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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 protein leveli

Functioni

Protein phosphatase involved in regulation of Akt and PKC signaling. Mediates dephosphorylation in the C-terminal domain hydrophobic motif of members of the AGC Ser/Thr protein kinase family; specifically acts on 'Ser-473' of AKT2 and AKT3, 'Ser-660' of PRKCB and 'Ser-657' of PRKCA (By similarity). Isoform 2 seems to have a major role in regulating Akt signaling in hippocampal neurons (By similarity). Akt 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 Akt triggers apoptosis and suppression of tumor growth. Dephosphorylation of PRKCA and PRKCB leads to their destabilization and degradation. Dephosphorylates STK4 on 'Thr-387' leading to STK4 activation and apoptosis. Dephosphorylates RPS6KB1 and is involved in regulation of cap-dependent translation. Inhibits cancer cell proliferation and may act as a tumor suppressor. Dephosphorylates RAF1 inhibiting its kinase activity. May act as a negative regulator of K-Ras signaling in membrane rafts (By similarity). Involved in the hippocampus-dependent long-term memory formation (PubMed:17382888). Involved in circadian control by regulating the consolidation of circadian periodicity after resetting (PubMed:20080691). Involved in development and function of regulatory T-cells (PubMed:21498666).By similarity3 Publications

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)DescriptionActionsGraphical viewLength
Metal bindingi1166Manganese 1By similarity1
Metal bindingi1166Manganese 2By similarity1
Metal bindingi1167Manganese 1; via carbonyl oxygenBy similarity1
Metal bindingi1330Manganese 2By similarity1
Metal bindingi1369Manganese 2By similarity1

GO - Molecular functioni

GO - Biological processi

  • apoptotic process Source: UniProtKB-KW
  • entrainment of circadian clock Source: MGI
  • negative regulation of protein kinase B signaling Source: MGI
  • regulation of apoptotic process Source: MGI
  • regulation of JNK cascade Source: MGI
  • regulation of MAPK cascade Source: MGI
  • regulation of p38MAPK cascade Source: MGI
  • regulation of T cell anergy Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protein phosphatase

Keywords - Biological processi

Apoptosis

Keywords - Ligandi

Manganese, Metal-binding

Enzyme and pathway databases

ReactomeiR-MMU-199418. 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
Proteomesi
  • UP000000589 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)DescriptionActionsGraphical viewLength
ChainiPRO_00000577821 – 1687PH domain leucine-rich repeat-containing protein phosphatase 1Add BLAST1687

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineBy similarity1
Modified residuei286PhosphoserineBy similarity1
Modified residuei372PhosphoserineBy similarity1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

PaxDbiQ8CHE4.
PeptideAtlasiQ8CHE4.
PRIDEiQ8CHE4.

PTM databases

iPTMnetiQ8CHE4.
PhosphoSitePlusiQ8CHE4.

Expressioni

Tissue specificityi

Isoforms 1 and 2 are expressed in the retina (PubMed:20089132).1 Publication

Inductioni

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

Gene expression databases

BgeeiENSMUSG00000044340.
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

BioGridi221058. 1 interactor.
IntActiQ8CHE4. 2 interactors.
MINTiMINT-4997715.
STRINGi10090.ENSMUSP00000056530.

Structurei

3D structure databases

ProteinModelPortaliQ8CHE4.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini492 – 592PHPROSITE-ProRule annotationAdd BLAST101
Repeati594 – 615LRR 1Add BLAST22
Repeati617 – 638LRR 2Add BLAST22
Repeati648 – 669LRR 3Add BLAST22
Repeati671 – 692LRR 4Add BLAST22
Repeati694 – 715LRR 5Add BLAST22
Repeati717 – 739LRR 6Add BLAST23
Repeati740 – 760LRR 7Add BLAST21
Repeati764 – 785LRR 8Add BLAST22
Repeati788 – 809LRR 9Add BLAST22
Repeati829 – 850LRR 10Add BLAST22
Repeati851 – 872LRR 11Add BLAST22
Repeati874 – 895LRR 12Add BLAST22
Repeati897 – 918LRR 13Add BLAST22
Repeati919 – 940LRR 14Add BLAST22
Repeati943 – 964LRR 15Add BLAST22
Repeati969 – 989LRR 16Add BLAST21
Repeati993 – 1014LRR 17Add BLAST22
Repeati1017 – 1038LRR 18Add BLAST22
Repeati1040 – 1061LRR 19Add BLAST22
Repeati1062 – 1083LRR 20Add BLAST22
Repeati1085 – 1106LRR 21Add BLAST22
Domaini1131 – 1378PPM-type phosphatasePROSITE-ProRule annotationAdd BLAST248

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi1685 – 1687PDZ-binding3

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi4 – 9Poly-Ala6
Compositional biasi21 – 27Poly-Ala7
Compositional biasi112 – 116Poly-Ala5
Compositional biasi337 – 340Poly-Gly4
Compositional biasi341 – 345Poly-Ser5
Compositional biasi399 – 404Poly-Ala6
Compositional biasi1424 – 1427Poly-Ser4
Compositional biasi1638 – 1648Poly-GlnAdd BLAST11

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

eggNOGiKOG0619. Eukaryota.
COG0631. LUCA.
COG4886. LUCA.
GeneTreeiENSGT00440000037833.
HOGENOMiHOG000115529.
InParanoidiQ8CHE4.
KOiK16340.
OMAiFTNGSRV.
OrthoDBiEOG091G03A3.
PhylomeDBiQ8CHE4.
TreeFamiTF315993.

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
3.60.40.10. 1 hit.
3.80.10.10. 3 hits.
InterProiIPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR003591. Leu-rich_rpt_typical-subtyp.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
IPR001932. PPM-type_phosphatase_dom.
[Graphical view]
PfamiPF13516. LRR_6. 1 hit.
PF13855. LRR_8. 1 hit.
PF00169. PH. 1 hit.
PF00481. PP2C. 1 hit.
[Graphical view]
SMARTiSM00369. LRR_TYP. 9 hits.
SM00332. PP2Cc. 1 hit.
[Graphical view]
SUPFAMiSSF50729. SSF50729. 2 hits.
SSF52058. SSF52058. 1 hit.
SSF81606. SSF81606. 1 hit.
PROSITEiPS51450. LRR. 17 hits.
PS50003. PH_DOMAIN. 1 hit.
PS51746. PPM_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8CHE4-1) [UniParc]FASTAAdd to basket
Also known as: beta

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.

« 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
Isoform 2 (identifier: Q8CHE4-2) [UniParc]FASTAAdd to basket
Also known as: alpha

The sequence of this isoform differs from the canonical sequence as follows:
     1-468: Missing.

Show »
Length:1,219
Mass (Da):134,965
Checksum:iEB222C83571C9050
GO

Sequence cautioni

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

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti724S → F in AAH59254 (PubMed:15489334).Curated1
Sequence conflicti1506E → K in AAH22703 (PubMed:15489334).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0578101 – 468Missing in isoform 2. Add BLAST468

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. [Q8CHE4-1]
RefSeqiNP_598582.3. NM_133821.3. [Q8CHE4-1]
UniGeneiMm.24115.

Genome annotation databases

EnsembliENSMUST00000061047; ENSMUSP00000056530; ENSMUSG00000044340. [Q8CHE4-1]
GeneIDi98432.
KEGGimmu:98432.
UCSCiuc007cgv.2. mouse. [Q8CHE4-1]

Keywords - Coding sequence diversityi

Alternative splicing

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. [Q8CHE4-1]
RefSeqiNP_598582.3. NM_133821.3. [Q8CHE4-1]
UniGeneiMm.24115.

3D structure databases

ProteinModelPortaliQ8CHE4.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi221058. 1 interactor.
IntActiQ8CHE4. 2 interactors.
MINTiMINT-4997715.
STRINGi10090.ENSMUSP00000056530.

PTM databases

iPTMnetiQ8CHE4.
PhosphoSitePlusiQ8CHE4.

Proteomic databases

PaxDbiQ8CHE4.
PeptideAtlasiQ8CHE4.
PRIDEiQ8CHE4.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000061047; ENSMUSP00000056530; ENSMUSG00000044340. [Q8CHE4-1]
GeneIDi98432.
KEGGimmu:98432.
UCSCiuc007cgv.2. mouse. [Q8CHE4-1]

Organism-specific databases

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

Phylogenomic databases

eggNOGiKOG0619. Eukaryota.
COG0631. LUCA.
COG4886. LUCA.
GeneTreeiENSGT00440000037833.
HOGENOMiHOG000115529.
InParanoidiQ8CHE4.
KOiK16340.
OMAiFTNGSRV.
OrthoDBiEOG091G03A3.
PhylomeDBiQ8CHE4.
TreeFamiTF315993.

Enzyme and pathway databases

ReactomeiR-MMU-199418. Negative regulation of the PI3K/AKT network.

Miscellaneous databases

PROiQ8CHE4.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000044340.
GenevisibleiQ8CHE4. MM.

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
3.60.40.10. 1 hit.
3.80.10.10. 3 hits.
InterProiIPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR003591. Leu-rich_rpt_typical-subtyp.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
IPR001932. PPM-type_phosphatase_dom.
[Graphical view]
PfamiPF13516. LRR_6. 1 hit.
PF13855. LRR_8. 1 hit.
PF00169. PH. 1 hit.
PF00481. PP2C. 1 hit.
[Graphical view]
SMARTiSM00369. LRR_TYP. 9 hits.
SM00332. PP2Cc. 1 hit.
[Graphical view]
SUPFAMiSSF50729. SSF50729. 2 hits.
SSF52058. SSF52058. 1 hit.
SSF81606. SSF81606. 1 hit.
PROSITEiPS51450. LRR. 17 hits.
PS50003. PH_DOMAIN. 1 hit.
PS51746. PPM_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

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: November 30, 2016
This is version 126 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

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 one 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.