CK5P1_RAT
ID CK5P1_RAT Reviewed; 586 AA.
AC Q9JLH6;
DT 16-JUN-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=Mitochondrial tRNA methylthiotransferase CDK5RAP1;
DE EC=2.8.4.3 {ECO:0000250|UniProtKB:Q96SZ6};
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;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND INTERACTION WITH CDK5R1.
RC TISSUE=Brain;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Prostate;
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).
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) (By similarity). Essential for efficient
CC and highly accurate protein translation by the ribosome (By
CC similarity). Specifically inhibits CDK5 activation by CDK5R1 (By
CC similarity). Essential for efficient mitochondrial protein synthesis
CC and respiratory chain (By similarity). {ECO:0000250|UniProtKB:Q96SZ6}.
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:0000250|UniProtKB:Q96SZ6};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:37068;
CC Evidence={ECO:0000250|UniProtKB:Q96SZ6};
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) (PubMed:10721722). CDK5RAP1,
CC CDK5RAP2 and CDK5RAP3 show competitive binding to CDK5R1 (By
CC similarity). Forms a complex with CDK5R1 and CDK5 (By similarity).
CC {ECO:0000250|UniProtKB:Q96SZ6, ECO:0000269|PubMed:10721722}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000250|UniProtKB:Q96SZ6}.
CC -!- TISSUE SPECIFICITY: Expressed in brain. {ECO:0000269|PubMed:10721722}.
CC -!- SIMILARITY: Belongs to the methylthiotransferase family. MiaB
CC subfamily. {ECO:0000305}.
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DR EMBL; AF177477; AAF60223.1; -; mRNA.
DR EMBL; BC066666; AAH66666.1; -; mRNA.
DR RefSeq; NP_663773.1; NM_145721.2.
DR RefSeq; XP_006235369.1; XM_006235307.2.
DR AlphaFoldDB; Q9JLH6; -.
DR SMR; Q9JLH6; -.
DR BioGRID; 251627; 1.
DR IntAct; Q9JLH6; 2.
DR STRING; 10116.ENSRNOP00000021418; -.
DR PaxDb; Q9JLH6; -.
DR GeneID; 252827; -.
DR KEGG; rno:252827; -.
DR CTD; 51654; -.
DR RGD; 708387; Cdk5rap1.
DR eggNOG; KOG2492; Eukaryota.
DR HOGENOM; CLU_018697_2_1_1; -.
DR InParanoid; Q9JLH6; -.
DR OMA; CEHFHIP; -.
DR OrthoDB; 835984at2759; -.
DR PhylomeDB; Q9JLH6; -.
DR TreeFam; TF101033; -.
DR PRO; PR:Q9JLH6; -.
DR Proteomes; UP000002494; Chromosome 3.
DR Bgee; ENSRNOG00000015696; Expressed in quadriceps femoris and 19 other tissues.
DR Genevisible; Q9JLH6; RN.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005743; C:mitochondrial inner membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:RGD.
DR GO; GO:0007420; P:brain development; TAS:RGD.
DR GO; GO:0070900; P:mitochondrial tRNA modification; ISO:RGD.
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; IDA:RGD.
DR GO; GO:0070131; P:positive regulation of mitochondrial translation; ISO:RGD.
DR GO; GO:0045903; P:positive regulation of translational fidelity; ISO:RGD.
DR GO; GO:0000079; P:regulation of cyclin-dependent protein serine/threonine kinase activity; IDA: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; Membrane; Metal-binding; Mitochondrion;
KW Mitochondrion inner membrane; Reference proteome; S-adenosyl-L-methionine;
KW Transferase; Transit peptide; tRNA processing.
FT TRANSIT 1..30
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 31..586
FT /note="Mitochondrial tRNA methylthiotransferase CDK5RAP1"
FT /evidence="ECO:0000255"
FT /id="PRO_0000141766"
FT DOMAIN 97..217
FT /note="MTTase N-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00780"
FT DOMAIN 241..495
FT /note="Radical SAM core"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01266"
FT DOMAIN 498..573
FT /note="TRAM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00208"
FT REGION 68..90
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 106
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00780"
FT BINDING 142
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00780"
FT BINDING 180
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00780"
FT BINDING 255
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 259
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"
SQ SEQUENCE 586 AA; 65866 MW; 95AC432AA3FF552C CRC64;
MHPLQRVFRA QRLSAPLTSM CWVLLRTFRA HNSTSCPDPE GKSSEGVQKD FSSRLATGPT
FQHFLRSASV PQEKPSSPEV EDPPPYLSGD ELLGRQRKVY LETYGCQMNV NDTEIAWSIL
QKSGYLRTSN LQEADVILLV TCSIREKAEQ TIWNRLHQLK VLKAKRPRSR VPLRIGILGC
MAERLKGEIL NREKMVDLLA GPDAYRDLPR LLAVVESGQQ AANVLLSLDE TYADIMPVQT
SPSATSAFVS IMRGCDNMCS YCIVPFTRGR ERSRPVASIL DEVRKLSEQG LKEVTLLGQN
VNSFRDNSEV QFSSTGSANL SRGFTTNYKP KQGGLRFSHL LDQVSRIDPE MRIRFTSPHP
KDFPDEVLQL IRERHNICKQ IHLPAQSGSS RVLEAMRRGY SREAYVALVH HIREAIPGVG
LSSDFITGFC GETEDDHLQT VSLLREVQYN TGFLFAYSMR QKTRAYHRLK DDVPEEVKLR
RLEELITVFR EEASKVNATS VGCTQLVLVE GFSKRSTTDL CGRNDANLKV IFPDAEVEDI
TDPGLKVRAQ PGDYVLVKII SASSQTLKGH ILCRTTMKDS SMNCLT
