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

NAXD
Identifiers
AliasesNAXD, LP3298, CARKD, NAD(P)HX dehydratase, PEBEL2
External IDsOMIM: 615910 MGI: 1913353 HomoloGene: 6333 GeneCards: NAXD
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001242881
NM_001242882
NM_001242883
NM_018210

NM_001190357
NM_001293661
NM_026995

RefSeq (protein)

NP_001229810
NP_001229811
NP_001229812
NP_060680

NP_001177286
NP_001280590
NP_081271
NP_001389565

Location (UCSC)Chr 13: 110.62 – 110.64 MbChr 8: 11.55 – 11.56 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse
Carbohydrate kinase
Crystallographic structure of a putative Bacillus subtilis carbohydrate kinase (rainbow colored, N-terminus = blue, C-terminus = red).[5]
Identifiers
SymbolCarb_kinase
PfamPF01256
Pfam clanCL0118
InterProIPR000631
PROSITEPDOC00806
SCOP21kyh / SCOPe / SUPFAM
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary
PDB1kyh​, 2ax3

Structure edit

Gene edit

Human CARKD gene has 10 exons and resides on Chromosome 13 at q34. The following genes are near CARKD on the chromosome:[7]

  • 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 edit

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.[8] CARKD contains a carbohydrate kinase domain (Pfam PF01256).[8] This family is related to Pfam PF02210 and Pfam PF00294 implying that it also is a carbohydrate kinase.

Predicted properties edit

The following properties of CARKD were predicted using bioinformatic analysis:

Function edit

Tissue distribution edit

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.[13][14] 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.[15]

Binding partners edit

The human protein apolipoprotein A-1 binding precursor (APOA1BP) was predicted to be a binding partner for CARKD.[16] 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,[17] are likely interaction partners even in species such as humans where the two proteins are not produced as a single polypeptide.

Clinical significance edit

Based on allele-specific expression of CARKD, CARKD may play a role in acute lymphoblastic leukemia.[18] In addition, microarray data indicates that CARKD is up-regulated in Glioblastoma multiforme tumors.[19]

References edit

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000213995Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000031505Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ 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.
  6. ^ 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. doi:10.1042/bj20131482. PMID 24611804.
  7. ^ "UCSC Genome Browser: CARKD".
  8. ^ a b "CDD: Conserved Domain Database (NCBI)".
  9. ^ 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. Bibcode:1992PNAS...89.2002B. doi:10.1073/pnas.89.6.2002. PMC 48584. PMID 1549558.
  10. ^ a b "PI Program (Isoelectric Point Prediction)". Archived from the original on 2008-10-26.
  11. ^ a b "UniProt Database".
  12. ^ 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. CiteSeerX 10.1.1.165.2784. doi:10.1016/j.jmb.2004.05.028. PMID 15223320.
  13. ^ "Unigene (EST profile viewer) Human CARKD".
  14. ^ "Unigene (EST profile viewer) Mouse CARKD".
  15. ^ 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.
  16. ^ "STRING: Known and Predicted Protein-Protein Interactions".
  17. ^ Date SV (2008). "The Rosetta Stone Method". Bioinformatics. Methods in Molecular Biology. Vol. 453. Totowa, NJ: Humana Press. pp. 169–80. doi:10.1007/978-1-60327-429-6_7. ISBN 978-1-60327-428-9. PMID 18712302.
  18. ^ 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.
  19. ^ 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.

External links edit