Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Choline kinase alpha

Gene

CHKA

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Has a key role in phospholipid biosynthesis and may contribute to tumor cell growth. Catalyzes the first step in phosphatidylcholine biosynthesis. Contributes to phosphatidylethanolamine biosynthesis. Phosphorylates choline and ethanolamine. Has higher activity with choline.1 Publication

Catalytic activityi

ATP + choline = ADP + phosphocholine.1 Publication
ATP + ethanolamine = ADP + O-phosphoethanolamine.1 Publication

Kineticsi

  1. KM=0.2 mM for choline2 Publications
  2. KM=0.4 mM for ATP2 Publications
  3. KM=12 mM for ethanolamine2 Publications

    Pathway: phosphatidylcholine biosynthesis

    This protein is involved in step 1 of the subpathway that synthesizes phosphocholine from choline.
    Proteins known to be involved in this subpathway in this organism are:
    1. Choline kinase alpha (CHKA)
    This subpathway is part of the pathway phosphatidylcholine biosynthesis, which is itself part of Phospholipid metabolism.
    View all proteins of this organism that are known to be involved in the subpathway that synthesizes phosphocholine from choline, the pathway phosphatidylcholine biosynthesis and in Phospholipid metabolism.

    Pathway: phosphatidylethanolamine biosynthesis

    This protein is involved in step 1 of the subpathway that synthesizes phosphatidylethanolamine from ethanolamine.
    Proteins known to be involved in the 3 steps of the subpathway in this organism are:
    1. Choline/ethanolamine kinase (CHKB), Ethanolamine kinase 2 (ETNK2), Choline kinase alpha (CHKA), Ethanolamine kinase 1 (ETNK1)
    2. Ethanolamine-phosphate cytidylyltransferase (PCYT2)
    3. Ethanolaminephosphotransferase 1 (EPT1), Choline/ethanolaminephosphotransferase 1 (CEPT1)
    This subpathway is part of the pathway phosphatidylethanolamine biosynthesis, which is itself part of Phospholipid metabolism.
    View all proteins of this organism that are known to be involved in the subpathway that synthesizes phosphatidylethanolamine from ethanolamine, the pathway phosphatidylethanolamine biosynthesis and in Phospholipid metabolism.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei146 – 1461ATP
    Binding sitei308 – 3081ATPCurated
    Binding sitei330 – 3301ATP

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi117 – 1237ATP
    Nucleotide bindingi207 – 2137ATP

    GO - Molecular functioni

    • ATP binding Source: UniProtKB-KW
    • choline binding Source: Ensembl
    • choline kinase activity Source: UniProtKB
    • cholinesterase activity Source: Ensembl
    • drug binding Source: UniProtKB
    • ethanolamine kinase activity Source: UniProtKB
    • signal transducer activity Source: ProtInc

    GO - Biological processi

    • CDP-choline pathway Source: GOC
    • choline metabolic process Source: Ensembl
    • glycerophospholipid biosynthetic process Source: Reactome
    • lipid metabolic process Source: ProtInc
    • lipid transport Source: ProtInc
    • phosphatidylcholine biosynthetic process Source: UniProtKB
    • phosphatidylethanolamine biosynthetic process Source: UniProtKB
    • phospholipid metabolic process Source: Reactome
    • signal transduction Source: GOC
    • small molecule metabolic process Source: Reactome
    Complete GO annotation...

    Keywords - Molecular functioni

    Kinase, Transferase

    Keywords - Biological processi

    Lipid biosynthesis, Lipid metabolism, Phospholipid biosynthesis, Phospholipid metabolism

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    BRENDAi2.7.1.32. 2681.
    ReactomeiREACT_120919. Synthesis of PE.
    REACT_121238. Synthesis of PC.
    SABIO-RKP35790.
    UniPathwayiUPA00558; UER00741.
    UPA00753; UER00737.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Choline kinase alpha (EC:2.7.1.32)
    Short name:
    CK
    Alternative name(s):
    CHETK-alpha
    Ethanolamine kinase (EC:2.7.1.82)
    Short name:
    EK
    Gene namesi
    Name:CHKA
    Synonyms:CHK, CKI
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640 Componenti: Chromosome 11

    Organism-specific databases

    HGNCiHGNC:1937. CHKA.

    Subcellular locationi

    GO - Cellular componenti

    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA26468.

    Chemistry

    DrugBankiDB00122. Choline.

    Polymorphism and mutation databases

    BioMutaiCHKA.
    DMDMi226694197.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 457457Choline kinase alphaPRO_0000206219Add
    BLAST

    Proteomic databases

    MaxQBiP35790.
    PaxDbiP35790.
    PRIDEiP35790.

    PTM databases

    PhosphoSiteiP35790.

    Expressioni

    Gene expression databases

    BgeeiP35790.
    CleanExiHS_CHKA.
    ExpressionAtlasiP35790. baseline and differential.
    GenevisibleiP35790. HS.

    Organism-specific databases

    HPAiHPA024153.

    Interactioni

    Subunit structurei

    Heterodimer with CHKB (By similarity). Homodimer.By similarity2 Publications

    Protein-protein interaction databases

    BioGridi107543. 6 interactions.
    IntActiP35790. 1 interaction.
    STRINGi9606.ENSP00000265689.

    Structurei

    Secondary structure

    1
    457
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi85 – 9814Combined sources
    Helixi101 – 1033Combined sources
    Helixi108 – 1103Combined sources
    Beta strandi112 – 1176Combined sources
    Beta strandi119 – 12810Combined sources
    Beta strandi136 – 1383Combined sources
    Beta strandi141 – 1499Combined sources
    Helixi175 – 18915Combined sources
    Beta strandi196 – 2005Combined sources
    Beta strandi203 – 2075Combined sources
    Beta strandi211 – 2133Combined sources
    Helixi216 – 2205Combined sources
    Helixi222 – 23615Combined sources
    Helixi248 – 26215Combined sources
    Helixi268 – 27811Combined sources
    Helixi282 – 29413Combined sources
    Beta strandi300 – 3034Combined sources
    Helixi309 – 3113Combined sources
    Beta strandi312 – 3154Combined sources
    Helixi318 – 3203Combined sources
    Beta strandi322 – 3243Combined sources
    Beta strandi326 – 3283Combined sources
    Beta strandi335 – 3384Combined sources
    Helixi339 – 34911Combined sources
    Beta strandi352 – 3543Combined sources
    Helixi366 – 3683Combined sources
    Helixi372 – 38615Combined sources
    Helixi388 – 3925Combined sources
    Helixi395 – 43036Combined sources
    Beta strandi433 – 4353Combined sources
    Helixi437 – 45620Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2CKOX-ray2.15A/B50-457[»]
    2CKPX-ray3.10A/B50-457[»]
    2CKQX-ray2.40A/B50-457[»]
    2I7QX-ray1.90A75-457[»]
    3F2RX-ray2.35A/B75-457[»]
    3G15X-ray1.70A/B75-457[»]
    3ZM9X-ray1.90A/B75-457[»]
    4BR3X-ray2.20A/B75-457[»]
    4CG8X-ray1.75A75-457[»]
    4CG9X-ray1.83A75-457[»]
    4CGAX-ray1.74A75-457[»]
    4DA5X-ray2.40A/B1-457[»]
    5AFVX-ray2.25A/B80-457[»]
    ProteinModelPortaliP35790.
    SMRiP35790. Positions 81-457.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP35790.

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni119 – 1213Substrate binding

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi50 – 8536Pro-richAdd
    BLAST

    Sequence similaritiesi

    Belongs to the choline/ethanolamine kinase family.Curated

    Phylogenomic databases

    eggNOGiCOG0510.
    GeneTreeiENSGT00530000062991.
    HOGENOMiHOG000041274.
    HOVERGENiHBG050943.
    InParanoidiP35790.
    KOiK14156.
    OMAiRAYLWCK.
    OrthoDBiEOG72VH68.
    PhylomeDBiP35790.
    TreeFamiTF313549.

    Family and domain databases

    InterProiIPR011009. Kinase-like_dom.
    [Graphical view]
    SUPFAMiSSF56112. SSF56112. 1 hit.

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: P35790-1) [UniParc]FASTAAdd to basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

            10         20         30         40         50
    MKTKFCTGGE AEPSPLGLLL SCGSGSAAPA PGVGQQRDAA SDLESKQLGG
    60 70 80 90 100
    QQPPLALPPP PPLPLPLPLP QPPPPQPPAD EQPEPRTRRR AYLWCKEFLP
    110 120 130 140 150
    GAWRGLREDE FHISVIRGGL SNMLFQCSLP DTTATLGDEP RKVLLRLYGA
    160 170 180 190 200
    ILQMRSCNKE GSEQAQKENE FQGAEAMVLE SVMFAILAER SLGPKLYGIF
    210 220 230 240 250
    PQGRLEQFIP SRRLDTEELS LPDISAEIAE KMATFHGMKM PFNKEPKWLF
    260 270 280 290 300
    GTMEKYLKEV LRIKFTEESR IKKLHKLLSY NLPLELENLR SLLESTPSPV
    310 320 330 340 350
    VFCHNDCQEG NILLLEGREN SEKQKLMLID FEYSSYNYRG FDIGNHFCEW
    360 370 380 390 400
    MYDYSYEKYP FFRANIRKYP TKKQQLHFIS SYLPAFQNDF ENLSTEEKSI
    410 420 430 440 450
    IKEEMLLEVN RFALASHFLW GLWSIVQAKI SSIEFGYMDY AQARFDAYFH

    QKRKLGV
    Length:457
    Mass (Da):52,249
    Last modified:April 14, 2009 - v3
    Checksum:i65F177ABE1AA3A12
    GO
    Isoform 2 (identifier: P35790-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         155-172: Missing.

    Show »
    Length:439
    Mass (Da):50,155
    Checksum:i73507D716F15F9E4
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti49 – 546GGQQPP → APTAA in BAA01547 (PubMed:1618328).Curated
    Sequence conflicti87 – 871T → A in BAA01547 (PubMed:1618328).Curated
    Sequence conflicti154 – 1541M → V in BAA01547 (PubMed:1618328).Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti220 – 2201S → G.1 Publication
    Corresponds to variant rs17853641 [ dbSNP | Ensembl ].
    VAR_054863
    Natural varianti422 – 4221L → Q.1 Publication
    Corresponds to variant rs17853642 [ dbSNP | Ensembl ].
    VAR_054864

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei155 – 17218Missing in isoform 2. 1 PublicationVSP_009683Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    D10704 mRNA. Translation: BAA01547.1.
    AP002807 Genomic DNA. No translation available.
    AP002992 Genomic DNA. No translation available.
    BC036471 mRNA. Translation: AAH36471.1.
    CCDSiCCDS8178.1. [P35790-1]
    CCDS8179.1. [P35790-2]
    PIRiS23104.
    RefSeqiNP_001268.2. NM_001277.2. [P35790-1]
    NP_997634.1. NM_212469.1. [P35790-2]
    UniGeneiHs.77221.

    Genome annotation databases

    EnsembliENST00000265689; ENSP00000265689; ENSG00000110721. [P35790-1]
    ENST00000356135; ENSP00000348454; ENSG00000110721. [P35790-2]
    GeneIDi1119.
    KEGGihsa:1119.
    UCSCiuc001onj.3. human. [P35790-1]
    uc001onk.3. human. [P35790-2]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    D10704 mRNA. Translation: BAA01547.1.
    AP002807 Genomic DNA. No translation available.
    AP002992 Genomic DNA. No translation available.
    BC036471 mRNA. Translation: AAH36471.1.
    CCDSiCCDS8178.1. [P35790-1]
    CCDS8179.1. [P35790-2]
    PIRiS23104.
    RefSeqiNP_001268.2. NM_001277.2. [P35790-1]
    NP_997634.1. NM_212469.1. [P35790-2]
    UniGeneiHs.77221.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2CKOX-ray2.15A/B50-457[»]
    2CKPX-ray3.10A/B50-457[»]
    2CKQX-ray2.40A/B50-457[»]
    2I7QX-ray1.90A75-457[»]
    3F2RX-ray2.35A/B75-457[»]
    3G15X-ray1.70A/B75-457[»]
    3ZM9X-ray1.90A/B75-457[»]
    4BR3X-ray2.20A/B75-457[»]
    4CG8X-ray1.75A75-457[»]
    4CG9X-ray1.83A75-457[»]
    4CGAX-ray1.74A75-457[»]
    4DA5X-ray2.40A/B1-457[»]
    5AFVX-ray2.25A/B80-457[»]
    ProteinModelPortaliP35790.
    SMRiP35790. Positions 81-457.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi107543. 6 interactions.
    IntActiP35790. 1 interaction.
    STRINGi9606.ENSP00000265689.

    Chemistry

    BindingDBiP35790.
    ChEMBLiCHEMBL3117.
    DrugBankiDB00122. Choline.

    PTM databases

    PhosphoSiteiP35790.

    Polymorphism and mutation databases

    BioMutaiCHKA.
    DMDMi226694197.

    Proteomic databases

    MaxQBiP35790.
    PaxDbiP35790.
    PRIDEiP35790.

    Protocols and materials databases

    DNASUi1119.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000265689; ENSP00000265689; ENSG00000110721. [P35790-1]
    ENST00000356135; ENSP00000348454; ENSG00000110721. [P35790-2]
    GeneIDi1119.
    KEGGihsa:1119.
    UCSCiuc001onj.3. human. [P35790-1]
    uc001onk.3. human. [P35790-2]

    Organism-specific databases

    CTDi1119.
    GeneCardsiGC11M067820.
    H-InvDBHIX0017419.
    HGNCiHGNC:1937. CHKA.
    HPAiHPA024153.
    MIMi118491. gene.
    neXtProtiNX_P35790.
    PharmGKBiPA26468.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiCOG0510.
    GeneTreeiENSGT00530000062991.
    HOGENOMiHOG000041274.
    HOVERGENiHBG050943.
    InParanoidiP35790.
    KOiK14156.
    OMAiRAYLWCK.
    OrthoDBiEOG72VH68.
    PhylomeDBiP35790.
    TreeFamiTF313549.

    Enzyme and pathway databases

    UniPathwayiUPA00558; UER00741.
    UPA00753; UER00737.
    BRENDAi2.7.1.32. 2681.
    ReactomeiREACT_120919. Synthesis of PE.
    REACT_121238. Synthesis of PC.
    SABIO-RKP35790.

    Miscellaneous databases

    ChiTaRSiCHKA. human.
    EvolutionaryTraceiP35790.
    GeneWikiiCHKA.
    GenomeRNAii1119.
    NextBioi4642.
    PROiP35790.
    SOURCEiSearch...

    Gene expression databases

    BgeeiP35790.
    CleanExiHS_CHKA.
    ExpressionAtlasiP35790. baseline and differential.
    GenevisibleiP35790. HS.

    Family and domain databases

    InterProiIPR011009. Kinase-like_dom.
    [Graphical view]
    SUPFAMiSSF56112. SSF56112. 1 hit.
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "Cloning of a human choline kinase cDNA by complementation of the yeast cki mutation."
      Hosaka K., Tanaka S., Nikawa J., Yamashita S.
      FEBS Lett. 304:229-232(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANTS GLY-220 AND GLN-422.
      Tissue: Testis.
    4. "Differential role of human choline kinase alpha and beta enzymes in lipid metabolism: implications in cancer onset and treatment."
      Gallego-Ortega D., Ramirez de Molina A., Ramos M.A., Valdes-Mora F., Barderas M.G., Sarmentero-Estrada J., Lacal J.C.
      PLoS ONE 4:E7819-E7819(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES.
    5. "Elucidation of human choline kinase crystal structures in complex with the products ADP or phosphocholine."
      Malito E., Sekulic N., Too W.C., Konrad M., Lavie A.
      J. Mol. Biol. 364:136-151(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 50-439 IN COMPLEX WITH ADP AND PHOSPHOCHOLINE, SUBUNIT, BIOPHYSICOCHEMICAL PROPERTIES.
    6. "Crystal structures of human choline kinase isoforms in complex with hemicholinium-3: single amino acid near the active site influences inhibitor sensitivity."
      Hong B.S., Allali-Hassani A., Tempel W., Finerty P.J. Jr., Mackenzie F., Dimov S., Vedadi M., Park H.W.
      J. Biol. Chem. 285:16330-16340(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 75-457 IN COMPLEX WITH HEMICHOLINIUM-3 AND ADP.

    Entry informationi

    Entry nameiCHKA_HUMAN
    AccessioniPrimary (citable) accession number: P35790
    Secondary accession number(s): Q8NE29
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: June 1, 1994
    Last sequence update: April 14, 2009
    Last modified: June 24, 2015
    This is version 140 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 11
      Human chromosome 11: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    6. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    7. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.