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Q8CHE4 (PHLP1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 102. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Phlpp1
Synonyms:Kiaa0606, Phlpp, Plekhe1, Scop
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1687 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

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 activity

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

Subcellular location

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

Induction

Up-regulated in the hippocampus upon chronic methamphetamine treatment. Ref.4

Domain

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

Sequence similarities

Contains 21 LRR (leucine-rich) repeats.

Contains 1 PH domain.

Contains 1 PP2C-like domain.

Sequence caution

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

Ontologies

Keywords
   Biological processApoptosis
   Cellular componentCytoplasm
Membrane
Nucleus
   DomainLeucine-rich repeat
Repeat
   LigandManganese
Metal-binding
   Molecular functionHydrolase
Protein phosphatase
   PTMAcetylation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processapoptotic process

Inferred from electronic annotation. Source: UniProtKB-KW

entrainment of circadian clock

Inferred from mutant phenotype PubMed 20080691. Source: MGI

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionmetal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

phosphoprotein phosphatase activity

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 16871687PH domain leucine-rich repeat-containing protein phosphatase 1
PRO_0000057782

Regions

Domain492 – 592101PH
Repeat594 – 61522LRR 1
Repeat617 – 63822LRR 2
Repeat648 – 66922LRR 3
Repeat671 – 69222LRR 4
Repeat694 – 71522LRR 5
Repeat717 – 73923LRR 6
Repeat740 – 76021LRR 7
Repeat764 – 78522LRR 8
Repeat788 – 80922LRR 9
Repeat829 – 85022LRR 10
Repeat851 – 87222LRR 11
Repeat874 – 89522LRR 12
Repeat897 – 91822LRR 13
Repeat919 – 94022LRR 14
Repeat943 – 96422LRR 15
Repeat969 – 98921LRR 16
Repeat993 – 101422LRR 17
Repeat1017 – 103822LRR 18
Repeat1040 – 106122LRR 19
Repeat1062 – 108322LRR 20
Repeat1085 – 110622LRR 21
Domain1121 – 1376256PP2C-like
Motif1685 – 16873PDZ-binding
Compositional bias4 – 96Poly-Ala
Compositional bias21 – 277Poly-Ala
Compositional bias112 – 1165Poly-Ala
Compositional bias337 – 3404Poly-Gly
Compositional bias341 – 3455Poly-Ser
Compositional bias399 – 4046Poly-Ala
Compositional bias1424 – 14274Poly-Ser
Compositional bias1638 – 164811Poly-Gln

Sites

Metal binding11661Manganese 1 By similarity
Metal binding11661Manganese 2 By similarity
Metal binding11671Manganese 1; via carbonyl oxygen By similarity
Metal binding13301Manganese 2 By similarity
Metal binding13691Manganese 2 By similarity

Amino acid modifications

Modified residue11N-acetylmethionine By similarity

Experimental info

Sequence conflict7241S → F in AAH59254. Ref.3
Sequence conflict15061E → K in AAH22703. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Q8CHE4 [UniParc].

Last modified June 7, 2005. Version 2.
Checksum: 32B0809AAB3D2412

FASTA1,687182,367
        10         20         30         40         50         60 
MEPAAAAPAQ RLADPTGEDQ ALAAAAAEGG RCPDPALSAA APSGGNGGAA REEAPCEAPP 

        70         80         90        100        110        120 
GPLPGRAGGT GRRRRRGAPQ PAAGGAAPVP AAGGGANSLL LKRGRLKRNL SAAAAASSSS 

       130        140        150        160        170        180 
SPSSASSAAG GLPASCSASA SLCTRSLDRK TLLLKHRQLL QLQPSDRDWV RHQLQRGCVH 

       190        200        210        220        230        240 
VFDRHMASSY LRPVLCTLDT TAAEVAARLL QLGHKGGGVV KVLGYGPPPA AAPAASDQTL 

       250        260        270        280        290        300 
DGEHGRDVEP PPSSGTVGAV RGPARAPPAD LPLPGGAWTR CAPRISPAPS DSSPGELFAG 

       310        320        330        340        350        360 
GPGSPPRAPR PASDTESFSL SPSAESVSDR LDPYSSGGGG SSSSSEELEA DPAMPHRPGR 

       370        380        390        400        410        420 
PAQPRPPSPK TSALLQPKAP TGVDSTGVIA GEGPGDDKAM AAAAPDVPLS TSGRIRETVQ 

       430        440        450        460        470        480 
KTSPPSLYVQ LHGETTRRLE ADEKPLQIQN DYLFQLGFGE LWRVQEEGMD SEIGCLIRFY 

       490        500        510        520        530        540 
AGKPHSTGSS ERIQLSGMYN VRKGKMQLPV NRWTRRQVIL CGTCLIVSSV KDSVSGKMHV 

       550        560        570        580        590        600 
LPLIGGKVEE VKKHQHCLAF SSSGPQSQTY YICFDTFTEY LRWLRQVSKV ASQRISSVDL 

       610        620        630        640        650        660 
SCCSLEHLPA NLFYSQDLTH LNLKQNFLRQ TPTLPAARGL GELQRFTKLK SLNLSNNHLG 

       670        680        690        700        710        720 
AFPSAVCSIP TLAELNVSCN ALREVPAAVG DMQNLQTFLL DGNFLQSLPA ELESMHQLSY 

       730        740        750        760        770        780 
LGLSFNEFTD IPEVLEKLTA VDKLCMAGNC VETLRLQALR RMPHIKHVDL RLNILRKLMA 

       790        800        810        820        830        840 
DEVDFVQHVT QLDLRDNKLG DLDAMIFNNI EVLHCERNQL VTLNVCGYFL KALYASSNEL 

       850        860        870        880        890        900 
AQLDVYPVPN YLSYMDVSRN CLESVPEWVC ESRKLEVLDI GHNQICELPA RLFCNSSLRK 

       910        920        930        940        950        960 
LLAGHNRLAR LPERLERTSV EVLDVQHNQI TELPPNLLMK ADSLRFLNAS ANKLETLPPA 

       970        980        990       1000       1010       1020 
TLSEETSSIL QELYLTNNCL TDKCVPLLTG HPRLKILHMA YNRLQSFPAS KMAKLEELEE 

      1030       1040       1050       1060       1070       1080 
IDISGNKLKA IPTTIMNCRR MHTVIAHSNC IEVFPEVMQL PEVKCVDLSC NELSEITLPE 

      1090       1100       1110       1120       1130       1140 
NLPPKLQELD LTGNPRLALD HKSLELLNNI RCFKIDQPSA GDASGAPAVW SHGYTEASGV 

      1150       1160       1170       1180       1190       1200 
KNKLCVAALS VNNFRDNREA LYGVFDGDRN VEVPYLLQCT MSDILAEELQ KTKNEEEYMV 

      1210       1220       1230       1240       1250       1260 
NTFIVMQRKL GTAGQKLGGA AVLCHIKPDP VDLGGSFTLT SANVGKCQTV LCRNGKPLSL 

      1270       1280       1290       1300       1310       1320 
SRSYIMSCEE ERKRIKQHKA IITEDGKVNG VTESTRILGY TFLHPSVVPR PHVQSVLLTP 

      1330       1340       1350       1360       1370       1380 
QDEFFILGSK GLWDSLSIDE AVEAVRNVPD ALAAAKKLCT LAQSYGCHDS ISAVVVQLSV 

      1390       1400       1410       1420       1430       1440 
TEDSFCCCEL SAGGSMPPPS PGIFPPSVNM VIKDRPSDGL GVPSSSSGMA SEISSELSTS 

      1450       1460       1470       1480       1490       1500 
EMSSEVGSTA SDEPPSGVLN ESSPAYPNEQ RCMLHPVCLS NSFQRQLSSA TFSSAFSDNG 

      1510       1520       1530       1540       1550       1560 
LDSDDEEPIE GVFSNGSRVE VEVDIHCSRA KEKERQQHLL QVPAEASDEG IVISANEDES 

      1570       1580       1590       1600       1610       1620 
GLSKKADFSA VGTIGRRRAN GSVAPQERSH NVIEVAADAP LRKPGGYFAA PAQPDPDDQF 

      1630       1640       1650       1660       1670       1680 
IIPPELEEEV KEIMKHHQEQ QQQQQQQQLP PPPQPPQPQP QPQPQPQPQP QRHFQMDHLP 


DCYDTPL 

« Hide

References

« Hide 'large scale' references
[1]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_598582.3. NM_133821.3.
UniGeneMm.24115.

3D structure databases

ProteinModelPortalQ8CHE4.
SMRQ8CHE4. Positions 585-1381.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ8CHE4. 1 interaction.
MINTMINT-4997715.

PTM databases

PhosphoSiteQ8CHE4.

Proteomic databases

PaxDbQ8CHE4.
PRIDEQ8CHE4.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000061047; ENSMUSP00000056530; ENSMUSG00000044340.
GeneID98432.
KEGGmmu:98432.
UCSCuc007cgv.2. mouse.

Organism-specific databases

CTD23239.
MGIMGI:2138327. Phlpp1.
RougeSearch...

Phylogenomic databases

eggNOGCOG4886.
GeneTreeENSGT00440000037833.
HOGENOMHOG000115529.
InParanoidQ8CHE4.
KOK16340.
OMAFTNGSRV.
OrthoDBEOG7RFTGK.
PhylomeDBQ8CHE4.
TreeFamTF315993.

Gene expression databases

BgeeQ8CHE4.
GenevestigatorQ8CHE4.

Family and domain databases

Gene3D2.30.29.30. 1 hit.
3.60.40.10. 1 hit.
InterProIPR001611. Leu-rich_rpt.
IPR011993. PH_like_dom.
IPR001849. Pleckstrin_homology.
IPR001932. PP2C-like_dom.
[Graphical view]
PfamPF00560. LRR_1. 3 hits.
PF00481. PP2C. 1 hit.
[Graphical view]
SMARTSM00233. PH. 1 hit.
SM00332. PP2Cc. 1 hit.
[Graphical view]
SUPFAMSSF81606. SSF81606. 1 hit.
PROSITEPS51450. LRR. 17 hits.
PS50003. PH_DOMAIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio353478.
PROQ8CHE4.
SOURCESearch...

Entry information

Entry namePHLP1_MOUSE
AccessionPrimary (citable) accession number: Q8CHE4
Secondary accession number(s): Q6PCN0 expand/collapse secondary AC list , Q8QZU8, Q8R5E5, Q99KL6
Entry history
Integrated into UniProtKB/Swiss-Prot: June 7, 2005
Last sequence update: June 7, 2005
Last modified: April 16, 2014
This is version 102 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot