P35790 (CHKA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Choline kinase alpha
Short name=CK
EC=2.7.1.32

Alternative name(s):
CHETK-alpha
Ethanolamine kinase
Short name=EK
EC=2.7.1.82

Gene names

Name:	CHKA
Synonyms:	CHK, CKI

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	457 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Ref.4
Catalytic activity	ATP + choline = ADP + phosphocholine. Ref.4 ATP + ethanolamine = ADP + O-phosphoethanolamine. Ref.4
Pathway	Phospholipid metabolism; phosphatidylcholine biosynthesis; phosphocholine from choline: step 1/1. Phospholipid metabolism; phosphatidylethanolamine biosynthesis; phosphatidylethanolamine from ethanolamine: step 1/3.
Subunit structure	Heterodimer with CHKB By similarity. Homodimer. Ref.5
Subcellular location	Cytoplasm.
Sequence similarities	Belongs to the choline/ethanolamine kinase family.
Biophysicochemical properties	Kinetic parameters: KM=0.2 mM for choline Ref.4 Ref.5 KM=0.4 mM for ATP KM=12 mM for ethanolamine

Ontologies

Keywords
Biological process	Lipid biosynthesis Lipid metabolism Phospholipid biosynthesis Phospholipid metabolism
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	choline metabolic process Inferred from electronic annotation. Source: Compara lipid transport Traceable author statement PubMed 10363580. Source: ProtInc phosphatidylethanolamine biosynthetic process Inferred from direct assay Ref.4. Source: UniProtKB
Cellular_component	cytosol Traceable author statement. Source: Reactome
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW choline binding Inferred from electronic annotation. Source: Compara choline kinase activity Inferred from direct assay Ref.4. Source: UniProtKB cholinesterase activity Inferred from electronic annotation. Source: Compara drug binding Inferred from direct assay Ref.4. Source: UniProtKB ethanolamine kinase activity Inferred from direct assay Ref.4. Source: UniProtKB signal transducer activity Traceable author statement PubMed 10363580. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P35790-1)

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.

Isoform 2 (identifier: P35790-2)

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

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 457

457

Choline kinase alpha

PRO_0000206219

Regions

Nucleotide binding

117 – 123

7

ATP

Nucleotide binding

207 – 213

7

ATP

Region

119 – 121

3

Substrate binding

Compositional bias

50 – 85

36

Pro-rich

Sites

Binding site

146

1

ATP

Binding site

308

1

ATP Probable

Binding site

330

1

ATP

Natural variations

Alternative sequence

155 – 172

18

Missing in isoform 2.

VSP_009683

Natural variant

220

1

S → G. Ref.3
Corresponds to variant rs17853641 [ dbSNP | Ensembl ].

VAR_054863

Natural variant

422

1

L → Q. Ref.3
Corresponds to variant rs17853642 [ dbSNP | Ensembl ].

VAR_054864

Experimental info

Sequence conflict

49 – 54

6

GGQQPP → APTAA in BAA01547. Ref.1

Sequence conflict

87

1

T → A in BAA01547. Ref.1

Sequence conflict

154

1

M → V in BAA01547. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

457

Helix Strand Turn

Details...

Helix

85 – 98

14

Helix

101 – 103

3

Helix

108 – 110

3

Beta strand

112 – 117

6

Beta strand

119 – 128

10

Beta strand

136 – 138

3

Beta strand

141 – 149

9

Helix

175 – 189

15

Beta strand

196 – 200

5

Beta strand

203 – 207

5

Beta strand

211 – 213

3

Helix

216 – 220

5

Helix

222 – 236

15

Helix

248 – 262

15

Helix

268 – 278

11

Helix

282 – 294

13

Beta strand

300 – 303

4

Helix

309 – 311

3

Beta strand

312 – 315

4

Helix

318 – 320

3

Beta strand

322 – 324

3

Beta strand

326 – 328

3

Beta strand

335 – 338

4

Helix

339 – 349

11

Beta strand

352 – 354

3

Helix

366 – 368

3

Helix

372 – 386

15

Helix

388 – 392

5

Helix

395 – 430

36

Beta strand

433 – 435

3

Helix

437 – 456

20

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified April 14, 2009. Version 3. Checksum: 65F177ABE1AA3A12	FASTA	457	52,249
	10 20 30 40 50 60 MKTKFCTGGE AEPSPLGLLL SCGSGSAAPA PGVGQQRDAA SDLESKQLGG QQPPLALPPP 70 80 90 100 110 120 PPLPLPLPLP QPPPPQPPAD EQPEPRTRRR AYLWCKEFLP GAWRGLREDE FHISVIRGGL 130 140 150 160 170 180 SNMLFQCSLP DTTATLGDEP RKVLLRLYGA ILQMRSCNKE GSEQAQKENE FQGAEAMVLE 190 200 210 220 230 240 SVMFAILAER SLGPKLYGIF PQGRLEQFIP SRRLDTEELS LPDISAEIAE KMATFHGMKM 250 260 270 280 290 300 PFNKEPKWLF GTMEKYLKEV LRIKFTEESR IKKLHKLLSY NLPLELENLR SLLESTPSPV 310 320 330 340 350 360 VFCHNDCQEG NILLLEGREN SEKQKLMLID FEYSSYNYRG FDIGNHFCEW MYDYSYEKYP 370 380 390 400 410 420 FFRANIRKYP TKKQQLHFIS SYLPAFQNDF ENLSTEEKSI IKEEMLLEVN RFALASHFLW 430 440 450 GLWSIVQAKI SSIEFGYMDY AQARFDAYFH QKRKLGV
	Isoform 2 [UniParc]. Checksum: 73507D716F15F9E4	FASTA	439	50,155
	10 20 30 40 50 60 MKTKFCTGGE AEPSPLGLLL SCGSGSAAPA PGVGQQRDAA SDLESKQLGG QQPPLALPPP 70 80 90 100 110 120 PPLPLPLPLP QPPPPQPPAD EQPEPRTRRR AYLWCKEFLP GAWRGLREDE FHISVIRGGL 130 140 150 160 170 180 SNMLFQCSLP DTTATLGDEP RKVLLRLYGA ILQMGAEAMV LESVMFAILA ERSLGPKLYG 190 200 210 220 230 240 IFPQGRLEQF IPSRRLDTEE LSLPDISAEI AEKMATFHGM KMPFNKEPKW LFGTMEKYLK 250 260 270 280 290 300 EVLRIKFTEE SRIKKLHKLL SYNLPLELEN LRSLLESTPS PVVFCHNDCQ EGNILLLEGR 310 320 330 340 350 360 ENSEKQKLML IDFEYSSYNY RGFDIGNHFC EWMYDYSYEK YPFFRANIRK YPTKKQQLHF 370 380 390 400 410 420 ISSYLPAFQN DFENLSTEEK SIIKEEMLLE VNRFALASHF LWGLWSIVQA KISSIEFGYM 430 DYAQARFDAY FHQKRKLGV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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]	"Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y. Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract] 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.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

D10704 mRNA. Translation: BAA01547.1.
AP002807 Genomic DNA. No translation available.
AP002992 Genomic DNA. No translation available.
BC036471 mRNA. Translation: AAH36471.1.

IPI

IPI00409761.
IPI00409762.

PIR

S23104.

RefSeq

NP_001268.2. NM_001277.2.
NP_997634.1. NM_212469.1.

UniGene

Hs.77221.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2CKO	X-ray	2.15	A/B	50-439	[»]
2CKP	X-ray	3.10	A/B	50-439	[»]
2CKQ	X-ray	2.40	A/B	50-457	[»]
2I7Q	X-ray	1.90	A	75-457	[»]
3F2R	X-ray	2.35	A/B	75-457	[»]
3G15	X-ray	1.70	A/B	75-457	[»]
3ZM9	X-ray	1.90	A/B	75-457	[»]

ProteinModelPortal

P35790.

ModBase

Search...

Protein-protein interaction databases

IntAct

P35790. 1 interaction.

STRING

9606.ENSP00000265689.

PTM databases

PhosphoSite

P35790.

Polymorphism databases

DMDM

226694197.

Proteomic databases

PaxDb

P35790.

PRIDE

P35790.

Protocols and materials databases

DNASU

1119.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000265689; ENSP00000265689; ENSG00000110721.
ENST00000356135; ENSP00000348454; ENSG00000110721.

GeneID

1119.

KEGG

hsa:1119.

UCSC

uc001onj.3. human.
uc001onk.3. human.

Organism-specific databases

CTD

1119.

GeneCards

GC11M067820.

H-InvDB

HIX0017419.

HGNC

HGNC:1937. CHKA.

HPA

HPA024153.

MIM

118491. gene.

neXtProt

NX_P35790.

PharmGKB

PA26468.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0510.

HOGENOM

HOG000041274.

HOVERGEN

HBG050943.

InParanoid

P35790.

KO

K14156.

OMA

TRRRAYL.

OrthoDB

EOG49GKH0.

PhylomeDB

P35790.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.

SABIO-RK

P35790.

UniPathway

UPA00558; UER00741.
UPA00753; UER00737.

Gene expression databases

ArrayExpress

P35790.

Bgee

P35790.

CleanEx

HS_CHKA.

Genevestigator

P35790.

GermOnline

ENSG00000110721. Homo sapiens.

Family and domain databases

InterPro

IPR026712. Cho/Etha_kinase.
IPR011009. Kinase-like_dom.
[Graphical view]

PANTHER

PTHR22603. PTHR22603. 1 hit.

SUPFAM

SSF56112. Kinase_like. 1 hit.

ProtoNet

Search...

Other

BindingDB

P35790.

ChEMBL

CHEMBL3117.

ChiTaRS

CHKA. human.

DrugBank

DB00122. Choline.

EvolutionaryTrace

P35790.

GenomeRNAi

1119.

NextBio

4642.

SOURCE

Search...

Entry information

Entry name

CHKA_HUMAN

Accession

Primary (citable) accession number: P35790
Secondary accession number(s): Q8NE29

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 1994
Last sequence update:	April 14, 2009
Last modified:	May 1, 2013
This is version 118 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.