CDKAL1

CDKAL1 (Cdk5 regulatory associated protein 1-like 1) is a gene in the methylthiotransferase family. The complete physiological function and implications of this have not been fully determined. CDKAL1 is known to code for CDK5, a regulatory subunit-associated protein 1.^[5] This protein CDK5 regulatory subunit-associated protein 1 is found broadly across tissue types including neuronal tissues and pancreatic beta cells.^[6] CDKAL1 is suspected to be involved in the CDK5/p35 pathway, in which p35 is the activator for CDK5 which regulates several neuronal functions.^[7]

CDKAL1
Identifiers
Aliases	CDKAL1, CDK5 regulatory subunit associated protein 1 like 1
External IDs	OMIM: 611259; MGI: 1921765; HomoloGene: 9830; GeneCards: CDKAL1; OMA:CDKAL1 - orthologs
Gene location (Human) Chr. Chromosome 6 (human)[1] Band 6p22.3 Start 20,534,457 bp[1] End 21,232,404 bp[1]
Gene location (Mouse) Chr. Chromosome 13 (mouse)[2] Band 13|13 A3.1- A3.2 Start 29,375,729 bp[2] End 30,039,657 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in buccal mucosa cell Achilles tendon ganglionic eminence ventricular zone testicle gonad muscle of thigh gastrocnemius muscle epithelium of colon stromal cell of endometrium Top expressed in spermatocyte ascending aorta spermatid aortic valve muscle of thigh triceps brachii muscle sternocleidomastoid muscle zygote seminiferous tubule temporal muscle More reference expression data BioGPS n/a
Gene ontology Molecular function transferase activity N6-threonylcarbomyladenosine methylthiotransferase activity iron-sulfur cluster binding metal ion binding protein binding catalytic activity tRNA (N(6)-L-threonylcarbamoyladenosine(37)-C(2))-methylthiotransferase 4 iron, 4 sulfur cluster binding Cellular component integral component of membrane rough endoplasmic reticulum endoplasmic reticulum membrane membrane endoplasmic reticulum Biological process maintenance of translational fidelity tRNA methylthiolation tRNA processing tRNA modification biological process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 54901 68916 Ensembl ENSG00000145996 ENSMUSG00000006191 UniProt Q5VV42 Q91WE6 RefSeq (mRNA) NM_017774 NM_144536 NM_001308486 RefSeq (protein) NP_060244 NP_001295415 NP_653119 Location (UCSC) Chr 6: 20.53 – 21.23 Mb Chr 13: 29.38 – 30.04 Mb PubMed search [3] [4]
Wikidata
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Structure and function

Structurally CDKAL1 contains two iron (Fe) sulfur (S) clusters, therefore its function can be reduced by inhibiting Fe-S cluster biosynthesis.^[8] Enzymatically, CDKAL1 catalyzes methylthiolation of N6-threonylcarbamoyl adenosine 37 (t6A37) in cytosolic tRNA, which has been determined to stabilize anticodon-codon interactions during translation.^[9][10]

Clinical significance

In humans, CDKAL1 is indicated to be involved in type II diabetes. Mutations in CDKAL1 and TCF7L2 have been associated with low production of insulin.^[11] Some studies indicate that CDKAL1 variants modify tRNA resulting in increased risks of type II diabetes as well as obesity.^[12] Variation in CDKAL1 was also attributed to differences in energy regulation. Single nucleotide polymorphism analysis resulted in the discovery of the mechanism of glucose and insulin responses demonstrated in the figure. From this relationship, it has been hypothesized that the regulatory genes CDKAL1 and GIP (glucose-dependent insulinotropic polypeptide) are related to environmental selectivity and adaptive immunity.^[13]

Schematic of CDKAL1 involvement with insulin and glucose regulation.^[13]

Genome-wide association studies have linked single nucleotide polymorphisms in an intron on chromosome 6 with susceptibility to type 2 diabetes`. [provided by RefSeq, May 2010].^[14]

Animal studies

In mice, CDKAL1 impairment reduces the mouse's ability to maintain glucose homeostasis and causes pancreatic islet hypertrophy, or pancreatic lesions.^[15]