P31321 (KAP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
cAMP-dependent protein kinase type I-beta regulatory subunit

Gene names

Name:

PRKAR1B

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	381 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	Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells. Ref.9
Subunit structure	The inactive holoenzyme is composed of two regulatory chains and two catalytic chains. Activation by cAMP releases the two active catalytic monomers and the regulatory dimer. Interacts with PRKX; regulates this cAMP-dependent protein kinase. Interacts with C2orf88/smAKAP; this interaction may target PRKAR1B to the plasma membrane. Ref.9 Ref.10
Subcellular location	Cell membrane Ref.10.
Tissue specificity	Four types of regulatory chains are found: I-alpha, I-beta, II-alpha, and II-beta. Their expression varies among tissues and is in some cases constitutive and in others inducible.
Post-translational modification	The pseudophosphorylation site binds to the substrate-binding region of the catalytic chain, resulting in the inhibition of its activity.
Sequence similarities	Belongs to the cAMP-dependent kinase regulatory chain family. Contains 2 cyclic nucleotide-binding domains.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Domain	Repeat
Ligand	Nucleotide-binding cAMP cAMP-binding
PTM	Acetylation Disulfide bond Nitration Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	activation of phospholipase C activity Traceable author statement. Source: Reactome activation of protein kinase A activity Traceable author statement. Source: Reactome blood coagulation Traceable author statement. Source: Reactome cellular response to glucagon stimulus Traceable author statement. Source: Reactome energy reserve metabolic process Traceable author statement. Source: Reactome epidermal growth factor receptor signaling pathway Traceable author statement. Source: Reactome fibroblast growth factor receptor signaling pathway Traceable author statement. Source: Reactome innate immune response Traceable author statement. Source: Reactome learning or memory Inferred from electronic annotation. Source: Compara neurotrophin TRK receptor signaling pathway Traceable author statement. Source: Reactome protein phosphorylation Non-traceable author statement Ref.1. Source: UniProtKB regulation of insulin secretion Traceable author statement. Source: Reactome small molecule metabolic process Traceable author statement. Source: Reactome transmembrane transport Traceable author statement. Source: Reactome water transport Traceable author statement. Source: Reactome
Cellular_component	cAMP-dependent protein kinase complex Non-traceable author statement Ref.1. Source: UniProtKB cytosol Traceable author statement. Source: Reactome plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	cAMP binding Inferred from electronic annotation. Source: UniProtKB-KW cAMP-dependent protein kinase regulator activity Non-traceable author statement Ref.1. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed By similarity

Chain

2 – 381

380

cAMP-dependent protein kinase type I-beta regulatory subunit

PRO_0000205381

Regions

Nucleotide binding

137 – 254

118

cAMP 1

Nucleotide binding

255 – 381

127

cAMP 2

Region

2 – 136

135

Dimerization and phosphorylation

Motif

96 – 100

5

Pseudophosphorylation motif

Sites

Binding site

202

1

cAMP 1

Binding site

211

1

cAMP 1

Binding site

326

1

cAMP 2

Binding site

335

1

cAMP 2

Amino acid modifications

Modified residue

2

1

N-acetylalanine Probable

Modified residue

21

1

Nitrated tyrosine Ref.5

Modified residue

77

1

Phosphoserine Ref.7

Modified residue

83

1

Phosphoserine Ref.7 Ref.8

Disulfide bond

18

Interchain (with C-39) By similarity

Disulfide bond

39

Interchain (with C-18) By similarity

Experimental info

Sequence conflict

270

1

A → R in AAC37564. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

381

Helix Strand Turn

Details...

Helix

19 – 24

6

Turn

27 – 31

5

Helix

32 – 41

10

Helix

46 – 68

23

Sequences

	Sequence		Length	Mass (Da)
	P31321 [UniParc]. Last modified May 5, 2009. Version 4. Checksum: 1ED7BFEC30897191	FASTA	381	43,073
	10 20 30 40 50 60 MASPPACPSE EDESLKGCEL YVQLHGIQQV LKDCIVHLCI SKPERPMKFL REHFEKLEKE 70 80 90 100 110 120 ENRQILARQK SNSQSDSHDE EVSPTPPNPV VKARRRRGGV SAEVYTEEDA VSYVRKVIPK 130 140 150 160 170 180 DYKTMTALAK AISKNVLFAH LDDNERSDIF DAMFPVTHIA GETVIQQGNE GDNFYVVDQG 190 200 210 220 230 240 EVDVYVNGEW VTNISEGGSF GELALIYGTP RAATVKAKTD LKLWGIDRDS YRRILMGSTL 250 260 270 280 290 300 RKRKMYEEFL SKVSILESLE KWERLTVADA LEPVQFEDGE KIVVQGEPGD DFYIITEGTA 310 320 330 340 350 360 SVLQRRSPNE EYVEVGRLGP SDYFGEIALL LNRPRAATVV ARGPLKCVKL DRPRFERVLG 370 380 PCSEILKRNI QRYNSFISLT V

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning, cDNA structure and tissue-specific expression of the human regulatory subunit RI beta of cAMP-dependent protein kinases." Solberg R., Tasken K., Keiserud A., Jahnsen T. Biochem. Biophys. Res. Commun. 176:166-172(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Human regulatory subunit RI beta of cAMP-dependent protein kinases: expression, holoenzyme formation and microinjection into living cells." Solberg R., Tasken K., Wen W., Coghlan V.M., Meinkoth J.L., Scott J.D., Jahnsen T., Taylor S.S. Exp. Cell Res. 214:595-605(1994) [PubMed] [Europe PMC] [Abstract] Cited for: SEQUENCE REVISION TO 98-100. Tissue: Testis.
[3]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Amygdala and Brain.
[4]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain and Cervix.
[5]	"Nitroproteins from a human pituitary adenoma tissue discovered with a nitrotyrosine affinity column and tandem mass spectrometry." Zhan X., Desiderio D.M. Anal. Biochem. 354:279-289(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NITRATION [LARGE SCALE ANALYSIS] AT TYR-21, MASS SPECTROMETRY. Tissue: Pituitary adenoma.
[6]	"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] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[7]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-77 AND SER-83, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[8]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-83, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[9]	"Regulation of cAMP-dependent protein kinases: the human protein kinase X (PrKX) reveals the role of the catalytic subunit alphaH-alphaI loop." Diskar M., Zenn H.M., Kaupisch A., Kaufholz M., Brockmeyer S., Sohmen D., Berrera M., Zaccolo M., Boshart M., Herberg F.W., Prinz A. J. Biol. Chem. 285:35910-35918(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH PRKX.
[10]	"A small novel A-kinase anchoring protein (AKAP) that localizes specifically protein kinase A-regulatory subunit I (PKA-RI) to the plasma membrane." Burgers P.P., Ma Y., Margarucci L., Mackey M., van der Heyden M.A., Ellisman M., Scholten A., Taylor S.S., Heck A.J. J. Biol. Chem. 287:43789-43797(2012) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH C2ORF88/SMAKAP, SUBCELLULAR LOCATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M65066 mRNA. Translation: AAC37564.1.
AK315951 mRNA. Translation: BAH14322.1.
AK315990 mRNA. Translation: BAH14361.1.
BC026734 mRNA. Translation: AAH26734.1.
BC036828 mRNA. Translation: AAH36828.2.

IPI

IPI00554488.

PIR

OKHUR1. JH0392.

RefSeq

NP_001158230.1. NM_001164758.1.
NP_001158231.1. NM_001164759.1.
NP_001158232.1. NM_001164760.1.
NP_001158233.1. NM_001164761.1.
NP_001158234.1. NM_001164762.1.
NP_002726.1. NM_002735.2.

UniGene

Hs.520851.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
4DIN	X-ray	3.70	B	1-381	[»]
4F9K	X-ray	2.80	A/B/C/D	11-73	[»]

ProteinModelPortal

P31321.

ModBase

Search...

Protein-protein interaction databases

IntAct

P31321. 7 interactions.

MINT

MINT-240609.

STRING

9606.ENSP00000353415.

PTM databases

PhosphoSite

P31321.

Polymorphism databases

DMDM

229463042.

Proteomic databases

PaxDb

P31321.

PRIDE

P31321.

Protocols and materials databases

DNASU

5575.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000360274; ENSP00000353415; ENSG00000188191.
ENST00000403562; ENSP00000385349; ENSG00000188191.
ENST00000406797; ENSP00000385749; ENSG00000188191.
ENST00000537384; ENSP00000440449; ENSG00000188191.
ENST00000544935; ENSP00000444487; ENSG00000188191.

GeneID

5575.

KEGG

hsa:5575.

UCSC

uc003siu.2. human.

Organism-specific databases

CTD

5575.

GeneCards

GC07M000588.

HGNC

HGNC:9390. PRKAR1B.

HPA

HPA026719.

MIM

176911. gene.

neXtProt

NX_P31321.

PharmGKB

PA33756.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0664.

HOGENOM

HOG000196669.

HOVERGEN

HBG002025.

InParanoid

P31321.

KO

K04739.

OMA

LEKEECK.

OrthoDB

EOG4JQ3XP.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.
REACT_111217. Metabolism.
REACT_116125. Disease.
REACT_15518. Transmembrane transport of small molecules.
REACT_604. Hemostasis.
REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P31321.

Bgee

P31321.

CleanEx

HS_PRKAR1B.

Genevestigator

P31321.

GermOnline

ENSG00000188191. Homo sapiens.

Family and domain databases

Gene3D

2.60.120.10. 2 hits.

InterPro

IPR002373. cAMP/cGMP_kin.
IPR012198. cAMP_dep_PK_reg_su.
IPR003117. cAMP_dep_PK_reg_su_I/II_a/b.
IPR018490. cNMP-bd-like.
IPR018488. cNMP-bd_CS.
IPR000595. cNMP-bd_dom.
IPR014710. RmlC-like_jellyroll.
[Graphical view]

Pfam

PF00027. cNMP_binding. 2 hits.
PF02197. RIIa. 1 hit.
[Graphical view]

PIRSF

PIRSF000548. PK_regulatory. 1 hit.

PRINTS

PR00103. CAMPKINASE.

SMART

SM00100. cNMP. 2 hits.
SM00394. RIIa. 1 hit.
[Graphical view]

SUPFAM

SSF47391. cAMP-dep_prot_kin_reg_I/II_a/b. 1 hit.
SSF51206. cNMP_binding. 2 hits.

PROSITE

PS00888. CNMP_BINDING_1. 2 hits.
PS00889. CNMP_BINDING_2. 2 hits.
PS50042. CNMP_BINDING_3. 2 hits.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P31321.

ChEMBL

CHEMBL2320.

ChiTaRS

PRKAR1B. human.

GenomeRNAi

5575.

NextBio

21612.

SOURCE

Search...

Entry information

Entry name

KAP1_HUMAN

Accession

Primary (citable) accession number: P31321
Secondary accession number(s): Q8N422

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1993
Last sequence update:	May 5, 2009
Last modified:	May 29, 2013
This is version 128 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.