UniProtKB - Q5VV42 (CDKAL_HUMAN)
Protein
Threonylcarbamoyladenosine tRNA methylthiotransferase
Gene
CDKAL1
Organism
Homo sapiens (Human)
Status
Functioni
Catalyzes the methylthiolation of N6-threonylcarbamoyladenosine (t6A), leading to the formation of 2-methylthio-N6-threonylcarbamoyladenosine (ms2t6A) at position 37 in tRNAs that read codons beginning with adenine.By similarity
Catalytic activityi
- [sulfur carrier]-SH + AH2 + N6-L-threonylcarbamoyladenosine37 in tRNA + 2 S-adenosyl-L-methionine = 2-methylsulfanyl-N6-L-threonylcarbamoyladenosine37 in tRNA + 5'-deoxyadenosine + [sulfur carrier]-H + A + 2 H+ + L-methionine + S-adenosyl-L-homocysteineBy similarityEC:2.8.4.5By similarity
Cofactori
[4Fe-4S] clusterPROSITE-ProRule annotationNote: Binds 2 [4Fe-4S] clusters. One cluster is coordinated with 3 cysteines and an exchangeable S-adenosyl-L-methionine.PROSITE-ProRule annotation
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 73 | Iron-sulfur (4Fe-4S)PROSITE-ProRule annotation | 1 | |
Metal bindingi | 109 | Iron-sulfur (4Fe-4S)PROSITE-ProRule annotation | 1 | |
Metal bindingi | 138 | Iron-sulfur (4Fe-4S)PROSITE-ProRule annotation | 1 | |
Metal bindingi | 214 | Iron-sulfur (4Fe-4S-S-AdoMet)PROSITE-ProRule annotation | 1 | |
Metal bindingi | 218 | Iron-sulfur (4Fe-4S-S-AdoMet)PROSITE-ProRule annotation | 1 | |
Metal bindingi | 221 | Iron-sulfur (4Fe-4S-S-AdoMet)PROSITE-ProRule annotation | 1 |
GO - Molecular functioni
- 4 iron, 4 sulfur cluster binding Source: UniProtKB-KW
- metal ion binding Source: UniProtKB-KW
- N6-threonylcarbomyladenosine methylthiotransferase activity Source: GO_Central
- tRNA (N(6)-L-threonylcarbamoyladenosine(37)-C(2))-methylthiotransferase Source: UniProtKB-EC
GO - Biological processi
- maintenance of translational fidelity Source: Ensembl
- tRNA methylthiolation Source: GO_Central
- tRNA modification Source: Reactome
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 | Q5VV42 |
Reactomei | R-HSA-6782315, tRNA modification in the nucleus and cytosol |
Names & Taxonomyi
Protein namesi | Recommended name: Threonylcarbamoyladenosine tRNA methylthiotransferase (EC:2.8.4.5By similarity)Alternative name(s): CDK5 regulatory subunit-associated protein 1-like 1 tRNA-t(6)A37 methylthiotransferase |
Gene namesi | Name:CDKAL1 |
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:21050, CDKAL1 |
MIMi | 611259, gene |
neXtProti | NX_Q5VV42 |
VEuPathDBi | HostDB:ENSG00000145996.11 |
Subcellular locationi
Endoplasmic reticulum
- Endoplasmic reticulum membrane 1 Publication; Single-pass membrane protein Sequence analysis
Note: Is a tail-anchored protein that exploits the TCR40 pathway for insertion into the endoplasmic reticulum.1 Publication
Endoplasmic reticulum
- endoplasmic reticulum Source: GO_Central
- endoplasmic reticulum membrane Source: Reactome
- rough endoplasmic reticulum Source: Ensembl
Other locations
- integral component of membrane Source: UniProtKB-KW
- membrane Source: UniProtKB
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Transmembranei | 556 – 578 | HelicalSequence analysisAdd BLAST | 23 |
Keywords - Cellular componenti
Endoplasmic reticulum, MembranePathology & Biotechi
Involvement in diseasei
Diabetes mellitus, non-insulin-dependent (NIDDM)2 Publications
Disease susceptibility is associated with variants affecting the gene represented in this entry.
Disease descriptionA multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to the body's own insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.
Related information in OMIMKeywords - Diseasei
Diabetes mellitusOrganism-specific databases
DisGeNETi | 54901 |
MIMi | 125853, phenotype |
OpenTargetsi | ENSG00000145996 |
PharmGKBi | PA134871999 |
Miscellaneous databases
Pharosi | Q5VV42, Tbio |
Genetic variation databases
BioMutai | CDKAL1 |
DMDMi | 74747199 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000298670 | 1 – 579 | Threonylcarbamoyladenosine tRNA methylthiotransferaseAdd BLAST | 579 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 53 | PhosphoserineCombined sources | 1 | |
Modified residuei | 122 | PhosphoserineCombined sources | 1 | |
Modified residuei | 499 | PhosphothreonineCombined sources | 1 |
Keywords - PTMi
PhosphoproteinProteomic databases
EPDi | Q5VV42 |
jPOSTi | Q5VV42 |
MassIVEi | Q5VV42 |
MaxQBi | Q5VV42 |
PaxDbi | Q5VV42 |
PeptideAtlasi | Q5VV42 |
PRIDEi | Q5VV42 |
ProteomicsDBi | 65438 [Q5VV42-1] 65439 [Q5VV42-2] 65440 [Q5VV42-3] |
PTM databases
iPTMneti | Q5VV42 |
MetOSitei | Q5VV42 |
PhosphoSitePlusi | Q5VV42 |
SwissPalmi | Q5VV42 |
Expressioni
Tissue specificityi
Expressed in pancreatic islets.1 Publication
Gene expression databases
Bgeei | ENSG00000145996, Expressed in buccal mucosa cell and 178 other tissues |
Genevisiblei | Q5VV42, HS |
Organism-specific databases
HPAi | ENSG00000145996, Low tissue specificity |
Interactioni
Binary interactionsi
Hide detailsQ5VV42
With | #Exp. | IntAct |
---|---|---|
ATXN3 [P54252] | 3 | EBI-10194801,EBI-946046 |
LCK [P06239] | 3 | EBI-10194801,EBI-1348 |
WFS1 [O76024] | 3 | EBI-10194801,EBI-720609 |
Protein-protein interaction databases
BioGRIDi | 120247, 78 interactors |
IntActi | Q5VV42, 36 interactors |
MINTi | Q5VV42 |
STRINGi | 9606.ENSP00000274695 |
Miscellaneous databases
RNActi | Q5VV42, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 64 – 172 | MTTase N-terminalPROSITE-ProRule annotationAdd BLAST | 109 | |
Domaini | 200 – 431 | Radical SAM corePROSITE-ProRule annotationAdd BLAST | 232 | |
Domaini | 431 – 493 | TRAMPROSITE-ProRule annotationAdd BLAST | 63 |
Sequence similaritiesi
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG4355, Eukaryota |
GeneTreei | ENSGT00940000155952 |
HOGENOMi | CLU_018697_4_1_1 |
InParanoidi | Q5VV42 |
OMAi | HFHIPLQ |
OrthoDBi | 835984at2759 |
PhylomeDBi | Q5VV42 |
TreeFami | TF317476 |
Family and domain databases
Gene3Di | 3.40.50.12160, 1 hit 3.80.30.20, 1 hit |
InterProi | View protein in InterPro IPR006638, Elp3/MiaB/NifB IPR005839, Methylthiotransferase IPR020612, Methylthiotransferase_CS IPR013848, Methylthiotransferase_N IPR038135, Methylthiotransferase_N_sf IPR006466, MiaB-like_B 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 | SFLDG01061, methylthiotransferase, 1 hit SFLDS00029, Radical_SAM, 1 hit |
SMARTi | View protein in SMART SM00729, Elp3, 1 hit |
TIGRFAMsi | TIGR01578, MiaB-like-B, 1 hit 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 (3)i Sequence
Sequence statusi: Complete.
This entry describes 3 produced by isoformsialternative splicing. AlignAdd to basketIsoform 1 (identifier: Q5VV42-1) [UniParc]FASTAAdd to basket
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
MPSASCDTLL DDIEDIVSQE DSKPQDRHFV RKDVVPKVRR RNTQKYLQEE
60 70 80 90 100
ENSPPSDSTI PGIQKIWIRT WGCSHNNSDG EYMAGQLAAY GYKITENASD
110 120 130 140 150
ADLWLLNSCT VKNPAEDHFR NSIKKAQEEN KKIVLAGCVP QAQPRQDYLK
160 170 180 190 200
GLSIIGVQQI DRVVEVVEET IKGHSVRLLG QKKDNGRRLG GARLDLPKIR
210 220 230 240 250
KNPLIEIISI NTGCLNACTY CKTKHARGNL ASYPIDELVD RAKQSFQEGV
260 270 280 290 300
CEIWLTSEDT GAYGRDIGTN LPTLLWKLVE VIPEGAMLRL GMTNPPYILE
310 320 330 340 350
HLEEMAKILN HPRVYAFLHI PVQSASDSVL MEMKREYCVA DFKRVVDFLK
360 370 380 390 400
EKVPGITIAT DIICGFPGET DQDFQETVKL VEEYKFPSLF INQFYPRPGT
410 420 430 440 450
PAAKMEQVPA QVKKQRTKDL SRVFHSYSPY DHKIGERQQV LVTEESFDSK
460 470 480 490 500
FYVAHNQFYE QVLVPKNPAF MGKMVEVDIY ESGKHFMKGQ PVSDAKVYTP
510 520 530 540 550
SISKPLAKGE VSGLTKDFRN GLGNQLSSGS HTSAASQCDS ASSRMVLPMP
560 570
RLHQDCALRM SVGLALLGLL FAFFVKVYN
Sequence cautioni
The sequence BAC87494 differs from that shown. Reason: Frameshift.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 211 | N → S in BAA91102 (PubMed:14702039).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_052705 | 484 | K → R. Corresponds to variant dbSNP:rs9460608Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_027450 | 1 – 94 | MPSAS…YGYKI → MLSRRYEGEIPKNICKRKKT VHQV in isoform 2. 1 PublicationAdd BLAST | 94 | |
Alternative sequenceiVSP_027451 | 96 – 97 | EN → GE in isoform 3. 1 Publication | 2 | |
Alternative sequenceiVSP_027452 | 98 – 579 | Missing in isoform 3. 1 PublicationAdd BLAST | 482 | |
Alternative sequenceiVSP_027453 | 413 – 433 | Missing in isoform 2. 1 PublicationAdd BLAST | 21 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK000349 mRNA Translation: BAA91102.1 AK128546 mRNA Translation: BAC87494.1 Frameshift. AK291735 mRNA Translation: BAF84424.1 AL022717 Genomic DNA No translation available. AL033521 Genomic DNA No translation available. AL035090 Genomic DNA No translation available. AL451080 Genomic DNA No translation available. AL512405 Genomic DNA No translation available. AL513015 Genomic DNA No translation available. AL513188 Genomic DNA No translation available. AL513549 Genomic DNA No translation available. CH471087 Genomic DNA Translation: EAW55426.1 BC064145 mRNA Translation: AAH64145.1 BC121020 mRNA Translation: AAI21021.1 BC121021 mRNA Translation: AAI21022.1 |
CCDSi | CCDS4546.1 [Q5VV42-1] |
RefSeqi | NP_060244.2, NM_017774.3 [Q5VV42-1] |
Genome annotation databases
Ensembli | ENST00000274695; ENSP00000274695; ENSG00000145996 [Q5VV42-1] ENST00000378610; ENSP00000367873; ENSG00000145996 [Q5VV42-1] ENST00000613575; ENSP00000481755; ENSG00000145996 [Q5VV42-3] |
GeneIDi | 54901 |
KEGGi | hsa:54901 |
UCSCi | uc003ndb.2, human [Q5VV42-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK000349 mRNA Translation: BAA91102.1 AK128546 mRNA Translation: BAC87494.1 Frameshift. AK291735 mRNA Translation: BAF84424.1 AL022717 Genomic DNA No translation available. AL033521 Genomic DNA No translation available. AL035090 Genomic DNA No translation available. AL451080 Genomic DNA No translation available. AL512405 Genomic DNA No translation available. AL513015 Genomic DNA No translation available. AL513188 Genomic DNA No translation available. AL513549 Genomic DNA No translation available. CH471087 Genomic DNA Translation: EAW55426.1 BC064145 mRNA Translation: AAH64145.1 BC121020 mRNA Translation: AAI21021.1 BC121021 mRNA Translation: AAI21022.1 |
CCDSi | CCDS4546.1 [Q5VV42-1] |
RefSeqi | NP_060244.2, NM_017774.3 [Q5VV42-1] |
3D structure databases
SMRi | Q5VV42 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 120247, 78 interactors |
IntActi | Q5VV42, 36 interactors |
MINTi | Q5VV42 |
STRINGi | 9606.ENSP00000274695 |
PTM databases
iPTMneti | Q5VV42 |
MetOSitei | Q5VV42 |
PhosphoSitePlusi | Q5VV42 |
SwissPalmi | Q5VV42 |
Genetic variation databases
BioMutai | CDKAL1 |
DMDMi | 74747199 |
Proteomic databases
EPDi | Q5VV42 |
jPOSTi | Q5VV42 |
MassIVEi | Q5VV42 |
MaxQBi | Q5VV42 |
PaxDbi | Q5VV42 |
PeptideAtlasi | Q5VV42 |
PRIDEi | Q5VV42 |
ProteomicsDBi | 65438 [Q5VV42-1] 65439 [Q5VV42-2] 65440 [Q5VV42-3] |
Protocols and materials databases
Antibodypediai | 2738, 239 antibodies |
Genome annotation databases
Ensembli | ENST00000274695; ENSP00000274695; ENSG00000145996 [Q5VV42-1] ENST00000378610; ENSP00000367873; ENSG00000145996 [Q5VV42-1] ENST00000613575; ENSP00000481755; ENSG00000145996 [Q5VV42-3] |
GeneIDi | 54901 |
KEGGi | hsa:54901 |
UCSCi | uc003ndb.2, human [Q5VV42-1] |
Organism-specific databases
CTDi | 54901 |
DisGeNETi | 54901 |
GeneCardsi | CDKAL1 |
HGNCi | HGNC:21050, CDKAL1 |
HPAi | ENSG00000145996, Low tissue specificity |
MIMi | 125853, phenotype 611259, gene |
neXtProti | NX_Q5VV42 |
OpenTargetsi | ENSG00000145996 |
PharmGKBi | PA134871999 |
VEuPathDBi | HostDB:ENSG00000145996.11 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG4355, Eukaryota |
GeneTreei | ENSGT00940000155952 |
HOGENOMi | CLU_018697_4_1_1 |
InParanoidi | Q5VV42 |
OMAi | HFHIPLQ |
OrthoDBi | 835984at2759 |
PhylomeDBi | Q5VV42 |
TreeFami | TF317476 |
Enzyme and pathway databases
PathwayCommonsi | Q5VV42 |
Reactomei | R-HSA-6782315, tRNA modification in the nucleus and cytosol |
Miscellaneous databases
BioGRID-ORCSi | 54901, 10 hits in 997 CRISPR screens |
ChiTaRSi | CDKAL1, human |
GeneWikii | CDKAL1 |
GenomeRNAii | 54901 |
Pharosi | Q5VV42, Tbio |
PROi | PR:Q5VV42 |
RNActi | Q5VV42, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000145996, Expressed in buccal mucosa cell and 178 other tissues |
Genevisiblei | Q5VV42, HS |
Family and domain databases
Gene3Di | 3.40.50.12160, 1 hit 3.80.30.20, 1 hit |
InterProi | View protein in InterPro IPR006638, Elp3/MiaB/NifB IPR005839, Methylthiotransferase IPR020612, Methylthiotransferase_CS IPR013848, Methylthiotransferase_N IPR038135, Methylthiotransferase_N_sf IPR006466, MiaB-like_B 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 | SFLDG01061, methylthiotransferase, 1 hit SFLDS00029, Radical_SAM, 1 hit |
SMARTi | View protein in SMART SM00729, Elp3, 1 hit |
TIGRFAMsi | TIGR01578, MiaB-like-B, 1 hit 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 |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | CDKAL_HUMAN | |
Accessioni | Q5VV42Primary (citable) accession number: Q5VV42 Secondary accession number(s): A8K6S0 Q9NXB3 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | September 11, 2007 |
Last sequence update: | December 7, 2004 | |
Last modified: | April 7, 2021 | |
This is version 153 of the entry and version 1 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 6
Human chromosome 6: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families