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Q8CHE4

- PHLP1_MOUSE

UniProt

Q8CHE4 - PHLP1_MOUSE

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Protein

PH domain leucine-rich repeat-containing protein phosphatase 1

Gene
Phlpp1, Kiaa0606, Phlpp, Plekhe1, Scop
Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at transcript leveli

Functioni

Protein phosphatase that mediates dephosphorylation of 'Ser-473' of AKT1, 'Ser-660' of PRKCB, 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. May act as a negative regulator of K-Ras signaling in membrane rafts By similarity.

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 bindingi1166 – 11661Manganese 1 By similarity
Metal bindingi1166 – 11661Manganese 2 By similarity
Metal bindingi1167 – 11671Manganese 1; via carbonyl oxygen By similarity
Metal bindingi1330 – 13301Manganese 2 By similarity
Metal bindingi1369 – 13691Manganese 2 By similarity

GO - Molecular functioni

  1. metal ion binding Source: UniProtKB-KW
  2. phosphoprotein phosphatase activity Source: UniProtKB-KW

GO - Biological processi

  1. apoptotic process Source: UniProtKB-KW
  2. entrainment of circadian clock Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protein phosphatase

Keywords - Biological processi

Apoptosis

Keywords - Ligandi

Manganese, Metal-binding

Enzyme and pathway databases

ReactomeiREACT_214733. Negative regulation of the PI3K/AKT network.

Names & Taxonomyi

Protein namesi
Recommended name:
PH domain leucine-rich repeat-containing 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:Kiaa0606, Phlpp, Plekhe1, Scop
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 1

Organism-specific databases

MGIiMGI:2138327. Phlpp1.

Subcellular locationi

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 16871687PH domain leucine-rich repeat-containing protein phosphatase 1PRO_0000057782Add
BLAST

Amino acid modifications

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

Keywords - PTMi

Acetylation

Proteomic databases

PaxDbiQ8CHE4.
PRIDEiQ8CHE4.

PTM databases

PhosphoSiteiQ8CHE4.

Expressioni

Inductioni

Up-regulated in the hippocampus upon chronic methamphetamine treatment.1 Publication

Gene expression databases

BgeeiQ8CHE4.
GenevestigatoriQ8CHE4.

Interactioni

Subunit structurei

Interacts with the nucleotide free form of K-Ras (KRAS) via its LRR repeats. Interacts with AKT2, AKT3 and PRKCB By similarity.

Protein-protein interaction databases

IntActiQ8CHE4. 1 interaction.
MINTiMINT-4997715.

Structurei

3D structure databases

ProteinModelPortaliQ8CHE4.
SMRiQ8CHE4. Positions 598-1378.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini492 – 592101PHAdd
BLAST
Repeati594 – 61522LRR 1Add
BLAST
Repeati617 – 63822LRR 2Add
BLAST
Repeati648 – 66922LRR 3Add
BLAST
Repeati671 – 69222LRR 4Add
BLAST
Repeati694 – 71522LRR 5Add
BLAST
Repeati717 – 73923LRR 6Add
BLAST
Repeati740 – 76021LRR 7Add
BLAST
Repeati764 – 78522LRR 8Add
BLAST
Repeati788 – 80922LRR 9Add
BLAST
Repeati829 – 85022LRR 10Add
BLAST
Repeati851 – 87222LRR 11Add
BLAST
Repeati874 – 89522LRR 12Add
BLAST
Repeati897 – 91822LRR 13Add
BLAST
Repeati919 – 94022LRR 14Add
BLAST
Repeati943 – 96422LRR 15Add
BLAST
Repeati969 – 98921LRR 16Add
BLAST
Repeati993 – 101422LRR 17Add
BLAST
Repeati1017 – 103822LRR 18Add
BLAST
Repeati1040 – 106122LRR 19Add
BLAST
Repeati1062 – 108322LRR 20Add
BLAST
Repeati1085 – 110622LRR 21Add
BLAST
Domaini1121 – 1376256PP2C-likeAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi1685 – 16873PDZ-binding

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi4 – 96Poly-Ala
Compositional biasi21 – 277Poly-Ala
Compositional biasi112 – 1165Poly-Ala
Compositional biasi337 – 3404Poly-Gly
Compositional biasi341 – 3455Poly-Ser
Compositional biasi399 – 4046Poly-Ala
Compositional biasi1424 – 14274Poly-Ser
Compositional biasi1638 – 164811Poly-GlnAdd
BLAST

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.
GeneTreeiENSGT00440000037833.
HOGENOMiHOG000115529.
InParanoidiQ8CHE4.
KOiK16340.
OMAiFTNGSRV.
OrthoDBiEOG7RFTGK.
PhylomeDBiQ8CHE4.
TreeFamiTF315993.

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. 3 hits.
PF13855. LRR_8. 1 hit.
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.

Q8CHE4-1 [UniParc]FASTAAdd to Basket

« Hide

MEPAAAAPAQ RLADPTGEDQ ALAAAAAEGG RCPDPALSAA APSGGNGGAA     50
REEAPCEAPP GPLPGRAGGT GRRRRRGAPQ PAAGGAAPVP AAGGGANSLL 100
LKRGRLKRNL SAAAAASSSS SPSSASSAAG GLPASCSASA SLCTRSLDRK 150
TLLLKHRQLL QLQPSDRDWV RHQLQRGCVH VFDRHMASSY LRPVLCTLDT 200
TAAEVAARLL QLGHKGGGVV KVLGYGPPPA AAPAASDQTL DGEHGRDVEP 250
PPSSGTVGAV RGPARAPPAD LPLPGGAWTR CAPRISPAPS DSSPGELFAG 300
GPGSPPRAPR PASDTESFSL SPSAESVSDR LDPYSSGGGG SSSSSEELEA 350
DPAMPHRPGR PAQPRPPSPK TSALLQPKAP TGVDSTGVIA GEGPGDDKAM 400
AAAAPDVPLS TSGRIRETVQ KTSPPSLYVQ LHGETTRRLE ADEKPLQIQN 450
DYLFQLGFGE LWRVQEEGMD SEIGCLIRFY AGKPHSTGSS ERIQLSGMYN 500
VRKGKMQLPV NRWTRRQVIL CGTCLIVSSV KDSVSGKMHV LPLIGGKVEE 550
VKKHQHCLAF SSSGPQSQTY YICFDTFTEY LRWLRQVSKV ASQRISSVDL 600
SCCSLEHLPA NLFYSQDLTH LNLKQNFLRQ TPTLPAARGL GELQRFTKLK 650
SLNLSNNHLG AFPSAVCSIP TLAELNVSCN ALREVPAAVG DMQNLQTFLL 700
DGNFLQSLPA ELESMHQLSY LGLSFNEFTD IPEVLEKLTA VDKLCMAGNC 750
VETLRLQALR RMPHIKHVDL RLNILRKLMA DEVDFVQHVT QLDLRDNKLG 800
DLDAMIFNNI EVLHCERNQL VTLNVCGYFL KALYASSNEL AQLDVYPVPN 850
YLSYMDVSRN CLESVPEWVC ESRKLEVLDI GHNQICELPA RLFCNSSLRK 900
LLAGHNRLAR LPERLERTSV EVLDVQHNQI TELPPNLLMK ADSLRFLNAS 950
ANKLETLPPA TLSEETSSIL QELYLTNNCL TDKCVPLLTG HPRLKILHMA 1000
YNRLQSFPAS KMAKLEELEE IDISGNKLKA IPTTIMNCRR MHTVIAHSNC 1050
IEVFPEVMQL PEVKCVDLSC NELSEITLPE NLPPKLQELD LTGNPRLALD 1100
HKSLELLNNI RCFKIDQPSA GDASGAPAVW SHGYTEASGV KNKLCVAALS 1150
VNNFRDNREA LYGVFDGDRN VEVPYLLQCT MSDILAEELQ KTKNEEEYMV 1200
NTFIVMQRKL GTAGQKLGGA AVLCHIKPDP VDLGGSFTLT SANVGKCQTV 1250
LCRNGKPLSL SRSYIMSCEE ERKRIKQHKA IITEDGKVNG VTESTRILGY 1300
TFLHPSVVPR PHVQSVLLTP QDEFFILGSK GLWDSLSIDE AVEAVRNVPD 1350
ALAAAKKLCT LAQSYGCHDS ISAVVVQLSV TEDSFCCCEL SAGGSMPPPS 1400
PGIFPPSVNM VIKDRPSDGL GVPSSSSGMA SEISSELSTS EMSSEVGSTA 1450
SDEPPSGVLN ESSPAYPNEQ RCMLHPVCLS NSFQRQLSSA TFSSAFSDNG 1500
LDSDDEEPIE GVFSNGSRVE VEVDIHCSRA KEKERQQHLL QVPAEASDEG 1550
IVISANEDES GLSKKADFSA VGTIGRRRAN GSVAPQERSH NVIEVAADAP 1600
LRKPGGYFAA PAQPDPDDQF IIPPELEEEV KEIMKHHQEQ QQQQQQQQLP 1650
PPPQPPQPQP QPQPQPQPQP QRHFQMDHLP DCYDTPL 1687
Length:1,687
Mass (Da):182,367
Last modified:June 7, 2005 - v2
Checksum:i32B0809AAB3D2412
GO

Sequence cautioni

The sequence AAH59254.1 differs from that shown. Reason: Frameshift at position 34.

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti724 – 7241S → F in AAH59254. 1 Publication
Sequence conflicti1506 – 15061E → K in AAH22703. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AC101663 Genomic DNA. No translation available.
AC124710 Genomic DNA. No translation available.
AC144773 Genomic DNA. No translation available.
AB093251 mRNA. Translation: BAC41435.1.
BC004581 mRNA. Translation: AAH04581.1.
BC022703 mRNA. Translation: AAH22703.1.
BC024670 mRNA. Translation: AAH24670.1.
BC059254 mRNA. Translation: AAH59254.1. Frameshift.
CCDSiCCDS48337.1.
RefSeqiNP_598582.3. NM_133821.3.
UniGeneiMm.24115.

Genome annotation databases

EnsembliENSMUST00000061047; ENSMUSP00000056530; ENSMUSG00000044340.
GeneIDi98432.
KEGGimmu:98432.
UCSCiuc007cgv.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AC101663 Genomic DNA. No translation available.
AC124710 Genomic DNA. No translation available.
AC144773 Genomic DNA. No translation available.
AB093251 mRNA. Translation: BAC41435.1 .
BC004581 mRNA. Translation: AAH04581.1 .
BC022703 mRNA. Translation: AAH22703.1 .
BC024670 mRNA. Translation: AAH24670.1 .
BC059254 mRNA. Translation: AAH59254.1 . Frameshift.
CCDSi CCDS48337.1.
RefSeqi NP_598582.3. NM_133821.3.
UniGenei Mm.24115.

3D structure databases

ProteinModelPortali Q8CHE4.
SMRi Q8CHE4. Positions 598-1378.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

IntActi Q8CHE4. 1 interaction.
MINTi MINT-4997715.

PTM databases

PhosphoSitei Q8CHE4.

Proteomic databases

PaxDbi Q8CHE4.
PRIDEi Q8CHE4.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000061047 ; ENSMUSP00000056530 ; ENSMUSG00000044340 .
GeneIDi 98432.
KEGGi mmu:98432.
UCSCi uc007cgv.2. mouse.

Organism-specific databases

CTDi 23239.
MGIi MGI:2138327. Phlpp1.
Rougei Search...

Phylogenomic databases

eggNOGi COG4886.
GeneTreei ENSGT00440000037833.
HOGENOMi HOG000115529.
InParanoidi Q8CHE4.
KOi K16340.
OMAi FTNGSRV.
OrthoDBi EOG7RFTGK.
PhylomeDBi Q8CHE4.
TreeFami TF315993.

Enzyme and pathway databases

Reactomei REACT_214733. Negative regulation of the PI3K/AKT network.

Miscellaneous databases

NextBioi 353478.
PROi Q8CHE4.
SOURCEi Search...

Gene expression databases

Bgeei Q8CHE4.
Genevestigatori Q8CHE4.

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. 3 hits.
PF13855. LRR_8. 1 hit.
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

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  2. "Prediction of the coding sequences of mouse homologues of KIAA gene: I. The complete nucleotide sequences of 100 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries."
    Okazaki N., Kikuno R., Ohara R., Inamoto S., Hara Y., Nagase T., Ohara O., Koga H.
    DNA Res. 9:179-188(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 370-1687.
    Tissue: Brain.
  3. "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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 424-1687.
    Strain: C57BL/6, Czech II and FVB/N.
    Tissue: Brain and Mammary tumor.
  4. "Changes in expression of the mouse homologues of KIAA genes after subchronic methamphetamine treatment."
    Yamamoto H., Imai K., Takamatsu Y., Kamegaya E., Hara Y., Shimada K., Yamamoto T., Shen H.W., Hagino Y., Kobayashi H., Ide S., Sora I., Koga H., Ikedaa K.
    Ann. N. Y. Acad. Sci. 1025:92-101(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION.

Entry informationi

Entry nameiPHLP1_MOUSE
AccessioniPrimary (citable) accession number: Q8CHE4
Secondary accession number(s): Q6PCN0
, Q8QZU8, Q8R5E5, Q99KL6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 7, 2005
Last sequence update: June 7, 2005
Last modified: September 3, 2014
This is version 106 of the entry and version 2 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi