Calcium/calmodulin-dependent protein kinase type 1

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Reviewed, UniProtKB/Swiss-Prot Q14012 (KCC1A_HUMAN)

Last modified January 19, 2010. Version 103. History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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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

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	370 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

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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. Ref.6
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 intrasteric autoinhibition. Must be phosphorylated to be maximally active. Phosphorylated by CAMKK1 or CAMKK2. Ref.1
Subunit structure	Monomer. Interacts with XPO1 By similarity.
Subcellular location	Cytoplasm By similarity. Nucleus By similarity. Note: Predominantly cytoplasmic By similarity.
Tissue specificity	Ubiquitous.
Domain	The autoinhibitory domain overlaps with the calmodulin binding region and interacts in the inactive folded state with the catalytic domain as a pseudosubstrate By similarity.
Sequence similarities	Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CaMK subfamily. Contains 1 protein kinase domain.

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Ontologies

Keywords
Biological process	Differentiation Neurogenesis
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Calmodulin-binding Nucleotide-binding
Molecular function	Developmental protein Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Allosteric enzyme Complete proteome 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 positive regulation of muscle cell differentiation Inferred from mutant phenotype. Source: UniProtKB protein amino acid phosphorylation Traceable author statement. Source: ProtInc signal transduction Ref.1 Traceable author statement. Source: ProtInc
Cellular component	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 electronic annotation. Source: EC
Complete GO annotation...

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 370

370

Calcium/calmodulin-dependent protein kinase type 1

PRO_0000086076

Regions

Domain

20 – 276

257

Protein kinase

Nucleotide binding

26 – 34

ATP By similarity

Region

276 – 316

Autoinhibitory domain By similarity

Region

296 – 317

Calmodulin-binding By similarity

Motif

315 – 321

Nuclear export signal By similarity

Sites

Active site

141

Proton acceptor By similarity

Binding site

ATP

Amino acid modifications

Modified residue

177

Phosphothreonine; by CaMKK1 and CaMKK2 Ref.1

Natural variations

Natural variant

217

P → S in a metastatic melanoma sample; somatic mutation. Ref.8

VAR_040596

Natural variant

361

E → K: dbSNP rs56033923. Ref.8

VAR_040597

Experimental info

Mutagenesis

K → A: Loss of activity. Ref.1

Mutagenesis

177

T → A: Loss of activation by CaMKK1. Ref.1

Mutagenesis

177

T → D: Partial activation in absence of CAMKK1. Ref.1

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Sequences

Sequence

Length

Mass (Da)

Tools

Q14012-1 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 57FA20ECE00FA76C
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FASTA

370

41,337

        10         20         30         40         50         60 
MLGAVEGPRW KQAEDIRDIY DFRDVLGTGA FSEVILAEDK RTQKLVAIKC IAKEALEGKE 

        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 VAGGPAAGCC CRDCCVEPGT 

       370 
ELSPTLPHQL

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human calcium-calmodulin dependent protein kinase I: cDNA cloning, domain structure and activation by phosphorylation at threonine-177 by calcium-calmodulin dependent protein kinase I kinase." Haribabu B., Hook S.S., Selbert M.A., Goldstein E.G., Tomhave E.D., Edelman A.M., Snyderman R., Means A.R. EMBO J. 14:3679-3686(1995) [PubMed: 7641687] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PHOSPHORYLATION AT THR-177, MUTAGENESIS OF LYS-49 AND THR-177, ENZYME REGULATION.
[2]	"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].
[3]	"Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides." Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., Vandekerckhove J. Nat. Biotechnol. 21:566-569(2003) [PubMed: 12665801] [Abstract] Cited for: PROTEIN SEQUENCE OF 1-9. Tissue: Platelet.
[4]	"Cloning, expression and chromosomal localization of human Ca2+/calmodulin-dependent protein kinase kinase." Hsu L.-S., Tsou A.-P., Chi C.-W., Lee C.-H., Chen J.-Y. J. Biomed. Sci. 5:141-149(1998) [PubMed: 9662074] [Abstract] Cited for: PHOSPHORYLATION BY CAMKK1.
[5]	"Human Ca2+/calmodulin-dependent protein kinase kinase beta gene encodes multiple isoforms that display distinct kinase activity." Hsu L.-S., Chen G.-D., Lee L.-S., Chi C.-W., Cheng J.-F., Chen J.-Y. J. Biol. Chem. 276:31113-31123(2001) [PubMed: 11395482] [Abstract] Cited for: PHOSPHORYLATION BY CAMKK2.
[6]	"Phosphorylation screening identifies translational initiation factor 4GII as an intracellular target of Ca(2+)/calmodulin-dependent protein kinase I." Qin H., Raught B., Sonenberg N., Goldstein E.G., Edelman A.M. J. Biol. Chem. 278:48570-48579(2003) [PubMed: 14507913] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF EIF4G3.
[7]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[8]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] SER-217 AND LYS-361.
+	Additional computationally mapped references.

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Cross-references

Sequence databases
EMBL GenBank DDBJ	L41816 mRNA. Translation: AAA99458.1. BC106754 mRNA. Translation: AAI06755.1. BC106755 mRNA. Translation: AAI06756.1.
IPI	IPI00028296.
PIR	S57347.
RefSeq	NP_003647.1.
UniGene	Hs.434875
3D structure databases
SMR	Q14012. Positions 10-316.
ModBase	Search...
Protein-protein interaction databases
STRING	Q14012.
PTM databases
PhosphoSite	Q14012.
Proteomic databases
PeptideAtlas	Q14012.
PRIDE	Q14012.
Genome annotation databases
Ensembl	ENST00000256460; ENSP00000256460; ENSG00000134072; Homo sapiens. [Genome view]
GeneID	8536.
KEGG	hsa:8536.
NMPDR	fig\|9606.3.peg.22087.
UCSC	uc003bst.1. human.
Organism-specific databases
CTD	8536.
GeneCards	GC03M009774.
H-InvDB	HIX0018244.
HGNC	HGNC:1459. CAMK1.
MIM	604998. gene.
PharmGKB	PA26048.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG07976.
HOGENOM	HBG755340.
HOVERGEN	Q14012.
InParanoid	Q14012.
OMA	GNTAYTH.
OrthoDB	EOG9N5ZGB.
PhylomeDB	Q14012.
Enzyme and pathway databases
BRENDA	2.7.11.17. 247.
Gene expression databases
ArrayExpress	Q14012.
Bgee	Q14012.
CleanEx	HS_CAMK1.
Genevestigator	Q14012.
GermOnline	ENSG00000134072. Homo sapiens.
Family and domain databases
InterPro	IPR020636. Ca/CaM-dep_prot_kinase-like. IPR015734. Ca/CaM-dep_prot_kinase1. IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_prot_kinase-like_dom. IPR008271. Ser/Thr_prot_kinase_AS. IPR002290. Ser/Thr_prot_kinase_dom. [Graphical view]
PANTHER	PTHR22982. Ca/CaM-dep_prot_kinase-like. 1 hit. PTHR22982:SF34. CaMKI. 1 hit.
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
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	31972.
SOURCE	Search...

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Entry information

Entry name

KCC1A_HUMAN

Accession

Primary (citable) accession number: Q14012
Secondary accession number(s): Q3KPF6

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	November 1, 1996
Last modified:	January 19, 2010
This is version 103 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

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SIMILARITY comments

Index of protein domains and families

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Natural variations

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents