KCC1D_MOUSE
ID KCC1D_MOUSE Reviewed; 385 AA.
AC Q8BW96; Q3U450; Q80W64; Q8BWI7;
DT 07-DEC-2004, integrated into UniProtKB/Swiss-Prot.
DT 07-DEC-2004, sequence version 2.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Calcium/calmodulin-dependent protein kinase type 1D;
DE EC=2.7.11.17;
DE AltName: Full=CaM kinase I delta;
DE Short=CaM-KI delta;
DE Short=CaMKI delta;
DE AltName: Full=CaM kinase ID;
DE AltName: Full=CaMKI-like protein kinase;
DE Short=CKLiK;
DE Short=mCKLiK;
GN Name=Camk1d;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, AND TISSUE
RP SPECIFICITY.
RX PubMed=14980499; DOI=10.1016/j.yexcr.2003.10.023;
RA Yamada T., Suzuki M., Satoh H., Kihara-Negishi F., Nakano H., Oikawa T.;
RT "Effects of PU.1-induced mouse calcium-calmodulin-dependent kinase I-like
RT kinase (CKLiK) on apoptosis of murine erythroleukemia cells.";
RL Exp. Cell Res. 294:39-50(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), AND INDUCTION.
RC STRAIN=C57BL/6J; TISSUE=Liver;
RX PubMed=12897189; DOI=10.1194/jlr.m300203-jlr200;
RA Maxwell K.N., Soccio R.E., Duncan E.M., Sehayek E., Breslow J.L.;
RT "Novel putative SREBP and LXR target genes identified by microarray
RT analysis in liver of cholesterol-fed mice.";
RL J. Lipid Res. 44:2109-2119(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J, and NOD; TISSUE=Brain, and Lung;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP FUNCTION, DEVELOPMENTAL STAGE, AND MUTAGENESIS OF 289-ILE--SER-292 AND
RP PHE-301.
RX PubMed=18400360; DOI=10.1016/j.exphem.2008.02.009;
RA Gaines P., Lamoureux J., Marisetty A., Chi J., Berliner N.;
RT "A cascade of Ca(2+)/calmodulin-dependent protein kinases regulates the
RT differentiation and functional activation of murine neutrophils.";
RL Exp. Hematol. 36:832-844(2008).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Pancreas, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Calcium/calmodulin-dependent protein kinase that operates in
CC the calcium-triggered CaMKK-CaMK1 signaling cascade and, upon calcium
CC influx, activates CREB-dependent gene transcription, regulates calcium-
CC mediated granulocyte function and respiratory burst and promotes basal
CC dendritic growth of hippocampal neurons. In neutrophil cells, required
CC for cytokine-induced proliferative responses and activation of the
CC respiratory burst. Activates the transcription factor CREB1 in
CC hippocampal neuron nuclei. May play a role in apoptosis of
CC erythroleukemia cells. In vitro, phosphorylates transcription factor
CC CREM isoform Beta (By similarity). Isoform 1 but not isoform 2
CC activates CREB1. {ECO:0000250, ECO:0000269|PubMed:14980499,
CC ECO:0000269|PubMed:18400360}.
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 results in conformational change that relieves intrasteric
CC autoinhibition and allows phosphorylation of Thr-180 within the
CC activation loop by CaMKK1 or CaMKK2. Phosphorylation of Thr-180 results
CC in several fold increase in total activity. Unlike CaMK4, may be unable
CC to exhibit autonomous activity after Ca(2+)/calmodulin activation (By
CC similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC Note=Predominantly cytoplasmic. Nuclear upon activation. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=Alpha;
CC IsoId=Q8BW96-1; Sequence=Displayed;
CC Name=2; Synonyms=Beta;
CC IsoId=Q8BW96-2; Sequence=VSP_012137;
CC Name=3;
CC IsoId=Q8BW96-3; Sequence=VSP_012136;
CC -!- TISSUE SPECIFICITY: Expressed ubiquitously with high levels in brain
CC and low levels in kidney. Isoform 2 is highly expressed in brain
CC compared to other tissues. In hematopoietic cell lines predominant
CC expression was detected in T and EC cells.
CC {ECO:0000269|PubMed:14980499}.
CC -!- DEVELOPMENTAL STAGE: In EML cell line differentiation, expression
CC increases 4 to 8 hours after treatment with all-trans retinoic acid
CC (ATRA) and then declines after 24 hours of ATRA induction.
CC {ECO:0000269|PubMed:18400360}.
CC -!- INDUCTION: Down-regulated upon cholesterol-rich diet.
CC {ECO:0000269|PubMed:12897189}.
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 -!- MISCELLANEOUS: [Isoform 2]: Inactive. Does not activate CREB1.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. CaMK subfamily. {ECO:0000305}.
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DR EMBL; AY273822; AAP31673.1; -; mRNA.
DR EMBL; AK052401; BAC34975.1; -; mRNA.
DR EMBL; AK053173; BAC35295.1; -; mRNA.
DR EMBL; AK147616; BAE28027.1; -; mRNA.
DR EMBL; AK154434; BAE32584.1; -; mRNA.
DR EMBL; AK170777; BAE42022.1; -; mRNA.
DR CCDS; CCDS15665.1; -. [Q8BW96-1]
DR CCDS; CCDS70975.1; -. [Q8BW96-3]
DR RefSeq; NP_001277303.1; NM_001290374.1.
DR RefSeq; NP_001277304.1; NM_001290375.1.
DR RefSeq; NP_001277305.1; NM_001290376.1. [Q8BW96-3]
DR RefSeq; NP_796317.2; NM_177343.4. [Q8BW96-1]
DR AlphaFoldDB; Q8BW96; -.
DR SMR; Q8BW96; -.
DR BioGRID; 230634; 8.
DR IntAct; Q8BW96; 1.
DR STRING; 10090.ENSMUSP00000037028; -.
DR iPTMnet; Q8BW96; -.
DR PhosphoSitePlus; Q8BW96; -.
DR EPD; Q8BW96; -.
DR jPOST; Q8BW96; -.
DR MaxQB; Q8BW96; -.
DR PaxDb; Q8BW96; -.
DR PeptideAtlas; Q8BW96; -.
DR PRIDE; Q8BW96; -.
DR ProteomicsDB; 263579; -. [Q8BW96-1]
DR ProteomicsDB; 263580; -. [Q8BW96-2]
DR ProteomicsDB; 263581; -. [Q8BW96-3]
DR Antibodypedia; 1550; 449 antibodies from 37 providers.
DR DNASU; 227541; -.
DR Ensembl; ENSMUST00000044009; ENSMUSP00000037028; ENSMUSG00000039145. [Q8BW96-1]
DR Ensembl; ENSMUST00000114987; ENSMUSP00000110638; ENSMUSG00000039145. [Q8BW96-3]
DR GeneID; 227541; -.
DR KEGG; mmu:227541; -.
DR UCSC; uc008ifp.2; mouse. [Q8BW96-1]
DR UCSC; uc056zje.1; mouse. [Q8BW96-3]
DR CTD; 57118; -.
DR MGI; MGI:2442190; Camk1d.
DR VEuPathDB; HostDB:ENSMUSG00000039145; -.
DR eggNOG; KOG0032; Eukaryota.
DR GeneTree; ENSGT00940000156776; -.
DR HOGENOM; CLU_000288_63_0_1; -.
DR InParanoid; Q8BW96; -.
DR OMA; ADCPEGK; -.
DR PhylomeDB; Q8BW96; -.
DR TreeFam; TF314166; -.
DR BioGRID-ORCS; 227541; 0 hits in 77 CRISPR screens.
DR ChiTaRS; Camk1d; mouse.
DR PRO; PR:Q8BW96; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q8BW96; protein.
DR Bgee; ENSMUSG00000039145; Expressed in olfactory tubercle and 201 other tissues.
DR ExpressionAtlas; Q8BW96; baseline and differential.
DR Genevisible; Q8BW96; MM.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
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; ISO:MGI.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:MGI.
DR GO; GO:0007399; P:nervous system development; IEA:UniProtKB-KW.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:MGI.
DR GO; GO:0032793; P:positive regulation of CREB transcription factor activity; ISS:UniProtKB.
DR GO; GO:0010976; P:positive regulation of neuron projection development; IMP:UniProtKB.
DR GO; GO:0090023; P:positive regulation of neutrophil chemotaxis; IMP:UniProtKB.
DR GO; GO:0050766; P:positive regulation of phagocytosis; ISS:UniProtKB.
DR GO; GO:0060267; P:positive regulation of respiratory burst; ISS:UniProtKB.
DR GO; GO:0050773; P:regulation of dendrite development; ISS:UniProtKB.
DR GO; GO:0071622; P:regulation of granulocyte chemotaxis; ISS:UniProtKB.
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 Allosteric enzyme; Alternative splicing; ATP-binding; Calcium;
KW Calmodulin-binding; Cytoplasm; Inflammatory response; Isopeptide bond;
KW Kinase; Neurogenesis; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Transferase;
KW Ubl conjugation.
FT CHAIN 1..385
FT /note="Calcium/calmodulin-dependent protein kinase type 1D"
FT /id="PRO_0000086083"
FT DOMAIN 23..279
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 279..319
FT /note="Autoinhibitory domain"
FT /evidence="ECO:0000250"
FT REGION 299..320
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000250"
FT REGION 363..385
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 318..324
FT /note="Nuclear export signal"
FT /evidence="ECO:0000250"
FT ACT_SITE 144
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 MOD_RES 122
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8IU85"
FT MOD_RES 180
FT /note="Phosphothreonine; by CaMKK1 and CaMKK2"
FT /evidence="ECO:0000250|UniProtKB:Q8IU85"
FT CROSSLNK 113
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q8IU85"
FT VAR_SEQ 1..31
FT /note="MARENGESSSSWKKQAEDIKKIFEFKETLGT -> MAEFVSWSCLNFRWSWI
FT KGSRNS (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:12897189"
FT /id="VSP_012136"
FT VAR_SEQ 333..385
FT /note="ASVSSNLSLASQKDCLAPSTLCSFLSSSSGVAGVGAERRPRPTTVTTGHTGS
FT K -> VWHLPRSVVSFLLRRGSQESELRGDPQPPL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14980499"
FT /id="VSP_012137"
FT MUTAGEN 52
FT /note="K->D: Catalytically inactive form."
FT MUTAGEN 289..292
FT /note="IHES->DEDD: Constitutively active form; when
FT associated with A-301."
FT /evidence="ECO:0000269|PubMed:18400360"
FT MUTAGEN 301
FT /note="F->A: Constitutively active form; when associated
FT with 289-A--A-292."
FT /evidence="ECO:0000269|PubMed:18400360"
FT CONFLICT 30
FT /note="G -> Q (in Ref. 3; BAC35295)"
FT /evidence="ECO:0000305"
FT CONFLICT 327
FT /note="S -> N (in Ref. 3; BAC35295)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 385 AA; 42919 MW; 320EB0D3D5670055 CRC64;
MARENGESSS SWKKQAEDIK KIFEFKETLG TGAFSEVVLA EEKATGKLFA VKCIPKKALK
GKESSIENEI AVLRKIKHEN IVALEDIYES PNHLYLVMQL VSGGELFDRI VEKGFYTEKD
ASTLIRQVLD AVYYLHRMGI VHRDLKPENL LYYSQDEESK IMISDFGLSK MEGKGDVMST
ACGTPGYVAP EVLAQKPYSK AVDCWSIGVI AYILLCGYPP FYDENDSKLF EQILKAEYEF
DSPYWDDISD SAKDFIRNLM EKDPNKRYTC EQAARHPWIA GDTALSKNIH ESVSAQIRKN
FAKSKWRQAF NATAVVRHMR RLQLGSSLDS SNASVSSNLS LASQKDCLAP STLCSFLSSS
SGVAGVGAER RPRPTTVTTG HTGSK
