NAD(P)H-hydrate epimerase

Search
PMC	articles
PubMed	articles
NCBI	proteins

NAD(P)H-hydrate epimerase
NAD(P)H-hydrate epimerase
Identifiers
EC no.	5.1.99.6
Databases
BRENDA	enzyme data
ExPASy	NiceZyme view
KEGG	enzyme entry
MetaCyc	metabolic pathway
Rhea	reactions
PDB structures	RCSB PDB PDBe PDBsum
PMC
Search
PMC	articles
PubMed	articles
NCBI	proteins

NAXE
Identifiers
Aliases	NAXE, AIBP, YJEFN1, APOA1BP, NAD(P)HX epimerase, PEBEL
External IDs	OMIM: 608862; MGI: 2180167; GeneCards: NAXE
Enzyme activity
Gene location (Human)
Chr.	Chromosome 1 (human)
End	156,609,507 bp
Gene location (Mouse)
Chr.	Chromosome 3 (mouse)
End	87,965,802 bp
RNA expression pattern
	Top expressed in
	apex of heart; ; cardiac muscle tissue of right atrium; ; myocardium of left ventricle; ; islet of Langerhans; ; mucosa of transverse colon; ; prefrontal cortex; ; right auricle of heart; ; corpus epididymis; ; anterior pituitary; ; human kidney;
	Top expressed in
	choroid plexus of fourth ventricle; ; facial motor nucleus; ; right kidney; ; utricle; ; right lung lobe; ; Ileal epithelium; ; proximal tubule; ; vestibular sensory epithelium; ; external carotid artery; ; transitional epithelium of urinary bladder;
	More reference expression data
	n/a
Gene ontology
Molecular function	nucleotide binding; NADHX epimerase activity; protein binding; protein homodimerization activity; isomerase activity; metal ion binding; NADPHX epimerase activity;
Cellular component	cell body; extracellular region; cilium; extracellular exosome; intracellular membrane-bounded organelle; mitochondrion; nucleus; nucleoplasm; mitochondrial matrix; extracellular space; cytosol;
Biological process	protein homotetramerization; NAD biosynthesis via nicotinamide riboside salvage pathway; nicotinamide nucleotide metabolic process; NADH metabolic process; NADP metabolic process;
	Sources:Amigo / QuickGO
Orthologs
Databases	NCBI: entry; OMA: entry
	128240
	246703
	ENSG00000163382
	ENSMUSG00000028070
	Q8NCW5
	Q8K4Z3
	NM_144772
	NM_144897
	NP_658985
	NP_659146
	Wikidata
View/Edit Human	View/Edit Mouse

NAD(P)H-hydrate epimerase is an enzyme that in humans is encoded by the NAXE gene (previously APOA1BP).

Mutations in NAXE gene are associated with progressive encephalopathy with brain edema and/or leukoencephalopathy-1 (PEBEL-1), a rare, lethal, neurometabolic disorder.

Structure

NAXE gene is located on chromosome 1, with its specific location being 1q22. The gene contains 6 exons, 5 introns, and spans 2.5 kb. Expression is ubiquitous across all human tissues, with highest observed in kidney, heart, liver, testis, thyroid gland, adrenal gland. NAXE contains Yje_FN domain.

Function

NAXE binds to APOA1, APOA2, and high-density lipoprotein (HDL). In addition, APOA1BP appears to play a role in sperm capacitation. It has been demonstrated that APOA1BP is involved in angiogenesis regulation, by accelerating cholesterol efflux from endothelial cells to HDL. It is known that zebrafish NAXE ortholog Aibp is involved in angiogenesis regulation. The protein was also shown to be involved in atherosclerosis protection.

Enzyme class

More generally, an NAD(P)H-hydrate epimerase (EC 5.1.99.6, NAD(P)HX epimerase) is a type of enzyme with systematic name (6R)-6beta-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide 6-epimerase. Enzymes of this class, especially NAXE and its orthologs, catalyse the following chemical reaction

(1) (6R)-6beta-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide

\rightleftharpoons

(6S)-6beta-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide

(2) (6R)-6beta-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide phosphate

\rightleftharpoons

(6S)-6beta-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide phosphate

The enzyme can use either (R)-NADH-hydrate or (R)-NADPH-hydrate as a substrate.

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000163382 – Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000028070 – 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.
1 2 3 4 Ritter M, Buechler C, Boettcher A, Barlage S, Schmitz-Madry A, Orsó E, et al. (May 2002). "Cloning and characterization of a novel apolipoprotein A-I binding protein, AI-BP, secreted by cells of the kidney proximal tubules in response to HDL or ApoA-I". Genomics. 79 (5): 693–702. doi:10.1006/geno.2002.6761. PMID 11991719.
↑ Chiu LW, Lin SS, Chen CH, Lin CH, Lee NC, Hong SY, et al. (October 2021). "NAXE gene mutation-related progressive encephalopathy: A case report and literature review". Medicine. 100 (42) e27548. Baltimore. doi:10.1097/MD.0000000000027548. PMC 8542128. PMID 34678889.
↑ "NAXE NAD(P)HX epimerase [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2024-03-28.
↑ Rudolph C, Sigruener A, Hartmann A, Orso E, Bals-Pratsch M, Gronwald W, et al. (May 2007). "ApoA-I-binding protein (AI-BP) and its homologues hYjeF_N2 and hYjeF_N3 comprise the YjeF_N domain protein family in humans with a role in spermiogenesis and oogenesis". Hormone and Metabolic Research = Hormon- und Stoffwechselforschung = Hormones et Metabolisme. 39 (5): 322–335. doi:10.1055/s-2007-977699. PMID 17533573.
↑ Jha KN, Shumilin IA, Digilio LC, Chertihin O, Zheng H, Schmitz G, et al. (May 2008). "Biochemical and Structural Characterization of Apolipoprotein A-I Binding Protein, a Novel Phosphoprotein with a Potential Role in Sperm Capacitation". Endocrinology. 149 (5): 2108–2120. doi:10.1210/en.2007-0582. PMC 2329272. PMID 18202122.
1 2 Fang L, Choi SH, Baek JS, Liu C, Almazan F, Ulrich F, et al. (June 2013). "Control of angiogenesis by AIBP-mediated cholesterol efflux". Nature. 498 (7452): 118–122. Bibcode:2013Natur.498..118F. doi:10.1038/nature12166. PMC 3760669. PMID 23719382.
1 2 Schneider DA, Choi SH, Agatisa-Boyle C, Zhu L, Kim J, Pattison J, et al. (May 2018). "AIBP protects against metabolic abnormalities and atherosclerosis". Journal of Lipid Research. 59 (5): 854–863. doi:10.1194/jlr.m083618. PMC 5928435. PMID 29559522.
↑ Marbaix AY, Noël G, Detroux AM, Vertommen D, Van Schaftingen E, Linster CL (December 2011). "Extremely conserved ATP- or ADP-dependent enzymatic system for nicotinamide nucleotide repair". The Journal of Biological Chemistry. 286 (48): 41246–52. doi:10.1074/jbc.c111.310847. PMC 3308837. PMID 21994945.

External links

NAD(P)H-hydrate+epimerase at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

This article on a gene on human chromosome 1 is a stub. You can help Wikipedia by adding missing information.

[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000163382 – Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000028070 – 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.

[Ritter_2002-5] 1 2 3 4 Ritter M, Buechler C, Boettcher A, Barlage S, Schmitz-Madry A, Orsó E, et al. (May 2002). "Cloning and characterization of a novel apolipoprotein A-I binding protein, AI-BP, secreted by cells of the kidney proximal tubules in response to HDL or ApoA-I". Genomics. 79 (5): 693–702. doi:10.1006/geno.2002.6761. PMID 11991719.

[6] Chiu LW, Lin SS, Chen CH, Lin CH, Lee NC, Hong SY, et al. (October 2021). "NAXE gene mutation-related progressive encephalopathy: A case report and literature review". Medicine. 100 (42) e27548. Baltimore. doi:10.1097/MD.0000000000027548. PMC 8542128. PMID 34678889.

[7] "NAXE NAD(P)HX epimerase [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2024-03-28.

[8] Rudolph C, Sigruener A, Hartmann A, Orso E, Bals-Pratsch M, Gronwald W, et al. (May 2007). "ApoA-I-binding protein (AI-BP) and its homologues hYjeF_N2 and hYjeF_N3 comprise the YjeF_N domain protein family in humans with a role in spermiogenesis and oogenesis". Hormone and Metabolic Research = Hormon- und Stoffwechselforschung = Hormones et Metabolisme. 39 (5): 322–335. doi:10.1055/s-2007-977699. PMID 17533573.

[Jha_2008-9] Jha KN, Shumilin IA, Digilio LC, Chertihin O, Zheng H, Schmitz G, et al. (May 2008). "Biochemical and Structural Characterization of Apolipoprotein A-I Binding Protein, a Novel Phosphoprotein with a Potential Role in Sperm Capacitation". Endocrinology. 149 (5): 2108–2120. doi:10.1210/en.2007-0582. PMC 2329272. PMID 18202122.

[Fang_2013-10] 1 2 Fang L, Choi SH, Baek JS, Liu C, Almazan F, Ulrich F, et al. (June 2013). "Control of angiogenesis by AIBP-mediated cholesterol efflux". Nature. 498 (7452): 118–122. Bibcode:2013Natur.498..118F. doi:10.1038/nature12166. PMC 3760669. PMID 23719382.

[Schneider_2018-11] 1 2 Schneider DA, Choi SH, Agatisa-Boyle C, Zhu L, Kim J, Pattison J, et al. (May 2018). "AIBP protects against metabolic abnormalities and atherosclerosis". Journal of Lipid Research. 59 (5): 854–863. doi:10.1194/jlr.m083618. PMC 5928435. PMID 29559522.

[12] Marbaix AY, Noël G, Detroux AM, Vertommen D, Van Schaftingen E, Linster CL (December 2011). "Extremely conserved ATP- or ADP-dependent enzymatic system for nicotinamide nucleotide repair". The Journal of Biological Chemistry. 286 (48): 41246–52. doi:10.1074/jbc.c111.310847. PMC 3308837. PMID 21994945.

v t e Isomerases: Epimerase and racemases (EC 5.1)
5.1.1: Amino acids	Amino-acid racemase: Phenylalanine racemase (ATP-hydrolysing) Serine racemase
5.1.2: Hydroxy acids	Mandelate racemase Isocitrate epimerase
5.1.3: Carbohydrates	UDP-glucose 4-epimerase N-acetylneuraminate epimerase Phosphopentose epimerase
5.1.99: Other	Methylmalonyl CoA epimerase

v t e Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Diffusion-limited enzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list)