ID   IPKA_RABIT              Reviewed;          76 AA.
AC   P61926; P04541;
DT   13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 2.
DT   03-AUG-2022, entry version 93.
DE   RecName: Full=cAMP-dependent protein kinase inhibitor alpha;
DE            Short=PKI-alpha;
DE   AltName: Full=cAMP-dependent protein kinase inhibitor, muscle/brain isoform;
GN   Name=PKIA; Synonyms=PRKACN1;
OS   Oryctolagus cuniculus (Rabbit).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX   NCBI_TaxID=9986;
RN   [1]
RP   PROTEIN SEQUENCE OF 2-76.
RC   TISSUE=Skeletal muscle;
RX   PubMed=3898070; DOI=10.1073/pnas.82.17.5732;
RA   Scott J.D., Fischer E.H., Takio K., Demaille J.G., Krebs E.G.;
RT   "Amino acid sequence of the heat-stable inhibitor of the cAMP-dependent
RT   protein kinase from rabbit skeletal muscle.";
RL   Proc. Natl. Acad. Sci. U.S.A. 82:5732-5736(1985).
RN   [2]
RP   INHIBITORY SITE.
RX   PubMed=2989819; DOI=10.1073/pnas.82.13.4379;
RA   Scott J.D., Fischer E.H., Demaille J.G., Krebs E.G.;
RT   "Identification of an inhibitory region of the heat-stable protein
RT   inhibitor of the cAMP-dependent protein kinase.";
RL   Proc. Natl. Acad. Sci. U.S.A. 82:4379-4383(1985).
RN   [3]
RP   X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 6-25 IN COMPLEX WITH PRKACA.
RX   PubMed=1862343; DOI=10.1126/science.1862343;
RA   Knighton D.R., Zheng J., ten Eyck L.F., Xuong N.-H., Taylor S.S.,
RA   Sowadski J.M.;
RT   "Structure of a peptide inhibitor bound to the catalytic subunit of cyclic
RT   adenosine monophosphate-dependent protein kinase.";
RL   Science 253:414-420(1991).
RN   [4]
RP   X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 6-25 IN COMPLEX WITH PRKACA.
RX   PubMed=9109651; DOI=10.1021/bi961947+;
RA   Narayana N., Cox S., Shaltiel S., Taylor S.S., Xuong N.;
RT   "Crystal structure of a polyhistidine-tagged recombinant catalytic subunit
RT   of cAMP-dependent protein kinase complexed with the peptide inhibitor
RT   PKI(5-24) and adenosine.";
RL   Biochemistry 36:4438-4448(1997).
CC   -!- FUNCTION: Extremely potent competitive inhibitor of cAMP-dependent
CC       protein kinase activity, this protein interacts with the catalytic
CC       subunit of the enzyme after the cAMP-induced dissociation of its
CC       regulatory chains.
CC   -!- MISCELLANEOUS: The inhibitory site contains regions very similar to the
CC       hinge regions (sites that directly interact with the enzyme active
CC       site) and 'pseudosubstrate site' of the regulatory chains; but, unlike
CC       these chains, PKI does not contain cAMP-binding sites. The arginine
CC       residues within the inhibitory site are essential for inhibition and
CC       recognition of the enzyme active site.
CC   -!- SIMILARITY: Belongs to the PKI family. {ECO:0000305}.
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DR   PIR; A01340; OKRBCI.
DR   RefSeq; XP_008253905.1; XM_008255683.2.
DR   PDB; 1CDK; X-ray; 2.00 A; I/J=6-25.
DR   PDB; 1CTP; X-ray; 2.90 A; I=6-25.
DR   PDB; 1FMO; X-ray; 2.20 A; I=6-25.
DR   PDB; 1JBP; X-ray; 2.20 A; S=6-25.
DR   PDB; 1Q8W; X-ray; 2.20 A; B=6-25.
DR   PDB; 1SMH; X-ray; 2.04 A; B=6-25.
DR   PDB; 1STC; X-ray; 2.30 A; I=6-25.
DR   PDB; 1SVE; X-ray; 2.49 A; B=6-25.
DR   PDB; 1SVG; X-ray; 2.02 A; B=6-25.
DR   PDB; 2ERZ; X-ray; 2.20 A; I=6-25.
DR   PDB; 2F7Z; X-ray; 3.00 A; I=6-25.
DR   PDB; 2GFC; X-ray; 1.87 A; I=6-25.
DR   PDB; 2GNH; X-ray; 2.05 A; I=6-25.
DR   PDB; 2GNL; X-ray; 2.60 A; I=6-25.
DR   PDB; 3DND; X-ray; 2.26 A; I=6-25.
DR   PDB; 3DNE; X-ray; 2.00 A; I=6-25.
DR   PDB; 4XW4; X-ray; 1.82 A; B=6-25.
DR   PDB; 4XW5; X-ray; 1.95 A; B=6-25.
DR   PDB; 4XW6; X-ray; 1.90 A; B=6-25.
DR   PDB; 4YXS; X-ray; 2.11 A; I=6-25.
DR   PDB; 5UZK; X-ray; 2.30 A; I=6-23.
DR   PDBsum; 1CDK; -.
DR   PDBsum; 1CTP; -.
DR   PDBsum; 1FMO; -.
DR   PDBsum; 1JBP; -.
DR   PDBsum; 1Q8W; -.
DR   PDBsum; 1SMH; -.
DR   PDBsum; 1STC; -.
DR   PDBsum; 1SVE; -.
DR   PDBsum; 1SVG; -.
DR   PDBsum; 2ERZ; -.
DR   PDBsum; 2F7Z; -.
DR   PDBsum; 2GFC; -.
DR   PDBsum; 2GNH; -.
DR   PDBsum; 2GNL; -.
DR   PDBsum; 3DND; -.
DR   PDBsum; 3DNE; -.
DR   PDBsum; 4XW4; -.
DR   PDBsum; 4XW5; -.
DR   PDBsum; 4XW6; -.
DR   PDBsum; 4YXS; -.
DR   PDBsum; 5UZK; -.
DR   AlphaFoldDB; P61926; -.
DR   BMRB; P61926; -.
DR   SMR; P61926; -.
DR   STRING; 9986.ENSOCUP00000018622; -.
DR   iPTMnet; P61926; -.
DR   Ensembl; ENSOCUT00000026858; ENSOCUP00000018622; ENSOCUG00000021115.
DR   GeneID; 100343293; -.
DR   KEGG; ocu:100343293; -.
DR   CTD; 5569; -.
DR   eggNOG; ENOG502S6JP; Eukaryota.
DR   GeneTree; ENSGT00530000064276; -.
DR   InParanoid; P61926; -.
DR   OrthoDB; 1884193at2759; -.
DR   TreeFam; TF330809; -.
DR   EvolutionaryTrace; P61926; -.
DR   Proteomes; UP000001811; Chromosome 3.
DR   Bgee; ENSOCUG00000021115; Expressed in skeletal muscle tissue and 16 other tissues.
DR   ExpressionAtlas; P61926; baseline.
DR   GO; GO:0005737; C:cytoplasm; IEA:Ensembl.
DR   GO; GO:0005634; C:nucleus; IEA:Ensembl.
DR   GO; GO:0004862; F:cAMP-dependent protein kinase inhibitor activity; IDA:CAFA.
DR   GO; GO:0034236; F:protein kinase A catalytic subunit binding; IPI:CAFA.
DR   GO; GO:2000480; P:negative regulation of cAMP-dependent protein kinase activity; IDA:CAFA.
DR   GO; GO:0042308; P:negative regulation of protein import into nucleus; IEA:Ensembl.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR   GO; GO:0010389; P:regulation of G2/M transition of mitotic cell cycle; IEA:Ensembl.
DR   DisProt; DP00015; -.
DR   IDEAL; IID50121; -.
DR   InterPro; IPR004171; cAMP_dep_PKI.
DR   PANTHER; PTHR15416; PTHR15416; 1.
DR   Pfam; PF02827; PKI; 1.
DR   PIRSF; PIRSF001667; PKI; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Acetylation; Direct protein sequencing;
KW   Protein kinase inhibitor; Reference proteome.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000250|UniProtKB:P61925,
FT                   ECO:0000269|PubMed:3898070"
FT   CHAIN           2..76
FT                   /note="cAMP-dependent protein kinase inhibitor alpha"
FT                   /id="PRO_0000154535"
FT   REGION          49..76
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        61..76
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   SITE            16
FT                   /note="Important for inhibition"
FT   SITE            19
FT                   /note="Important for inhibition"
FT   SITE            20
FT                   /note="Important for inhibition"
FT   MOD_RES         2
FT                   /note="Blocked amino end (Thr); alternate"
FT   MOD_RES         2
FT                   /note="N-acetylthreonine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P61925"
FT   HELIX           7..12
FT                   /evidence="ECO:0007829|PDB:4XW4"
FT   STRAND          23..25
FT                   /evidence="ECO:0007829|PDB:3DND"
SQ   SEQUENCE   76 AA;  7989 MW;  BDCE072810435951 CRC64;
     MTDVETTYAD FIASGRTGRR NAIHDILVSS ASGNSNELAL KLAGLDINKT EGEEDAQRSS
     TEQSGEAQGE AAKSES