Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

O75807 (PR15A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 93. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Protein phosphatase 1 regulatory subunit 15A
Alternative name(s):
Growth arrest and DNA damage-inducible protein GADD34
Myeloid differentiation primary response protein MyD116 homolog
Gene names
Name:PPP1R15A
Synonyms:GADD34
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length674 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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'. Ref.6 Ref.9 Ref.12 Ref.13 Ref.15

Subunit structure

Interacts with PCNA By similarity. Interacts with LYN and KMT2A/MLL1. Interacts with PP1, PPP1R1A and SMARCB1. Interacts with SMAD7. Interacts with BAG1. Ref.7 Ref.8 Ref.9 Ref.10 Ref.14 Ref.15 Ref.16

Subcellular location

Endoplasmic reticulum Ref.13.

Induction

By methyl methanesulfonate and ionizing irradiation. By IL24/interleukin-24 in melanoma cells; which induces apoptosis. Ref.1 Ref.7 Ref.11

Post-translational modification

Phosphorylated on tyrosine by LYN; which impairs its antiproliferative activity. Ref.8

Miscellaneous

The phosphatase activity of the PPP1R15A-PP1 complex toward EIF2S1 is specifically inhibited by Salubrinal, a drug that protects cells from endoplasmic reticulum stress.

Sequence similarities

Belongs to the PPP1R15 family.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

CTBP2P565452EBI-714746,EBI-741533
PPP1R1AQ135224EBI-714746,EBI-1568511

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 674674Protein phosphatase 1 regulatory subunit 15A
PRO_0000320518

Regions

Repeat337 – 369331
Repeat384 – 417342
Repeat427 – 460343
Repeat477 – 510344
Region1 – 180180Required for localization in the endoplasmic reticulum
Region337 – 5101744 X 34 AA approximate repeats
Region337 – 510174Interaction with SMAD7
Region483 – 55573Interaction with KMT2A/MLL1
Region536 – 58348Interaction with SMARCB1
Compositional bias112 – 1154Poly-Asp
Compositional bias160 – 503344Glu-rich
Compositional bias518 – 5214Poly-Pro
Compositional bias661 – 6666Poly-Ala

Natural variations

Natural variant311R → H.
Corresponds to variant rs564196 [ dbSNP | Ensembl ].
VAR_039186
Natural variant321A → T. Ref.2
Corresponds to variant rs3786734 [ dbSNP | Ensembl ].
VAR_039187
Natural variant1991V → A.
Corresponds to variant rs611251 [ dbSNP | Ensembl ].
VAR_039188
Natural variant2511R → P.
Corresponds to variant rs557806 [ dbSNP | Ensembl ].
VAR_039189
Natural variant2771K → E. Ref.3
Corresponds to variant rs610308 [ dbSNP | Ensembl ].
VAR_039190
Natural variant3121G → S. Ref.3
Corresponds to variant rs11541192 [ dbSNP | Ensembl ].
VAR_062226
Natural variant3161A → P. Ref.3
Corresponds to variant rs556052 [ dbSNP | Ensembl ].
VAR_039191
Natural variant3811A → V.
Corresponds to variant rs1050166 [ dbSNP | Ensembl ].
VAR_039192
Natural variant4761R → S. Ref.3
Corresponds to variant rs35087747 [ dbSNP | Ensembl ].
VAR_039193
Natural variant5941R → C.
Corresponds to variant rs2270946 [ dbSNP | Ensembl ].
VAR_039194
Natural variant5971T → A. Ref.3
Corresponds to variant rs500079 [ dbSNP | Ensembl ].
VAR_039195

Experimental info

Mutagenesis555 – 5584KVRF → AAAA: Reduces interaction with SMARCB1. Ref.10
Mutagenesis556 – 5583VRF → ARA: Impairs PP1 activation. Ref.13
Mutagenesis6121R → K: Reduces PP1-binding; when associated with K-614. Ref.13
Mutagenesis6141R → K: Reduces PP1-binding; when associated with K-612. Ref.13
Mutagenesis6181R → D: Reduces PP1-binding. Ref.13
Sequence conflict801E → G in BAA91649. Ref.3
Sequence conflict2971P → L in CAG33540. Ref.2

Sequences

Sequence LengthMass (Da)Tools
O75807 [UniParc].

Last modified November 1, 1998. Version 1.
Checksum: B257AA17456D1403

FASTA67473,478
        10         20         30         40         50         60 
MAPGQAPHQA TPWRDAHPFF LLSPVMGLLS RAWSRLRGLG PLEPWLVEAV KGAALVEAGL 

        70         80         90        100        110        120 
EGEARTPLAI PHTPWGRRPE EEAEDSGGPG EDRETLGLKT SSSLPEAWGL LDDDDGMYGE 

       130        140        150        160        170        180 
REATSVPRGQ GSQFADGQRA PLSPSLLIRT LQGSDKNPGE EKAEEEGVAE EEGVNKFSYP 

       190        200        210        220        230        240 
PSHRECCPAV EEEDDEEAVK KEAHRTSTSA LSPGSKPSTW VSCPGEEENQ ATEDKRTERS 

       250        260        270        280        290        300 
KGARKTSVSP RSSGSDPRSW EYRSGEASEE KEEKAHKETG KGEAAPGPQS SAPAQRPQLK 

       310        320        330        340        350        360 
SWWCQPSDEE EGEVKALGAA EKDGEAECPP CIPPPSAFLK AWVYWPGEDT EEEEDEEEDE 

       370        380        390        400        410        420 
DSDSGSDEEE GEAEASSSTP ATGVFLKSWV YQPGEDTEEE EDEDSDTGSA EDEREAETSA 

       430        440        450        460        470        480 
STPPASAFLK AWVYRPGEDT EEEEDEDVDS EDKEDDSEAA LGEAESDPHP SHPDQRAHFR 

       490        500        510        520        530        540 
GWGYRPGKET EEEEAAEDWG EAEPCPFRVA IYVPGEKPPP PWAPPRLPLR LQRRLKRPET 

       550        560        570        580        590        600 
PTHDPDPETP LKARKVRFSE KVTVHFLAVW AGPAQAARQG PWEQLARDRS RFARRITQAQ 

       610        620        630        640        650        660 
EELSPCLTPA ARARAWARLR NPPLAPIPAL TQTLPSSSVP SSPVQTTPLS QAVATPSRSS 

       670 
AAAAAALDLS GRRG 

« Hide

References

« Hide 'large scale' references
[1]"Mammalian GADD34, an apoptosis- and DNA damage-inducible gene."
Hollander M.C., Zhan Q., Bae I., Fornace A.J. Jr.
J. Biol. Chem. 272:13731-13737(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], INDUCTION.
[2]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT THR-32.
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS GLU-277; SER-312; PRO-316; SER-476 AND ALA-597.
[4]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[6]"The gadd and MyD genes define a novel set of mammalian genes encoding acidic proteins that synergistically suppress cell growth."
Zhan Q., Lord K.A., Alamo I. Jr., Hollander M.C., Carrier F., Ron D., Kohn K.W., Hoffman B., Liebermann D.A., Fornace A.J. Jr.
Mol. Cell. Biol. 14:2361-2371(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[7]"Leukemic HRX fusion proteins inhibit GADD34-induced apoptosis and associate with the GADD34 and hSNF5/INI1 proteins."
Adler H.T., Chinery R., Wu D.Y., Kussick S.J., Payne J.M., Fornace A.J. Jr., Tkachuk D.C.
Mol. Cell. Biol. 19:7050-7060(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH KMT2A/MLL1 AND SMARCB1, INDUCTION.
[8]"Interaction between growth arrest-DNA damage protein 34 and Src kinase Lyn negatively regulates genotoxic apoptosis."
Grishin A.V., Azhipa O., Semenov I., Corey S.J.
Proc. Natl. Acad. Sci. U.S.A. 98:10172-10177(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH LYN, PHOSPHORYLATION.
[9]"Growth arrest and DNA damage-inducible protein GADD34 assembles a novel signaling complex containing protein phosphatase 1 and inhibitor 1."
Connor J.H., Weiser D.C., Li S., Hallenbeck J.M., Shenolikar S.
Mol. Cell. Biol. 21:6841-6850(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PP1 AND PPP1R1A, FUNCTION.
[10]"The human SNF5/INI1 protein facilitates the function of the growth arrest and DNA damage-inducible protein (GADD34) and modulates GADD34-bound protein phosphatase-1 activity."
Wu D.Y., Tkachuck D.C., Roberson R.S., Schubach W.H.
J. Biol. Chem. 277:27706-27715(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SMARCB1 AND PP1, MUTAGENESIS OF 555-LYS--PHE-558.
[11]"mda-7 (IL-24) Mediates selective apoptosis in human melanoma cells by inducing the coordinated overexpression of the GADD family of genes by means of p38 MAPK."
Sarkar D., Su Z.-Z., Lebedeva I.V., Sauane M., Gopalkrishnan R.V., Valerie K., Dent P., Fisher P.B.
Proc. Natl. Acad. Sci. U.S.A. 99:10054-10059(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[12]"GADD34 induces p53 phosphorylation and p21/WAF1 transcription."
Yagi A., Hasegawa Y., Xiao H., Haneda M., Kojima E., Nishikimi A., Hasegawa T., Shimokata K., Isobe K.
J. Cell. Biochem. 90:1242-1249(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[13]"Growth arrest and DNA damage-inducible protein GADD34 targets protein phosphatase 1 alpha to the endoplasmic reticulum and promotes dephosphorylation of the alpha subunit of eukaryotic translation initiation factor 2."
Brush M.H., Weiser D.C., Shenolikar S.
Mol. Cell. Biol. 23:1292-1303(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF 556-VAL--SER-558; ARG-612; ARG-614 AND ARG-618, SUBCELLULAR LOCATION.
[14]"Human BAG-1 proteins bind to the cellular stress response protein GADD34 and interfere with GADD34 functions."
Hung W.J., Roberson R.S., Taft J., Wu D.Y.
Mol. Cell. Biol. 23:3477-3486(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH BAG1.
[15]"GADD34-PP1c recruited by Smad7 dephosphorylates TGFbeta type I receptor."
Shi W., Sun C., He B., Xiong W., Shi X., Yao D., Cao X.
J. Cell Biol. 164:291-300(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH SMAD7.
[16]"A selective inhibitor of eIF2alpha dephosphorylation protects cells from ER stress."
Boyce M., Bryant K.F., Jousse C., Long K., Harding H.P., Scheuner D., Kaufman R.J., Ma D., Coen D.M., Ron D., Yuan J.
Science 307:935-939(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PP1.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U83981 mRNA. Translation: AAC25631.1.
CR457259 mRNA. Translation: CAG33540.1.
AK001361 mRNA. Translation: BAA91649.1.
CH471177 Genomic DNA. Translation: EAW52409.1.
BC003067 mRNA. Translation: AAH03067.1.
RefSeqNP_055145.3. NM_014330.3.
UniGeneHs.631593.

3D structure databases

ProteinModelPortalO75807.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid117172. 23 interactions.
IntActO75807. 12 interactions.
MINTMINT-1192304.
STRING9606.ENSP00000200453.

PTM databases

PhosphoSiteO75807.

Proteomic databases

PaxDbO75807.
PRIDEO75807.

Protocols and materials databases

DNASU23645.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000200453; ENSP00000200453; ENSG00000087074.
GeneID23645.
KEGGhsa:23645.
UCSCuc002pky.4. human.

Organism-specific databases

CTD23645.
GeneCardsGC19P049375.
H-InvDBHIX0015305.
HIX0174313.
HGNCHGNC:14375. PPP1R15A.
HPACAB018395.
HPA020240.
MIM611048. gene.
neXtProtNX_O75807.
PharmGKBPA33632.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG75356.
HOGENOMHOG000060154.
HOVERGENHBG052542.
InParanoidO75807.
KOK14019.
OMAWRDAHPF.
OrthoDBEOG75QR48.
PhylomeDBO75807.
TreeFamTF105547.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_116125. Disease.
SignaLinkO75807.

Gene expression databases

BgeeO75807.
CleanExHS_PPP1R15A.
GenevestigatorO75807.

Family and domain databases

InterProIPR019523. Prot_Pase1_reg-su15A/B_C.
[Graphical view]
PfamPF10488. PP1c_bdg. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPPP1R15A. human.
GeneWikiPPP1R15A.
GenomeRNAi23645.
NextBio46457.
PROO75807.
SOURCESearch...

Entry information

Entry namePR15A_HUMAN
AccessionPrimary (citable) accession number: O75807
Secondary accession number(s): Q6IA96, Q9NVU6
Entry history
Integrated into UniProtKB/Swiss-Prot: February 26, 2008
Last sequence update: November 1, 1998
Last modified: April 16, 2014
This is version 93 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM