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   24-JAN-2024, entry version 150.
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   SwissPalm; Q8BTW8; -.
DR   EPD; Q8BTW8; -.
DR   MaxQB; Q8BTW8; -.
DR   PaxDb; 10090-ENSMUSP00000105353; -.
DR   PeptideAtlas; Q8BTW8; -.
DR   ProteomicsDB; 279088; -.
DR   Pumba; Q8BTW8; -.
DR   Antibodypedia; 43007; 210 antibodies from 27 providers.
DR   Ensembl; ENSMUST00000028990.10; ENSMUSP00000028990.4; ENSMUSG00000027487.12.
DR   Ensembl; ENSMUST00000109731.8; ENSMUSP00000105353.2; ENSMUSG00000027487.12.
DR   GeneID; 66971; -.
DR   KEGG; mmu:66971; -.
DR   UCSC; uc008njb.1; mouse.
DR   AGR; MGI:1914221; -.
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 78 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 248 other cell types or tissues.
DR   ExpressionAtlas; Q8BTW8; baseline and differential.
DR   GO; GO:0005829; C:cytosol; ISO:MGI.
DR   GO; GO:0005739; C:mitochondrion; IDA:MGI.
DR   GO; GO:0005654; C:nucleoplasm; ISO: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: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; Methylthiotransferase, N-terminal domain; 1.
DR   Gene3D; 3.80.30.20; tm_1862 like domain; 1.
DR   HAMAP; MF_01864; tRNA_metthiotr_MiaB; 1.
DR   InterPro; IPR006638; Elp3/MiaA/NifB-like_rSAM.
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   NCBIfam; TIGR01574; miaB-methiolase; 1.
DR   NCBIfam; TIGR00089; MiaB/RimO family radical SAM methylthiotransferase; 1.
DR   PANTHER; PTHR43020; CDK5 REGULATORY SUBUNIT-ASSOCIATED PROTEIN 1; 1.
DR   PANTHER; PTHR43020:SF2; MITOCHONDRIAL TRNA METHYLTHIOTRANSFERASE CDK5RAP1; 1.
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; SFLDG01082; B12-binding_domain_containing; 1.
DR   SFLD; SFLDF00413; CDK5RAP1; 1.
DR   SFLD; SFLDS00029; Radical_SAM; 1.
DR   SMART; SM00729; Elp3; 1.
DR   SUPFAM; SSF102114; Radical SAM enzymes; 1.
DR   PROSITE; PS51449; MTTASE_N; 1.
DR   PROSITE; PS01278; MTTASE_RADICAL; 1.
DR   PROSITE; PS51918; RADICAL_SAM; 1.
DR   PROSITE; PS50926; TRAM; 1.
DR   Genevisible; Q8BTW8; MM.
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
//