Reviewed, UniProtKB/Swiss-Prot Q63450 (KCC1A_RAT)

Names and origin

Protein names

Recommended name:
    Calcium/calmodulin-dependent protein kinase type 1
    EC=2.7.11.17
Alternative name(s):
    CaM kinase I
      Short name=CaM-KI
    CaM kinase I alpha
      Short name=CaMKI-alpha

Gene names

Name:

Camk1

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	374 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Calcium/calmodulin-dependent protein kinase belonging to a proposed calcium-triggered signaling cascade involved in a number of cellular processes like transcriptional regulation, hormone production, translational regulation, regulation of actin filament organization and neurite outgrowth. Involved in calcium-dependent activation of the ERK pathway By similarity. Recognizes the substrate consensus sequence [MVLIF]-x-R-x(2)-[ST]-x(3)-[MVLIF]. Phosphorylates EIF4G3/eIF4GII. In vitro phosphorylates CREB1, ATF1, CTFR, MYL9, SYN1/synapsin I and SYNII/synapsin II By similarity.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Enzyme regulation	Activated by Ca2+/calmodulin. Binding of calmodulin results in a conformational change that generates functional binding sites for both, substrate and ATP, and thus releaves autoinhibition. Must be phosphorylated to be maximally active. Phosphorylated by CAMKK1 or CAMKK2. Ref.10 Ref.11
Subunit structure	Monomer. Interacts with XPO1. Ref.14
Subcellular location	Cytoplasm. Nucleus. Note: Predominantly cytoplasmic. Ref.14 Ref.8 Ref.12 Ref.13
Tissue specificity	Ubiquitous. Ref.8
Domain	The autoinhibitory domain overlaps with the calmodulin binding region and interacts in the inactive folded state with the catalytic domain as a pseudosubstrate. Ref.17
Sequence similarities	Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CaMK subfamily. Contains 1 protein kinase domain.
Sequence caution	The sequence AAA19670.1 differs from that shown. Reason: Frameshift at positions 321 and 363.

Ontologies

Keywords
Biological process	Differentiation Neurogenesis
Cellular component	Cytoplasm Nucleus
Ligand	ATP-binding Calmodulin-binding Nucleotide-binding
Molecular function	Developmental protein Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Allosteric enzyme Direct protein sequencing
Gene Ontology (GO)
Biological process	cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW nervous system development Inferred from electronic annotation. Source: UniProtKB-KW protein amino acid phosphorylation Inferred from electronic annotation. Source: InterPro
Cellular component	calcium- and calmodulin-dependent protein kinase complex Traceable author statement. Source: UniProtKB cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW calmodulin binding Inferred from electronic annotation. Source: UniProtKB-KW calmodulin-dependent protein kinase activity Inferred from direct assay. Source: RGD
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 374

374

Calcium/calmodulin-dependent protein kinase type 1

PRO_0000086078

Regions

Domain

20 – 276

257

Protein kinase

Nucleotide binding

26 – 34

9

ATP By similarity

Region

276 – 316

41

Autoinhibitory domain

Region

296 – 317

22

Calmodulin-binding

Motif

263 – 264

2

Involved in nuclear import Probable

Motif

315 – 321

7

Nuclear export signal

Sites

Active site

141

1

Proton acceptor

Binding site

49

1

ATP By similarity

Amino acid modifications

Modified residue

177

1

Phosphothreonine; by CaMKK1 and CaMKK2

Experimental info

Mutagenesis

177

1

T → A: Loss of activation by CAMKK1 and CAMKK2. Ref.10

Mutagenesis

263 – 264

2

KR → AA: Partially excluded from the nucleus; when associated with 319-AQA-321.

Mutagenesis

319 – 321

3

LQL → AQA: Retention in the nucleus. Partially excluded from the nucleus; when associated with 263-AA-264. Ref.14

Sequence conflict

37

1

A → T AA sequence Ref.5

Sequence conflict

112

1

F → G in AAA19670. Ref.1

Sequence conflict

118

1

A → R in AAA19670. Ref.1

Sequence conflict

239

1

S → V AA sequence Ref.5

Sequence conflict

309

1

A → R in AAA19670. Ref.1

Secondary structure

1

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374

Helix Strand Turn

Details...

Helix

16 – 18

3

Beta strand

20 – 28

9

Helix

29 – 33

5

Beta strand

34 – 39

6

Turn

40 – 42

3

Beta strand

45 – 52

8

Helix

65 – 71

7

Beta strand

81 – 86

6

Beta strand

88 – 95

8

Helix

103 – 108

6

Helix

115 – 134

20

Helix

144 – 146

3

Beta strand

147 – 153

7

Beta strand

158 – 160

3

Helix

187 – 190

4

Helix

198 – 213

16

Helix

223 – 231

9

Turn

239 – 244

6

Helix

247 – 256

10

Helix

261 – 263

3

Helix

267 – 272

6

Turn

274 – 276

3

Beta strand

277 – 279

3

Helix

298 – 317

20

Sequences

	Sequence		Length	Mass (Da)
	Q63450-1 [UniParc]. Last modified July 15, 1998. Version 2. Checksum: 37889B3DEF033AB2	FASTA	374	41,638
	10 20 30 40 50 60 MPGAVEGPRW KQAEDIRDIY DFRDVLGTGA FSEVILAEDK RTQKLVAIKC IAKKALEGKE 70 80 90 100 110 120 GSMENEIAVL HKIKHPNIVA LDDIYESGGH LYLIMQLVSG GELFDRIVEK GFYTERDASR 130 140 150 160 170 180 LIFQVLDAVK YLHDLGIVHR DLKPENLLYY SLDEDSKIMI SDFGLSKMED PGSVLSTACG 190 200 210 220 230 240 TPGYVAPEVL AQKPYSKAVD CWSIGVIAYI LLCGYPPFYD ENDAKLFEQI LKAEYEFDSP 250 260 270 280 290 300 YWDDISDSAK DFIRHLMEKD PEKRFTCEQA LQHPWIAGDT ALDKNIHQSV SEQIKKNFAK 310 320 330 340 350 360 SKWKQAFNAT AVVRHMRKLQ LGTSQEGQGQ TASHGELLTP TAGGPAAGCC CRDCCVEPGS 370 ELPPAPPPSS RAMD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Calcium/calmodulin-dependent protein kinase I. cDNA cloning and identification of autophosphorylation site." Picciotto M.R., Czernik A.J., Nairn A.C. J. Biol. Chem. 268:26512-26521(1993) [PubMed: 8253780] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	Erratum Picciotto M.R., Czernik A.J., Nairn A.C. J. Biol. Chem. 270:10358-10358(1995)
[3]	"Characterization of a rat cDNA clone encoding calcium/calmodulin-dependent protein kinase I." Cho F.S., Phillips K.S., Bogucki B., Weaver T.E. Biochim. Biophys. Acta 1224:156-160(1994) [PubMed: 7948038] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Sprague-Dawley. Tissue: Lung.
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lung.
[5]	"Purification and characterization of Ca2+/calmodulin-dependent protein kinase V from rat cerebrum." Mochizuki H., Ito T., Hidaka H. J. Biol. Chem. 268:9143-9147(1993) [PubMed: 8386178] [Abstract] Cited for: PROTEIN SEQUENCE OF 12-37; 158-167; 233-241 AND 285-295.
[6]	"CREB: a Ca(2+)-regulated transcription factor phosphorylated by calmodulin-dependent kinases." Sheng M., Thompson M.A., Greenberg M.E. Science 252:1427-1430(1991) [PubMed: 1646483] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF CREB1.
[7]	"Similar substrate recognition motifs for mammalian AMP-activated protein kinase, higher plant HMG-CoA reductase kinase-A, yeast SNF1, and mammalian calmodulin-dependent protein kinase I." Dale S., Wilson W.A., Edelman A.M., Hardie D.G. FEBS Lett. 361:191-195(1995) [PubMed: 7698321] [Abstract] Cited for: SUBSTRATE RECOGNITION MOTIF.
[8]	"Immunochemical localization of calcium/calmodulin-dependent protein kinase I." Picciotto M.R., Zoli M., Bertuzzi G., Nairn A.C. Synapse 20:75-84(1995) [PubMed: 7624832] [Abstract] Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[9]	"Regulation of activating transcription factor-1 and the cAMP response element-binding protein by Ca2+/calmodulin-dependent protein kinases type I, II, and IV." Sun P., Lou L., Maurer R.A. J. Biol. Chem. 271:3066-3073(1996) [PubMed: 8621702] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF ATF1 AND CREB1.
[10]	"Multiple Ca(2+)-calmodulin-dependent protein kinase kinases from rat brain. Purification, regulation by Ca(2+)-calmodulin, and partial amino acid sequence." Edelman A.M., Mitchelhill K.I., Selbert M.A., Anderson K.A., Hook S.S., Stapleton D., Goldstein E.G., Means A.R., Kemp B.E. J. Biol. Chem. 271:10806-10810(1996) [PubMed: 8631893] [Abstract] Cited for: ENZYME REGULATION, PHOSPHORYLATION BY CAMKK1 AND CAMKK2, MUTAGENESIS OF THR-177.
[11]	"Activation of a calcium-calmodulin-dependent protein kinase I cascade in PC12 cells." Aletta J.M., Selbert M.A., Nairn A.C., Edelman A.M. J. Biol. Chem. 271:20930-20934(1996) [PubMed: 8702851] [Abstract] Cited for: ENZYME REGULATION.
[12]	"Expression and subcellular localization of multifunctional calmodulin-dependent protein kinases-I, -II and -IV are altered in rat hippocampal CA1 neurons after induction of long-term potentiation." Ahmed B.Y., Yamaguchi F., Tsumura T., Gotoh T., Sugimoto K., Tai Y., Konishi R., Kobayashi R., Tokuda M. Neurosci. Lett. 290:149-153(2000) [PubMed: 10936699] [Abstract] Cited for: SUBCELLULAR LOCATION.
[13]	"Characterization of Ca2+/calmodulin-dependent protein kinase I as a myosin II regulatory light chain kinase in vitro and in vivo." Suizu F., Fukuta Y., Ueda K., Iwasaki T., Tokumitsu H., Hosoya H. Biochem. J. 367:335-345(2002) [PubMed: 12081505] [Abstract] Cited for: SUBCELLULAR LOCATION, FUNCTION IN PHOSPHORYLATION OF MYL9.
[14]	"Cytoplasmic localization of calcium/calmodulin-dependent protein kinase I-alpha depends on a nuclear export signal in its regulatory domain." Stedman D.R., Uboha N.V., Stedman T.T., Nairn A.C., Picciotto M.R. FEBS Lett. 566:275-280(2004) [PubMed: 15147908] [Abstract] Cited for: SUBCELLULAR LOCATION, NUCLEAR EXPORT SIGNAL, MUTAGENESIS OF 319-LEU--LEU-321 AND 263-LYS-ARG-264, INTERACTION WITH XPO1.
[15]	"Regulation of axonal extension and growth cone motility by calmodulin-dependent protein kinase I." Wayman G.A., Kaech S., Grant W.F., Davare M., Impey S., Tokumitsu H., Nozaki N., Banker G., Soderling T.R. J. Neurosci. 24:3786-3794(2004) [PubMed: 15084659] [Abstract] Cited for: FUNCTION.
[16]	"Structural basis for the autoinhibition of calcium/calmodulin-dependent protein kinase I." Goldberg J., Nairn A.C., Kuriyan J. Cell 84:875-887(1996) [PubMed: 8601311] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS). Tissue: Brain.
[17]	"Structure of the complex of calmodulin with the target sequence of calmodulin-dependent protein kinase I: studies of the kinase activation mechanism." Clapperton J.A., Martin S.R., Smerdon S.J., Gamblin S.J., Bayley P.M. Biochemistry 41:14669-14679(2002) [PubMed: 12475216] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 294-318 IN COMPLEX WITH CALMODULIN, DOMAIN.

Cross-references

Sequence databases

EMBLGenBankDDBJ

L24907 mRNA. Translation: AAA19670.1. Frameshift.
L26288 mRNA. Translation: AAA66944.1.
BC071177 mRNA. Translation: AAH71177.1.

IPI

IPI00209064.

PIR

S50193.

RefSeq

NP_604463.1.

UniGene

Rn.11018

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1A06	X-ray	2.50	A	1-322	[»]
1MXE	X-ray	1.70	E/F	294-318	[»]

ModBase

Search...

PTM databases

PhosphoSite

Q63450.

Genome annotation databases

GeneID

171503.

KEGG

rno:171503.

Organism-specific databases

RGD

629473. Camk1.

Phylogenomic databases

HOVERGEN

Q63450.

Enzyme and pathway databases

BRENDA

2.7.11.17. 248.

Family and domain databases

InterPro

IPR015734. Ca/calmodulin-dep_kinase_1.
IPR000719. Prot_kinase_core.
IPR017441. Protein_kinase_ATP_BS.
IPR017442. Se/Thr_pkinase-rel.
IPR008271. Ser_thr_pkin_AS.
IPR002290. Ser_thr_pkinase.
[Graphical view]

PANTHER

PTHR22982:SF34. CaMKI. 1 hit.

Pfam

PF00069. Pkinase. 1 hit.
[Graphical view]

ProDom

PD000001. Prot_kinase. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00220. S_TKc. 1 hit.
[Graphical view]

PROSITE

PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

622477.

Entry information

Entry name

KCC1A_RAT

Accession

Primary (citable) accession number: Q63450
Secondary accession number(s): Q63084

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	July 15, 1998
Last modified:	June 16, 2009
This is version 94 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)