CARKD explained

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.^[1] The protein is conserved throughout many species, and has predicted orthologs through eukaryotes, bacteria, and archea.__TOC__

Structure

Gene

Human CARKD gene has 10 exons and resides on Chromosome 13 at q34. The following genes are near CARKD on the chromosome:^[2]

• 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.^[3] CARKD contains a carbohydrate kinase domain . This family is related to and 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^[4]
• Isoelectric point: 9.377^[5]
  • CARKD orthologs have highly variable isoelectric points.^[5]
• Post-translational modification: Three post-translational modifications are predicted:
  • Modified Phosphotyrosine Residue^[6]
  • Two N-Linked Glycosylation Sites^[6]
• A Signal Peptide and signal peptide cleavage site was predicted.^[7]

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.^{[8] [9]} 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.^[10]

Binding partners

The human protein apolipoprotein A-1 binding precursor (APOA1BP) was predicted to be a binding partner for CARKD.^[11] 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,^[12] 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.^[13] In addition, microarray data indicates that CARKD is up-regulated in Glioblastoma multiforme tumors.^[14]

Notes and References

1. Marbaix. AY. Tyteca. D. Niehaus. TD. Hanson. AD. Linster. CL. Van Schaftingen. E. Occurrence and subcellular distribution of the NADPHX repair system in mammals.. The Biochemical Journal. 15 May 2014. 460. 1. 49–58. 24611804. 10.1042/bj20131482.
2. Web site: UCSC Genome Browser: CARKD .
3. Web site: CDD: Conserved Domain Database (NCBI) .
4. Brendel V, Bucher P, Nourbakhsh IR, Blaisdell BE, Karlin S . 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 . March 1992 . 1549558 . 48584 . 10.1073/pnas.89.6.2002. 1992PNAS...89.2002B . free .
5. Web site: PI Program (Isoelectric Point Prediction) . dead . https://web.archive.org/web/20081026062821/http://www.embl-heidelberg.de/cgi/pi-wrapper.pl . 2008-10-26 .
6. Web site: UniProt Database .
7. Bendtsen JD, Nielsen H, von Heijne G, Brunak S . Improved prediction of signal peptides: SignalP 3.0 . Journal of Molecular Biology . 340 . 4 . 783–95 . July 2004 . 15223320 . 10.1016/j.jmb.2004.05.028 . 10.1.1.165.2784 .
8. Web site: Unigene (EST profile viewer) Human CARKD .
9. Web site: Unigene (EST profile viewer) Mouse CARKD .
10. Nielsen JA, Maric D, Lau P, Barker JL, Hudson LD . Identification of a novel oligodendrocyte cell adhesion protein using gene expression profiling . Journal of Neuroscience . 26 . 39 . 9881–91 . September 2006 . 17005852 . 1613258 . 10.1523/JNEUROSCI.2246-06.2006 .
11. Web site: STRING: Known and Predicted Protein-Protein Interactions .
12. Book: Date SV . Bioinformatics . 2008 . The Rosetta Stone Method . 453 . 169–80 . 10.1007/978-1-60327-429-6_7 . 18712302 . Methods in Molecular Biology . Humana Press . Totowa, NJ . 978-1-60327-428-9 .
13. Milani L, Lundmark A, Nordlund J, Kiialainen A, Flaegstad T, Jonmundsson G, Kanerva J, Schmiegelow K, Gunderson KL, Lönnerholm G, Syvänen AC . Allele-specific gene expression patterns in primary leukemic cells reveal regulation of gene expression by CpG site methylation . Genome Research . 19 . 1 . 1–11 . January 2009 . 18997001 . 2612957 . 10.1101/gr.083931.108 .
14. Ruano Y, Mollejo M, Ribalta T, Fiaño C, Camacho FI, Gómez E, de Lope AR, Hernández-Moneo JL, Martínez P, Meléndez B . Identification of novel candidate target genes in amplicons of Glioblastoma multiforme tumors detected by expression and CGH microarray profiling . Molecular Cancer . 5 . 1. 39 . 2006 . 17002787 . 1592108 . 10.1186/1476-4598-5-39 . free .