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 27-MAR-2024, entry version 178. 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 Q6NZY4; Q9Y580: RBM7; NbExp=11; IntAct=EBI-1263058, EBI-746903; 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 syndrome, CC telomere-related, 5 (PFBMFT5) [MIM:618674]: A disease associated with CC shortened telomeres. Pulmonary fibrosis is the most common CC manifestation. Other manifestations include aplastic anemia due to bone CC marrow failure, hepatic fibrosis, and increased cancer risk, CC particularly myelodysplastic syndrome and acute myeloid leukemia. CC Phenotype, age at onset, and severity are determined by telomere CC length. PFBMFT5 inheritance is autosomal dominant. CC {ECO:0000269|PubMed:31488579}. Note=The disease may be caused by CC variants affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the ZCCHC8 family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 CCDS; CCDS91763.1; -. [Q6NZY4-1] 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 PDB; 7S7B; EM; 4.06 A; B/F=1-707. DR PDB; 7S7C; EM; 3.62 A; B/F=1-707. DR PDB; 7Z4Y; EM; 4.50 A; A/C=41-337. DR PDB; 7Z4Z; EM; 4.00 A; A/C=41-337. DR PDB; 7Z52; EM; 3.40 A; A=1-707. DR PDBsum; 5LXR; -. DR PDBsum; 5LXY; -. DR PDBsum; 6C90; -. DR PDBsum; 7S7B; -. DR PDBsum; 7S7C; -. DR PDBsum; 7Z4Y; -. DR PDBsum; 7Z4Z; -. DR PDBsum; 7Z52; -. DR AlphaFoldDB; Q6NZY4; -. DR EMDB; EMD-14510; -. DR EMDB; EMD-14511; -. DR EMDB; EMD-14513; -. DR EMDB; EMD-14514; -. DR EMDB; EMD-14515; -. DR EMDB; EMD-24882; -. DR EMDB; EMD-24883; -. DR EMDB; EMD-24884; -. DR SMR; Q6NZY4; -. DR BioGRID; 120739; 151. DR ComplexPortal; CPX-2735; Nuclear exosome targeting complex. DR CORUM; Q6NZY4; -. DR IntAct; Q6NZY4; 55. DR MINT; Q6NZY4; -. DR STRING; 9606.ENSP00000438993; -. DR GlyCosmos; Q6NZY4; 1 site, 1 glycan. 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; 9606-ENSP00000438993; -. DR PeptideAtlas; Q6NZY4; -. DR ProteomicsDB; 66798; -. [Q6NZY4-1] DR ProteomicsDB; 66799; -. [Q6NZY4-2] DR Pumba; Q6NZY4; -. DR Antibodypedia; 31655; 143 antibodies from 23 providers. DR DNASU; 55596; -. DR Ensembl; ENST00000536306.5; ENSP00000441423.1; ENSG00000033030.16. [Q6NZY4-2] DR Ensembl; ENST00000543897.5; ENSP00000438993.1; ENSG00000033030.16. [Q6NZY4-2] DR Ensembl; ENST00000633063.3; ENSP00000488055.1; ENSG00000033030.16. [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 AGR; HGNC:25265; -. 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; DAEVPHG; -. DR OrthoDB; 1275937at2759; -. DR PhylomeDB; Q6NZY4; -. DR TreeFam; TF321837; -. DR PathwayCommons; Q6NZY4; -. DR SignaLink; Q6NZY4; -. DR BioGRID-ORCS; 55596; 18 hits in 361 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 194 other cell types or tissues. DR ExpressionAtlas; Q6NZY4; baseline and differential. 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:HPA. 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 PANTHER; PTHR13316:SF0; ZINC FINGER CCHC DOMAIN-CONTAINING PROTEIN 8; 1. DR PANTHER; PTHR13316; ZINC FINGER, CCHC DOMAIN CONTAINING 8; 1. 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. DR Genevisible; Q6NZY4; HS. 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 //