Full text data of PPP6C
PPP6C
(PPP6)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Serine/threonine-protein phosphatase 6 catalytic subunit; PP6C; 3.1.3.16; Serine/threonine-protein phosphatase 6 catalytic subunit, N-terminally processed
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Serine/threonine-protein phosphatase 6 catalytic subunit; PP6C; 3.1.3.16; Serine/threonine-protein phosphatase 6 catalytic subunit, N-terminally processed
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
O00743
ID PPP6_HUMAN Reviewed; 305 AA.
AC O00743; B2R5V6; B7Z2W9; B7Z5K9; Q5U0A2; Q9UIC9;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JUL-1997, sequence version 1.
DT 22-JAN-2014, entry version 135.
DE RecName: Full=Serine/threonine-protein phosphatase 6 catalytic subunit;
DE Short=PP6C;
DE EC=3.1.3.16;
DE Contains:
DE RecName: Full=Serine/threonine-protein phosphatase 6 catalytic subunit, N-terminally processed;
GN Name=PPP6C; Synonyms=PPP6;
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), FUNCTION, AND TISSUE
RP SPECIFICITY.
RX PubMed=9013334;
RA Bastians H., Ponstingl H.;
RT "The novel human protein serine/threonine phosphatase 6 is a
RT functional homologue of budding yeast Sit4p and fission yeast ppe1,
RT which are involved in cell cycle regulation.";
RL J. Cell Sci. 109:2865-2874(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND INDUCTION.
RC TISSUE=Brain;
RX PubMed=10227379;
RX DOI=10.1002/(SICI)1097-4644(19990501)73:2<153::AID-JCB2>3.3.CO;2-Z;
RA Filali M., Li S., Kim H.W., Wadzinski B., Kamoun M.;
RT "Identification of a type 6 protein Ser/Thr phosphatase regulated by
RT interleukin-2 stimulation.";
RL J. Cell. Biochem. 73:153-163(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
RC TISSUE=Cerebellum;
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 [4]
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 [5]
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 [6]
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Urinary bladder;
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 [8]
RP PROTEIN SEQUENCE OF 2-14; 67-100; 118-140; 145-171; 211-231 AND
RP 252-275, CLEAVAGE OF INITIATOR METHIONINE, LACK OF N-TERMINAL
RP ACETYLATION, AND MASS SPECTROMETRY.
RC TISSUE=Embryonic kidney;
RA Bienvenut W.V., Waridel P., Quadroni M.;
RL Submitted (MAR-2009) to UniProtKB.
RN [9]
RP INTERACTION WITH IGBP1.
RX PubMed=9647778; DOI=10.1006/bbrc.1998.8792;
RA Chen J., Peterson R.T., Schreiber S.L.;
RT "Alpha 4 associates with protein phosphatases 2A, 4, and 6.";
RL Biochem. Biophys. Res. Commun. 247:827-832(1998).
RN [10]
RP INTERACTION WITH NFKBIE; PPP6R1 AND PPP6R2, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RX PubMed=16769727; DOI=10.1074/jbc.M601772200;
RA Stefansson B., Brautigan D.L.;
RT "Protein phosphatase 6 subunit with conserved Sit4-associated protein
RT domain targets IkappaBepsilon.";
RL J. Biol. Chem. 281:22624-22634(2006).
RN [11]
RP FUNCTION, AND INTERACTION WITH MAP3K7.
RX PubMed=17079228; DOI=10.1074/jbc.M608155200;
RA Kajino T., Ren H., Iemura S., Natsume T., Stefansson B.,
RA Brautigan D.L., Matsumoto K., Ninomiya-Tsuji J.;
RT "Protein phosphatase 6 down-regulates TAK1 kinase activation in the
RT IL-1 signaling pathway.";
RL J. Biol. Chem. 281:39891-39896(2006).
RN [12]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=17568194;
RA Stefansson B., Brautigan D.L.;
RT "Protein phosphatase PP6 N terminal domain restricts G1 to S phase
RT progression in human cancer cells.";
RL Cell Cycle 6:1386-1392(2007).
RN [13]
RP INTERACTION WITH ANKRD28; PPP6R1; PPP6R2 AND PPP6R3.
RX PubMed=18186651; DOI=10.1021/bi7022877;
RA Stefansson B., Ohama T., Daugherty A.E., Brautigan D.L.;
RT "Protein phosphatase 6 regulatory subunits composed of ankyrin repeat
RT domains.";
RL Biochemistry 47:1442-1451(2008).
RN [14]
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 [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
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.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
CC -!- FUNCTION: Catalytic subunit of protein phosphatase 6 (PP6). PP6 is
CC a component of a signaling pathway regulating cell cycle
CC progression in response to IL2 receptor stimulation. N-terminal
CC domain restricts G1 to S phase progression in cancer cells, in
CC part through control of cyclin D1. Downregulates MAP3K7 kinase
CC activation of the IL1 signaling pathway by dephosphorylation of
CC MAP3K7.
CC -!- CATALYTIC ACTIVITY: A phosphoprotein + H(2)O = a protein +
CC phosphate.
CC -!- COFACTOR: Binds 1 iron ion per subunit (By similarity).
CC -!- COFACTOR: Binds 1 manganese ion per subunit (By similarity).
CC -!- SUBUNIT: Protein phosphatase 6 (PP6) holoenzyme is proposed to be
CC a heterotrimeric complex formed by the catalytic subunit, a SAPS
CC domain-containing subunit (PP6R) and an ankyrin repeat-domain
CC containing regulatory subunit (ARS). Interacts with IGBP1, MAP3K7,
CC NFKBIE, PPP6R1, PPP6R2 and PPP6R3.
CC -!- INTERACTION:
CC O15084:ANKRD28; NbExp=9; IntAct=EBI-359751, EBI-359567;
CC P78318:IGBP1; NbExp=10; IntAct=EBI-359751, EBI-1055954;
CC O43318:MAP3K7; NbExp=4; IntAct=EBI-359751, EBI-358684;
CC Q9UPN7:PPP6R1; NbExp=11; IntAct=EBI-359751, EBI-359745;
CC O75170:PPP6R2; NbExp=8; IntAct=EBI-359751, EBI-359739;
CC Q5H9R7:PPP6R3; NbExp=5; IntAct=EBI-359751, EBI-355498;
CC O75663:TIPRL; NbExp=4; IntAct=EBI-359751, EBI-1054735;
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=O00743-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O00743-2; Sequence=VSP_038376;
CC Name=3;
CC IsoId=O00743-3; Sequence=VSP_041158;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed in all tissues tested
CC with highest expression levels in testis, heart, kidney, brain,
CC stomach, liver and skeletal muscle and lowest in placenta, lung
CC colon and spleen.
CC -!- INDUCTION: Regulated by IL2/interleukin-2 in peripheral blood T
CC cells.
CC -!- SIMILARITY: Belongs to the PPP phosphatase family. PP-6 (PP-V)
CC subfamily.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; X92972; CAA63549.1; -; mRNA.
DR EMBL; AF035158; AAD45400.2; -; mRNA.
DR EMBL; AK295190; BAH12005.1; -; mRNA.
DR EMBL; AK299087; BAH12945.1; -; mRNA.
DR EMBL; AK312332; BAG35253.1; -; mRNA.
DR EMBL; BT019708; AAV38514.1; -; mRNA.
DR EMBL; AL445930; CAI13677.1; -; Genomic_DNA.
DR EMBL; CH471090; EAW87611.1; -; Genomic_DNA.
DR EMBL; BC006990; AAH06990.1; -; mRNA.
DR RefSeq; NP_001116827.1; NM_001123355.1.
DR RefSeq; NP_001116841.1; NM_001123369.1.
DR RefSeq; NP_002712.1; NM_002721.4.
DR UniGene; Hs.744091; -.
DR ProteinModelPortal; O00743; -.
DR SMR; O00743; 5-276.
DR DIP; DIP-27581N; -.
DR IntAct; O00743; 19.
DR MINT; MINT-1139697; -.
DR STRING; 9606.ENSP00000392147; -.
DR PhosphoSite; O00743; -.
DR OGP; O00743; -.
DR PaxDb; O00743; -.
DR PeptideAtlas; O00743; -.
DR PRIDE; O00743; -.
DR DNASU; 5537; -.
DR Ensembl; ENST00000373547; ENSP00000362648; ENSG00000119414.
DR Ensembl; ENST00000415905; ENSP00000411744; ENSG00000119414.
DR Ensembl; ENST00000451402; ENSP00000392147; ENSG00000119414.
DR GeneID; 5537; -.
DR KEGG; hsa:5537; -.
DR UCSC; uc004bpg.4; human.
DR CTD; 5537; -.
DR GeneCards; GC09M127908; -.
DR HGNC; HGNC:9323; PPP6C.
DR HPA; HPA050940; -.
DR MIM; 612725; gene.
DR neXtProt; NX_O00743; -.
DR PharmGKB; PA33687; -.
DR eggNOG; COG0639; -.
DR HOGENOM; HOG000172696; -.
DR HOVERGEN; HBG000216; -.
DR InParanoid; O00743; -.
DR KO; K15498; -.
DR OMA; VPETSYI; -.
DR OrthoDB; EOG74N5H2; -.
DR PhylomeDB; O00743; -.
DR ChiTaRS; PPP6C; human.
DR GeneWiki; PPP6C; -.
DR GenomeRNAi; 5537; -.
DR NextBio; 21450; -.
DR PRO; PR:O00743; -.
DR ArrayExpress; O00743; -.
DR Bgee; O00743; -.
DR CleanEx; HS_PPP6C; -.
DR Genevestigator; O00743; -.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004722; F:protein serine/threonine phosphatase activity; IDA:MGI.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; TAS:ProtInc.
DR GO; GO:0006470; P:protein dephosphorylation; IDA:MGI.
DR InterPro; IPR004843; PEstase_dom.
DR InterPro; IPR006186; Ser/Thr-sp_prot-phosphatase.
DR Pfam; PF00149; Metallophos; 1.
DR PRINTS; PR00114; STPHPHTASE.
DR SMART; SM00156; PP2Ac; 1.
DR PROSITE; PS00125; SER_THR_PHOSPHATASE; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Cell cycle; Complete proteome;
KW Cytoplasm; Direct protein sequencing; Hydrolase; Iron; Manganese;
KW Metal-binding; Protein phosphatase; Reference proteome.
FT CHAIN 1 305 Serine/threonine-protein phosphatase 6
FT catalytic subunit.
FT /FTId=PRO_0000424504.
FT INIT_MET 1 1 Removed; alternate.
FT CHAIN 2 305 Serine/threonine-protein phosphatase 6
FT catalytic subunit, N-terminally
FT processed.
FT /FTId=PRO_0000058877.
FT ACT_SITE 114 114 Proton donor (By similarity).
FT METAL 53 53 Iron (By similarity).
FT METAL 55 55 Iron (By similarity).
FT METAL 81 81 Iron (By similarity).
FT METAL 81 81 Manganese (By similarity).
FT METAL 113 113 Manganese (By similarity).
FT METAL 163 163 Manganese (By similarity).
FT METAL 237 237 Manganese (By similarity).
FT MOD_RES 1 1 N-acetylmethionine.
FT VAR_SEQ 25 25 K -> KVSPICGLAPSGCGAPAGRPFLSPGPPPVFHFLRFL
FT KE (in isoform 3).
FT /FTId=VSP_041158.
FT VAR_SEQ 58 79 Missing (in isoform 2).
FT /FTId=VSP_038376.
FT CONFLICT 61 64 LCEL -> AG (in Ref. 2; AAD45400).
SQ SEQUENCE 305 AA; 35144 MW; 55E95DB6CEA7CFF4 CRC64;
MAPLDLDKYV EIARLCKYLP ENDLKRLCDY VCDLLLEESN VQPVSTPVTV CGDIHGQFYD
LCELFRTGGQ VPDTNYIFMG DFVDRGYYSL ETFTYLLALK AKWPDRITLL RGNHESRQIT
QVYGFYDECQ TKYGNANAWR YCTKVFDMLT VAALIDEQIL CVHGGLSPDI KTLDQIRTIE
RNQEIPHKGA FCDLVWSDPE DVDTWAISPR GAGWLFGAKV TNEFVHINNL KLICRAHQLV
HEGYKFMFDE KLVTVWSAPN YCYRCGNIAS IMVFKDVNTR EPKLFRAVPD SERVIPPRTT
TPYFL
//
ID PPP6_HUMAN Reviewed; 305 AA.
AC O00743; B2R5V6; B7Z2W9; B7Z5K9; Q5U0A2; Q9UIC9;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JUL-1997, sequence version 1.
DT 22-JAN-2014, entry version 135.
DE RecName: Full=Serine/threonine-protein phosphatase 6 catalytic subunit;
DE Short=PP6C;
DE EC=3.1.3.16;
DE Contains:
DE RecName: Full=Serine/threonine-protein phosphatase 6 catalytic subunit, N-terminally processed;
GN Name=PPP6C; Synonyms=PPP6;
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), FUNCTION, AND TISSUE
RP SPECIFICITY.
RX PubMed=9013334;
RA Bastians H., Ponstingl H.;
RT "The novel human protein serine/threonine phosphatase 6 is a
RT functional homologue of budding yeast Sit4p and fission yeast ppe1,
RT which are involved in cell cycle regulation.";
RL J. Cell Sci. 109:2865-2874(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND INDUCTION.
RC TISSUE=Brain;
RX PubMed=10227379;
RX DOI=10.1002/(SICI)1097-4644(19990501)73:2<153::AID-JCB2>3.3.CO;2-Z;
RA Filali M., Li S., Kim H.W., Wadzinski B., Kamoun M.;
RT "Identification of a type 6 protein Ser/Thr phosphatase regulated by
RT interleukin-2 stimulation.";
RL J. Cell. Biochem. 73:153-163(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
RC TISSUE=Cerebellum;
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 [4]
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 [5]
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 [6]
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Urinary bladder;
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 [8]
RP PROTEIN SEQUENCE OF 2-14; 67-100; 118-140; 145-171; 211-231 AND
RP 252-275, CLEAVAGE OF INITIATOR METHIONINE, LACK OF N-TERMINAL
RP ACETYLATION, AND MASS SPECTROMETRY.
RC TISSUE=Embryonic kidney;
RA Bienvenut W.V., Waridel P., Quadroni M.;
RL Submitted (MAR-2009) to UniProtKB.
RN [9]
RP INTERACTION WITH IGBP1.
RX PubMed=9647778; DOI=10.1006/bbrc.1998.8792;
RA Chen J., Peterson R.T., Schreiber S.L.;
RT "Alpha 4 associates with protein phosphatases 2A, 4, and 6.";
RL Biochem. Biophys. Res. Commun. 247:827-832(1998).
RN [10]
RP INTERACTION WITH NFKBIE; PPP6R1 AND PPP6R2, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RX PubMed=16769727; DOI=10.1074/jbc.M601772200;
RA Stefansson B., Brautigan D.L.;
RT "Protein phosphatase 6 subunit with conserved Sit4-associated protein
RT domain targets IkappaBepsilon.";
RL J. Biol. Chem. 281:22624-22634(2006).
RN [11]
RP FUNCTION, AND INTERACTION WITH MAP3K7.
RX PubMed=17079228; DOI=10.1074/jbc.M608155200;
RA Kajino T., Ren H., Iemura S., Natsume T., Stefansson B.,
RA Brautigan D.L., Matsumoto K., Ninomiya-Tsuji J.;
RT "Protein phosphatase 6 down-regulates TAK1 kinase activation in the
RT IL-1 signaling pathway.";
RL J. Biol. Chem. 281:39891-39896(2006).
RN [12]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=17568194;
RA Stefansson B., Brautigan D.L.;
RT "Protein phosphatase PP6 N terminal domain restricts G1 to S phase
RT progression in human cancer cells.";
RL Cell Cycle 6:1386-1392(2007).
RN [13]
RP INTERACTION WITH ANKRD28; PPP6R1; PPP6R2 AND PPP6R3.
RX PubMed=18186651; DOI=10.1021/bi7022877;
RA Stefansson B., Ohama T., Daugherty A.E., Brautigan D.L.;
RT "Protein phosphatase 6 regulatory subunits composed of ankyrin repeat
RT domains.";
RL Biochemistry 47:1442-1451(2008).
RN [14]
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 [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
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.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
CC -!- FUNCTION: Catalytic subunit of protein phosphatase 6 (PP6). PP6 is
CC a component of a signaling pathway regulating cell cycle
CC progression in response to IL2 receptor stimulation. N-terminal
CC domain restricts G1 to S phase progression in cancer cells, in
CC part through control of cyclin D1. Downregulates MAP3K7 kinase
CC activation of the IL1 signaling pathway by dephosphorylation of
CC MAP3K7.
CC -!- CATALYTIC ACTIVITY: A phosphoprotein + H(2)O = a protein +
CC phosphate.
CC -!- COFACTOR: Binds 1 iron ion per subunit (By similarity).
CC -!- COFACTOR: Binds 1 manganese ion per subunit (By similarity).
CC -!- SUBUNIT: Protein phosphatase 6 (PP6) holoenzyme is proposed to be
CC a heterotrimeric complex formed by the catalytic subunit, a SAPS
CC domain-containing subunit (PP6R) and an ankyrin repeat-domain
CC containing regulatory subunit (ARS). Interacts with IGBP1, MAP3K7,
CC NFKBIE, PPP6R1, PPP6R2 and PPP6R3.
CC -!- INTERACTION:
CC O15084:ANKRD28; NbExp=9; IntAct=EBI-359751, EBI-359567;
CC P78318:IGBP1; NbExp=10; IntAct=EBI-359751, EBI-1055954;
CC O43318:MAP3K7; NbExp=4; IntAct=EBI-359751, EBI-358684;
CC Q9UPN7:PPP6R1; NbExp=11; IntAct=EBI-359751, EBI-359745;
CC O75170:PPP6R2; NbExp=8; IntAct=EBI-359751, EBI-359739;
CC Q5H9R7:PPP6R3; NbExp=5; IntAct=EBI-359751, EBI-355498;
CC O75663:TIPRL; NbExp=4; IntAct=EBI-359751, EBI-1054735;
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=O00743-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O00743-2; Sequence=VSP_038376;
CC Name=3;
CC IsoId=O00743-3; Sequence=VSP_041158;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed in all tissues tested
CC with highest expression levels in testis, heart, kidney, brain,
CC stomach, liver and skeletal muscle and lowest in placenta, lung
CC colon and spleen.
CC -!- INDUCTION: Regulated by IL2/interleukin-2 in peripheral blood T
CC cells.
CC -!- SIMILARITY: Belongs to the PPP phosphatase family. PP-6 (PP-V)
CC subfamily.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; X92972; CAA63549.1; -; mRNA.
DR EMBL; AF035158; AAD45400.2; -; mRNA.
DR EMBL; AK295190; BAH12005.1; -; mRNA.
DR EMBL; AK299087; BAH12945.1; -; mRNA.
DR EMBL; AK312332; BAG35253.1; -; mRNA.
DR EMBL; BT019708; AAV38514.1; -; mRNA.
DR EMBL; AL445930; CAI13677.1; -; Genomic_DNA.
DR EMBL; CH471090; EAW87611.1; -; Genomic_DNA.
DR EMBL; BC006990; AAH06990.1; -; mRNA.
DR RefSeq; NP_001116827.1; NM_001123355.1.
DR RefSeq; NP_001116841.1; NM_001123369.1.
DR RefSeq; NP_002712.1; NM_002721.4.
DR UniGene; Hs.744091; -.
DR ProteinModelPortal; O00743; -.
DR SMR; O00743; 5-276.
DR DIP; DIP-27581N; -.
DR IntAct; O00743; 19.
DR MINT; MINT-1139697; -.
DR STRING; 9606.ENSP00000392147; -.
DR PhosphoSite; O00743; -.
DR OGP; O00743; -.
DR PaxDb; O00743; -.
DR PeptideAtlas; O00743; -.
DR PRIDE; O00743; -.
DR DNASU; 5537; -.
DR Ensembl; ENST00000373547; ENSP00000362648; ENSG00000119414.
DR Ensembl; ENST00000415905; ENSP00000411744; ENSG00000119414.
DR Ensembl; ENST00000451402; ENSP00000392147; ENSG00000119414.
DR GeneID; 5537; -.
DR KEGG; hsa:5537; -.
DR UCSC; uc004bpg.4; human.
DR CTD; 5537; -.
DR GeneCards; GC09M127908; -.
DR HGNC; HGNC:9323; PPP6C.
DR HPA; HPA050940; -.
DR MIM; 612725; gene.
DR neXtProt; NX_O00743; -.
DR PharmGKB; PA33687; -.
DR eggNOG; COG0639; -.
DR HOGENOM; HOG000172696; -.
DR HOVERGEN; HBG000216; -.
DR InParanoid; O00743; -.
DR KO; K15498; -.
DR OMA; VPETSYI; -.
DR OrthoDB; EOG74N5H2; -.
DR PhylomeDB; O00743; -.
DR ChiTaRS; PPP6C; human.
DR GeneWiki; PPP6C; -.
DR GenomeRNAi; 5537; -.
DR NextBio; 21450; -.
DR PRO; PR:O00743; -.
DR ArrayExpress; O00743; -.
DR Bgee; O00743; -.
DR CleanEx; HS_PPP6C; -.
DR Genevestigator; O00743; -.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004722; F:protein serine/threonine phosphatase activity; IDA:MGI.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; TAS:ProtInc.
DR GO; GO:0006470; P:protein dephosphorylation; IDA:MGI.
DR InterPro; IPR004843; PEstase_dom.
DR InterPro; IPR006186; Ser/Thr-sp_prot-phosphatase.
DR Pfam; PF00149; Metallophos; 1.
DR PRINTS; PR00114; STPHPHTASE.
DR SMART; SM00156; PP2Ac; 1.
DR PROSITE; PS00125; SER_THR_PHOSPHATASE; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Cell cycle; Complete proteome;
KW Cytoplasm; Direct protein sequencing; Hydrolase; Iron; Manganese;
KW Metal-binding; Protein phosphatase; Reference proteome.
FT CHAIN 1 305 Serine/threonine-protein phosphatase 6
FT catalytic subunit.
FT /FTId=PRO_0000424504.
FT INIT_MET 1 1 Removed; alternate.
FT CHAIN 2 305 Serine/threonine-protein phosphatase 6
FT catalytic subunit, N-terminally
FT processed.
FT /FTId=PRO_0000058877.
FT ACT_SITE 114 114 Proton donor (By similarity).
FT METAL 53 53 Iron (By similarity).
FT METAL 55 55 Iron (By similarity).
FT METAL 81 81 Iron (By similarity).
FT METAL 81 81 Manganese (By similarity).
FT METAL 113 113 Manganese (By similarity).
FT METAL 163 163 Manganese (By similarity).
FT METAL 237 237 Manganese (By similarity).
FT MOD_RES 1 1 N-acetylmethionine.
FT VAR_SEQ 25 25 K -> KVSPICGLAPSGCGAPAGRPFLSPGPPPVFHFLRFL
FT KE (in isoform 3).
FT /FTId=VSP_041158.
FT VAR_SEQ 58 79 Missing (in isoform 2).
FT /FTId=VSP_038376.
FT CONFLICT 61 64 LCEL -> AG (in Ref. 2; AAD45400).
SQ SEQUENCE 305 AA; 35144 MW; 55E95DB6CEA7CFF4 CRC64;
MAPLDLDKYV EIARLCKYLP ENDLKRLCDY VCDLLLEESN VQPVSTPVTV CGDIHGQFYD
LCELFRTGGQ VPDTNYIFMG DFVDRGYYSL ETFTYLLALK AKWPDRITLL RGNHESRQIT
QVYGFYDECQ TKYGNANAWR YCTKVFDMLT VAALIDEQIL CVHGGLSPDI KTLDQIRTIE
RNQEIPHKGA FCDLVWSDPE DVDTWAISPR GAGWLFGAKV TNEFVHINNL KLICRAHQLV
HEGYKFMFDE KLVTVWSAPN YCYRCGNIAS IMVFKDVNTR EPKLFRAVPD SERVIPPRTT
TPYFL
//
MIM
612725
*RECORD*
*FIELD* NO
612725
*FIELD* TI
*612725 PROTEIN PHOSPHATASE 6, CATALYTIC SUBUNIT; PPP6C
*FIELD* TX
DESCRIPTION
Reversible phosphorylation of proteins on serine and threonine residues
read moreis an important biochemical event that regulates a broad variety of
intracellular processes. The phosphorylation state is determined by the
well-controlled balance of activities of serine/threonine-specific
protein kinases and protein phosphatases. PPP6C is the catalytic subunit
of human serine/threonine protein phosphatase-6 (Bastians and Ponstingl,
1996).
CLONING
Using a homology-based RT-PCR approach, Bastians and Ponstingl (1996)
cloned a cDNA encoding PPP6C. The predicted 305-amino acid protein
shares 59%, 56 to 57%, 68%, and 61% identity with PPP4C (602035),
isoforms of PPP2A (see 176915 and 176916), S. pombe ppe1, and S.
cerevisiae Sit4, respectively. All 42 amino acids that are invariant
among serine/threonine PPPs and essential for catalytic activity are
present in PPP6C. Northern blot analysis showed that PPP6C was expressed
as 3 transcripts of 1.8 kb, 4.2 kb, and 4.7 kb in all 16 human tissues
examined. Expression levels were highest in testis, heart, and skeletal
muscle and lowest in placenta, lung, and kidney. Immunoblot analysis
detected a 35-kD PPP6C protein in lysates from human heart muscle and
bull testis.
GENE FUNCTION
Bastians and Ponstingl (1996) demonstrated that PPP6C could complement
mutations in the S. cerevisiae Sit4 and S. pombe ppe1 genes, indicating
that PPP6C is the functional homolog of yeast Sit4 and ppe1. Since Sit4
is required for the G1-to-S transition of the cell cycle, and ppe1 is
involved in cell shape control and mitotic division, Bastians and
Ponstingl (1996) suggested that PPP6C functions in cell cycle
regulation.
Using coimmunoprecipitation and protein pull-down assays, Stefansson and
Brautigan (2006) showed that epitope-tagged PP6R1 (SAPS1; 610875), PP6R2
(SAPS2; 610877), and PP6R3 (SAPS3; 610879) bound endogenous PPP6C, but
not PPP2CA. The SAPS domain of PP6R1 was sufficient for its association
with PPP6C. Immunoprecipitates containing PPP6C and PP6R1 or PP6R2
showed phosphatase activity against a test protein, and the activity was
inhibited by okadaic acid, a serine/threonine phosphatase inhibitor.
Stefansson and Brautigan (2006) found that PPP6C and PP6R1 or PP6R2
associated with I-kappa-B-epsilon (IKBE, or NFKBIE; 604548) in HeLa
cells, and knockdown of PP6R1 or PPP6C enhanced degradation of
endogenous IKBE in response to TNF-alpha (191160).
MAPPING
By fluorescence in situ hybridization followed by fine-mapping on a YAC
contig, Bastians et al. (1997) localized the PPP6C gene to chromosome
Xq22.3. However, Hartz (2009) mapped the PPP6C gene to chromosome 9q33.3
based on an alignment of the PPP6C sequence submitted by Bastians et al.
(1997) (GenBank GENBANK X92972) with the genomic sequence (build 36.1).
A sequence highly related to PPP6C maps to chromosome Xq22.3.
*FIELD* RF
1. Bastians, H.; Krebber, H.; Vetrie, D.; Hoheisel, J.; Lichter, P.;
Ponstingl, H.; Joos, S.: Localization of the novel serine/threonine
protein phosphatase 6 gene (PPP6C) to human chromosome Xq22.3. Genomics 41:
296-297, 1997.
2. Bastians, H.; Ponstingl, H.: The novel human protein serine/threonine
phosphatase 6 is a functional homologue of budding yeast Sit4p and
fission yeast ppe1, which are involved in cell cycle regulation. J.
Cell Sci. 109: 2865-2874, 1996.
3. Hartz, P. A.: Personal Communication. Baltimore, Md. 4/10/2009.
4. Stefansson, B.; Brautigan, D. L.: Protein phosphatase 6 subunit
with conserved Sit4-associated protein domain targets I-kappa-B-epsilon. J.
Biol. Chem. 281: 22624-22634, 2006.
*FIELD* CD
Patricia A. Hartz: 4/10/2009
*FIELD* ED
mgross: 04/10/2009
*RECORD*
*FIELD* NO
612725
*FIELD* TI
*612725 PROTEIN PHOSPHATASE 6, CATALYTIC SUBUNIT; PPP6C
*FIELD* TX
DESCRIPTION
Reversible phosphorylation of proteins on serine and threonine residues
read moreis an important biochemical event that regulates a broad variety of
intracellular processes. The phosphorylation state is determined by the
well-controlled balance of activities of serine/threonine-specific
protein kinases and protein phosphatases. PPP6C is the catalytic subunit
of human serine/threonine protein phosphatase-6 (Bastians and Ponstingl,
1996).
CLONING
Using a homology-based RT-PCR approach, Bastians and Ponstingl (1996)
cloned a cDNA encoding PPP6C. The predicted 305-amino acid protein
shares 59%, 56 to 57%, 68%, and 61% identity with PPP4C (602035),
isoforms of PPP2A (see 176915 and 176916), S. pombe ppe1, and S.
cerevisiae Sit4, respectively. All 42 amino acids that are invariant
among serine/threonine PPPs and essential for catalytic activity are
present in PPP6C. Northern blot analysis showed that PPP6C was expressed
as 3 transcripts of 1.8 kb, 4.2 kb, and 4.7 kb in all 16 human tissues
examined. Expression levels were highest in testis, heart, and skeletal
muscle and lowest in placenta, lung, and kidney. Immunoblot analysis
detected a 35-kD PPP6C protein in lysates from human heart muscle and
bull testis.
GENE FUNCTION
Bastians and Ponstingl (1996) demonstrated that PPP6C could complement
mutations in the S. cerevisiae Sit4 and S. pombe ppe1 genes, indicating
that PPP6C is the functional homolog of yeast Sit4 and ppe1. Since Sit4
is required for the G1-to-S transition of the cell cycle, and ppe1 is
involved in cell shape control and mitotic division, Bastians and
Ponstingl (1996) suggested that PPP6C functions in cell cycle
regulation.
Using coimmunoprecipitation and protein pull-down assays, Stefansson and
Brautigan (2006) showed that epitope-tagged PP6R1 (SAPS1; 610875), PP6R2
(SAPS2; 610877), and PP6R3 (SAPS3; 610879) bound endogenous PPP6C, but
not PPP2CA. The SAPS domain of PP6R1 was sufficient for its association
with PPP6C. Immunoprecipitates containing PPP6C and PP6R1 or PP6R2
showed phosphatase activity against a test protein, and the activity was
inhibited by okadaic acid, a serine/threonine phosphatase inhibitor.
Stefansson and Brautigan (2006) found that PPP6C and PP6R1 or PP6R2
associated with I-kappa-B-epsilon (IKBE, or NFKBIE; 604548) in HeLa
cells, and knockdown of PP6R1 or PPP6C enhanced degradation of
endogenous IKBE in response to TNF-alpha (191160).
MAPPING
By fluorescence in situ hybridization followed by fine-mapping on a YAC
contig, Bastians et al. (1997) localized the PPP6C gene to chromosome
Xq22.3. However, Hartz (2009) mapped the PPP6C gene to chromosome 9q33.3
based on an alignment of the PPP6C sequence submitted by Bastians et al.
(1997) (GenBank GENBANK X92972) with the genomic sequence (build 36.1).
A sequence highly related to PPP6C maps to chromosome Xq22.3.
*FIELD* RF
1. Bastians, H.; Krebber, H.; Vetrie, D.; Hoheisel, J.; Lichter, P.;
Ponstingl, H.; Joos, S.: Localization of the novel serine/threonine
protein phosphatase 6 gene (PPP6C) to human chromosome Xq22.3. Genomics 41:
296-297, 1997.
2. Bastians, H.; Ponstingl, H.: The novel human protein serine/threonine
phosphatase 6 is a functional homologue of budding yeast Sit4p and
fission yeast ppe1, which are involved in cell cycle regulation. J.
Cell Sci. 109: 2865-2874, 1996.
3. Hartz, P. A.: Personal Communication. Baltimore, Md. 4/10/2009.
4. Stefansson, B.; Brautigan, D. L.: Protein phosphatase 6 subunit
with conserved Sit4-associated protein domain targets I-kappa-B-epsilon. J.
Biol. Chem. 281: 22624-22634, 2006.
*FIELD* CD
Patricia A. Hartz: 4/10/2009
*FIELD* ED
mgross: 04/10/2009