CARKD

Carbohydrate kinase domain containing
Identifiers
Symbols	CARKD ; LP3298
External IDs	OMIM: 615910 MGI: 1913353 HomoloGene: 6333 GeneCards: CARKD Gene
EC number	4.2.1.93
Gene ontology Molecular function • molecular_function • protein binding • ATP binding • ATP-dependent NAD(P)H-hydrate dehydratase activity • ADP-dependent NAD(P)H-hydrate dehydratase activity Cellular component • cellular_component • mitochondrion Biological process • biological_process • metabolic process Sources: Amigo / QuickGO
Protein domains
Orthologs
Species	Human	Mouse
Entrez	55739	69225
Ensembl	ENSG00000213995	ENSMUSG00000031505
UniProt	Q8IW45	Q9CZ42
RefSeq (mRNA)	NM_001242881	NM_001190357
RefSeq (protein)	NP_001229810	NP_001177286
Location (UCSC)	Chr 13: 110.62 – 110.64 Mb	Chr 8: 11.5 – 11.51 Mb
PubMed search

Carbohydrate kinase
Crystallographic structure of a putative Bacillus subtilis carbohydrate kinase (rainbow colored, N-terminus = blue, C-terminus = red).[1]
Identifiers
Symbol	Carb_kinase
Pfam	PF01256
Pfam clan	CL0118
InterPro	IPR000631
PROSITE	PDOC00806
SCOP	1kyh
SUPERFAMILY	1kyh
Available protein structures: Pfam structures PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Carbohydrate kinase domain containing protein (abbreviated as CARKD), encoded by CARKD gene, is a human protein of unknown function. The CARKD gene encodes proteins with a predicted mitochondrial propeptide (mCARKD), a signal peptide (spCARKD) or neither of them (cCARKD). Confocal microscopy analysis of transfected CHO (Chinese-hamster ovary) cells indicated that cCARKD remains in the cytosol, whereas mCARKD and spCARKD are targeted to the mitochondria and the endoplasmic reticulum respectively.^[2] The protein is conserved throughout many species, and has predicted orthologs through eukaryotes, bacteria, and archea.

Structure

Gene

Human CARKD gene has 10 exons and resides on Chromosome 13 at q34. The following genes are near CARKD on the chromosome:^[3]

• COL4A2: A2 Subunit of type IV collagen
• RAB20: Potential regulator of Connexin 43 trafficking.
• CARS2: Mitochondrial Cystienyl-tRNA Synthetase 2
• ING1: Tumor-Suppressor Protein

Protein

This protein is part of the phosphomethylpyrimidine kinase: ribokinase / pfkB superfamily. This family is characterized by the presence of a domain shared by the family.^[4] CARKD contains a carbohydrate kinase domain (Pfam PF01256).^[4] This family is related to Pfam PF02210 and Pfam PF00294 implying that it also is a carbohydrate kinase.

Predicted properties

The following properties of CARKD were predicted using bioinformatic analysis:

• Molecular Weight: 41.4 KDal^[5]
• Isoelectric point: 9.377^[6]
  • CARKD orthologs have highly variable isoelectric points.^[6]
• Post-translational modification: Three post-translational modifications are predicted:
  • Modified Phosphotyrosine Residue^[7]
  • Two N-Linked Glycosylation Sites^[7]
• A Signal Peptide and signal peptide cleavage site was predicted.^[8]

Function

Tissue distribution

CARKD appears to be ubiquitously expressed at high levels. Expression data in the human protein, and the mouse ortholog, indicate its expression in almost all tissues.^[9][10] One peculiar expression pattern of CARKD is its differential expression through the development of oligodendrocytes. Its expression is lower in oligodendrocyte progenitor cells than in mature oligodendrocytes.^[11]

Binding partners

The human protein apolipoprotein A-1 binding precursor (APOA1BP) was predicted to be a binding partner for CARKD.^[12] This prediction is based on co-occurrence across genomes and co-expression. In addition to these data, the orthologs of CARKD in E. coli contain a domain similar to APOA1BP. This indicates that the two proteins are likely to have originated from a common evolutionary ancestor and, according to Rosetta stone analysis theory,^[13] are likely interaction partners even in species such as humans where the two proteins are not produced as a single polypeptide.

Clinical significance

Based on allele-specific expression of CARKD, CARKD may play a role in acute lymphoblastic leukemia.^[14] In addition, microarray data indicates that CARKD is up-regulated in Glioblastoma multiforme tumors.^[15]

References

1. PDB: 1kyh​; Zhang RG, Grembecka J, Vinokour E, Collart F, Dementieva I, Minor W, Joachimiak A (September 2002). "Structure of Bacillus subtilis YXKO--a member of the UPF0031 family and a putative kinase". Journal of Structural Biology 139 (3): 161–70. doi:10.1016/S1047-8477(02)00532-4. PMC 2793413. PMID 12457846.
2. Marbaix, AY; Tyteca, D; Niehaus, TD; Hanson, AD; Linster, CL; Van Schaftingen, E (15 May 2014). "Occurrence and subcellular distribution of the NADPHX repair system in mammals.". The Biochemical journal 460 (1): 49–58. PMID 24611804.
3. "UCSC Genome Browser: CARKD".
4. "CDD: Conserved Domain Database (NCBI)".
5. Brendel V, Bucher P, Nourbakhsh IR, Blaisdell BE, Karlin S (March 1992). "Methods and algorithms for statistical analysis of protein sequences". Proceedings of the National Academy of Sciences of the United States of America 89 (6): 2002–6. doi:10.1073/pnas.89.6.2002. PMC 48584. PMID 1549558.
6. "PI Program (Isoelectric Point Prediction)".
7. "UniProt Database".
8. Bendtsen JD, Nielsen H, von Heijne G, Brunak S (July 2004). "Improved prediction of signal peptides: SignalP 3.0". Journal of Molecular Biology 340 (4): 783–95. doi:10.1016/j.jmb.2004.05.028. PMID 15223320.
9. "Unigene (EST profile viewer) Human CARKD".
10. "Unigene (EST profile viewer) Mouse CARKD".
11. Nielsen JA, Maric D, Lau P, Barker JL, Hudson LD (September 2006). "Identification of a novel oligodendrocyte cell adhesion protein using gene expression profiling". Journal of Neuroscience 26 (39): 9881–91. doi:10.1523/JNEUROSCI.2246-06.2006. PMC 1613258. PMID 17005852.
12. "STRING: Known and Predicted Protein-Protein Interactions".
13. The Rosetta stone method, Date SV. Methods Mol Biol. 2008;453:169-80.
14. Milani L, Lundmark A, Nordlund J, Kiialainen A, Flaegstad T, Jonmundsson G, Kanerva J, Schmiegelow K, Gunderson KL, Lönnerholm G, Syvänen AC (January 2009). "Allele-specific gene expression patterns in primary leukemic cells reveal regulation of gene expression by CpG site methylation". Genome Research 19 (1): 1–11. doi:10.1101/gr.083931.108. PMC 2612957. PMID 18997001.
15. Ruano Y, Mollejo M, Ribalta T, Fiaño C, Camacho FI, Gómez E, de Lope AR, Hernández-Moneo JL, Martínez P, Meléndez B (2006). "Identification of novel candidate target genes in amplicons of Glioblastoma multiforme tumors detected by expression and CGH microarray profiling". Molecular Cancer 5 (1): 39. doi:10.1186/1476-4598-5-39. PMC 1592108. PMID 17002787.