Q9WTR8 (PHLP1_RAT) Reviewed, UniProtKB/Swiss-Prot
Last modified
April 3, 2013.
Version 91.
History...
Clusters with 
Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended name: PH domain leucine-rich repeat protein phosphatase 1 EC=3.1.3.16 Alternative name(s): Pleckstrin homology domain-containing family E member 1 Short name=PH domain-containing family E member 1 Suprachiasmatic nucleus circadian oscillatory protein | ||||
| Gene names |
| ||||
| Organism | Rattus norvegicus (Rat) [Reference proteome] | ||||
| Taxonomic identifier | 10116 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus |
Protein attributes
| Sequence length | 1696 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence at protein level |
General annotation (Comments)
| Function | Protein phosphatase that mediates dephosphorylation of 'Ser-473' of AKT1, 'Ser-660' of PRKCB isoform beta-II and 'Ser-657' of PRKCA. AKT1 regulates the balance between cell survival and apoptosis through a cascade that primarily alters the function of transcription factors that regulate pro- and antiapoptotic genes. Dephosphorylation of 'Ser-473' of AKT1 triggers apoptosis and suppression of tumor growth. Controls the phosphorylation of AKT2 and AKT3 more efficiently than that of AKT1. Dephosphorylation of PRKCA and PRKCB leads to their destabilization and degradation. Inhibits cancer cell proliferation and may act as a tumor suppressor By similarity. May act as a negative regulator of K-Ras signaling in membrane rafts. |
| Catalytic activity | A phosphoprotein + H2O = a protein + phosphate. |
| Cofactor | Binds 2 manganese ions per subunit By similarity. |
| Enzyme regulation | Insensitive to okadaic acid By similarity. |
| Subunit structure | Interacts with the nucleotide free form of K-Ras (KRAS) via its LRR repeats. Interacts with AKT2, AKT3 and PRKCB isoform beta-II By similarity. Ref.2 |
| Subcellular location | Cytoplasm. Membrane; Peripheral membrane protein. Nucleus By similarity Ref.2. |
| Tissue specificity | Mainly present in brain (at protein level). Ref.1 |
| Developmental stage | In the suprachiasmatic nucleus, it increases during subjective night with a peak at midnight under constant dark conditions. Expressed at a constant level in neurons throughout the brain (at protein level). Ref.1 |
| Domain | The PH domain is required for interaction with PRKCB and its dephosphorylation By similarity. |
| Sequence similarities | Contains 18 LRR (leucine-rich) repeats. Contains 1 PH domain. Contains 1 PP2C-like domain. |
Ontologies
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 1696 | 1696 | PH domain leucine-rich repeat protein phosphatase 1 | PRO_0000057783 | |||||
Regions | |||||||||
| Domain | 499 – 599 | 101 | PH | ||||||
| Repeat | 601 – 622 | 22 | LRR 1 | ||||||
| Repeat | 624 – 645 | 22 | LRR 2 | ||||||
| Repeat | 655 – 676 | 22 | LRR 3 | ||||||
| Repeat | 678 – 699 | 22 | LRR 4 | ||||||
| Repeat | 701 – 722 | 22 | LRR 5 | ||||||
| Repeat | 724 – 746 | 23 | LRR 6 | ||||||
| Repeat | 836 – 857 | 22 | LRR 7 | ||||||
| Repeat | 858 – 879 | 22 | LRR 8 | ||||||
| Repeat | 881 – 902 | 22 | LRR 9 | ||||||
| Repeat | 904 – 925 | 22 | LRR 10 | ||||||
| Repeat | 926 – 947 | 22 | LRR 11 | ||||||
| Repeat | 950 – 971 | 22 | LRR 12 | ||||||
| Repeat | 976 – 996 | 21 | LRR 13 | ||||||
| Repeat | 1000 – 1021 | 22 | LRR 14 | ||||||
| Repeat | 1024 – 1045 | 22 | LRR 15 | ||||||
| Repeat | 1047 – 1068 | 22 | LRR 16 | ||||||
| Repeat | 1069 – 1090 | 22 | LRR 17 | ||||||
| Repeat | 1092 – 1113 | 22 | LRR 18 | ||||||
| Domain | 1128 – 1383 | 256 | PP2C-like | ||||||
| Motif | 1694 – 1696 | 3 | PDZ-binding | ||||||
| Compositional bias | 4 – 9 | 6 | Poly-Ala | ||||||
| Compositional bias | 21 – 28 | 8 | Poly-Ala | ||||||
| Compositional bias | 116 – 126 | 11 | Poly-Ser | ||||||
| Compositional bias | 339 – 343 | 5 | Poly-Ser | ||||||
| Compositional bias | 405 – 410 | 6 | Poly-Ala | ||||||
| Compositional bias | 1431 – 1434 | 4 | Poly-Ser | ||||||
| Compositional bias | 1645 – 1661 | 17 | Poly-Gln | ||||||
| Compositional bias | 1662 – 1669 | 8 | Poly-Pro | ||||||
Sites | |||||||||
| Metal binding | 1173 | 1 | Manganese 1 By similarity | ||||||
| Metal binding | 1173 | 1 | Manganese 2 By similarity | ||||||
| Metal binding | 1174 | 1 | Manganese 1; via carbonyl oxygen By similarity | ||||||
| Metal binding | 1337 | 1 | Manganese 2 By similarity | ||||||
| Metal binding | 1376 | 1 | Manganese 2 By similarity | ||||||
Sequences
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References
| [1] | "SCOP, a novel gene product expressed in a circadian manner in rat suprachiasmatic nucleus." Shimizu K., Okada M., Takano A., Nagai K. FEBS Lett. 458:363-369(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, DEVELOPMENTAL STAGE. Tissue: Brain. |
| [2] | "Suprachiasmatic nucleus circadian oscillatory protein, a novel binding partner of K-Ras in the membrane rafts, negatively regulates MAPK pathway." Shimizu K., Okada M., Nagai K., Fukada Y. J. Biol. Chem. 278:14920-14925(2003) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH KRAS. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | AB023624 mRNA. Translation: BAA77767.1. |
| IPI | IPI00201074. |
| RefSeq | NP_067689.1. NM_021657.1. |
| UniGene | Rn.163214. |
3D structure databases | |
| ProteinModelPortal | Q9WTR8. |
| ModBase | Search... |
Protein-protein interaction databases | |
| STRING | 10116.ENSRNOP00000003840. |
Proteomic databases | |
| PaxDb | Q9WTR8. |
| PRIDE | Q9WTR8. |
Protocols and materials databases | |
| StructuralBiologyKnowledgebase | Search... |
Genome annotation databases | |
| GeneID | 59265. |
| KEGG | rno:59265. |
| UCSC | RGD:621308. rat. |
Organism-specific databases | |
| CTD | 23239. |
| RGD | 621308. Phlpp1. |
Phylogenomic databases | |
| eggNOG | COG4886. |
| HOGENOM | HOG000115529. |
| InParanoid | Q9WTR8. |
| KO | K16340. |
| OrthoDB | EOG4HMJ8G. |
Gene expression databases | |
| ArrayExpress | Q9WTR8. |
| Genevestigator | Q9WTR8. |
| GermOnline | ENSRNOG00000002821. Rattus norvegicus. |
Family and domain databases | |
| Gene3D | 2.30.29.30. 1 hit. 3.60.40.10. 1 hit. |
| InterPro | IPR001611. Leu-rich_rpt. IPR011993. PH_like_dom. IPR001849. Pleckstrin_homology. IPR001932. PP2C-like. [Graphical view] |
| Pfam | PF00560. LRR_1. 2 hits. PF00481. PP2C. 1 hit. [Graphical view] |
| SMART | SM00233. PH. 1 hit. SM00332. PP2Cc. 1 hit. [Graphical view] |
| SUPFAM | SSF81606. PP2C-related. 1 hit. |
| PROSITE | PS51450. LRR. 17 hits. PS50003. PH_DOMAIN. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other | |
| NextBio | 611783. |
Entry information
| Entry name | PHLP1_RAT | ||||||||
| Accession | Primary (citable) accession number: Q9WTR8 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation program | Chordata Protein Annotation Program | ||||||||
Relevant documents
| SIMILARITY comments Index of protein domains and families |