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Protein

PH domain leucine-rich repeat-containing protein phosphatase 2

Gene

Phlpp2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at protein 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 decreases cell proliferation. Also controls the phosphorylation of AKT3. Dephosphorylation of PRKCA and PRKCB leads to their destabilization and degradation. Inhibits cancer cell proliferation and may act as a tumor suppressor (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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi817 – 8171Manganese 1By similarity
Metal bindingi817 – 8171Manganese 2By similarity
Metal bindingi818 – 8181Manganese 1; via carbonyl oxygenBy similarity
Metal bindingi982 – 9821Manganese 2By similarity
Metal bindingi1021 – 10211Manganese 2By similarity

GO - Molecular functioni

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protein phosphatase

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 2 (EC:3.1.3.16)
Alternative name(s):
PH domain leucine-rich repeat-containing protein phosphatase-like
Short name:
PHLPP-like
Gene namesi
Name:Phlpp2
Synonyms:Phlppl
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 8

Organism-specific databases

MGIiMGI:2444928. Phlpp2.

Subcellular locationi

GO - Cellular componenti

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 – 13201320PH domain leucine-rich repeat-containing protein phosphatase 2PRO_0000057785Add
BLAST

Proteomic databases

MaxQBiQ8BXA7.
PaxDbiQ8BXA7.
PRIDEiQ8BXA7.

PTM databases

PhosphoSiteiQ8BXA7.

Expressioni

Gene expression databases

BgeeiQ8BXA7.
ExpressionAtlasiQ8BXA7. baseline and differential.
GenevisibleiQ8BXA7. MM.

Interactioni

Subunit structurei

Interacts with AKT1, AKT3 and PRKCB.By similarity

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000136166.

Structurei

3D structure databases

ProteinModelPortaliQ8BXA7.
SMRiQ8BXA7. Positions 249-769, 783-1030.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini147 – 24599PHAdd
BLAST
Repeati247 – 26822LRR 1Add
BLAST
Repeati270 – 29324LRR 2Add
BLAST
Repeati297 – 31822LRR 3Add
BLAST
Repeati320 – 34122LRR 4Add
BLAST
Repeati343 – 36422LRR 5Add
BLAST
Repeati366 – 38823LRR 6Add
BLAST
Repeati389 – 40921LRR 7Add
BLAST
Repeati413 – 43422LRR 8Add
BLAST
Repeati437 – 45721LRR 9Add
BLAST
Repeati458 – 47720LRR 10Add
BLAST
Repeati478 – 49922LRR 11Add
BLAST
Repeati500 – 52122LRR 12Add
BLAST
Repeati523 – 54422LRR 13Add
BLAST
Repeati546 – 56722LRR 14Add
BLAST
Repeati568 – 58922LRR 15Add
BLAST
Repeati592 – 61322LRR 16Add
BLAST
Repeati618 – 64124LRR 17Add
BLAST
Repeati642 – 66322LRR 18Add
BLAST
Repeati666 – 68722LRR 19Add
BLAST
Repeati689 – 71022LRR 20Add
BLAST
Repeati711 – 73222LRR 21Add
BLAST
Repeati734 – 75522LRR 22Add
BLAST
Domaini782 – 1030249PPM-type phosphatasePROSITE-ProRule annotationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi40 – 478Poly-Thr
Compositional biasi48 – 5710Poly-Ser
Compositional biasi1068 – 10714Poly-Ser

Sequence similaritiesi

Contains 22 LRR (leucine-rich) repeats.Curated
Contains 1 PH domain.Curated
Contains 1 PPM-type phosphatase domain.PROSITE-ProRule annotation

Keywords - Domaini

Leucine-rich repeat, Repeat

Phylogenomic databases

eggNOGiCOG4886.
GeneTreeiENSGT00440000037833.
HOGENOMiHOG000115529.
HOVERGENiHBG062748.
InParanoidiQ8BXA7.
KOiK16340.
OrthoDBiEOG7RFTGK.

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
3.60.40.10. 1 hit.
InterProiIPR001611. Leu-rich_rpt.
IPR025875. Leu-rich_rpt_4.
IPR003591. Leu-rich_rpt_typical-subtyp.
IPR011993. PH_like_dom.
IPR001932. PPM-type_phosphatase_dom.
[Graphical view]
PfamiPF12799. LRR_4. 1 hit.
PF13504. LRR_7. 1 hit.
PF13855. LRR_8. 3 hits.
PF00481. PP2C. 1 hit.
[Graphical view]
SMARTiSM00369. LRR_TYP. 1 hit.
SM00332. PP2Cc. 1 hit.
[Graphical view]
SUPFAMiSSF81606. SSF81606. 1 hit.
PROSITEiPS51450. LRR. 17 hits.
PS51746. PPM_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q8BXA7-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKHNGSRTCL NRRSRFGSRE RDWLREDVKR GCVYLYGADT TTATTTTSSS
60 70 80 90 100
SSSSSSSDLH LVLCTVETPA SEICAGEGRE SLYLQLHGDL VRRLEPSERP
110 120 130 140 150
LQIVYDYLSR LGFEDPVRIQ EEATNPDLSC MIRFYGEKPC QMDHLDRILL
160 170 180 190 200
SGIYNVRKGK TQLHKWAERL VVLCGTCLIV SSVKDCQTGK MHILPLVGGK
210 220 230 240 250
IEEVKRRQHS LAFSSAGAQA QTYHVSFETL AEYQRWQRQA SKVVSQRMST
260 270 280 290 300
VDLSCYSLEE VPEHLFYSQD ITYLNLRHNF MQLERPGGLD TLHKFSQLKG
310 320 330 340 350
LNLSHNKLGL FPVLLCEIST LTELSLSCNG FHDLPSQIGK LLNLQTLSLD
360 370 380 390 400
GNGLTALPDE LGNLRQLTSL GISFNDFRHI PEVLEKLTML DKVAMAGNRL
410 420 430 440 450
EVLNLGALTR MSQVKHVDLR MNHLKTVITE NMEGNKHITH MDLRDNQLTD
460 470 480 490 500
LDLSSLCSLE QLHCERNQLR ELTLSGFSLR TLYASWNRLT AVNVYPVPSL
510 520 530 540 550
LTSLELSQNL LECVPDWACE AKKLEILDIS HNLLTEVPMR ILSSLSLRKL
560 570 580 590 600
MVGHNHIHVL PALVEHIPLE VLDIQHNTLS RLPDTLFSKA LNLRYLNASA
610 620 630 640 650
NSLESLPSAC AGEESLSVLQ LLYLTSNLLT DQCIPVLVGH PHLRVLHLAN
660 670 680 690 700
NQLQTFPASK LNKLEQLEEL NLSGNKLTAI PTTIANCKRL HTLVAHANNI
710 720 730 740 750
SIFPEILQLP QIQFVDLSCN DLTEILIPEA LPATLQDLDL TGNTNLVLEH
760 770 780 790 800
KTLDMFSHIT ALKIDQKPLP ATDSAVTSTF WSHGLAEMAG QRNKLCVSAL
810 820 830 840 850
AMDNFAEGVG AVYGMFDGDR NEELPRLLQC TMADVLLEEV QHSTNDTVFM
860 870 880 890 900
TNTFLVSHRK LGMAGQKLGS SALLCYIRPD TADPTSSFSL TVANVGMCQA
910 920 930 940 950
VLCRGGKPVP LSKVFSLEHD PEEAQRVKDQ KAIITEDNKV NGVTCCTRLL
960 970 980 990 1000
GCTYLYPWIL PKPHIASTPL TIQDELLILG NKALWEHLSY LEAVNAVRHV
1010 1020 1030 1040 1050
QDPLAAAKKL CTLAQSYGCQ DNVGAMVVYL NIGEEGCTCE MNGLTLPGPV
1060 1070 1080 1090 1100
GFASTAALKD TPKPTTPSSS SGIASEFSSE MSTSEVSSEV GSTASDEHNT
1110 1120 1130 1140 1150
VGLEASLLPR PERRCSLHPA SSAGVFQRQP SCATFSSNQS DNGLDSDDDQ
1160 1170 1180 1190 1200
PVEGVITNGS RVEVEVDIHC CRGREPESSP PLPKNSSNAC SEERARGAGF
1210 1220 1230 1240 1250
GIRRQNSVNS GILLPANRDK MELQKSPSTS CLYGKKLSNG SIVPLEDSLN
1260 1270 1280 1290 1300
LIEVATEAPK RKTGYFAAPT QLEPEDQFVV PRDLEEEVKE QMKQHQEGRP
1310 1320
EPEPRGEERT EPLEEFDTAL
Length:1,320
Mass (Da):145,947
Last modified:July 27, 2011 - v3
Checksum:i302407C231BD539B
GO

Sequence cautioni

The sequence BAC33347.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti67 – 671E → Q in BAC33288 (PubMed:16141072).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC122807 Genomic DNA. No translation available.
BC117961 mRNA. Translation: AAI17962.1.
BC117962 mRNA. Translation: AAI17963.1.
AK048260 mRNA. Translation: BAC33288.1.
AK048472 mRNA. Translation: BAC33347.2. Different initiation.
RefSeqiNP_001116066.2. NM_001122594.2.
UniGeneiMm.23494.

Genome annotation databases

EnsembliENSMUST00000034175; ENSMUSP00000034175; ENSMUSG00000031732.
GeneIDi244650.
KEGGimmu:244650.
UCSCiuc009njn.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC122807 Genomic DNA. No translation available.
BC117961 mRNA. Translation: AAI17962.1.
BC117962 mRNA. Translation: AAI17963.1.
AK048260 mRNA. Translation: BAC33288.1.
AK048472 mRNA. Translation: BAC33347.2. Different initiation.
RefSeqiNP_001116066.2. NM_001122594.2.
UniGeneiMm.23494.

3D structure databases

ProteinModelPortaliQ8BXA7.
SMRiQ8BXA7. Positions 249-769, 783-1030.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000136166.

PTM databases

PhosphoSiteiQ8BXA7.

Proteomic databases

MaxQBiQ8BXA7.
PaxDbiQ8BXA7.
PRIDEiQ8BXA7.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000034175; ENSMUSP00000034175; ENSMUSG00000031732.
GeneIDi244650.
KEGGimmu:244650.
UCSCiuc009njn.2. mouse.

Organism-specific databases

CTDi23035.
MGIiMGI:2444928. Phlpp2.

Phylogenomic databases

eggNOGiCOG4886.
GeneTreeiENSGT00440000037833.
HOGENOMiHOG000115529.
HOVERGENiHBG062748.
InParanoidiQ8BXA7.
KOiK16340.
OrthoDBiEOG7RFTGK.

Enzyme and pathway databases

ReactomeiREACT_284913. Negative regulation of the PI3K/AKT network.

Miscellaneous databases

ChiTaRSiPhlpp2. mouse.
NextBioi386351.
PROiQ8BXA7.
SOURCEiSearch...

Gene expression databases

BgeeiQ8BXA7.
ExpressionAtlasiQ8BXA7. baseline and differential.
GenevisibleiQ8BXA7. MM.

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
3.60.40.10. 1 hit.
InterProiIPR001611. Leu-rich_rpt.
IPR025875. Leu-rich_rpt_4.
IPR003591. Leu-rich_rpt_typical-subtyp.
IPR011993. PH_like_dom.
IPR001932. PPM-type_phosphatase_dom.
[Graphical view]
PfamiPF12799. LRR_4. 1 hit.
PF13504. LRR_7. 1 hit.
PF13855. LRR_8. 3 hits.
PF00481. PP2C. 1 hit.
[Graphical view]
SMARTiSM00369. LRR_TYP. 1 hit.
SM00332. PP2Cc. 1 hit.
[Graphical view]
SUPFAMiSSF81606. SSF81606. 1 hit.
PROSITEiPS51450. LRR. 17 hits.
PS51746. PPM_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  2. "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].
  3. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-1259.
    Strain: C57BL/6J.
    Tissue: Head.
  4. "Large scale localization of protein phosphorylation by use of electron capture dissociation mass spectrometry."
    Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.
    Mol. Cell. Proteomics 8:904-912(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Embryonic fibroblast.

Entry informationi

Entry nameiPHLP2_MOUSE
AccessioniPrimary (citable) accession number: Q8BXA7
Secondary accession number(s): Q148U6, Q8BX96
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 7, 2005
Last sequence update: July 27, 2011
Last modified: June 24, 2015
This is version 115 of the entry and version 3 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.