Full text data of PPP2R4
PPP2R4
(PTPA)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Serine/threonine-protein phosphatase 2A activator; 5.2.1.8 (PP2A, subunit B', PR53 isoform; Phosphotyrosyl phosphatase activator; PTPA; Serine/threonine-protein phosphatase 2A regulatory subunit 4; Serine/threonine-protein phosphatase 2A regulatory subunit B')
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Serine/threonine-protein phosphatase 2A activator; 5.2.1.8 (PP2A, subunit B', PR53 isoform; Phosphotyrosyl phosphatase activator; PTPA; Serine/threonine-protein phosphatase 2A regulatory subunit 4; Serine/threonine-protein phosphatase 2A regulatory subunit B')
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00477616
IPI00477616 Protein phosphatase 2A, regulatory subunit B phosphatase activator activity soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
IPI00477616 Protein phosphatase 2A, regulatory subunit B phosphatase activator activity soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
UniProt
Q15257
ID PTPA_HUMAN Reviewed; 358 AA.
AC Q15257; A2A347; A9IZU4; B4DXM4; Q15258; Q53GZ3; Q5TZQ2; Q9BUK1;
read moreAC Q9NNZ7; Q9NNZ8; Q9NNZ9;
DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 3.
DT 22-JAN-2014, entry version 121.
DE RecName: Full=Serine/threonine-protein phosphatase 2A activator;
DE EC=5.2.1.8;
DE AltName: Full=PP2A, subunit B', PR53 isoform;
DE AltName: Full=Phosphotyrosyl phosphatase activator;
DE Short=PTPA;
DE AltName: Full=Serine/threonine-protein phosphatase 2A regulatory subunit 4;
DE AltName: Full=Serine/threonine-protein phosphatase 2A regulatory subunit B';
GN Name=PPP2R4; Synonyms=PTPA;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Heart;
RX PubMed=8195217;
RA Cayla X., Van Hoof C., Bosch M., Waelkens E., Peeters B.,
RA Merlevede W., Goris J.;
RT "Molecular cloning, expression, and characterization of PTPA, a
RT protein that activates the tyrosyl phosphatase activity of protein
RT phosphatase 2A.";
RL J. Biol. Chem. 269:15668-15675(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
RC TISSUE=Blood;
RX PubMed=8530035; DOI=10.1006/geno.1995.1140;
RA Van Hoof C., Aly M., Garcia A., Cayla X., Cassiman J.-J.,
RA Merlevede W., Goris J.;
RT "Structure and chromosomal localization of the human gene of the
RT phosphotyrosyl phosphatase activator (PTPA) of protein phosphatase
RT 2A.";
RL Genomics 28:261-272(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 2; 3 AND 4).
RX PubMed=10880964; DOI=10.1046/j.1432-1327.2000.01486.x;
RA Janssens V., van Hoof C., Martens E., de Baere I., Merlevede W.,
RA Goris J.;
RT "Identification and characterization of alternative splice products
RT encoded by the human phosphotyrosyl phosphatase activator gene.";
RL Eur. J. Biochem. 267:4406-4413(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT
RP LEU-357.
RC TISSUE=Liver;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E.,
RA Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S.,
RA Babbage A.K., Babbage S., Bagguley C.L., Bailey J., Banerjee R.,
RA Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W.,
RA Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G.,
RA Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M.,
RA Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W.,
RA Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A.,
RA Frankland J.A., French L., Fricker D.G., Garner P., Garnett J.,
RA Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M.,
RA Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S.,
RA McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J.,
RA Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R.,
RA Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M.,
RA Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M.,
RA Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A.,
RA Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W.,
RA Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S.,
RA Rogers J., Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP FUNCTION IN APOPTOSIS, AND SUBCELLULAR LOCATION.
RX PubMed=17333320; DOI=10.1007/s10495-006-0050-8;
RA Azam S., Drobetsky E., Ramotar D.;
RT "Overexpression of the cis/trans isomerase PTPA triggers caspase 3-
RT dependent apoptosis.";
RL Apoptosis 12:1243-1255(2007).
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [13]
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.,
RA Buerckstuemmer T., 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 [14]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 22-358.
RX PubMed=16782712; DOI=10.1074/jbc.C600100200;
RA Magnusdottir A., Stenmark P., Flodin S., Nyman T., Hammarstroem M.,
RA Ehn M., Bakali H M.A., Berglund H., Nordlund P.;
RT "The crystal structure of a human PP2A phosphatase activator reveals a
RT novel fold and highly conserved cleft implicated in protein-protein
RT interactions.";
RL J. Biol. Chem. 281:22434-22438(2006).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 20-357.
RX PubMed=16885030; DOI=10.1016/j.molcel.2006.07.008;
RA Leulliot N., Vicentini G., Jordens J., Quevillon-Cheruel S.,
RA Schiltz M., Barford D., van Tilbeurgh H., Goris J.;
RT "Crystal structure of the PP2A phosphatase activator: implications for
RT its PP2A-specific PPIase activity.";
RL Mol. Cell 23:413-424(2006).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS), FUNCTION IN MODULATION OF PP2A
RP SUBSTRATE SPECIFICITY, ATP-BINDING, MUTAGENESIS OF ASP-185; ALA-239;
RP GLY-240; VAL-244; GLU-305; GLY-325; MET-329 AND LYS-337, AND
RP INTERACTION WITH THE PP2A(D) COMPLEX.
RX PubMed=16916641; DOI=10.1016/j.molcel.2006.07.027;
RA Chao Y., Xing Y., Chen Y., Xu Y., Lin Z., Li Z., Jeffrey P.D.,
RA Stock J.B., Shi Y.;
RT "Structure and mechanism of the phosphotyrosyl phosphatase
RT activator.";
RL Mol. Cell 23:535-546(2006).
CC -!- FUNCTION: PPIases accelerate the folding of proteins. It catalyzes
CC the cis-trans isomerization of proline imidic peptide bonds in
CC oligopeptides. Acts as a regulatory subunit for serine/threonine-
CC protein phosphatase 2A (PP2A) modulating its activity or substrate
CC specificity, probably by inducing a conformational change in the
CC catalytic subunit, a proposed direct target of the PPIase. Can
CC reactivate inactive phosphatase PP2A-phosphatase methylesterase
CC complexes (PP2A(i)) in presence of ATP and Mg(2+) (By similarity).
CC Reversibly stimulates the variable phosphotyrosyl phosphatase
CC activity of PP2A core heterodimer PP2A(D) in presence of ATP and
CC Mg(2+) (in vitro). The phosphotyrosyl phosphatase activity is
CC dependent of an ATPase activity of the PP2A(D):PPP2R4 complex. Is
CC involved in apoptosis; the function appears to be independent from
CC PP2A.
CC -!- CATALYTIC ACTIVITY: Peptidylproline (omega=180) = peptidylproline
CC (omega=0).
CC -!- SUBUNIT: Associates with PP2A heterodimeric core enzyme PP2A(D),
CC composed of a 36 kDa catalytic subunit (subunit C) and a 65 kDa
CC constant regulatory subunit (PR65 or subunit A). Interacts with
CC PPP2CB (By similarity).
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=2; Synonyms=Beta;
CC IsoId=Q15257-1; Sequence=Displayed;
CC Name=1; Synonyms=Alpha;
CC IsoId=Q15257-2; Sequence=VSP_005123;
CC Name=3; Synonyms=Delta;
CC IsoId=Q15257-3; Sequence=VSP_005122;
CC Name=4; Synonyms=Epsilon;
CC IsoId=Q15257-4; Sequence=VSP_005124;
CC -!- TISSUE SPECIFICITY: Widely expressed.
CC -!- SIMILARITY: Belongs to the PTPA-type PPIase family.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/PPP2R4ID41817ch9q34.html";
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DR EMBL; X73478; CAA51873.1; -; mRNA.
DR EMBL; X86428; CAA60163.1; -; Genomic_DNA.
DR EMBL; X86429; CAA60163.1; JOINED; Genomic_DNA.
DR EMBL; X86430; CAA60163.1; JOINED; Genomic_DNA.
DR EMBL; X86432; CAA60163.1; JOINED; Genomic_DNA.
DR EMBL; X86434; CAA60163.1; JOINED; Genomic_DNA.
DR EMBL; X86435; CAA60163.1; JOINED; Genomic_DNA.
DR EMBL; X86436; CAA60163.1; JOINED; Genomic_DNA.
DR EMBL; X86437; CAA60163.1; JOINED; Genomic_DNA.
DR EMBL; X86438; CAA60163.1; JOINED; Genomic_DNA.
DR EMBL; X86439; CAA60163.1; JOINED; Genomic_DNA.
DR EMBL; X86428; CAB77601.1; -; Genomic_DNA.
DR EMBL; X86429; CAB77601.1; JOINED; Genomic_DNA.
DR EMBL; X86430; CAB77601.1; JOINED; Genomic_DNA.
DR EMBL; X86431; CAB77601.1; JOINED; Genomic_DNA.
DR EMBL; X86432; CAB77601.1; JOINED; Genomic_DNA.
DR EMBL; X86434; CAB77601.1; JOINED; Genomic_DNA.
DR EMBL; X86435; CAB77601.1; JOINED; Genomic_DNA.
DR EMBL; X86436; CAB77601.1; JOINED; Genomic_DNA.
DR EMBL; X86437; CAB77601.1; JOINED; Genomic_DNA.
DR EMBL; X86438; CAB77601.1; JOINED; Genomic_DNA.
DR EMBL; X86439; CAB77601.1; JOINED; Genomic_DNA.
DR EMBL; X86428; CAB77602.1; -; Genomic_DNA.
DR EMBL; X86429; CAB77602.1; JOINED; Genomic_DNA.
DR EMBL; X86432; CAB77602.1; JOINED; Genomic_DNA.
DR EMBL; X86434; CAB77602.1; JOINED; Genomic_DNA.
DR EMBL; X86435; CAB77602.1; JOINED; Genomic_DNA.
DR EMBL; X86436; CAB77602.1; JOINED; Genomic_DNA.
DR EMBL; X86437; CAB77602.1; JOINED; Genomic_DNA.
DR EMBL; X86438; CAB77602.1; JOINED; Genomic_DNA.
DR EMBL; X86439; CAB77602.1; JOINED; Genomic_DNA.
DR EMBL; X86428; CAB77603.1; -; Genomic_DNA.
DR EMBL; X86429; CAB77603.1; JOINED; Genomic_DNA.
DR EMBL; X86430; CAB77603.1; JOINED; Genomic_DNA.
DR EMBL; X86434; CAB77603.1; JOINED; Genomic_DNA.
DR EMBL; X86435; CAB77603.1; JOINED; Genomic_DNA.
DR EMBL; X86436; CAB77603.1; JOINED; Genomic_DNA.
DR EMBL; X86437; CAB77603.1; JOINED; Genomic_DNA.
DR EMBL; X86438; CAB77603.1; JOINED; Genomic_DNA.
DR EMBL; X86439; CAB77603.1; JOINED; Genomic_DNA.
DR EMBL; AK302043; BAG63436.1; -; mRNA.
DR EMBL; BT020119; AAV38922.1; -; mRNA.
DR EMBL; AK222788; BAD96508.1; -; mRNA.
DR EMBL; AL158151; CAM14695.1; -; Genomic_DNA.
DR EMBL; AL158151; CAP58847.2; -; Genomic_DNA.
DR EMBL; CH471090; EAW87876.1; -; Genomic_DNA.
DR EMBL; CH471090; EAW87882.1; -; Genomic_DNA.
DR EMBL; BC002545; AAH02545.1; -; mRNA.
DR EMBL; BC011605; AAH11605.1; -; mRNA.
DR PIR; A54021; A54021.
DR RefSeq; NP_001180326.1; NM_001193397.1.
DR RefSeq; NP_001258761.1; NM_001271832.1.
DR RefSeq; NP_066954.2; NM_021131.4.
DR RefSeq; NP_821067.1; NM_178000.2.
DR RefSeq; NP_821068.1; NM_178001.2.
DR RefSeq; NP_821070.1; NM_178003.2.
DR UniGene; Hs.400740; -.
DR PDB; 2G62; X-ray; 1.60 A; A=22-358.
DR PDB; 2HV6; X-ray; 1.90 A; A/B=1-358.
DR PDB; 2HV7; X-ray; 2.50 A; A/B/C/D/E/F/G/H=1-358.
DR PDB; 2IXM; X-ray; 1.50 A; A=20-357.
DR PDB; 4LAC; X-ray; 2.82 A; B=19-358.
DR PDBsum; 2G62; -.
DR PDBsum; 2HV6; -.
DR PDBsum; 2HV7; -.
DR PDBsum; 2IXM; -.
DR PDBsum; 4LAC; -.
DR ProteinModelPortal; Q15257; -.
DR SMR; Q15257; 23-357.
DR IntAct; Q15257; 10.
DR MINT; MINT-3031079; -.
DR BindingDB; Q15257; -.
DR ChEMBL; CHEMBL2505; -.
DR PhosphoSite; Q15257; -.
DR DMDM; 116242737; -.
DR OGP; Q15257; -.
DR PaxDb; Q15257; -.
DR PRIDE; Q15257; -.
DR DNASU; 5524; -.
DR Ensembl; ENST00000337738; ENSP00000337448; ENSG00000119383.
DR Ensembl; ENST00000355007; ENSP00000347109; ENSG00000119383.
DR Ensembl; ENST00000357197; ENSP00000349726; ENSG00000119383.
DR Ensembl; ENST00000358994; ENSP00000351885; ENSG00000119383.
DR Ensembl; ENST00000393370; ENSP00000377036; ENSG00000119383.
DR GeneID; 5524; -.
DR KEGG; hsa:5524; -.
DR UCSC; uc004bxm.2; human.
DR CTD; 5524; -.
DR GeneCards; GC09P131873; -.
DR HGNC; HGNC:9308; PPP2R4.
DR HPA; CAB022068; -.
DR HPA; CAB035999; -.
DR HPA; HPA005695; -.
DR MIM; 600756; gene.
DR neXtProt; NX_Q15257; -.
DR PharmGKB; PA33671; -.
DR eggNOG; COG5057; -.
DR HOVERGEN; HBG019168; -.
DR KO; K17605; -.
DR OrthoDB; EOG7KQ21W; -.
DR PhylomeDB; Q15257; -.
DR ChiTaRS; PPP2R4; human.
DR EvolutionaryTrace; Q15257; -.
DR GeneWiki; PPP2R4; -.
DR GenomeRNAi; 5524; -.
DR NextBio; 21382; -.
DR PRO; PR:Q15257; -.
DR ArrayExpress; Q15257; -.
DR Bgee; Q15257; -.
DR CleanEx; HS_PPP2R4; -.
DR Genevestigator; Q15257; -.
DR GO; GO:0034704; C:calcium channel complex; IDA:BHF-UCL.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0000159; C:protein phosphatase type 2A complex; TAS:HGNC.
DR GO; GO:0005524; F:ATP binding; IDA:HGNC.
DR GO; GO:0003755; F:peptidyl-prolyl cis-trans isomerase activity; IBA:RefGenome.
DR GO; GO:0046982; F:protein heterodimerization activity; TAS:HGNC.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:HGNC.
DR GO; GO:0051721; F:protein phosphatase 2A binding; IDA:HGNC.
DR GO; GO:0008601; F:protein phosphatase type 2A regulator activity; IDA:HGNC.
DR GO; GO:0008160; F:protein tyrosine phosphatase activator activity; IDA:HGNC.
DR GO; GO:0006200; P:ATP catabolic process; IDA:GOC.
DR GO; GO:0030472; P:mitotic spindle organization in nucleus; IBA:RefGenome.
DR GO; GO:0032515; P:negative regulation of phosphoprotein phosphatase activity; IDA:HGNC.
DR GO; GO:0035308; P:negative regulation of protein dephosphorylation; IDA:HGNC.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:0032516; P:positive regulation of phosphoprotein phosphatase activity; IDA:HGNC.
DR GO; GO:0035307; P:positive regulation of protein dephosphorylation; IDA:HGNC.
DR GO; GO:0006457; P:protein folding; IEA:UniProtKB-KW.
DR InterPro; IPR004327; Phstyr_phstse_ac.
DR PANTHER; PTHR10012; PTHR10012; 1.
DR Pfam; PF03095; PTPA; 1.
DR PIRSF; PIRSF016325; Phstyr_phstse_ac; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; ATP-binding;
KW Complete proteome; Cytoplasm; Direct protein sequencing; Isomerase;
KW Nucleotide-binding; Nucleus; Polymorphism; Reference proteome;
KW Rotamase.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 358 Serine/threonine-protein phosphatase 2A
FT activator.
FT /FTId=PRO_0000071524.
FT NP_BIND 183 189 ATP.
FT NP_BIND 240 242 ATP.
FT NP_BIND 342 343 ATP.
FT MOD_RES 2 2 N-acetylalanine.
FT VAR_SEQ 45 108 Missing (in isoform 3).
FT /FTId=VSP_005122.
FT VAR_SEQ 73 149 Missing (in isoform 4).
FT /FTId=VSP_005124.
FT VAR_SEQ 73 107 Missing (in isoform 1).
FT /FTId=VSP_005123.
FT VARIANT 28 28 K -> R (in dbSNP:rs17481693).
FT /FTId=VAR_028101.
FT VARIANT 208 208 R -> Q (in dbSNP:rs4836639).
FT /FTId=VAR_028102.
FT VARIANT 357 357 S -> L (in dbSNP:rs2480452).
FT /FTId=VAR_028103.
FT MUTAGEN 185 185 D->A: Impairs ATPase activity of the
FT PP2A(D):PPP2R4 complex; no effect on
FT interaction with the PP2A(D) complex.
FT MUTAGEN 239 239 A->D: Impairs ATPase activity of the
FT PP2A(D):PPP2R4 complex; no effect on
FT interaction with the PP2A(D) complex.
FT MUTAGEN 240 240 G->D: Impairs ATPase activity of the
FT PP2A(D):PPP2R4 complex; no effect on
FT interaction with the PP2A(D) complex.
FT MUTAGEN 244 244 V->D: Impairs interaction with the
FT PP2A(D) complex.
FT MUTAGEN 305 305 E->A: Abolishes interaction with the
FT PP2A(D) complex.
FT MUTAGEN 316 316 V->D: Impairs interaction with the
FT PP2A(D) complex.
FT MUTAGEN 325 325 G->D: Abolishes interaction with the
FT PP2A(D) complex.
FT MUTAGEN 329 329 M->D: Abolishes interaction with the
FT PP2A(D) complex.
FT MUTAGEN 337 337 K->G: Impairs interaction with the
FT PP2A(D) complex.
FT CONFLICT 113 113 V -> L (in Ref. 1; CAA51873, 2; CAA60163
FT and 3; CAB77601/CAB77602).
FT CONFLICT 297 297 Missing (in Ref. 2; CAA60163 and 3;
FT CAB77601/CAB77602/CAB77603).
FT CONFLICT 357 357 S -> V (in Ref. 1; AA sequence).
FT HELIX 34 40
FT HELIX 43 58
FT TURN 59 61
FT HELIX 107 124
FT STRAND 134 136
FT HELIX 139 156
FT HELIX 161 166
FT HELIX 167 175
FT TURN 181 184
FT HELIX 188 203
FT HELIX 209 211
FT HELIX 212 217
FT HELIX 219 233
FT STRAND 237 240
FT HELIX 243 245
FT STRAND 247 250
FT HELIX 253 261
FT TURN 262 264
FT HELIX 270 274
FT HELIX 276 282
FT HELIX 283 285
FT HELIX 287 298
FT HELIX 303 306
FT HELIX 308 313
FT HELIX 319 333
FT TURN 334 336
FT HELIX 338 341
FT STRAND 348 350
FT STRAND 352 354
SQ SEQUENCE 358 AA; 40668 MW; 2A962521AF5B4CF7 CRC64;
MAEGERQPPP DSSEEAPPAT QNFIIPKKEI HTVPDMGKWK RSQAYADYIG FILTLNEGVK
GKKLTFEYRV SEMWNEVHEE KEQAAKQSVS CDECIPLPRA GHCAPSEAIE KLVALLNTLD
RWIDETPPVD QPSRFGNKAY RTWYAKLDEE AENLVATVVP THLAAAVPEV AVYLKESVGN
STRIDYGTGH EAAFAAFLCC LCKIGVLRVD DQIAIVFKVF NRYLEVMRKL QKTYRMEPAG
SQGVWGLDDF QFLPFIWGSS QLIDHPYLEP RHFVDEKAVN ENHKDYMFLE CILFITEMKT
GPFAEHSNQL WNISAVPSWS KVNQGLIRMY KAECLEKFPV IQHFKFGSLL PIHPVTSG
//
ID PTPA_HUMAN Reviewed; 358 AA.
AC Q15257; A2A347; A9IZU4; B4DXM4; Q15258; Q53GZ3; Q5TZQ2; Q9BUK1;
read moreAC Q9NNZ7; Q9NNZ8; Q9NNZ9;
DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 3.
DT 22-JAN-2014, entry version 121.
DE RecName: Full=Serine/threonine-protein phosphatase 2A activator;
DE EC=5.2.1.8;
DE AltName: Full=PP2A, subunit B', PR53 isoform;
DE AltName: Full=Phosphotyrosyl phosphatase activator;
DE Short=PTPA;
DE AltName: Full=Serine/threonine-protein phosphatase 2A regulatory subunit 4;
DE AltName: Full=Serine/threonine-protein phosphatase 2A regulatory subunit B';
GN Name=PPP2R4; Synonyms=PTPA;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Heart;
RX PubMed=8195217;
RA Cayla X., Van Hoof C., Bosch M., Waelkens E., Peeters B.,
RA Merlevede W., Goris J.;
RT "Molecular cloning, expression, and characterization of PTPA, a
RT protein that activates the tyrosyl phosphatase activity of protein
RT phosphatase 2A.";
RL J. Biol. Chem. 269:15668-15675(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
RC TISSUE=Blood;
RX PubMed=8530035; DOI=10.1006/geno.1995.1140;
RA Van Hoof C., Aly M., Garcia A., Cayla X., Cassiman J.-J.,
RA Merlevede W., Goris J.;
RT "Structure and chromosomal localization of the human gene of the
RT phosphotyrosyl phosphatase activator (PTPA) of protein phosphatase
RT 2A.";
RL Genomics 28:261-272(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 2; 3 AND 4).
RX PubMed=10880964; DOI=10.1046/j.1432-1327.2000.01486.x;
RA Janssens V., van Hoof C., Martens E., de Baere I., Merlevede W.,
RA Goris J.;
RT "Identification and characterization of alternative splice products
RT encoded by the human phosphotyrosyl phosphatase activator gene.";
RL Eur. J. Biochem. 267:4406-4413(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT
RP LEU-357.
RC TISSUE=Liver;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E.,
RA Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S.,
RA Babbage A.K., Babbage S., Bagguley C.L., Bailey J., Banerjee R.,
RA Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W.,
RA Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G.,
RA Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M.,
RA Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W.,
RA Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A.,
RA Frankland J.A., French L., Fricker D.G., Garner P., Garnett J.,
RA Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M.,
RA Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S.,
RA McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J.,
RA Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R.,
RA Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M.,
RA Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M.,
RA Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A.,
RA Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W.,
RA Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S.,
RA Rogers J., Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP FUNCTION IN APOPTOSIS, AND SUBCELLULAR LOCATION.
RX PubMed=17333320; DOI=10.1007/s10495-006-0050-8;
RA Azam S., Drobetsky E., Ramotar D.;
RT "Overexpression of the cis/trans isomerase PTPA triggers caspase 3-
RT dependent apoptosis.";
RL Apoptosis 12:1243-1255(2007).
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [13]
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.,
RA Buerckstuemmer T., 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 [14]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 22-358.
RX PubMed=16782712; DOI=10.1074/jbc.C600100200;
RA Magnusdottir A., Stenmark P., Flodin S., Nyman T., Hammarstroem M.,
RA Ehn M., Bakali H M.A., Berglund H., Nordlund P.;
RT "The crystal structure of a human PP2A phosphatase activator reveals a
RT novel fold and highly conserved cleft implicated in protein-protein
RT interactions.";
RL J. Biol. Chem. 281:22434-22438(2006).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 20-357.
RX PubMed=16885030; DOI=10.1016/j.molcel.2006.07.008;
RA Leulliot N., Vicentini G., Jordens J., Quevillon-Cheruel S.,
RA Schiltz M., Barford D., van Tilbeurgh H., Goris J.;
RT "Crystal structure of the PP2A phosphatase activator: implications for
RT its PP2A-specific PPIase activity.";
RL Mol. Cell 23:413-424(2006).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS), FUNCTION IN MODULATION OF PP2A
RP SUBSTRATE SPECIFICITY, ATP-BINDING, MUTAGENESIS OF ASP-185; ALA-239;
RP GLY-240; VAL-244; GLU-305; GLY-325; MET-329 AND LYS-337, AND
RP INTERACTION WITH THE PP2A(D) COMPLEX.
RX PubMed=16916641; DOI=10.1016/j.molcel.2006.07.027;
RA Chao Y., Xing Y., Chen Y., Xu Y., Lin Z., Li Z., Jeffrey P.D.,
RA Stock J.B., Shi Y.;
RT "Structure and mechanism of the phosphotyrosyl phosphatase
RT activator.";
RL Mol. Cell 23:535-546(2006).
CC -!- FUNCTION: PPIases accelerate the folding of proteins. It catalyzes
CC the cis-trans isomerization of proline imidic peptide bonds in
CC oligopeptides. Acts as a regulatory subunit for serine/threonine-
CC protein phosphatase 2A (PP2A) modulating its activity or substrate
CC specificity, probably by inducing a conformational change in the
CC catalytic subunit, a proposed direct target of the PPIase. Can
CC reactivate inactive phosphatase PP2A-phosphatase methylesterase
CC complexes (PP2A(i)) in presence of ATP and Mg(2+) (By similarity).
CC Reversibly stimulates the variable phosphotyrosyl phosphatase
CC activity of PP2A core heterodimer PP2A(D) in presence of ATP and
CC Mg(2+) (in vitro). The phosphotyrosyl phosphatase activity is
CC dependent of an ATPase activity of the PP2A(D):PPP2R4 complex. Is
CC involved in apoptosis; the function appears to be independent from
CC PP2A.
CC -!- CATALYTIC ACTIVITY: Peptidylproline (omega=180) = peptidylproline
CC (omega=0).
CC -!- SUBUNIT: Associates with PP2A heterodimeric core enzyme PP2A(D),
CC composed of a 36 kDa catalytic subunit (subunit C) and a 65 kDa
CC constant regulatory subunit (PR65 or subunit A). Interacts with
CC PPP2CB (By similarity).
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=2; Synonyms=Beta;
CC IsoId=Q15257-1; Sequence=Displayed;
CC Name=1; Synonyms=Alpha;
CC IsoId=Q15257-2; Sequence=VSP_005123;
CC Name=3; Synonyms=Delta;
CC IsoId=Q15257-3; Sequence=VSP_005122;
CC Name=4; Synonyms=Epsilon;
CC IsoId=Q15257-4; Sequence=VSP_005124;
CC -!- TISSUE SPECIFICITY: Widely expressed.
CC -!- SIMILARITY: Belongs to the PTPA-type PPIase family.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/PPP2R4ID41817ch9q34.html";
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DR EMBL; X73478; CAA51873.1; -; mRNA.
DR EMBL; X86428; CAA60163.1; -; Genomic_DNA.
DR EMBL; X86429; CAA60163.1; JOINED; Genomic_DNA.
DR EMBL; X86430; CAA60163.1; JOINED; Genomic_DNA.
DR EMBL; X86432; CAA60163.1; JOINED; Genomic_DNA.
DR EMBL; X86434; CAA60163.1; JOINED; Genomic_DNA.
DR EMBL; X86435; CAA60163.1; JOINED; Genomic_DNA.
DR EMBL; X86436; CAA60163.1; JOINED; Genomic_DNA.
DR EMBL; X86437; CAA60163.1; JOINED; Genomic_DNA.
DR EMBL; X86438; CAA60163.1; JOINED; Genomic_DNA.
DR EMBL; X86439; CAA60163.1; JOINED; Genomic_DNA.
DR EMBL; X86428; CAB77601.1; -; Genomic_DNA.
DR EMBL; X86429; CAB77601.1; JOINED; Genomic_DNA.
DR EMBL; X86430; CAB77601.1; JOINED; Genomic_DNA.
DR EMBL; X86431; CAB77601.1; JOINED; Genomic_DNA.
DR EMBL; X86432; CAB77601.1; JOINED; Genomic_DNA.
DR EMBL; X86434; CAB77601.1; JOINED; Genomic_DNA.
DR EMBL; X86435; CAB77601.1; JOINED; Genomic_DNA.
DR EMBL; X86436; CAB77601.1; JOINED; Genomic_DNA.
DR EMBL; X86437; CAB77601.1; JOINED; Genomic_DNA.
DR EMBL; X86438; CAB77601.1; JOINED; Genomic_DNA.
DR EMBL; X86439; CAB77601.1; JOINED; Genomic_DNA.
DR EMBL; X86428; CAB77602.1; -; Genomic_DNA.
DR EMBL; X86429; CAB77602.1; JOINED; Genomic_DNA.
DR EMBL; X86432; CAB77602.1; JOINED; Genomic_DNA.
DR EMBL; X86434; CAB77602.1; JOINED; Genomic_DNA.
DR EMBL; X86435; CAB77602.1; JOINED; Genomic_DNA.
DR EMBL; X86436; CAB77602.1; JOINED; Genomic_DNA.
DR EMBL; X86437; CAB77602.1; JOINED; Genomic_DNA.
DR EMBL; X86438; CAB77602.1; JOINED; Genomic_DNA.
DR EMBL; X86439; CAB77602.1; JOINED; Genomic_DNA.
DR EMBL; X86428; CAB77603.1; -; Genomic_DNA.
DR EMBL; X86429; CAB77603.1; JOINED; Genomic_DNA.
DR EMBL; X86430; CAB77603.1; JOINED; Genomic_DNA.
DR EMBL; X86434; CAB77603.1; JOINED; Genomic_DNA.
DR EMBL; X86435; CAB77603.1; JOINED; Genomic_DNA.
DR EMBL; X86436; CAB77603.1; JOINED; Genomic_DNA.
DR EMBL; X86437; CAB77603.1; JOINED; Genomic_DNA.
DR EMBL; X86438; CAB77603.1; JOINED; Genomic_DNA.
DR EMBL; X86439; CAB77603.1; JOINED; Genomic_DNA.
DR EMBL; AK302043; BAG63436.1; -; mRNA.
DR EMBL; BT020119; AAV38922.1; -; mRNA.
DR EMBL; AK222788; BAD96508.1; -; mRNA.
DR EMBL; AL158151; CAM14695.1; -; Genomic_DNA.
DR EMBL; AL158151; CAP58847.2; -; Genomic_DNA.
DR EMBL; CH471090; EAW87876.1; -; Genomic_DNA.
DR EMBL; CH471090; EAW87882.1; -; Genomic_DNA.
DR EMBL; BC002545; AAH02545.1; -; mRNA.
DR EMBL; BC011605; AAH11605.1; -; mRNA.
DR PIR; A54021; A54021.
DR RefSeq; NP_001180326.1; NM_001193397.1.
DR RefSeq; NP_001258761.1; NM_001271832.1.
DR RefSeq; NP_066954.2; NM_021131.4.
DR RefSeq; NP_821067.1; NM_178000.2.
DR RefSeq; NP_821068.1; NM_178001.2.
DR RefSeq; NP_821070.1; NM_178003.2.
DR UniGene; Hs.400740; -.
DR PDB; 2G62; X-ray; 1.60 A; A=22-358.
DR PDB; 2HV6; X-ray; 1.90 A; A/B=1-358.
DR PDB; 2HV7; X-ray; 2.50 A; A/B/C/D/E/F/G/H=1-358.
DR PDB; 2IXM; X-ray; 1.50 A; A=20-357.
DR PDB; 4LAC; X-ray; 2.82 A; B=19-358.
DR PDBsum; 2G62; -.
DR PDBsum; 2HV6; -.
DR PDBsum; 2HV7; -.
DR PDBsum; 2IXM; -.
DR PDBsum; 4LAC; -.
DR ProteinModelPortal; Q15257; -.
DR SMR; Q15257; 23-357.
DR IntAct; Q15257; 10.
DR MINT; MINT-3031079; -.
DR BindingDB; Q15257; -.
DR ChEMBL; CHEMBL2505; -.
DR PhosphoSite; Q15257; -.
DR DMDM; 116242737; -.
DR OGP; Q15257; -.
DR PaxDb; Q15257; -.
DR PRIDE; Q15257; -.
DR DNASU; 5524; -.
DR Ensembl; ENST00000337738; ENSP00000337448; ENSG00000119383.
DR Ensembl; ENST00000355007; ENSP00000347109; ENSG00000119383.
DR Ensembl; ENST00000357197; ENSP00000349726; ENSG00000119383.
DR Ensembl; ENST00000358994; ENSP00000351885; ENSG00000119383.
DR Ensembl; ENST00000393370; ENSP00000377036; ENSG00000119383.
DR GeneID; 5524; -.
DR KEGG; hsa:5524; -.
DR UCSC; uc004bxm.2; human.
DR CTD; 5524; -.
DR GeneCards; GC09P131873; -.
DR HGNC; HGNC:9308; PPP2R4.
DR HPA; CAB022068; -.
DR HPA; CAB035999; -.
DR HPA; HPA005695; -.
DR MIM; 600756; gene.
DR neXtProt; NX_Q15257; -.
DR PharmGKB; PA33671; -.
DR eggNOG; COG5057; -.
DR HOVERGEN; HBG019168; -.
DR KO; K17605; -.
DR OrthoDB; EOG7KQ21W; -.
DR PhylomeDB; Q15257; -.
DR ChiTaRS; PPP2R4; human.
DR EvolutionaryTrace; Q15257; -.
DR GeneWiki; PPP2R4; -.
DR GenomeRNAi; 5524; -.
DR NextBio; 21382; -.
DR PRO; PR:Q15257; -.
DR ArrayExpress; Q15257; -.
DR Bgee; Q15257; -.
DR CleanEx; HS_PPP2R4; -.
DR Genevestigator; Q15257; -.
DR GO; GO:0034704; C:calcium channel complex; IDA:BHF-UCL.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0000159; C:protein phosphatase type 2A complex; TAS:HGNC.
DR GO; GO:0005524; F:ATP binding; IDA:HGNC.
DR GO; GO:0003755; F:peptidyl-prolyl cis-trans isomerase activity; IBA:RefGenome.
DR GO; GO:0046982; F:protein heterodimerization activity; TAS:HGNC.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:HGNC.
DR GO; GO:0051721; F:protein phosphatase 2A binding; IDA:HGNC.
DR GO; GO:0008601; F:protein phosphatase type 2A regulator activity; IDA:HGNC.
DR GO; GO:0008160; F:protein tyrosine phosphatase activator activity; IDA:HGNC.
DR GO; GO:0006200; P:ATP catabolic process; IDA:GOC.
DR GO; GO:0030472; P:mitotic spindle organization in nucleus; IBA:RefGenome.
DR GO; GO:0032515; P:negative regulation of phosphoprotein phosphatase activity; IDA:HGNC.
DR GO; GO:0035308; P:negative regulation of protein dephosphorylation; IDA:HGNC.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:0032516; P:positive regulation of phosphoprotein phosphatase activity; IDA:HGNC.
DR GO; GO:0035307; P:positive regulation of protein dephosphorylation; IDA:HGNC.
DR GO; GO:0006457; P:protein folding; IEA:UniProtKB-KW.
DR InterPro; IPR004327; Phstyr_phstse_ac.
DR PANTHER; PTHR10012; PTHR10012; 1.
DR Pfam; PF03095; PTPA; 1.
DR PIRSF; PIRSF016325; Phstyr_phstse_ac; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; ATP-binding;
KW Complete proteome; Cytoplasm; Direct protein sequencing; Isomerase;
KW Nucleotide-binding; Nucleus; Polymorphism; Reference proteome;
KW Rotamase.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 358 Serine/threonine-protein phosphatase 2A
FT activator.
FT /FTId=PRO_0000071524.
FT NP_BIND 183 189 ATP.
FT NP_BIND 240 242 ATP.
FT NP_BIND 342 343 ATP.
FT MOD_RES 2 2 N-acetylalanine.
FT VAR_SEQ 45 108 Missing (in isoform 3).
FT /FTId=VSP_005122.
FT VAR_SEQ 73 149 Missing (in isoform 4).
FT /FTId=VSP_005124.
FT VAR_SEQ 73 107 Missing (in isoform 1).
FT /FTId=VSP_005123.
FT VARIANT 28 28 K -> R (in dbSNP:rs17481693).
FT /FTId=VAR_028101.
FT VARIANT 208 208 R -> Q (in dbSNP:rs4836639).
FT /FTId=VAR_028102.
FT VARIANT 357 357 S -> L (in dbSNP:rs2480452).
FT /FTId=VAR_028103.
FT MUTAGEN 185 185 D->A: Impairs ATPase activity of the
FT PP2A(D):PPP2R4 complex; no effect on
FT interaction with the PP2A(D) complex.
FT MUTAGEN 239 239 A->D: Impairs ATPase activity of the
FT PP2A(D):PPP2R4 complex; no effect on
FT interaction with the PP2A(D) complex.
FT MUTAGEN 240 240 G->D: Impairs ATPase activity of the
FT PP2A(D):PPP2R4 complex; no effect on
FT interaction with the PP2A(D) complex.
FT MUTAGEN 244 244 V->D: Impairs interaction with the
FT PP2A(D) complex.
FT MUTAGEN 305 305 E->A: Abolishes interaction with the
FT PP2A(D) complex.
FT MUTAGEN 316 316 V->D: Impairs interaction with the
FT PP2A(D) complex.
FT MUTAGEN 325 325 G->D: Abolishes interaction with the
FT PP2A(D) complex.
FT MUTAGEN 329 329 M->D: Abolishes interaction with the
FT PP2A(D) complex.
FT MUTAGEN 337 337 K->G: Impairs interaction with the
FT PP2A(D) complex.
FT CONFLICT 113 113 V -> L (in Ref. 1; CAA51873, 2; CAA60163
FT and 3; CAB77601/CAB77602).
FT CONFLICT 297 297 Missing (in Ref. 2; CAA60163 and 3;
FT CAB77601/CAB77602/CAB77603).
FT CONFLICT 357 357 S -> V (in Ref. 1; AA sequence).
FT HELIX 34 40
FT HELIX 43 58
FT TURN 59 61
FT HELIX 107 124
FT STRAND 134 136
FT HELIX 139 156
FT HELIX 161 166
FT HELIX 167 175
FT TURN 181 184
FT HELIX 188 203
FT HELIX 209 211
FT HELIX 212 217
FT HELIX 219 233
FT STRAND 237 240
FT HELIX 243 245
FT STRAND 247 250
FT HELIX 253 261
FT TURN 262 264
FT HELIX 270 274
FT HELIX 276 282
FT HELIX 283 285
FT HELIX 287 298
FT HELIX 303 306
FT HELIX 308 313
FT HELIX 319 333
FT TURN 334 336
FT HELIX 338 341
FT STRAND 348 350
FT STRAND 352 354
SQ SEQUENCE 358 AA; 40668 MW; 2A962521AF5B4CF7 CRC64;
MAEGERQPPP DSSEEAPPAT QNFIIPKKEI HTVPDMGKWK RSQAYADYIG FILTLNEGVK
GKKLTFEYRV SEMWNEVHEE KEQAAKQSVS CDECIPLPRA GHCAPSEAIE KLVALLNTLD
RWIDETPPVD QPSRFGNKAY RTWYAKLDEE AENLVATVVP THLAAAVPEV AVYLKESVGN
STRIDYGTGH EAAFAAFLCC LCKIGVLRVD DQIAIVFKVF NRYLEVMRKL QKTYRMEPAG
SQGVWGLDDF QFLPFIWGSS QLIDHPYLEP RHFVDEKAVN ENHKDYMFLE CILFITEMKT
GPFAEHSNQL WNISAVPSWS KVNQGLIRMY KAECLEKFPV IQHFKFGSLL PIHPVTSG
//
MIM
600756
*RECORD*
*FIELD* NO
600756
*FIELD* TI
*600756 PROTEIN PHOSPHATASE 2, REGULATORY SUBUNIT B-PRIME; PPP2R4
;;PROTEIN PHOSPHATASE 2A, REGULATORY SUBUNIT B-PRIME;;
read morePHOSPHOTYROSYL PHOSPHATASE ACTIVATOR; PTPA;;
PR53
*FIELD* TX
DESCRIPTION
PPP2R4, or PTPA, encodes a specific phosphotyrosyl phosphatase activator
of the dimeric form of protein phosphatase-2A (PP2A; see 176915) (Van
Hoof et al., 1995).
GENE FUNCTION
The core component of PP2A consists of a catalytic (C) subunit (e.g.,
PPP2CA; 176915) and a scaffold protein (A) subunit (e.g., PPP2R1A;
605983). Using purified recombinant proteins, Chao et al. (2006) found
that PTPA and PP2A A-C dimers constituted a composite ATPase, and the
interaction was independent of ATP or magnesium ion. The inclusion of
PTPA altered the substrate specificity of PP2A, with enhanced
phosphotyrosine phosphatase activity and decreased phosphoserine
phosphatase activity.
BIOCHEMICAL FEATURES
Chao et al. (2006) reported the 1.9-angstrom crystal structure of human
PTPA, which revealed a fold consisting of a core, a lid, and an extended
linker joining the core and lid. Structural analysis uncovered a highly
conserved surface patch bordering these 3 subdomains, as well as an
associated deep pocket between the core and linker subdomains. Further
analysis showed that the surface patch binds the PP2A A-C dimer, and the
deep pocket binds ATP.
GENE STRUCTURE
Van Hoof et al. (1995) demonstrated that human PTPA is encoded by a
single-copy gene composed of 10 exons and 9 introns with a total length
of about 60 kb. The 5-prime flanking sequence of the transcription start
site was analyzed for its potential as a promoter. This region lacks a
TATA sequence in the appropriate position relative to the transcription
start. However, this region is very GC-rich and contains 4 Sp1 sites
(SP1; 189906) upstream of the transcription start site, a feature common
to many TATA-less promoters. Based on homology with DNA-binding
consensus sequences of transcription factors, Van Hoof et al. (1995)
identified several additional putative transcription factor binding
sites in the promoter region. Transfection experiments with a construct
containing the PTPA promoter region inserted 5-prime of a luciferase
reporter gene demonstrated that the 5-prime flanking sequence of the
PTPA gene indeed has promoter activity that seems to be cell-line
dependent.
MAPPING
By fluorescence in situ hybridization, Van Hoof et al. (1995) mapped the
PTPA gene to 9q34. Fluorescence in situ analysis of metaphase
chromosomes of patients bearing the Philadelphia chromosome indicated
that PTPA is positioned centromeric of ABL1 (189980) and probably is not
involved in chronic myeloid leukemia.
*FIELD* SA
McCright et al. (1996)
*FIELD* RF
1. Chao, Y.; Xing, Y.; Chen, Y.; Xu, Y.; Lin, Z.; Li, Z.; Jeffrey,
P. D.; Stock, J. B.; Shi, Y.: Structure and mechanism of the phosphotyrosyl
phosphatase activator. Molec. Cell 23: 535-546, 2006.
2. McCright, B.; Rivers, A. M.; Audlin, S.; Virshup, D. M.: The B56
family of protein phosphatase 2A (PP2A) regulatory subunits encodes
differentiation-induced phosphoproteins that target PP2A to both nucleus
and cytoplasm. J. Biol. Chem. 271: 22081-22089, 1996.
3. Van Hoof, C.; Aly, M. S.; Garcia, A.; Cayla, X.; Cassiman, J. J.;
Merlevede, W.; Goris, J.: Structure and chromosomal localization
of the human gene of the phosphotyrosyl phosphatase activator (PTPA)
of protein phosphatase 2A. Genomics 28: 261-272, 1995.
*FIELD* CN
Patricia A. Hartz - updated: 11/1/2006
Jennifer P. Macke - updated: 4/14/1997
*FIELD* CD
Victor A. McKusick: 8/29/1995
*FIELD* ED
mgross: 02/04/2009
mgross: 12/1/2006
terry: 11/1/2006
mgross: 3/15/2006
carol: 12/3/2004
alopez: 5/5/1997
alopez: 4/14/1997
mark: 8/29/1995
*RECORD*
*FIELD* NO
600756
*FIELD* TI
*600756 PROTEIN PHOSPHATASE 2, REGULATORY SUBUNIT B-PRIME; PPP2R4
;;PROTEIN PHOSPHATASE 2A, REGULATORY SUBUNIT B-PRIME;;
read morePHOSPHOTYROSYL PHOSPHATASE ACTIVATOR; PTPA;;
PR53
*FIELD* TX
DESCRIPTION
PPP2R4, or PTPA, encodes a specific phosphotyrosyl phosphatase activator
of the dimeric form of protein phosphatase-2A (PP2A; see 176915) (Van
Hoof et al., 1995).
GENE FUNCTION
The core component of PP2A consists of a catalytic (C) subunit (e.g.,
PPP2CA; 176915) and a scaffold protein (A) subunit (e.g., PPP2R1A;
605983). Using purified recombinant proteins, Chao et al. (2006) found
that PTPA and PP2A A-C dimers constituted a composite ATPase, and the
interaction was independent of ATP or magnesium ion. The inclusion of
PTPA altered the substrate specificity of PP2A, with enhanced
phosphotyrosine phosphatase activity and decreased phosphoserine
phosphatase activity.
BIOCHEMICAL FEATURES
Chao et al. (2006) reported the 1.9-angstrom crystal structure of human
PTPA, which revealed a fold consisting of a core, a lid, and an extended
linker joining the core and lid. Structural analysis uncovered a highly
conserved surface patch bordering these 3 subdomains, as well as an
associated deep pocket between the core and linker subdomains. Further
analysis showed that the surface patch binds the PP2A A-C dimer, and the
deep pocket binds ATP.
GENE STRUCTURE
Van Hoof et al. (1995) demonstrated that human PTPA is encoded by a
single-copy gene composed of 10 exons and 9 introns with a total length
of about 60 kb. The 5-prime flanking sequence of the transcription start
site was analyzed for its potential as a promoter. This region lacks a
TATA sequence in the appropriate position relative to the transcription
start. However, this region is very GC-rich and contains 4 Sp1 sites
(SP1; 189906) upstream of the transcription start site, a feature common
to many TATA-less promoters. Based on homology with DNA-binding
consensus sequences of transcription factors, Van Hoof et al. (1995)
identified several additional putative transcription factor binding
sites in the promoter region. Transfection experiments with a construct
containing the PTPA promoter region inserted 5-prime of a luciferase
reporter gene demonstrated that the 5-prime flanking sequence of the
PTPA gene indeed has promoter activity that seems to be cell-line
dependent.
MAPPING
By fluorescence in situ hybridization, Van Hoof et al. (1995) mapped the
PTPA gene to 9q34. Fluorescence in situ analysis of metaphase
chromosomes of patients bearing the Philadelphia chromosome indicated
that PTPA is positioned centromeric of ABL1 (189980) and probably is not
involved in chronic myeloid leukemia.
*FIELD* SA
McCright et al. (1996)
*FIELD* RF
1. Chao, Y.; Xing, Y.; Chen, Y.; Xu, Y.; Lin, Z.; Li, Z.; Jeffrey,
P. D.; Stock, J. B.; Shi, Y.: Structure and mechanism of the phosphotyrosyl
phosphatase activator. Molec. Cell 23: 535-546, 2006.
2. McCright, B.; Rivers, A. M.; Audlin, S.; Virshup, D. M.: The B56
family of protein phosphatase 2A (PP2A) regulatory subunits encodes
differentiation-induced phosphoproteins that target PP2A to both nucleus
and cytoplasm. J. Biol. Chem. 271: 22081-22089, 1996.
3. Van Hoof, C.; Aly, M. S.; Garcia, A.; Cayla, X.; Cassiman, J. J.;
Merlevede, W.; Goris, J.: Structure and chromosomal localization
of the human gene of the phosphotyrosyl phosphatase activator (PTPA)
of protein phosphatase 2A. Genomics 28: 261-272, 1995.
*FIELD* CN
Patricia A. Hartz - updated: 11/1/2006
Jennifer P. Macke - updated: 4/14/1997
*FIELD* CD
Victor A. McKusick: 8/29/1995
*FIELD* ED
mgross: 02/04/2009
mgross: 12/1/2006
terry: 11/1/2006
mgross: 3/15/2006
carol: 12/3/2004
alopez: 5/5/1997
alopez: 4/14/1997
mark: 8/29/1995