PPR1A_HUMAN
ID PPR1A_HUMAN Reviewed; 171 AA.
AC Q13522; Q6IB01; Q8TBJ2; Q8WWV2;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 2.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Protein phosphatase 1 regulatory subunit 1A;
DE AltName: Full=Protein phosphatase inhibitor 1;
DE Short=I-1;
DE Short=IPP-1;
GN Name=PPP1R1A; Synonyms=IPP1;
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], PROTEIN SEQUENCE OF 1-23 AND 53-61, MUTAGENESIS
RP OF THR-35, AND VARIANT GLY-109.
RC TISSUE=Brain;
RX PubMed=8611507; DOI=10.1021/bi952940f;
RA Endo S., Zhou X., Connor J., Wang B., Shenolikar S.;
RT "Multiple structural elements define the specificity of recombinant human
RT inhibitor-1 as a protein phosphatase-1 inhibitor.";
RL Biochemistry 35:5220-5228(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT GLY-109.
RC TISSUE=Heart;
RA Mishra S., Tiwari N., Sabbah H.N., Gupta R.C.;
RT "Cloning of inhibitor-1 of protein phosphatase type 1 from human heart.";
RL Submitted (NOV-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLY-109.
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLY-109.
RC TISSUE=Brain;
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 INTERACTION WITH PPP1R15A, AND PHOSPHORYLATION AT THR-35.
RX PubMed=11564868; DOI=10.1128/mcb.21.20.6841-6850.2001;
RA Connor J.H., Weiser D.C., Li S., Hallenbeck J.M., Shenolikar S.;
RT "Growth arrest and DNA damage-inducible protein GADD34 assembles a novel
RT signaling complex containing protein phosphatase 1 and inhibitor 1.";
RL Mol. Cell. Biol. 21:6841-6850(2001).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-67, AND IDENTIFICATION BY
RP 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 protein-phosphatase 1. This protein may be
CC important in hormonal control of glycogen metabolism. Hormones that
CC elevate intracellular cAMP increase I-1 activity in many tissues. I-1
CC activation may impose cAMP control over proteins that are not directly
CC phosphorylated by PKA. Following a rise in intracellular calcium, I-1
CC is inactivated by calcineurin (or PP2B). Does not inhibit type-2
CC phosphatases.
CC -!- SUBUNIT: Interacts with PPP1R15A. {ECO:0000269|PubMed:11564868}.
CC -!- INTERACTION:
CC Q13522; O75807: PPP1R15A; NbExp=4; IntAct=EBI-1568511, EBI-714746;
CC -!- PTM: Phosphorylation of Thr-35 is required for activity.
CC {ECO:0000269|PubMed:11564868}.
CC -!- SIMILARITY: Belongs to the protein phosphatase inhibitor 1 family.
CC {ECO:0000305}.
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DR EMBL; U48707; AAB02402.1; -; mRNA.
DR EMBL; AY063766; AAL48321.1; -; mRNA.
DR EMBL; CR457003; CAG33284.1; -; mRNA.
DR EMBL; BC022470; AAH22470.1; -; mRNA.
DR CCDS; CCDS44912.1; -.
DR RefSeq; NP_006732.3; NM_006741.3.
DR AlphaFoldDB; Q13522; -.
DR BMRB; Q13522; -.
DR BioGRID; 111496; 16.
DR IntAct; Q13522; 11.
DR STRING; 9606.ENSP00000257905; -.
DR BindingDB; Q13522; -.
DR iPTMnet; Q13522; -.
DR PhosphoSitePlus; Q13522; -.
DR BioMuta; PPP1R1A; -.
DR DMDM; 296452864; -.
DR EPD; Q13522; -.
DR MassIVE; Q13522; -.
DR PaxDb; Q13522; -.
DR PeptideAtlas; Q13522; -.
DR PRIDE; Q13522; -.
DR ProteomicsDB; 59517; -.
DR Antibodypedia; 27544; 87 antibodies from 30 providers.
DR DNASU; 5502; -.
DR Ensembl; ENST00000257905.13; ENSP00000257905.8; ENSG00000135447.17.
DR GeneID; 5502; -.
DR KEGG; hsa:5502; -.
DR UCSC; uc001sgg.3; human.
DR CTD; 5502; -.
DR DisGeNET; 5502; -.
DR GeneCards; PPP1R1A; -.
DR HGNC; HGNC:9286; PPP1R1A.
DR HPA; ENSG00000135447; Tissue enhanced (adipose tissue, skeletal muscle, tongue).
DR MIM; 613246; gene.
DR neXtProt; NX_Q13522; -.
DR PharmGKB; PA33636; -.
DR VEuPathDB; HostDB:ENSG00000135447; -.
DR eggNOG; ENOG502S1WG; Eukaryota.
DR HOGENOM; CLU_092269_1_0_1; -.
DR InParanoid; Q13522; -.
DR OrthoDB; 1571652at2759; -.
DR PhylomeDB; Q13522; -.
DR TreeFam; TF332576; -.
DR PathwayCommons; Q13522; -.
DR SignaLink; Q13522; -.
DR SIGNOR; Q13522; -.
DR BioGRID-ORCS; 5502; 21 hits in 1070 CRISPR screens.
DR GenomeRNAi; 5502; -.
DR Pharos; Q13522; Tbio.
DR PRO; PR:Q13522; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q13522; protein.
DR Bgee; ENSG00000135447; Expressed in triceps brachii and 179 other tissues.
DR ExpressionAtlas; Q13522; baseline and differential.
DR Genevisible; Q13522; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0004865; F:protein serine/threonine phosphatase inhibitor activity; TAS:ProtInc.
DR GO; GO:0005977; P:glycogen metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR InterPro; IPR008466; PPP1R1A/B/C.
DR PANTHER; PTHR15417; PTHR15417; 1.
DR Pfam; PF05395; DARPP-32; 1.
PE 1: Evidence at protein level;
KW Acetylation; Carbohydrate metabolism; Direct protein sequencing;
KW Glycogen metabolism; Phosphoprotein; Protein phosphatase inhibitor;
KW Reference proteome.
FT CHAIN 1..171
FT /note="Protein phosphatase 1 regulatory subunit 1A"
FT /id="PRO_0000071477"
FT REGION 1..171
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 9..12
FT /note="Essential for activity"
FT REGION 42..54
FT /note="Essential for activity"
FT /evidence="ECO:0000305"
FT REGION 143..171
FT /note="Interaction with PPP1R15A"
FT /evidence="ECO:0000269|PubMed:11564868"
FT COMPBIAS 100..115
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 138..153
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 154..171
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:P01099"
FT MOD_RES 35
FT /note="Phosphothreonine; by PKA"
FT /evidence="ECO:0000269|PubMed:11564868"
FT MOD_RES 43
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9ERT9"
FT MOD_RES 46
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9ERT9"
FT MOD_RES 47
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9ERT9"
FT MOD_RES 67
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT VARIANT 109
FT /note="E -> G (in dbSNP:rs1249958)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:8611507, ECO:0000269|Ref.2,
FT ECO:0000269|Ref.3"
FT /id="VAR_053898"
FT VARIANT 147
FT /note="G -> D (in dbSNP:rs34376731)"
FT /id="VAR_053899"
FT MUTAGEN 35
FT /note="T->A: No activity."
FT /evidence="ECO:0000269|PubMed:8611507"
FT MUTAGEN 35
FT /note="T->D: 1000-fold reduction in activity, inhibits
FT equally PP1 and PP2A."
FT /evidence="ECO:0000269|PubMed:8611507"
FT CONFLICT 8
FT /note="R -> Q (in Ref. 4; AAH22470)"
FT /evidence="ECO:0000305"
FT CONFLICT 43
FT /note="S -> G (in Ref. 2; AAL48321)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 171 AA; 19011 MW; 6F61FF08E4305729 CRC64;
MEQDNSPRKI QFTVPLLEPH LDPEAAEQIR RRRPTPATLV LTSDQSSPEI DEDRIPNPHL
KSTLAMSPRQ RKKMTRITPT MKELQMMVEH HLGQQQQGEE PEGAAESTET QESRPPGIPD
TEVESRLGTS GTAKKTAECI PKTHERGSKE PSTKEPSTHI PPLDSKGANS V
