Reviewed, UniProtKB/Swiss-Prot P17612 (KAPCA_HUMAN)

Names and origin

Protein names

Recommended name:
    cAMP-dependent protein kinase catalytic subunit alpha
      Short name=PKA C-alpha
    EC=2.7.11.11

Gene names

Name:	PRKACA
Synonyms:	PKACA

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

Protein attributes

Sequence length	351 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Phosphorylates a large number of substrates in the cytoplasm and the nucleus.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Enzyme regulation	Activated by cAMP.
Subunit structure	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.
Subcellular location	Cytoplasm By similarity. Nucleus By similarity. Note: Translocates into the nucleus (monomeric catalytic subunit) By similarity. The inactive holoenzyme is found in the cytoplasm By similarity.
Tissue specificity	Isoform 2 is sperm specific.
Post-translational modification	Asn-3 is partially deaminated to Asp giving rise to 2 major isoelectric variants, called CB and CA respectively By similarity.
Sequence similarities	Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. cAMP subfamily. Contains 1 AGC-kinase C-terminal domain. Contains 1 protein kinase domain.

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	ATP-binding Nucleotide-binding cAMP
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Lipoprotein Myristate Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	activation of protein kinase A activity Inferred from Experiment. Source: Reactome hormone-mediated signaling pathway Inferred from Experiment. Source: Reactome protein kinase cascade Inferred from Experiment. Source: Reactome
Cellular component	cAMP-dependent protein kinase complex Ref.1 Non-traceable author statement. Source: UniProtKB cytosol Inferred from Experiment. Source: Reactome nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Non-traceable author statement. Source: UniProtKB cAMP-dependent protein kinase activity Ref.1 Non-traceable author statement. Source: UniProtKB cAMP-dependent protein kinase inhibitor activity Inferred from Experiment. Source: Reactome protein kinase binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BCA3	Q9NQ31	2	EBI-476586,EBI-517035
PKIG	Q9Y2B9	1	EBI-476586,EBI-1052231
PRKAR1A	P10644	2	EBI-476586,EBI-476431

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P17612-1)

Also known as: C-alpha-1;

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: P17612-2)

Also known as: C-alpha-2; C-alpha-S; C(s);

The sequence of this isoform differs from the canonical sequence as follows:
     1-15: MGNAAAAKKGSEQES → MASNSSD

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed By similarity

Chain

2 – 351

350

cAMP-dependent protein kinase catalytic subunit alpha

PRO_0000086052

Regions

Domain

44 – 298

255

Protein kinase

Domain

299 – 351

53

AGC-kinase C-terminal

Nucleotide binding

50 – 58

9

ATP By similarity

Sites

Active site

167

1

Proton acceptor By similarity

Binding site

73

1

ATP By similarity

Amino acid modifications

Modified residue

3

1

Deamidated asparagine By similarity

Modified residue

11

1

Phosphoserine; by autocatalysis By similarity

Modified residue

49

1

Phosphothreonine Ref.12

Modified residue

140

1

Phosphoserine By similarity

Modified residue

196

1

Phosphothreonine Ref.12

Modified residue

198

1

Phosphothreonine Ref.11

Modified residue

202

1

Phosphothreonine Ref.10

Modified residue

339

1

Phosphoserine Ref.12 Ref.9 Ref.15

Lipidation

2

1

N-myristoyl glycine By similarity

Natural variations

Alternative sequence

1 – 15

15

MGNAA…SEQES → MASNSSD in isoform 2.

VSP_004759

Natural variant

41

1

L → V: dbSNP rs56029020. Ref.16

VAR_040591

Natural variant

46

1

R → Q: dbSNP rs56085217. Ref.16

VAR_040592

Natural variant

264

1

S → C: dbSNP rs35635531. Ref.16

VAR_040593

Secondary structure

1

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351

Helix Strand Turn

Details...

Helix

16 – 32

17

Helix

41 – 43

3

Beta strand

44 – 49

6

Beta strand

58 – 64

7

Beta strand

69 – 76

8

Helix

77 – 82

6

Helix

86 – 96

11

Beta strand

107 – 112

6

Beta strand

114 – 122

9

Helix

129 – 135

7

Helix

141 – 160

20

Helix

170 – 172

3

Beta strand

173 – 175

3

Beta strand

181 – 183

3

Helix

203 – 205

3

Helix

208 – 211

4

Helix

219 – 224

6

Helix

228 – 233

6

Helix

244 – 252

9

Helix

264 – 273

10

Turn

278 – 280

3

Helix

290 – 293

4

Helix

296 – 298

3

Helix

303 – 308

6

Turn

347 – 350

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (C-alpha-1) [UniParc]. Last modified January 23, 2007. Version 2. Checksum: BF6D3ECD2614E5AB	FASTA	351	40,590
	10 20 30 40 50 60 MGNAAAAKKG SEQESVKEFL AKAKEDFLKK WESPAQNTAH LDQFERIKTL GTGSFGRVML 70 80 90 100 110 120 VKHKETGNHY AMKILDKQKV VKLKQIEHTL NEKRILQAVN FPFLVKLEFS FKDNSNLYMV 130 140 150 160 170 180 MEYVPGGEMF SHLRRIGRFS EPHARFYAAQ IVLTFEYLHS LDLIYRDLKP ENLLIDQQGY 190 200 210 220 230 240 IQVTDFGFAK RVKGRTWTLC GTPEYLAPEI ILSKGYNKAV DWWALGVLIY EMAAGYPPFF 250 260 270 280 290 300 ADQPIQIYEK IVSGKVRFPS HFSSDLKDLL RNLLQVDLTK RFGNLKNGVN DIKNHKWFAT 310 320 330 340 350 TDWIAIYQRK VEAPFIPKFK GPGDTSNFDD YEEEEIRVSI NEKCGKEFSE F
	Isoform 2 (C-alpha-2) (C-alpha-S) (C(s)). Checksum: 5AD33AECC261EA16	FASTA	343	39,822
	10 20 30 40 50 60 MASNSSDVKE FLAKAKEDFL KKWESPAQNT AHLDQFERIK TLGTGSFGRV MLVKHKETGN 70 80 90 100 110 120 HYAMKILDKQ KVVKLKQIEH TLNEKRILQA VNFPFLVKLE FSFKDNSNLY MVMEYVPGGE 130 140 150 160 170 180 MFSHLRRIGR FSEPHARFYA AQIVLTFEYL HSLDLIYRDL KPENLLIDQQ GYIQVTDFGF 190 200 210 220 230 240 AKRVKGRTWT LCGTPEYLAP EIILSKGYNK AVDWWALGVL IYEMAAGYPP FFADQPIQIY 250 260 270 280 290 300 EKIVSGKVRF PSHFSSDLKD LLRNLLQVDL TKRFGNLKNG VNDIKNHKWF ATTDWIAIYQ 310 320 330 340 RKVEAPFIPK FKGPGDTSNF DDYEEEEIRV SINEKCGKEF SEF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A cDNA clone encoding human cAMP-dependent protein kinase catalytic subunit C alpha." Maldonado F., Hanks S.K. Nucleic Acids Res. 16:8189-8190(1988) [PubMed: 2843813] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Thalamus.
[3]	SeattleSNPs variation discovery resource Submitted (JUN-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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] (ISOFORM 1). Tissue: Eye and Testis.
[6]	"A novel isoform of human cAMP-dependent protein kinase, C-alpha-s, localizes to the sperm midpiece." Reinton N., Orstavik S., Haugen T.B., Jahnsen T., Tasken K., Skalhegg B.S. Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-189 (ISOFORM 2).
[7]	"The unique catalytic subunit of sperm cAMP-dependent protein kinase is the product of an alternative C-alpha mRNA expressed specifically in spermatogenic cells." San Agustin J.T., Wilkerson C.G., Witman G.B. Mol. Biol. Cell 11:3031-3044(2000) [PubMed: 10982398] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-152 (ISOFORM 2). Tissue: Testis.
[8]	"Expression of a nonmyristylated variant of the catalytic subunit of protein kinase A during male germ-cell development." Desseyn J.-L., Burton K.A., McKnight G.S. Proc. Natl. Acad. Sci. U.S.A. 97:6433-6438(2000) [PubMed: 10841548] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-39 (ISOFORM 2). Tissue: Testis.
[9]	"Phosphoproteome analysis of capacitated human sperm. Evidence of tyrosine phosphorylation of a kinase-anchoring protein 3 and valosin-containing protein/p97 during capacitation." Ficarro S., Chertihin O., Westbrook V.A., White F., Jayes F., Kalab P., Marto J.A., Shabanowitz J., Herr J.C., Hunt D.F., Visconti P.E. J. Biol. Chem. 278:11579-11589(2003) [PubMed: 12509440] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-339, MASS SPECTROMETRY. Tissue: Sperm.
[10]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-202, MASS SPECTROMETRY. Tissue: Epithelium.
[11]	"Proteomics analysis of protein kinases by target class-selective prefractionation and tandem mass spectrometry." Wissing J., Jaensch L., Nimtz M., Dieterich G., Hornberger R., Keri G., Wehland J., Daub H. Mol. Cell. Proteomics 6:537-547(2007) [PubMed: 17192257] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-198, MASS SPECTROMETRY.
[12]	"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 THR-49; THR-196 AND SER-339, MASS SPECTROMETRY.
[13]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[14]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-196 AND SER-339, MASS SPECTROMETRY.
[15]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-339, MASS SPECTROMETRY. Tissue: T-cell.
[16]	"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] VAL-41; GLN-46 AND CYS-264.
+	Additional computationally mapped references.

Web resources

SeattleSNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X07767 mRNA. Translation: CAA30597.1.
AK290147 mRNA. Translation: BAF82836.1.
DQ667173 Genomic DNA. Translation: ABG25918.1.
CH471106 Genomic DNA. Translation: EAW84399.1.
BC039846 mRNA. Translation: AAH39846.1.
BC108259 mRNA. Translation: AAI08260.1.
AF208004 mRNA. Translation: AAG35720.1.
AF239744 mRNA. Translation: AAF76426.1.
AF224718 mRNA. Translation: AAF75622.1.

IPI

IPI00217960.
IPI00396630.

PIR

OKHU2C. S01404.

RefSeq

NP_002721.1.
NP_997401.1.

UniGene

Hs.631630

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2GU8	X-ray	2.20	A	15-351	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-33878N.
DIP-46349N.

IntAct

P17612. 3 interactions.

STRING

P17612.

PTM databases

PhosphoSite

P17612.

Proteomic databases

PRIDE

P17612.

Genome annotation databases

Ensembl

ENST00000308677; ENSP00000309591; ENSG00000072062; Homo sapiens. [Genome view]

GeneID

5566.

KEGG

hsa:5566.

UCSC

uc002myb.1. human.
uc002myc.1. human.

Organism-specific databases

CTD

5566.

GeneCards

GC19M014063.

H-InvDB

HIX0014832.

HGNC

HGNC:9380. PRKACA.

HPA

CAB010361.

MIM

601639. gene.

PharmGKB

PA33748.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG17070.

HOGENOM

HBG755340.

HOVERGEN

P17612.

InParanoid

P17612.

OMA

GKEFTEF.

OrthoDB

EOG9MKR1W.

PhylomeDB

P17612.

Enzyme and pathway databases

BRENDA

2.7.11.11. 247.

Pathway_Interaction_DB

aurora_a_pathway. Aurora A signaling.
tcrcalciumpathway. Calcium signaling in the CD4+ TCR pathway.
pi3kciaktpathway. Class I PI3K signaling events mediated by Akt.
hedgehog_glipathway. Hedgehog signaling events mediated by Gli proteins.
lpa4_pathway. LPA4-mediated signaling events.
a4b1_paxdep_pathway. Paxillin-dependent events mediated by a4b1.
retinoic_acid_pathway. Retinoic acid receptors-mediated signaling.
nfat_3pathway. Role of Calcineurin-dependent NFAT signaling in lymphocytes.
hdac_classi_pathway. Signaling events mediated by HDAC Class I.
vegfr1_2_pathway. Signaling events mediated by VEGFR1 and VEGFR2.
syndecan_1_pathway. Syndecan-1-mediated signaling events.
syndecan_2_pathway. Syndecan-2-mediated signaling events.
txa2pathway. Thromboxane A2 receptor signaling.
vegfr1_pathway. VEGFR1 specific signals.

Reactome

REACT_11061. Signalling by NGF.
REACT_1505. Integration of energy metabolism.
REACT_152. Cell Cycle, Mitotic.
REACT_15295. Opioid Signalling.
REACT_15380. Diabetes pathways.
REACT_602. Metabolism of lipids and lipoproteins.

Gene expression databases

ArrayExpress

P17612.

Bgee

P17612.

CleanEx

HS_PRKACA.

Genevestigator

P17612.

GermOnline

ENSG00000072062. Homo sapiens.

Family and domain databases

InterPro

IPR000961. AGC-kinase_C.
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]

Pfam

PF00069. Pkinase. 1 hit.
[Graphical view]

SMART

SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]

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.
[Graphical view]

ProtoNet

Search...

Other Resources

BindingDB

P17612.

NextBio

21564.

SOURCE

Search...

Entry information

Entry name

KAPCA_HUMAN

Accession

Primary (citable) accession number: P17612
Secondary accession number(s): Q32P54 , Q9H2Y0, Q9NRB4, Q9NRH9

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1990
Last sequence update:	January 23, 2007
Last modified:	February 9, 2010
This is version 119 of the entry and version 2 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.