CKA2_CAEEL
ID CKA2_CAEEL Reviewed; 429 AA.
AC Q22942; Q2XN11;
DT 04-MAR-2015, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 2.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=Choline kinase A2 {ECO:0000303|PubMed:12758145};
DE EC=2.7.1.32 {ECO:0000269|PubMed:12758145, ECO:0000269|PubMed:14960577};
DE AltName: Full=Ethanolamine kinase {ECO:0000303|PubMed:12758145};
DE EC=2.7.1.82 {ECO:0000269|PubMed:12758145};
GN Name=cka-2 {ECO:0000312|WormBase:C52B9.1a};
GN ORFNames=C52B9.1 {ECO:0000312|WormBase:C52B9.1a};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), FUNCTION, CATALYTIC ACTIVITY,
RP COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, PATHWAY, AND SUBUNIT.
RX PubMed=12758145; DOI=10.1016/s1570-9639(03)00106-7;
RA Gee P., Kent C.;
RT "Multiple isoforms of choline kinase from Caenorhabditis elegans: cloning,
RT expression, purification, and characterization.";
RL Biochim. Biophys. Acta 1648:33-42(2003).
RN [2] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND ALTERNATIVE SPLICING.
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [3] {ECO:0000305}
RP CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND MUTAGENESIS OF SER-86; ARG-111; GLU-125; HIS-253; ASN-254;
RP ASP-255; ASN-260; ASP-301; GLU-303; GLU-320 AND TRP-387.
RX PubMed=14960577; DOI=10.1074/jbc.m401382200;
RA Yuan C., Kent C.;
RT "Identification of critical residues of choline kinase A2 from
RT Caenorhabditis elegans.";
RL J. Biol. Chem. 279:17801-17809(2004).
RN [4] {ECO:0000312|PDB:1NW1}
RP X-RAY CRYSTALLOGRAPHY (2.02 ANGSTROMS) IN COMPLEX WITH CALCIUM, AND
RP SUBUNIT.
RX PubMed=12791258; DOI=10.1016/s0969-2126(03)00094-7;
RA Peisach D., Gee P., Kent C., Xu Z.;
RT "The crystal structure of choline kinase reveals a eukaryotic protein
RT kinase fold.";
RL Structure 11:703-713(2003).
CC -!- FUNCTION: Catalyzes the first step in phosphatidylcholine biosynthesis.
CC May contribute to phosphatidylethanolamine biosynthesis. Phosphorylates
CC choline and ethanolamine but the activity is much higher with choline.
CC {ECO:0000269|PubMed:12758145, ECO:0000269|PubMed:14960577}.
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:0000269|PubMed:12758145,
CC ECO:0000269|PubMed:14960577};
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:0000269|PubMed:12758145};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:12758145, ECO:0000269|PubMed:14960577};
CC Note=Mn(2+) is a poor substitute (PubMed:12758145).
CC {ECO:0000269|PubMed:12758145};
CC -!- ACTIVITY REGULATION: Inhibited by Ca(2+). Mild inhibition by high
CC levels of Mg(2+)(>10 mM) (PubMed:14960577).
CC {ECO:0000269|PubMed:14960577}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.6 mM for choline (at 37 degrees Celsius and pH 10)
CC {ECO:0000269|PubMed:12758145};
CC KM=2.4 mM for ATP (at 37 degrees Celsius and pH 10)
CC {ECO:0000269|PubMed:12758145};
CC KM=103 uM for Mg(2+) (at 37 degrees Celsius and pH 10)
CC {ECO:0000269|PubMed:14960577};
CC Vmax=90 umol/min/mg enzyme (at 37 degrees Celsius and pH 10)
CC {ECO:0000269|PubMed:12758145};
CC pH dependence:
CC Optimum pH is 10. {ECO:0000269|PubMed:12758145};
CC -!- PATHWAY: Phospholipid metabolism; phosphatidylcholine biosynthesis;
CC phosphocholine from choline: step 1/1. {ECO:0000269|PubMed:12758145}.
CC -!- PATHWAY: Phospholipid metabolism; phosphatidylethanolamine
CC biosynthesis; phosphatidylethanolamine from ethanolamine: step 1/3.
CC {ECO:0000305|PubMed:12758145}.
CC -!- SUBUNIT: Homodimer (PubMed:12791258, PubMed:12758145). A small
CC proportion exists as higher oligomers (PubMed:12758145).
CC {ECO:0000269|PubMed:12758145, ECO:0000269|PubMed:12791258}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=a {ECO:0000312|WormBase:C52B9.1a};
CC IsoId=Q22942-1; Sequence=Displayed;
CC Name=b {ECO:0000312|WormBase:C52B9.1b};
CC IsoId=Q22942-2; Sequence=VSP_057474;
CC -!- SIMILARITY: Belongs to the choline/ethanolamine kinase family.
CC {ECO:0000305}.
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DR EMBL; FO080644; CCD65407.1; -; Genomic_DNA.
DR EMBL; FO080644; CCD65408.1; -; Genomic_DNA.
DR RefSeq; NP_001024480.1; NM_001029309.4. [Q22942-1]
DR RefSeq; NP_001024481.1; NM_001029310.3. [Q22942-2]
DR PDB; 1NW1; X-ray; 2.02 A; A/B=1-429.
DR PDBsum; 1NW1; -.
DR AlphaFoldDB; Q22942; -.
DR SMR; Q22942; -.
DR STRING; 6239.C52B9.1a; -.
DR EPD; Q22942; -.
DR PaxDb; Q22942; -.
DR PeptideAtlas; Q22942; -.
DR EnsemblMetazoa; C52B9.1a.1; C52B9.1a.1; WBGene00000510. [Q22942-1]
DR EnsemblMetazoa; C52B9.1b.1; C52B9.1b.1; WBGene00000510. [Q22942-2]
DR EnsemblMetazoa; C52B9.1b.2; C52B9.1b.2; WBGene00000510. [Q22942-2]
DR GeneID; 180703; -.
DR KEGG; cel:CELE_C52B9.1; -.
DR UCSC; C52B9.1a; c. elegans.
DR CTD; 180703; -.
DR WormBase; C52B9.1a; CE27113; WBGene00000510; cka-2. [Q22942-1]
DR WormBase; C52B9.1b; CE38493; WBGene00000510; cka-2. [Q22942-2]
DR eggNOG; KOG2686; Eukaryota.
DR GeneTree; ENSGT00950000182939; -.
DR InParanoid; Q22942; -.
DR OMA; PLSCHEI; -.
DR OrthoDB; 1469912at2759; -.
DR PhylomeDB; Q22942; -.
DR Reactome; R-CEL-1483191; Synthesis of PC.
DR Reactome; R-CEL-1483213; Synthesis of PE.
DR UniPathway; UPA00558; UER00741.
DR UniPathway; UPA00753; UER00737.
DR EvolutionaryTrace; Q22942; -.
DR PRO; PR:Q22942; -.
DR Proteomes; UP000001940; Chromosome X.
DR Bgee; WBGene00000510; Expressed in pharyngeal muscle cell (C elegans) and 3 other tissues.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004103; F:choline kinase activity; IDA:WormBase.
DR GO; GO:0004305; F:ethanolamine kinase activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006657; P:CDP-choline pathway; IDA:WormBase.
DR GO; GO:0006656; P:phosphatidylcholine biosynthetic process; IBA:GO_Central.
DR GO; GO:0006646; P:phosphatidylethanolamine biosynthetic process; IBA:GO_Central.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR DisProt; DP02987; -.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR SUPFAM; SSF56112; SSF56112; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Calcium; Kinase;
KW Lipid biosynthesis; Lipid metabolism; Magnesium; Metal-binding;
KW Nucleotide-binding; Phospholipid biosynthesis; Phospholipid metabolism;
KW Reference proteome; Transferase.
FT CHAIN 1..429
FT /note="Choline kinase A2"
FT /id="PRO_0000432071"
FT BINDING 82..88
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P35790"
FT BINDING 84..86
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P35790"
FT BINDING 111
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P35790"
FT BINDING 152..158
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P35790"
FT BINDING 257
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P35790"
FT BINDING 258
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0007744|PDB:1NW1"
FT BINDING 301
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P35790"
FT BINDING 320
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0007744|PDB:1NW1"
FT BINDING 323
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0007744|PDB:1NW1"
FT VAR_SEQ 1..21
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_057474"
FT MUTAGEN 86
FT /note="S->A: Severe decrease in catalytic efficiency."
FT /evidence="ECO:0000269|PubMed:14960577"
FT MUTAGEN 111
FT /note="R->A: 10-fold reduction in catalytic efficiency for
FT ATP."
FT /evidence="ECO:0000269|PubMed:14960577"
FT MUTAGEN 125
FT /note="E->A: Moderate decrease in catalytic efficiency with
FT a 3-fold decrease in the affinity for ATP and for Mg(2+).
FT Activated by low concentrations of Ca(2+) and inhibited by
FT high concentrations of Ca(2+)."
FT /evidence="ECO:0000269|PubMed:14960577"
FT MUTAGEN 253
FT /note="H->A: Linear activity for only a short time,
FT suggesting a role in maintaining enzyme conformation."
FT /evidence="ECO:0000269|PubMed:14960577"
FT MUTAGEN 254
FT /note="N->A: Linear activity for only a short time,
FT suggesting a role in maintaining enzyme conformation."
FT /evidence="ECO:0000269|PubMed:14960577"
FT MUTAGEN 255
FT /note="D->A,N: Complete loss of activity."
FT /evidence="ECO:0000269|PubMed:14960577"
FT MUTAGEN 255
FT /note="D->E: Severe decrease in catalytic efficiency with a
FT 5-fold decrease in the affinity for choline."
FT /evidence="ECO:0000269|PubMed:14960577"
FT MUTAGEN 260
FT /note="N->A: Severe decrease in catalytic efficiency with a
FT 3-fold decrease in the affinity for ATP and for Mg(2+). No
FT inhibition at high Mg(2+) concentrations. Activated by low
FT concentrations of Ca(2+) and inhibited by high
FT concentrations of Ca(2+)."
FT /evidence="ECO:0000269|PubMed:14960577"
FT MUTAGEN 301
FT /note="D->A,E,N: Complete loss of activity."
FT /evidence="ECO:0000269|PubMed:14960577"
FT MUTAGEN 303
FT /note="E->A: Severe decrease in catalytic efficiency with a
FT decreased affinity for Mg(2+). No inhibition at high Mg(2+)
FT concentrations. Activated by low concentrations of Ca(2+)
FT and inhibited by high concentrations of Ca(2+)."
FT /evidence="ECO:0000269|PubMed:14960577"
FT MUTAGEN 303
FT /note="E->N,Q: Moderate decrease in catalytic efficiency."
FT /evidence="ECO:0000269|PubMed:14960577"
FT MUTAGEN 320
FT /note="E->A: Linear activity for only a short time,
FT suggesting a role in maintaining enzyme conformation.
FT Substantial decrease in the affinity for ATP."
FT /evidence="ECO:0000269|PubMed:14960577"
FT MUTAGEN 387
FT /note="W->A: Severe decrease in catalytic efficiency but no
FT effect on the affinity for ATP and choline. No inhibition
FT at high Mg(2+) concentrations."
FT /evidence="ECO:0000269|PubMed:14960577"
FT HELIX 33..37
FT /evidence="ECO:0007829|PDB:1NW1"
FT HELIX 46..48
FT /evidence="ECO:0007829|PDB:1NW1"
FT HELIX 50..64
FT /evidence="ECO:0007829|PDB:1NW1"
FT HELIX 67..70
FT /evidence="ECO:0007829|PDB:1NW1"
FT HELIX 73..75
FT /evidence="ECO:0007829|PDB:1NW1"
FT STRAND 76..81
FT /evidence="ECO:0007829|PDB:1NW1"
FT STRAND 87..94
FT /evidence="ECO:0007829|PDB:1NW1"
FT STRAND 101..103
FT /evidence="ECO:0007829|PDB:1NW1"
FT STRAND 106..113
FT /evidence="ECO:0007829|PDB:1NW1"
FT HELIX 119..134
FT /evidence="ECO:0007829|PDB:1NW1"
FT STRAND 137..139
FT /evidence="ECO:0007829|PDB:1NW1"
FT STRAND 141..145
FT /evidence="ECO:0007829|PDB:1NW1"
FT STRAND 148..151
FT /evidence="ECO:0007829|PDB:1NW1"
FT STRAND 156..158
FT /evidence="ECO:0007829|PDB:1NW1"
FT HELIX 163..165
FT /evidence="ECO:0007829|PDB:1NW1"
FT HELIX 167..180
FT /evidence="ECO:0007829|PDB:1NW1"
FT HELIX 193..208
FT /evidence="ECO:0007829|PDB:1NW1"
FT HELIX 219..221
FT /evidence="ECO:0007829|PDB:1NW1"
FT HELIX 228..242
FT /evidence="ECO:0007829|PDB:1NW1"
FT STRAND 249..252
FT /evidence="ECO:0007829|PDB:1NW1"
FT HELIX 258..260
FT /evidence="ECO:0007829|PDB:1NW1"
FT STRAND 261..264
FT /evidence="ECO:0007829|PDB:1NW1"
FT STRAND 306..309
FT /evidence="ECO:0007829|PDB:1NW1"
FT HELIX 310..320
FT /evidence="ECO:0007829|PDB:1NW1"
FT HELIX 337..339
FT /evidence="ECO:0007829|PDB:1NW1"
FT HELIX 343..357
FT /evidence="ECO:0007829|PDB:1NW1"
FT HELIX 362..364
FT /evidence="ECO:0007829|PDB:1NW1"
FT HELIX 365..376
FT /evidence="ECO:0007829|PDB:1NW1"
FT HELIX 377..379
FT /evidence="ECO:0007829|PDB:1NW1"
FT HELIX 380..397
FT /evidence="ECO:0007829|PDB:1NW1"
FT STRAND 400..402
FT /evidence="ECO:0007829|PDB:1NW1"
FT HELIX 404..417
FT /evidence="ECO:0007829|PDB:1NW1"
FT HELIX 419..423
FT /evidence="ECO:0007829|PDB:1NW1"
SQ SEQUENCE 429 AA; 49240 MW; B536F35871DCEFD1 CRC64;
MSSRKVSRAH YDEDELASAA NMSLVAEGHF RGMKELLSTM DLDTDANTIP ELKERAHMLC
ARFLGGAWKT VPLEHLRISR IKGGMSNMLF LCRLSEVYPP IRNEPNKVLL RVYFNPETES
HLVAESVIFT LLSERHLGPK LYGIFSGGRL EEYIPSRPLS CHEISLAHMS TKIAKRVAKV
HQLEVPIWKE PDYLCEALQR WLKQLTGTVD AEHRFDLPEE CGVSSVNCLD LARELEFLRA
HISLSKSPVT FCHNDLQEGN ILLPKASSGN IRMPSLSDET QALGNSLSAF NPADPRLVLI
DFEYASYNYR AFDFANHFIE WTIDYDIDEA PFYKIQTENF PENDQMLEFF LNYLREQGNT
RENELYKKSE DLVQETLPFV PVSHFFWGVW GLLQVELSPV GFGFADYGRD RLSLYFKHKQ
LLKNLASHQ
