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Protein

PH domain leucine-rich repeat-containing protein phosphatase 1

Gene

Phlpp1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: 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).By similarity

Catalytic activityi

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

Cofactori

Mn2+By similarityNote: 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 1By similarity
Metal bindingi1166 – 11661Manganese 2By similarity
Metal bindingi1167 – 11671Manganese 1; via carbonyl oxygenBy similarity
Metal bindingi1330 – 13301Manganese 2By similarity
Metal bindingi1369 – 13691Manganese 2By similarity

GO - Molecular functioni

GO - Biological processi

  • apoptotic process Source: UniProtKB-KW
  • 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_284913. 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 Componenti: Chromosome 1

Organism-specific databases

MGIiMGI:2138327. Phlpp1.

Subcellular locationi

GO - Cellular componenti

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-acetylmethionineBy similarity

Keywords - PTMi

Acetylation

Proteomic databases

MaxQBiQ8CHE4.
PaxDbiQ8CHE4.
PRIDEiQ8CHE4.

PTM databases

PhosphoSiteiQ8CHE4.

Expressioni

Inductioni

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

Gene expression databases

BgeeiQ8CHE4.
GenevisibleiQ8CHE4. MM.

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).By similarity

Protein-protein interaction databases

IntActiQ8CHE4. 1 interaction.
MINTiMINT-4997715.
STRINGi10090.ENSMUSP00000056530.

Structurei

3D structure databases

ProteinModelPortaliQ8CHE4.
SMRiQ8CHE4. Positions 582-1378.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini492 – 592101PHPROSITE-ProRule annotationAdd
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
Domaini1131 – 1378248PPM-type phosphatasePROSITE-ProRule annotationAdd
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 21 LRR (leucine-rich) repeats.Curated
Contains 1 PH domain.PROSITE-ProRule annotation
Contains 1 PPM-type phosphatase domain.PROSITE-ProRule annotation

Keywords - Domaini

Leucine-rich repeat, Repeat

Phylogenomic databases

eggNOGiCOG4886.
GeneTreeiENSGT00440000037833.
HOGENOMiHOG000115529.
InParanoidiQ8CHE4.
KOiK16340.
OMAiCLSNSFQ.
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. PPM-type_phosphatase_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.
PS51746. PPM_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q8CHE4-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEPAAAAPAQ RLADPTGEDQ ALAAAAAEGG RCPDPALSAA APSGGNGGAA
60 70 80 90 100
REEAPCEAPP GPLPGRAGGT GRRRRRGAPQ PAAGGAAPVP AAGGGANSLL
110 120 130 140 150
LKRGRLKRNL SAAAAASSSS SPSSASSAAG GLPASCSASA SLCTRSLDRK
160 170 180 190 200
TLLLKHRQLL QLQPSDRDWV RHQLQRGCVH VFDRHMASSY LRPVLCTLDT
210 220 230 240 250
TAAEVAARLL QLGHKGGGVV KVLGYGPPPA AAPAASDQTL DGEHGRDVEP
260 270 280 290 300
PPSSGTVGAV RGPARAPPAD LPLPGGAWTR CAPRISPAPS DSSPGELFAG
310 320 330 340 350
GPGSPPRAPR PASDTESFSL SPSAESVSDR LDPYSSGGGG SSSSSEELEA
360 370 380 390 400
DPAMPHRPGR PAQPRPPSPK TSALLQPKAP TGVDSTGVIA GEGPGDDKAM
410 420 430 440 450
AAAAPDVPLS TSGRIRETVQ KTSPPSLYVQ LHGETTRRLE ADEKPLQIQN
460 470 480 490 500
DYLFQLGFGE LWRVQEEGMD SEIGCLIRFY AGKPHSTGSS ERIQLSGMYN
510 520 530 540 550
VRKGKMQLPV NRWTRRQVIL CGTCLIVSSV KDSVSGKMHV LPLIGGKVEE
560 570 580 590 600
VKKHQHCLAF SSSGPQSQTY YICFDTFTEY LRWLRQVSKV ASQRISSVDL
610 620 630 640 650
SCCSLEHLPA NLFYSQDLTH LNLKQNFLRQ TPTLPAARGL GELQRFTKLK
660 670 680 690 700
SLNLSNNHLG AFPSAVCSIP TLAELNVSCN ALREVPAAVG DMQNLQTFLL
710 720 730 740 750
DGNFLQSLPA ELESMHQLSY LGLSFNEFTD IPEVLEKLTA VDKLCMAGNC
760 770 780 790 800
VETLRLQALR RMPHIKHVDL RLNILRKLMA DEVDFVQHVT QLDLRDNKLG
810 820 830 840 850
DLDAMIFNNI EVLHCERNQL VTLNVCGYFL KALYASSNEL AQLDVYPVPN
860 870 880 890 900
YLSYMDVSRN CLESVPEWVC ESRKLEVLDI GHNQICELPA RLFCNSSLRK
910 920 930 940 950
LLAGHNRLAR LPERLERTSV EVLDVQHNQI TELPPNLLMK ADSLRFLNAS
960 970 980 990 1000
ANKLETLPPA TLSEETSSIL QELYLTNNCL TDKCVPLLTG HPRLKILHMA
1010 1020 1030 1040 1050
YNRLQSFPAS KMAKLEELEE IDISGNKLKA IPTTIMNCRR MHTVIAHSNC
1060 1070 1080 1090 1100
IEVFPEVMQL PEVKCVDLSC NELSEITLPE NLPPKLQELD LTGNPRLALD
1110 1120 1130 1140 1150
HKSLELLNNI RCFKIDQPSA GDASGAPAVW SHGYTEASGV KNKLCVAALS
1160 1170 1180 1190 1200
VNNFRDNREA LYGVFDGDRN VEVPYLLQCT MSDILAEELQ KTKNEEEYMV
1210 1220 1230 1240 1250
NTFIVMQRKL GTAGQKLGGA AVLCHIKPDP VDLGGSFTLT SANVGKCQTV
1260 1270 1280 1290 1300
LCRNGKPLSL SRSYIMSCEE ERKRIKQHKA IITEDGKVNG VTESTRILGY
1310 1320 1330 1340 1350
TFLHPSVVPR PHVQSVLLTP QDEFFILGSK GLWDSLSIDE AVEAVRNVPD
1360 1370 1380 1390 1400
ALAAAKKLCT LAQSYGCHDS ISAVVVQLSV TEDSFCCCEL SAGGSMPPPS
1410 1420 1430 1440 1450
PGIFPPSVNM VIKDRPSDGL GVPSSSSGMA SEISSELSTS EMSSEVGSTA
1460 1470 1480 1490 1500
SDEPPSGVLN ESSPAYPNEQ RCMLHPVCLS NSFQRQLSSA TFSSAFSDNG
1510 1520 1530 1540 1550
LDSDDEEPIE GVFSNGSRVE VEVDIHCSRA KEKERQQHLL QVPAEASDEG
1560 1570 1580 1590 1600
IVISANEDES GLSKKADFSA VGTIGRRRAN GSVAPQERSH NVIEVAADAP
1610 1620 1630 1640 1650
LRKPGGYFAA PAQPDPDDQF IIPPELEEEV KEIMKHHQEQ QQQQQQQQLP
1660 1670 1680
PPPQPPQPQP QPQPQPQPQP QRHFQMDHLP DCYDTPL
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. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti724 – 7241S → F in AAH59254 (PubMed:15489334).Curated
Sequence conflicti1506 – 15061E → K in AAH22703 (PubMed:15489334).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

ProteinModelPortaliQ8CHE4.
SMRiQ8CHE4. Positions 582-1378.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ8CHE4. 1 interaction.
MINTiMINT-4997715.
STRINGi10090.ENSMUSP00000056530.

PTM databases

PhosphoSiteiQ8CHE4.

Proteomic databases

MaxQBiQ8CHE4.
PaxDbiQ8CHE4.
PRIDEiQ8CHE4.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi23239.
MGIiMGI:2138327. Phlpp1.
RougeiSearch...

Phylogenomic databases

eggNOGiCOG4886.
GeneTreeiENSGT00440000037833.
HOGENOMiHOG000115529.
InParanoidiQ8CHE4.
KOiK16340.
OMAiCLSNSFQ.
OrthoDBiEOG7RFTGK.
PhylomeDBiQ8CHE4.
TreeFamiTF315993.

Enzyme and pathway databases

ReactomeiREACT_284913. Negative regulation of the PI3K/AKT network.

Miscellaneous databases

NextBioi353478.
PROiQ8CHE4.
SOURCEiSearch...

Gene expression databases

BgeeiQ8CHE4.
GenevisibleiQ8CHE4. MM.

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. PPM-type_phosphatase_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.
PS51746. PPM_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

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: June 24, 2015
This is version 113 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

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.