CK5P1_HUMAN
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 03-AUG-2022, entry version 182.
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};
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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 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; 140.
DR IntAct; Q96SZ6; 20.
DR MINT; Q96SZ6; -.
DR STRING; 9606.ENSP00000217372; -.
DR iPTMnet; Q96SZ6; -.
DR PhosphoSitePlus; Q96SZ6; -.
DR BioMuta; CDK5RAP1; -.
DR DMDM; 32129446; -.
DR EPD; Q96SZ6; -.
DR jPOST; Q96SZ6; -.
DR MassIVE; Q96SZ6; -.
DR MaxQB; Q96SZ6; -.
DR PaxDb; Q96SZ6; -.
DR PeptideAtlas; Q96SZ6; -.
DR PRIDE; 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 Antibodypedia; 43007; 180 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 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; 835984at2759; -.
DR PhylomeDB; Q96SZ6; -.
DR TreeFam; TF101033; -.
DR PathwayCommons; Q96SZ6; -.
DR SignaLink; Q96SZ6; -.
DR BioGRID-ORCS; 51654; 11 hits in 1078 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 203 other tissues.
DR ExpressionAtlas; Q96SZ6; baseline and differential.
DR Genevisible; Q96SZ6; HS.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
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; -; 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; 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
