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Reviewed, UniProtKB/Swiss-Prot Q8N5S9 (KKCC1_HUMAN)

Last modified June 16, 2009. Version 67. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    Calcium/calmodulin-dependent protein kinase kinase 1
      Short name=CaMKK 1
    EC=2.7.11.17
Alternative name(s):
    Calcium/calmodulin-dependent protein kinase kinase alpha
      Short name=CaM-kinase kinase alpha
      Short name=CaM-KK alpha
      Short name=CaMKK alpha
    CaM-kinase IV kinase
Gene names
Name: CAMKK1
Synonyms: CAMKKA
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length505 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

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General annotation (Comments)

Function

Calcium/calmodulin-dependent protein kinase that belongs to a proposed calcium-triggered signaling cascade involved in a number of cellular processes. Phosphorylates CAMK1, CAMK1D, CAMK1G and CAMK4. Involved in regulating cell apoptosis. Promotes cell survival by phosphorylating AKT1/PKB that inhibits pro-apoptotic BAD/Bcl2-antagonist of cell death. Ref.4

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulation

Activated by Ca2+/calmodulin. Binding of calmodulin may releave intrasteric autoinhibition. Partially inhibited upon phosphorylation by PRCAKA/PKA By similarity. May be regulated through phosphorylation by CAMK1 and CAMK4.

Subunit structure

Interacts with CAMK4 and calmodulin By similarity.

Subcellular location

Cytoplasm By similarity. Nucleus By similarity.

Domain

The autoinhibitory domain overlaps with the calmodulin binding region and may be involved in intrasteric autoinhibition.

The RP domain (arginine/proline-rich) is involved in the recognition of CAMKI and CAMK4 as substrates By similarity.

Post-translational modification

Appears to be autophosphorylated in a Ca2+/calmodulin-dependent manner. Phosphorylated at multiple sites by PRCAKA/PKA. Phosphorylation of Ser-458 is blocked upon binding to Ca2+/calmodulin. In vitro, phosphorylated by CAMK1 and CAMK4 By similarity.

Sequence similarities

Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.

Contains 1 protein kinase domain.

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Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8N5S9-1)

Also known as: A; Variant 3;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q8N5S9-2)

Also known as: B; Variant 1;

The sequence of this isoform differs from the canonical sequence as follows:
     228-228: L → LALQNQAQNIQLDSTNIAKPHSLLPSEQQDSGSTWAARS
     483-505: Missing.

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 505505Calcium/calmodulin-dependent protein kinase kinase 1
PRO_0000086141

Regions

Domain128 – 409282Protein kinase
Nucleotide binding134 – 1429ATP By similarity
Region167 – 18923RP domain
Region435 – 4406Autoinhibitory domain By similarity
Region438 – 46326Calmodulin-binding By similarity

Sites

Active site2751Proton acceptor By similarity
Binding site1571ATP By similarity

Amino acid modifications

Modified residue741Phosphoserine Ref.5
Modified residue1081Phosphothreonine By similarity
Modified residue4581Phosphoserine Ref.5
Modified residue4751Phosphoserine By similarity
Modified residue4921Phosphoserine Ref.5 Ref.6

Natural variations

Alternative sequence2281L → LALQNQAQNIQLDSTNIAKP HSLLPSEQQDSGSTWAARS in isoform 2.
VSP_012140
Alternative sequence483 – 50523Missing in isoform 2.
VSP_012141
Natural variant3751E → G: dbSNP rs7214723. Ref.3 Ref.7
VAR_020531

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Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (A) (Variant 3) [UniParc].

Last modified December 7, 2004. Version 2.
Checksum: 92A055D20E487C86

FASTA50555,735
        10         20         30         40         50         60 
MEGGPAVCCQ DPRAELVERV AAIDVTHLEE ADGGPEPTRN GVDPPPRARA ASVIPGSTSR 

        70         80         90        100        110        120 
LLPARPSLSA RKLSLQERPA GSYLEAQAGP YATGPASHIS PRAWRRPTIE SHHVAISDAE 

       130        140        150        160        170        180 
DCVQLNQYKL QSEIGKGAYG VVRLAYNESE DRHYAMKVLS KKKLLKQYGF PRRPPPRGSQ 

       190        200        210        220        230        240 
AAQGGPAKQL LPLERVYQEI AILKKLDHVN VVKLIEVLDD PAEDNLYLVF DLLRKGPVME 

       250        260        270        280        290        300 
VPCDKPFSEE QARLYLRDVI LGLEYLHCQK IVHRDIKPSN LLLGDDGHVK IADFGVSNQF 

       310        320        330        340        350        360 
EGNDAQLSST AGTPAFMAPE AISDSGQSFS GKALDVWATG VTLYCFVYGK CPFIDDFILA 

       370        380        390        400        410        420 
LHRKIKNEPV VFPEEPEISE ELKDLILKML DKNPETRIGV PDIKLHPWVT KNGEEPLPSE 

       430        440        450        460        470        480 
EEHCSVVEVT EEEVKNSVRL IPSWTTVILV KSMLRKRSFG NPFEPQARRE ERSMSAPGNL 

       490        500 
LVKEGFGEGG KSPELPGVQE DEAAS

« Hide

Isoform 2 (B) (Variant 1).

Checksum: 7FDC2623527C827E
Show »

FASTA52057,523

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References

« Hide 'large scale' references
[1]"Characterization of human CaMKK alpha gene structure."
Harvey M., Carra S., Tascedda F., Barden N.
Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
Tissue: Brain.
[2]"Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs."
Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., Ottenwaelder B., Obermaier B. expand/collapse author list , Tampe J., Heubner D., Wambutt R., Korn B., Klein M., Poustka A.
Genome Res. 11:422-435(2001) [PubMed: 11230166] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Amygdala.
[3]"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] (ISOFORMS 1 AND 2), VARIANT GLY-375.
Tissue: Brain.
[4]"Identification and characterization of novel components of a Ca2+/calmodulin-dependent protein kinase cascade in HeLa cells."
Ishikawa Y., Tokumitsu H., Inuzuka H., Murata-Hori M., Hosoya H., Kobayashi R.
FEBS Lett. 550:57-63(2003) [PubMed: 12935886] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF CAMK1D.
[5]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-74; SER-458 AND SER-492, MASS SPECTROMETRY.
[6]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-492, MASS SPECTROMETRY.
[7]"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. expand/collapse author list , 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: VARIANT [LARGE SCALE ANALYSIS] GLY-375.
+Additional computationally mapped references.

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Cross-references

Sequence databases

AF425232 mRNA. Translation: AAN37386.1.
AF425301 mRNA. Translation: AAN37387.1.
AL136576 mRNA. Translation: CAB66511.1.
BC031647 mRNA. Translation: AAH31647.1.
BC043487 mRNA. Translation: AAH43487.1.
IPIIPI00017083.
IPI00166909.
RefSeqNP_115670.1.
NP_757343.1.
NP_757344.2.
UniGeneHs.8417

3D structure databases

HSSPHSSP built from PDB template 1J3H based on UniProtKB P05132.
ModBaseSearch...

PTM databases

PhosphoSiteQ8N5S9.

Proteomic databases

PRIDEQ8N5S9.

Genome annotation databases

EnsemblENSG00000004660. Homo sapiens. [Contig view]
GeneID84254.
KEGGhsa:84254.

Organism-specific databases

GeneCardsGC17M003710.
H-InvDBHIX0013435.
HIX0039373.
HGNCHGNC:1469. CAMKK1.
HPACAB009111.
MIM611411. gene.
PharmGKBPA26051.
GenAtlasSearch...

Phylogenomic databases

HOGENOMQ8N5S9.
HOVERGENQ8N5S9.

Enzyme and pathway databases

BRENDA2.7.11.17. 247.

Gene expression databases

ArrayExpressQ8N5S9.
BgeeQ8N5S9.
CleanExHS_CAMKK1.
GermOnlineENSG00000004660. Homo sapiens.

Family and domain databases

InterProIPR000719. Prot_kinase_core.
IPR017441. Protein_kinase_ATP_BS.
IPR017442. Se/Thr_pkinase-rel.
IPR008271. Ser_thr_pkin_AS.
IPR002290. Ser_thr_pkinase.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
ProDomPD000001. Prot_kinase. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio73756.
PMAP-CutDBQ8N5S9.
SOURCESearch...

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Entry information

Entry nameKKCC1_HUMAN
AccessionPrimary (citable) accession number: Q8N5S9
Secondary accession number(s): Q9BQH3
Entry history
Integrated into UniProtKB/Swiss-Prot: December 7, 2004
Last sequence update: December 7, 2004
Last modified: June 16, 2009
This is version 67 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

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