PPP5C protein phosphatase 5 catalytic subunit [Homo sapiens (human)] - Gene

Summary

Official Symbol: PPP5Cprovided by HGNC
Official Full Name: protein phosphatase 5 catalytic subunitprovided by HGNC
Primary source: HGNC:HGNC:9322
See related: Ensembl:ENSG00000011485 MIM:600658; AllianceGenome:HGNC:9322
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: PP5; PPT; PPP5
Summary: This gene encodes a serine/threonine phosphatase which is a member of the protein phosphatase catalytic subunit family. Proteins in this family participate in pathways regulated by reversible phosphorylation at serine and threonine residues; many of these pathways are involved in the regulation of cell growth and differentiation. The product of this gene has been shown to participate in signaling pathways in response to hormones or cellular stress, and elevated levels of this protein may be associated with breast cancer development. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2011]
Expression: Ubiquitous expression in heart (RPKM 18.5), brain (RPKM 17.4) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 19q13.32

Exon count:: 13

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	19	NC_000019.10 (46347087..46390975)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	19	NC_060943.1 (49174533..49218356)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (46850344..46894232)

Chromosome 19 - NC_000019.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Over-expression of human PP5 gene in mice induces corneal hyperplasia and leads to ocular surface squamous neoplasia.
Title: Over-expression of human PP5 gene in mice induces corneal hyperplasia and leads to ocular surface squamous neoplasia.
These data demonstrate that LB-100 is a catalytic inhibitor of both PP2AC and PPP5C and suggest that the observed antitumor activity might be due to an additive effect achieved by suppressing both PP2A and PPP5C.
Title: The Antitumor Drug LB-100 Is a Catalytic Inhibitor of Protein Phosphatase 2A (PPP2CA) and 5 (PPP5C) Coordinating with the Active-Site Catalytic Metals in PPP5C.
The role of the catalytic Mn(2+) ions in regulating the binding of PP5 with its substrate was investigated through MD simulations. Results reveal that the different states of Mn(2+) ions can alter the structure of the active site and the conformations of the residues coordinating the Mn(2+) ions or the substrate.
Title: Exploring the role of active site Mn(2+) ions in the binding of protein phosphatase 5 with its substrate using molecular dynamics simulations.
This work offers insights of how cantharidin-like inhibitors interact with human PP5, potentially allowing the design of more specific and even less cytotoxic drugs for cancer treatments.
Title: Interactions of cantharidin-like inhibitors with human protein phosphatase-5 in a Mg(2+) system: molecular dynamics and quantum calculations.
PP5 binds and dephosphorylates the elastic N2B-unique sequence (N2Bus) of titin in cardiomyocytes. PP5 is pathologically elevated and likely contributes to hypo-phosphorylation of N2Bus in failing human hearts. Furthermore, Hsp90-activated PP5 interacts with components of a sarcomeric, N2Bus-associated, mechanosensor complex, and blocks mitogen-activated protein-kinase signaling in this complex.
Title: Protein phosphatase 5 regulates titin phosphorylation and function at a sarcomere-associated mechanosensor complex in cardiomyocytes.
High PPP5C expression is associated with urinary bladder cancer.
Title: Disruption of serine/threonine protein phosphatase 5 inhibits tumorigenesis of urinary bladder cancer cells.
PP5-dependent impairment of GRalpha function represents a novel mechanism driving GC insensitivity in ASM in severe asthma.
Title: Protein phosphatase 5 mediates corticosteroid insensitivity in airway smooth muscle in patients with severe asthma.
Our results showed 1) a critical role for PP5 in cytokine-induced resistance to GC-mediated eosinophil death, 2) supported the dependence of GCR phosphorylation on PP5 activity, and 3) revealed that PP5 is a target of the lipoxin A4-induced pathway countering cytokine-induced resistance to GCs in eosinophils.
Title: Cytokine-Induced Glucocorticoid Resistance from Eosinophil Activation: Protein Phosphatase 5 Modulation of Glucocorticoid Receptor Phosphorylation and Signaling.
PPP5C could be essential for glioma cell growth.
Title: Serine/Threonine Protein Phosphatase-5 Accelerates Cell Growth and Migration in Human Glioma.
Measles Virus Infection Inactivates Cellular Protein Phosphatase 5 with Consequent Suppression of Sp1 and c-Myc Activities.
Title: Measles Virus Infection Inactivates Cellular Protein Phosphatase 5 with Consequent Suppression of Sp1 and c-Myc Activities.

Submit: New GeneRIF Correction See all GeneRIFs (37)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See Variation Viewer (GRCh37.p13)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

MARC_24308-24309:1030110035:1 (e-PCR)
- UniSTS:268882

AW558946 (e-PCR)
- UniSTS:208075

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ADP binding	IDA Inferred from Direct Assay more info	PubMed
enables ATP binding	IDA Inferred from Direct Assay more info	PubMed
enables Hsp90 protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables RNA binding	IEA Inferred from Electronic Annotation more info
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables lipid binding	IEA Inferred from Electronic Annotation more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables myosin phosphatase activity	IEA Inferred from Electronic Annotation more info
enables phosphatase activity	IDA Inferred from Direct Assay more info	PubMed
enables phosphoprotein phosphatase activity	ISS Inferred from Sequence or Structural Similarity more info	PubMed
enables phosphoprotein phosphatase activity	TAS Traceable Author Statement more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein serine/threonine phosphatase activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein serine/threonine phosphatase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein serine/threonine phosphatase activity	ISS Inferred from Sequence or Structural Similarity more info	PubMed
enables protein serine/threonine phosphatase activity	TAS Traceable Author Statement more info	PubMed
enables tau protein binding	NAS Non-traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
involved_in DNA-templated transcription	TAS Traceable Author Statement more info	PubMed
involved_in MAPK cascade	TAS Traceable Author Statement more info
involved_in double-strand break repair	TAS Traceable Author Statement more info
involved_in mitotic cell cycle	TAS Traceable Author Statement more info	PubMed
involved_in peptidyl-serine dephosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in peptidyl-serine dephosphorylation	TAS Traceable Author Statement more info	PubMed
involved_in peptidyl-threonine dephosphorylation	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of canonical NF-kappaB signal transduction	HMP more info	PubMed
involved_in protein dephosphorylation	TAS Traceable Author Statement more info	PubMed
involved_in response to arachidonate	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in response to lead ion	ISS Inferred from Sequence or Structural Similarity more info
involved_in response to morphine	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	IDA Inferred from Direct Assay more info
located_in cytosol	TAS Traceable Author Statement more info
located_in intracellular membrane-bounded organelle	IDA Inferred from Direct Assay more info
located_in nucleoplasm	TAS Traceable Author Statement more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IEA Inferred from Electronic Annotation more info
part_of protein folding chaperone complex	IDA Inferred from Direct Assay more info	PubMed
part_of protein-containing complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: serine/threonine-protein phosphatase 5

Names: PP-T; protein phosphatase T

NP_001191213.1

EC 3.1.3.16

NP_006238.1

EC 3.1.3.16

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_028163.1 RefSeqGene

Range

5094..48982

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001204284.2 → NP_001191213.1 serine/threonine-protein phosphatase 5 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an alternate in-frame exon compared to variant 1. The resulting protein (isoform 2) is shorter compared to isoform 1.

Source sequence(s)

AC007193, DA545760

UniProtKB/TrEMBL

B2R6R6, Q53FR0

Conserved Domains (7) summary

smart00028
Location:28 → 61

TPR; Tetratricopeptide repeats

smart00156
Location:212 → 458

PP2Ac; Protein phosphatase 2A homologues, catalytic domain

sd00006
Location:28 → 56

TPR; TPR repeat [structural motif]

cd07417
Location:176 → 469

MPP_PP5_C; PP5, C-terminal metallophosphatase domain

pfam08321
Location:138 → 211

PPP5; PPP5 TPR repeat region

pfam13371
Location:71 → 134

TPR_9; Tetratricopeptide repeat

pfam13414
Location:27 → 93

TPR_11; TPR repeat
NM_006247.4 → NP_006238.1 serine/threonine-protein phosphatase 5 isoform 1

See identical proteins and their annotated locations for NP_006238.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer protein (isoform 1).

Source sequence(s)

AC007193, BC001970

Consensus CDS

CCDS12684.1

UniProtKB/Swiss-Prot

P53041, Q16722, Q53XV2

UniProtKB/TrEMBL

B2R6R6, Q53FR0

Related

ENSP00000012443.4, ENST00000012443.9

Conserved Domains (7) summary

smart00028
Location:28 → 61

TPR; Tetratricopeptide repeats

smart00156
Location:204 → 480

PP2Ac; Protein phosphatase 2A homologues, catalytic domain

sd00006
Location:28 → 56

TPR; TPR repeat [structural motif]

cd15830
Location:38 → 153

BamD; BamD lipoprotein, a component of the beta-barrel assembly machinery

cd07417
Location:176 → 491

MPP_PP5_C; PP5, C-terminal metallophosphatase domain

pfam13371
Location:71 → 134

TPR_9; Tetratricopeptide repeat

pfam13414
Location:27 → 93

TPR_11; TPR repeat