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Protein

cAMP-dependent protein kinase catalytic subunit gamma

Gene

PRKACG

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Phosphorylates a large number of substrates in the cytoplasm and the nucleus.

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulationi

Activated by cAMP.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei73ATPPROSITE-ProRule annotation1
Active sitei167Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi50 – 58ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
LigandATP-binding, cAMP, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.11. 2681.
ReactomeiR-HSA-111931. PKA-mediated phosphorylation of CREB.
R-HSA-163358. PKA-mediated phosphorylation of key metabolic factors.
R-HSA-163560. Triglyceride catabolism.
R-HSA-163615. PKA activation.
R-HSA-164378. PKA activation in glucagon signalling.
R-HSA-180024. DARPP-32 events.
R-HSA-381676. Glucagon-like Peptide-1 (GLP1) regulates insulin secretion.
R-HSA-392517. Rap1 signalling.
R-HSA-422356. Regulation of insulin secretion.
R-HSA-432040. Vasopressin regulates renal water homeostasis via Aquaporins.
R-HSA-4420097. VEGFA-VEGFR2 Pathway.
R-HSA-442720. CREB phosphorylation through the activation of Adenylate Cyclase.
R-HSA-5610780. Degradation of GLI1 by the proteasome.
R-HSA-5610783. Degradation of GLI2 by the proteasome.
R-HSA-5610785. GLI3 is processed to GLI3R by the proteasome.
R-HSA-5610787. Hedgehog 'off' state.
R-HSA-5621575. CD209 (DC-SIGN) signaling.
R-HSA-5687128. MAPK6/MAPK4 signaling.
R-HSA-70263. Gluconeogenesis.
R-HSA-8853659. RET signaling.
R-HSA-8963896. HDL assembly.
R-HSA-983231. Factors involved in megakaryocyte development and platelet production.
SABIO-RKiP22612.
SignaLinkiP22612.
SIGNORiP22612.

Names & Taxonomyi

Protein namesi
Recommended name:
cAMP-dependent protein kinase catalytic subunit gamma (EC:2.7.11.11)
Short name:
PKA C-gamma
Gene namesi
Name:PRKACG
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

HGNCiHGNC:9382. PRKACG.

Subcellular locationi

GO - Cellular componenti

Pathology & Biotechi

Involvement in diseasei

Bleeding disorder, platelet-type 19 (BDPLT19)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder characterized by increased bleeding tendency due to platelet dysfunction. Clinical features include epistaxis, hematomas, bleeding after tooth extraction, and menorrhagia.
See also OMIM:616176
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07267274I → M in BDPLT19; patient platelets show impaired activation. 1 PublicationCorresponds to variant dbSNP:rs724159972Ensembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi5568.
MalaCardsiPRKACG.
MIMi616176. phenotype.
OpenTargetsiENSG00000165059.
PharmGKBiPA33750.

Chemistry databases

ChEMBLiCHEMBL2743.
GuidetoPHARMACOLOGYi1478.

Polymorphism and mutation databases

BioMutaiPRKACG.
DMDMi33860173.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved
ChainiPRO_00000860642 – 351cAMP-dependent protein kinase catalytic subunit gammaAdd BLAST350

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycineBy similarity1
Modified residuei198Phosphothreonine; by autocatalysisBy similarity1
Modified residuei339Phosphoserine; by autocatalysisBy similarity1

Keywords - PTMi

Lipoprotein, Myristate, Phosphoprotein

Proteomic databases

EPDiP22612.
MaxQBiP22612.
PaxDbiP22612.
PeptideAtlasiP22612.
PRIDEiP22612.

PTM databases

iPTMnetiP22612.
PhosphoSitePlusiP22612.

Expressioni

Tissue specificityi

Testis specific. But important tissues such as brain and ovary have not been analyzed for the content of transcript.

Gene expression databases

BgeeiENSG00000165059.
CleanExiHS_PRKACG.
GenevisibleiP22612. HS.

Organism-specific databases

HPAiCAB004530.
HPA071185.

Interactioni

Subunit structurei

A number of inactive tetrameric holoenzymes are produced by the combination of homo- or heterodimers of the different regulatory subunits associated with two catalytic subunits. cAMP causes the dissociation of the inactive holoenzyme into a dimer of regulatory subunits bound to four cAMP and two free monomeric catalytic subunits.

Protein-protein interaction databases

BioGridi111555. 37 interactors.
IntActiP22612. 3 interactors.
MINTiMINT-3009782.
STRINGi9606.ENSP00000366488.

Chemistry databases

BindingDBiP22612.

Structurei

3D structure databases

ProteinModelPortaliP22612.
SMRiP22612.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini44 – 298Protein kinasePROSITE-ProRule annotationAdd BLAST255
Domaini299 – 351AGC-kinase C-terminalAdd BLAST53

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0616. Eukaryota.
ENOG410XPQQ. LUCA.
GeneTreeiENSGT00810000125385.
HOGENOMiHOG000233033.
HOVERGENiHBG108317.
InParanoidiP22612.
KOiK04345.
OMAiAKKDTEQ.
OrthoDBiEOG091G10O8.
PhylomeDBiP22612.
TreeFamiTF313399.

Family and domain databases

InterProiView protein in InterPro
IPR000961. AGC-kinase_C.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
PfamiView protein in Pfam
PF00069. Pkinase. 1 hit.
SMARTiView protein in SMART
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiView protein in PROSITE
PS51285. AGC_KINASE_CTER. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P22612-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGNAPAKKDT EQEESVNEFL AKARGDFLYR WGNPAQNTAS SDQFERLRTL
60 70 80 90 100
GMGSFGRVML VRHQETGGHY AMKILNKQKV VKMKQVEHIL NEKRILQAID
110 120 130 140 150
FPFLVKLQFS FKDNSYLYLV MEYVPGGEMF SRLQRVGRFS EPHACFYAAQ
160 170 180 190 200
VVLAVQYLHS LDLIHRDLKP ENLLIDQQGY LQVTDFGFAK RVKGRTWTLC
210 220 230 240 250
GTPEYLAPEI ILSKGYNKAV DWWALGVLIY EMAVGFPPFY ADQPIQIYEK
260 270 280 290 300
IVSGRVRFPS KLSSDLKHLL RSLLQVDLTK RFGNLRNGVG DIKNHKWFAT
310 320 330 340 350
TSWIAIYEKK VEAPFIPKYT GPGDASNFDD YEEEELRISI NEKCAKEFSE

F
Length:351
Mass (Da):40,434
Last modified:January 23, 2007 - v3
Checksum:iE66BB4BFB8AF9B50
GO

Sequence cautioni

The sequence AAC41690 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti345A → P in AAH39888 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07267274I → M in BDPLT19; patient platelets show impaired activation. 1 PublicationCorresponds to variant dbSNP:rs724159972Ensembl.1
Natural variantiVAR_040595251I → N1 PublicationCorresponds to variant dbSNP:rs56287972Ensembl.1
Natural variantiVAR_033902268H → D3 PublicationsCorresponds to variant dbSNP:rs3730386Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M34182 mRNA. Translation: AAC41690.1. Different initiation.
AJ001597 Genomic DNA. Translation: CAA04863.1.
DQ667175 Genomic DNA. Translation: ABG25920.1.
AL162730 Genomic DNA. No translation available.
BC039888 mRNA. Translation: AAH39888.1.
CCDSiCCDS6625.1.
PIRiB34724. OKHUCG.
RefSeqiNP_002723.2. NM_002732.3.
UniGeneiHs.158029.

Genome annotation databases

EnsembliENST00000377276; ENSP00000366488; ENSG00000165059.
GeneIDi5568.
KEGGihsa:5568.
UCSCiuc004agy.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiKAPCG_HUMAN
AccessioniPrimary (citable) accession number: P22612
Secondary accession number(s): O60850, Q5VZ02, Q86YI1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: January 23, 2007
Last modified: August 30, 2017
This is version 172 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  6. SIMILARITY comments
    Index of protein domains and families