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Protein

Serine/threonine-protein phosphatase 4 catalytic subunit

Gene

PPP4C

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Protein phosphatase that is involved in many processes such as microtubule organization at centrosomes, maturation of spliceosomal snRNPs, apoptosis, DNA repair, tumor necrosis factor (TNF)-alpha signaling, activation of c-Jun N-terminal kinase MAPK8, regulation of histone acetylation, DNA damage checkpoint signaling, NF-kappa-B activation and cell migration. The PPP4C-PPP4R1 PP4 complex may play a role in dephosphorylation and regulation of HDAC3. The PPP4C-PPP4R2-PPP4R3A PP4 complex specifically dephosphorylates H2AFX phosphorylated on Ser-140 (gamma-H2AFX) generated during DNA replication and required for DNA double strand break repair. Dephosphorylates NDEL1 at CDK1 phosphorylation sites and negatively regulates CDK1 activity in interphase (By similarity). In response to DNA damage, catalyzes RPA2 dephosphorylation, an essential step for DNA repair since it allows the efficient RPA2-mediated recruitment of RAD51 to chromatin.By similarity10 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 bindingi54Manganese 1By similarity1
Metal bindingi56Manganese 1By similarity1
Metal bindingi82Manganese 1By similarity1
Metal bindingi82Manganese 2By similarity1
Metal bindingi114Manganese 2By similarity1
Active sitei115Proton donorBy similarity1
Metal bindingi164Manganese 2By similarity1
Metal bindingi238Manganese 2By similarity1

GO - Molecular functioni

  • metal ion binding Source: UniProtKB-KW
  • NF-kappaB-inducing kinase activity Source: UniProtKB
  • protein serine/threonine phosphatase activity Source: UniProtKB

GO - Biological processi

  • regulation of double-strand break repair via homologous recombination Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protein phosphatase

Keywords - Ligandi

Manganese, Metal-binding

Enzyme and pathway databases

BioCyciZFISH:HS07646-MONOMER.
ReactomeiR-HSA-5693607. Processing of DNA double-strand break ends.
SignaLinkiP60510.
SIGNORiP60510.

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein phosphatase 4 catalytic subunit (EC:3.1.3.16)
Short name:
PP4C
Short name:
Pp4
Alternative name(s):
Protein phosphatase X
Short name:
PP-X
Gene namesi
Name:PPP4C
Synonyms:PPP4, PPX
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

HGNCiHGNC:9319. PPP4C.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi39E → K: Diminishes interaction with PPP4R4. 1 Publication1
Mutagenesisi64E → K: Abolishes interaction with PPP4R4. 1 Publication1
Mutagenesisi76N → D: Diminishes interaction with PPP4R4. 1 Publication1
Mutagenesisi82D → A: Loss of activity. 1 Publication1
Mutagenesisi107R → E: Diminishes interaction with PPP4R4. 1 Publication1
Mutagenesisi277E → K: Abolishes interaction with PPP4R4; no effect on interaction with PPP4R1 and PPP4R2. 1 Publication1
Mutagenesisi307L → A: Unable to dephosphorylate 53BP1 and KAR1, loss of DSB repair activity. 1 Publication1

Organism-specific databases

DisGeNETi5531.
OpenTargetsiENSG00000149923.
PharmGKBiPA33683.

Polymorphism and mutation databases

BioMutaiPPP4C.
DMDMi44888846.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00000588832 – 307Serine/threonine-protein phosphatase 4 catalytic subunitAdd BLAST306

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei307Leucine methyl ester1 Publication1

Post-translational modificationi

Methylation at the C-terminal Leu-307 is critical for interactions with regulatory subunits and functions in DNA repair.1 Publication

Keywords - PTMi

Acetylation, Methylation

Proteomic databases

EPDiP60510.
MaxQBiP60510.
PaxDbiP60510.
PeptideAtlasiP60510.
PRIDEiP60510.

PTM databases

DEPODiP60510.
iPTMnetiP60510.
PhosphoSitePlusiP60510.

Expressioni

Gene expression databases

BgeeiENSG00000149923.
CleanExiHS_PPP4C.
ExpressionAtlasiP60510. baseline and differential.
GenevisibleiP60510. HS.

Organism-specific databases

HPAiHPA043837.

Interactioni

Subunit structurei

Serine/threonine-protein phosphatase 4 (PP4) occurs in different assemblies of the catalytic and one or more regulatory subunits. Component of the PP4 complexes PPP4C-PPP4R1, PPP4C-PPP4R2, PPP4C-PPP4R2-PPP4R3A, PPP4C-PPP4R2-PPP4R3B and PPP4C-PPP4R4. The PPP4C-PPP4R2 complex appears to be a tetramer composed of 2 molecules of PPP4C and 2 molecules of PPP4R2. Interacts with REL, NFKB1/p50 and RELA. Interacts with SMN1 AND GEMIN4. Interacts with IRS4 (phosphorylated). Interacts with SMEK1/PPP4R3A; the interaction requires PP4R2. Interacts with HDAC3.7 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
HDAC3O153794EBI-1046072,EBI-607682
IGBP1P783189EBI-1046072,EBI-1055954
PPP2R1AP301533EBI-1046072,EBI-302388
PPP4R1Q8TF057EBI-1046072,EBI-1056262
PPP4R2Q9NY2710EBI-1046072,EBI-1048740
PPP4R4Q6NUP76EBI-1046072,EBI-1774189
TIPRLO756634EBI-1046072,EBI-1054735

Protein-protein interaction databases

BioGridi111523. 60 interactors.
IntActiP60510. 32 interactors.
MINTiMINT-5004373.
STRINGi9606.ENSP00000279387.

Structurei

3D structure databases

ProteinModelPortaliP60510.
SMRiP60510.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0372. Eukaryota.
COG0639. LUCA.
GeneTreeiENSGT00550000074618.
HOGENOMiHOG000172696.
HOVERGENiHBG000216.
InParanoidiP60510.
KOiK15423.
OMAiVFNHRND.
OrthoDBiEOG091G0B6S.
PhylomeDBiP60510.
TreeFamiTF105559.

Family and domain databases

Gene3Di3.60.21.10. 1 hit.
InterProiIPR004843. Calcineurin-like_PHP_ApaH.
IPR029052. Metallo-depent_PP-like.
IPR006186. Ser/Thr-sp_prot-phosphatase.
[Graphical view]
PfamiPF00149. Metallophos. 1 hit.
[Graphical view]
PRINTSiPR00114. STPHPHTASE.
SMARTiSM00156. PP2Ac. 1 hit.
[Graphical view]
SUPFAMiSSF56300. SSF56300. 1 hit.
PROSITEiPS00125. SER_THR_PHOSPHATASE. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

P60510-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAEISDLDRQ IEQLRRCELI KESEVKALCA KAREILVEES NVQRVDSPVT
60 70 80 90 100
VCGDIHGQFY DLKELFRVGG DVPETNYLFM GDFVDRGFYS VETFLLLLAL
110 120 130 140 150
KVRYPDRITL IRGNHESRQI TQVYGFYDEC LRKYGSVTVW RYCTEIFDYL
160 170 180 190 200
SLSAIIDGKI FCVHGGLSPS IQTLDQIRTI DRKQEVPHDG PMCDLLWSDP
210 220 230 240 250
EDTTGWGVSP RGAGYLFGSD VVAQFNAAND IDMICRAHQL VMEGYKWHFN
260 270 280 290 300
ETVLTVWSAP NYCYRCGNVA AILELDEHLQ KDFIIFEAAP QETRGIPSKK

PVADYFL
Length:307
Mass (Da):35,080
Last modified:March 1, 2004 - v1
Checksum:iD6FE470A5C6CBCAC
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X70218 mRNA. Translation: CAA49753.1.
AF097996 mRNA. Translation: AAC96318.1.
BC001416 mRNA. Translation: AAH01416.1.
CCDSiCCDS10669.1.
PIRiS28173.
RefSeqiNP_001290432.1. NM_001303503.1.
NP_001290433.1. NM_001303504.1.
NP_001290435.1. NM_001303506.1.
NP_001290436.1. NM_001303507.1.
NP_002711.1. NM_002720.2.
UniGeneiHs.534338.

Genome annotation databases

EnsembliENST00000279387; ENSP00000279387; ENSG00000149923.
ENST00000561610; ENSP00000455995; ENSG00000149923.
GeneIDi5531.
KEGGihsa:5531.
UCSCiuc002dwf.4. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X70218 mRNA. Translation: CAA49753.1.
AF097996 mRNA. Translation: AAC96318.1.
BC001416 mRNA. Translation: AAH01416.1.
CCDSiCCDS10669.1.
PIRiS28173.
RefSeqiNP_001290432.1. NM_001303503.1.
NP_001290433.1. NM_001303504.1.
NP_001290435.1. NM_001303506.1.
NP_001290436.1. NM_001303507.1.
NP_002711.1. NM_002720.2.
UniGeneiHs.534338.

3D structure databases

ProteinModelPortaliP60510.
SMRiP60510.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111523. 60 interactors.
IntActiP60510. 32 interactors.
MINTiMINT-5004373.
STRINGi9606.ENSP00000279387.

PTM databases

DEPODiP60510.
iPTMnetiP60510.
PhosphoSitePlusiP60510.

Polymorphism and mutation databases

BioMutaiPPP4C.
DMDMi44888846.

Proteomic databases

EPDiP60510.
MaxQBiP60510.
PaxDbiP60510.
PeptideAtlasiP60510.
PRIDEiP60510.

Protocols and materials databases

DNASUi5531.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000279387; ENSP00000279387; ENSG00000149923.
ENST00000561610; ENSP00000455995; ENSG00000149923.
GeneIDi5531.
KEGGihsa:5531.
UCSCiuc002dwf.4. human.

Organism-specific databases

CTDi5531.
DisGeNETi5531.
GeneCardsiPPP4C.
HGNCiHGNC:9319. PPP4C.
HPAiHPA043837.
MIMi602035. gene.
neXtProtiNX_P60510.
OpenTargetsiENSG00000149923.
PharmGKBiPA33683.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0372. Eukaryota.
COG0639. LUCA.
GeneTreeiENSGT00550000074618.
HOGENOMiHOG000172696.
HOVERGENiHBG000216.
InParanoidiP60510.
KOiK15423.
OMAiVFNHRND.
OrthoDBiEOG091G0B6S.
PhylomeDBiP60510.
TreeFamiTF105559.

Enzyme and pathway databases

BioCyciZFISH:HS07646-MONOMER.
ReactomeiR-HSA-5693607. Processing of DNA double-strand break ends.
SignaLinkiP60510.
SIGNORiP60510.

Miscellaneous databases

GeneWikiiPPP4C.
GenomeRNAii5531.
PROiP60510.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000149923.
CleanExiHS_PPP4C.
ExpressionAtlasiP60510. baseline and differential.
GenevisibleiP60510. HS.

Family and domain databases

Gene3Di3.60.21.10. 1 hit.
InterProiIPR004843. Calcineurin-like_PHP_ApaH.
IPR029052. Metallo-depent_PP-like.
IPR006186. Ser/Thr-sp_prot-phosphatase.
[Graphical view]
PfamiPF00149. Metallophos. 1 hit.
[Graphical view]
PRINTSiPR00114. STPHPHTASE.
SMARTiSM00156. PP2Ac. 1 hit.
[Graphical view]
SUPFAMiSSF56300. SSF56300. 1 hit.
PROSITEiPS00125. SER_THR_PHOSPHATASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPP4C_HUMAN
AccessioniPrimary (citable) accession number: P60510
Secondary accession number(s): P33172
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 1, 2004
Last sequence update: March 1, 2004
Last modified: November 30, 2016
This is version 133 of the entry and version 1 of the sequence. [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, Reference proteome

Documents

  1. Human chromosome 16
    Human chromosome 16: 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.