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Protein

Protein phosphatase 1 regulatory subunit 15A

Gene

Ppp1r15a

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Recruits the serine/threonine-protein phosphatase PP1 to dephosphorylate the translation initiation factor eIF-2A/EIF2S1, thereby reversing the shut-off of protein synthesis initiated by stress-inducible kinases and facilitating recovery of cells from stress. Down-regulates the TGF-beta signaling pathway by promoting dephosphorylation of TGFB1 by PP1. May promote apoptosis by inducing TP53 phosphorylation on 'Ser-15'. In case of infection with vesicular stomatitis virus (VSV), impairs viral replication.5 Publications

GO - Molecular functioni

  • protein kinase binding Source: MGI
  • protein phosphatase 1 binding Source: MGI
  • protein phosphatase binding Source: ParkinsonsUK-UCL
  • protein phosphatase regulator activity Source: ParkinsonsUK-UCL

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Apoptosis, Stress response, Translation regulation

Names & Taxonomyi

Protein namesi
Recommended name:
Protein phosphatase 1 regulatory subunit 15A
Alternative name(s):
Growth arrest and DNA damage-inducible protein GADD34
Myeloid differentiation primary response protein MyD116
Gene namesi
Name:Ppp1r15a
Synonyms:Gadd34, Myd116
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:1927072. Ppp1r15a.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 2121CytoplasmicBy similarityAdd
BLAST
Intramembranei22 – 3918HelicalBy similarityAdd
BLAST
Topological domaini40 – 657618CytoplasmicBy similarityAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Mitochondrion, Mitochondrion outer membrane

Pathology & Biotechi

Disruption phenotypei

Mice display abnormal erythrocytes and reduced hemoglobin content due to defects in hemoglobin synthesis.2 Publications

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi549 – 5491V → E: Abolishes interaction with PP1. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 657657Protein phosphatase 1 regulatory subunit 15APRO_0000096665Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei239 – 2391PhosphotyrosineBy similarity
Modified residuei368 – 3681PhosphotyrosineBy similarity
Modified residuei406 – 4061PhosphotyrosineBy similarity
Modified residuei505 – 5051PhosphotyrosineBy similarity

Post-translational modificationi

Phosphorylated at multiple Ser/Thr residues. Phosphorylated on tyrosine by LYN; which impairs its antiproliferative activity. Phosphorylation at Tyr-239 enhances proteasomal degradation, this position is dephosphorylated by PTPN2.By similarity
Polyubiquitinated. Exhibits a rapid proteasomal degradation with a half-life under 1 hour, ubiquitination depends on endoplasmic reticulum association.By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP17564.
PRIDEiP17564.

PTM databases

iPTMnetiP17564.
PhosphoSiteiP17564.

Expressioni

Tissue specificityi

Expressed strongly in spleen and lung, moderately in thymus and muscle, and weakly in brain.1 Publication

Developmental stagei

Expression starts at E8.5, and decreases to undetectable levels at E10.5 and E11.5. Expression is strongly up-regulated at E12.5, decreases at E16.5 and reappears at E18.5. At E12.5, ubiquitously expressed, with high levels in brain, spinal cord, tongue, lung and genital tubercle.1 Publication

Inductioni

By IL6 and various endoplasmic stresses such as methyl methanesulfonate. By infection with various viruses such as vesicular stomatitis virus (VSV).4 Publications

Gene expression databases

BgeeiENSMUSG00000040435.
CleanExiMM_MYD116.
ExpressionAtlasiP17564. baseline and differential.
GenevisibleiP17564. MM.

Interactioni

Subunit structurei

Interacts with KMT2A/MLL1. Interacts with SMARCB1. Interacts with SMAD7. Interacts with BAG1 (By similarity). Interacts with PCNA. Interacts with LYN. Interacts with PP1 and PPP1R1A.By similarity4 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi201637. 2 interactions.
STRINGi10090.ENSMUSP00000049488.

Structurei

3D structure databases

ProteinModelPortaliP17564.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati283 – 322401Add
BLAST
Repeati323 – 360382Add
BLAST
Repeati361 – 398383Add
BLAST
Repeati399 – 436384Add
BLAST
Repeati437 – 451155; truncatedAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 6060Required for localization in the endoplasmic reticulumBy similarityAdd
BLAST
Regioni283 – 4511694.5 X approximate repeatsAdd
BLAST
Regioni323 – 503181Interaction with SMAD7By similarityAdd
BLAST
Regioni443 – 548106Interaction with KMT2A/MLL1By similarityAdd
BLAST
Regioni529 – 57648Interaction with SMARCB1By similarityAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi455 – 4584Poly-Glu

Sequence similaritiesi

Belongs to the PPP1R15 family.Curated

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiENOG410ITE6. Eukaryota.
ENOG410Y1YJ. LUCA.
GeneTreeiENSGT00510000049287.
HOGENOMiHOG000060154.
HOVERGENiHBG052542.
InParanoidiP17564.
KOiK14019.
OMAiVRAWVYR.
OrthoDBiEOG091G19MD.
PhylomeDBiP17564.
TreeFamiTF105547.

Family and domain databases

InterProiIPR019523. Prot_Pase1_reg-su15A/B_C.
[Graphical view]
PfamiPF10488. PP1c_bdg. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P17564-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAPSPRPQHV LHWRDAHNFY LLSPLMGLLS RAWSRLRGPE VPEAWLAKTV
60 70 80 90 100
TGADQIEAAA LLTPTPVSGN LLPHGETEES GSPEQSQAAQ RLCLVEAESS
110 120 130 140 150
PPETWGLSNV DEYNAKPGQD DLREKEMERT AGKATLQPAG LQGADKRLGE
160 170 180 190 200
VVAREEGVAE PAYPTSQLEG GPAENEEDGE TVKTYQASAA SIAPGYKPST
210 220 230 240 250
PVPFLGEAEH QATEEKGTEN KADPSNSPSS GSHSRAWEYY SREKPKQEGE
260 270 280 290 300
AKVEAHRAGQ GHPCRNAEAE EGGPETTFVC TGNAFLKAWV YRPGEDTEEE
310 320 330 340 350
DNSDSDSAEE DTAQTGATPH TSAFLKAWVY RPGEDTEEED SDSDSAEEDT
360 370 380 390 400
AQTGATPHTS AFLKAWVYRP GEDTEEENSD LDSAEEDTAQ TGATPHTSAF
410 420 430 440 450
LKAWVYRPGE DTEEENSDLD SAEEDTAQTG ATPHTSPFLK AWVYRPGEDT
460 470 480 490 500
EDDTEEEEDS ENVAPGDSET ADSSQSPCLQ PQRCLPGEKT KGRGEEPPLF
510 520 530 540 550
QVAFYLPGEK PESPWAAPKL PLRLQRRLRL FKAPTRDQDP EIPLKARKVH
560 570 580 590 600
FAEKVTVHFL AVWAGPAQAA RRGPWEQFAR DRSRFARRIA QAEEKLGPYL
610 620 630 640 650
TPDSRARAWA RLRNPSLPQS EPRSSSEATP LTQDVTTPSP LPSETPSPSL

YLGGRRG
Length:657
Mass (Da):71,840
Last modified:August 1, 1990 - v1
Checksum:i9B217001019C38A7
GO
Isoform 2 (identifier: P17564-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     284-360: Missing.

Show »
Length:580
Mass (Da):63,474
Checksum:i5458712B7E548445
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti224 – 2241P → H in BAE39419 (PubMed:16141072).Curated
Sequence conflicti271 – 2711E → G in BAE32770 (PubMed:16141072).Curated
Sequence conflicti505 – 5051Y → C in BAE32770 (PubMed:16141072).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei284 – 36077Missing in isoform 2. 1 PublicationVSP_031651Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X51829 mRNA. Translation: CAA36128.1.
AK079339 mRNA. Translation: BAC37613.1.
AK154697 mRNA. Translation: BAE32770.1.
AK167317 mRNA. Translation: BAE39419.1.
CCDSiCCDS21249.1. [P17564-1]
PIRiS10001.
RefSeqiNP_032680.1. NM_008654.2. [P17564-1]
UniGeneiMm.4048.

Genome annotation databases

EnsembliENSMUST00000042105; ENSMUSP00000049488; ENSMUSG00000040435. [P17564-1]
ENSMUST00000167273; ENSMUSP00000128497; ENSMUSG00000040435. [P17564-1]
GeneIDi17872.
KEGGimmu:17872.
UCSCiuc009gvt.3. mouse. [P17564-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X51829 mRNA. Translation: CAA36128.1.
AK079339 mRNA. Translation: BAC37613.1.
AK154697 mRNA. Translation: BAE32770.1.
AK167317 mRNA. Translation: BAE39419.1.
CCDSiCCDS21249.1. [P17564-1]
PIRiS10001.
RefSeqiNP_032680.1. NM_008654.2. [P17564-1]
UniGeneiMm.4048.

3D structure databases

ProteinModelPortaliP17564.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi201637. 2 interactions.
STRINGi10090.ENSMUSP00000049488.

PTM databases

iPTMnetiP17564.
PhosphoSiteiP17564.

Proteomic databases

PaxDbiP17564.
PRIDEiP17564.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000042105; ENSMUSP00000049488; ENSMUSG00000040435. [P17564-1]
ENSMUST00000167273; ENSMUSP00000128497; ENSMUSG00000040435. [P17564-1]
GeneIDi17872.
KEGGimmu:17872.
UCSCiuc009gvt.3. mouse. [P17564-1]

Organism-specific databases

CTDi23645.
MGIiMGI:1927072. Ppp1r15a.

Phylogenomic databases

eggNOGiENOG410ITE6. Eukaryota.
ENOG410Y1YJ. LUCA.
GeneTreeiENSGT00510000049287.
HOGENOMiHOG000060154.
HOVERGENiHBG052542.
InParanoidiP17564.
KOiK14019.
OMAiVRAWVYR.
OrthoDBiEOG091G19MD.
PhylomeDBiP17564.
TreeFamiTF105547.

Miscellaneous databases

PROiP17564.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000040435.
CleanExiMM_MYD116.
ExpressionAtlasiP17564. baseline and differential.
GenevisibleiP17564. MM.

Family and domain databases

InterProiIPR019523. Prot_Pase1_reg-su15A/B_C.
[Graphical view]
PfamiPF10488. PP1c_bdg. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPR15A_MOUSE
AccessioniPrimary (citable) accession number: P17564
Secondary accession number(s): Q3TJS6, Q3U3L5, Q8C579
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: August 1, 1990
Last modified: September 7, 2016
This is version 114 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.