KCC1G_HUMAN
ID KCC1G_HUMAN Reviewed; 476 AA.
AC Q96NX5; Q86UH5; Q9Y3J7;
DT 07-DEC-2004, integrated into UniProtKB/Swiss-Prot.
DT 16-AUG-2005, sequence version 3.
DT 03-AUG-2022, entry version 185.
DE RecName: Full=Calcium/calmodulin-dependent protein kinase type 1G;
DE EC=2.7.11.17;
DE AltName: Full=CaM kinase I gamma;
DE Short=CaM kinase IG;
DE Short=CaM-KI gamma;
DE Short=CaMKI gamma;
DE Short=CaMKIG;
DE AltName: Full=CaMK-like CREB kinase III;
DE Short=CLICK III;
GN Name=CAMK1G; Synonyms=CLICK3, VWS1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT ILE-329.
RX PubMed=10645953;
RA Schutte B.C., Bjork B.C., Coppage K.B., Malik M.I., Gregory S.G.,
RA Scott D.J., Brentzell L.M., Watanabe Y., Dixon M.J., Murray J.C.;
RT "A preliminary gene map for the Van der Woude syndrome critical region
RT derived from 900 kb of genomic sequence at 1q32-q41.";
RL Genome Res. 10:81-94(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND TISSUE SPECIFICITY.
RX PubMed=12637513; DOI=10.1074/jbc.m300578200;
RA Takemoto-Kimura S., Terai H., Takamoto M., Ohmae S., Kikumura S., Segi E.,
RA Arakawa Y., Furuyashiki T., Narumiya S., Bito H.;
RT "Molecular cloning and characterization of CLICK-III/CaMKIgamma, a novel
RT membrane-anchored neuronal Ca2+/calmodulin-dependent protein kinase
RT (CaMK).";
RL J. Biol. Chem. 278:18597-18605(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Rhodes S.;
RL Submitted (APR-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP VARIANTS [LARGE SCALE ANALYSIS] GLN-259; ILE-329 AND THR-443.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Calcium/calmodulin-dependent protein kinase belonging to a
CC proposed calcium-triggered signaling cascade. In vitro phosphorylates
CC transcription factor CREB1 (By similarity). {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.17;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.17;
CC -!- ACTIVITY REGULATION: Activated by Ca(2+)/calmodulin. Binding of
CC calmodulin is thought to result in a conformational change and leads to
CC activation through phosphorylation by CAMKK1 (By similarity).
CC {ECO:0000250}.
CC -!- INTERACTION:
CC Q96NX5; P21333-2: FLNA; NbExp=3; IntAct=EBI-3920838, EBI-9641086;
CC Q96NX5; P28799: GRN; NbExp=3; IntAct=EBI-3920838, EBI-747754;
CC Q96NX5; O60333-2: KIF1B; NbExp=3; IntAct=EBI-3920838, EBI-10975473;
CC Q96NX5; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-3920838, EBI-10171774;
CC Q96NX5; P31153: MAT2A; NbExp=3; IntAct=EBI-3920838, EBI-1050743;
CC Q96NX5; O76024: WFS1; NbExp=3; IntAct=EBI-3920838, EBI-720609;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Golgi apparatus membrane
CC {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Cell membrane
CC {ECO:0000250}; Peripheral membrane protein {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q96NX5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96NX5-2; Sequence=VSP_012138;
CC -!- TISSUE SPECIFICITY: Mainly expressed in brain with small amounts in
CC skeletal muscles, kidney, spleen and liver. Strongly expressed in
CC forebrain neocortex, striatum and limbic system.
CC {ECO:0000269|PubMed:12637513}.
CC -!- DOMAIN: The autoinhibitory domain overlaps with the calmodulin binding
CC region and interacts in the inactive folded state with the catalytic
CC domain as a pseudosubstrate. {ECO:0000250}.
CC -!- PTM: May be prenylated on Cys-473. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. CaMK subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAB41259.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF428261; AAL28100.1; -; mRNA.
DR EMBL; AY212935; AAP29964.1; -; mRNA.
DR EMBL; AL049688; CAB41259.1; ALT_INIT; mRNA.
DR EMBL; AL023754; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC032787; AAH32787.1; -; mRNA.
DR CCDS; CCDS1486.1; -. [Q96NX5-1]
DR RefSeq; NP_065172.1; NM_020439.2. [Q96NX5-1]
DR RefSeq; XP_016857355.1; XM_017001866.1. [Q96NX5-1]
DR PDB; 2JAM; X-ray; 1.70 A; A/B=18-316.
DR PDBsum; 2JAM; -.
DR AlphaFoldDB; Q96NX5; -.
DR SMR; Q96NX5; -.
DR BioGRID; 121424; 14.
DR IntAct; Q96NX5; 12.
DR STRING; 9606.ENSP00000009105; -.
DR BindingDB; Q96NX5; -.
DR ChEMBL; CHEMBL5258; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB08009; SU-11652.
DR DrugCentral; Q96NX5; -.
DR iPTMnet; Q96NX5; -.
DR PhosphoSitePlus; Q96NX5; -.
DR BioMuta; CAMK1G; -.
DR DMDM; 73620970; -.
DR jPOST; Q96NX5; -.
DR MassIVE; Q96NX5; -.
DR PaxDb; Q96NX5; -.
DR PeptideAtlas; Q96NX5; -.
DR PRIDE; Q96NX5; -.
DR ProteomicsDB; 77570; -. [Q96NX5-1]
DR ProteomicsDB; 77571; -. [Q96NX5-2]
DR Antibodypedia; 20698; 305 antibodies from 30 providers.
DR DNASU; 57172; -.
DR Ensembl; ENST00000009105.5; ENSP00000009105.1; ENSG00000008118.10. [Q96NX5-1]
DR Ensembl; ENST00000361322.3; ENSP00000354861.2; ENSG00000008118.10. [Q96NX5-1]
DR GeneID; 57172; -.
DR KEGG; hsa:57172; -.
DR MANE-Select; ENST00000361322.3; ENSP00000354861.2; NM_020439.3; NP_065172.1.
DR UCSC; uc001hhd.4; human. [Q96NX5-1]
DR CTD; 57172; -.
DR DisGeNET; 57172; -.
DR GeneCards; CAMK1G; -.
DR HGNC; HGNC:14585; CAMK1G.
DR HPA; ENSG00000008118; Group enriched (brain, ovary).
DR MIM; 614994; gene.
DR neXtProt; NX_Q96NX5; -.
DR OpenTargets; ENSG00000008118; -.
DR PharmGKB; PA26049; -.
DR VEuPathDB; HostDB:ENSG00000008118; -.
DR eggNOG; KOG0032; Eukaryota.
DR GeneTree; ENSGT00940000156872; -.
DR HOGENOM; CLU_000288_63_0_1; -.
DR InParanoid; Q96NX5; -.
DR OMA; TGVCAIM; -.
DR OrthoDB; 330091at2759; -.
DR PhylomeDB; Q96NX5; -.
DR TreeFam; TF314166; -.
DR BRENDA; 2.7.11.17; 2681.
DR PathwayCommons; Q96NX5; -.
DR SignaLink; Q96NX5; -.
DR SIGNOR; Q96NX5; -.
DR BioGRID-ORCS; 57172; 10 hits in 1102 CRISPR screens.
DR EvolutionaryTrace; Q96NX5; -.
DR GenomeRNAi; 57172; -.
DR Pharos; Q96NX5; Tchem.
DR PRO; PR:Q96NX5; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q96NX5; protein.
DR Bgee; ENSG00000008118; Expressed in frontal pole and 132 other tissues.
DR ExpressionAtlas; Q96NX5; baseline and differential.
DR Genevisible; Q96NX5; HS.
DR GO; GO:0005954; C:calcium- and calmodulin-dependent protein kinase complex; IEA:Ensembl.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0043005; C:neuron projection; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005516; F:calmodulin binding; IBA:GO_Central.
DR GO; GO:0004683; F:calmodulin-dependent protein kinase activity; IBA:GO_Central.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Allosteric enzyme; Alternative splicing; ATP-binding;
KW Calmodulin-binding; Cell membrane; Cytoplasm; Golgi apparatus; Kinase;
KW Lipoprotein; Membrane; Nucleotide-binding; Prenylation; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..476
FT /note="Calcium/calmodulin-dependent protein kinase type 1G"
FT /id="PRO_0000086084"
FT DOMAIN 23..277
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 277..317
FT /note="Autoinhibitory domain"
FT /evidence="ECO:0000250"
FT REGION 297..318
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000250"
FT REGION 325..352
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 338..352
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 143
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 29..37
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 52
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT VAR_SEQ 448..476
FT /note="NFKSEVMVPVKASGSSHCRAGQTGVCLIM -> YVFLAKDGAPAWV (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:12637513"
FT /id="VSP_012138"
FT VARIANT 259
FT /note="E -> Q (in dbSNP:rs35561962)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040600"
FT VARIANT 329
FT /note="V -> I (in dbSNP:rs11119315)"
FT /evidence="ECO:0000269|PubMed:10645953,
FT ECO:0000269|PubMed:17344846"
FT /id="VAR_020530"
FT VARIANT 443
FT /note="A -> T (in a breast infiltrating ductal carcinoma
FT sample; somatic mutation; dbSNP:rs1228276529)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040601"
FT CONFLICT 427
FT /note="S -> N (in Ref. 1; AAL28100)"
FT /evidence="ECO:0000305"
FT HELIX 19..22
FT /evidence="ECO:0007829|PDB:2JAM"
FT STRAND 23..31
FT /evidence="ECO:0007829|PDB:2JAM"
FT STRAND 33..42
FT /evidence="ECO:0007829|PDB:2JAM"
FT TURN 43..45
FT /evidence="ECO:0007829|PDB:2JAM"
FT STRAND 48..55
FT /evidence="ECO:0007829|PDB:2JAM"
FT HELIX 64..74
FT /evidence="ECO:0007829|PDB:2JAM"
FT STRAND 83..88
FT /evidence="ECO:0007829|PDB:2JAM"
FT STRAND 90..97
FT /evidence="ECO:0007829|PDB:2JAM"
FT HELIX 105..112
FT /evidence="ECO:0007829|PDB:2JAM"
FT HELIX 117..136
FT /evidence="ECO:0007829|PDB:2JAM"
FT HELIX 146..148
FT /evidence="ECO:0007829|PDB:2JAM"
FT STRAND 150..155
FT /evidence="ECO:0007829|PDB:2JAM"
FT STRAND 160..162
FT /evidence="ECO:0007829|PDB:2JAM"
FT HELIX 177..180
FT /evidence="ECO:0007829|PDB:2JAM"
FT TURN 188..190
FT /evidence="ECO:0007829|PDB:2JAM"
FT STRAND 191..193
FT /evidence="ECO:0007829|PDB:2JAM"
FT HELIX 198..214
FT /evidence="ECO:0007829|PDB:2JAM"
FT TURN 218..221
FT /evidence="ECO:0007829|PDB:2JAM"
FT HELIX 224..233
FT /evidence="ECO:0007829|PDB:2JAM"
FT TURN 240..245
FT /evidence="ECO:0007829|PDB:2JAM"
FT HELIX 248..258
FT /evidence="ECO:0007829|PDB:2JAM"
FT TURN 262..264
FT /evidence="ECO:0007829|PDB:2JAM"
FT HELIX 268..272
FT /evidence="ECO:0007829|PDB:2JAM"
FT HELIX 275..278
FT /evidence="ECO:0007829|PDB:2JAM"
FT HELIX 288..298
FT /evidence="ECO:0007829|PDB:2JAM"
SQ SEQUENCE 476 AA; 53087 MW; DD009D9CF2FE3CBE CRC64;
MGRKEEDDCS SWKKQTTNIR KTFIFMEVLG SGAFSEVFLV KQRLTGKLFA LKCIKKSPAF
RDSSLENEIA VLKKIKHENI VTLEDIYEST THYYLVMQLV SGGELFDRIL ERGVYTEKDA
SLVIQQVLSA VKYLHENGIV HRDLKPENLL YLTPEENSKI MITDFGLSKM EQNGIMSTAC
GTPGYVAPEV LAQKPYSKAV DCWSIGVITY ILLCGYPPFY EETESKLFEK IKEGYYEFES
PFWDDISESA KDFICHLLEK DPNERYTCEK ALSHPWIDGN TALHRDIYPS VSLQIQKNFA
KSKWRQAFNA AAVVHHMRKL HMNLHSPGVR PEVENRPPET QASETSRPSS PEITITEAPV
LDHSVALPAL TQLPCQHGRR PTAPGGRSLN CLVNGSLHIS SSLVPMHQGS LAAGPCGCCS
SCLNIGSKGK SSYCSEPTLL KKANKKQNFK SEVMVPVKAS GSSHCRAGQT GVCLIM
