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PP14A_HUMAN
ID   PP14A_HUMAN             Reviewed;         147 AA.
AC   Q96A00; Q7Z4X7; Q96S54;
DT   09-NOV-2004, integrated into UniProtKB/Swiss-Prot.
DT   01-DEC-2001, sequence version 1.
DT   03-AUG-2022, entry version 156.
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=PPP1R14A; Synonyms=CPI17, PPP1INL;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND TISSUE SPECIFICITY.
RC   TISSUE=Aorta;
RX   PubMed=11467857; DOI=10.1006/bbrc.2001.5290;
RA   Yamawaki K., Ito M., Machida H., Moriki N., Okamoto R., Isaka N.,
RA   Shimpo H., Kohda A., Okumura K., Hartshorne D.J., Nakano T.;
RT   "Identification of human CPI-17, an inhibitory phosphoprotein for myosin
RT   phosphatase.";
RL   Biochem. Biophys. Res. Commun. 285:1040-1045(2001).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA   Cui W.C., Yu L., Zhao S.Y.;
RT   "Cloning a new human cDNA homologous to Sus scrofa mRNA for 17-KDa PKC-
RT   potentiated inhibitory protein of PP1.";
RL   Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
RC   TISSUE=Smooth muscle;
RX   PubMed=12974676; DOI=10.1042/bj20030128;
RA   Liu Q.-R., Zhang P.-W., Lin Z., Li Q.-F., Woods A.S., Troncoso J.,
RA   Uhl G.R.;
RT   "GBPI, a novel gastrointestinal- and brain-specific PP1-inhibitory protein,
RT   is activated by PKC and inactivated by PKA.";
RL   Biochem. J. 377:171-181(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Pancreas;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [5]
RP   PHOSPHORYLATION AT THR-38.
RX   PubMed=15003508; DOI=10.1016/j.bbrc.2004.02.014;
RA   Zemlickova E., Johannes F.J., Aitken A., Dubois T.;
RT   "Association of CPI-17 with protein kinase C and casein kinase I.";
RL   Biochem. Biophys. Res. Commun. 316:39-47(2004).
RN   [6]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-26, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Platelet;
RX   PubMed=18088087; DOI=10.1021/pr0704130;
RA   Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA   Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT   "Phosphoproteome of resting human platelets.";
RL   J. Proteome Res. 7:526-534(2008).
RN   [7]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA   Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA   Bennett K.L., Superti-Furga G., Colinge J.;
RT   "Initial characterization of the human central proteome.";
RL   BMC Syst. Biol. 5:17-17(2011).
RN   [8]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-136, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA   Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA   Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT   "System-wide temporal characterization of the proteome and phosphoproteome
RT   of human embryonic stem cell differentiation.";
RL   Sci. Signal. 4:RS3-RS3(2011).
RN   [9]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-26; SER-128; SER-134 AND
RP   SER-136, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Erythroleukemia;
RX   PubMed=23186163; DOI=10.1021/pr300630k;
RA   Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA   Mohammed S.;
RT   "Toward a comprehensive characterization of a human cancer cell
RT   phosphoproteome.";
RL   J. Proteome Res. 12:260-271(2013).
RN   [10]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA   Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT   phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
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.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1; Synonyms=CPI-17alpha;
CC         IsoId=Q96A00-1; Sequence=Displayed;
CC       Name=2; Synonyms=CPI-17beta;
CC         IsoId=Q96A00-2; Sequence=VSP_011841;
CC   -!- TISSUE SPECIFICITY: Isoform 1 is detected in aorta and testis. Isoform
CC       2 is detected in aorta. {ECO:0000269|PubMed:11467857}.
CC   -!- SIMILARITY: Belongs to the PP1 inhibitor family. {ECO:0000305}.
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DR   EMBL; AB056508; BAB62502.1; -; mRNA.
DR   EMBL; AB056509; BAB62503.1; -; mRNA.
DR   EMBL; AF123763; AAP97242.1; -; mRNA.
DR   EMBL; AY050668; AAL24445.1; -; Genomic_DNA.
DR   EMBL; AY050670; AAL25828.1; -; mRNA.
DR   EMBL; BC021089; AAH21089.1; -; mRNA.
DR   CCDS; CCDS12509.1; -. [Q96A00-1]
DR   CCDS; CCDS58660.1; -. [Q96A00-2]
DR   PIR; JC7719; JC7719.
DR   RefSeq; NP_001230876.1; NM_001243947.1. [Q96A00-2]
DR   RefSeq; NP_150281.1; NM_033256.2. [Q96A00-1]
DR   AlphaFoldDB; Q96A00; -.
DR   SMR; Q96A00; -.
DR   BioGRID; 125153; 23.
DR   IntAct; Q96A00; 2.
DR   MINT; Q96A00; -.
DR   STRING; 9606.ENSP00000301242; -.
DR   iPTMnet; Q96A00; -.
DR   PhosphoSitePlus; Q96A00; -.
DR   BioMuta; PPP1R14A; -.
DR   DMDM; 55583974; -.
DR   EPD; Q96A00; -.
DR   jPOST; Q96A00; -.
DR   MassIVE; Q96A00; -.
DR   MaxQB; Q96A00; -.
DR   PaxDb; Q96A00; -.
DR   PeptideAtlas; Q96A00; -.
DR   PRIDE; Q96A00; -.
DR   ProteomicsDB; 75885; -. [Q96A00-1]
DR   ProteomicsDB; 75886; -. [Q96A00-2]
DR   Antibodypedia; 3563; 390 antibodies from 35 providers.
DR   DNASU; 94274; -.
DR   Ensembl; ENST00000301242.9; ENSP00000301242.3; ENSG00000167641.11. [Q96A00-1]
DR   Ensembl; ENST00000347262.8; ENSP00000301243.3; ENSG00000167641.11. [Q96A00-2]
DR   GeneID; 94274; -.
DR   KEGG; hsa:94274; -.
DR   MANE-Select; ENST00000301242.9; ENSP00000301242.3; NM_033256.3; NP_150281.1.
DR   UCSC; uc002ohq.3; human. [Q96A00-1]
DR   CTD; 94274; -.
DR   DisGeNET; 94274; -.
DR   GeneCards; PPP1R14A; -.
DR   HGNC; HGNC:14871; PPP1R14A.
DR   HPA; ENSG00000167641; Tissue enhanced (brain).
DR   MIM; 608153; gene.
DR   neXtProt; NX_Q96A00; -.
DR   OpenTargets; ENSG00000167641; -.
DR   PharmGKB; PA33623; -.
DR   VEuPathDB; HostDB:ENSG00000167641; -.
DR   eggNOG; ENOG502S2I4; Eukaryota.
DR   GeneTree; ENSGT00950000182985; -.
DR   HOGENOM; CLU_114155_2_0_1; -.
DR   InParanoid; Q96A00; -.
DR   OMA; LHKQPGF; -.
DR   OrthoDB; 1492626at2759; -.
DR   PhylomeDB; Q96A00; -.
DR   TreeFam; TF105546; -.
DR   PathwayCommons; Q96A00; -.
DR   Reactome; R-HSA-5625740; RHO GTPases activate PKNs.
DR   SignaLink; Q96A00; -.
DR   SIGNOR; Q96A00; -.
DR   BioGRID-ORCS; 94274; 13 hits in 1081 CRISPR screens.
DR   ChiTaRS; PPP1R14A; human.
DR   GeneWiki; PPP1R14A; -.
DR   GenomeRNAi; 94274; -.
DR   Pharos; Q96A00; Tbio.
DR   PRO; PR:Q96A00; -.
DR   Proteomes; UP000005640; Chromosome 19.
DR   RNAct; Q96A00; protein.
DR   Bgee; ENSG00000167641; Expressed in right coronary artery and 147 other tissues.
DR   ExpressionAtlas; Q96A00; baseline and differential.
DR   Genevisible; Q96A00; HS.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
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   Alternative splicing; Cytoplasm; Phosphoprotein;
KW   Protein phosphatase inhibitor; Reference proteome.
FT   CHAIN           1..147
FT                   /note="Protein phosphatase 1 regulatory subunit 14A"
FT                   /id="PRO_0000071486"
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:0007744|PubMed:18088087,
FT                   ECO:0007744|PubMed:23186163"
FT   MOD_RES         38
FT                   /note="Phosphothreonine; by PKC"
FT                   /evidence="ECO:0000269|PubMed:15003508"
FT   MOD_RES         128
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         134
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         136
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21406692,
FT                   ECO:0007744|PubMed:23186163"
FT   VAR_SEQ         68..94
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:11467857"
FT                   /id="VSP_011841"
FT   CONFLICT        123
FT                   /note="G -> R (in Ref. 2; AAP97242)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   147 AA;  16693 MW;  470EE2C082FF7319 CRC64;
     MAAQRLGKRV LSKLQSPSRA RGPGGSPGGL QKRHARVTVK YDRRELQRRL DVEKWIDGRL
     EELYRGMEAD MPDEINIDEL LELESEEERS RKIQGLLKSC GKPVEDFIQE LLAKLQGLHR
     QPGLRQPSPS HDGSLSPLQD RARTAHP
 
 
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