CLP1_MOUSE
ID CLP1_MOUSE Reviewed; 425 AA.
AC Q99LI9; Q3TEC7; Q3ULZ9;
DT 04-JAN-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 127.
DE RecName: Full=Polyribonucleotide 5'-hydroxyl-kinase Clp1 {ECO:0000255|HAMAP-Rule:MF_03035};
DE EC=2.7.1.78 {ECO:0000255|HAMAP-Rule:MF_03035};
DE AltName: Full=Polyadenylation factor Clp1 {ECO:0000255|HAMAP-Rule:MF_03035};
DE AltName: Full=Polynucleotide kinase Clp1 {ECO:0000255|HAMAP-Rule:MF_03035};
DE AltName: Full=Pre-mRNA cleavage complex II protein Clp1 {ECO:0000255|HAMAP-Rule:MF_03035};
GN Name=Clp1;
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=Embryo, Mammary gland, and Thymus;
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].
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
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, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF LYS-127.
RX PubMed=23474986; DOI=10.1038/nature11923;
RA Hanada T., Weitzer S., Mair B., Bernreuther C., Wainger B.J., Ichida J.,
RA Hanada R., Orthofer M., Cronin S.J., Komnenovic V., Minis A., Sato F.,
RA Mimata H., Yoshimura A., Tamir I., Rainer J., Kofler R., Yaron A.,
RA Eggan K.C., Woolf C.J., Glatzel M., Herbst R., Martinez J., Penninger J.M.;
RT "CLP1 links tRNA metabolism to progressive motor-neuron loss.";
RL Nature 495:474-480(2013).
RN [4]
RP FUNCTION, AND MUTAGENESIS OF LYS-127.
RX PubMed=24766809; DOI=10.1016/j.cell.2014.02.058;
RG Baylor Hopkins Center for Mendelian Genomics;
RA Karaca E., Weitzer S., Pehlivan D., Shiraishi H., Gogakos T., Hanada T.,
RA Jhangiani S.N., Wiszniewski W., Withers M., Campbell I.M., Erdin S.,
RA Isikay S., Franco L.M., Gonzaga-Jauregui C., Gambin T., Gelowani V.,
RA Hunter J.V., Yesil G., Koparir E., Yilmaz S., Brown M., Briskin D.,
RA Hafner M., Morozov P., Farazi T.A., Bernreuther C., Glatzel M.,
RA Trattnig S., Friske J., Kronnerwetter C., Bainbridge M.N., Gezdirici A.,
RA Seven M., Muzny D.M., Boerwinkle E., Ozen M., Clausen T., Tuschl T.,
RA Yuksel A., Hess A., Gibbs R.A., Martinez J., Penninger J.M., Lupski J.R.;
RT "Human CLP1 mutations alter tRNA biogenesis, affecting both peripheral and
RT central nervous system function.";
RL Cell 157:636-650(2014).
CC -!- FUNCTION: Polynucleotide kinase that can phosphorylate the 5'-hydroxyl
CC groups of double-stranded RNA (dsRNA), single-stranded RNA (ssRNA),
CC double-stranded DNA (dsDNA) and double-stranded DNA:RNA hybrids. dsRNA
CC is phosphorylated more efficiently than dsDNA, and the RNA component of
CC a DNA:RNA hybrid is phosphorylated more efficiently than the DNA
CC component. Plays a key role in both tRNA splicing and mRNA 3'-end
CC formation. Component of the tRNA splicing endonuclease complex:
CC phosphorylates the 5'-terminus of the tRNA 3'-exon during tRNA
CC splicing; this phosphorylation event is a prerequisite for the
CC subsequent ligation of the two exon halves and the production of a
CC mature tRNA (PubMed:23474986, PubMed:24766809). Its role in tRNA
CC splicing and maturation is required for cerebellar development
CC (PubMed:24766809). Component of the pre-mRNA cleavage complex II (CF-
CC II), which seems to be required for mRNA 3'-end formation. Also
CC phosphorylates the 5'-terminus of exogenously introduced short
CC interfering RNAs (siRNAs), which is a necessary prerequisite for their
CC incorporation into the RNA-induced silencing complex (RISC). However,
CC endogenous siRNAs and microRNAs (miRNAs) that are produced by the
CC cleavage of dsRNA precursors by DICER1 already contain a 5'-phosphate
CC group, so this protein may be dispensible for normal RNA-mediated gene
CC silencing. {ECO:0000269|PubMed:23474986, ECO:0000269|PubMed:24766809}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 5'-end dephospho-2'-deoxyribonucleoside-DNA + ATP = a 5'-end
CC 5'-monophospho-2'-deoxyribonucleoside-DNA + ADP + H(+);
CC Xref=Rhea:RHEA:15669, Rhea:RHEA-COMP:13180, Rhea:RHEA-COMP:13184,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:136412,
CC ChEBI:CHEBI:136416, ChEBI:CHEBI:456216; EC=2.7.1.78;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03035};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 5'-end dephospho-ribonucleoside-RNA + ATP = a 5'-end 5'-
CC monophospho-ribonucleoside-RNA + ADP + H(+); Xref=Rhea:RHEA:54580,
CC Rhea:RHEA-COMP:13935, Rhea:RHEA-COMP:13936, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:138282, ChEBI:CHEBI:138284,
CC ChEBI:CHEBI:456216; EC=2.7.1.78; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_03035};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03035};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03035};
CC Name=Ni(2+); Xref=ChEBI:CHEBI:49786;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03035};
CC -!- SUBUNIT: Component of the tRNA splicing endonuclease complex, composed
CC of CLP1, TSEN2, TSEN15, TSEN34 and TSEN54. Component of pre-mRNA
CC cleavage complex II (CF-II). Also associates with numerous components
CC of the pre-mRNA cleavage complex I (CF-I/CFIm), including NUDT21,
CC CPSF2, CPSF3, CPSF6 and CPSF7. Interacts with CSTF2 and SYMPK.
CC {ECO:0000255|HAMAP-Rule:MF_03035}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|HAMAP-Rule:MF_03035}.
CC -!- DISRUPTION PHENOTYPE: Early embryonic lethality.
CC {ECO:0000269|PubMed:23474986}.
CC -!- SIMILARITY: Belongs to the Clp1 family. Clp1 subfamily.
CC {ECO:0000255|HAMAP-Rule:MF_03035}.
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; AK077647; BAC36924.1; -; mRNA.
DR EMBL; AK145209; BAE26299.1; -; mRNA.
DR EMBL; AK169709; BAE41321.1; -; mRNA.
DR EMBL; BC003237; AAH03237.1; -; mRNA.
DR CCDS; CCDS16191.1; -.
DR RefSeq; NP_598601.1; NM_133840.2.
DR AlphaFoldDB; Q99LI9; -.
DR SMR; Q99LI9; -.
DR BioGRID; 221164; 9.
DR IntAct; Q99LI9; 9.
DR STRING; 10090.ENSMUSP00000028475; -.
DR iPTMnet; Q99LI9; -.
DR PhosphoSitePlus; Q99LI9; -.
DR EPD; Q99LI9; -.
DR MaxQB; Q99LI9; -.
DR PaxDb; Q99LI9; -.
DR PeptideAtlas; Q99LI9; -.
DR PRIDE; Q99LI9; -.
DR ProteomicsDB; 283860; -.
DR Antibodypedia; 27467; 198 antibodies from 28 providers.
DR DNASU; 98985; -.
DR Ensembl; ENSMUST00000028475; ENSMUSP00000028475; ENSMUSG00000027079.
DR Ensembl; ENSMUST00000165219; ENSMUSP00000129300; ENSMUSG00000027079.
DR GeneID; 98985; -.
DR KEGG; mmu:98985; -.
DR UCSC; uc008kja.1; mouse.
DR CTD; 10978; -.
DR MGI; MGI:2138968; Clp1.
DR VEuPathDB; HostDB:ENSMUSG00000027079; -.
DR eggNOG; KOG2749; Eukaryota.
DR GeneTree; ENSGT00940000153668; -.
DR HOGENOM; CLU_018195_1_0_1; -.
DR InParanoid; Q99LI9; -.
DR OMA; VQYVNCH; -.
DR OrthoDB; 814241at2759; -.
DR PhylomeDB; Q99LI9; -.
DR TreeFam; TF105795; -.
DR Reactome; R-MMU-72163; mRNA Splicing - Major Pathway.
DR Reactome; R-MMU-72187; mRNA 3'-end processing.
DR Reactome; R-MMU-73856; RNA Polymerase II Transcription Termination.
DR Reactome; R-MMU-77595; Processing of Intronless Pre-mRNAs.
DR BioGRID-ORCS; 98985; 30 hits in 72 CRISPR screens.
DR PRO; PR:Q99LI9; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q99LI9; protein.
DR Bgee; ENSMUSG00000027079; Expressed in fetal liver hematopoietic progenitor cell and 258 other tissues.
DR Genevisible; Q99LI9; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005849; C:mRNA cleavage factor complex; IEA:UniProtKB-UniRule.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0000214; C:tRNA-intron endonuclease complex; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule.
DR GO; GO:0046404; F:polydeoxyribonucleotide 5'-hydroxyl-kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0051733; F:polydeoxyribonucleotide kinase activity; ISS:UniProtKB.
DR GO; GO:0051731; F:polynucleotide 5'-hydroxyl-kinase activity; IBA:GO_Central.
DR GO; GO:0051736; F:polyribonucleotide 5'-hydroxyl-kinase activity; ISS:UniProtKB.
DR GO; GO:0021695; P:cerebellar cortex development; IMP:UniProtKB.
DR GO; GO:0098795; P:global gene silencing by mRNA cleavage; ISS:UniProtKB.
DR GO; GO:0006378; P:mRNA polyadenylation; IBA:GO_Central.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0070922; P:RISC complex assembly; ISS:UniProtKB.
DR GO; GO:0006396; P:RNA processing; IBA:GO_Central.
DR GO; GO:0006388; P:tRNA splicing, via endonucleolytic cleavage and ligation; ISS:UniProtKB.
DR Gene3D; 2.40.30.330; -; 1.
DR Gene3D; 2.60.120.1030; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR HAMAP; MF_03035; Clp1; 1.
DR InterPro; IPR028606; Clp1.
DR InterPro; IPR045116; Clp1/Grc3.
DR InterPro; IPR010655; Clp1_C.
DR InterPro; IPR038238; Clp1_C_sf.
DR InterPro; IPR032324; Clp1_N.
DR InterPro; IPR038239; Clp1_N_sf.
DR InterPro; IPR032319; CLP1_P.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR12755; PTHR12755; 1.
DR Pfam; PF06807; Clp1; 1.
DR Pfam; PF16573; CLP1_N; 1.
DR Pfam; PF16575; CLP1_P; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Kinase; Magnesium; Manganese; mRNA processing;
KW Neurodegeneration; Nickel; Nucleotide-binding; Nucleus; Reference proteome;
KW Transferase; tRNA processing.
FT CHAIN 1..425
FT /note="Polyribonucleotide 5'-hydroxyl-kinase Clp1"
FT /id="PRO_0000089864"
FT BINDING 22
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03035"
FT BINDING 62
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03035"
FT BINDING 124..129
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03035"
FT MUTAGEN 127
FT /note="K->A: Progressive loss of motor neurons, axonal
FT motor neuropathy, and muscle paralysis leading to death
FT within hours of birth. Mice exhibit microcephaly due to
FT reduced numbers of cortical neurons. Embryos have normal
FT numbers and proliferation of neuronal progenitors, but
FT neuronal progenitor cells undergo enhanced cell death,
FT resulting in reduced numbers of cortical neurons."
FT /evidence="ECO:0000269|PubMed:23474986,
FT ECO:0000269|PubMed:24766809"
FT CONFLICT 79
FT /note="T -> N (in Ref. 1; BAE26299)"
FT /evidence="ECO:0000305"
FT CONFLICT 264
FT /note="N -> D (in Ref. 1; BAE41321)"
FT /evidence="ECO:0000305"
FT CONFLICT 394
FT /note="V -> L (in Ref. 1; BAE26299)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 425 AA; 47738 MW; C1AED7978B383097 CRC64;
MSEESNDDKK PTTKFELERE TELRFEVEAS QSVQLELLAG MAEIFGTELT RNKKFTFDAG
AKVAVFTWHG CSLQLSGRTE VAYVSKDTPM LLYLNTHTAL EQMRRQAEKE EERGPRVMVV
GPTDVGKSTV CRLLLNYAVR LGRRPTYVEL DVGQGSVSIP GTMGALYIER PADVEEGFSI
QAPLVYHFGS TTPGTNIKLY NKITSRLADV FNQRCEVNRR ASVSGCVINT CGWVKGYGYQ
ALVHAASAFE VDVVVVLDQE RLYNELKRDL PHFVRTVLLP KSGGVVERSK DFRRECRDER
IREYFYGFRG CFYPHAFNVK FSDVKIYKVG APTIPDSCLP LGMSQEDNQL KLVPVTPGRD
MVHHLLSVST AEGTEENLSE TSVAGFIVVT SVDVEHQVFT VLSPAPRPLP KNFLLIMDIR
FMDLK
