CHKA_RAT
ID CHKA_RAT Reviewed; 453 AA.
AC Q01134; Q63114;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2000, sequence version 2.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=Choline kinase alpha;
DE Short=CK;
DE EC=2.7.1.32 {ECO:0000250|UniProtKB:P35790};
DE AltName: Full=CHETK-alpha;
DE AltName: Full=Ethanolamine kinase;
DE Short=EK;
DE EC=2.7.1.82 {ECO:0000250|UniProtKB:P35790};
GN Name=Chka; Synonyms=Chk, Ckr;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND TISSUE SPECIFICITY.
RC STRAIN=Wistar; TISSUE=Liver;
RX PubMed=1577786; DOI=10.1016/s0021-9258(19)50213-7;
RA Uchida T., Yamashita S.;
RT "Molecular cloning, characterization, and expression in Escherichia coli of
RT a cDNA encoding mammalian choline kinase.";
RL J. Biol. Chem. 267:10156-10162(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
RC STRAIN=Sprague-Dawley, and Wistar; TISSUE=Liver, and Testis;
RX PubMed=7852267; DOI=10.1093/oxfordjournals.jbchem.a124554;
RA Uchida T.;
RT "Regulation of choline kinase R: analyses of alternatively spliced choline
RT kinases and the promoter region.";
RL J. Biochem. 116:508-518(1994).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-71, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Plays a key role in phospholipid biosynthesis by catalyzing
CC the phosphorylation of free choline to phosphocholine, the first step
CC in phosphatidylcholine biosynthesis. Also phosphorylates ethanolamine,
CC thereby contributing to phosphatidylethanolamine biosynthesis. Has
CC higher activity with choline. May contribute to tumor cell growth.
CC {ECO:0000250|UniProtKB:P35790}.
CC -!- FUNCTION: [Isoform 1]: This isoform plays a key role in lipolysis of
CC lipid droplets following glucose deprivation (By similarity). In
CC response to glucose deprivation, phosphorylated by AMPK, promoting
CC localization to lipid droplets (By similarity). Phosphorylation is
CC followed by acetylation by KAT5, leading to dissociation of the
CC homodimer into a monomer (By similarity). Monomeric CHKA isoform 1 is
CC converted into a tyrosine-protein kinase, which phosphorylates lipid
CC droplet structural proteins PLIN2 and PLIN3, leading to lipolysis of
CC lipid droplets (By similarity). {ECO:0000250|UniProtKB:P35790}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + choline = ADP + H(+) + phosphocholine;
CC Xref=Rhea:RHEA:12837, ChEBI:CHEBI:15354, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:295975, ChEBI:CHEBI:456216;
CC EC=2.7.1.32; Evidence={ECO:0000250|UniProtKB:P35790};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12838;
CC Evidence={ECO:0000250|UniProtKB:P35790};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + ethanolamine = ADP + H(+) + phosphoethanolamine;
CC Xref=Rhea:RHEA:13069, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:57603, ChEBI:CHEBI:58190, ChEBI:CHEBI:456216;
CC EC=2.7.1.82; Evidence={ECO:0000250|UniProtKB:P35790};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13070;
CC Evidence={ECO:0000250|UniProtKB:P35790};
CC -!- CATALYTIC ACTIVITY: [Isoform 1]:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:P35790};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10597;
CC Evidence={ECO:0000250|UniProtKB:P35790};
CC -!- PATHWAY: Phospholipid metabolism; phosphatidylcholine biosynthesis;
CC phosphocholine from choline: step 1/1. {ECO:0000250|UniProtKB:P35790}.
CC -!- PATHWAY: Phospholipid metabolism; phosphatidylethanolamine
CC biosynthesis; phosphatidylethanolamine from ethanolamine: step 1/3.
CC {ECO:0000250|UniProtKB:P35790}.
CC -!- SUBUNIT: Heterodimer with CHKB (By similarity). Homodimer (By
CC similarity). {ECO:0000250|UniProtKB:O54804}.
CC -!- SUBUNIT: [Isoform 1]: Monomer; acetylation by KAT5 promotes
CC dissociation of the homodimer and monomerization.
CC {ECO:0000250|UniProtKB:P35790}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:P35790}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Lipid droplet
CC {ECO:0000250|UniProtKB:P35790}. Note=Isoform 1 localizes to lipid
CC droplets following phosphorylation by AMPK.
CC {ECO:0000250|UniProtKB:P35790}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=R2;
CC IsoId=Q01134-1; Sequence=Displayed;
CC Name=2; Synonyms=R1;
CC IsoId=Q01134-2; Sequence=VSP_001067;
CC -!- TISSUE SPECIFICITY: Testis, brain, lung, kidney and liver.
CC {ECO:0000269|PubMed:1577786}.
CC -!- PTM: [Isoform 1]: Phosphorylated at Ser-275 by AMPK in response to
CC glucose deprivation, leading to localization to lipid droplets.
CC {ECO:0000250|UniProtKB:P35790}.
CC -!- PTM: [Isoform 1]: Acetylated by KAT5 at Lys-243 following
CC phosphorylation by AMPK, leading to monomerization and conversion into
CC a tyrosine-protein kinase. {ECO:0000250|UniProtKB:P35790}.
CC -!- SIMILARITY: Belongs to the choline/ethanolamine kinase family.
CC {ECO:0000305}.
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DR EMBL; D10261; BAA01102.1; -; mRNA.
DR EMBL; D37884; BAA07126.1; -; Genomic_DNA.
DR EMBL; D37885; BAA07127.1; -; mRNA.
DR PIR; A42672; A42672.
DR PIR; JX0342; JX0342.
DR RefSeq; NP_058823.1; NM_017127.1. [Q01134-2]
DR RefSeq; XP_006230770.1; XM_006230708.3. [Q01134-1]
DR AlphaFoldDB; Q01134; -.
DR SMR; Q01134; -.
DR STRING; 10116.ENSRNOP00000023020; -.
DR iPTMnet; Q01134; -.
DR PhosphoSitePlus; Q01134; -.
DR PaxDb; Q01134; -.
DR PRIDE; Q01134; -.
DR Ensembl; ENSRNOT00000022824; ENSRNOP00000022824; ENSRNOG00000016791. [Q01134-2]
DR Ensembl; ENSRNOT00000023020; ENSRNOP00000023020; ENSRNOG00000016791. [Q01134-1]
DR GeneID; 29194; -.
DR KEGG; rno:29194; -.
DR UCSC; RGD:61944; rat. [Q01134-1]
DR CTD; 1119; -.
DR RGD; 61944; Chka.
DR eggNOG; KOG2686; Eukaryota.
DR GeneTree; ENSGT00950000182939; -.
DR HOGENOM; CLU_012712_2_1_1; -.
DR InParanoid; Q01134; -.
DR OMA; HEWTADY; -.
DR OrthoDB; 1469912at2759; -.
DR PhylomeDB; Q01134; -.
DR TreeFam; TF313549; -.
DR Reactome; R-RNO-1483191; Synthesis of PC.
DR Reactome; R-RNO-1483213; Synthesis of PE.
DR SABIO-RK; Q01134; -.
DR UniPathway; UPA00558; UER00741.
DR UniPathway; UPA00753; UER00737.
DR PRO; PR:Q01134; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000016791; Expressed in liver and 20 other tissues.
DR ExpressionAtlas; Q01134; baseline and differential.
DR Genevisible; Q01134; RN.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005811; C:lipid droplet; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IDA:RGD.
DR GO; GO:0033265; F:choline binding; IDA:RGD.
DR GO; GO:0004103; F:choline kinase activity; IDA:RGD.
DR GO; GO:0004104; F:cholinesterase activity; ISO:RGD.
DR GO; GO:0004305; F:ethanolamine kinase activity; IDA:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0004713; F:protein tyrosine kinase activity; ISS:UniProtKB.
DR GO; GO:0006657; P:CDP-choline pathway; IBA:GO_Central.
DR GO; GO:0042149; P:cellular response to glucose starvation; ISS:UniProtKB.
DR GO; GO:0019695; P:choline metabolic process; IDA:RGD.
DR GO; GO:0006580; P:ethanolamine metabolic process; IDA:RGD.
DR GO; GO:1905691; P:lipid droplet disassembly; ISS:UniProtKB.
DR GO; GO:0006656; P:phosphatidylcholine biosynthetic process; ISS:UniProtKB.
DR GO; GO:0006646; P:phosphatidylethanolamine biosynthetic process; ISS:UniProtKB.
DR GO; GO:1904681; P:response to 3-methylcholanthrene; IEP:RGD.
DR GO; GO:0009636; P:response to toxic substance; IEP:RGD.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR SUPFAM; SSF56112; SSF56112; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; ATP-binding; Cytoplasm; Kinase;
KW Lipid biosynthesis; Lipid droplet; Lipid metabolism; Nucleotide-binding;
KW Phospholipid biosynthesis; Phospholipid metabolism; Phosphoprotein;
KW Reference proteome; Transferase.
FT CHAIN 1..453
FT /note="Choline kinase alpha"
FT /id="PRO_0000206221"
FT REGION 22..81
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 53..77
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 113..119
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P35790"
FT BINDING 115..117
FT /ligand="phosphocholine"
FT /ligand_id="ChEBI:CHEBI:295975"
FT /evidence="ECO:0000250|UniProtKB:P35790"
FT BINDING 142
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P35790"
FT BINDING 203..209
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P35790"
FT BINDING 304
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P35790"
FT BINDING 326
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P35790"
FT MOD_RES 71
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 243
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P35790"
FT MOD_RES 275
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P35790"
FT VAR_SEQ 151..168
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_001067"
SQ SEQUENCE 453 AA; 51824 MW; DBF5643F321F0A2E CRC64;
MKTKFCTGGE AEPSPLGLLL SCGGSAAPTP GVGQQRDAAG ELESKQLGGR SQPLALPPPP
PPPLPLPPPP SPPLADEQPE PRTRRRAYLW CKEFLPGAWR GLREDQFHIS VIRGGLSNML
FQCSLPDSIA SVGDEPRKVL LRLYGAILKM RSCNKEGSEQ AQNENEFQGA EAMVLESVMF
AILAERSLGP KLYGIFPQGR LEQFIPSRRL DTEELCLPDI SAEIAEKMAT FHGMKMPFNK
EPKWLFGTME KYLNQVLRLK FSREARVQQL HKFLSYNLPL ELENLRSLLQ YTRSPVVFCH
NDCQEGNILL LEGQENSEKQ KLMLIDFEYS SYNYRGFDIG NHFCEWMYDY TYEKYPFFRA
NIQKYPTRKQ QLHFISSYLT TFQNDFESLS SEEQSATKED MLLEVNRFAL ASHFLWGLWS
IVQAKISSIE FGYMEYAQAR FDAYFDQKRK LGV
