UniProtKB - O00743 (PPP6_HUMAN)
Serine/threonine-protein phosphatase 6 catalytic subunit
PPP6C
Functioni
Catalytic subunit of protein phosphatase 6 (PP6) (PubMed:17079228, PubMed:29053956, PubMed:32474700).
PP6 is a component of a signaling pathway regulating cell cycle progression in response to IL2 receptor stimulation (PubMed:10227379).
N-terminal domain restricts G1 to S phase progression in cancer cells, in part through control of cyclin D1 (PubMed:17568194).
During mitosis, regulates spindle positioning (PubMed:27335426).
Down-regulates MAP3K7 kinase activation of the IL1 signaling pathway by dephosphorylation of MAP3K7 (PubMed:17079228).
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 (PubMed:29053956).
Also regulates innate immunity by acting as a negative regulator of the cGAS-STING pathway: mediates dephosphorylation and inactivation of CGAS and STING1 (PubMed:32753499, PubMed:32474700).
CGAS dephosphorylation at 'Ser-435' impairs its ability to bind GTP, thereby inactivating it (PubMed:32474700).
7 PublicationsCatalytic activityi
Cofactori
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 53 | Manganese 1By similarity | 1 | |
Metal bindingi | 55 | Manganese 1By similarity | 1 | |
Metal bindingi | 81 | Manganese 1By similarity | 1 | |
Metal bindingi | 81 | Manganese 2By similarity | 1 | |
Metal bindingi | 113 | Manganese 2By similarity | 1 | |
Active sitei | 114 | Proton donorBy similarity | 1 | |
Metal bindingi | 163 | Manganese 2By similarity | 1 | |
Metal bindingi | 237 | Manganese 2By similarity | 1 |
GO - Molecular functioni
- metal ion binding Source: UniProtKB-KW
- protein serine/threonine phosphatase activity Source: UniProtKB
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 function | Hydrolase, Protein phosphatase |
Biological process | Cell cycle, Immunity, Innate immunity |
Ligand | Manganese, Metal-binding |
Enzyme and pathway databases
PathwayCommonsi | O00743 |
Reactomei | R-HSA-171319, Telomere Extension By Telomerase R-HSA-204005, COPII-mediated vesicle transport |
SignaLinki | O00743 |
SIGNORi | O00743 |
Names & Taxonomyi
Protein namesi | Recommended name: Serine/threonine-protein phosphatase 6 catalytic subunitCurated (EC:3.1.3.163 Publications)Short name: PP6C1 Publication Cleaved into the following chain: |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:9323, PPP6C |
MIMi | 612725, gene |
neXtProti | NX_O00743 |
VEuPathDBi | HostDB:ENSG00000119414 |
Subcellular locationi
Cytoplasm and Cytosol
- Cytoplasm 2 Publications
Mitochondrion
- Mitochondrion 1 Publication
Cytosol
- cytosol Source: MGI
Mitochondrion
- mitochondrion Source: UniProtKB-SubCell
Nucleus
- nucleoplasm Source: Reactome
Keywords - Cellular componenti
Cytoplasm, MitochondrionPathology & Biotechi
Organism-specific databases
DisGeNETi | 5537 |
OpenTargetsi | ENSG00000119414 |
PharmGKBi | PA33687 |
Miscellaneous databases
Pharosi | O00743, Tbio |
Chemistry databases
ChEMBLi | CHEMBL4105731 |
Genetic variation databases
BioMutai | PPP6C |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000424504 | 1 – 305 | Serine/threonine-protein phosphatase 6 catalytic subunitAdd BLAST | 305 | |
Initiator methioninei | Removed; alternate1 Publication | |||
ChainiPRO_0000058877 | 2 – 305 | Serine/threonine-protein phosphatase 6 catalytic subunit, N-terminally processedAdd BLAST | 304 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 1 | N-acetylmethionineCombined sources | 1 |
Keywords - PTMi
AcetylationProteomic databases
EPDi | O00743 |
jPOSTi | O00743 |
MassIVEi | O00743 |
MaxQBi | O00743 |
PeptideAtlasi | O00743 |
PRIDEi | O00743 |
ProteomicsDBi | 48009 [O00743-1] 48010 [O00743-2] 48011 [O00743-3] |
2D gel databases
OGPi | O00743 |
PTM databases
DEPODi | PPP6C |
iPTMneti | O00743 |
PhosphoSitePlusi | O00743 |
Expressioni
Tissue specificityi
Inductioni
Gene expression databases
Bgeei | ENSG00000119414, Expressed in oocyte and 250 other tissues |
ExpressionAtlasi | O00743, baseline and differential |
Genevisiblei | O00743, HS |
Organism-specific databases
HPAi | ENSG00000119414, Low tissue specificity |
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) (PubMed:18186651).
Interacts with subunits PPP6R1, PPP6R2 and PPP6R3 (PubMed:16769727, PubMed:18186651).
Interacts with subunit ANKRD28 (PubMed:18186651).
Interacts with IGBP1 (PubMed:9647778).
Interacts with MAP3K7 (PubMed:17079228).
Interacts with NFKBIE (PubMed:16769727).
Interacts with TRIM14 and WRNIP1; these interactions positively regulate the RIG-I/DDX58 signaling pathway (PubMed:29053956).
5 PublicationsBinary interactionsi
O00743
Protein-protein interaction databases
BioGRIDi | 111529, 185 interactors |
CORUMi | O00743 |
DIPi | DIP-27581N |
IntActi | O00743, 77 interactors |
MINTi | O00743 |
Miscellaneous databases
RNActi | O00743, protein |
Family & Domainsi
Sequence similaritiesi
Phylogenomic databases
GeneTreei | ENSGT00550000074961 |
HOGENOMi | CLU_004962_8_1_1 |
InParanoidi | O00743 |
OMAi | CQNKYGN |
OrthoDBi | 808922at2759 |
PhylomeDBi | O00743 |
TreeFami | TF105563 |
Family and domain databases
Gene3Di | 3.60.21.10, 1 hit |
InterProi | View protein in InterPro IPR004843, Calcineurin-like_PHP_ApaH IPR029052, Metallo-depent_PP-like IPR006186, Ser/Thr-sp_prot-phosphatase |
Pfami | View protein in Pfam PF00149, Metallophos, 1 hit |
PRINTSi | PR00114, STPHPHTASE |
SMARTi | View protein in SMART SM00156, PP2Ac, 1 hit |
SUPFAMi | SSF56300, SSF56300, 1 hit |
PROSITEi | View protein in PROSITE PS00125, SER_THR_PHOSPHATASE, 1 hit |
s (3+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 3 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 3 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketQ5T1S7 | Q5T1S7_HUMAN | Serine/threonine-protein phosphatas... | PPP6C | 125 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 61 – 64 | LCEL → AG in AAD45400 (PubMed:10227379).Curated | 4 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_085528 | 55 | H → Y Found in patients with melanomas; decreased protein phosphatase activity, leading to increased phosphorylation of STING1. 1 Publication | 1 | |
Natural variantiVAR_085529 | 114 | H → Y Found in patients with melanomas; decreased protein phosphatase activity, leading to increased phosphorylation of STING1. 1 Publication | 1 | |
Natural variantiVAR_085530 | 189 | G → R Found in patients with melanomas; decreased protein phosphatase activity, leading to increased phosphorylation of STING1. 1 Publication | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_041158 | 25 | K → KVSPICGLAPSGCGAPAGRP FLSPGPPPVFHFLRFLKE in isoform 3. 1 Publication | 1 | |
Alternative sequenceiVSP_038376 | 58 – 79 | Missing in isoform 2. 1 PublicationAdd BLAST | 22 |
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 |
CCDSi | CCDS48018.1 [O00743-3] CCDS48019.1 [O00743-2] CCDS6861.1 [O00743-1] |
RefSeqi | NP_001116827.1, NM_001123355.1 [O00743-3] NP_001116841.1, NM_001123369.1 [O00743-2] NP_002712.1, NM_002721.4 [O00743-1] |
Genome annotation databases
Ensembli | ENST00000373547.9; ENSP00000362648.4; ENSG00000119414.12 ENST00000415905.5; ENSP00000411744.1; ENSG00000119414.12 [O00743-2] ENST00000451402.5; ENSP00000392147.1; ENSG00000119414.12 [O00743-3] |
GeneIDi | 5537 |
KEGGi | hsa:5537 |
MANE-Selecti | ENST00000373547.9; ENSP00000362648.4; NM_002721.5; NP_002712.1 |
UCSCi | uc004bpg.5, human [O00743-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
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 |
CCDSi | CCDS48018.1 [O00743-3] CCDS48019.1 [O00743-2] CCDS6861.1 [O00743-1] |
RefSeqi | NP_001116827.1, NM_001123355.1 [O00743-3] NP_001116841.1, NM_001123369.1 [O00743-2] NP_002712.1, NM_002721.4 [O00743-1] |
3D structure databases
AlphaFoldDBi | O00743 |
SMRi | O00743 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 111529, 185 interactors |
CORUMi | O00743 |
DIPi | DIP-27581N |
IntActi | O00743, 77 interactors |
MINTi | O00743 |
Chemistry databases
ChEMBLi | CHEMBL4105731 |
PTM databases
DEPODi | PPP6C |
iPTMneti | O00743 |
PhosphoSitePlusi | O00743 |
Genetic variation databases
BioMutai | PPP6C |
2D gel databases
OGPi | O00743 |
Proteomic databases
EPDi | O00743 |
jPOSTi | O00743 |
MassIVEi | O00743 |
MaxQBi | O00743 |
PeptideAtlasi | O00743 |
PRIDEi | O00743 |
ProteomicsDBi | 48009 [O00743-1] 48010 [O00743-2] 48011 [O00743-3] |
Protocols and materials databases
Antibodypediai | 30522, 291 antibodies from 32 providers |
DNASUi | 5537 |
Genome annotation databases
Ensembli | ENST00000373547.9; ENSP00000362648.4; ENSG00000119414.12 ENST00000415905.5; ENSP00000411744.1; ENSG00000119414.12 [O00743-2] ENST00000451402.5; ENSP00000392147.1; ENSG00000119414.12 [O00743-3] |
GeneIDi | 5537 |
KEGGi | hsa:5537 |
MANE-Selecti | ENST00000373547.9; ENSP00000362648.4; NM_002721.5; NP_002712.1 |
UCSCi | uc004bpg.5, human [O00743-1] |
Organism-specific databases
CTDi | 5537 |
DisGeNETi | 5537 |
GeneCardsi | PPP6C |
HGNCi | HGNC:9323, PPP6C |
HPAi | ENSG00000119414, Low tissue specificity |
MIMi | 612725, gene |
neXtProti | NX_O00743 |
OpenTargetsi | ENSG00000119414 |
PharmGKBi | PA33687 |
VEuPathDBi | HostDB:ENSG00000119414 |
GenAtlasi | Search... |
Phylogenomic databases
GeneTreei | ENSGT00550000074961 |
HOGENOMi | CLU_004962_8_1_1 |
InParanoidi | O00743 |
OMAi | CQNKYGN |
OrthoDBi | 808922at2759 |
PhylomeDBi | O00743 |
TreeFami | TF105563 |
Enzyme and pathway databases
PathwayCommonsi | O00743 |
Reactomei | R-HSA-171319, Telomere Extension By Telomerase R-HSA-204005, COPII-mediated vesicle transport |
SignaLinki | O00743 |
SIGNORi | O00743 |
Miscellaneous databases
BioGRID-ORCSi | 5537, 432 hits in 1093 CRISPR screens |
ChiTaRSi | PPP6C, human |
GeneWikii | PPP6C |
GenomeRNAii | 5537 |
Pharosi | O00743, Tbio |
PROi | PR:O00743 |
RNActi | O00743, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000119414, Expressed in oocyte and 250 other tissues |
ExpressionAtlasi | O00743, baseline and differential |
Genevisiblei | O00743, HS |
Family and domain databases
Gene3Di | 3.60.21.10, 1 hit |
InterProi | View protein in InterPro IPR004843, Calcineurin-like_PHP_ApaH IPR029052, Metallo-depent_PP-like IPR006186, Ser/Thr-sp_prot-phosphatase |
Pfami | View protein in Pfam PF00149, Metallophos, 1 hit |
PRINTSi | PR00114, STPHPHTASE |
SMARTi | View protein in SMART SM00156, PP2Ac, 1 hit |
SUPFAMi | SSF56300, SSF56300, 1 hit |
PROSITEi | View protein in PROSITE PS00125, SER_THR_PHOSPHATASE, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | PPP6_HUMAN | |
Accessioni | O00743Primary (citable) accession number: O00743 Secondary accession number(s): B2R5V6 Q9UIC9 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 15, 1998 |
Last sequence update: | July 1, 1997 | |
Last modified: | May 25, 2022 | |
This is version 201 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
Direct protein sequencing, Reference proteomeDocuments
- Human chromosome 9
Human chromosome 9: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families