NAXD

Available protein structures:
PDB	1kyh, 2ax3 IPR000631 PF01256 (ECOD; PDBsum)
AlphaFold	IPR000631; PF01256;

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

NAXD
Identifiers
Aliases	NAXD, LP3298, CARKD, NAD(P)HX dehydratase, PEBEL2
External IDs	OMIM: 615910; MGI: 1913353; GeneCards: NAXD
Enzyme activity
Gene location (Human)
Chr.	Chromosome 13 (human)
End	110,639,996 bp
Gene location (Mouse)
Chr.	Chromosome 8 (mouse)
End	11,564,960 bp
RNA expression pattern
	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
	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
Databases	NCBI: entry; OMA: entry
	55739
	69225
	ENSG00000213995
	ENSMUSG00000031505
	Q8IW45
	Q9CZ42
	NM_001242881; NM_001242882; NM_001242883; NM_018210
	NM_001190357; NM_001293661; NM_026995
	NP_001229810; NP_001229811; NP_001229812; NP_060680
	NP_001177286; NP_001280590; NP_081271; NP_001389565
	Wikidata
View/Edit Human	View/Edit Mouse

NAD(P)HX dehydratase is an enzyme that in humans is encoded by the NAXD gene (previously CARKD). The NAXD protein is a ATP-dependent NAD(P)H-hydrate dehydratase enzyme that is involved in repairing NAD(P)HX, a type of damaged NAD(P)H.

Gene

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

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

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. 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.

Structure

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. CARKD contains a carbohydrate kinase domain (Pfam PF01256). 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
Isoelectric point: 9.377
- CARKD orthologs have highly variable isoelectric points.
Post-translational modification: Three post-translational modifications are predicted:
- Modified Phosphotyrosine Residue
- Two N-Linked Glycosylation Sites
A Signal Peptide and signal peptide cleavage site was predicted.

Binding partners

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

Mutations of the NAXD gene cause the rare disease early-onset progressive encephalopathy with brain edema and/or leukoencephalopathy-2 (PEBEL2).

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000213995 – Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000031505 – Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ PDB: 1kyh; Zhang RG, Grembecka J, Vinokour E, Collart F, Dementieva I, Minor W, et al. (September 2002). "Structure of Bacillus subtilis YXKO--a member of the UPF0031 family and a putative kinase". Journal of Structural Biology. 139 (3): 161–170. doi:10.1016/S1047-8477(02)00532-4. PMC 2793413. PMID 12457846.
↑ "Q8IW45 · Nnrd_human". uniprot.org. UniProt consortium. Retrieved 2026-09-08.
↑ "UCSC Genome Browser: CARKD".
↑ "Unigene (EST profile viewer) Human CARKD". Archived from the original on November 14, 2012.
↑ "Unigene (EST profile viewer) Mouse CARKD". Archived from the original on November 14, 2012.
↑ Nielsen JA, Maric D, Lau P, Barker JL, Hudson LD (September 2006). "Identification of a novel oligodendrocyte cell adhesion protein using gene expression profiling". The Journal of Neuroscience. 26 (39): 9881–9891. doi:10.1523/JNEUROSCI.2246-06.2006. PMC 1613258. PMID 17005852.
1 2 "CDD: Conserved Domain Database (NCBI)".
↑ 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): 2002–2006. Bibcode:1992PNAS...89.2002B. doi:10.1073/pnas.89.6.2002. PMC 48584. PMID 1549558.
1 2 "PI Program (Isoelectric Point Prediction)". Archived from the original on 2008-10-26.
1 2 "UniProt Database". UniProt.
↑ 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): 783–795. doi:10.1016/j.jmb.2004.05.028. PMID 15223320.
↑ "STRING: Known and Predicted Protein-Protein Interactions".
↑ Date SV (2008). "The Rosetta Stone Method". Bioinformatics. Methods in Molecular Biology. Vol. 453. Totowa, NJ: Humana Press. pp. 169–180. doi:10.1007/978-1-60327-429-6_7. ISBN 978-1-60327-428-9. PMID 18712302.
↑ Milani L, Lundmark A, Nordlund J, Kiialainen A, Flaegstad T, Jonmundsson G, et al. (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.
↑ Ruano Y, Mollejo M, Ribalta T, Fiaño C, Camacho FI, Gómez E, et al. (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

Human CARKD genome location and CARKD gene details page in the UCSC Genome Browser.

[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000213995 – Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000031505 – Ensembl, 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.

[Zhang_2002-5] PDB: 1kyh; Zhang RG, Grembecka J, Vinokour E, Collart F, Dementieva I, Minor W, et al. (September 2002). "Structure of Bacillus subtilis YXKO--a member of the UPF0031 family and a putative kinase". Journal of Structural Biology. 139 (3): 161–170. doi:10.1016/S1047-8477(02)00532-4. PMC 2793413. PMID 12457846.

[6] "Q8IW45 · Nnrd_human". uniprot.org. UniProt consortium. Retrieved 2026-09-08.

[UCSC-7] "UCSC Genome Browser: CARKD".

[ESTHuman-8] "Unigene (EST profile viewer) Human CARKD". Archived from the original on November 14, 2012.

[CARKDmouse-9] "Unigene (EST profile viewer) Mouse CARKD". Archived from the original on November 14, 2012.

[Nielsen_2006-10] Nielsen JA, Maric D, Lau P, Barker JL, Hudson LD (September 2006). "Identification of a novel oligodendrocyte cell adhesion protein using gene expression profiling". The Journal of Neuroscience. 26 (39): 9881–9891. doi:10.1523/JNEUROSCI.2246-06.2006. PMC 1613258. PMID 17005852.

[CDD-11] 1 2 "CDD: Conserved Domain Database (NCBI)".

[SAPS-12] 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): 2002–2006. Bibcode:1992PNAS...89.2002B. doi:10.1073/pnas.89.6.2002. PMC 48584. PMID 1549558.

[PI-13] 1 2 "PI Program (Isoelectric Point Prediction)". Archived from the original on 2008-10-26.

[Uniprot-14] 1 2 "UniProt Database". UniProt.

[SignalP-15] 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): 783–795. doi:10.1016/j.jmb.2004.05.028. PMID 15223320.

[String-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. 169–180. doi:10.1007/978-1-60327-429-6_7. ISBN 978-1-60327-428-9. PMID 18712302.

[Milani_2009-18] Milani L, Lundmark A, Nordlund J, Kiialainen A, Flaegstad T, Jonmundsson G, et al. (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.

[Ruano_2006-19] Ruano Y, Mollejo M, Ribalta T, Fiaño C, Camacho FI, Gómez E, et al. (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.