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 isof... See more...

Aliases for PPP1R8 Gene

Aliases for PPP1R8 Gene

  • Protein Phosphatase 1 Regulatory Subunit 8 2 3 5
  • NIPP-1 2 3 4
  • NIPP1 2 3 4
  • ARD1 2 3 4
  • Protein Phosphatase 1, Regulatory (Inhibitor) Subunit 8 2 3
  • Nuclear Inhibitor Of Protein Phosphatase 1 3 4
  • Nuclear Subunit Of PP-1 2 3
  • Activator Of RNA Decay 2 3
  • RNase E 2 3
  • PRO2047 2 3
  • Protein Phosphatase 1 Regulatory Inhibitor Subunit 8 4
  • Nuclear Inhibitor Of Protein Phosphatase-1 Alpha 3
  • Nuclear Inhibitor Of Protein Phosphatase-1 Beta 3
  • Protein Phosphatase 1, Regulatory Subunit 8 2
  • Nuclear Inhibitor Of Protein Phosphatase-1 2
  • PPP1R8 5
  • ARD-1 3
  • Ard-1 2

External Ids for PPP1R8 Gene

Previous GeneCards Identifiers for PPP1R8 Gene

  • GC01M027287
  • GC01P027131
  • GC01P027390
  • GC01P027761
  • GC01P027842
  • GC01P028029
  • GC01P028157
  • GC01P026413

Summaries for PPP1R8 Gene

Entrez Gene Summary for PPP1R8 Gene

  • 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]

GeneCards Summary for PPP1R8 Gene

PPP1R8 (Protein Phosphatase 1 Regulatory Subunit 8) is a Protein Coding gene. Diseases associated with PPP1R8 include Hyperoxaluria, Primary, Type Iii and Polycystic Kidney Disease 3 With Or Without Polycystic Liver Disease. Among its related pathways are Beta-Adrenergic Signaling and Apoptotic Pathways in Synovial Fibroblasts. Gene Ontology (GO) annotations related to this gene include RNA binding. An important paralog of this gene is SLC4A1AP.

UniProtKB/Swiss-Prot Summary for PPP1R8 Gene

  • Inhibitor subunit of the major nuclear protein phosphatase-1 (PP-1). It has RNA-binding activity but does not cleave RNA and may target PP-1 to RNA-associated substrates. May also be involved in pre-mRNA splicing. Binds DNA and might act as a transcriptional repressor. Seems to be required for cell proliferation.
  • Isoform Gamma is a site-specific single-strand endoribonuclease that cleaves single strand RNA 3' to purines and pyrimidines in A+U-rich regions. It generates 5'-phosphate termini at the site of cleavage. This isoform does not inhibit PP-1. May be implicated in mRNA splicing.

Gene Wiki entry for PPP1R8 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for PPP1R8 Gene

Genomics for PPP1R8 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for PPP1R8 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around PPP1R8 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for PPP1R8

Top Transcription factor binding sites by QIAGEN in the PPP1R8 gene promoter:
  • CREB
  • deltaCREB
  • FOXC1
  • Lmo2
  • Nkx2-5

Genomic Locations for PPP1R8 Gene

Latest Assembly
chr1:27,830,782-27,851,676
(GRCh38/hg38)
Size:
20,895 bases
Orientation:
Plus strand

Previous Assembly
chr1:28,157,293-28,178,187
(GRCh37/hg19 by Entrez Gene)
Size:
20,895 bases
Orientation:
Plus strand

chr1:28,157,289-28,178,187
(GRCh37/hg19 by Ensembl)
Size:
20,899 bases
Orientation:
Plus strand

Genomic View for PPP1R8 Gene

Genes around PPP1R8 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
PPP1R8 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for PPP1R8 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for PPP1R8 Gene

Proteins for PPP1R8 Gene

  • Protein details for PPP1R8 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q12972-PP1R8_HUMAN
    Recommended name:
    Nuclear inhibitor of protein phosphatase 1
    Protein Accession:
    Q12972
    Secondary Accessions:
    • Q5TEJ2
    • Q5TEJ4
    • Q5TIF2
    • Q6PKF6
    • Q9UBH1
    • Q9UBZ0

    Protein attributes for PPP1R8 Gene

    Size:
    351 amino acids
    Molecular mass:
    38479 Da
    Cofactor:
    Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
    Quaternary structure:
    • Interacts with phosphorylated CDC5L, SF3B1 and MELK. Interacts with EED, in a nucleic acid-stimulated manner. Part of a complex consisting of PPP1R8, EED, HDAC2 and PP-1. Part of the spliceosome. Interacts with PPP1CA, PPP1CB and PPP1CC.
    Miscellaneous:
    • A synthetic peptide, NIPP-1(330-351), is able to inhibit PP-1. Phosphorylation of Tyr-335 reduces PP-1 inhibition, whereas phosphorylation of Thr-346 or Ser-348 has no effect.

    Three dimensional structures from OCA and Proteopedia for PPP1R8 Gene

    Alternative splice isoforms for PPP1R8 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for PPP1R8 Gene

Post-translational modifications for PPP1R8 Gene

  • May be inactivated by phosphorylation on Ser-199 or Ser-204 (By similarity). Phosphorylated by Lyn in vitro on Tyr-264, and also on Tyr-335 in the presence of RNA.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for PPP1R8 Gene

No data available for DME Specific Peptides for PPP1R8 Gene

Domains & Families for PPP1R8 Gene

Protein Domains for PPP1R8 Gene

InterPro:
Blocks:
  • Forkhead-associated (FHA)

Suggested Antigen Peptide Sequences for PPP1R8 Gene

GenScript: Design optimal peptide antigens:
  • Protein phosphatase 1 regulatory inhibitor subunit 8 (PP1R8_HUMAN)
  • Protein phosphatase 1 regulatory subunit 8 testis splice variant (Q38J66_HUMAN)
  • Protein phosphatase 1, regulatory (Inhibitor) subunit 8 (Q561W4_HUMAN)
  • cDNA FLJ77357, highly similar to Homo sapiens protein phosphatase 1, regulatory (inhibitor) subunit 8 (PPP1R8), transcript variant 1, mRNA (Q5TEJ4_HUMAN)
  • cDNA, FLJ94432, Homo sapiens protein phosphatase 1, regulatory (inhibitor) subunit8 (PPP1R8), transcript variant 3, mRNA (Q6ICT4_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q12972

UniProtKB/Swiss-Prot:

PP1R8_HUMAN :
  • Has a basic N- and C-terminal and an acidic central domain.
Domain:
  • Has a basic N- and C-terminal and an acidic central domain.
  • The FHA domain mediates interactions with threonine-phosphorylated MELK.
genes like me logo Genes that share domains with PPP1R8: view

Function for PPP1R8 Gene

Molecular function for PPP1R8 Gene

UniProtKB/Swiss-Prot Function:
Inhibitor subunit of the major nuclear protein phosphatase-1 (PP-1). It has RNA-binding activity but does not cleave RNA and may target PP-1 to RNA-associated substrates. May also be involved in pre-mRNA splicing. Binds DNA and might act as a transcriptional repressor. Seems to be required for cell proliferation.
UniProtKB/Swiss-Prot Function:
Isoform Gamma is a site-specific single-strand endoribonuclease that cleaves single strand RNA 3' to purines and pyrimidines in A+U-rich regions. It generates 5'-phosphate termini at the site of cleavage. This isoform does not inhibit PP-1. May be implicated in mRNA splicing.
GENATLAS Biochemistry:
protein phosphatase 1,regulatory (inhibitor) subunit 8,also encoding a site specific single strand endoribonuclease,functionally ressembling E Coli RNase E

Phenotypes From GWAS Catalog for PPP1R8 Gene

Gene Ontology (GO) - Molecular Function for PPP1R8 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003677 DNA binding IEA --
GO:0003723 RNA binding TAS 9153239
GO:0003729 mRNA binding IBA 21873635
GO:0004518 nuclease activity IEA --
GO:0004519 endonuclease activity IEA --
genes like me logo Genes that share ontologies with PPP1R8: view
genes like me logo Genes that share phenotypes with PPP1R8: view

Animal Models for PPP1R8 Gene

MGI Knock Outs for PPP1R8:

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for PPP1R8

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for PPP1R8 Gene

Localization for PPP1R8 Gene

Subcellular locations from UniProtKB/Swiss-Prot for PPP1R8 Gene

Nucleus. Nucleus speckle. Note=Primarily, but not exclusively, nuclear.
[Isoform Gamma]: Cytoplasm. Note=Found mainly in the cytoplasm.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for PPP1R8 gene
Compartment Confidence
nucleus 5
cytosol 3
plasma membrane 2
extracellular 2
cytoskeleton 2
mitochondrion 1
endoplasmic reticulum 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nuclear speckles (4)
  • Nucleoplasm (4)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for PPP1R8 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus TAS 7499293
GO:0005654 nucleoplasm IDA --
GO:0005681 spliceosomal complex IEA --
GO:0005737 cytoplasm IEA --
GO:0016607 nuclear speck IDA 11739654
genes like me logo Genes that share ontologies with PPP1R8: view

Pathways & Interactions for PPP1R8 Gene

PathCards logo

SuperPathways for PPP1R8 Gene

SuperPathway Contained pathways
1 Activation of cAMP-Dependent PKA
.77
.77
.71
.56
2 Beta-Adrenergic Signaling
.37
.37
.37
.36
3 mTOR Pathway
4 GPCR Pathway
.58
5 Dopamine-DARPP32 Feedback onto cAMP Pathway
-
genes like me logo Genes that share pathways with PPP1R8: view

Pathways by source for PPP1R8 Gene

1 Tocris pathway for PPP1R8 Gene
14 Qiagen pathways for PPP1R8 Gene
  • Activation of cAMP-Dependent PKA
  • Activation of PKA through GPCR
  • Beta-Adrenergic Signaling
  • Breast Cancer Regulation by Stathmin1
  • cAMP Pathway

SIGNOR curated interactions for PPP1R8 Gene

Activates:
Inactivates:
Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for PPP1R8 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006397 mRNA processing IEA --
GO:0006401 RNA catabolic process TAS 9153239
GO:0008283 cell proliferation IEA --
GO:0008380 RNA splicing IEA --
GO:0032515 negative regulation of phosphoprotein phosphatase activity IEA --
genes like me logo Genes that share ontologies with PPP1R8: view

Drugs & Compounds for PPP1R8 Gene

(3) Drugs for PPP1R8 Gene - From: HMDB and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Magnesium Approved, Experimental, Investigational Pharma 0
Phosphate Experimental Pharma 0
genes like me logo Genes that share compounds with PPP1R8: view

Transcripts for PPP1R8 Gene

mRNA/cDNA for PPP1R8 Gene

3 REFSEQ mRNAs :
20 NCBI additional mRNA sequence :
5 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for PPP1R8

Alternative Splicing Database (ASD) splice patterns (SP) for PPP1R8 Gene

ExUns: 1a · 1b · 1c · 1d ^ 2 ^ 3 ^ 4a · 4b ^ 5a · 5b · 5c ^ 6a · 6b · 6c · 6d ^ 7 ^ 8
SP1: - - - -
SP2: - -
SP3: - - - - -
SP4: - - -
SP5: - - -
SP6: - -
SP7: - -

Relevant External Links for PPP1R8 Gene

GeneLoc Exon Structure for
PPP1R8

Expression for PPP1R8 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for PPP1R8 Gene

Protein differential expression in normal tissues from HIPED for PPP1R8 Gene

This gene is overexpressed in CD8 Tcells (9.4) and Peripheral blood mononuclear cells (6.3).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for PPP1R8 Gene



Protein tissue co-expression partners for PPP1R8 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for PPP1R8

SOURCE GeneReport for Unigene cluster for PPP1R8 Gene:

Hs.533474

mRNA Expression by UniProt/SwissProt for PPP1R8 Gene:

Q12972-PP1R8_HUMAN
Tissue specificity: Ubiquitously expressed, with highest levels in heart and skeletal muscle, followed by brain, placenta, lung, liver and pancreas. Less abundant in kidney. The concentration and ratio between isoforms is cell-type dependent. Isoform Alpha (>90%) and isoform Beta were found in brain, heart and kidney. Isoform Gamma is mainly found in B-cells and T-lymphocytes, and has been found in 293 embryonic kidney cells.

Evidence on tissue expression from TISSUES for PPP1R8 Gene

  • Thyroid gland(4.6)
  • Blood(4.4)
  • Nervous system(4.2)
  • Skin(3.3)
  • Intestine(3.1)
  • Kidney(3)
  • Stomach(2.8)
  • Lung(2.7)
  • Adrenal gland(2.4)
  • Bone marrow(2.4)
  • Gall bladder(2.4)
  • Lymph node(2.4)
  • Pancreas(2.4)
  • Spleen(2.1)
  • Heart(2)
genes like me logo Genes that share expression patterns with PPP1R8: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for PPP1R8 Gene

Orthologs for PPP1R8 Gene

This gene was present in the common ancestor of animals.

Orthologs for PPP1R8 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia PPP1R8 29 30
  • 99.53 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia PPP1R8 30
  • 99 (a)
OneToOne
Cow
(Bos Taurus)
Mammalia PPP1R8 29 30
  • 94.49 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia PPP1R8 29 30
  • 94.21 (n)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia PPP1R8 30
  • 92 (a)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Ppp1r8 29
  • 91.17 (n)
Mouse
(Mus musculus)
Mammalia Ppp1r8 29 16 30
  • 90.69 (n)
OneToOne
Chicken
(Gallus gallus)
Aves PPP1R8 29 30
  • 80.44 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia PPP1R8 30
  • 89 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia ppp1r8 29
  • 73.82 (n)
African clawed frog
(Xenopus laevis)
Amphibia MGC69160 29
Zebrafish
(Danio rerio)
Actinopterygii ppp1r8b 30
  • 73 (a)
OneToMany
ppp1r8a 29 30
  • 71.37 (n)
OneToMany
-- 29
Fruit Fly
(Drosophila melanogaster)
Insecta NiPp1 29 30
  • 55.59 (n)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP012089 29
  • 55.49 (n)
Worm
(Caenorhabditis elegans)
Secernentea B0511.7 29 30
  • 53.28 (n)
OneToOne
Sea Vase
(Ciona intestinalis)
Ascidiacea Cin.6111 29
Species where no ortholog for PPP1R8 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for PPP1R8 Gene

ENSEMBL:
Gene Tree for PPP1R8 (if available)
TreeFam:
Gene Tree for PPP1R8 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for PPP1R8: view image
Alliance of Genome Resources:
Additional Orthologs for PPP1R8

Paralogs for PPP1R8 Gene

Paralogs for PPP1R8 Gene

Pseudogenes.org Pseudogenes for PPP1R8 Gene

genes like me logo Genes that share paralogs with PPP1R8: view

Variants for PPP1R8 Gene

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for PPP1R8 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for PPP1R8 Gene

Variant ID Type Subtype PubMed ID
nsv509069 CNV insertion 20534489

Variation tolerance for PPP1R8 Gene

Residual Variation Intolerance Score: 33.2% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.76; 33.32% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for PPP1R8 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
PPP1R8
Leiden Open Variation Database (LOVD)
PPP1R8

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for PPP1R8 Gene

Disorders for PPP1R8 Gene

MalaCards: The human disease database

(5) MalaCards diseases for PPP1R8 Gene - From: COP

- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for PPP1R8

genes like me logo Genes that share disorders with PPP1R8: view

No data available for UniProtKB/Swiss-Prot and Genatlas for PPP1R8 Gene

Publications for PPP1R8 Gene

  1. ard-1: a human gene that reverses the effects of temperature-sensitive and deletion mutations in the Escherichia coli rne gene and encodes an activity producing RNase E-like cleavages. (PMID: 7524097) Wang M … Cohen SN (Proceedings of the National Academy of Sciences of the United States of America 1994) 2 3 4 22
  2. Inhibition of spliceosome assembly by the cell cycle-regulated protein kinase MELK and involvement of splicing factor NIPP1. (PMID: 14699119) Vulsteke V … Bollen M (The Journal of biological chemistry 2004) 3 4 22
  3. Phosphorylation-dependent interaction between the splicing factors SAP155 and NIPP1. (PMID: 12105215) Boudrez A … Bollen M (The Journal of biological chemistry 2002) 3 4 22
  4. Dynamic targeting of protein phosphatase 1 within the nuclei of living mammalian cells. (PMID: 11739654) Trinkle-Mulcahy L … Lamond AI (Journal of cell science 2001) 3 4 22
  5. NIPP1-mediated interaction of protein phosphatase-1 with CDC5L, a regulator of pre-mRNA splicing and mitotic entry. (PMID: 10827081) Boudrez A … Bollen M (The Journal of biological chemistry 2000) 3 4 22

Products for PPP1R8 Gene

Sources for PPP1R8 Gene