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   27-MAR-2024, entry version 171.
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; 90.
DR   ComplexPortal; CPX-2712; Little elongation complex, ELL variant.
DR   ComplexPortal; CPX-2713; Little elongation complex, ELL2 variant.
DR   ComplexPortal; CPX-2714; Little elongation complex, ELL3 variant.
DR   IntAct; Q8N5P1; 26.
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; 9606-ENSP00000386488; -.
DR   PeptideAtlas; Q8N5P1; -.
DR   ProteomicsDB; 72080; -.
DR   Pumba; Q8N5P1; -.
DR   Antibodypedia; 47908; 299 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   AGR; HGNC:30941; -.
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; QKYIRAK; -.
DR   OrthoDB; 254197at2759; -.
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; 595 hits in 1165 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 187 other cell types or tissues.
DR   ExpressionAtlas; Q8N5P1; baseline and differential.
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:0045892; P:negative regulation of DNA-templated transcription; IDA:UniProtKB.
DR   GO; GO:0033085; P:negative regulation of T cell differentiation in thymus; IMP: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   Gene3D; 2.30.30.1190; -; 1.
DR   Gene3D; 4.10.1000.10; Zinc finger, CCCH-type; 1.
DR   InterPro; IPR045124; Su(sable)-like.
DR   InterPro; IPR000571; Znf_CCCH.
DR   InterPro; IPR036855; Znf_CCCH_sf.
DR   PANTHER; PTHR13119; ZINC FINGER CCCH DOMAIN-CONTAINING PROTEI; 1.
DR   PANTHER; PTHR13119:SF32; ZINC FINGER CCCH DOMAIN-CONTAINING PROTEIN 8; 1.
DR   Pfam; PF00642; zf-CCCH; 1.
DR   Pfam; PF14608; zf-CCCH_2; 1.
DR   Pfam; PF18345; zf_CCCH_4; 1.
DR   SMART; SM00356; ZnF_C3H1; 3.
DR   SUPFAM; SSF90229; CCCH zinc finger; 3.
DR   PROSITE; PS50103; ZF_C3H1; 3.
DR   Genevisible; Q8N5P1; HS.
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
//