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Protein

Serine/threonine-protein phosphatase 6 catalytic subunit

Gene

PPP6C

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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. Participates also in the innate immune defense against viruses by desphosphorylating RIG-I/DDX58, an essential step that triggers RIG-I/DDX58-mediated signaling activation.5 Publications

Catalytic activityi

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

Cofactori

Mn2+By similarityNote: Binds 2 manganese ions per subunit.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi53Manganese 1By similarity1
Metal bindingi55Manganese 1By similarity1
Metal bindingi81Manganese 1By similarity1
Metal bindingi81Manganese 2By similarity1
Metal bindingi113Manganese 2By similarity1
Active sitei114Proton donorBy similarity1
Metal bindingi163Manganese 2By similarity1
Metal bindingi237Manganese 2By similarity1

GO - Molecular functioni

  • metal ion binding Source: UniProtKB-KW
  • protein serine/threonine phosphatase activity Source: MGI

GO - Biological processi

  • COPII vesicle coating Source: Reactome
  • G1/S transition of mitotic cell cycle Source: ProtInc
  • innate immune response Source: UniProtKB-KW
  • protein dephosphorylation Source: MGI

Keywordsi

Molecular functionHydrolase, Protein phosphatase
Biological processCell cycle, Immunity, Innate immunity
LigandManganese, Metal-binding

Enzyme and pathway databases

ReactomeiR-HSA-204005 COPII-mediated vesicle transport
SIGNORiO00743

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein phosphatase 6 catalytic subunit (EC:3.1.3.16)
Short name:
PP6C
Cleaved into the following chain:
Gene namesi
Name:PPP6C
Synonyms:PPP6
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

EuPathDBiHostDB:ENSG00000119414.11
HGNCiHGNC:9323 PPP6C
MIMi612725 gene
neXtProtiNX_O00743

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Mitochondrion

Pathology & Biotechi

Organism-specific databases

DisGeNETi5537
OpenTargetsiENSG00000119414
PharmGKBiPA33687

Polymorphism and mutation databases

BioMutaiPPP6C

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00004245041 – 305Serine/threonine-protein phosphatase 6 catalytic subunitAdd BLAST305
Initiator methionineiRemoved; alternate1 Publication
ChainiPRO_00000588772 – 305Serine/threonine-protein phosphatase 6 catalytic subunit, N-terminally processedAdd BLAST304

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiO00743
MaxQBiO00743
PeptideAtlasiO00743
PRIDEiO00743
ProteomicsDBi48009
48010 [O00743-2]
48011 [O00743-3]

2D gel databases

OGPiO00743

PTM databases

DEPODiO00743
iPTMnetiO00743
PhosphoSitePlusiO00743

Expressioni

Tissue specificityi

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.2 Publications

Inductioni

Regulated by IL2/interleukin-2 in peripheral blood T cells.1 Publication

Gene expression databases

BgeeiENSG00000119414
CleanExiHS_PPP6C
ExpressionAtlasiO00743 baseline and differential
GenevisibleiO00743 HS

Organism-specific databases

HPAiHPA050940

Interactioni

Subunit structurei

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. Interacts with TRIM14 and WRNIP1; these interactions positively regulate the RIG-I/DDX58 signaling pathway (PubMed:29053956).5 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi111529, 52 interactors
CORUMiO00743
DIPiDIP-27581N
IntActiO00743, 51 interactors
MINTiO00743

Structurei

3D structure databases

ProteinModelPortaliO00743
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

GeneTreeiENSGT00550000074961
HOGENOMiHOG000172696
HOVERGENiHBG000216
InParanoidiO00743
KOiK15498
OMAiKYCCRVF
OrthoDBiEOG091G0B6S
PhylomeDBiO00743
TreeFamiTF105563

Family and domain databases

Gene3Di3.60.21.10, 1 hit
InterProiView protein in InterPro
IPR004843 Calcineurin-like_PHP_ApaH
IPR029052 Metallo-depent_PP-like
IPR006186 Ser/Thr-sp_prot-phosphatase
PfamiView protein in Pfam
PF00149 Metallophos, 1 hit
PRINTSiPR00114 STPHPHTASE
SMARTiView protein in SMART
SM00156 PP2Ac, 1 hit
PROSITEiView protein in PROSITE
PS00125 SER_THR_PHOSPHATASE, 1 hit

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O00743-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MAPLDLDKYV EIARLCKYLP ENDLKRLCDY VCDLLLEESN VQPVSTPVTV
60 70 80 90 100
CGDIHGQFYD LCELFRTGGQ VPDTNYIFMG DFVDRGYYSL ETFTYLLALK
110 120 130 140 150
AKWPDRITLL RGNHESRQIT QVYGFYDECQ TKYGNANAWR YCTKVFDMLT
160 170 180 190 200
VAALIDEQIL CVHGGLSPDI KTLDQIRTIE RNQEIPHKGA FCDLVWSDPE
210 220 230 240 250
DVDTWAISPR GAGWLFGAKV TNEFVHINNL KLICRAHQLV HEGYKFMFDE
260 270 280 290 300
KLVTVWSAPN YCYRCGNIAS IMVFKDVNTR EPKLFRAVPD SERVIPPRTT

TPYFL
Length:305
Mass (Da):35,144
Last modified:July 1, 1997 - v1
Checksum:i55E95DB6CEA7CFF4
GO
Isoform 2 (identifier: O00743-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     58-79: Missing.

Show »
Length:283
Mass (Da):32,532
Checksum:iC2334512732059DC
GO
Isoform 3 (identifier: O00743-3) [UniParc]FASTAAdd to basket

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

Show »
Length:342
Mass (Da):38,947
Checksum:iC26CAD5C8016F112
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti61 – 64LCEL → AG in AAD45400 (PubMed:10227379).Curated4

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04115825K → KVSPICGLAPSGCGAPAGRP FLSPGPPPVFHFLRFLKE in isoform 3. 1 Publication1
Alternative sequenceiVSP_03837658 – 79Missing in isoform 2. 1 PublicationAdd BLAST22

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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 No translation available.
CH471090 Genomic DNA Translation: EAW87611.1
BC006990 mRNA Translation: AAH06990.1
CCDSiCCDS48018.1 [O00743-3]
CCDS48019.1 [O00743-2]
CCDS6861.1 [O00743-1]
RefSeqiNP_001116827.1, NM_001123355.1 [O00743-3]
NP_001116841.1, NM_001123369.1 [O00743-2]
NP_002712.1, NM_002721.4 [O00743-1]
UniGeneiHs.744091

Genome annotation databases

EnsembliENST00000373547; ENSP00000362648; ENSG00000119414 [O00743-1]
ENST00000415905; ENSP00000411744; ENSG00000119414 [O00743-2]
ENST00000451402; ENSP00000392147; ENSG00000119414 [O00743-3]
GeneIDi5537
KEGGihsa:5537
UCSCiuc004bpg.5 human [O00743-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiPPP6_HUMAN
AccessioniPrimary (citable) accession number: O00743
Secondary accession number(s): B2R5V6
, B7Z2W9, B7Z5K9, Q5U0A2, Q9UIC9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: July 1, 1997
Last modified: July 18, 2018
This is version 178 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

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