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Reviewed, UniProtKB/Swiss-Prot P05129 (KPCG_HUMAN)

Last modified September 2, 2008. Version 103. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    Protein kinase C gamma type
      Short name=PKC-gamma
    EC=2.7.11.13
Gene names
Name: PRKCG
Synonyms: PKCG
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 length697 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

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General annotation (Comments)

Function

This is a calcium-activated, phospholipid-dependent, serine- and threonine-specific enzyme.

PKC is activated by diacylglycerol which in turn phosphorylates a range of cellular proteins. PKC also serves as the receptor for phorbol esters, a class of tumor promoters.

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Cofactor

Binds 3 calcium ions per subunit. The ions are bound to the C2 domain By similarity.

Subunit structure

Interacts with CDCP1.

Involvement in disease

Defects in PRKCG are the cause of spinocerebellar ataxia type 14 (SCA14) [MIM:605361]. Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA14 is an autosomal dominant cerebellar ataxia (ADCA).

Sequence similarities

Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily.

Contains 1 AGC-kinase C-terminal domain.

Contains 1 C2 domain.

Contains 2 phorbol-ester/DAG-type zinc fingers.

Contains 1 protein kinase domain.

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical view

Molecule processing

Chain1 – 697697Protein kinase C gamma type

Regions

Domain170 – 26091C2
Domain351 – 614264Protein kinase
Domain615 – 68571AGC-kinase C-terminal
Zinc finger35 – 8551Phorbol-ester/DAG-type 1
Zinc finger100 – 15051Phorbol-ester/DAG-type 2
Nucleotide binding357 – 3659ATP By similarity

Sites

Active site4801Proton acceptor By similarity
Metal binding1861Calcium 1; via carbonyl oxygen By similarity
Metal binding1871Calcium 1 By similarity
Metal binding1871Calcium 2 By similarity
Metal binding1931Calcium 2 By similarity
Metal binding2461Calcium 1 By similarity
Metal binding2461Calcium 2 By similarity
Metal binding2471Calcium 2; via carbonyl oxygen By similarity
Metal binding2481Calcium 1 By similarity
Metal binding2481Calcium 2 By similarity
Metal binding2481Calcium 3 By similarity
Metal binding2511Calcium 3 By similarity
Metal binding2521Calcium 3; via carbonyl oxygen By similarity
Metal binding2541Calcium 1 By similarity
Metal binding2541Calcium 3 By similarity
Binding site3801ATP By similarity

Amino acid modifications

Modified residue1951Phosphotyrosine
Modified residue3121Phosphotyrosine By similarity
Modified residue3221Phosphoserine By similarity
Modified residue3301Phosphoserine By similarity
Modified residue5141Phosphothreonine By similarity
Modified residue5181Phosphothreonine By similarity
Modified residue6481Phosphothreonine; by autocatalysis Potential
Modified residue6551Phosphothreonine; by autocatalysis Potential
Modified residue6871Phosphoserine By similarity

Natural variations

Natural variant1011H → Y in SCA14.
Natural variant1191S → P in SCA14.
Natural variant1281G → D in SCA14.
Natural variant1411R → C
Natural variant4151H → Q
Natural variant5231A → D
Natural variant6591R → S

Secondary structure

1 ...................... 697
Helix Strand Turn

Details...

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Sequences

Sequence LengthMass (Da)Tools
P05129-1 [UniParc].

Last modified February 1, 1994. Version 3.
Checksum: 3F911B5BEF713C41

FASTA69778,448
        10         20         30         40         50         60 
MAGLGPGVGD SEGGPRPLFC RKGALRQKVV HEVKSHKFTA RFFKQPTFCS HCTDFIWGIG 

        70         80         90        100        110        120 
KQGLQCQVCS FVVHRRCHEF VTFECPGAGK GPQTDDPRNK HKFRLHSYSS PTFCDHCGSL 

       130        140        150        160        170        180 
LYGLVHQGMK CSCCEMNVHR RCVRSVPSLC GVDHTERRGR LQLEIRAPTA DEIHVTVGEA 

       190        200        210        220        230        240 
RNLIPMDPNG LSDPYVKLKL IPDPRNLTKQ KTRTVKATLN PVWNETFVFN LKPGDVERRL 

       250        260        270        280        290        300 
SVEVWDWDRT SRNDFMGAMS FGVSELLKAP VDGWYKLLNQ EEGEYYNVPV ADADNCSLLQ 

       310        320        330        340        350        360 
KFEACNYPLE LYERVRMGPS SSPIPSPSPS PTDPKRCFFG ASPGRLHISD FSFLMVLGKG 

       370        380        390        400        410        420 
SFGKVMLAER RGSDELYAIK ILKKDVIVQD DDVDCTLVEK RVLALGGRGP GGRPHFLTQL 

       430        440        450        460        470        480 
HSTFQTPDRL YFVMEYVTGG DLMYHIQQLG KFKEPHAAFY AAEIAIGLFF LHNQGIIYRD 

       490        500        510        520        530        540 
LKLDNVMLDA EGHIKITDFG MCKENVFPGT TTRTFCGTPD YIAPEIIAYQ PYGKSVDWWS 

       550        560        570        580        590        600 
FGVLLYEMLA GQPPFDGEDE EELFQAIMEQ TVTYPKSLSR EAVAICKGFL TKHPGKRLGS 

       610        620        630        640        650        660 
GPDGEPTIRA HGFFRWIDWE RLERLEIPPP FRPRPCGRSG ENFDKFFTRA APALTPPDRL 

       670        680        690 
VLASIDQADF QGFTYVNPDF VHPDARSPTS PVPVPVM

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References

« Hide 'large scale' references
[1]Cui W.C., Yu L., Chu Y.Y., Wang J., Zheng L.H., Zhou G.J., Zhao S.Y.
Submitted (FEB-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[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].
Tissue: Brain.
[3]"Multiple, distinct forms of bovine and human protein kinase C suggest diversity in cellular signaling pathways."
Coussens L., Parker P.J., Rhee L., Yang-Feng T.L., Chen E., Waterfield M.D., Francke U., Ullrich A.
Science 233:859-866(1986) [PubMed: 3755548] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-318.
Tissue: Brain.
[4]"Activation and substrate specificity of the human protein kinase C alpha and zeta isoenzymes."
Kochs G., Hummel R., Meyer D., Hug H., Marme D., Sarre T.F.
Eur. J. Biochem. 216:597-606(1993) [PubMed: 8375396] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 162-697.
Tissue: Hippocampus.
[5]"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer."
Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. expand/collapse author list , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J.
Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-195, MASS SPECTROMETRY.
[6]"Segregation of a PRKCG mutation in two RP11 families."
Al-Maghtheh M., Vithana E.N., Inglehearn C.F., Moore T., Bird A.C., Bhattacharya S.S.
Am. J. Hum. Genet. 62:1248-1252(1998) [PubMed: 9545390] [Abstract]
Cited for: VARIANTS CYS-141; GLN-415; ASP-523 AND SER-659.
[7]"No mutations in the coding region of the PRKCG gene in three families with retinitis pigmentosa linked to the RP11 locus on chromosome 19q."
Dryja T.P., McEvoy J., McGee T.L., Berson E.L.
Am. J. Hum. Genet. 65:926-928(1999) [PubMed: 10441600] [Abstract]
Cited for: SHOWS THAT THE VARIANTS ARE NOT A CAUSE OF RP11.
[8]"Missense mutations in the regulatory domain of PKC gamma: a new mechanism for dominant nonepisodic cerebellar ataxia."
Chen D.-H., Brkanac Z., Verlinde C.L.M.J., Tan X.-J., Bylenok L., Nochlin D., Matsushita M., Lipe H., Wolff J., Fernandez M., Cimino P.J., Bird T.D., Raskind W.H.
Am. J. Hum. Genet. 72:839-849(2003) [PubMed: 12644968] [Abstract]
Cited for: VARIANTS SCA14 TYR-101; PRO-119 AND ASP-128.
[9]"The C2 domain of PKCdelta is a phosphotyrosine binding domain."
Benes C.H., Wu N., Elia A.E.H., Dharia T., Cantley L.C., Soltoff S.P.
Cell 121:271-280(2005) [PubMed: 15851033] [Abstract]
Cited for: INTERACTION WITH CDCP1.
+Additional computationally mapped references.

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Web resources

Mutations of the PRKCG gene

Retina International's Scientific Newsletter

GeneReviews

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Cross-references

Sequence databases

AF345987 mRNA. Translation: AAK13533.1.
BC047876 mRNA. Translation: AAH47876.1.
M13977 mRNA. Translation: AAA60102.1. Different termination.
Z15114 mRNA. Translation: CAA78820.1.
PIRD24664.
RefSeqNP_002730.1.
UniGeneHs.631564

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
2E73NMR-A36-105[»]
2UZPX-ray2.00A/B/C154-295[»]
SMRP05129. Positions 93-158, 348-683.
ModBaseSearch...

Protein-protein interaction databases

IntActP05129.

PTM databases

PhosphoSiteP05129.

Proteomic databases

PeptideAtlasP05129.

Genome annotation databases

EnsemblENSG00000126583. Homo sapiens. [Contig view]
GeneID5582.
KEGGhsa:5582.

Organism-specific databases

H-InvDBHIX0027463.
HGNCHGNC:9402. PRKCG.
HPACAB013051.
MIM176980. gene.
605361. phenotype.
Orphanet99. Cerebellar ataxia, autosomal dominant.
PharmGKBPA33766.
GenAtlasSearch...
GeneCardsSearch...

Phylogenomic databases

HOGENOMP05129.
HOVERGENP05129.

Gene expression databases

ArrayExpressP05129.
CleanExHS_PRKCG.
GermOnlineENSG00000126583. Homo sapiens.

Family and domain databases

InterProIPR000008. C2_Ca-dep.
IPR002219. DAG_PE_bd.
IPR015745. PKC.
IPR000961. Pkinase_C.
IPR014375. Prot_kin_PKC_alpha.
IPR000719. Prot_kinase_core.
IPR017441. Protein_kinase_ATP_bd_CS.
IPR017442. Se/Thr_pkinase-rel.
IPR008271. Ser_thr_pkin_AS.
IPR002290. Ser_thr_pkinase.
[Graphical view]
PANTHERPTHR22985:SF86. PKC. 1 hit.
PfamPF00130. C1_1. 2 hits.
PF00168. C2. 1 hit.
PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
[Graphical view]
PIRSFPIRSF000550. PKC_alpha. 1 hit.
PRINTSPR00360. C2DOMAIN.
PR00008. DAGPEDOMAIN.
ProDomPD000001. Prot_kinase. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTSM00109. C1. 2 hits.
SM00239. C2. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
PROSITEPS51285. AGC_KINASE_CTER. 1 hit.
PS50004. C2. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS00479. ZF_DAG_PE_1. 2 hits.
PS50081. ZF_DAG_PE_2. 2 hits.
[Graphical view]
BLOCKSSearch...

Other Resources

SOURCESearch...
ProtoNetSearch...

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Entry information

Entry nameKPCG_HUMAN
AccessionPrimary (citable) accession number: P05129
Entry history
Integrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: February 1, 1994
Last modified: September 2, 2008
This is version 103 of the entry and version 3 of the sequence. [Complete history]