CHKB (gene)

Last updated
CHKB
Protein CHKB PDB 2ig7.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases CHKB , CHETK, CHKL, CK, CKB, CKEKB, EK, EKB, MDCMC, choline kinase beta
External IDs OMIM: 612395 MGI: 1328313 HomoloGene: 88718 GeneCards: CHKB
Orthologs
SpeciesHumanMouse
Entrez

1120

12651

Ensembl

ENSG00000100288

ENSMUSG00000022617

UniProt

Q9Y259

O55229

RefSeq (mRNA)

NM_152253
NM_005198

NM_007692

RefSeq (protein)

NP_005189

NP_031718

Location (UCSC) Chr 22: 50.58 – 50.6 Mb Chr 15: 89.31 – 89.31 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Choline kinase beta (CK), also known as Ethanolamine kinase (EK), Choline kinase-like protein , choline/ethanolamine kinase beta (CKEKB), or Choline/ethanolamine kinase is a protein encoded by the CHKB gene. [5] [6] This gene is found on chromosome 22 in humans. The encoded protein plays a key role in phospholipid biosynthesis. Choline kinase (CK) and ethanolamine kinase (EK) catalyzes the first step in phosphatidylethanolamine biosynthesis. Read-through transcripts are expressed from this locus that include exons from the downstream CPT1B locus. [7] [8] [9]

Contents

Structure

The CHKB gene is located on the q arm of chromosome 22 at position 13.3 and it spans 4,041 base pairs. [7] The CHKB gene produces a 7 kDa protein composed of 60 amino acids. [10] [11] The structure of the protein has been found to be a homodimer, and forms a heterodimer with the CHKA protein. [9] [8] It has also been found to contain multiple highly conserved domains, such as a Brenner phosphotransferase consensus sequence essential in catalytic function. [12]

Function

The CHKB gene encodes for a key protein in phospholipid biosynthesis. The choline kinase (CK) and ethanolamine kinase (EK) proteins, which are coded by the CHKB gene, catalyze the phosphorylation of choline/ethanolamine in vitro to phosphocholine/phosphoethanolamine. The catalysis is controlled by ATP in the presence of magnesium and ADP, and commits choline to the enzymatic pathway for biosynthesis of phosphatidylcholine. This is the first step in the biosynthesis of phosphocholine/phosphoethanolamine in all animal cells, and is done by the Kennedy pathway. The highly purified choline kinases from mammalian sources and their recombinant gene products have been shown to have ethanolamine kinase activity as well, indicating that both activities reside on the same protein. However, it has been shown that the protein has higher activity with ethanolamine and may not significantly contribute to in vivo phosphatidylcholine biosynthesis. The choline kinase-like protein encoded by CHKB belongs to the choline/ethanolamine kinase family; however, its exact function is not known. At least two transcript variants encoding two different isoforms have been found for this gene, and one of the transcripts is bicistronic. [7] [8] [9] [13] [14]

Clinical significance

Mutations in CHKB have been found to result in mitochondrial deficiencies and associated disorders. Knockdown of the gene has been known to result in decreased choline kinase and phosphatidylcholine activity. This impairment in activity may lead to a modified composition of the phospholipid composition in the mitochondrial membrane resulting in major disorders in the function and structure of the mitochondria. Major disorders include as Megaconial Congenital Muscular Dystrophy (MDCMC), and Narcolepsy. [7] [15]

Megaconial Congenital Muscular Dystrophy (MDCMC)

CHKB mutations have been majorly associated with Megaconial Congenital Muscular Dystrophy (MDCMC). Megaconial Congenital Muscular Dystrophy (MDCMC) is an autosomal recessive congenital muscular dystrophy characterized by muscle biopsy results displaying an enlarged mitochondria which are common in the periphery of the fibers but scarce around the center. [16]

Common clinical manifestations of MDCMC include: [15] [17]

Symptoms such as neurogenic atrophy, enlarged mitochondria in the periphery of the fibers, and complex I deficiency were shown in a Spanish patient with a homozygous mutation of c.810T>A. [15] Another patient with a homozygous mutation (p.E292X) in the CHKB gene exhibited rhythmic jerkings of arms, which were characterized as muscle spasms. [14] Finally, a patient with a homozygous c.810T>A showed signs of Gower's sign, hypotonia, and proximal muscle weakness. [18]

Narcolepsy

Narcolepsy is a neurological disabling sleep disorder, characterized by excessive daytime sleepiness, sleep fragmentation, symptoms of abnormal rapid-eye-movement (REM) sleep, cataplexy, hypnagogic hallucinations, and sleep paralysis. Cataplexy is a sudden loss of muscle tone triggered by emotions, which is the most valuable clinical feature used to diagnose narcolepsy. Human narcolepsy is primarily a sporadically occurring disorder but familial clustering has been observed. [19]

Interactions

CHKB has been shown to have Protein-protein interactions with the following. [20] [8]

Related Research Articles

<span class="mw-page-title-main">Fukuyama congenital muscular dystrophy</span> Medical condition

Fukuyama congenital muscular dystrophy (FCMD) is a rare, autosomal recessive form of muscular dystrophy (weakness and breakdown of muscular tissue) mainly described in Japan but also identified in Turkish and Ashkenazi Jewish patients; fifteen cases were first described on 1960 by Dr. Yukio Fukuyama.

<span class="mw-page-title-main">Mitochondrial myopathy</span> Medical condition

Mitochondrial myopathies are types of myopathies associated with mitochondrial disease. Adenosine triphosphate (ATP), the chemical used to provide energy for the cell, cannot be produced sufficiently by oxidative phosphorylation when the mitochondrion is either damaged or missing necessary enzymes or transport proteins. With ATP production deficient in mitochondria, there is an over-reliance on anaerobic glycolysis which leads to lactic acidosis either at rest or exercise-induced.

<span class="mw-page-title-main">Fukutin</span> Mammalian protein found in Homo sapiens

Fukutin is a eukaryotic protein necessary for the maintenance of muscle integrity, cortical histogenesis, and normal ocular development. Mutations in the fukutin gene have been shown to result in Fukuyama congenital muscular dystrophy (FCMD) characterised by brain malformation - one of the most common autosomal-recessive disorders in Japan. In humans this protein is encoded by the FCMD gene, located on chromosome 9q31. Human fukutin exhibits a length of 461 amino acids and a predicted molecular mass of 53.7 kDa.

Calpain-3 is a protein that in humans is encoded by the CAPN3 gene.

<span class="mw-page-title-main">Myotonin-protein kinase</span> Protein-coding gene in the species Homo sapiens

Myotonin-protein kinase (MT-PK) also known as myotonic dystrophy protein kinase (MDPK) or dystrophia myotonica protein kinase (DMPK) is an enzyme that in humans is encoded by the DMPK gene.

Choline kinase is an enzyme which catalyzes the first reaction in the choline pathway for phosphatidylcholine (PC) biosynthesis. This reaction involves the transfer of a phosphate group from adenosine triphosphate (ATP) to choline in order to form phosphocholine.

<span class="mw-page-title-main">PRKAA2</span> Protein-coding gene in the species Homo sapiens

5'-AMP-activated protein kinase catalytic subunit alpha-2 is an enzyme that in humans is encoded by the PRKAA2 gene.

<span class="mw-page-title-main">Laminin subunit alpha-2</span> Protein-coding gene in the species Homo sapiens

Laminin subunit alpha-2 is a protein that in humans is encoded by the LAMA2 gene.

<span class="mw-page-title-main">Integrin alpha 7</span>

Alpha-7 integrin is a protein that in humans is encoded by the ITGA7 gene. Alpha-7 integrin is critical for modulating cell-matrix interactions. Alpha-7 integrin is highly expressed in cardiac muscle, skeletal muscle and smooth muscle cells, and localizes to Z-disc and costamere structures. Mutations in ITGA7 have been associated with congenital myopathies and noncompaction cardiomyopathy, and altered expression levels of alpha-7 integrin have been identified in various forms of muscular dystrophy.

<span class="mw-page-title-main">POMGNT1</span> Human gene

Protein O-linked-mannose beta-1,2-N-acetylglucosaminyltransferase 1 is an enzyme that in humans is encoded by the POMGNT1 gene.

<span class="mw-page-title-main">CHKA</span> Protein-coding gene in the species Homo sapiens

Choline kinase alpha is an enzyme that in humans is encoded by the CHKA gene.

<span class="mw-page-title-main">POMT1</span> Mammalian protein found in Homo sapiens

Protein O-mannosyl-transferase 1 is an enzyme that in humans is encoded by the POMT1 gene. It is a member of the dolichyl-phosphate-mannose-protein mannosyltransferases.

<span class="mw-page-title-main">FASTK</span> Protein-coding gene in the species Homo sapiens

Fas-activated serine/threonine kinase is an enzyme that in humans is encoded by the FASTK gene.

<span class="mw-page-title-main">ANKRD1</span> Protein-coding gene in the species Homo sapiens

Ankyrin repeat domain-containing protein 1, or Cardiac ankyrin repeat protein is a protein that in humans is encoded by the ANKRD1 gene also known as CARP. CARP is highly expressed in cardiac and skeletal muscle, and is a transcription factor involved in development and under conditions of stress. CARP has been implicated in several diseases, including dilated cardiomyopathy, hypertrophic cardiomyopathy, and several skeletal muscle myopathies.

<span class="mw-page-title-main">LDB3</span> Protein-coding gene in the species Homo sapiens

LIM domain binding 3 (LDB3), also known as Z-band alternatively spliced PDZ-motif (ZASP), is a protein which in humans is encoded by the LDB3 gene. ZASP belongs to the Enigma subfamily of proteins and stabilizes the sarcomere during contraction, through interactions with actin in cardiac and skeletal muscles. Mutations in the ZASP gene has been associated with several muscular diseases.

<span class="mw-page-title-main">POMT2</span>

Protein O-mannosyl-transferase 2 is an enzyme that in humans is encoded by the POMT2 gene.

<span class="mw-page-title-main">Ullrich congenital muscular dystrophy</span> Medical condition

Ullrich congenital muscular dystrophy (UCMD) is a form of congenital muscular dystrophy. There are two forms: UCMD1 and UCMD2.

Collagen VI (ColVI) is a type of collagen primarily associated with the extracellular matrix of skeletal muscle. ColVI maintains regularity in muscle function and stabilizes the cell membrane. It is synthesized by a complex, multistep pathway that leads to the formation of a unique network of linked microfilaments located in the extracellular matrix (ECM). ColVI plays a vital role in numerous cell types, including chondrocytes, neurons, myocytes, fibroblasts, and cardiomyocytes. ColVI molecules are made up of three alpha chains: α1(VI), α2(VI), and α3(VI). It is encoded by 6 genes: COL6A1, COL6A2, COL6A3, COL6A4, COL6A5, and COL6A6. The chain lengths of α1(VI) and α2(VI) are about 1,000 amino acids. The chain length of α3(VI) is roughly a third larger than those of α1(VI) and α2(VI), and it consists of several spliced variants within the range of 2,500 to 3,100 amino acids.

<span class="mw-page-title-main">Choline/ethanolamine kinase family</span>

In molecular biology, the choline/ethanolamine kinase family includes choline kinase(EC 2.7.1.32) and ethanolamine kinase.

<span class="mw-page-title-main">CDP-choline pathway</span>

The CDP-choline pathway, first identified by Eugene P. Kennedy in 1956, is the predominant mechanism by which mammalian cells synthesize phosphatidylcholine (PC) for incorporation into membranes or lipid-derived signalling molecules. The CDP-choline pathway represents one half of what is known as the Kennedy pathway. The other half is the CDP-ethanolamine pathway which is responsible for the biosynthesis of the phospholipid phosphatidylethanolamine (PE).

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000100288 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000022617 - 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.
  5. ↑ Yamazaki N, Yamanaka Y, Hashimoto Y, Shinohara Y, Shima A, Terada H (June 1997). "Structural features of the gene encoding human muscle type carnitine palmitoyltransferase I". FEBS Lett. 409 (3): 401–6. doi: 10.1016/S0014-5793(97)00561-9 . PMID   9224698.
  6. ↑ Aoyama C, Liao H, Ishidate K (May 2004). "Structure and function of choline kinase isoforms in mammalian cells". Prog. Lipid Res. 43 (3): 266–81. doi:10.1016/j.plipres.2003.12.001. PMID   15003397.
  7. 1 2 3 4 "Entrez Gene: CHKB choline kinase beta".PD-icon.svg This article incorporates text from this source, which is in the public domain .
  8. 1 2 3 4 "CHKB - Choline/ethanolamine kinase - Homo sapiens (Human) - CHKB gene & protein" . Retrieved 2018-08-23. Creative Commons by small.svg  This article incorporates text available under the CC BY 4.0 license.
  9. 1 2 3 "UniProt: the universal protein knowledgebase". Nucleic Acids Research. 45 (D1): D158–D169. January 2017. doi:10.1093/nar/gkw1099. PMC   5210571 . PMID   27899622.
  10. ↑ Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, Deng N, Kim AK, Choi JH, Zelaya I, Liem D, Meyer D, Odeberg J, Fang C, Lu HJ, Xu T, Weiss J, Duan H, Uhlen M, Yates JR, Apweiler R, Ge J, Hermjakob H, Ping P (Oct 2013). "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research. 113 (9): 1043–53. doi:10.1161/CIRCRESAHA.113.301151. PMC   4076475 . PMID   23965338.
  11. ↑ "Protein CHKB-CPT1B". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB). Archived from the original on 2018-08-24. Retrieved 2018-08-23.
  12. ↑ Aoyama C, Yamazaki N, Terada H, Ishidate K (2000). "Structure and characterization of the genes for murine choline/ethanolamine kinase isozymes alpha and beta". J. Lipid Res. 41 (3): 452–64. doi: 10.1016/S0022-2275(20)34484-9 . PMID   10706593.
  13. ↑ Ishidate K (1997). "Choline/ethanolamine kinase from mammalian tissues". Biochim. Biophys. Acta. 1348 (1–2): 70–8. doi:10.1016/s0005-2760(97)00118-5. PMID   9370318.
  14. 1 2 Gutiérrez Ríos, P; Kalra, AA; Wilson, JD; Tanji, K; Akman, HO; Area Gómez, E; Schon, EA; DiMauro, S (May 2012). "Congenital megaconial myopathy due to a novel defect in the choline kinase Beta gene". Archives of Neurology. 69 (5): 657–61. doi: 10.1001/archneurol.2011.2333 . PMC   8276349 . PMID   22782513.
  15. 1 2 3 Castro-Gago, M; Dacruz-Alvarez, D; Pintos-Martínez, E; Beiras-Iglesias, A; Arenas, J; Martín, MÁ; Martínez-Azorín, F (January 2016). "Congenital neurogenic muscular atrophy in megaconial myopathy due to a mutation in CHKB gene". Brain & Development. 38 (1): 167–72. doi:10.1016/j.braindev.2015.05.008. PMID   26006750. S2CID   27237112.
  16. ↑ Mitsuhashi, S; Ohkuma, A; Talim, B; Karahashi, M; Koumura, T; Aoyama, C; Kurihara, M; Quinlivan, R; Sewry, C; Mitsuhashi, H; Goto, K; Koksal, B; Kale, G; Ikeda, K; Taguchi, R; Noguchi, S; Hayashi, YK; Nonaka, I; Sher, RB; Sugimoto, H; Nakagawa, Y; Cox, GA; Topaloglu, H; Nishino, I (10 June 2011). "A congenital muscular dystrophy with mitochondrial structural abnormalities caused by defective de novo phosphatidylcholine biosynthesis". American Journal of Human Genetics. 88 (6): 845–851. doi:10.1016/j.ajhg.2011.05.010. PMC   3113344 . PMID   21665002.
  17. ↑ "Muscular dystrophy, congenital, megaconial type Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". Rarediseases.info.nih.gov.
  18. ↑ Nishino, I; Kobayashi, O; Goto, Y; Kurihara, M; Kumagai, K; Fujita, T; Hashimoto, K; Horai, S; Nonaka, I (January 1998). "A new congenital muscular dystrophy with mitochondrial structural abnormalities". Muscle & Nerve. 21 (1): 40–7. doi:10.1002/(SICI)1097-4598(199801)21:1<40::AID-MUS6>3.0.CO;2-G. PMID   9427222. S2CID   452150.
  19. ↑ "Narcolepsy 7". www.uniprot.org.
  20. ↑ Mick DU, Dennerlein S, Wiese H, Reinhold R, Pacheu-Grau D, Lorenzi I, Sasarman F, Weraarpachai W, Shoubridge EA, Warscheid B, Rehling P (December 2012). "MITRAC links mitochondrial protein translocation to respiratory-chain assembly and translational regulation". Cell. 151 (7): 1528–41. doi: 10.1016/j.cell.2012.11.053 . hdl: 11858/00-001M-0000-000E-DDDF-4 . PMID   23260140.

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.