ZCHC8_HUMAN
ID ZCHC8_HUMAN Reviewed; 707 AA.
AC Q6NZY4; Q7L2P6; Q8N2K5; Q96SK7; Q9NSS2; Q9NSS3;
DT 10-MAY-2005, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2005, sequence version 2.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=Zinc finger CCHC domain-containing protein 8;
DE AltName: Full=TRAMP-like complex RNA-binding factor ZCCHC8;
GN Name=ZCCHC8;
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 MRNA] (ISOFORM 1).
RC TISSUE=Embryo;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain, and Duodenum;
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 [4]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE SPLICEOSOMAL
RP C COMPLEX.
RX PubMed=11991638; DOI=10.1017/s1355838202021088;
RA Jurica M.S., Licklider L.J., Gygi S.P., Grigorieff N., Moore M.J.;
RT "Purification and characterization of native spliceosomes suitable for
RT three-dimensional structural analysis.";
RL RNA 8:426-439(2002).
RN [5]
RP FUNCTION, PHOSPHORYLATION AT THR-492, MUTAGENESIS OF THR-492, PTM,
RP INTERACTION WITH MTREX AND RBM7, SUBCELLULAR LOCATION, AND INDUCTION.
RX PubMed=16263084; DOI=10.1016/j.bbrc.2005.10.090;
RA Gustafson M.P., Welcker M., Hwang H.C., Clurman B.E.;
RT "Zcchc8 is a glycogen synthase kinase-3 substrate that interacts with RNA-
RT binding proteins.";
RL Biochem. Biophys. Res. Commun. 338:1359-1367(2005).
RN [6]
RP IDENTIFICATION BY 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 [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-598 AND SER-658, AND
RP IDENTIFICATION BY 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 [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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 [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-658, 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 [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-479; THR-485 AND SER-658, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [11]
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 [12]
RP IDENTIFICATION IN A TRAMP-LIKE COMPLEX, SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=21855801; DOI=10.1016/j.molcel.2011.06.028;
RA Lubas M., Christensen M.S., Kristiansen M.S., Domanski M., Falkenby L.G.,
RA Lykke-Andersen S., Andersen J.S., Dziembowski A., Jensen T.H.;
RT "Interaction profiling identifies the human nuclear exosome targeting
RT complex.";
RL Mol. Cell 43:624-637(2011).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [14]
RP REVIEW ON RNA EXOSOMES.
RX PubMed=22817747; DOI=10.1042/bst20120061;
RA Sloan K.E., Schneider C., Watkins N.J.;
RT "Comparison of the yeast and human nuclear exosome complexes.";
RL Biochem. Soc. Trans. 40:850-855(2012).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-342; THR-479; THR-485;
RP THR-492; THR-577; SER-598; THR-648; SER-649; SER-658 AND SER-695, AND
RP 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 [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-472; THR-479; THR-492 AND
RP SER-658, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [17]
RP FUNCTION, SUBUNIT, AND INTERACTION WITH RBM7 AND MTREX.
RX PubMed=27871484; DOI=10.1016/j.molcel.2016.09.025;
RA Meola N., Domanski M., Karadoulama E., Chen Y., Gentil C., Pultz D.,
RA Vitting-Seerup K., Lykke-Andersen S., Andersen J.S., Sandelin A.,
RA Jensen T.H.;
RT "Identification of a nuclear exosome decay pathway for processed
RT transcripts.";
RL Mol. Cell 64:520-533(2016).
RN [18]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-413, 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).
RN [19]
RP FUNCTION, INTERACTION WITH TERC, INVOLVEMENT IN PFBMFT5, VARIANT PFBMFT5
RP LEU-186, AND CHARACTERIZATION OF VARIANT PFBMFT5 LEU-186.
RX PubMed=31488579; DOI=10.1101/gad.326785.119;
RA Gable D.L., Gaysinskaya V., Atik C.C., Talbot C.C. Jr., Kang B.,
RA Stanley S.E., Pugh E.W., Amat-Codina N., Schenk K.M., Arcasoy M.O.,
RA Brayton C., Florea L., Armanios M.;
RT "ZCCHC8, the nuclear exosome targeting component, is mutated in familial
RT pulmonary fibrosis and is required for telomerase RNA maturation.";
RL Genes Dev. 33:1381-1396(2019).
RN [20] {ECO:0007744|PDB:5LXR, ECO:0007744|PDB:5LXY}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 285-324 IN COMPLEX WITH RBM7 AND
RP MTREX, SUBUNIT, INTERACTION WITH RBM7 AND MTREX, AND MUTAGENESIS OF
RP LEU-295; LEU-299; PHE-309 AND MET-313.
RX PubMed=27905398; DOI=10.1038/ncomms13573;
RA Falk S., Finogenova K., Melko M., Benda C., Lykke-Andersen S., Jensen T.H.,
RA Conti E.;
RT "Structure of the RBM7-ZCCHC8 core of the NEXT complex reveals connections
RT to splicing factors.";
RL Nat. Commun. 7:13573-13573(2016).
RN [21] {ECO:0007744|PDB:6C90}
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 659-707 IN COMPLEX WITH MTREX,
RP INTERACTION WITH MTREX, MUTAGENESIS OF ASP-662; PHE-666; PHE-673; GLU-674;
RP PHE-675; GLU-676; ILE-688 AND LEU-692, REGION, AND DOMAIN.
RX PubMed=29844170; DOI=10.1073/pnas.1803530115;
RA Puno M.R., Lima C.D.;
RT "Structural basis for MTR4-ZCCHC8 interactions that stimulate the MTR4
RT helicase in the nuclear exosome-targeting complex.";
RL Proc. Natl. Acad. Sci. U.S.A. 115:E5506-E5515(2018).
CC -!- FUNCTION: Scaffolding subunit of the trimeric nuclear exosome targeting
CC (NEXT) complex that is involved in the surveillance and turnover of
CC aberrant transcripts and non-coding RNAs (PubMed:27871484). NEXT
CC functions as an RNA exosome cofactor that directs a subset of non-
CC coding short-lived RNAs for exosomal degradation. May be involved in
CC pre-mRNA splicing (Probable). It is required for 3'-end maturation of
CC telomerase RNA component (TERC), TERC 3'-end targeting to the nuclear
CC RNA exosome, and for telomerase function (PubMed:31488579).
CC {ECO:0000269|PubMed:27871484, ECO:0000269|PubMed:31488579,
CC ECO:0000305|PubMed:16263084}.
CC -!- SUBUNIT: Component of a nuclear TRAMP-like complex, an ATP-dependent
CC exosome regulatory complex consisting of a helicase (MTREX), an
CC oligadenylate polymerase (TENT4B or TENT4A), and a substrate specific
CC RNA-binding factor (ZCCHC7 or ZCCHC8). Several TRAMP-like complexes
CC exist with specific compositions and are associated with nuclear, or
CC nucleolar RNA exosomes. Identified in the spliceosome C complex.
CC Component of the nuclear exosome targeting (NEXT) complex composed of
CC MTREX, ZCCHC8, and RBM7 that directs a subset of non-coding short-lived
CC RNAs for exosomal degradation (PubMed:27905398, PubMed:27871484).
CC Interacts with proteins involved in RNA processing and degradation such
CC as MTREX and RBM7; interaction with MTREX enhances MTREX RNA helicase
CC activity and bridges between RBM7 and MTREX (PubMed:16263084,
CC PubMed:27905398, PubMed:27871484). Interacts with TERC, the telomerase
CC RNA component (PubMed:31488579). {ECO:0000269|PubMed:11991638,
CC ECO:0000269|PubMed:16263084, ECO:0000269|PubMed:21855801,
CC ECO:0000269|PubMed:29844170, ECO:0000269|PubMed:31488579}.
CC -!- INTERACTION:
CC Q6NZY4; P38398: BRCA1; NbExp=2; IntAct=EBI-1263058, EBI-349905;
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleoplasm
CC {ECO:0000269|PubMed:16263084, ECO:0000269|PubMed:21855801}. Nucleus
CC {ECO:0000255|PROSITE-ProRule:PRU00768}. Note=Excluded from nucleolus.
CC {ECO:0000269|PubMed:21855801}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6NZY4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6NZY4-2; Sequence=VSP_013717;
CC -!- INDUCTION: Slight accumulation in cells entering S phase of the cell
CC cycle. {ECO:0000269|PubMed:16263084}.
CC -!- DOMAIN: The C-terminal part (659-707) contributes to MTREX RNA helicase
CC activity, in part, by enhancing its RNA-dependent ATPase activity.
CC {ECO:0000269|PubMed:29844170}.
CC -!- PTM: Phosphorylation at Thr-492 by GSK3 is triggered in cells entering
CC mitosis; this phosphorylation is greatly enhanced by nocodazole
CC treatment, but reduced by lithium. {ECO:0000269|PubMed:16263084}.
CC -!- DISEASE: Pulmonary fibrosis, and/or bone marrow failure, telomere-
CC related, 5 (PFBMFT5) [MIM:618674]: A disease associated with shortened
CC telomeres. Pulmonary fibrosis is the most common manifestation. Other
CC manifestations include aplastic anemia due to bone marrow failure,
CC hepatic fibrosis, and increased cancer risk, particularly
CC myelodysplastic syndrome and acute myeloid leukemia. Phenotype, age at
CC onset, and severity are determined by telomere length. PFBMFT5
CC inheritance is autosomal dominant. {ECO:0000269|PubMed:31488579}.
CC Note=The disease may be caused by variants affecting the gene
CC represented in this entry.
CC -!- SIMILARITY: Belongs to the ZCCHC8 family. {ECO:0000305}.
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DR EMBL; AK027702; BAB55308.1; -; mRNA.
DR EMBL; AK074638; BAC11105.1; -; mRNA.
DR EMBL; AL157433; CAB75657.1; -; mRNA.
DR EMBL; AL157434; CAB75658.1; -; mRNA.
DR EMBL; BC017704; AAH17704.2; -; mRNA.
DR EMBL; BC065918; AAH65918.1; -; mRNA.
DR CCDS; CCDS86340.1; -. [Q6NZY4-2]
DR PIR; T46929; T46929.
DR PIR; T46930; T46930.
DR RefSeq; NP_060082.2; NM_017612.4. [Q6NZY4-1]
DR PDB; 5LXR; X-ray; 2.00 A; B=285-324.
DR PDB; 5LXY; X-ray; 2.85 A; C/D/F/H/J/L/N=285-324.
DR PDB; 6C90; X-ray; 2.20 A; B=659-707.
DR PDBsum; 5LXR; -.
DR PDBsum; 5LXY; -.
DR PDBsum; 6C90; -.
DR AlphaFoldDB; Q6NZY4; -.
DR SMR; Q6NZY4; -.
DR BioGRID; 120739; 120.
DR CORUM; Q6NZY4; -.
DR IntAct; Q6NZY4; 51.
DR MINT; Q6NZY4; -.
DR STRING; 9606.ENSP00000438993; -.
DR GlyGen; Q6NZY4; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q6NZY4; -.
DR PhosphoSitePlus; Q6NZY4; -.
DR BioMuta; ZCCHC8; -.
DR DMDM; 66774213; -.
DR CPTAC; CPTAC-1021; -.
DR EPD; Q6NZY4; -.
DR jPOST; Q6NZY4; -.
DR MassIVE; Q6NZY4; -.
DR MaxQB; Q6NZY4; -.
DR PaxDb; Q6NZY4; -.
DR PeptideAtlas; Q6NZY4; -.
DR PRIDE; Q6NZY4; -.
DR ProteomicsDB; 66798; -. [Q6NZY4-1]
DR ProteomicsDB; 66799; -. [Q6NZY4-2]
DR Antibodypedia; 31655; 120 antibodies from 22 providers.
DR DNASU; 55596; -.
DR Ensembl; ENST00000536306.5; ENSP00000441423.1; ENSG00000033030.15. [Q6NZY4-2]
DR Ensembl; ENST00000543897.5; ENSP00000438993.1; ENSG00000033030.15. [Q6NZY4-2]
DR Ensembl; ENST00000633063.3; ENSP00000488055.1; ENSG00000033030.15. [Q6NZY4-1]
DR Ensembl; ENST00000672018.1; ENSP00000500728.1; ENSG00000033030.15. [Q6NZY4-1]
DR GeneID; 55596; -.
DR KEGG; hsa:55596; -.
DR MANE-Select; ENST00000633063.3; ENSP00000488055.1; NM_017612.5; NP_060082.2.
DR UCSC; uc009zxp.4; human. [Q6NZY4-1]
DR CTD; 55596; -.
DR DisGeNET; 55596; -.
DR GeneCards; ZCCHC8; -.
DR GeneReviews; ZCCHC8; -.
DR HGNC; HGNC:25265; ZCCHC8.
DR HPA; ENSG00000033030; Tissue enhanced (bone).
DR MalaCards; ZCCHC8; -.
DR MIM; 616381; gene.
DR MIM; 618674; phenotype.
DR neXtProt; NX_Q6NZY4; -.
DR OpenTargets; ENSG00000033030; -.
DR PharmGKB; PA134889410; -.
DR VEuPathDB; HostDB:ENSG00000033030; -.
DR eggNOG; KOG2673; Eukaryota.
DR GeneTree; ENSGT00390000011475; -.
DR InParanoid; Q6NZY4; -.
DR OMA; WQMFGSI; -.
DR OrthoDB; 338817at2759; -.
DR PhylomeDB; Q6NZY4; -.
DR TreeFam; TF321837; -.
DR PathwayCommons; Q6NZY4; -.
DR SignaLink; Q6NZY4; -.
DR BioGRID-ORCS; 55596; 16 hits in 291 CRISPR screens.
DR ChiTaRS; ZCCHC8; human.
DR GeneWiki; ZCCHC8; -.
DR GenomeRNAi; 55596; -.
DR Pharos; Q6NZY4; Tbio.
DR PRO; PR:Q6NZY4; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q6NZY4; protein.
DR Bgee; ENSG00000033030; Expressed in cervix squamous epithelium and 192 other tissues.
DR ExpressionAtlas; Q6NZY4; baseline and differential.
DR Genevisible; Q6NZY4; HS.
DR GO; GO:0071013; C:catalytic step 2 spliceosome; IDA:UniProtKB.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0031499; C:TRAMP complex; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0000398; P:mRNA splicing, via spliceosome; IC:UniProtKB.
DR GO; GO:0034470; P:ncRNA processing; IMP:UniProtKB.
DR GO; GO:0016076; P:snRNA catabolic process; ISS:UniProtKB.
DR InterPro; IPR006568; PSP_pro-rich.
DR InterPro; IPR001878; Znf_CCHC.
DR Pfam; PF04046; PSP; 1.
DR Pfam; PF00098; zf-CCHC; 1.
DR SMART; SM00581; PSP; 1.
DR SMART; SM00343; ZnF_C2HC; 1.
DR PROSITE; PS50158; ZF_CCHC; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Coiled coil;
KW Disease variant; Isopeptide bond; Metal-binding; mRNA processing;
KW mRNA splicing; Nucleus; Phosphoprotein; Reference proteome; Spliceosome;
KW Ubl conjugation; Zinc; Zinc-finger.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330"
FT CHAIN 2..707
FT /note="Zinc finger CCHC domain-containing protein 8"
FT /id="PRO_0000150960"
FT ZN_FING 227..244
FT /note="CCHC-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00047"
FT REGION 16..44
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 286..299
FT /note="RBM7 binding"
FT /evidence="ECO:0000269|PubMed:27905398,
FT ECO:0007744|PDB:5LXR, ECO:0007744|PDB:5LXY"
FT REGION 309..324
FT /note="RBM7 binding"
FT /evidence="ECO:0000269|PubMed:27905398,
FT ECO:0007744|PDB:5LXR, ECO:0007744|PDB:5LXY"
FT REGION 409..518
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 531..607
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 641..660
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 659..707
FT /note="MTREX binding"
FT /evidence="ECO:0000269|PubMed:29844170,
FT ECO:0007744|PDB:6C90"
FT COILED 45..80
FT /evidence="ECO:0000255"
FT COILED 516..539
FT /evidence="ECO:0000255"
FT COMPBIAS 16..35
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 409..442
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 466..496
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 534..559
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 573..589
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 641..658
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:19413330"
FT MOD_RES 342
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 472
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 479
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 485
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 492
FT /note="Phosphothreonine; by GSK3"
FT /evidence="ECO:0000269|PubMed:16263084,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 577
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 598
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 648
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 649
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 658
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 695
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT CROSSLNK 413
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 1..238
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_013717"
FT VARIANT 186
FT /note="P -> L (in PFBMFT5; decreased levels of mature TERC
FT in patient cells consistent with impaired function in RNA
FT processing; decreased levels of mutant protein in patient
FT cells)"
FT /evidence="ECO:0000269|PubMed:31488579"
FT /id="VAR_083448"
FT VARIANT 672
FT /note="P -> A (in dbSNP:rs1063155)"
FT /id="VAR_034585"
FT MUTAGEN 295
FT /note="L->E: Impaired interaction with ZCCHC8; when
FT associated with E-299."
FT /evidence="ECO:0000269|PubMed:27905398"
FT MUTAGEN 299
FT /note="L->E: Impaired interaction with ZCCHC8; when
FT associated with E-295."
FT /evidence="ECO:0000269|PubMed:27905398"
FT MUTAGEN 309
FT /note="F->A: Reduced interaction with ZCCHC8; when
FT associated with E-313."
FT /evidence="ECO:0000269|PubMed:27905398"
FT MUTAGEN 313
FT /note="M->E: Reduced interaction with ZCCHC8; when
FT associated with A-309."
FT /evidence="ECO:0000269|PubMed:27905398"
FT MUTAGEN 492
FT /note="T->A: Impaired phosphorylation by GSK3."
FT /evidence="ECO:0000269|PubMed:16263084"
FT MUTAGEN 662
FT /note="D->A: Does not alter RNA helicase activity of NEXT
FT complex; when associated with K-666."
FT /evidence="ECO:0000269|PubMed:29844170"
FT MUTAGEN 666
FT /note="F->K: Does not alter RNA helicase activity of NEXT
FT complex; when associated with A-662."
FT /evidence="ECO:0000269|PubMed:29844170"
FT MUTAGEN 673
FT /note="F->A: Does not affect RNA helicase activity of NEXT
FT complex; when associated with A-675."
FT /evidence="ECO:0000269|PubMed:29844170"
FT MUTAGEN 674
FT /note="E->A: Does not affect RNA helicase activity of NEXT
FT complex; when associated with A-676."
FT /evidence="ECO:0000269|PubMed:29844170"
FT MUTAGEN 675
FT /note="F->A: Does not affect RNA helicase activity of NEXT
FT complex; when associated with A-673."
FT /evidence="ECO:0000269|PubMed:29844170"
FT MUTAGEN 676
FT /note="E->A: Does not affect RNA helicase activity of NEXT
FT complex; when associated with A-674."
FT /evidence="ECO:0000269|PubMed:29844170"
FT MUTAGEN 688
FT /note="I->E: Loss of RNA helicase activity of NEXT complex;
FT when associated with E-692."
FT /evidence="ECO:0000269|PubMed:29844170"
FT MUTAGEN 692
FT /note="L->E: Loss of RNA helicase activity of NEXT complex;
FT when associated with E-688."
FT /evidence="ECO:0000269|PubMed:29844170"
FT CONFLICT 20
FT /note="E -> G (in Ref. 1; BAB55308)"
FT /evidence="ECO:0000305"
FT CONFLICT 216..219
FT /note="QEIQ -> DAWV (in Ref. 3; AAH17704)"
FT /evidence="ECO:0000305"
FT CONFLICT 326
FT /note="A -> V (in Ref. 3; AAH65918)"
FT /evidence="ECO:0000305"
FT CONFLICT 461
FT /note="S -> G (in Ref. 1; BAB55308)"
FT /evidence="ECO:0000305"
FT CONFLICT 582
FT /note="E -> G (in Ref. 1; BAC11105)"
FT /evidence="ECO:0000305"
FT CONFLICT 663
FT /note="M -> V (in Ref. 2; CAB75658)"
FT /evidence="ECO:0000305"
FT HELIX 293..299
FT /evidence="ECO:0007829|PDB:5LXR"
FT HELIX 308..316
FT /evidence="ECO:0007829|PDB:5LXR"
FT HELIX 320..322
FT /evidence="ECO:0007829|PDB:5LXR"
FT HELIX 663..667
FT /evidence="ECO:0007829|PDB:6C90"
FT HELIX 684..690
FT /evidence="ECO:0007829|PDB:6C90"
FT HELIX 696..699
FT /evidence="ECO:0007829|PDB:6C90"
SQ SEQUENCE 707 AA; 78577 MW; 7BE6E30F919A4771 CRC64;
MAAEVYFGDL ELFEPFDHPE ESIPKPVHTR FKDDDGDEED ENGVGDAELR ERLRQCEETI
EQLRAENQEL KRKLNILTRP SGILVNDTKL DGPILQILFM NNAISKQYHQ EIEEFVSNLV
KRFEEQQKND VEKTSFNLLP QPSSIVLEED HKVEESCAIK NNKEAFSVVG SVLYFTNFCL
DKLGQPLLNE NPQLSEGWEI PKYHQVFSHI VSLEGQEIQV KAKRPKPHCF NCGSEEHQMK
DCPMPRNAAR ISEKRKEYMD ACGEANNQNF QQRYHAEEVE ERFGRFKPGV ISEELQDALG
VTDKSLPPFI YRMRQLGYPP GWLKEAELEN SGLALYDGKD GTDGETEVGE IQQNKSVTYD
LSKLVNYPGF NISTPRGIPD EWRIFGSIPM QACQQKDVFA NYLTSNFQAP GVKSGNKRSS
SHSSPGSPKK QKNESNSAGS PADMELDSDM EVPHGSQSSE SFQFQPPLPP DTPPLPRGTP
PPVFTPPLPK GTPPLTPSDS PQTRTASGAV DEDALTLEEL EEQQRRIWAA LEQAESVNSD
SDVPVDTPLT GNSVASSPCP NELDLPVPEG KTSEKQTLDE PEVPEIFTKK SEAGHASSPD
SEVTSLCQKE KAELAPVNTE GALLDNGSVV PNCDISNGGS QKLFPADTSP STATKIHSPI
PDMSKFATGI TPFEFENMAE STGMYLRIRS LLKNSPRNQQ KNKKASE
