; ENSP00000386488.1; NM_032494.3; NP_115883.2.
DR UCSC; uc032nyp.2; human.
DR CTD; 84524; -.
DR DisGeNET; 84524; -.
DR GeneCards; ZC3H8; -.
DR HGNC; HGNC:30941; ZC3H8.
DR HPA; ENSG00000144161; Low tissue specificity.
DR neXtProt; NX_Q8N5P1; -.
DR OpenTargets; ENSG00000144161; -.
DR PharmGKB; PA134956342; -.
DR VEuPathDB; HostDB:ENSG00000144161; -.
DR eggNOG; KOG1040; Eukaryota.
DR GeneTree; ENSGT00940000161918; -.
DR HOGENOM; CLU_059008_0_0_1; -.
DR InParanoid; Q8N5P1; -.
DR OMA; KWPGTGN; -.
DR OrthoDB; 145192at2759; -.
DR PhylomeDB; Q8N5P1; -.
DR TreeFam; TF318143; -.
DR PathwayCommons; Q8N5P1; -.
DR Reactome; R-HSA-6807505; RNA polymerase II transcribes snRNA genes.
DR SignaLink; Q8N5P1; -.
DR BioGRID-ORCS; 84524; 563 hits in 1087 CRISPR screens.
DR GenomeRNAi; 84524; -.
DR Pharos; Q8N5P1; Tbio.
DR PRO; PR:Q8N5P1; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q8N5P1; protein.
DR Bgee; ENSG00000144161; Expressed in secondary oocyte and 186 other tissues.
DR ExpressionAtlas; Q8N5P1; baseline and differential.
DR Genevisible; Q8N5P1; HS.
DR GO; GO:0015030; C:Cajal body; IDA:UniProtKB.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0000791; C:euchromatin; IDA:UniProtKB.
DR GO; GO:0035363; C:histone locus body; IDA:UniProtKB.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0008023; C:transcription elongation factor complex; IDA:UniProtKB.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IEA:Ensembl.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0001162; F:RNA polymerase II intronic transcription regulatory region sequence-specific DNA binding; IEA:Ensembl.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0033085; P:negative regulation of T cell differentiation in thymus; IMP:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0070245; P:positive regulation of thymocyte apoptotic process; IMP:UniProtKB.
DR GO; GO:0045945; P:positive regulation of transcription by RNA polymerase III; IMP:UniProtKB.
DR GO; GO:0046677; P:response to antibiotic; IDA:UniProtKB.
DR GO; GO:0042795; P:snRNA transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0042796; P:snRNA transcription by RNA polymerase III; IMP:UniProtKB.
DR GO; GO:0043029; P:T cell homeostasis; IMP:UniProtKB.
DR InterPro; IPR045124; Su(sable)-like.
DR InterPro; IPR000571; Znf_CCCH.
DR InterPro; IPR036855; Znf_CCCH_sf.
DR PANTHER; PTHR13119; PTHR13119; 1.
DR Pfam; PF00642; zf-CCCH; 1.
DR SMART; SM00356; ZnF_C3H1; 3.
DR SUPFAM; SSF90229; SSF90229; 3.
DR PROSITE; PS50103; ZF_C3H1; 3.
PE 1: Evidence at protein level;
KW Apoptosis; Isopeptide bond; Metal-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Repressor; RNA-binding; Transcription;
KW Transcription regulation; Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..291
FT /note="Zinc finger CCCH domain-containing protein 8"
FT /id="PRO_0000213903"
FT ZN_FING 191..218
FT /note="C3H1-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00723"
FT ZN_FING 220..247
FT /note="C3H1-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00723"
FT ZN_FING 248..271
FT /note="C3H1-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00723"
FT REGION 1..26
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 51..75
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 93..179
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 108..123
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 130..149
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 22
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 32
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 59
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 63
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 77
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17525332,
FT ECO:0007744|PubMed:18669648"
FT MOD_RES 83
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JJ48"
FT CROSSLNK 43
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VARIANT 240
FT /note="C -> W (in dbSNP:rs35782954)"
FT /id="VAR_057489"
FT CONFLICT 233..235
FT /note="YCT -> FCS (in Ref. 1; AAK13496)"
FT /evidence="ECO:0000305"
FT CONFLICT 265
FT /note="K -> Q (in Ref. 1; AAK13496)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 291 AA; 33576 MW; 5DFDA42280916034 CRC64;
MDFENLFSKP PNPALGKTAT DSDERIDDEI DTEVEETQEE KIKLECEQIP KKFRHSAISP
KSSLHRKSRS KDYDVYSDND ICSQESEDNF AKELQQYIQA REMANAAQPE ESTKKEGVKD
TPQAAKQKNK NLKAGHKNGK QKKMKRKWPG PGNKGSNALL RNSGSQEEDG KPKEKQQHLS
QAFINQHTVE RKGKQICKYF LERKCIKGDQ CKFDHDAEIE KKKEMCKFYV QGYCTRGENC
LYLHNEYPCK FYHTGTKCYQ GEYCKFSHAP LTPETQELLA KVLDTEKKSC K
