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O00743 (PPP6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 138. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Serine/threonine-protein phosphatase 6 catalytic subunit

Short name=PP6C
EC=3.1.3.16
Gene names
Name:PPP6C
Synonyms:PPP6
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length305 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Catalytic subunit of protein phosphatase 6 (PP6). PP6 is a component of a signaling pathway regulating cell cycle progression in response to IL2 receptor stimulation. N-terminal domain restricts G1 to S phase progression in cancer cells, in part through control of cyclin D1. Downregulates MAP3K7 kinase activation of the IL1 signaling pathway by dephosphorylation of MAP3K7. Ref.1 Ref.2 Ref.11 Ref.12

Catalytic activity

[a protein]-serine/threonine phosphate + H2O = [a protein]-serine/threonine + phosphate.

Cofactor

Binds 1 iron ion per subunit By similarity.

Binds 1 manganese ion per subunit By similarity.

Subunit structure

Protein phosphatase 6 (PP6) holoenzyme is proposed to be a heterotrimeric complex formed by the catalytic subunit, a SAPS domain-containing subunit (PP6R) and an ankyrin repeat-domain containing regulatory subunit (ARS). Interacts with IGBP1, MAP3K7, NFKBIE, PPP6R1, PPP6R2 and PPP6R3. Ref.9 Ref.10 Ref.11 Ref.13

Subcellular location

Cytoplasm Ref.10 Ref.12.

Tissue specificity

Ubiquitously expressed in all tissues tested with highest expression levels in testis, heart, kidney, brain, stomach, liver and skeletal muscle and lowest in placenta, lung colon and spleen. Ref.1 Ref.10

Induction

Regulated by IL2/interleukin-2 in peripheral blood T cells. Ref.2

Sequence similarities

Belongs to the PPP phosphatase family. PP-6 (PP-V) subfamily.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O00743-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: O00743-2)

The sequence of this isoform differs from the canonical sequence as follows:
     58-79: Missing.
Isoform 3 (identifier: O00743-3)

The sequence of this isoform differs from the canonical sequence as follows:
     25-25: K → KVSPICGLAPSGCGAPAGRPFLSPGPPPVFHFLRFLKE

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 305305Serine/threonine-protein phosphatase 6 catalytic subunit
PRO_0000424504
Initiator methionine11Removed; alternate Ref.8
Chain2 – 305304Serine/threonine-protein phosphatase 6 catalytic subunit, N-terminally processed
PRO_0000058877

Sites

Active site1141Proton donor By similarity
Metal binding531Iron By similarity
Metal binding551Iron By similarity
Metal binding811Iron By similarity
Metal binding811Manganese By similarity
Metal binding1131Manganese By similarity
Metal binding1631Manganese By similarity
Metal binding2371Manganese By similarity

Amino acid modifications

Modified residue11N-acetylmethionine Ref.15

Natural variations

Alternative sequence251K → KVSPICGLAPSGCGAPAGRP FLSPGPPPVFHFLRFLKE in isoform 3.
VSP_041158
Alternative sequence58 – 7922Missing in isoform 2.
VSP_038376

Experimental info

Sequence conflict61 – 644LCEL → AG in AAD45400. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified July 1, 1997. Version 1.
Checksum: 55E95DB6CEA7CFF4

FASTA30535,144
        10         20         30         40         50         60 
MAPLDLDKYV EIARLCKYLP ENDLKRLCDY VCDLLLEESN VQPVSTPVTV CGDIHGQFYD 

        70         80         90        100        110        120 
LCELFRTGGQ VPDTNYIFMG DFVDRGYYSL ETFTYLLALK AKWPDRITLL RGNHESRQIT 

       130        140        150        160        170        180 
QVYGFYDECQ TKYGNANAWR YCTKVFDMLT VAALIDEQIL CVHGGLSPDI KTLDQIRTIE 

       190        200        210        220        230        240 
RNQEIPHKGA FCDLVWSDPE DVDTWAISPR GAGWLFGAKV TNEFVHINNL KLICRAHQLV 

       250        260        270        280        290        300 
HEGYKFMFDE KLVTVWSAPN YCYRCGNIAS IMVFKDVNTR EPKLFRAVPD SERVIPPRTT 


TPYFL 

« Hide

Isoform 2 [UniParc].

Checksum: C2334512732059DC
Show »

FASTA28332,532
Isoform 3 [UniParc].

Checksum: C26CAD5C8016F112
Show »

FASTA34238,947

References

« Hide 'large scale' references
[1]"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."
Bastians H., Ponstingl H.
J. Cell Sci. 109:2865-2874(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY.
[2]"Identification of a type 6 protein Ser/Thr phosphatase regulated by interleukin-2 stimulation."
Filali M., Li S., Kim H.W., Wadzinski B., Kamoun M.
J. Cell. Biochem. 73:153-163(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INDUCTION.
Tissue: Brain.
[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] (ISOFORMS 1; 2 AND 3).
Tissue: Cerebellum.
[4]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[5]"DNA sequence and analysis of human chromosome 9."
Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. expand/collapse author list , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I.
Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]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].
[7]"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] (ISOFORM 1).
Tissue: Urinary bladder.
[8]Bienvenut W.V., Waridel P., Quadroni M.
Submitted (MAR-2009) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 2-14; 67-100; 118-140; 145-171; 211-231 AND 252-275, CLEAVAGE OF INITIATOR METHIONINE, IDENTIFICATION BY MASS SPECTROMETRY.
Tissue: Embryonic kidney.
[9]"Alpha 4 associates with protein phosphatases 2A, 4, and 6."
Chen J., Peterson R.T., Schreiber S.L.
Biochem. Biophys. Res. Commun. 247:827-832(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH IGBP1.
[10]"Protein phosphatase 6 subunit with conserved Sit4-associated protein domain targets IkappaBepsilon."
Stefansson B., Brautigan D.L.
J. Biol. Chem. 281:22624-22634(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NFKBIE; PPP6R1 AND PPP6R2, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[11]"Protein phosphatase 6 down-regulates TAK1 kinase activation in the IL-1 signaling pathway."
Kajino T., Ren H., Iemura S., Natsume T., Stefansson B., Brautigan D.L., Matsumoto K., Ninomiya-Tsuji J.
J. Biol. Chem. 281:39891-39896(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH MAP3K7.
[12]"Protein phosphatase PP6 N terminal domain restricts G1 to S phase progression in human cancer cells."
Stefansson B., Brautigan D.L.
Cell Cycle 6:1386-1392(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[13]"Protein phosphatase 6 regulatory subunits composed of ankyrin repeat domains."
Stefansson B., Ohama T., Daugherty A.E., Brautigan D.L.
Biochemistry 47:1442-1451(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ANKRD28; PPP6R1; PPP6R2 AND PPP6R3.
[14]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[15]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X92972 mRNA. Translation: CAA63549.1.
AF035158 mRNA. Translation: AAD45400.2.
AK295190 mRNA. Translation: BAH12005.1.
AK299087 mRNA. Translation: BAH12945.1.
AK312332 mRNA. Translation: BAG35253.1.
BT019708 mRNA. Translation: AAV38514.1.
AL445930 Genomic DNA. Translation: CAI13677.1.
CH471090 Genomic DNA. Translation: EAW87611.1.
BC006990 mRNA. Translation: AAH06990.1.
RefSeqNP_001116827.1. NM_001123355.1.
NP_001116841.1. NM_001123369.1.
NP_002712.1. NM_002721.4.
UniGeneHs.744091.

3D structure databases

ProteinModelPortalO00743.
SMRO00743. Positions 5-276.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111529. 31 interactions.
DIPDIP-27581N.
IntActO00743. 20 interactions.
MINTMINT-1139697.
STRING9606.ENSP00000392147.

PTM databases

PhosphoSiteO00743.

2D gel databases

OGPO00743.

Proteomic databases

PaxDbO00743.
PeptideAtlasO00743.
PRIDEO00743.

Protocols and materials databases

DNASU5537.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000373547; ENSP00000362648; ENSG00000119414. [O00743-1]
ENST00000415905; ENSP00000411744; ENSG00000119414. [O00743-2]
ENST00000451402; ENSP00000392147; ENSG00000119414. [O00743-3]
GeneID5537.
KEGGhsa:5537.
UCSCuc004bpg.4. human. [O00743-1]
uc010mwv.3. human. [O00743-3]
uc010mww.3. human. [O00743-2]

Organism-specific databases

CTD5537.
GeneCardsGC09M127908.
HGNCHGNC:9323. PPP6C.
HPAHPA050940.
MIM612725. gene.
neXtProtNX_O00743.
PharmGKBPA33687.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0639.
HOGENOMHOG000172696.
HOVERGENHBG000216.
InParanoidO00743.
KOK15498.
OMAVPETSYI.
OrthoDBEOG74N5H2.
PhylomeDBO00743.
TreeFamTF105563.

Gene expression databases

ArrayExpressO00743.
BgeeO00743.
CleanExHS_PPP6C.
GenevestigatorO00743.

Family and domain databases

InterProIPR004843. Calcineurin-like_PHP_apaH.
IPR006186. Ser/Thr-sp_prot-phosphatase.
[Graphical view]
PfamPF00149. Metallophos. 1 hit.
[Graphical view]
PRINTSPR00114. STPHPHTASE.
SMARTSM00156. PP2Ac. 1 hit.
[Graphical view]
PROSITEPS00125. SER_THR_PHOSPHATASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPPP6C. human.
GeneWikiPPP6C.
GenomeRNAi5537.
NextBio21450.
PROO00743.
SOURCESearch...

Entry information

Entry namePPP6_HUMAN
AccessionPrimary (citable) accession number: O00743
Secondary accession number(s): B2R5V6 expand/collapse secondary AC list , B7Z2W9, B7Z5K9, Q5U0A2, Q9UIC9
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: July 1, 1997
Last modified: April 16, 2014
This is version 138 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 chromosome 9

Human chromosome 9: entries, gene names and cross-references to MIM