Human Gene CDKAL1 (uc003ndd.2) Description and Page Index
  Description: Homo sapiens CDK5 regulatory subunit associated protein 1-like 1 (CDKAL1), mRNA.
RefSeq Summary (NM_017774): The protein encoded by this gene is a member of the methylthiotransferase family. The function of this gene is not known. Genome-wide association studies have linked single nucleotide polymorphisms in an intron of this gene with susceptibilty to type 2 diabetes. [provided by RefSeq, May 2010]. Sequence Note: This RefSeq record was created from transcript and genomic sequence data to make the sequence consistent with the reference genome assembly. The genomic coordinates used for the transcript record were based on transcript alignments. Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications. ##Evidence-Data-START## Transcript exon combination :: SRR1803611.146631.1, SRR1803616.131533.1 [ECO:0000332] RNAseq introns :: single sample supports all introns SAMEA1965299, SAMEA1966682 [ECO:0000348] ##Evidence-Data-END## ##RefSeq-Attributes-START## MANE Ensembl match :: ENST00000274695.8/ ENSP00000274695.4 RefSeq Select criteria :: based on conservation, expression ##RefSeq-Attributes-END##
Transcript (Including UTRs)
   Position: hg19 chr6:20,534,688-21,232,634 Size: 697,947 Total Exon Count: 16 Strand: +
Coding Region
   Position: hg19 chr6:20,546,582-21,231,270 Size: 684,689 Coding Exon Count: 14 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr6:20,534,688-21,232,634)mRNA (may differ from genome)Protein (579 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
GeneNetworkH-INVHGNCHPRDLynxMGI
neXtProtOMIMPubMedReactomeStanford SOURCETreefam
UniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: CDKAL_HUMAN
DESCRIPTION: RecName: Full=Threonylcarbamoyladenosine tRNA methylthiotransferase; EC=2.-.-.-; AltName: Full=CDK5 regulatory subunit-associated protein 1-like 1; AltName: Full=tRNA-t(6)A37 methylthiotransferase;
FUNCTION: Catalyzes the methylthiolation of N6- threonylcarbamoyladenosine (t(6)A), leading to the formation of 2- methylthio-N6-threonylcarbamoyladenosine (ms(2)t(6)A) at position 37 in tRNAs that read codons beginning with adenine.
COFACTOR: Binds 2 4Fe-4S clusters. One cluster is coordinated with 3 cysteines and an exchangeable S-adenosyl-L-methionine (By similarity).
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass membrane protein. Note=Is a tail-anchored protein that exploits the TCR40 pathway for insertion into the endoplasmic reticulum.
TISSUE SPECIFICITY: Expressed in pancreatic islets.
DISEASE: Genetic variations in CDKAL1 are a cause of susceptibility to diabetes mellitus, non-insulin-dependent (NIDDM) [MIM:125853]. A 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.
SIMILARITY: Belongs to the methylthiotransferase family. CDKAL1 subfamily.
SIMILARITY: Contains 1 MTTase N-terminal domain.
SIMILARITY: Contains 1 TRAM domain.
SEQUENCE CAUTION: Sequence=BAC87494.1; Type=Frameshift; Positions=575;

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): CDKAL1
CDC HuGE Published Literature: CDKAL1
Positive Disease Associations: Albuminuria , Body Mass Index , Crohn Disease , Crohn's disease , Diabetes Mellitus, Type 2 , Diabetes, Gestational , diabetes, type 2 , Heart Failure , Hemoglobin A, Glycosylated , Myocardial Infarction , Posttransplantation diabetes mellitus (PTDM) , Stroke , type 2 diabetes , type 2 diabetes and other traits , ulcerative colitis
Related Studies:
  1. Albuminuria
    Shih-Jen Hwang et al. BMC medical genetics 2007, A genome-wide association for kidney function and endocrine-related traits in the NHLBI's Framingham Heart Study., BMC medical genetics. [PubMed 17903292]
    Kidney function traits and TSH are associated with SNPs on the Affymetrix GeneChip Human Mapping 100K SNP set. These data will serve as a valuable resource for replication as more SNPs associated with kidney function and endocrine traits are identified.
  2. Body Mass Index
    Wanqing Wen et al. Nature genetics 2012, Meta-analysis identifies common variants associated with body mass index in east Asians., Nature genetics. [PubMed 22344219]
  3. Body Mass Index
    Yukinori Okada et al. Nature genetics 2012, Common variants at CDKAL1 and KLF9 are associated with body mass index in east Asian populations., Nature genetics. [PubMed 22344221]
           more ... click here to view the complete list

-  MalaCards Disease Associations
  MalaCards Gene Search: CDKAL1
Diseases sorted by gene-association score: diabetes mellitus, noninsulin-dependent* (103), sapho syndrome (15)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 6.51 RPKM in Cells - EBV-transformed lymphocytes
Total median expression: 149.51 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -39.90167-0.239 Picture PostScript Text
3' UTR -384.491364-0.282 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR006638 - Elp3/MiaB/NifB
IPR005839 - Methylthiotransferase
IPR020612 - Methylthiotransferase_CS
IPR013848 - Methylthiotransferase_N
IPR006466 - MiaB-like_B
IPR007197 - rSAM
IPR023404 - rSAM_horseshoe
IPR002792 - TRAM_dom

Pfam Domains:
PF00919 - Uncharacterized protein family UPF0004
PF01938 - TRAM domain
PF04055 - Radical SAM superfamily

SCOP Domains:
102114 - Radical SAM enzymes

ModBase Predicted Comparative 3D Structure on Q5VV42
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
      
      
      

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0003674 molecular_function
GO:0003824 catalytic activity
GO:0005515 protein binding
GO:0016740 transferase activity
GO:0035598 N6-threonylcarbomyladenosine methylthiotransferase activity
GO:0046872 metal ion binding
GO:0051536 iron-sulfur cluster binding
GO:0051539 4 iron, 4 sulfur cluster binding
GO:0061712 tRNA (N(6)-L-threonylcarbamoyladenosine(37)-C(2))-methylthiotransferase

Biological Process:
GO:0006400 tRNA modification
GO:0008033 tRNA processing
GO:0008150 biological_process
GO:0035600 tRNA methylthiolation
GO:1990145 maintenance of translational fidelity

Cellular Component:
GO:0005783 endoplasmic reticulum
GO:0005789 endoplasmic reticulum membrane
GO:0005791 rough endoplasmic reticulum
GO:0016020 membrane
GO:0016021 integral component of membrane


-  Descriptions from all associated GenBank mRNAs
  AK128546 - Homo sapiens cDNA FLJ46705 fis, clone TRACH3015346.
AK291735 - Homo sapiens cDNA FLJ77738 complete cds, highly similar to Homo sapiens CDK5 regulatory subunit associated protein 1-like 1 (CDKAL1), mRNA.
AK000349 - Homo sapiens cDNA FLJ20342 fis, clone HEP13572.
BC121020 - Homo sapiens CDK5 regulatory subunit associated protein 1-like 1, mRNA (cDNA clone MGC:149679 IMAGE:40117357), complete cds.
BC121021 - Homo sapiens CDK5 regulatory subunit associated protein 1-like 1, mRNA (cDNA clone MGC:149680 IMAGE:40117363), complete cds.
KJ894083 - Synthetic construct Homo sapiens clone ccsbBroadEn_03477 CDKAL1 gene, encodes complete protein.
AK310219 - Homo sapiens cDNA, FLJ17261.
AK024151 - Homo sapiens cDNA FLJ14089 fis, clone MAMMA1000257.
AK309457 - Homo sapiens cDNA, FLJ99498.
BC064145 - Homo sapiens CDK5 regulatory subunit associated protein 1-like 1, mRNA (cDNA clone IMAGE:30379056), complete cds.
JD196004 - Sequence 177028 from Patent EP1572962.
KJ904780 - Synthetic construct Homo sapiens clone ccsbBroadEn_14174 CDKAL1-like gene, encodes complete protein.
JD516959 - Sequence 497983 from Patent EP1572962.
JD154251 - Sequence 135275 from Patent EP1572962.
JD262378 - Sequence 243402 from Patent EP1572962.
JD295936 - Sequence 276960 from Patent EP1572962.
JD547171 - Sequence 528195 from Patent EP1572962.
JD226439 - Sequence 207463 from Patent EP1572962.
JD119406 - Sequence 100430 from Patent EP1572962.
JD274860 - Sequence 255884 from Patent EP1572962.
JD255951 - Sequence 236975 from Patent EP1572962.
JD426708 - Sequence 407732 from Patent EP1572962.
JD409250 - Sequence 390274 from Patent EP1572962.
JD396146 - Sequence 377170 from Patent EP1572962.
JD546547 - Sequence 527571 from Patent EP1572962.
JD492138 - Sequence 473162 from Patent EP1572962.
JD274950 - Sequence 255974 from Patent EP1572962.
JD455578 - Sequence 436602 from Patent EP1572962.
JD217859 - Sequence 198883 from Patent EP1572962.
JD211986 - Sequence 193010 from Patent EP1572962.
JD505199 - Sequence 486223 from Patent EP1572962.
JD505200 - Sequence 486224 from Patent EP1572962.
JD332759 - Sequence 313783 from Patent EP1572962.
JD234226 - Sequence 215250 from Patent EP1572962.
JD293529 - Sequence 274553 from Patent EP1572962.
JD521055 - Sequence 502079 from Patent EP1572962.
JD356422 - Sequence 337446 from Patent EP1572962.
JD505900 - Sequence 486924 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein Q5VV42 (Reactome details) participates in the following event(s):

R-HSA-6782315 tRNA modification in the nucleus and cytosol
R-HSA-72306 tRNA processing
R-HSA-8953854 Metabolism of RNA

-  Other Names for This Gene
  Alternate Gene Symbols: A8K6S0, CDKAL_HUMAN, NM_017774, NP_060244, Q5VV42, Q6P385, Q6ZR27, Q9NXB3
UCSC ID: uc003ndd.2
RefSeq Accession: NM_017774
Protein: Q5VV42 (aka CDKAL_HUMAN)
CCDS: CCDS4546.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_017774.3
exon count: 16CDS single in 3' UTR: no RNA size: 3272
ORF size: 1740CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 3591.50frame shift in genome: no % Coverage: 99.97
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.