ZCHC8_MOUSE
ID ZCHC8_MOUSE Reviewed; 709 AA.
AC Q9CYA6; Q3TK71; Q8CCB7; Q91WQ1;
DT 10-MAY-2005, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2005, sequence version 3.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Zinc finger CCHC domain-containing protein 8;
DE AltName: Full=TRAMP-like complex RNA-binding factor ZCCHC8;
GN Name=Zcchc8;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Amnion, Colon, and Spleen;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 79-709.
RC STRAIN=FVB/N; TISSUE=Kidney;
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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Lung, Pancreas, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP DISRUPTION PHENOTYPE.
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).
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. NEXT functions as an RNA
CC exosome cofactor that directs a subset of non-coding short-lived RNAs
CC for exosomal degradation. May be involved in pre-mRNA splicing. It is
CC required for 3'-end maturation of telomerase RNA component (TERC), TERC
CC 3'-end targeting to the nuclear RNA exosome, and for telomerase
CC function. {ECO:0000250|UniProtKB:Q6NZY4}.
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. Interacts with proteins involved in RNA
CC processing and degradation such as MTREX and RBM7; interaction with
CC MTREX enhances MTREX RNA helicase activity and bridges between RBM7 and
CC MTREX. Interacts with TERC, the telomerase RNA component.
CC {ECO:0000250|UniProtKB:Q6NZY4}.
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleoplasm
CC {ECO:0000250|UniProtKB:Q6NZY4}. Note=Excluded from nucleolus.
CC {ECO:0000250|UniProtKB:Q6NZY4}.
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:0000250|UniProtKB:Q6NZY4}.
CC -!- PTM: Phosphorylation at Thr-495 by GSK3 is triggered in cells entering
CC mitosis. {ECO:0000250|UniProtKB:Q6NZY4}.
CC -!- DISRUPTION PHENOTYPE: ZCCHC8-null mice have a small brain volume,
CC cranial deformities with domed-shaped heads, and severe hydrocephalus
CC with ventriculomegaly. Defective turnover of low abundance RNA
CC polymerase II transcripts is detected in developing brain of knockout
CC animals. {ECO:0000269|PubMed:31488579}.
CC -!- SIMILARITY: Belongs to the ZCCHC8 family. {ECO:0000305}.
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DR EMBL; AK017857; BAB30977.2; -; mRNA.
DR EMBL; AK033469; BAC28304.1; -; mRNA.
DR EMBL; AK156770; BAE33847.1; -; mRNA.
DR EMBL; AK167126; BAE39274.1; -; mRNA.
DR EMBL; AK167736; BAE39776.1; -; mRNA.
DR EMBL; BC013555; AAH13555.1; -; mRNA.
DR CCDS; CCDS80406.1; -.
DR RefSeq; NP_081770.3; NM_027494.3.
DR AlphaFoldDB; Q9CYA6; -.
DR SMR; Q9CYA6; -.
DR BioGRID; 214189; 10.
DR IntAct; Q9CYA6; 3.
DR MINT; Q9CYA6; -.
DR STRING; 10090.ENSMUSP00000031376; -.
DR iPTMnet; Q9CYA6; -.
DR PhosphoSitePlus; Q9CYA6; -.
DR EPD; Q9CYA6; -.
DR jPOST; Q9CYA6; -.
DR MaxQB; Q9CYA6; -.
DR PaxDb; Q9CYA6; -.
DR PRIDE; Q9CYA6; -.
DR ProteomicsDB; 298509; -.
DR Antibodypedia; 31655; 120 antibodies from 22 providers.
DR DNASU; 70650; -.
DR Ensembl; ENSMUST00000031376; ENSMUSP00000031376; ENSMUSG00000029427.
DR Ensembl; ENSMUST00000196282; ENSMUSP00000142363; ENSMUSG00000029427.
DR GeneID; 70650; -.
DR KEGG; mmu:70650; -.
DR UCSC; uc008zoh.2; mouse.
DR CTD; 55596; -.
DR MGI; MGI:1917900; Zcchc8.
DR VEuPathDB; HostDB:ENSMUSG00000029427; -.
DR eggNOG; KOG2673; Eukaryota.
DR GeneTree; ENSGT00390000011475; -.
DR InParanoid; Q9CYA6; -.
DR OMA; WQMFGSI; -.
DR OrthoDB; 338817at2759; -.
DR PhylomeDB; Q9CYA6; -.
DR TreeFam; TF321837; -.
DR BioGRID-ORCS; 70650; 14 hits in 66 CRISPR screens.
DR PRO; PR:Q9CYA6; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q9CYA6; protein.
DR Bgee; ENSMUSG00000029427; Expressed in animal zygote and 253 other tissues.
DR ExpressionAtlas; Q9CYA6; baseline and differential.
DR Genevisible; Q9CYA6; MM.
DR GO; GO:0071013; C:catalytic step 2 spliceosome; ISO:MGI.
DR GO; GO:0016604; C:nuclear body; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0031499; C:TRAMP complex; ISO:MGI.
DR GO; GO:0003723; F:RNA binding; ISO:MGI.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
DR GO; GO:0034470; P:ncRNA processing; ISS:UniProtKB.
DR GO; GO:0008380; P:RNA splicing; IEA:UniProtKB-KW.
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 Acetylation; Coiled coil; Metal-binding; mRNA processing; mRNA splicing;
KW Nucleus; Phosphoprotein; Reference proteome; Spliceosome; Zinc;
KW Zinc-finger.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q6NZY4"
FT CHAIN 2..709
FT /note="Zinc finger CCHC domain-containing protein 8"
FT /id="PRO_0000150961"
FT ZN_FING 230..247
FT /note="CCHC-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00047"
FT REGION 1..47
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 289..302
FT /note="RBM7 binding"
FT /evidence="ECO:0000250|UniProtKB:Q6NZY4"
FT REGION 312..327
FT /note="RBM7 binding"
FT /evidence="ECO:0000250|UniProtKB:Q6NZY4"
FT REGION 409..518
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 533..667
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 661..709
FT /note="MTREX binding"
FT /evidence="ECO:0000250|UniProtKB:Q6NZY4"
FT COILED 48..83
FT /evidence="ECO:0000255"
FT COMPBIAS 409..435
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 468..503
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 548..562
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 632..648
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q6NZY4"
FT MOD_RES 474
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q6NZY4"
FT MOD_RES 482
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q6NZY4"
FT MOD_RES 488
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q6NZY4"
FT MOD_RES 495
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q6NZY4"
FT MOD_RES 601
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6NZY4"
FT MOD_RES 660
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6NZY4"
FT MOD_RES 697
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6NZY4"
FT CONFLICT 2
FT /note="A -> G (in Ref. 1; BAC28304)"
FT /evidence="ECO:0000305"
FT CONFLICT 11
FT /note="E -> K (in Ref. 1; BAC28304)"
FT /evidence="ECO:0000305"
FT CONFLICT 330
FT /note="E -> G (in Ref. 1; BAC28304)"
FT /evidence="ECO:0000305"
FT CONFLICT 659
FT /note="H -> R (in Ref. 1; BAC28304)"
FT /evidence="ECO:0000305"
FT CONFLICT 695
FT /note="K -> E (in Ref. 1; BAB30977)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 709 AA; 78026 MW; BDBB3EEF1C6A74F4 CRC64;
MAAGVDFGDL ELFEAFDPPE ESTPKPVHTR FKDDEEEEDD DDDENGVGDA ELQEQLRRCE
ATIEQLRAEN QELKRKLNIL TRPSGILVSN TKIDGPLLQI LFMNNAISKQ YHQEIEEFVS
NLVKRFEEQQ KNDVEKTSFS LLPQPSSVML EEDHKVEESC AVKNNKEAFS VVGSVLYFTN
FCLDKLGQPL LNENPQLTEG WEIPKYQQVF SHIVPLEGQE MQVKAKRPKP HCFNCGSEEH
QMKECPMPRN AARISEKRKE YMDACGEASG QSFQQRYHAE EVEERFGRFK PGVISEELQD
ALGVTDKSLP PFIYRMRQLG YPPGWLKEAE LENSGLALYD GNDDADGETE TGEIQNKNVT
YDLSKLVNYP GFNISTPRGI PDEWRMFGSI PMQACQQKDV FASYLNSNIQ SPSMRSSGKR
SSSQSSPNSP KKQRKEGSAA ASPADMELDS DVEIPPGSQS SKAFQFQPPL PPGTPPPLPQ
GTPPPLFTPP LPKGTPPLTP SDSPQARPAA SAMDEDALTL EELEEQQRQI WAALQQAEGG
NGDSDVPGDT PLTGNSVASS PCPNEFDLPV PEGKALEKPV LAEPQEPAAS VDTAGPEPSC
SPAAGAAVLS QREEEAAAEG GPGDALLDNG GVLNMNMSNG SNQQPIHPDS RPPMAPKTHS
PVPDMSKFAT GITPFEFENM AESTGMYLRI RNLLKNSPRN QQKNKKTCE
