Conserved Protein Domain Family
PH_alsin

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cd13269: PH_alsin 
Alsin Pleckstrin homology (PH) domain
The ALS2 gene encodes alsin, a GEF, that has dual specificity for Rac1 and Rab5 GTPases. Alsin mutations in the form of truncated proteins are responsible for motor function disorders including juvenile-onset amyotrophic lateral sclerosis, familial juvenile primary lateral sclerosis, and infantile-onset ascending hereditary spastic paralysis. The alsin protein is widely expressed in the developing CNS including neurons of the cerebral cortex, brain stem, spinal cord, and cerebellum. Alsin contains a regulator of chromosome condensation 1 (RCC1) domain, a Rho guanine nucleotide exchanging factor (RhoGEF) domain, a PH domain, a Membrane Occupation and Recognition Nexus (MORN), a vacuolar protein sorting 9 (Vps9) domain, and a Dbl homology (DH) domain. Alsin interacts with Rab5 through its Vps9 domain and through this interaction modulates early endosome fusion and trafficking. The GEF activity of alsin towards Rab5 is regulated by Rac1 function. The GEF activity of alsin for Rac1 occurs via its DH domain and this interaction plays a role in promoting spinal motor neuron survival via multiple Rac-dependent signaling pathways. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.
Statistics
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PSSM-Id: 241423
View PSSM: cd13269
Aligned: 12 rows
Threshold Bit Score: 156.784
Threshold Setting Gi: 320163592
Created: 9-Jan-2012
Updated: 2-Mar-2014
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:
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 348518257 1112 DSLRKPYRRLICESSNKs--LTLQNAGRFSVNWFILFNDVLVHAQFS-----------THHIFPLATLWVEPIPEEDTg- 1177
gi 47211897   907 ESLRLPQRRVVCESSSRr-sLTLQNAGRFSNHGFILFNDALVHTQFS-----------THHVYPLTCLWVKPVAEDSSg- 973
gi 326668450  935 DSLRKPSRRLICESSNKa--LTLQNAGRFSVNWFILFNDALVHAQFS-----------THHIFPLATLWVEPISEESTg- 1000
gi 320163592  911 KSLSAPDRRLLRHSKTNplsFAKTSTLDLSTHWFILFSDVLVRSQWVipsrpnssstwTMSVAPLLVTWLGDIEDTPSl- 989
gi 118093428  897 DSLRKPDRRLICESSNRg--LSLQHAGRFSVNWFILFNDALVHAQFS-----------THHIFALSTLWVEALSEEAGn- 962
gi 115313722  888 DSLRKPDRRLICDSSNRg--LSLQNAGRFSVNWFILFNDALVHAQFS-----------THHIFPLSTVWVEPLSEEVNg- 953
gi 390353468  144 ESIKSPDRRLIRDSRTKp--LQVANAKRLSTHWFLLFNDILVHAYFS-----------NHQIFSLALVWAEPIPDTDQv- 209
gi 307194211  801 ELLRSPDRRLIRESRTHp--LSILNSGRFSSHWFVLLTDIFIHVTGT-----------THTVHPLRTLWVEPLPDSENv- 866
gi 357613910  693 DQYRTPERRLIRDSKSRp--LNLVNPGRFSSHWFILFNDLFVHVNGS-----------TANIHPLETLWIEAVPNTDSl- 758
gi 321474689    1 DALRTPVRRLIRESRTHp--ITLVNSGRFSSHWFIILTDVLVHVSGSs----------NHVTYPLATIWVEPMQDSDNiq 68
gi 270008037  784 DQLKSPDRRLIRDSHKYp--IHLQNASRFSSHWFVLFSDLFVHMNGS-----------TAHLHNLTTIWIEPQQDETSqq 850
gi 296434394  905 DSLRKPERRLLCESSNRa--LSLQHAGRFSVNWFILFNDALVHAQFS-----------THHVFPLATLWAEPLSEEAGg- 970
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 348518257 1178 -lYGLKVITPeeTLTLLAS-SPMEKAKWLRSINQAVDKALSG 1217
gi 47211897   974 -lFAIRIICPeeSFTIVAS-TPQEKNKWLRSINRALDQVLGG 1013
gi 326668450 1001 -vYGLKVTSPeeSFALLAS-SPAEKAKWLRSINQAVEQALSG 1040
gi 320163592  990 -rNAFRIITAddSFTVFAA-NPKDKAQWMEAITGGIDGAIAR 1029
gi 118093428  963 -vNGLKITTPeeQFVLLSS-TPQEKTKWLRAISQAVDQALKG 1002
gi 115313722  954 -vNGLKITIPeeQLTLVSS-SQQEKAKWLWAISQAVDQALKG 993
gi 390353468  210 -iNAIQLNMPeeSLVLQAP-SPVEKAEWLWSINQAIDSILTT 249
gi 307194211  867 -qNAISIVTPedSFVLYTP-TPSERNEWLHALQNTIKCSLQR 906
gi 357613910  759 -qNVIQLTTPe-EVICVSTiSEQEKTEWIHSLNASIRTALNK 798
gi 321474689   69 tkNGLSLTMPeeTMTLACP-TAGDKMEWLVALQSAIRHALLI 109
gi 270008037  851 yqICLKMPEE--TLVLCTS-EPEAKIEWFHALQNAIKAAMNK 889
gi 296434394  971 -vNGLKITTPeeQFTLISS-TPQEKTKWLRAISQAVDQALRG 1010
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