Conserved Protein Domain Family
RA_PHLPP

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cd17213: RA_PHLPP 
Ras-associating (RA) domain found in PH domain leucine-rich repeat-containing protein phosphatase PHLPP1, PHLPP2, and similar proteins
PHLPP represents a novel family of Ser/Thr protein phosphatases, which is involved in two key signaling pathways, the phosphatidylinositol 3-kinase and diacylglycerol signaling pathways, by directly dephosphorylating and inactivating Akt serine-threonine kinases (Akt1, Akt2, Akt3) and protein kinase C (PKC) isoforms. PHLPP targets oncogenic kinases and may act as a tumor suppressor in several types of cancers. Two PHLPP isoforms are included in this family, PHLPP1 and PHLPP2. They regulate Akt activation together when both phosphatases are expressed. PHLPP1 is also termed pleckstrin homology domain-containing family E member 1, or PH domain-containing family E member 1, or suprachiasmatic nucleus circadian oscillatory protein (SCOP). It plays a suppression role in inflammatory response of glioma. Its loss contributes to gliomas development and progression. Loss of PHLPP1 also protects against colitis by inhibiting intestinal epithelial cell apoptosis. The overexpression of PHLPP1 impairs hippocampus-dependent learning, suggesting a role for PHLPP1 in learning and memory. PHLPP2 is also termed PH domain leucine-rich repeat-containing protein phosphatase-like (PHLPP-like). Both PHLPP1 and PHLPP2 contain a putative Ras-associating (RA) domain followed by a pleckstrin homology (PH) domain, a series of leucine-rich repeats and a protein phosphatase 2C (PP2C) domain.
Statistics
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PSSM-Id: 340733
Aligned: 13 rows
Threshold Bit Score: 118.553
Created: 27-Oct-2016
Updated: 2-Oct-2020
Structure
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Aligned Rows:
PubMed ReferencesClick to see Conserved Features Help

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Q6ZVD8         31 GCVYLYGAdtttattttttsssssssssssDLHLVLCTvetPASEICAGEGREsl------------------------- 85   human
ETN60766      183 GWLRVYCGpdrse------------issedRSRMIHVVttaTTLDVVKDMNLPgdyt----------------------- 227  Anopheles dar...
XP_011434907  166 GFVRVFQPds-------------------eVSKVFPCTlstSAHKLCLQCGRPpns------------------------ 202  Pacific oyster
KRZ86116       92 GFIRLYDPdaq-----------------laSSLVVPCSletTCLQIASRLSVDpdd------------------------ 130  Trichinella s...
XP_013390226  147 GFIRVFIPdsd-----------------lsKSYLIPLTlntPAGRVCQILGIPpns------------------------ 185  Lingula anatina
O60346        202 GCVHVFDRhma-----------------stYLRPVLCTldtTAGEVAARLLQLghkgggvvkvlgqgpgaaaarepaepp 264  human
EPB69883       33 GRIRLFSPeg-------------------dRSALATISldtTAVDLAKAYEVDsi------------------------- 68   Ancylostoma c...
XP_019629405   75 GIIRVYEVds-------------------dLCVAVRCTlqtNAAEICQKLGLDaaevplpacddltttdaaprlpadtek 135  Belcher's lan...
XP_018902708   14 GWVRLYDCdds-----------------ssSGNLVYIDhesDVRQICKDMSINdhyt----------------------- 53   Bemisia tabaci
CRZ21995       68 GFIRLYAPtg-------------------lRSLIYPVTlqtTVQDICSVLGFEsl------------------------- 103  Brugia malayi
KPI93766       68 GWIRVFDGlepf--------------aveaPSKLIKISskaTVEDVNKKLGFSdelt----------------------- 110  Papilio xuthus
XP_019862356   36 GAIRVYQPgs-------------------tYSELTQCDtetHAEVIMSKCVTSnl------------------------- 71   Amphimedon qu...
CEF65276       56 GFIRLYTPng-------------------eKSTVIAVTidqTTEDICNKINISsi------------------------- 91   Strongyloides...
Q6ZVD8            --------------------------------------------------------------------------------      human
ETN60766          --------------------------------------------------------------------------------      Anopheles dar...
XP_011434907      --------------------------------------------------------------------------------      Pacific oyster
KRZ86116          --------------------------------------------------------------------------------      Trichinella s...
XP_013390226      --------------------------------------------------------------------------------      Lingula anatina
O60346        265 peagprlappeprdsevpparsapgafggpprappadlplpvggpggwsrraspapsdsspgepfvggpvsspraprpvv 344  human
EPB69883          --------------------------------------------------------------------------------      Ancylostoma c...
XP_019629405      --------------------------------------------------------------------------------      Belcher's lan...
XP_018902708      --------------------------------------------------------------------------------      Bemisia tabaci
CRZ21995          --------------------------------------------------------------------------------      Brugia malayi
KPI93766          --------------------------------------------------------------------------------      Papilio xuthus
XP_019862356      --------------------------------------------------------------------------------      Amphimedon qu...
CEF65276          --------------------------------------------------------------------------------      Strongyloides...
Q6ZVD8            --------------------------------------------------------------------------------      human
ETN60766          --------------------------------------------------------------------------------      Anopheles dar...
XP_011434907      --------------------------------------------------------------------------------      Pacific oyster
KRZ86116          --------------------------------------------------------------------------------      Trichinella s...
XP_013390226      --------------------------------------------------------------------------------      Lingula anatina
O60346        345 sdtesfslspsaesvsdrldpyssgggssssseeleadaasaptgvpgqprrpghpaqplplpqtasspqpqqkapraid 424  human
EPB69883          --------------------------------------------------------------------------------      Ancylostoma c...
XP_019629405      --------------------------------------------------------------------------------      Belcher's lan...
XP_018902708      --------------------------------------------------------------------------------      Bemisia tabaci
CRZ21995          --------------------------------------------------------------------------------      Brugia malayi
KPI93766          --------------------------------------------------------------------------------      Papilio xuthus
XP_019862356      --------------------------------------------------------------------------------      Amphimedon qu...
CEF65276          --------------------------------------------------------------------------------      Strongyloides...
Q6ZVD8         86 -----------------------------------------------ylQLHGDLVRRLEpTERPLQIVYDYLSRLGFDd 118  human
ETN60766      228 ----------------------------------------------lwvQTGGGRTRRLEeNEYPLLVQEEFLRSLGYFd 261  Anopheles dar...
XP_011434907  203 ----------------------------------------------mhiQLNGDIIRRLEpFDCPLAIQNEYLQNVGYKd 236  Pacific oyster
KRZ86116      131 ----------------------------------------------lhvQFNGDMLKRLLlDDRPLAIQNKFLASIGIRn 164  Trichinella s...
XP_013390226  186 ----------------------------------------------lhvQLNGDIIQRLEpYENPLVIQNEYLATIGYTd 219  Lingula anatina
O60346        425 spggavregsceekaaaavapgglqstpgrsgvtaekappppppptlyvQLHGETTRRLEaEEKPLQIQNDYLFQLGFGe 504  human
EPB69883       69 -----------------------------------------------ylQIGNLHIRNLSpRARPLFILREFLASLGHSe 101  Ancylostoma c...
XP_019629405  136 ----------------------lngddnpvgkelsngltrtdkvcslhvQFNGGSVRRLGaGELPLVLQQEYLSRLGLTe 193  Belcher's lan...
XP_018902708   54 ----------------------------------------------iwvKYGGAEERRLKsDENPLIIQDEFLRQIGYSd 87   Bemisia tabaci
CRZ21995      104 -----------------------------------------------ylQIGGCKISNLSaGEYPLQLQNEFLLNIGYEt 136  Brugia malayi
KPI93766      111 ----------------------------------------------lwlQTGGEHLRRLEpNERPLQIQDDILMKNGWSs 144  Papilio xuthus
XP_019862356   72 -----------------------------------------------yvYYAGHSSEPLGyDDCPLKIQNKFLKSLGYDd 104  Amphimedon qu...
CEF65276       92 -----------------------------------------------yvQIGNLHIRKLPlDSRPLWMQNDILMTIGHKt 124  Strongyloides...
Q6ZVD8        119 pvriqeeaTNPDLGCMIRFYGEKP 142  human
ETN60766      262 esrrarlgIDPELKHLIRFHIGPA 285  Anopheles darlingi
XP_011434907  237 tkkiqqmgLCPDLSWLVKFYAGKP 260  Pacific oyster
KRZ86116      165 vdrqqaigDDVDLGHMIRFYAGHK 188  Trichinella sp. T8
XP_013390226  220 vtriqeegHNPEIGFQIRFYTGKP 243  Lingula anatina
O60346        505 lwrvqeegMDSEIGCLIRFYAGKP 528  human
EPB69883      102 tai-rtrgTDLKFRHLIAFFLGRP 124  Ancylostoma ceylanicum
XP_019629405  194 prrlqqegRAHDLGSLIRFYAGRP 217  Belcher's lancelet
XP_018902708   88 psrrdrlgVDINLKYLIKFHIGPT 111  Bemisia tabaci
CRZ21995      137 qsecmavgDATHLTHLFCFFIGRP 160  Brugia malayi
KPI93766      145 earrlrlaVDPELRHSLRWSAGPS 168  Papilio xuthus
XP_019862356  105 periqfegTRDDLLYMFKFVAGRE 128  Amphimedon queenslandica
CEF65276      125 ieeilslgDSNYLRYIIAFFIDCP 148  Strongyloides ratti
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