PP14A_PIG
ID PP14A_PIG Reviewed; 147 AA.
AC O18734; Q9TQZ8; Q9TQZ9; Q9TR00; Q9TR01; Q9TR02;
DT 09-NOV-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 115.
DE RecName: Full=Protein phosphatase 1 regulatory subunit 14A;
DE AltName: Full=17 kDa PKC-potentiated inhibitory protein of PP1;
DE AltName: Full=Protein kinase C-potentiated inhibitor protein of 17 kDa;
DE Short=CPI-17;
GN Name=CPI17;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY.
RC TISSUE=Aorta;
RX PubMed=9237662; DOI=10.1016/s0014-5793(97)00657-1;
RA Eto M., Senba S., Morita F., Yazawa M.;
RT "Molecular cloning of a novel phosphorylation-dependent inhibitory protein
RT of protein phosphatase-1 (CPI-17) in smooth muscle: its specific
RT localization in smooth muscle.";
RL FEBS Lett. 410:356-360(1997).
RN [2]
RP PROTEIN SEQUENCE OF 9-71 AND 93-145, FUNCTION, MUTAGENESIS OF THR-38, AND
RP PHOSPHORYLATION AT THR-38.
RX PubMed=8720121; DOI=10.1093/oxfordjournals.jbchem.a124993;
RA Eto M., Ohmori T., Suzuki M., Furuya K., Morita F.;
RT "A novel protein phosphatase-1 inhibitory protein potentiated by protein
RT kinase C. Isolation from porcine aorta media and characterization.";
RL J. Biochem. 118:1104-1107(1995).
RN [3]
RP PHOSPHORYLATION AT THR-38, AND FUNCTION.
RX PubMed=10924361; DOI=10.1006/bbrc.2000.3225;
RA Hamaguchi T., Ito M., Feng J., Seko T., Koyama M., Machida H., Takase K.,
RA Amano M., Kaibuchi K., Hartshorne D.J., Nakano T.;
RT "Phosphorylation of CPI-17, an inhibitor of myosin phosphatase, by protein
RT kinase N.";
RL Biochem. Biophys. Res. Commun. 274:825-830(2000).
RN [4]
RP PHOSPHORYLATION AT THR-38, MUTAGENESIS OF THR-38, AND FUNCTION.
RX PubMed=10869555; DOI=10.1016/s0014-5793(00)01654-9;
RA Koyama M., Ito M., Feng J., Seko T., Shiraki K., Takase K.,
RA Hartshorne D.J., Nakano T.;
RT "Phosphorylation of CPI-17, an inhibitory phosphoprotein of smooth muscle
RT myosin phosphatase, by Rho-kinase.";
RL FEBS Lett. 475:197-200(2000).
RN [5]
RP MUTAGENESIS OF THR-38; TYR-41; ASP-42; ARG-43 AND ARG-44, AND SUBCELLULAR
RP LOCATION.
RX PubMed=11517233; DOI=10.1074/jbc.m107302200;
RA Hayashi Y., Senba S., Yazawa M., Brautigan D.L., Eto M.;
RT "Defining the structural determinants and a potential mechanism for
RT inhibition of myosin phosphatase by the protein kinase C-potentiated
RT inhibitor protein of 17 kDa.";
RL J. Biol. Chem. 276:39858-39863(2001).
RN [6]
RP STRUCTURE BY NMR OF 35-120.
RX PubMed=11734001; DOI=10.1006/jmbi.2001.5200;
RA Ohki S.-Y., Eto M., Kariya E., Hayano T., Hayashi Y., Yazawa M.,
RA Brautigan D.L., Kainosho M.;
RT "Solution NMR structure of the myosin phosphatase inhibitor protein CPI-17
RT shows phosphorylation-induced conformational changes responsible for
RT activation.";
RL J. Mol. Biol. 314:839-849(2001).
RN [7]
RP STRUCTURE BY NMR OF 22-120 OF MUTANT ASP-38.
RX PubMed=12595264; DOI=10.1016/s0022-2836(03)00048-2;
RA Ohki S.-Y., Eto M., Shimizu M., Takada R., Brautigan D.L., Kainosho M.;
RT "Distinctive solution conformation of phosphatase inhibitor CPI-17
RT substituted with aspartate at the phosphorylation-site threonine residue.";
RL J. Mol. Biol. 326:1539-1547(2003).
CC -!- FUNCTION: Inhibitor of PPP1CA. Has over 1000-fold higher inhibitory
CC activity when phosphorylated, creating a molecular switch for
CC regulating the phosphorylation status of PPP1CA substrates and smooth
CC muscle contraction. {ECO:0000269|PubMed:10869555,
CC ECO:0000269|PubMed:10924361, ECO:0000269|PubMed:8720121,
CC ECO:0000269|PubMed:9237662}.
CC -!- INTERACTION:
CC O18734; O14974: PPP1R12A; Xeno; NbExp=2; IntAct=EBI-15674919, EBI-351726;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11517233}.
CC -!- TISSUE SPECIFICITY: Detected in aorta smooth muscle and bladder.
CC {ECO:0000269|PubMed:9237662}.
CC -!- PTM: Phosphorylation of Thr-38 induces a conformation change.
CC {ECO:0000269|PubMed:10869555, ECO:0000269|PubMed:10924361,
CC ECO:0000269|PubMed:8720121}.
CC -!- SIMILARITY: Belongs to the PP1 inhibitor family. {ECO:0000305}.
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DR EMBL; AB008376; BAA22995.1; -; mRNA.
DR RefSeq; NP_999502.1; NM_214337.1.
DR PDB; 1J2M; NMR; -; A=22-120.
DR PDB; 1J2N; NMR; -; A=22-120.
DR PDB; 1K5O; NMR; -; A=35-120.
DR PDB; 2RLT; NMR; -; A=22-120.
DR PDBsum; 1J2M; -.
DR PDBsum; 1J2N; -.
DR PDBsum; 1K5O; -.
DR PDBsum; 2RLT; -.
DR AlphaFoldDB; O18734; -.
DR BMRB; O18734; -.
DR SMR; O18734; -.
DR DIP; DIP-48426N; -.
DR IntAct; O18734; 1.
DR STRING; 9823.ENSSSCP00000021211; -.
DR iPTMnet; O18734; -.
DR PaxDb; O18734; -.
DR PeptideAtlas; O18734; -.
DR PRIDE; O18734; -.
DR Ensembl; ENSSSCT00025003191; ENSSSCP00025001174; ENSSSCG00025002455.
DR Ensembl; ENSSSCT00030078693; ENSSSCP00030036012; ENSSSCG00030056455.
DR Ensembl; ENSSSCT00035046521; ENSSSCP00035018596; ENSSSCG00035035095.
DR Ensembl; ENSSSCT00040077589; ENSSSCP00040033383; ENSSSCG00040057186.
DR Ensembl; ENSSSCT00045004740; ENSSSCP00045003096; ENSSSCG00045002943.
DR Ensembl; ENSSSCT00050059824; ENSSSCP00050025706; ENSSSCG00050043939.
DR Ensembl; ENSSSCT00055061484; ENSSSCP00055049345; ENSSSCG00055030798.
DR Ensembl; ENSSSCT00060047176; ENSSSCP00060020207; ENSSSCG00060034795.
DR Ensembl; ENSSSCT00065048846; ENSSSCP00065021110; ENSSSCG00065035831.
DR Ensembl; ENSSSCT00070014421; ENSSSCP00070011901; ENSSSCG00070007478.
DR GeneID; 397610; -.
DR KEGG; ssc:397610; -.
DR CTD; 94274; -.
DR eggNOG; ENOG502S2I4; Eukaryota.
DR HOGENOM; CLU_114155_2_0_1; -.
DR InParanoid; O18734; -.
DR OrthoDB; 1492626at2759; -.
DR TreeFam; TF105546; -.
DR EvolutionaryTrace; O18734; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Chromosome 6.
DR Genevisible; O18734; SS.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0004865; F:protein serine/threonine phosphatase inhibitor activity; IBA:GO_Central.
DR GO; GO:0042325; P:regulation of phosphorylation; IEA:InterPro.
DR Gene3D; 1.10.150.220; -; 1.
DR InterPro; IPR008025; CPI-17.
DR InterPro; IPR036658; CPI-17_sf.
DR PANTHER; PTHR16188; PTHR16188; 1.
DR Pfam; PF05361; PP1_inhibitor; 1.
DR SUPFAM; SSF81790; SSF81790; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Direct protein sequencing; Phosphoprotein;
KW Protein phosphatase inhibitor; Reference proteome.
FT CHAIN 1..147
FT /note="Protein phosphatase 1 regulatory subunit 14A"
FT /id="PRO_0000071488"
FT REGION 1..37
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 35..120
FT /note="Inhibitory"
FT REGION 118..147
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 26
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96A00"
FT MOD_RES 38
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:10869555,
FT ECO:0000269|PubMed:10924361, ECO:0000269|PubMed:8720121"
FT MOD_RES 128
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96A00"
FT MOD_RES 134
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96A00"
FT MOD_RES 136
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96A00"
FT MUTAGEN 38
FT /note="T->A: Abolishes phosphorylation (in vitro) and
FT strongly reduces inhibitory activity."
FT /evidence="ECO:0000269|PubMed:10869555,
FT ECO:0000269|PubMed:11517233, ECO:0000269|PubMed:8720121"
FT MUTAGEN 38
FT /note="T->E: Reduces inhibitory activity at least 1000-
FT fold."
FT /evidence="ECO:0000269|PubMed:10869555,
FT ECO:0000269|PubMed:11517233, ECO:0000269|PubMed:8720121"
FT MUTAGEN 41
FT /note="Y->A: Promotes dephosphorylation of T-38. Abolishes
FT phosphorylation-dependent increase of inhibitory activity."
FT /evidence="ECO:0000269|PubMed:11517233"
FT MUTAGEN 42
FT /note="D->A: Strongly reduces inhibitory activity."
FT /evidence="ECO:0000269|PubMed:11517233"
FT MUTAGEN 43
FT /note="R->A: Strongly reduces inhibitory activity."
FT /evidence="ECO:0000269|PubMed:11517233"
FT MUTAGEN 44
FT /note="R->A: Reduces inhibitory activity."
FT /evidence="ECO:0000269|PubMed:11517233"
FT STRAND 24..26
FT /evidence="ECO:0007829|PDB:1J2M"
FT STRAND 34..37
FT /evidence="ECO:0007829|PDB:1J2M"
FT STRAND 45..47
FT /evidence="ECO:0007829|PDB:1J2M"
FT HELIX 48..62
FT /evidence="ECO:0007829|PDB:1J2M"
FT HELIX 65..67
FT /evidence="ECO:0007829|PDB:1K5O"
FT TURN 68..70
FT /evidence="ECO:0007829|PDB:1K5O"
FT HELIX 78..81
FT /evidence="ECO:0007829|PDB:1J2M"
FT TURN 84..87
FT /evidence="ECO:0007829|PDB:1J2M"
FT HELIX 88..98
FT /evidence="ECO:0007829|PDB:1J2M"
FT STRAND 99..102
FT /evidence="ECO:0007829|PDB:1J2N"
FT HELIX 105..114
FT /evidence="ECO:0007829|PDB:1J2M"
FT TURN 115..118
FT /evidence="ECO:0007829|PDB:1J2M"
SQ SEQUENCE 147 AA; 16672 MW; 315DAE461CF78BBF CRC64;
MAAQRLGKRV LSKLQSPSRA RGPGGSPGGL QKRHARVTVK YDRRELQRRL DVEKWIDGRL
EELYRGREAD MPDEVNIDEL LELESEEERS RKIQGLLKSC TNPTENFVQE LLVKLRGLHK
QPGLRQPSPS GDGSLSPRQD RARTAPP
