CARKD

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
Aliases	NAXD, LP3298, CARKD, NAD(P)HX dehydratase, PEBEL2
External IDs	OMIM: 615910; MGI: 1913353; HomoloGene: 6333; GeneCards: NAXD; OMA:NAXD - orthologs
Gene location (Human) Chr. Chromosome 13 (human)[1] Band 13q34 Start 110,615,545 bp[1] End 110,639,996 bp[1]
Gene location (Mouse) Chr. Chromosome 8 (mouse)[2] Band 8|8 A1.1 Start 11,547,506 bp[2] End 11,564,960 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in cardia left ovary right adrenal cortex pylorus right lobe of liver renal medulla right ovary postcentral gyrus left adrenal gland left adrenal cortex Top expressed in interventricular septum epithelium of lens transitional epithelium of urinary bladder renal corpuscle right kidney lacrimal gland fossa Epithelium of choroid plexus proximal tubule condyle More reference expression data BioGPS n/a
Gene ontology Molecular function nucleotide binding protein binding ATP binding ADP-dependent NAD(P)H-hydrate dehydratase activity lyase activity ATP-dependent NAD(P)H-hydrate dehydratase activity molecular function Cellular component mitochondrion mitochondrial matrix cellular component Biological process NAD biosynthesis via nicotinamide riboside salvage pathway biological process nicotinamide nucleotide metabolic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 55739 69225 Ensembl ENSG00000213995 ENSMUSG00000031505 UniProt Q8IW45 Q9CZ42 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 Mb Chr 8: 11.55 – 11.56 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Carbohydrate kinase
Crystallographic structure of a putative Bacillus subtilis carbohydrate kinase (rainbow colored, N-terminus = blue, C-terminus = red).[5]
Identifiers
Symbol	Carb_kinase
Pfam	PF01256
Pfam clan	CL0118
InterPro	IPR000631
PROSITE	PDOC00806
SCOP2	1kyh / SCOPe / SUPFAM
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary PDB 1kyh​, 2ax3​

Structure

Gene

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

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

The following properties of CARKD were predicted using bioinformatic analysis:

• Molecular Weight: 41.4 KDal^[9]
• Isoelectric point: 9.377^[10]
  • CARKD orthologs have highly variable isoelectric points.^[10]
• Post-translational modification: Three post-translational modifications are predicted:
  • Modified Phosphotyrosine Residue^[11]
  • Two N-Linked Glycosylation Sites^[11]
• A Signal Peptide and signal peptide cleavage site was predicted.^[12]

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.^[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

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

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]