CHKA choline kinase alpha [Homo sapiens (human)] - Gene

Summary

Official Symbol: CHKAprovided by HGNC
Official Full Name: choline kinase alphaprovided by HGNC
Primary source: HGNC:HGNC:1937
See related: Ensembl:ENSG00000110721 MIM:118491
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: CK; EK; CHK; CKI
Summary: The major pathway for the biosynthesis of phosphatidylcholine occurs via the CDP-choline pathway. The protein encoded by this gene is the initial enzyme in the sequence and may play a regulatory role. The encoded protein also catalyzes the phosphorylation of ethanolamine. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Expression: Broad expression in testis (RPKM 24.3), thyroid (RPKM 9.0) and 25 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 11q13.2

Exon count:: 14

Annotation release	Status	Assembly	Chr	Location
109	current	GRCh38.p12 (GCF_000001405.38)	11	NC_000011.10 (68052859..68121391, complement)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	11	NC_000011.9 (67820326..67888858, complement)

Chromosome 11 - NC_000011.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

miR-876-5p was able to significantly decrease the expression level of choline kinase alpha mRNA.
Title: Downregulation of human choline kinase α gene expression by miR-876-5p.
There is no correlation between single CHKA rs7928739 polymorphism and the incidence of intrauterine fetal death.
Title: Polymorphic variants of genes involved in choline pathway and the risk of intrauterine fetal death.
This study presents the detail the 2.35 A structure of choline kinase alpha in complex with inhibitor TCD-717.
Title: Identification of a Unique Inhibitor-Binding Site on Choline Kinase α.
Results indicate that choline kinase alpha (CHKA) contributes to tumor progression and metastasis and may serve as a prognostic biomarker and potential therapeutic target in colorectal carcinoma (CRC).
Title: Overexpression of CHKA contributes to tumor progression and metastasis and predicts poor prognosis in colorectal carcinoma.
hCKalpha functions as an indispensable regulator that bridges PI4KIIIalpha and hepatitis C virus NS5A and potentiates NS5A-stimulated PI4KIIIalpha activity, which then facilitates the targeting of the ternary complex to the endoplasmic reticulum for viral replication.
Title: Hepatitis C Virus Subverts Human Choline Kinase-α To Bridge Phosphatidylinositol-4-Kinase IIIα (PI4KIIIα) and NS5A and Upregulates PI4KIIIα Activation, Thereby Promoting the Translocation of the Ternary Complex to the Endoplasmic Reticulum for Viral Replication.
We found levels of CHKA to be increased in human HCCs compared to nontumor tissues, and increased expression to be associated with tumor aggressiveness. Overexpression of CHKA in HCC cell lines increased their invasiveness, resistance to EGFR inhibitors, and ability to form metastatic tumors in mice by promoting interaction of EGFR with mechanistic target of rapamycin complex 2.
Title: Choline Kinase α Mediates Interactions Between the Epidermal Growth Factor Receptor and Mechanistic Target of Rapamycin Complex 2 in Hepatocellular Carcinoma Cells to Promote Drug Resistance and Xenograft Tumor Progression.
These findings demonstrate that hCKalpha forms a complex with hepatitis C virus NS5A and that hCKalpha activity enhances the targeting of the complex to the endoplasmic reticulum, where hCKalpha protein, not activity, mediates NS5A binding to NS5B, thereby promoting functional membranous viral replication complex assembly and viral RNA replication.
Title: Human Choline Kinase-α Promotes Hepatitis C Virus RNA Replication through Modulation of Membranous Viral Replication Complex Formation.
Study shows increased CHKA expression in pancreatic ductal adenocarcinoma tumors and may be a predictive marker of response to chemotherapy.
Title: Choline Kinase Alpha (CHKα) as a Therapeutic Target in Pancreatic Ductal Adenocarcinoma: Expression, Predictive Value, and Sensitivity to Inhibitors.
These data also support the approach of antitumor strategies that destabilize Chk-alpha protein or downregulate PtdCho in breast cancer treatment.
Title: Choline kinase-α protein and phosphatidylcholine but not phosphocholine are required for breast cancer cell survival.
Downregulation of choline kinase-alpha enhances autophagy in tamoxifen-resistant breast cancer cells.
Title: Downregulation of Choline Kinase-Alpha Enhances Autophagy in Tamoxifen-Resistant Breast Cancer Cells.

Submit: New GeneRIF Correction See all GeneRIFs (44)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Pathways from BioSystems

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Acetylcholine Synthesis, organism-specific biosystem (from WikiPathways)
Acetylcholine Synthesis, organism-specific biosystemAcetylcholine is an important neurotransmitter. It can be rapidly released in the synaptic cleft upon activation of the neuron. In the synaptic cleft the compound is degraded rapidly into choline and...
Choline metabolism in cancer, organism-specific biosystem (from KEGG)
Choline metabolism in cancer, organism-specific biosystemAbnormal choline metabolism is emerging as a metabolic hallmark that is associated with oncogenesis and tumour progression. Following transformation, oncogenic signalling via pathways such as the RAS...
Choline metabolism in cancer, conserved biosystem (from KEGG)
Choline metabolism in cancer, conserved biosystemAbnormal choline metabolism is emerging as a metabolic hallmark that is associated with oncogenesis and tumour progression. Following transformation, oncogenic signalling via pathways such as the RAS...
Glycerophospholipid biosynthesis, organism-specific biosystem (from REACTOME)
Glycerophospholipid biosynthesis, organism-specific biosystemGlycerophospholipids are important structural and functional components of biological membranes and constituents of serum lipoproteins and the pulmonary surfactant. In addition, glycerophospholipids...
Glycerophospholipid metabolism, organism-specific biosystem (from KEGG)
Glycerophospholipid metabolism, organism-specific biosystem
Glycerophospholipid metabolism
Glycerophospholipid metabolism, conserved biosystem (from KEGG)
Glycerophospholipid metabolism, conserved biosystem
Glycerophospholipid metabolism
Metabolic pathways, organism-specific biosystem (from KEGG)
Metabolic pathways, organism-specific biosystem
Metabolic pathways
Metabolism, organism-specific biosystem (from REACTOME)
Metabolism, organism-specific biosystemMetabolic processes in human cells generate energy through the oxidation of molecules consumed in the diet and mediate the synthesis of diverse essential molecules not taken in the diet as well as th...
Metabolism of lipids and lipoproteins, organism-specific biosystem (from REACTOME)
Metabolism of lipids and lipoproteins, organism-specific biosystemLipids are hydrophobic but otherwise chemically diverse molecules that play a wide variety of roles in human biology. They include ketone bodies, fatty acids, triacylglycerols, phospholipids and sphi...
Phosphatidylcholine (PC) biosynthesis, choline => PC, organism-specific biosystem (from KEGG)
Phosphatidylcholine (PC) biosynthesis, choline => PC, organism-specific biosystemPathway module; Carbohydrate and lipid metabolism; Lipid metabolism
Phosphatidylcholine (PC) biosynthesis, choline => PC, conserved biosystem (from KEGG)
Phosphatidylcholine (PC) biosynthesis, choline => PC, conserved biosystemPathway module; Carbohydrate and lipid metabolism; Lipid metabolism
Phosphatidylethanolamine (PE) biosynthesis, ethanolamine => PE, organism-specific biosystem (from KEGG)
Phosphatidylethanolamine (PE) biosynthesis, ethanolamine => PE, organism-specific biosystemPathway module; Carbohydrate and lipid metabolism; Lipid metabolism
Phosphatidylethanolamine (PE) biosynthesis, ethanolamine => PE, conserved biosystem (from KEGG)
Phosphatidylethanolamine (PE) biosynthesis, ethanolamine => PE, conserved biosystemPathway module; Carbohydrate and lipid metabolism; Lipid metabolism
Phospholipid metabolism, organism-specific biosystem (from REACTOME)
Phospholipid metabolism, organism-specific biosystemPhospholipids contain a polar head group and two long-chain fatty acyl moieties, one of which is generally unsaturated. The head group is a glycerol or serine phosphate attached to a polar group such...
Synthesis of PC, organism-specific biosystem (from REACTOME)
Synthesis of PC, organism-specific biosystemDe novo (Kennedy pathway) synthesis of phosphatidylcholine (PC) involves phosphorylation of choline (Cho) to phosphocholine (PCho) followed by condensing with cytidine triphosphate (CTP) to form CDP-...
Synthesis of PE, organism-specific biosystem (from REACTOME)
Synthesis of PE, organism-specific biosystemDe novo (Kennedy pathway) synthesis of phosphatidylethanolamine (PE) involves phosphorylation of ethanolamine (ETA) to phosphoethanolamine (PETA) followed by condensing with cytidine triphosphate (CT...
phosphatidylcholine biosynthesis, organism-specific biosystem (from BIOCYC)
phosphatidylcholine biosynthesis, organism-specific biosystem
phosphatidylcholine biosynthesis

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D11S2921 (e-PCR)
- UniSTS:152074

D10S275 (e-PCR)
- UniSTS:147992

D8S2279 (e-PCR)
- UniSTS:473907

D11S3651 (e-PCR)
- UniSTS:152885

sY3084 (e-PCR)
- UniSTS:515126

STS-H94874 (e-PCR)
- UniSTS:28484

L17709 (e-PCR)
- UniSTS:42599

D10S16 (e-PCR)
- UniSTS:155756

D15S1477 (e-PCR)
- UniSTS:474482

RH36905 (e-PCR)
- UniSTS:87932

RH47025 (e-PCR)
- UniSTS:52860

RH94200 (e-PCR)
- UniSTS:91011

D11S3114 (e-PCR)
- UniSTS:152207

CHKA_8254 (e-PCR)
- UniSTS:467604

WI-17872 (e-PCR)
- UniSTS:153

D11S4327 (e-PCR)
- UniSTS:10165

Homology

Homologs of the CHKA gene: The CHKA gene is conserved in chimpanzee, dog, cow, mouse, rat, chicken, zebrafish, C.elegans, A.thaliana, rice, and frog.
Orthologs from Annotation Pipeline: 220 organisms have orthologs with human gene CHKA
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
ATP binding	IEA Inferred from Electronic Annotation more info
choline binding	IEA Inferred from Electronic Annotation more info
choline kinase activity	IDA Inferred from Direct Assay more info	PubMed
choline kinase activity	TAS Traceable Author Statement more info
cholinesterase activity	IEA Inferred from Electronic Annotation more info
drug binding	IDA Inferred from Direct Assay more info	PubMed
ethanolamine kinase activity	IDA Inferred from Direct Assay more info	PubMed
ethanolamine kinase activity	TAS Traceable Author Statement more info
protein homodimerization activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
CDP-choline pathway	IEA Inferred from Electronic Annotation more info
choline metabolic process	IEA Inferred from Electronic Annotation more info
ethanolamine metabolic process	IEA Inferred from Electronic Annotation more info
lipid metabolic process	TAS Traceable Author Statement more info	PubMed
lipid transport	TAS Traceable Author Statement more info	PubMed
phosphatidylcholine biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
phosphatidylcholine biosynthetic process	TAS Traceable Author Statement more info
phosphatidylethanolamine biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
phosphatidylethanolamine biosynthetic process	IEA Inferred from Electronic Annotation more info
phosphatidylethanolamine biosynthetic process	TAS Traceable Author Statement more info
phosphorylation	IEA Inferred from Electronic Annotation more info
response to 3-methylcholanthrene	IEA Inferred from Electronic Annotation more info
response to toxic substance	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
cytosol	TAS Traceable Author Statement more info

General protein information

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Preferred Names: choline kinase alpha

Names: CHETK-alpha; ethanolamine kinase

NP_001268.2

EC 2.7.1.32

EC 2.7.1.82

NP_997634.1

EC 2.7.1.32

EC 2.7.1.82

XP_016872636.1

EC 2.7.1.32

EC 2.7.1.82

XP_016872637.1

EC 2.7.1.32

EC 2.7.1.82

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001277.3 → NP_001268.2 choline kinase alpha isoform a

See identical proteins and their annotated locations for NP_001268.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (a).

Source sequence(s)

BC036471, BG703955, BG723115, BI195927, BU617910, D10704

Consensus CDS

CCDS8178.1

UniProtKB/Swiss-Prot

P35790

Related

ENSP00000265689.4, ENST00000265689.8

Conserved Domains (2) summary

PLN02236
Location:99 → 455

PLN02236; choline kinase

cd05156
Location:111 → 452

ChoK_euk; Euykaryotic Choline Kinase
NM_212469.1 → NP_997634.1 choline kinase alpha isoform b

See identical proteins and their annotated locations for NP_997634.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (b) has the same N- and C-termini but is shorter compared to isoform a.

Source sequence(s)

AI809679, AK054792, BC036471, BE260889, BG703955, BG723115, BU617910, D10704

Consensus CDS

CCDS8179.1

UniProtKB/Swiss-Prot

P35790

Related

ENSP00000348454.4, ENST00000356135.9

Conserved Domains (2) summary

PLN02236
Location:99 → 437

PLN02236; choline kinase

cd05156
Location:111 → 434

ChoK_euk; Euykaryotic Choline Kinase