ID CK5P1_HUMAN Reviewed; 601 AA. AC Q96SZ6; A8K7R0; Q5QP46; Q5QP47; Q5QP48; Q675N4; Q675N5; Q9BVG6; Q9BWZ5; AC Q9H859; Q9NZZ9; Q9Y3F0; DT 16-JUN-2003, integrated into UniProtKB/Swiss-Prot. DT 16-JUN-2003, sequence version 2. DT 27-MAR-2024, entry version 191. DE RecName: Full=Mitochondrial tRNA methylthiotransferase CDK5RAP1 {ECO:0000303|PubMed:22422838, ECO:0000303|PubMed:25738458}; DE EC=2.8.4.3 {ECO:0000269|PubMed:22422838, 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|HGNC:HGNC:15880}; Synonyms=C20orf34; GN ORFNames=CGI-05, HSPC167; 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). RX PubMed=10810093; DOI=10.1101/gr.10.5.703; RA Lai C.-H., Chou C.-Y., Ch'ang L.-Y., Liu C.-S., Lin W.-C.; RT "Identification of novel human genes evolutionarily conserved in RT Caenorhabditis elegans by comparative proteomics."; RL Genome Res. 10:703-713(2000). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Umbilical cord blood; RX PubMed=11042152; DOI=10.1101/gr.140200; RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G., RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W., RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.; RT "Cloning and functional analysis of cDNAs with open reading frames for 300 RT previously undefined genes expressed in CD34+ hematopoietic stem/progenitor RT cells."; RL Genome Res. 10:1546-1560(2000). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 5 AND 6). RX PubMed=15329498; DOI=10.1266/ggs.79.177; RA Zou X., Ji C., Jin F., Liu J., Wu M., Zheng H., Wang Y., Li X., Xu J., RA Gu S., Xie Y., Mao Y.; RT "Cloning, characterization and expression of CDK5RAP1_v3 and CDK5RAP1_v4, RT two novel splice variants of human CDK5RAP1."; RL Genes Genet. Syst. 79:177-182(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3). RC TISSUE=Retinoblastoma, Stomach, and Teratocarcinoma; 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=11780052; DOI=10.1038/414865a; RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 20."; RL Nature 414:865-871(2001). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4). RC TISSUE=Duodenum, and Lung; 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 [8] RP TISSUE SPECIFICITY. RX PubMed=10721722; DOI=10.1016/s0378-1119(99)00499-0; RA Ching Y.-P., Qi Z., Wang J.H.; RT "Cloning of three novel neuronal Cdk5 activator binding proteins."; RL Gene 242:285-294(2000). RN [9] RP FUNCTION, INTERACTION WITH CDK5 AND CDK5R1, AND TISSUE SPECIFICITY. RX PubMed=11882646; DOI=10.1074/jbc.c200032200; RA Ching Y.-P., Pang A.S.H., Lam W.-H., Qi R.Z., Wang J.H.; RT "Identification of a neuronal Cdk5 activator-binding protein as Cdk5 RT inhibitor."; RL J. Biol. Chem. 277:15237-15240(2002). RN [10] RP FUNCTION, SUBCELLULAR LOCATION, AND CATALYTIC ACTIVITY. RX PubMed=22422838; DOI=10.1093/nar/gks240; RA Reiter V., Matschkal D.M., Wagner M., Globisch D., Kneuttinger A.C., RA Mueller M., Carell T.; RT "The CDK5 repressor CDK5RAP1 is a methylthiotransferase acting on nuclear RT and mitochondrial RNA."; RL Nucleic Acids Res. 40:6235-6240(2012). RN [11] RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF CYS-258; CYS-262 AND RP CYS-265. 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). RN [12] RP FUNCTION. RX PubMed=28981754; DOI=10.1093/nar/gkx819; RA Fakruddin M., Wei F.Y., Emura S., Matsuda S., Yasukawa T., Kang D., RA Tomizawa K.; RT "Cdk5rap1-mediated 2-methylthio-N6-isopentenyladenosine modification is RT absent from nuclear-derived RNA species."; RL Nucleic Acids Res. 45:11954-11961(2017). 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:22422838, PubMed:25738458, CC PubMed:28981754). Essential for efficient and highly accurate protein CC translation by the ribosome (PubMed:22422838, PubMed:25738458, CC PubMed:28981754). Specifically inhibits CDK5 activation by CDK5R1 CC (PubMed:11882646). Essential for efficient mitochondrial protein CC synthesis and respiratory chain; shows pathological consequences in CC mitochondrial disease (PubMed:25738458). {ECO:0000269|PubMed:11882646, CC ECO:0000269|PubMed:22422838, ECO:0000269|PubMed:25738458, CC ECO:0000269|PubMed:28981754}. 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; Evidence={ECO:0000305|PubMed:22422838, CC ECO:0000305|PubMed:25738458}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:37068; CC Evidence={ECO:0000269|PubMed:25738458, ECO:0000305|PubMed:22422838}; 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. Forms a complex with CC CDK5R1 and CDK5. {ECO:0000269|PubMed:11882646}. CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:22422838}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=6; CC Name=1; CC IsoId=Q96SZ6-1; Sequence=Displayed; CC Name=2; CC IsoId=Q96SZ6-2; Sequence=VSP_007560, VSP_007562; CC Name=3; Synonyms=CDK5RAP1_v1 {ECO:0000303|PubMed:15329498}, isoform a; CC IsoId=Q96SZ6-3; Sequence=VSP_007562; CC Name=4; Synonyms=isoform d; CC IsoId=Q96SZ6-4; Sequence=VSP_007561; CC Name=5; Synonyms=CDK5RAP1_v4 {ECO:0000303|PubMed:15329498}; CC IsoId=Q96SZ6-5; Sequence=VSP_047799, VSP_047800, VSP_047801; CC Name=6; Synonyms=CDK5RAP1_v3 {ECO:0000303|PubMed:15329498}; CC IsoId=Q96SZ6-6; Sequence=VSP_047799, VSP_047802; CC -!- TISSUE SPECIFICITY: Expressed in heart, brain, placenta, lung, liver, CC skeletal muscle, kidney and pancreas (PubMed:10721722). Expressed in CC neurons of central nervous tissue (PubMed:10721722, PubMed:11882646). CC {ECO:0000269|PubMed:10721722, ECO:0000269|PubMed:11882646}. CC -!- TISSUE SPECIFICITY: [Isoform 5]: Mainly expressed in brain, placenta CC and testis. CC -!- TISSUE SPECIFICITY: [Isoform 6]: High expression in placenta and lung. CC -!- MISCELLANEOUS: [Isoform 1]: May be due to intron retention. CC -!- MISCELLANEOUS: [Isoform 2]: Absence of the mitochondrial target CC sequence which may lead to miss-localization. CC {ECO:0000303|PubMed:25738458}. CC -!- SIMILARITY: Belongs to the methylthiotransferase family. MiaB CC subfamily. {ECO:0000305}. CC -!- CAUTION: CDK5RAP1 was proposed to act on both nuclear and mitochondrial CC RNA (PubMed:22422838). However, another study shows that ms2i6A is a CC mitochondrial tRNA specific modification and is absent from nuclear CC encoded RNA species, implying that there is no methylthiotransferase CC activity on nuclear RNA (PubMed:28981754). CC {ECO:0000269|PubMed:22422838, ECO:0000269|PubMed:28981754}. CC -!- SEQUENCE CAUTION: CC Sequence=AAD34147.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=AAF29131.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=BAB55120.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={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; AF152097; AAD34147.1; ALT_FRAME; mRNA. DR EMBL; AF161516; AAF29131.1; ALT_FRAME; mRNA. DR EMBL; AY462283; AAS18317.1; -; mRNA. DR EMBL; AY462284; AAS18318.1; -; mRNA. DR EMBL; AK023992; BAB14760.1; -; mRNA. DR EMBL; AK027449; BAB55120.1; ALT_SEQ; mRNA. DR EMBL; AK292075; BAF84764.1; -; mRNA. DR EMBL; AL355392; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471077; EAW76319.1; -; Genomic_DNA. DR EMBL; CH471077; EAW76322.1; -; Genomic_DNA. DR EMBL; CH471077; EAW76323.1; -; Genomic_DNA. DR EMBL; BC001215; AAH01215.1; -; mRNA. DR EMBL; BC050706; AAH50706.1; -; mRNA. DR CCDS; CCDS13219.1; -. [Q96SZ6-3] DR CCDS; CCDS63255.1; -. [Q96SZ6-4] DR CCDS; CCDS93031.1; -. [Q96SZ6-1] DR RefSeq; NP_001265097.1; NM_001278168.1. [Q96SZ6-4] DR RefSeq; NP_001265098.1; NM_001278169.1. DR RefSeq; NP_057166.4; NM_016082.4. DR RefSeq; NP_057492.2; NM_016408.3. [Q96SZ6-3] DR AlphaFoldDB; Q96SZ6; -. DR SMR; Q96SZ6; -. DR BioGRID; 119661; 149. DR IntAct; Q96SZ6; 20. DR MINT; Q96SZ6; -. DR STRING; 9606.ENSP00000217372; -. DR iPTMnet; Q96SZ6; -. DR PhosphoSitePlus; Q96SZ6; -. DR SwissPalm; Q96SZ6; -. DR BioMuta; CDK5RAP1; -. DR DMDM; 32129446; -. DR EPD; Q96SZ6; -. DR jPOST; Q96SZ6; -. DR MassIVE; Q96SZ6; -. DR MaxQB; Q96SZ6; -. DR PaxDb; 9606-ENSP00000217372; -. DR PeptideAtlas; Q96SZ6; -. DR ProteomicsDB; 65981; -. DR ProteomicsDB; 78165; -. [Q96SZ6-1] DR ProteomicsDB; 78166; -. [Q96SZ6-2] DR ProteomicsDB; 78167; -. [Q96SZ6-3] DR ProteomicsDB; 78168; -. [Q96SZ6-4] DR Pumba; Q96SZ6; -. DR Antibodypedia; 43007; 210 antibodies from 27 providers. DR DNASU; 51654; -. DR Ensembl; ENST00000339269.5; ENSP00000341840.5; ENSG00000101391.21. [Q96SZ6-4] DR Ensembl; ENST00000346416.7; ENSP00000217372.2; ENSG00000101391.21. [Q96SZ6-3] DR Ensembl; ENST00000357886.8; ENSP00000350558.4; ENSG00000101391.21. [Q96SZ6-1] DR Ensembl; ENST00000473997.5; ENSP00000476857.1; ENSG00000101391.21. [Q96SZ6-2] DR GeneID; 51654; -. DR KEGG; hsa:51654; -. DR MANE-Select; ENST00000346416.7; ENSP00000217372.2; NM_016408.4; NP_057492.2. [Q96SZ6-3] DR UCSC; uc002wyz.5; human. [Q96SZ6-1] DR AGR; HGNC:15880; -. DR CTD; 51654; -. DR DisGeNET; 51654; -. DR GeneCards; CDK5RAP1; -. DR HGNC; HGNC:15880; CDK5RAP1. DR HPA; ENSG00000101391; Low tissue specificity. DR MIM; 608200; gene. DR neXtProt; NX_Q96SZ6; -. DR OpenTargets; ENSG00000101391; -. DR PharmGKB; PA26313; -. DR VEuPathDB; HostDB:ENSG00000101391; -. DR eggNOG; KOG2492; Eukaryota. DR GeneTree; ENSGT00940000160361; -. DR HOGENOM; CLU_018697_2_1_1; -. DR InParanoid; Q96SZ6; -. DR OMA; CEHFHIP; -. DR OrthoDB; 1122at2759; -. DR PhylomeDB; Q96SZ6; -. DR TreeFam; TF101033; -. DR PathwayCommons; Q96SZ6; -. DR SignaLink; Q96SZ6; -. DR BioGRID-ORCS; 51654; 12 hits in 1154 CRISPR screens. DR ChiTaRS; CDK5RAP1; human. DR GeneWiki; CDK5RAP1; -. DR GenomeRNAi; 51654; -. DR Pharos; Q96SZ6; Tbio. DR PRO; PR:Q96SZ6; -. DR Proteomes; UP000005640; Chromosome 20. DR RNAct; Q96SZ6; Protein. DR Bgee; ENSG00000101391; Expressed in granulocyte and 205 other cell types or tissues. DR ExpressionAtlas; Q96SZ6; baseline and differential. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005739; C:mitochondrion; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. 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; IBA:GO_Central. DR GO; GO:0019901; F:protein kinase binding; NAS:UniProtKB. DR GO; GO:0007420; P:brain development; NAS:UniProtKB. DR GO; GO:0070900; P:mitochondrial tRNA modification; IEA:Ensembl. DR GO; GO:0045736; P:negative regulation of cyclin-dependent protein serine/threonine kinase activity; IDA:UniProtKB. DR GO; GO:0070131; P:positive regulation of mitochondrial translation; IEA:Ensembl. DR GO; GO:0045903; P:positive regulation of translational fidelity; IEA:Ensembl. DR GO; GO:0045664; P:regulation of neuron differentiation; NAS: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; Q96SZ6; HS. PE 1: Evidence at protein level; KW 4Fe-4S; Alternative splicing; Iron; Iron-sulfur; Metal-binding; KW Mitochondrion; Reference proteome; S-adenosyl-L-methionine; Transferase; KW Transit peptide; tRNA processing. FT TRANSIT 1..33 FT /note="Mitochondrion" FT /evidence="ECO:0000255" FT CHAIN 34..601 FT /note="Mitochondrial tRNA methylthiotransferase CDK5RAP1" FT /evidence="ECO:0000255" FT /id="PRO_0000141764" FT DOMAIN 100..220 FT /note="MTTase N-terminal" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00780" FT DOMAIN 244..512 FT /note="Radical SAM core" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01266" FT DOMAIN 515..590 FT /note="TRAM" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00208" FT BINDING 109 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00780" FT BINDING 145 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00780" FT BINDING 183 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00780" FT BINDING 258 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 262 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 265 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 VAR_SEQ 1..90 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_007560" FT VAR_SEQ 292..305 FT /note="Missing (in isoform 5 and isoform 6)" FT /evidence="ECO:0000303|PubMed:15329498" FT /id="VSP_047799" FT VAR_SEQ 293..383 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_007561" FT VAR_SEQ 293..306 FT /note="Missing (in isoform 2 and isoform 3)" FT /evidence="ECO:0000303|PubMed:11042152, FT ECO:0000303|PubMed:14702039" FT /id="VSP_007562" FT VAR_SEQ 435..440 FT /note="GVSLSS -> EDTGIS (in isoform 5)" FT /evidence="ECO:0000303|PubMed:15329498" FT /id="VSP_047800" FT VAR_SEQ 441..601 FT /note="Missing (in isoform 5)" FT /evidence="ECO:0000303|PubMed:15329498" FT /id="VSP_047801" FT VAR_SEQ 576..601 FT /note="ITSASSQTLRGHVLCRTTLRDSSAYC -> VRSPFGLLACTVK (in FT isoform 6)" FT /evidence="ECO:0000303|PubMed:15329498" FT /id="VSP_047802" FT MUTAGEN 258 FT /note="C->A: Loss of mitochondrial tRNAs FT methylthiotransferase activity; when associated with A-262 FT and A-265." FT /evidence="ECO:0000269|PubMed:25738458" FT MUTAGEN 262 FT /note="C->A: Loss of mitochondrial tRNAs FT methylthiotransferase activity; when associated with A-258 FT and A-265." FT /evidence="ECO:0000269|PubMed:25738458" FT MUTAGEN 265 FT /note="C->A: Loss of mitochondrial tRNAs FT methylthiotransferase activity; when associated with A-258 FT and A-262." FT /evidence="ECO:0000269|PubMed:25738458" FT CONFLICT 213 FT /note="R -> Q (in Ref. 7; AAH01215)" FT /evidence="ECO:0000305" FT CONFLICT 217 FT /note="V -> D (in Ref. 2)" FT /evidence="ECO:0000305" FT CONFLICT 269 FT /note="F -> L (in Ref. 4; BAB55120)" FT /evidence="ECO:0000305" FT CONFLICT 282 FT /note="I -> T (in Ref. 4; BAB55120)" FT /evidence="ECO:0000305" FT CONFLICT 323 FT /note="D -> G (in Ref. 4; BAB55120)" FT /evidence="ECO:0000305" FT CONFLICT 464 FT /note="V -> A (in Ref. 4; BAB14760)" FT /evidence="ECO:0000305" FT CONFLICT 511 FT /note="T -> S (in Ref. 2; AAF29131)" FT /evidence="ECO:0000305" FT CONFLICT 579 FT /note="Missing (in Ref. 1)" FT /evidence="ECO:0000305" FT CONFLICT 585 FT /note="R -> K (in Ref. 4; BAB14760)" FT /evidence="ECO:0000305" SQ SEQUENCE 601 AA; 67689 MW; 4AEBFD7DA5400902 CRC64; MHPLQCVLQV QRSLGWGPLA SVSWLSLRMC RAHSSLSSTM CPSPERQEDG ARKDFSSRLA AGPTFQHFLK SASAPQEKLS SEVEDPPPYL MMDELLGRQR KVYLETYGCQ MNVNDTEIAW SILQKSGYLR TSNLQEADVI LLVTCSIREK AEQTIWNRLH QLKALKTRRP RSRVPLRIGI LGCMAERLKE EILNREKMVD ILAGPDAYRD LPRLLAVAES GQQAANVLLS LDETYADVMP VQTSASATSA FVSIMRGCDN MCSYCIVPFT RGRERSRPIA SILEEVKKLS EQVFLPPRPP KVLGLQGLKE VTLLGQNVNS FRDNSEVQFN SAVPTNLSRG FTTNYKTKQG GLRFAHLLDQ VSRVDPEMRI RFTSPHPKDF PDEVLQLIHE RDNICKQIHL PAQSGSSRVL EAMRRGYSRE AYVELVHHIR ESIPGVSLSS DFIAGFCGET EEDHVQTVSL LREVQYNMGF LFAYSMRQKT RAYHRLKDDV PEEVKLRRLE ELITIFREEA TKANQTSVGC TQLVLVEGLS KRSATDLCGR NDGNLKVIFP DAEMEDVNNP GLRVRAQPGD YVLVKITSAS SQTLRGHVLC RTTLRDSSAY C //