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Q9WTR8

- PHLP1_RAT

UniProt

Q9WTR8 - PHLP1_RAT

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Protein
PH domain leucine-rich repeat protein phosphatase 1
Gene
Phlpp1, Phlpp, Plekhe1, Scop
Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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 activityi

[a protein]-serine/threonine phosphate + H2O = [a protein]-serine/threonine + phosphate.

Cofactori

Binds 2 manganese ions per subunit By similarity.

Enzyme regulationi

Insensitive to okadaic acid By similarity.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi1173 – 11731Manganese 1 By similarity
Metal bindingi1173 – 11731Manganese 2 By similarity
Metal bindingi1174 – 11741Manganese 1; via carbonyl oxygen By similarity
Metal bindingi1337 – 13371Manganese 2 By similarity
Metal bindingi1376 – 13761Manganese 2 By similarity

GO - Molecular functioni

  1. metal ion binding Source: UniProtKB-KW
  2. protein serine/threonine phosphatase activity Source: RGD

GO - Biological processi

  1. apoptotic process Source: UniProtKB-KW
  2. circadian rhythm Source: RGD
  3. protein dephosphorylation Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protein phosphatase

Keywords - Biological processi

Apoptosis

Keywords - Ligandi

Manganese, Metal-binding

Names & Taxonomyi

Protein namesi
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 namesi
Name:Phlpp1
Synonyms:Phlpp, Plekhe1, Scop
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Unplaced

Organism-specific databases

RGDi621308. Phlpp1.

Subcellular locationi

Cytoplasm. Membrane; Peripheral membrane protein. Nucleus By similarity 1 Publication

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB-SubCell
  2. membrane Source: UniProtKB-SubCell
  3. nucleus Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Keywords - Diseasei

Tumor suppressor

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 16961696PH domain leucine-rich repeat protein phosphatase 1
PRO_0000057783Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionine By similarity

Keywords - PTMi

Acetylation

Proteomic databases

PaxDbiQ9WTR8.
PRIDEiQ9WTR8.

Expressioni

Tissue specificityi

Mainly present in brain (at protein level).1 Publication

Developmental stagei

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).1 Publication

Gene expression databases

GenevestigatoriQ9WTR8.

Interactioni

Subunit structurei

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.1 Publication

Protein-protein interaction databases

BioGridi248740. 1 interaction.
IntActiQ9WTR8. 2 interactions.
STRINGi10116.ENSRNOP00000003840.

Structurei

3D structure databases

ProteinModelPortaliQ9WTR8.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini499 – 599101PH
Add
BLAST
Repeati601 – 62222LRR 1
Add
BLAST
Repeati624 – 64522LRR 2
Add
BLAST
Repeati655 – 67622LRR 3
Add
BLAST
Repeati678 – 69922LRR 4
Add
BLAST
Repeati701 – 72222LRR 5
Add
BLAST
Repeati724 – 74623LRR 6
Add
BLAST
Repeati836 – 85722LRR 7
Add
BLAST
Repeati858 – 87922LRR 8
Add
BLAST
Repeati881 – 90222LRR 9
Add
BLAST
Repeati904 – 92522LRR 10
Add
BLAST
Repeati926 – 94722LRR 11
Add
BLAST
Repeati950 – 97122LRR 12
Add
BLAST
Repeati976 – 99621LRR 13
Add
BLAST
Repeati1000 – 102122LRR 14
Add
BLAST
Repeati1024 – 104522LRR 15
Add
BLAST
Repeati1047 – 106822LRR 16
Add
BLAST
Repeati1069 – 109022LRR 17
Add
BLAST
Repeati1092 – 111322LRR 18
Add
BLAST
Domaini1128 – 1383256PP2C-like
Add
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi1694 – 16963PDZ-binding

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi4 – 96Poly-Ala
Compositional biasi21 – 288Poly-Ala
Compositional biasi116 – 12611Poly-Ser
Add
BLAST
Compositional biasi339 – 3435Poly-Ser
Compositional biasi405 – 4106Poly-Ala
Compositional biasi1431 – 14344Poly-Ser
Compositional biasi1645 – 166117Poly-Gln
Add
BLAST
Compositional biasi1662 – 16698Poly-Pro

Domaini

The PH domain is required for interaction with PRKCB and its dephosphorylation By similarity.

Sequence similaritiesi

Contains 1 PH domain.
Contains 1 PP2C-like domain.

Keywords - Domaini

Leucine-rich repeat, Repeat

Phylogenomic databases

eggNOGiCOG4886.
HOGENOMiHOG000115529.
InParanoidiQ9WTR8.
KOiK16340.
PhylomeDBiQ9WTR8.

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
3.60.40.10. 1 hit.
InterProiIPR001611. Leu-rich_rpt.
IPR001849. PH_domain.
IPR011993. PH_like_dom.
IPR001932. PP2C-like_dom.
[Graphical view]
PfamiPF00560. LRR_1. 2 hits.
PF13855. LRR_8. 2 hits.
PF00481. PP2C. 1 hit.
[Graphical view]
SMARTiSM00233. PH. 1 hit.
SM00332. PP2Cc. 1 hit.
[Graphical view]
SUPFAMiSSF81606. SSF81606. 1 hit.
PROSITEiPS51450. LRR. 17 hits.
PS50003. PH_DOMAIN. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9WTR8-1 [UniParc]FASTAAdd to Basket

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MEPAAAAPAQ RLADPTGEDR APAAAAAAEG GRSPDSVLSA AAPSGGNGGA     50
AREEAPCEAP PGPLPGRAGG TGRRRRRGVP QPAAGGAAPV TAAGGGANSL 100
LLRRGRLKRN LSAAASSSSS PSSASSAAGG LPASCSASAS LCTRSLDRKT 150
LLQKHRQLLQ LQPSDRDWVR HQLQRGCVHV FDRHMASSYL RPVLCTLDTT 200
AAEVAARLLQ LGHKGGGVVK VLGHGPPPAA APAASDQTPA TELGRDVEPP 250
PSSSTVGAVR GPARAPPADL PLPGGAWTRC APRVNPAPSD SSPGELFAGG 300
PCSPSRAPRP ASDTESFSLS PSAESVSDRL DPYSSGGGSS SSSEELEADP 350
ATVLTGPSGP PHHPVRSSQP RPPSPKTSAL LQPKAPTGVD GTGLVVGEGP 400
GDDKAVAAAA PGVPLWTPGR IRETVQKTSS PPSLYVQLHG ETTRRLEADE 450
KPLQIQNDYL FQLGFGELWR VQEEGMDSEI GCLIRFYAGK PHSTGSSERI 500
QLSGMYNVRK GKMQLPVNRW TRRQVILCGT CLIVSSVKDS SSGKMHVLPL 550
IGGKVEEVKK HQHCLAFSSS GPQSQTYYIC FDTFTEYLRW LRQVSKVASQ 600
RISSVDLSCC SLEHLPANLF YSQDLTHLNL KQNFLRQNPS LPAARGLGEL 650
QRFTKLKSLN LSNNHLGAFP SAVCSIPTLA ELNVSCNALQ EVPAAVGAMQ 700
NLQTFLLDGN FLQSLPAELE NMHQLSYLGL SFNEFTDIPE VLEKLTAVDK 750
LCMAGNCMET LRLQALRRMP HIKHVDLRLN ILRKLITDEV DFLQHVTQLD 800
LRDNKLGDLD AMIFNNIEVL HCERNQLVTL NICGYFLKAL YASSNELVQL 850
DVYPVPNYLS YMDVSRNCLE SVPEWVCESR KLEVLDIGHN QICELPARLF 900
CNSSLRKLLA GHNRLARLPE RLERTSVEVL DVQHNQIIEL PPNLLMKADS 950
LRFLNASANK LETLPPATLS EETSSILQEL YLTNNSLTDK CVPLLTGHPR 1000
LKILHMAYNR LQSFPASKMA KLEELEEIDI SGNKLKAIPT TIMNCRRMHT 1050
VIAHSNCIEV FPEVMQLPEV KCVDLSCNEL SEITLPENLP PKLQELDLTG 1100
NPRLALDHKS LELLNNIRCF KIDQPSAGDA SGAPAVWSHG YTEASGVKNK 1150
LCVAALSVNN FRDNREALYG VFDGDRNVEV PYLLQCTMSD ILAEELQKTK 1200
NEEEYMVNTF IVMQRKLGTA GQKLGGAAVL CHIRHDPVDL GGSFTLTSAN 1250
VGKCQTVLCR NGKPLSLSRS YTMSCEEERK RIKQHKAIIT EDGKVNGVTE 1300
STRILGYTFL HPSVVPRPHV QSVLLTPQDE FFILGSKGLW DSLSIEEAVE 1350
AVRNVPDALA AAKKLCTLAQ SYGCHDSISA VVVQLSVTED SFCCCELSVG 1400
GSMPPPSPGI FPPSVSMVIK DRPSDGLGVP SSSSGMASEI SSELSTSEMS 1450
SEVGSTASDE PPSGALSESS PAYPSEQRCM LHPVCLSNSF QRQLSSATFS 1500
SAFSDNGLDS DDEEPIEGVF SNGSRVEVEV DIHCSRAKEK ERQQHLLQVP 1550
AEASDEGIVI SANEDESGLS KKTDISAVGT IGRRRANGSV PPQERSHNVI 1600
EVATDAPLRK PGGYFAAPAQ PDPDDQFIIP PELEEEVKEI MKHHQEQQQQ 1650
QQQQQQQQQQ QPPPPPQPPQ AQAQAQAQAQ RPFQMDHLPD CYDTPL 1696
Length:1,696
Mass (Da):183,364
Last modified:November 1, 1999 - v1
Checksum:iB4C3CC777B8BB6A9
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AB023624 mRNA. Translation: BAA77767.1.
RefSeqiNP_067689.1. NM_021657.1.
UniGeneiRn.163214.

Genome annotation databases

GeneIDi59265.
KEGGirno:59265.
UCSCiRGD:621308. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AB023624 mRNA. Translation: BAA77767.1 .
RefSeqi NP_067689.1. NM_021657.1.
UniGenei Rn.163214.

3D structure databases

ProteinModelPortali Q9WTR8.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 248740. 1 interaction.
IntActi Q9WTR8. 2 interactions.
STRINGi 10116.ENSRNOP00000003840.

Proteomic databases

PaxDbi Q9WTR8.
PRIDEi Q9WTR8.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 59265.
KEGGi rno:59265.
UCSCi RGD:621308. rat.

Organism-specific databases

CTDi 23239.
RGDi 621308. Phlpp1.

Phylogenomic databases

eggNOGi COG4886.
HOGENOMi HOG000115529.
InParanoidi Q9WTR8.
KOi K16340.
PhylomeDBi Q9WTR8.

Miscellaneous databases

NextBioi 611783.
PROi Q9WTR8.

Gene expression databases

Genevestigatori Q9WTR8.

Family and domain databases

Gene3Di 2.30.29.30. 1 hit.
3.60.40.10. 1 hit.
InterProi IPR001611. Leu-rich_rpt.
IPR001849. PH_domain.
IPR011993. PH_like_dom.
IPR001932. PP2C-like_dom.
[Graphical view ]
Pfami PF00560. LRR_1. 2 hits.
PF13855. LRR_8. 2 hits.
PF00481. PP2C. 1 hit.
[Graphical view ]
SMARTi SM00233. PH. 1 hit.
SM00332. PP2Cc. 1 hit.
[Graphical view ]
SUPFAMi SSF81606. SSF81606. 1 hit.
PROSITEi PS51450. LRR. 17 hits.
PS50003. PH_DOMAIN. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  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.

Entry informationi

Entry nameiPHLP1_RAT
AccessioniPrimary (citable) accession number: Q9WTR8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 7, 2005
Last sequence update: November 1, 1999
Last modified: September 3, 2014
This is version 100 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi