CK5P1_MOUSE
ID CK5P1_MOUSE Reviewed; 588 AA.
AC Q8BTW8; Q9D6Q4;
DT 16-JUN-2003, integrated into UniProtKB/Swiss-Prot.
DT 16-JUN-2003, sequence version 2.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Mitochondrial tRNA methylthiotransferase CDK5RAP1 {ECO:0000303|PubMed:25738458};
DE EC=2.8.4.3 {ECO:0000269|PubMed:25738458};
DE AltName: Full=CDK5 activator-binding protein C42;
DE AltName: Full=CDK5 regulatory subunit-associated protein 1;
DE AltName: Full=mt-tRNA-2-methylthio-N6-dimethylallyladenosine synthase;
DE AltName: Full=mt-tRNA-N6-(dimethylallyl)adenosine(37) methylthiotransferase;
DE Flags: Precursor;
GN Name=Cdk5rap1 {ECO:0000312|MGI:MGI:1914221};
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=Thymus, and Tongue;
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 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, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY,
RP AND TISSUE SPECIFICITY.
RX PubMed=25738458; DOI=10.1016/j.cmet.2015.01.019;
RA Wei F.Y., Zhou B., Suzuki T., Miyata K., Ujihara Y., Horiguchi H.,
RA Takahashi N., Xie P., Michiue H., Fujimura A., Kaitsuka T., Matsui H.,
RA Koga Y., Mohri S., Suzuki T., Oike Y., Tomizawa K.;
RT "Cdk5rap1-mediated 2-methylthio modification of mitochondrial tRNAs governs
RT protein translation and contributes to myopathy in mice and humans.";
RL Cell Metab. 21:428-442(2015).
CC -!- FUNCTION: Methylthiotransferase that catalyzes the conversion of N6-
CC (dimethylallyl)adenosine (i(6)A) to 2-methylthio-N6-
CC (dimethylallyl)adenosine (ms(2)i(6)A) at position 37 (adjacent to the
CC 3'-end of the anticodon) of four mitochondrial DNA-encoded tRNAs
CC (Ser(UCN), Phe, Tyr and Trp) (PubMed:25738458). Essential for efficient
CC and highly accurate protein translation by the ribosome
CC (PubMed:25738458). Specifically inhibits CDK5 activation by CDK5R1 (By
CC similarity). Essential for efficient mitochondrial protein synthesis
CC and respiratory chain (PubMed:25738458). {ECO:0000250|UniProtKB:Q96SZ6,
CC ECO:0000269|PubMed:25738458}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[sulfur carrier]-SH + AH2 + N(6)-dimethylallyladenosine(37) in
CC tRNA + 2 S-adenosyl-L-methionine = 2-methylsulfanyl-N(6)-
CC dimethylallyladenosine(37) in tRNA + 5'-deoxyadenosine + [sulfur
CC carrier]-H + A + 2 H(+) + L-methionine + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:37067, Rhea:RHEA-COMP:10375, Rhea:RHEA-COMP:10376,
CC Rhea:RHEA-COMP:14737, Rhea:RHEA-COMP:14739, ChEBI:CHEBI:13193,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17319, ChEBI:CHEBI:17499,
CC ChEBI:CHEBI:29917, ChEBI:CHEBI:57844, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:64428, ChEBI:CHEBI:74415,
CC ChEBI:CHEBI:74417; EC=2.8.4.3;
CC Evidence={ECO:0000305|PubMed:25738458};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:37068;
CC Evidence={ECO:0000269|PubMed:25738458};
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00780};
CC Note=Binds 2 [4Fe-4S] clusters. One cluster is coordinated with 3
CC cysteines and an exchangeable S-adenosyl-L-methionine.
CC {ECO:0000255|PROSITE-ProRule:PRU00780};
CC -!- SUBUNIT: Interacts with CDK5R1 (p35 form). CDK5RAP1, CDK5RAP2 and
CC CDK5RAP3 show competitive binding to CDK5R1. Probably forms a complex
CC with CDK5R1 and CDK5. {ECO:0000250|UniProtKB:Q96SZ6}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:25738458}.
CC -!- TISSUE SPECIFICITY: Expressed in brain, liver, skeletal muscle and
CC heart. {ECO:0000269|PubMed:25738458}.
CC -!- DISRUPTION PHENOTYPE: Knockout mice show a deficiency in ms(2)i(6)A
CC modification, resulting in impaired mitochondrial protein synthesis,
CC which leads to respiratory defects. {ECO:0000269|PubMed:25738458}.
CC -!- SIMILARITY: Belongs to the methylthiotransferase family. MiaB
CC subfamily. {ECO:0000305}.
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DR EMBL; AK010097; BAB26700.1; -; mRNA.
DR EMBL; AK088517; BAC40398.1; -; mRNA.
DR EMBL; BC025132; AAH25132.1; -; mRNA.
DR CCDS; CCDS16931.1; -.
DR RefSeq; NP_080152.1; NM_025876.2.
DR AlphaFoldDB; Q8BTW8; -.
DR SMR; Q8BTW8; -.
DR IntAct; Q8BTW8; 1.
DR MINT; Q8BTW8; -.
DR STRING; 10090.ENSMUSP00000105353; -.
DR PhosphoSitePlus; Q8BTW8; -.
DR EPD; Q8BTW8; -.
DR MaxQB; Q8BTW8; -.
DR PaxDb; Q8BTW8; -.
DR PeptideAtlas; Q8BTW8; -.
DR PRIDE; Q8BTW8; -.
DR ProteomicsDB; 279088; -.
DR Antibodypedia; 43007; 180 antibodies from 27 providers.
DR Ensembl; ENSMUST00000028990; ENSMUSP00000028990; ENSMUSG00000027487.
DR Ensembl; ENSMUST00000109731; ENSMUSP00000105353; ENSMUSG00000027487.
DR GeneID; 66971; -.
DR KEGG; mmu:66971; -.
DR UCSC; uc008njb.1; mouse.
DR CTD; 51654; -.
DR MGI; MGI:1914221; Cdk5rap1.
DR VEuPathDB; HostDB:ENSMUSG00000027487; -.
DR eggNOG; KOG2492; Eukaryota.
DR GeneTree; ENSGT00940000160361; -.
DR HOGENOM; CLU_018697_2_1_1; -.
DR InParanoid; Q8BTW8; -.
DR OMA; CEHFHIP; -.
DR PhylomeDB; Q8BTW8; -.
DR TreeFam; TF101033; -.
DR BioGRID-ORCS; 66971; 0 hits in 73 CRISPR screens.
DR ChiTaRS; Cdk5rap1; mouse.
DR PRO; PR:Q8BTW8; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q8BTW8; protein.
DR Bgee; ENSMUSG00000027487; Expressed in primary oocyte and 246 other tissues.
DR ExpressionAtlas; Q8BTW8; baseline and differential.
DR Genevisible; Q8BTW8; MM.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; IDA:MGI.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0035597; F:N6-isopentenyladenosine methylthiotransferase activity; IMP:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0070900; P:mitochondrial tRNA modification; IMP:MGI.
DR GO; GO:0045736; P:negative regulation of cyclin-dependent protein serine/threonine kinase activity; ISS:UniProtKB.
DR GO; GO:0045737; P:positive regulation of cyclin-dependent protein serine/threonine kinase activity; ISO:MGI.
DR GO; GO:0070131; P:positive regulation of mitochondrial translation; IMP:MGI.
DR GO; GO:0045903; P:positive regulation of translational fidelity; IGI:MGI.
DR GO; GO:0000079; P:regulation of cyclin-dependent protein serine/threonine kinase activity; ISS:UniProtKB.
DR Gene3D; 3.40.50.12160; -; 1.
DR Gene3D; 3.80.30.20; -; 1.
DR HAMAP; MF_01864; tRNA_metthiotr_MiaB; 1.
DR InterPro; IPR006638; Elp3/MiaB/NifB.
DR InterPro; IPR005839; Methylthiotransferase.
DR InterPro; IPR020612; Methylthiotransferase_CS.
DR InterPro; IPR013848; Methylthiotransferase_N.
DR InterPro; IPR038135; Methylthiotransferase_N_sf.
DR InterPro; IPR006463; MiaB_methiolase.
DR InterPro; IPR007197; rSAM.
DR InterPro; IPR023404; rSAM_horseshoe.
DR InterPro; IPR002792; TRAM_dom.
DR Pfam; PF04055; Radical_SAM; 1.
DR Pfam; PF01938; TRAM; 1.
DR Pfam; PF00919; UPF0004; 1.
DR SFLD; SFLDF00273; (dimethylallyl)adenosine_tRNA; 1.
DR SFLD; SFLDS00029; Radical_SAM; 1.
DR SMART; SM00729; Elp3; 1.
DR TIGRFAMs; TIGR00089; TIGR00089; 1.
DR PROSITE; PS51449; MTTASE_N; 1.
DR PROSITE; PS01278; MTTASE_RADICAL; 1.
DR PROSITE; PS51918; RADICAL_SAM; 1.
DR PROSITE; PS50926; TRAM; 1.
PE 1: Evidence at protein level;
KW 4Fe-4S; Iron; Iron-sulfur; Metal-binding; Mitochondrion;
KW Reference proteome; S-adenosyl-L-methionine; Transferase; Transit peptide;
KW tRNA processing.
FT TRANSIT 1..30
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 31..588
FT /note="Mitochondrial tRNA methylthiotransferase CDK5RAP1"
FT /evidence="ECO:0000255"
FT /id="PRO_0000141765"
FT DOMAIN 99..219
FT /note="MTTase N-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00780"
FT DOMAIN 243..498
FT /note="Radical SAM core"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01266"
FT DOMAIN 500..575
FT /note="TRAM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00208"
FT REGION 33..53
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 70..91
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 108
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00780"
FT BINDING 144
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00780"
FT BINDING 182
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00780"
FT BINDING 257
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="2"
FT /ligand_note="4Fe-4S-S-AdoMet"
FT /evidence="ECO:0000250|UniProtKB:Q9X2H6"
FT BINDING 261
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="2"
FT /ligand_note="4Fe-4S-S-AdoMet"
FT /evidence="ECO:0000250|UniProtKB:Q9X2H6"
FT BINDING 264
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="2"
FT /ligand_note="4Fe-4S-S-AdoMet"
FT /evidence="ECO:0000250|UniProtKB:Q9X2H6"
FT CONFLICT 505
FT /note="C -> Y (in Ref. 1; BAC40398)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 588 AA; 66110 MW; 4430C4F1A067093C CRC64;
MHPLRCVLQV QRLSAPFTSM CWVLLRTCRA QSSVSSTPCP SPEAKSSEAQ KDFSSRLATG
PTFQHFLRSA SVPQEKPSSP EVEDPPPYLS GDELLGRQRK VYLETYGCQM NVNDTEIAWS
ILQKSGYLRT SNLQEADVIL LVTCSIREKA EQTIWNRLHQ LKVLKTKRPR SRVPLRIGIL
GCMAERLKGE ILNREKMVDL LAGPDAYRDL PRLLAVVESG QQAANVLLSL DETYADIMPV
QTSPSATSAF VSIMRGCDNM CSYCIVPFTR GRERSRPVAS ILDEVRKLSE QGLKEVTLLG
QNVNSFRDNS EVQFNNAGSA NLSRGFTTNY KPKQGGLRFS HLLDQVSRID PEMRIRFTSP
HPKDFPDEVL QLIRERHNIC KQIHLPAQSG SSRVLDAMRR GYSREAYVAL VHHVRETIPG
VSLSSDFITG FCGETEDDHR QTVSLLREVQ YNTGFLFAYS MRQKTRAYHR LKDDVPEEVK
LRRLEELITV FREEASKANK TSVGCSQLVL VEGFSKRSTT DLCGRNDANL KVIFPDAEVE
DITNPGLKVR AQPGDYVLVK ITSASSQTLK GHILCRTTMK DSLTYCTT
