PP14C_HUMAN
ID PP14C_HUMAN Reviewed; 165 AA.
AC Q8TAE6; Q5VY83; Q96BB1; Q9H277;
DT 09-NOV-2004, integrated into UniProtKB/Swiss-Prot.
DT 21-MAR-2006, sequence version 3.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Protein phosphatase 1 regulatory subunit 14C;
DE AltName: Full=Kinase-enhanced PP1 inhibitor;
DE AltName: Full=PKC-potentiated PP1 inhibitory protein;
DE AltName: Full=Serologically defined breast cancer antigen NY-BR-81;
GN Name=PPP1R14C; Synonyms=KEPI;
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], TISSUE SPECIFICITY, AND VARIANT ALA-10.
RC TISSUE=Mammary gland;
RX PubMed=12747765;
RA Scanlan M.J., Gout I., Gordon C.M., Williamson B., Stockert E., Gure A.O.,
RA Jaeger D., Chen Y.-T., Mackay A., O'Hare M.J., Old L.J.;
RT "Humoral immunity to human breast cancer: antigen definition and
RT quantitative analysis of mRNA expression.";
RL Cancer Immun. 1:4-4(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=11812771; DOI=10.1074/jbc.m107558200;
RA Liu Q.-R., Zhang P.-W., Zhen Q., Walther D., Wang X.-B., Uhl G.;
RT "KEPI, a PKC-dependent protein phosphatase 1 inhibitor regulated by
RT morphine.";
RL J. Biol. Chem. 277:13312-13320(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ALA-10.
RC TISSUE=Skin;
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-73.
RX PubMed=12804574; DOI=10.1016/s0006-291x(03)00976-8;
RA Erdodi F., Kiss E., Walsh M.P., Stefansson B., Deng J.T., Eto M.,
RA Brautigan D.L., Hartshorne D.J.;
RT "Phosphorylation of protein phosphatase type-1 inhibitory proteins by
RT integrin-linked kinase and cyclic nucleotide-dependent protein kinases.";
RL Biochem. Biophys. Res. Commun. 306:382-387(2003).
RN [6]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
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 ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-25 AND SER-33, AND
RP 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).
CC -!- FUNCTION: Inhibitor of the PP1 regulatory subunit PPP1CA.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Membrane {ECO:0000250};
CC Peripheral membrane protein {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Detected in breast cancer.
CC {ECO:0000269|PubMed:12747765}.
CC -!- PTM: Has over 600-fold higher inhibitory activity when phosphorylated,
CC creating a molecular switch for regulating the phosphorylation status
CC of PPP1CA substrates and smooth muscle contraction (By similarity). The
CC main inhibitory site appears to be Thr-73. {ECO:0000250,
CC ECO:0000269|PubMed:12804574}.
CC -!- SIMILARITY: Belongs to the PP1 inhibitor family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAG48264.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF308297; AAG48264.1; ALT_INIT; mRNA.
DR EMBL; AF407165; AAL83506.1; -; mRNA.
DR EMBL; AF407166; AAL83507.1; -; Genomic_DNA.
DR EMBL; AL355497; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL096708; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC015773; AAH15773.1; -; mRNA.
DR CCDS; CCDS5226.1; -.
DR RefSeq; NP_112211.1; NM_030949.2.
DR AlphaFoldDB; Q8TAE6; -.
DR BioGRID; 123578; 13.
DR IntAct; Q8TAE6; 3.
DR STRING; 9606.ENSP00000355260; -.
DR iPTMnet; Q8TAE6; -.
DR PhosphoSitePlus; Q8TAE6; -.
DR BioMuta; PPP1R14C; -.
DR DMDM; 90110047; -.
DR EPD; Q8TAE6; -.
DR jPOST; Q8TAE6; -.
DR MassIVE; Q8TAE6; -.
DR MaxQB; Q8TAE6; -.
DR PaxDb; Q8TAE6; -.
DR PeptideAtlas; Q8TAE6; -.
DR PRIDE; Q8TAE6; -.
DR ProteomicsDB; 73866; -.
DR Antibodypedia; 54632; 103 antibodies from 22 providers.
DR DNASU; 81706; -.
DR Ensembl; ENST00000361131.5; ENSP00000355260.4; ENSG00000198729.5.
DR GeneID; 81706; -.
DR KEGG; hsa:81706; -.
DR MANE-Select; ENST00000361131.5; ENSP00000355260.4; NM_030949.3; NP_112211.1.
DR UCSC; uc003qnt.4; human.
DR CTD; 81706; -.
DR DisGeNET; 81706; -.
DR GeneCards; PPP1R14C; -.
DR HGNC; HGNC:14952; PPP1R14C.
DR HPA; ENSG00000198729; Tissue enhanced (heart muscle, skeletal muscle, skin, thyroid gland).
DR MIM; 613242; gene.
DR neXtProt; NX_Q8TAE6; -.
DR OpenTargets; ENSG00000198729; -.
DR PharmGKB; PA33630; -.
DR VEuPathDB; HostDB:ENSG00000198729; -.
DR eggNOG; ENOG502RYQF; Eukaryota.
DR GeneTree; ENSGT00950000182985; -.
DR HOGENOM; CLU_114155_1_0_1; -.
DR InParanoid; Q8TAE6; -.
DR OMA; KPSHPAM; -.
DR OrthoDB; 1492626at2759; -.
DR PhylomeDB; Q8TAE6; -.
DR TreeFam; TF105546; -.
DR PathwayCommons; Q8TAE6; -.
DR SignaLink; Q8TAE6; -.
DR SIGNOR; Q8TAE6; -.
DR BioGRID-ORCS; 81706; 8 hits in 1083 CRISPR screens.
DR ChiTaRS; PPP1R14C; human.
DR GeneWiki; PPP1R14C; -.
DR GenomeRNAi; 81706; -.
DR Pharos; Q8TAE6; Tbio.
DR PRO; PR:Q8TAE6; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q8TAE6; protein.
DR Bgee; ENSG00000198729; Expressed in upper arm skin and 168 other tissues.
DR Genevisible; Q8TAE6; HS.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; 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 Acetylation; Cytoplasm; Membrane; Methylation; Phosphoprotein;
KW Protein phosphatase inhibitor; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22814378"
FT CHAIN 2..165
FT /note="Protein phosphatase 1 regulatory subunit 14C"
FT /id="PRO_0000071494"
FT REGION 1..73
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 30..47
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 54..69
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22814378"
FT MOD_RES 25
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 27
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q8R4S0"
FT MOD_RES 33
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 73
FT /note="Phosphothreonine; by ILK1"
FT /evidence="ECO:0000269|PubMed:12804574"
FT VARIANT 10
FT /note="T -> A (in dbSNP:rs2297672)"
FT /evidence="ECO:0000269|PubMed:12747765,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_025547"
SQ SEQUENCE 165 AA; 17843 MW; 514CB1EC4B15E5BB CRC64;
MSVATGSSET AGGASGGGAR VFFQSPRGGA GGSPGSSSGS GSSREDSAPV ATAAAAGQVQ
QQQQRRHQQG KVTVKYDRKE LRKRLVLEEW IVEQLGQLYG CEEEEMPEVE IDIDDLLDAD
SDEERASKLQ EALVDCYKPT EEFIKELLSR IRGMRKLSPP QKKSV
