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)

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	CytoplasmBy similarity. NucleusBy 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
Gene Ontology (GO)
Biological process	hormone-mediated signaling Inferred from Experiment. Source: Reactome protein amino acid phosphorylation Ref.1 Non-traceable author statement. Source: UniProtKB protein kinase cascade Inferred from Experiment. Source: Reactome
Cellular component	cAMP-dependent protein kinase complex Ref.1 Non-traceable author statement. Source: UniProtKB
Molecular function	ATP binding Non-traceable author statement. Source: UniProtKB cAMP-dependent protein kinase activity Ref.1 Non-traceable author statement. Source: UniProtKB protein binding Inferred from physical interaction. Source: IntAct
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
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 351	350	cAMP-dependent protein kinase catalytic subunit alpha
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	140	1	Phosphoserine By similarity
	Modified residue	196	1	Phosphothreonine By similarity
	Modified residue	198	1	Phosphothreonine
	Modified residue	202	1	Phosphothreonine
	Modified residue	339	1	Phosphoserine
	Lipidation	2	1	N-myristoyl glycine By similarity
Natural variations
	Alternative sequence	1 – 15	15	MGNAA…SEQES → MASNSSD in isoform 2.
	Natural variant	41	1	L → V
	Natural variant	46	1	R → Q
	Natural variant	264	1	S → C

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)) [UniParc]. Checksum: 5AD33AECC261EA16		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 program for genomic applications 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]	"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

EMBLGenBankDDBJ

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.

PIR

OKHU2C. S01404.

RefSeq

NP_002721.1.
NP_997401.1.

UniGene

Hs.631630

3D structure databases

PDBMSD

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

SMR

P17612. Positions 10-351.

ModBase

Search...

Protein-protein interaction databases

IntAct

P17612.

PTM databases

PhosphoSite

P17612.

Genome annotation databases

Ensembl

ENSG00000072062. Homo sapiens. [Contig view]

GeneID

5566.

KEGG

hsa:5566.

Organism-specific databases

H-InvDB

HIX0014832.

HGNC

HGNC:9380. PRKACA.

HPA

CAB010361.

MIM

601639. gene.

PharmGKB

PA33748.

GenAtlas

Search...

GeneCards

Search...

Phylogenomic databases

HOGENOM

P17612.

HOVERGEN

P17612.

Enzyme and pathway databases

Reactome

REACT_1505. Integration of energy metabolism.
REACT_602. Lipid and lipoprotein metabolism.

Gene expression databases

ArrayExpress

P17612.

CleanEx

HS_PRKACA.

GermOnline

ENSG00000072062. Homo sapiens.

Family and domain databases

InterPro

IPR000961. Pkinase_C.
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]

Pfam

PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
[Graphical view]

ProDom

PD000001. Prot_kinase. 1 hit.
[Graphical view] [Entries sharing at least one domain]

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]

BLOCKS

Search...

Other Resources

BindingDB

P17612.

SOURCE

Search...

ProtoNet

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:	September 2, 2008
This is version 100 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)