Reviewed,
UniProtKB/Swiss-Prot Q12972 (PP1R8_HUMAN)
Last modified
July 7, 2009.
Version 87.
History...
Clusters with 100%,
90%,
50% identity |
Documents (3) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Nuclear inhibitor of protein phosphatase 1 Short name=NIPP-1 Alternative name(s): Protein phosphatase 1 regulatory inhibitor subunit 8 Including the following 1 domains: 1- Recommended name: Activator of RNA decay EC=3.1.4.- Alternative name(s): ARD-1 | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) [Complete proteome] | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 351 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| 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. Ref.8 Ref.10 Ref.11 Ref.13 Ref.15 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. Ref.8 Ref.10 Ref.11 Ref.13 Ref.15 |
| Cofactor | Magnesium. Endoribonuclease function is magnesium-dependent. |
| Subunit 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. Ref.11 Ref.15 Ref.14 Ref.16 |
| Subcellular location | Nucleus. Nucleus speckle. Note: Primarily, but not exclusively, nuclear. Ref.11 Ref.12 Isoform Gamma: Cytoplasm. Note: Found mainly in the cytoplasm. Ref.11 Ref.12 |
| 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. Ref.2 Ref.6 |
| Domain | Has a basic N- and C-terminal and an acidic central domain. |
| Post-translational modification | 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. |
| 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. |
| Sequence similarities | Contains 1 FHA domain. |
Ontologies
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| NME2 | P22392 | 1 | EBI-716633,EBI-713693 | |
| PPP1CB | P62140 | 1 | EBI-716633,EBI-352350 |
Alternative products
| This entry describes 3 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform Alpha (identifier: Q12972-1) This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. | ||||||
| Isoform Beta (identifier: Q12972-2) Also known as: Delta; The sequence of this isoform differs from the canonical sequence as follows: 1-142: Missing. | ||||||
| Isoform Gamma (identifier: Q12972-3) Also known as: ARD-1; The sequence of this isoform differs from the canonical sequence as follows: 1-224: Missing. | ||||||
| Note: Found mainly in the cytoplasm. Ref.11 Ref.12 |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 351 | 351 | Nuclear inhibitor of protein phosphatase 1 | PRO_0000071505 | |||||
Regions | |||||||||
| Domain | 49 – 101 | 53 | FHA | ||||||
| Region | 1 – 142 | 142 | Interaction with CDC5L, SF3B1 and MELK | ||||||
| Region | 143 – 224 | 82 | Interaction with EED | ||||||
| Region | 191 – 200 | 10 | Involved in PP-1 inhibition | ||||||
| Region | 200 – 203 | 4 | Involved in PP-1 binding | ||||||
| Region | 310 – 329 | 20 | Interaction with EED | ||||||
| Region | 330 – 351 | 22 | RNA-binding | ||||||
| Region | 331 – 337 | 7 | Involved in PP-1 inhibition | ||||||
| Motif | 185 – 209 | 25 | Nuclear localization signal 1 Ref.12 | ||||||
| Motif | 210 – 240 | 31 | Nuclear localization signal 2 Ref.12 | ||||||
Amino acid modifications | |||||||||
| Modified residue | 199 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 204 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 264 | 1 | Phosphotyrosine; by LYN; in vitro Ref.10 | ||||||
| Modified residue | 335 | 1 | Phosphotyrosine Probable | ||||||
Natural variations | |||||||||
| Alternative sequence | 1 – 224 | 224 | Missing in isoform Gamma. | VSP_005120 | |||||
| Alternative sequence | 1 – 142 | 142 | Missing in isoform Beta. | VSP_005119 | |||||
Experimental info | |||||||||
| Mutagenesis | 68 – 71 | 4 | SRVH → AAAA: Abolishes interaction with CDC5L, SF3B1 and MELK, and localization in nuclear speckles. No effect on repressor activity. Ref.11 Ref.14 Ref.16 | ||||||
| Mutagenesis | 193 – 197 | 5 | KRKRK → AAAAA: No effect on interaction with EED. | ||||||
| Mutagenesis | 195 – 197 | 3 | KRK → AAA: Abolishes nuclear import; when associated with A-234--237-A. | ||||||
| Mutagenesis | 199 | 1 | S → A or D: No change in subcellular location, no effect on interaction with EED or repressor activity; when associated with A-204 or D-204. Ref.15 Ref.12 | ||||||
| Mutagenesis | 201 | 1 | V → A: Reduces PP-1 binding, but no effect on subcellular location or repressor activity; when associated with A-203. Ref.15 Ref.12 | ||||||
| Mutagenesis | 203 | 1 | F → A: Reduces PP-1 binding, but no effect on subcellular location or repressor activity; when associated with A-201. Ref.15 Ref.12 | ||||||
| Mutagenesis | 204 | 1 | S → A or D: No change in subcellular location, no effect on interaction with EED or repressor activity; when associated with A-199 or D-199. Ref.15 Ref.12 | ||||||
| Mutagenesis | 234 – 237 | 4 | KKKR → AAAA: Abolishes nuclear import; when associated with A-195-197-A. Ref.12 | ||||||
| Mutagenesis | 264 | 1 | Y → D: Abolishes in vitro phosphorylation of isoform gamma by Lyn. Ref.10 | ||||||
| Mutagenesis | 335 | 1 | Y → D: Decreases the ability of isoform Gamma to bind and inhibit PP-1. Ref.10 | ||||||
| Mutagenesis | 346 | 1 | T → D: No effect on the ability of isoform Gamma to inhibit PP-1. Ref.10 | ||||||
| Mutagenesis | 348 | 1 | S → D: No effect on the ability of isoform Gamma to inhibit PP-1. Ref.10 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [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." Wang M., Cohen S.N. Proc. Natl. Acad. Sci. U.S.A. 91:10591-10595(1994) [PubMed: 7524097] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM GAMMA). Tissue: B-cell. |
| [2] | "Organization and alternate splice products of the gene encoding nuclear inhibitor of protein phosphatase-1 (NIPP-1)." Van Eynde A., Perez-Callejon E., Schoenmakers E., Jacquemin M., Stalmans W., Bollen M. Eur. J. Biochem. 261:291-300(1999) [PubMed: 10103062] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS ALPHA AND BETA), ALTERNATIVE SPLICING, TISSUE SPECIFICITY. Tissue: Parathyroid and T-cell. |
| [3] | "Complete cDNA sequence of NIPP-1 from human breast cancer cells." Liu J.P., Yang Z., Li H. Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA). Tissue: Mammary cancer. |
| [4] | "The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. Bentley D.R.Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [5] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM BETA), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 34-351 (ISOFORM ALPHA). Tissue: Lymph. |
| [6] | "Molecular cloning of NIPP-1, a nuclear inhibitor of protein phosphatase-1, reveals homology with polypeptides involved in RNA processing." Van Eynde A., Wera S., Beullens M., Torrekens S., Van Leuven F., Stalmans W., Bollen M. J. Biol. Chem. 270:28068-28074(1995) [PubMed: 7499293] [Abstract] Cited for: TISSUE SPECIFICITY. |
| [7] | "ARD-1 cDNA from human cells encodes a site-specific single-strand endoribonuclease that functionally resembles Escherichia coli RNase E." Claverie-Martin F., Wang M., Cohen S.N. J. Biol. Chem. 272:13823-13828(1997) [PubMed: 9153239] [Abstract] Cited for: CHARACTERIZATION OF ISOFORM GAMMA. |
| [8] | "Mapping of the RNA-binding and endoribonuclease domains of NIPP1, a nuclear targeting subunit of protein phosphatase 1." Jin Q., Beullens M., Jagiello I., Van Eynde A., Vulsteke V., Stalmans W., Bollen M. Biochem. J. 342:13-19(1999) [PubMed: 10432294] [Abstract] Cited for: RNA-BINDING, CHARACTERIZATION OF ISOFORM GAMMA, FUNCTION. |
| [9] | "Alternative splicing regulates the production of ARD-1 endoribonuclease and NIPP-1, an inhibitor of protein phosphatase-1, as isoforms encoded by the same gene." Chang A.C.Y., Sohlberg B., Trinkle-Mulcahy L., Claverie-Martin F., Cohen P., Cohen S.N. Gene 240:45-55(1999) [PubMed: 10564811] [Abstract] Cited for: IDENTIFICATION OF ALTERNATIVE SPLICING IN ISOFORM GAMMA. |
| [10] | "The C-terminus of NIPP1 (nuclear inhibitor of protein phosphatase-1) contains a novel binding site for protein phosphatase-1 that is controlled by tyrosine phosphorylation and RNA binding." Beullens M., Vulsteke V., Van Eynde A., Jagiello I., Stalmans W., Bollen M. Biochem. J. 352:651-658(2000) [PubMed: 11104670] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF TYR-264; TYR-335; THR-346 AND SER-348, PHOSPHORYLATION AT TYR-264 AND TYR-335. |
| [11] | "NIPP1-mediated interaction of protein phosphatase-1 with CDC5L, a regulator of pre-mRNA splicing and mitotic entry." Boudrez A., Beullens M., Groenen P.M.A., Van Eynde A., Vulsteke V., Jagiello I., Murray M., Krainer A.R., Stalmans W., Bollen M. J. Biol. Chem. 275:25411-25417(2000) [PubMed: 10827081] [Abstract] Cited for: INTERACTION WITH CDC5L, SUBCELLULAR LOCATION, MUTAGENESIS OF 68-SER--HIS-71, FUNCTION. |
| [12] | "Nuclear and subnuclear targeting sequences of the protein phosphatase-1 regulator NIPP1." Jagiello I., Van Eynde A., Vulsteke V., Beullens M., Boudrez A., Keppens S., Stalmans W., Bollen M. J. Cell Sci. 113:3761-3768(2000) [PubMed: 11034904] [Abstract] Cited for: NUCLEAR LOCALIZATION SIGNALS, MUTAGENESIS OF 68-SER--HIS-71; 195-LYS--LYS-197; SER-199; VAL-201; PHE-203; SER-204 AND 234-LYS--ARG-237, SUBCELLULAR LOCATION. |
| [13] | "The protein phosphatase-1 regulator NIPP1 is also a splicing factor involved in a late step of spliceosome assembly." Beullens M., Bollen M. J. Biol. Chem. 277:19855-19860(2002) [PubMed: 11909864] [Abstract] Cited for: IDENTIFICATION AS PART OF THE SPLICEOSOME, FUNCTION. |
| [14] | "Phosphorylation-dependent interaction between the splicing factors SAP155 and NIPP1." Boudrez A., Beullens M., Waelkens E., Stalmans W., Bollen M. J. Biol. Chem. 277:31834-31841(2002) [PubMed: 12105215] [Abstract] Cited for: INTERACTION WITH SF3B1, MUTAGENESIS OF 68-SER--HIS-71. |
| [15] | "The protein phosphatase-1 (PP1) regulator, nuclear inhibitor of PP1 (NIPP1), interacts with the polycomb group protein, embryonic ectoderm development (EED), and functions as a transcriptional repressor." Jin Q., van Eynde A., Beullens M., Roy N., Thiel G., Stalmans W., Bollen M. J. Biol. Chem. 278:30677-30685(2003) [PubMed: 12788942] [Abstract] Cited for: DNA-BINDING, INTERACTION WITH EED, IDENTIFICATION IN A COMPLEX WITH EED; HDAC2 AND PP1, MUTAGENESIS OF 68-SER--HIS-71; 193-LYS--LYS-197; SER-199; VAL-201; PHE-203 AND SER-204, FUNCTION. |
| [16] | "Inhibition of spliceosome assembly by the cell cycle-regulated protein kinase MELK and involvement of splicing factor NIPP1." Vulsteke V., Beullens M., Boudrez A., Keppens S., Van Eynde A., Rider M.H., Stalmans W., Bollen M. J. Biol. Chem. 279:8642-8647(2004) [PubMed: 14699119] [Abstract] Cited for: INTERACTION WITH MELK, MUTAGENESIS OF 68-SER--HIS-71. |
| [17] | Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| U14575 mRNA. Translation: AAA64749.1. AF061958 mRNA. Translation: AAD31541.1. AF061959 mRNA. Translation: AAD31542.1. AF064757 AF064756 Genomic DNA. Translation: AAD24669.1. AF064757 AF064756 Genomic DNA. Translation: AAD24670.1. AF126488 mRNA. Translation: AAD22486.1. AL020997, AL109927 Genomic DNA. Translation: CAI20577.1. AL109927, AL020997 Genomic DNA. Translation: CAI21780.1. BC001597 mRNA. Translation: AAH01597.1. BC013360 mRNA. Translation: AAH13360.1. | |
| IPI | IPI00030383. IPI00142629. IPI00218794. |
| PIR | I38856. |
| RefSeq | NP_002704.1. NP_054829.2. NP_612568.1. |
| UniGene | Hs.533474 |
3D structure databases | |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | Q12972. 8 interactions. |
PTM databases | |
| PhosphoSite | Q12972. |
Proteomic databases | |
| PeptideAtlas | Q12972. |
| PRIDE | Q12972. |
Genome annotation databases | |
| Ensembl | ENSG00000117751. Homo sapiens. [Contig view] |
| GeneID | 5511. |
| KEGG | hsa:5511. |
| UCSC | uc001bov.1. human. |
Organism-specific databases | |
| GeneCards | GC01P028029. |
| H-InvDB | HIX0000304. |
| HGNC | HGNC:9296. PPP1R8. |
| MIM | 602636. gene. |
| PharmGKB | PA33659. |
| GenAtlas | Search... |
Phylogenomic databases | |
| HOGENOM | Q12972. |
| HOVERGEN | Q12972. |
| OMA | Q12972. VKKKRME. |
Gene expression databases | |
| ArrayExpress | Q12972. |
| Bgee | Q12972. |
| CleanEx | HS_PPP1R8. |
Family and domain databases | |
| InterPro | IPR000253. FHA. [Graphical view] |
| Gene3D | G3DSA:2.60.200.20. FHA. 1 hit. |
| Pfam | PF00498. FHA. 1 hit. [Graphical view] |
| SMART | SM00240. FHA. 1 hit. [Graphical view] |
| PROSITE | PS50006. FHA_DOMAIN. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| NextBio | 21316. |
| SOURCE | Search... |
Entry information
| Entry name | PP1R8_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q12972 Secondary accession number(s): Q5TIF2 Q9UBZ0 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| Human chromosome 1 Human chromosome 1: entries, gene names and cross-references to MIM |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with


