Reviewed, UniProtKB/Swiss-Prot Q14012 (KCC1A_HUMAN)

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)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	370 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 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.

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 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 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...

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	9	ATP By similarity
	Region	276 – 316	41	Autoinhibitory domain By similarity
	Region	296 – 317	22	Calmodulin-binding By similarity
	Motif	315 – 321	7	Nuclear export signal By similarity
Sites
	Active site	141	1	Proton acceptor By similarity
	Binding site	49	1	ATP
Amino acid modifications
	Modified residue	177	1	Phosphothreonine; by CaMKK1 and CaMKK2 Ref.1
Natural variations
	Natural variant	217	1	P → S in a metastatic melanoma sample; somatic mutation. Ref.8		VAR_040596
	Natural variant	361	1	E → K Ref.8		VAR_040597
Experimental info
	Mutagenesis	49	1	K → A: Loss of activity. Ref.1
	Mutagenesis	177	1	T → A: Loss of activation by CaMKK1. Ref.1
	Mutagenesis	177	1	T → D: Partial activation in absence of CAMKK1. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q14012-1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 57FA20ECE00FA76C	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

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. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., 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.

Cross-references

Sequence databases
EMBLGenBankDDBJ	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
HSSP	HSSP built from PDB template 1A06 based on UniProtKB Q63450.
SMR	Q14012. Positions 10-316.
ModBase	Search...
PTM databases
PhosphoSite	Q14012.
Proteomic databases
PeptideAtlas	Q14012.
PRIDE	Q14012.
Genome annotation databases
Ensembl	ENSG00000134072. Homo sapiens. [Contig view]
GeneID	8536.
KEGG	hsa:8536.
NMPDR	fig|9606.3.peg.22087.
Organism-specific databases
GeneCards	GC03M009774.
H-InvDB	HIX0018244.
HGNC	HGNC:1459. CAMK1.
MIM	604998. gene.
PharmGKB	PA26048.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q14012.
HOVERGEN	Q14012.
OMA	Q14012. EEDSKIM.
Enzyme and pathway databases
BRENDA	2.7.11.17. 247.
Gene expression databases
ArrayExpress	Q14012.
Bgee	Q14012.
CleanEx	HS_CAMK1.
GermOnline	ENSG00000134072. Homo sapiens.
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	31972.
SOURCE	Search...

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:	June 16, 2009
This is version 94 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)