UniProtKB - Q96SZ6 (CK5P1_HUMAN)
Mitochondrial tRNA methylthiotransferase CDK5RAP1
CDK5RAP1
Functioni
Methylthiotransferase that catalyzes the conversion of N6-(dimethylallyl)adenosine (i6A) to 2-methylthio-N6-(dimethylallyl)adenosine (ms2i6A) at position 37 (adjacent to the 3'-end of the anticodon) of four mitochondrial DNA-encoded tRNAs (Ser(UCN), Phe, Tyr and Trp) (PubMed:22422838, PubMed:25738458, PubMed:28981754).
Essential for efficient and highly accurate protein translation by the ribosome (PubMed:22422838, PubMed:25738458, PubMed:28981754).
Specifically inhibits CDK5 activation by CDK5R1 (PubMed:11882646).
Essential for efficient mitochondrial protein synthesis and respiratory chain; shows pathological consequences in mitochondrial disease (PubMed:25738458).
4 PublicationsCaution
Catalytic activityi
- [sulfur carrier]-SH + AH2 + N6-dimethylallyladenosine37 in tRNA + 2 S-adenosyl-L-methionine = 2-methylsulfanyl-N6-dimethylallyladenosine37 in tRNA + 5'-deoxyadenosine + [sulfur carrier]-H + A + 2 H+ + L-methionine + S-adenosyl-L-homocysteine2 PublicationsEC:2.8.4.32 Publications
Cofactori
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 109 | Iron-sulfur (4Fe-4S) 1PROSITE-ProRule annotation | 1 | |
Metal bindingi | 145 | Iron-sulfur (4Fe-4S) 1PROSITE-ProRule annotation | 1 | |
Metal bindingi | 183 | Iron-sulfur (4Fe-4S) 1PROSITE-ProRule annotation | 1 | |
Metal bindingi | 258 | Iron-sulfur (4Fe-4S) 2; 4Fe-4S-S-AdoMetBy similarity | 1 | |
Metal bindingi | 262 | Iron-sulfur (4Fe-4S) 2; 4Fe-4S-S-AdoMetBy similarity | 1 | |
Metal bindingi | 265 | Iron-sulfur (4Fe-4S) 2; 4Fe-4S-S-AdoMetBy similarity | 1 |
GO - Molecular functioni
- 4 iron, 4 sulfur cluster binding Source: UniProtKB-KW
- metal ion binding Source: UniProtKB-KW
- N6-isopentenyladenosine methylthiotransferase activity Source: GO_Central
- protein kinase binding Source: UniProtKB
GO - Biological processi
- brain development Source: UniProtKB
- mitochondrial tRNA modification Source: Ensembl
- negative regulation of cyclin-dependent protein serine/threonine kinase activity Source: UniProtKB
- positive regulation of mitochondrial translation Source: Ensembl
- positive regulation of translational fidelity Source: Ensembl
- regulation of neuron differentiation Source: UniProtKB
Keywordsi
Molecular function | Transferase |
Biological process | tRNA processing |
Ligand | 4Fe-4S, Iron, Iron-sulfur, Metal-binding, S-adenosyl-L-methionine |
Enzyme and pathway databases
PathwayCommonsi | Q96SZ6 |
SignaLinki | Q96SZ6 |
Names & Taxonomyi
Protein namesi | Recommended name: Mitochondrial tRNA methylthiotransferase CDK5RAP12 Publications (EC:2.8.4.32 Publications)Alternative name(s): CDK5 activator-binding protein C42 CDK5 regulatory subunit-associated protein 1 mt-tRNA-2-methylthio-N6-dimethylallyladenosine synthase mt-tRNA-N6-(dimethylallyl)adenosine(37) methylthiotransferase |
Gene namesi | ORF Names:CGI-05, HSPC167 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:15880, CDK5RAP1 |
MIMi | 608200, gene |
neXtProti | NX_Q96SZ6 |
VEuPathDBi | HostDB:ENSG00000101391 |
Subcellular locationi
Mitochondrion
- Mitochondrion 1 Publication
Cytosol
- cytosol Source: GO_Central
Mitochondrion
- mitochondrion Source: GO_Central
Keywords - Cellular componenti
MitochondrionPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 258 | C → A: Loss of mitochondrial tRNAs methylthiotransferase activity; when associated with A-262 and A-265. 1 Publication | 1 | |
Mutagenesisi | 262 | C → A: Loss of mitochondrial tRNAs methylthiotransferase activity; when associated with A-258 and A-265. 1 Publication | 1 | |
Mutagenesisi | 265 | C → A: Loss of mitochondrial tRNAs methylthiotransferase activity; when associated with A-258 and A-262. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 51654 |
OpenTargetsi | ENSG00000101391 |
PharmGKBi | PA26313 |
Miscellaneous databases
Pharosi | Q96SZ6, Tbio |
Genetic variation databases
BioMutai | CDK5RAP1 |
DMDMi | 32129446 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Transit peptidei | 1 – 33 | MitochondrionSequence analysisAdd BLAST | 33 | |
ChainiPRO_0000141764 | 34 – 601 | Mitochondrial tRNA methylthiotransferase CDK5RAP1Sequence analysisAdd BLAST | 568 |
Proteomic databases
EPDi | Q96SZ6 |
jPOSTi | Q96SZ6 |
MassIVEi | Q96SZ6 |
MaxQBi | Q96SZ6 |
PaxDbi | Q96SZ6 |
PeptideAtlasi | Q96SZ6 |
PRIDEi | Q96SZ6 |
ProteomicsDBi | 65981 78165 [Q96SZ6-1] 78166 [Q96SZ6-2] 78167 [Q96SZ6-3] 78168 [Q96SZ6-4] |
PTM databases
iPTMneti | Q96SZ6 |
PhosphoSitePlusi | Q96SZ6 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000101391, Expressed in small intestine Peyer's patch and 239 other tissues |
ExpressionAtlasi | Q96SZ6, baseline and differential |
Genevisiblei | Q96SZ6, HS |
Organism-specific databases
HPAi | ENSG00000101391, Low tissue specificity |
Interactioni
Subunit structurei
Interacts with CDK5R1 (p35 form). CDK5RAP1, CDK5RAP2 and CDK5RAP3 show competitive binding to CDK5R1.
Forms a complex with CDK5R1 and CDK5.
1 PublicationGO - Molecular functioni
- protein kinase binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 119661, 139 interactors |
IntActi | Q96SZ6, 20 interactors |
MINTi | Q96SZ6 |
STRINGi | 9606.ENSP00000217372 |
Miscellaneous databases
RNActi | Q96SZ6, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 100 – 220 | MTTase N-terminalPROSITE-ProRule annotationAdd BLAST | 121 | |
Domaini | 244 – 512 | Radical SAM corePROSITE-ProRule annotationAdd BLAST | 269 | |
Domaini | 515 – 590 | TRAMPROSITE-ProRule annotationAdd BLAST | 76 |
Sequence similaritiesi
Keywords - Domaini
Transit peptidePhylogenomic databases
eggNOGi | KOG2492, Eukaryota |
GeneTreei | ENSGT00940000160361 |
HOGENOMi | CLU_018697_2_1_1 |
InParanoidi | Q96SZ6 |
OMAi | CEHFHIP |
OrthoDBi | 835984at2759 |
PhylomeDBi | Q96SZ6 |
TreeFami | TF101033 |
Family and domain databases
Gene3Di | 3.40.50.12160, 1 hit 3.80.30.20, 1 hit |
HAMAPi | MF_01864, tRNA_metthiotr_MiaB, 1 hit |
InterProi | View protein in InterPro IPR006638, Elp3/MiaB/NifB IPR005839, Methylthiotransferase IPR020612, Methylthiotransferase_CS IPR013848, Methylthiotransferase_N IPR038135, Methylthiotransferase_N_sf IPR006463, MiaB_methiolase IPR007197, rSAM IPR023404, rSAM_horseshoe IPR002792, TRAM_dom |
Pfami | View protein in Pfam PF04055, Radical_SAM, 1 hit PF01938, TRAM, 1 hit PF00919, UPF0004, 1 hit |
SFLDi | SFLDF00273, (dimethylallyl)adenosine_tRNA, 1 hit SFLDS00029, Radical_SAM, 1 hit |
SMARTi | View protein in SMART SM00729, Elp3, 1 hit |
TIGRFAMsi | TIGR00089, TIGR00089, 1 hit |
PROSITEi | View protein in PROSITE PS51449, MTTASE_N, 1 hit PS01278, MTTASE_RADICAL, 1 hit PS51918, RADICAL_SAM, 1 hit PS50926, TRAM, 1 hit |
s (6+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 6 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 6 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MHPLQCVLQV QRSLGWGPLA SVSWLSLRMC RAHSSLSSTM CPSPERQEDG
60 70 80 90 100
ARKDFSSRLA AGPTFQHFLK SASAPQEKLS SEVEDPPPYL MMDELLGRQR
110 120 130 140 150
KVYLETYGCQ MNVNDTEIAW SILQKSGYLR TSNLQEADVI LLVTCSIREK
160 170 180 190 200
AEQTIWNRLH QLKALKTRRP RSRVPLRIGI LGCMAERLKE EILNREKMVD
210 220 230 240 250
ILAGPDAYRD LPRLLAVAES GQQAANVLLS LDETYADVMP VQTSASATSA
260 270 280 290 300
FVSIMRGCDN MCSYCIVPFT RGRERSRPIA SILEEVKKLS EQVFLPPRPP
310 320 330 340 350
KVLGLQGLKE VTLLGQNVNS FRDNSEVQFN SAVPTNLSRG FTTNYKTKQG
360 370 380 390 400
GLRFAHLLDQ VSRVDPEMRI RFTSPHPKDF PDEVLQLIHE RDNICKQIHL
410 420 430 440 450
PAQSGSSRVL EAMRRGYSRE AYVELVHHIR ESIPGVSLSS DFIAGFCGET
460 470 480 490 500
EEDHVQTVSL LREVQYNMGF LFAYSMRQKT RAYHRLKDDV PEEVKLRRLE
510 520 530 540 550
ELITIFREEA TKANQTSVGC TQLVLVEGLS KRSATDLCGR NDGNLKVIFP
560 570 580 590 600
DAEMEDVNNP GLRVRAQPGD YVLVKITSAS SQTLRGHVLC RTTLRDSSAY
C
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketH0Y721 | H0Y721_HUMAN | Mitochondrial tRNA methylthiotransf... | CDK5RAP1 | 256 | Annotation score: |
Sequence cautioni
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 213 | R → Q in AAH01215 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 217 | V → D (PubMed:11042152).Curated | 1 | |
Sequence conflicti | 269 | F → L in BAB55120 (PubMed:14702039).Curated | 1 | |
Sequence conflicti | 282 | I → T in BAB55120 (PubMed:14702039).Curated | 1 | |
Sequence conflicti | 323 | D → G in BAB55120 (PubMed:14702039).Curated | 1 | |
Sequence conflicti | 464 | V → A in BAB14760 (PubMed:14702039).Curated | 1 | |
Sequence conflicti | 511 | T → S in AAF29131 (PubMed:11042152).Curated | 1 | |
Sequence conflicti | 579 | Missing (PubMed:10810093).Curated | 1 | |
Sequence conflicti | 585 | R → K in BAB14760 (PubMed:14702039).Curated | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_007560 | 1 – 90 | Missing in isoform 2. 1 PublicationAdd BLAST | 90 | |
Alternative sequenceiVSP_047799 | 292 – 305 | Missing in isoform 5 and isoform 6. 1 PublicationAdd BLAST | 14 | |
Alternative sequenceiVSP_007561 | 293 – 383 | Missing in isoform 4. 1 PublicationAdd BLAST | 91 | |
Alternative sequenceiVSP_007562 | 293 – 306 | Missing in isoform 2 and isoform 3. 2 PublicationsAdd BLAST | 14 | |
Alternative sequenceiVSP_047800 | 435 – 440 | GVSLSS → EDTGIS in isoform 5. 1 Publication | 6 | |
Alternative sequenceiVSP_047801 | 441 – 601 | Missing in isoform 5. 1 PublicationAdd BLAST | 161 | |
Alternative sequenceiVSP_047802 | 576 – 601 | ITSAS…SSAYC → VRSPFGLLACTVK in isoform 6. 1 PublicationAdd BLAST | 26 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF152097 mRNA Translation: AAD34147.1 Frameshift. AF161516 mRNA Translation: AAF29131.1 Frameshift. AY462283 mRNA Translation: AAS18317.1 AY462284 mRNA Translation: AAS18318.1 AK023992 mRNA Translation: BAB14760.1 AK027449 mRNA Translation: BAB55120.1 Sequence problems. AK292075 mRNA Translation: BAF84764.1 AL355392 Genomic DNA No translation available. CH471077 Genomic DNA Translation: EAW76319.1 CH471077 Genomic DNA Translation: EAW76322.1 CH471077 Genomic DNA Translation: EAW76323.1 BC001215 mRNA Translation: AAH01215.1 BC050706 mRNA Translation: AAH50706.1 |
CCDSi | CCDS13219.1 [Q96SZ6-3] CCDS63255.1 [Q96SZ6-4] |
RefSeqi | NP_001265097.1, NM_001278168.1 [Q96SZ6-4] NP_001265098.1, NM_001278169.1 NP_057166.4, NM_016082.4 NP_057492.2, NM_016408.3 [Q96SZ6-3] |
Genome annotation databases
Ensembli | ENST00000339269.5; ENSP00000341840.5; ENSG00000101391.21 [Q96SZ6-4] ENST00000346416.7; ENSP00000217372.2; ENSG00000101391.21 [Q96SZ6-3] ENST00000357886.8; ENSP00000350558.4; ENSG00000101391.21 ENST00000473997.5; ENSP00000476857.1; ENSG00000101391.21 [Q96SZ6-2] |
GeneIDi | 51654 |
KEGGi | hsa:51654 |
MANE-Selecti | ENST00000346416.7; ENSP00000217372.2; NM_016408.4; NP_057492.2 [Q96SZ6-3] |
UCSCi | uc002wyz.5, human [Q96SZ6-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF152097 mRNA Translation: AAD34147.1 Frameshift. AF161516 mRNA Translation: AAF29131.1 Frameshift. AY462283 mRNA Translation: AAS18317.1 AY462284 mRNA Translation: AAS18318.1 AK023992 mRNA Translation: BAB14760.1 AK027449 mRNA Translation: BAB55120.1 Sequence problems. AK292075 mRNA Translation: BAF84764.1 AL355392 Genomic DNA No translation available. CH471077 Genomic DNA Translation: EAW76319.1 CH471077 Genomic DNA Translation: EAW76322.1 CH471077 Genomic DNA Translation: EAW76323.1 BC001215 mRNA Translation: AAH01215.1 BC050706 mRNA Translation: AAH50706.1 |
CCDSi | CCDS13219.1 [Q96SZ6-3] CCDS63255.1 [Q96SZ6-4] |
RefSeqi | NP_001265097.1, NM_001278168.1 [Q96SZ6-4] NP_001265098.1, NM_001278169.1 NP_057166.4, NM_016082.4 NP_057492.2, NM_016408.3 [Q96SZ6-3] |
3D structure databases
AlphaFoldDBi | Q96SZ6 |
SMRi | Q96SZ6 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 119661, 139 interactors |
IntActi | Q96SZ6, 20 interactors |
MINTi | Q96SZ6 |
STRINGi | 9606.ENSP00000217372 |
PTM databases
iPTMneti | Q96SZ6 |
PhosphoSitePlusi | Q96SZ6 |
Genetic variation databases
BioMutai | CDK5RAP1 |
DMDMi | 32129446 |
Proteomic databases
EPDi | Q96SZ6 |
jPOSTi | Q96SZ6 |
MassIVEi | Q96SZ6 |
MaxQBi | Q96SZ6 |
PaxDbi | Q96SZ6 |
PeptideAtlasi | Q96SZ6 |
PRIDEi | Q96SZ6 |
ProteomicsDBi | 65981 78165 [Q96SZ6-1] 78166 [Q96SZ6-2] 78167 [Q96SZ6-3] 78168 [Q96SZ6-4] |
Protocols and materials databases
Antibodypediai | 43007, 178 antibodies from 27 providers |
DNASUi | 51654 |
Genome annotation databases
Ensembli | ENST00000339269.5; ENSP00000341840.5; ENSG00000101391.21 [Q96SZ6-4] ENST00000346416.7; ENSP00000217372.2; ENSG00000101391.21 [Q96SZ6-3] ENST00000357886.8; ENSP00000350558.4; ENSG00000101391.21 ENST00000473997.5; ENSP00000476857.1; ENSG00000101391.21 [Q96SZ6-2] |
GeneIDi | 51654 |
KEGGi | hsa:51654 |
MANE-Selecti | ENST00000346416.7; ENSP00000217372.2; NM_016408.4; NP_057492.2 [Q96SZ6-3] |
UCSCi | uc002wyz.5, human [Q96SZ6-1] |
Organism-specific databases
CTDi | 51654 |
DisGeNETi | 51654 |
GeneCardsi | CDK5RAP1 |
HGNCi | HGNC:15880, CDK5RAP1 |
HPAi | ENSG00000101391, Low tissue specificity |
MIMi | 608200, gene |
neXtProti | NX_Q96SZ6 |
OpenTargetsi | ENSG00000101391 |
PharmGKBi | PA26313 |
VEuPathDBi | HostDB:ENSG00000101391 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG2492, Eukaryota |
GeneTreei | ENSGT00940000160361 |
HOGENOMi | CLU_018697_2_1_1 |
InParanoidi | Q96SZ6 |
OMAi | CEHFHIP |
OrthoDBi | 835984at2759 |
PhylomeDBi | Q96SZ6 |
TreeFami | TF101033 |
Enzyme and pathway databases
PathwayCommonsi | Q96SZ6 |
SignaLinki | Q96SZ6 |
Miscellaneous databases
BioGRID-ORCSi | 51654, 11 hits in 1078 CRISPR screens |
ChiTaRSi | CDK5RAP1, human |
GeneWikii | CDK5RAP1 |
GenomeRNAii | 51654 |
Pharosi | Q96SZ6, Tbio |
PROi | PR:Q96SZ6 |
RNActi | Q96SZ6, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000101391, Expressed in small intestine Peyer's patch and 239 other tissues |
ExpressionAtlasi | Q96SZ6, baseline and differential |
Genevisiblei | Q96SZ6, HS |
Family and domain databases
Gene3Di | 3.40.50.12160, 1 hit 3.80.30.20, 1 hit |
HAMAPi | MF_01864, tRNA_metthiotr_MiaB, 1 hit |
InterProi | View protein in InterPro IPR006638, Elp3/MiaB/NifB IPR005839, Methylthiotransferase IPR020612, Methylthiotransferase_CS IPR013848, Methylthiotransferase_N IPR038135, Methylthiotransferase_N_sf IPR006463, MiaB_methiolase IPR007197, rSAM IPR023404, rSAM_horseshoe IPR002792, TRAM_dom |
Pfami | View protein in Pfam PF04055, Radical_SAM, 1 hit PF01938, TRAM, 1 hit PF00919, UPF0004, 1 hit |
SFLDi | SFLDF00273, (dimethylallyl)adenosine_tRNA, 1 hit SFLDS00029, Radical_SAM, 1 hit |
SMARTi | View protein in SMART SM00729, Elp3, 1 hit |
TIGRFAMsi | TIGR00089, TIGR00089, 1 hit |
PROSITEi | View protein in PROSITE PS51449, MTTASE_N, 1 hit PS01278, MTTASE_RADICAL, 1 hit PS51918, RADICAL_SAM, 1 hit PS50926, TRAM, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | CK5P1_HUMAN | |
Accessioni | Q96SZ6Primary (citable) accession number: Q96SZ6 Secondary accession number(s): A8K7R0 Q9Y3F0 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | June 16, 2003 |
Last sequence update: | June 16, 2003 | |
Last modified: | May 25, 2022 | |
This is version 181 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human chromosome 20
Human chromosome 20: entries, gene names and cross-references to MIM - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families