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 27-MAR-2024, entry version 167. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 GlyGen; Q8BW96; 6 sites, 1 O-linked glycan (6 sites). DR iPTMnet; Q8BW96; -. DR PhosphoSitePlus; Q8BW96; -. DR EPD; Q8BW96; -. DR jPOST; Q8BW96; -. DR MaxQB; Q8BW96; -. DR PaxDb; 10090-ENSMUSP00000037028; -. DR PeptideAtlas; Q8BW96; -. DR ProteomicsDB; 263579; -. [Q8BW96-1] DR ProteomicsDB; 263580; -. [Q8BW96-2] DR ProteomicsDB; 263581; -. [Q8BW96-3] DR Pumba; Q8BW96; -. DR Antibodypedia; 1550; 494 antibodies from 37 providers. DR DNASU; 227541; -. DR Ensembl; ENSMUST00000044009.14; ENSMUSP00000037028.8; ENSMUSG00000039145.17. [Q8BW96-1] DR Ensembl; ENSMUST00000114987.4; ENSMUSP00000110638.4; ENSMUSG00000039145.17. [Q8BW96-3] DR GeneID; 227541; -. DR KEGG; mmu:227541; -. DR UCSC; uc008ifp.2; mouse. [Q8BW96-1] DR UCSC; uc056zje.1; mouse. [Q8BW96-3] DR AGR; MGI:2442190; -. 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; RPKVQPC; -. DR OrthoDB; 1121238at2759; -. DR PhylomeDB; Q8BW96; -. DR TreeFam; TF314166; -. DR BioGRID-ORCS; 227541; 0 hits in 82 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 203 other cell types or tissues. DR ExpressionAtlas; Q8BW96; baseline and differential. 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:0016310; P:phosphorylation; IEA:UniProtKB-KW. 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 CDD; cd14168; STKc_CaMKI_delta; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. 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 PANTHER; PTHR24347:SF252; CALCIUM_CALMODULIN-DEPENDENT PROTEIN KINASE TYPE 1D; 1. DR PANTHER; PTHR24347; SERINE/THREONINE-PROTEIN KINASE; 1. DR Pfam; PF00069; Pkinase; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. DR Genevisible; Q8BW96; MM. 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 //