PPP1R8 protein phosphatase 1 regulatory subunit 8 [Homo sapiens (human)] - Gene

Summary

Official Symbol: PPP1R8provided by HGNC
Official Full Name: protein phosphatase 1 regulatory subunit 8provided by HGNC
Primary source: HGNC:HGNC:9296
See related: Ensembl:ENSG00000117751 MIM:602636; AllianceGenome:HGNC:9296
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: ARD1; ARD-1; NIPP1; NIPP-1; PRO2047
Summary: This gene, through alternative splicing, encodes three different isoforms. Two of the protein isoforms encoded by this gene are specific inhibitors of type 1 serine/threonine protein phosphatases and can bind but not cleave RNA. The third protein isoform lacks the phosphatase inhibitory function but is a single-strand endoribonuclease comparable to RNase E of E. coli. This isoform requires magnesium for its function and cleaves specific sites in A+U-rich regions of RNA. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in endometrium (RPKM 13.4), lymph node (RPKM 13.2) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 1p35.3

Exon count:: 7

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (27830782..27851676)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (27672075..27692970)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (28157293..28178187)

Chromosome 1 - NC_000001.11 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
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?

PP1 regulatory subunit NIPP1 regulates transcription of E2F1 target genes following DNA damage.
Title: PP1 regulatory subunit NIPP1 regulates transcription of E2F1 target genes following DNA damage.
PP1-NIPP1 expression resulted in the build up of RNA-DNA hybrids (R-loops), enhanced chromatin compaction and a diminished repair of DNA double-strand breaks.
Title: Overexpression of PP1-NIPP1 limits the capacity of cells to repair DNA double-strand breaks.
NIPP1 could be activated by hypoxia and contributed to hypoxia-induced invasive and metastatic potential in hepatocellular carcinoma.
Title: Hypoxia-induced NIPP1 activation enhances metastatic potential and predicts poor prognosis in hepatocellular carcinoma.
Data suggest overexpression of NIPP1 in HeLa cells causes induction of genes of mesenchymal lineage with reduction in cell proliferation; thus, key dephosphorylation events may be involved in epithelial-mesenchymal transition or transdifferentiation.
Title: Protein phosphatase PP1-NIPP1 activates mesenchymal genes in HeLa cells.
PP1/NIPP1 is a novel molecular compass that controls directed cell migration.
Title: A role for PP1/NIPP1 in steering migration of human cancer cells.
The molecular basis by which NIPP1 directs PP1 substrate specificity in the nucleus.
Title: The molecular basis for substrate specificity of the nuclear NIPP1:PP1 holoenzyme.
NIPP1 works as a molecular sensor for PP1 to recognize phosphorylated Sap155.
Title: Nuclear inhibitor of protein phosphatase-1 (NIPP1) directs protein phosphatase-1 (PP1) to dephosphorylate the U2 small nuclear ribonucleoprotein particle (snRNP) component, spliceosome-associated protein 155 (Sap155).
NMR structure of the NIPP1 FHA domain.
Title: The NMR structure of the NIPP1 FHA domain.
Required for the global trimethylation of histone3 at lysine27 and is implicated in gene silencing by enhancer of zeste homolog (EZH)2.
Title: The transcriptional repressor NIPP1 is an essential player in EZH2-mediated gene silencing.
NIPP1 is present in a complex with EED and EZH2 in vivo and has distinct binding sites for these proteins.
Title: The transcriptional repression by NIPP1 is mediated by Polycomb group proteins.

Submit: New GeneRIF Correction See all GeneRIFs (13)

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
Knockdown of protein phosphatase 1, regulatory subunit 8 (PPP1R8) by shRNA library screening inhibits HIV-1 replication in cultured Jurkat T-cells	PubMed

Protein interactions

Protein	Gene	Interaction	Pubs
Tat	tat	PP1 interacts with Tat in part through the binding of Val(36) and Phe(38) of Tat to PP1, and Tat is involved in the nuclear and subnuclear targeting of PP1	PubMed
	tat	Nuclear inhibitor of PP1 (NIPP1) inhibits HIV-1 Tat-induced transcription, an effect that can be reversed by co-expression of PP1, indicating Tat function is regulated by PP1/NIPP1	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D1S2380 (e-PCR)
- UniSTS:26745

D1S3446 (e-PCR)
- UniSTS:46498

A002Y18 (e-PCR)
- UniSTS:36261

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables DNA binding	IEA Inferred from Electronic Annotation more info
enables RNA binding	TAS Traceable Author Statement more info	PubMed
enables endonuclease activity	IEA Inferred from Electronic Annotation more info
enables mRNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables molecular function inhibitor activity	EXP Inferred from Experiment more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein serine/threonine phosphatase inhibitor activity	IBA Inferred from Biological aspect of Ancestor more info
enables ribonuclease E activity	TAS Traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
involved_in RNA catabolic process	TAS Traceable Author Statement more info	PubMed
involved_in cell population proliferation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of protein dephosphorylation	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
located_in cytoplasm	IEA Inferred from Electronic Annotation more info
is_active_in nuclear speck	IBA Inferred from Biological aspect of Ancestor more info
located_in nuclear speck	IDA Inferred from Direct Assay more info	PubMed
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleoplasm	TAS Traceable Author Statement more info
located_in nucleus	TAS Traceable Author Statement more info	PubMed
part_of spliceosomal complex	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: nuclear inhibitor of protein phosphatase 1

Names: RNase E; activator of RNA decay; nuclear inhibitor of protein phosphatase-1 alpha; nuclear inhibitor of protein phosphatase-1 beta; nuclear subunit of PP-1; protein phosphatase 1, regulatory (inhibitor) subunit 8

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.

mRNA and Protein(s)

NM_002713.4 → NP_002704.1 nuclear inhibitor of protein phosphatase 1 isoform gamma

See identical proteins and their annotated locations for NP_002704.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) encodes the shortest isoform (gamma, also called ARD-1). It has its first exon longer at the 3' end and lacks an internal exon as compared to that of transcript variant 1. The gamma isoform uses a different translation start site and is N-terminally truncated as compared to isoform alpha encoded by variant 1. Isoform gamma contains ribonuclease activity.

Source sequence(s)

AF061959, AL020997, AL109927, DA077576, U14575

Consensus CDS

CCDS313.1

UniProtKB/TrEMBL

Q6ICT4

Related

ENSP00000236412.7, ENST00000236412.11
NM_014110.5 → NP_054829.2 nuclear inhibitor of protein phosphatase 1 isoform alpha

See identical proteins and their annotated locations for NP_054829.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) is the shortest transcript but encodes the predominant and longest isoform (alpha). Isoform alpha contains protein phosphatase inhibitory actvity.

Source sequence(s)

AF061959, AK292077, AL109927, DA167043

Consensus CDS

CCDS311.1

UniProtKB/Swiss-Prot

Q12972, Q5TEJ2, Q5TEJ4, Q5TIF2, Q6PKF6, Q9UBH1, Q9UBZ0

UniProtKB/TrEMBL

Q561W4

Related

ENSP00000311677.5, ENST00000311772.10

Conserved Domains (2) summary

cd00060
Location:27 → 119

FHA; Forkhead associated domain (FHA); found in eukaryotic and prokaryotic proteins. Putative nuclear signalling domain. FHA domains may bind phosphothreonine, phosphoserine and sometimes phosphotyrosine. In eukaryotes, many FHA domain-containing proteins ...

pfam11945
Location:98 → 212

WASH_WAHD; WAHD domain of WASH complex
NM_138558.3 → NP_612568.1 nuclear inhibitor of protein phosphatase 1 isoform beta/delta

See identical proteins and their annotated locations for NP_612568.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) is the longest transcript and has its first exon longer at the 3' end as compared to that of transcript variant 1. The resulting isoform (beta/delta) uses a different translation start site and is N-terminally truncated as compared to isoform alpha encoded by variant 1. Isoform beta/delta contains protein phosphatase inhibitory activity.

Source sequence(s)

AF061959, AL020997, AL109927, DA693246

Consensus CDS

CCDS312.1

UniProtKB/TrEMBL

A0A0A0MT09

Related

ENSP00000363042.4, ENST00000373931.8