O00743 (PPP6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Serine/threonine-protein phosphatase 6 catalytic subunit
Short name=PP6C
EC=3.1.3.16

Gene names

Name:	PPP6C
Synonyms:	PPP6

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	305 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 phosphoprotein + H2O = a protein + 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.

Ontologies

Keywords
Biological process	Cell cycle
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing
Ligand	Iron Manganese Metal-binding
Molecular function	Hydrolase Protein phosphatase
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	G1/S transition of mitotic cell cycle Traceable author statement Ref.1. Source: ProtInc protein dephosphorylation Inferred from direct assay PubMed 16716191. Source: MGI
Cellular_component	cytosol Inferred from direct assay PubMed 16716191. Source: MGI
Molecular_function	metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein serine/threonine phosphatase activity Inferred from direct assay PubMed 16716191. Source: MGI
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ANKRD28	O15084	3	EBI-359751,EBI-359567
IGBP1	P78318	8	EBI-359751,EBI-1055954
PPP6R1	Q9UPN7	5	EBI-359751,EBI-359745
PPP6R2	O75170	2	EBI-359751,EBI-359739
PPP6R3	Q5H9R7	2	EBI-359751,EBI-355498

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed Ref.8
	Chain	2 – 305	304	Serine/threonine-protein phosphatase 6 catalytic subunit		PRO_0000058877
Sites
	Active site	114	1	Proton donor By similarity
	Metal binding	53	1	Iron By similarity
	Metal binding	55	1	Iron By similarity
	Metal binding	81	1	Iron By similarity
	Metal binding	81	1	Manganese By similarity
	Metal binding	113	1	Manganese By similarity
	Metal binding	163	1	Manganese By similarity
	Metal binding	237	1	Manganese By similarity
Natural variations
	Alternative sequence	25	1	K → KVSPICGLAPSGCGAPAGRP FLSPGPPPVFHFLRFLKE in isoform 3.		VSP_041158
	Alternative sequence	58 – 79	22	Missing in isoform 2.		VSP_038376
Experimental info
	Sequence conflict	61 – 64	4	LCEL → AG in AAD45400. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 1, 1997. Version 1. Checksum: 55E95DB6CEA7CFF4	FASTA	305	35,144
	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
	Isoform 2 [UniParc]. Checksum: C2334512732059DC	FASTA	283	32,532
	10 20 30 40 50 60 MAPLDLDKYV EIARLCKYLP ENDLKRLCDY VCDLLLEESN VQPVSTPVTV CGDIHGQGDF 70 80 90 100 110 120 VDRGYYSLET FTYLLALKAK WPDRITLLRG NHESRQITQV YGFYDECQTK YGNANAWRYC 130 140 150 160 170 180 TKVFDMLTVA ALIDEQILCV HGGLSPDIKT LDQIRTIERN QEIPHKGAFC DLVWSDPEDV 190 200 210 220 230 240 DTWAISPRGA GWLFGAKVTN EFVHINNLKL ICRAHQLVHE GYKFMFDEKL VTVWSAPNYC 250 260 270 280 YRCGNIASIM VFKDVNTREP KLFRAVPDSE RVIPPRTTTP YFL
	Isoform 3 [UniParc]. Checksum: C26CAD5C8016F112	FASTA	342	38,947
	10 20 30 40 50 60 MAPLDLDKYV EIARLCKYLP ENDLKVSPIC GLAPSGCGAP AGRPFLSPGP PPVFHFLRFL 70 80 90 100 110 120 KERLCDYVCD LLLEESNVQP VSTPVTVCGD IHGQFYDLCE LFRTGGQVPD TNYIFMGDFV 130 140 150 160 170 180 DRGYYSLETF TYLLALKAKW PDRITLLRGN HESRQITQVY GFYDECQTKY GNANAWRYCT 190 200 210 220 230 240 KVFDMLTVAA LIDEQILCVH GGLSPDIKTL DQIRTIERNQ EIPHKGAFCD LVWSDPEDVD 250 260 270 280 290 300 TWAISPRGAG WLFGAKVTNE FVHINNLKLI CRAHQLVHEG YKFMFDEKLV TVWSAPNYCY 310 320 330 340 RCGNIASIMV FKDVNTREPK LFRAVPDSER VIPPRTTTPY FL

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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, LACK OF N-TERMINAL ACETYLATION, 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].
+	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.
IPI	IPI00012970. IPI00890743. IPI00890827.
RefSeq	NP_001116827.1. NM_001123355.1. NP_001116841.1. NM_001123369.1. NP_002712.1. NM_002721.4.
UniGene	Hs.731864.
3D structure databases
ProteinModelPortal	O00743.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-27581N.
IntAct	O00743. 9 interactions.
MINT	MINT-1139697.
STRING	9606.ENSP00000392147.
PTM databases
PhosphoSite	O00743.
2D gel databases
OGP	O00743.
Proteomic databases
PaxDb	O00743.
PeptideAtlas	O00743.
PRIDE	O00743.
Protocols and materials databases
DNASU	5537.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000373547; ENSP00000362648; ENSG00000119414. ENST00000415905; ENSP00000411744; ENSG00000119414. ENST00000451402; ENSP00000392147; ENSG00000119414.
GeneID	5537.
KEGG	hsa:5537.
UCSC	uc004bpg.4. human. uc010mwv.3. human. uc010mww.3. human.
Organism-specific databases
CTD	5537.
GeneCards	GC09M127908.
HGNC	HGNC:9323. PPP6C.
HPA	HPA050940.
MIM	612725. gene.
neXtProt	NX_O00743.
PharmGKB	PA33687.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0639.
HOGENOM	HOG000172696.
HOVERGEN	HBG000216.
InParanoid	O00743.
KO	K15498.
OMA	NKYGNAN.
OrthoDB	EOG495ZS5.
PhylomeDB	O00743.
Gene expression databases
ArrayExpress	O00743.
Bgee	O00743.
CleanEx	HS_PPP6C.
Genevestigator	O00743.
GermOnline	ENSG00000119414. Homo sapiens.
Family and domain databases
InterPro	IPR004843. Metallo_PEstase_dom. IPR006186. Ser/Thr-sp_prot-phosphatase. [Graphical view]
Pfam	PF00149. Metallophos. 1 hit. [Graphical view]
PRINTS	PR00114. STPHPHTASE.
SMART	SM00156. PP2Ac. 1 hit. [Graphical view]
PROSITE	PS00125. SER_THR_PHOSPHATASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	PPP6C. human.
GenomeRNAi	5537.
NextBio	21450.
SOURCE	Search...

Entry information

Entry name

PPP6_HUMAN

Accession

Primary (citable) accession number: O00743
Secondary accession number(s): B2R5V6 , B7Z2W9, B7Z5K9, Q5U0A2, Q9UIC9

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	July 1, 1997
Last modified:	May 1, 2013
This is version 128 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.