Tectonin beta-propeller repeat-containing protein 1 Pleckstrin homology (PH) domain, repeat 1; TECPR1 is a tethering factor involved in autophagy. It promotes the autophagosome fusion with lysosomes by associating with both the ATG5-ATG12 conjugate and phosphatidylinositol-3-phosphate (PtdIns3P) present at the surface of autophagosomes. TECPR1 is also involved in selective autophagy against bacterial pathogens, by being required for phagophore/preautophagosomal structure biogenesis and maturation. It contains 2 DysFN (Dysferlin domains of unknown function, N-terminal), 2 Hyd_WA domains that is a probably beta-propeller, a PH-like domain, a TECPR domain, and a DysFC (C-terminal). The PH domain mediates the binding to phosphatidylinositol-3-phosphate (PtdIns3P). Binding to the ATG5-ATG12 conjugate exposes the PH domain, allowing the association with PtdIns3P. 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568939077  478 VEQSVWVKTGALQWWCDWKPHKWVDVRVALEQFTGHDGARDSILFIYYVVHEEKKYLHVFLNEVTVLVPVLNEA-KHSFA 556
Cdd:cd13300     1 VERSSWVKTGALQWWSDWKPHKWADCRVALEQGTGSDGRQDSIFFVYYTYHGEKKYIQFFLSEITCVVPVNNGGeKPSFA 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 568939077  557 LYTPERTRQRWPVRLAAATEQDMNDWLALLSLSCCESRKVHG 598
Cdd:cd13300    81 IYTPKRTKQRWPIRLAANTEQELEDWLSLLSMSCCEVRGIQG 122

Tectonin domain; This entry represents proteins homologous to tectonin. This protein adopts a 6 bladed beta propeller structure.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568939077   851 GSSWLHVgtDQPFASVSIGACYQVWAVARDGSAFYRGSVSPSQPAGDCWYHIPSppkqKLTQVSVGQTSVYALDENGNLW 930
Cdd:pfam19193   60 GGSWVPV--DGSLKQVDAGGDGQVWGVNSADDIYCLNGDDASSYAGLPWTQVDG----SLKYYSCGPGGCWGVNSNDDIY 133

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568939077   931 YRAGITPSYPQGSSWEHVSNNVRKVSVGPLDQVWVIAnkvqgshglSRGTVCRRMGVQPREPKGQGWDYGIGG-GWDHIS 1009
Cdd:pfam19193  134 YRRYVGPSTCGGTGWTQVPGKLKMIEVGSDGSVFGVN---------SNGNVYQRTGISSSNPTGTGWTQIPGSlSIKHVS 204

                   .
gi 568939077  1010 V 1010
Cdd:pfam19193  205 Y 205

Dysferlin domain, N-terminal region; Domain of unknown function present in yeast peroxisomal proteins, dysferlin, myoferlin and hypothetical proteins. Due to an insertion of a dysferlin domain within a second dysferlin domain we have chosen to predict these domains in two parts: the N-terminal region and the C-terminal region.

                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 568939077    690 SDVKSVYIYENQ-RWNPVtGYTSRGLPTdRFMWSDVTGLQECTKAGTKPPSLQWTWVSD-WYVD 751
Cdd:smart00693    1 PIRFTEEMYENQrRWLGG-GWKTTLLPY-RPKFSDASGGKECLPKENLLPPPGWEWEDDnWSLD 62

Beta propeller repeats in Physarum polycephalum tectonins, Limulus lectin L-6 and animal hypothetical proteins;

                            10        20        30
                    ....*....|....*....|....*....|....
gi 568939077    635 MFWRQMGGHLRIIEANSRGVVWGIGYDHTAWVYT 668
Cdd:smart00706    1 GSWTQVPGELVQVSVGPSDTVWAVNSDGNIYRRT 34

Tectonin beta-propeller repeat-containing protein 1 Pleckstrin homology (PH) domain, repeat 1; TECPR1 is a tethering factor involved in autophagy. It promotes the autophagosome fusion with lysosomes by associating with both the ATG5-ATG12 conjugate and phosphatidylinositol-3-phosphate (PtdIns3P) present at the surface of autophagosomes. TECPR1 is also involved in selective autophagy against bacterial pathogens, by being required for phagophore/preautophagosomal structure biogenesis and maturation. It contains 2 DysFN (Dysferlin domains of unknown function, N-terminal), 2 Hyd_WA domains that is a probably beta-propeller, a PH-like domain, a TECPR domain, and a DysFC (C-terminal). The PH domain mediates the binding to phosphatidylinositol-3-phosphate (PtdIns3P). Binding to the ATG5-ATG12 conjugate exposes the PH domain, allowing the association with PtdIns3P. 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568939077  478 VEQSVWVKTGALQWWCDWKPHKWVDVRVALEQFTGHDGARDSILFIYYVVHEEKKYLHVFLNEVTVLVPVLNEA-KHSFA 556
Cdd:cd13300     1 VERSSWVKTGALQWWSDWKPHKWADCRVALEQGTGSDGRQDSIFFVYYTYHGEKKYIQFFLSEITCVVPVNNGGeKPSFA 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 568939077  557 LYTPERTRQRWPVRLAAATEQDMNDWLALLSLSCCESRKVHG 598
Cdd:cd13300    81 IYTPKRTKQRWPIRLAANTEQELEDWLSLLSMSCCEVRGIQG 122

Tectonin domain; This entry represents proteins homologous to tectonin. This protein adopts a 6 bladed beta propeller structure.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568939077   851 GSSWLHVgtDQPFASVSIGACYQVWAVARDGSAFYRGSVSPSQPAGDCWYHIPSppkqKLTQVSVGQTSVYALDENGNLW 930
Cdd:pfam19193   60 GGSWVPV--DGSLKQVDAGGDGQVWGVNSADDIYCLNGDDASSYAGLPWTQVDG----SLKYYSCGPGGCWGVNSNDDIY 133

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568939077   931 YRAGITPSYPQGSSWEHVSNNVRKVSVGPLDQVWVIAnkvqgshglSRGTVCRRMGVQPREPKGQGWDYGIGG-GWDHIS 1009
Cdd:pfam19193  134 YRRYVGPSTCGGTGWTQVPGKLKMIEVGSDGSVFGVN---------SNGNVYQRTGISSSNPTGTGWTQIPGSlSIKHVS 204

                   .
gi 568939077  1010 V 1010
Cdd:pfam19193  205 Y 205

Dysferlin domain, N-terminal region; Domain of unknown function present in yeast peroxisomal proteins, dysferlin, myoferlin and hypothetical proteins. Due to an insertion of a dysferlin domain within a second dysferlin domain we have chosen to predict these domains in two parts: the N-terminal region and the C-terminal region.

                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 568939077    690 SDVKSVYIYENQ-RWNPVtGYTSRGLPTdRFMWSDVTGLQECTKAGTKPPSLQWTWVSD-WYVD 751
Cdd:smart00693    1 PIRFTEEMYENQrRWLGG-GWKTTLLPY-RPKFSDASGGKECLPKENLLPPPGWEWEDDnWSLD 62

Integral peroxisomal membrane peroxin; Peroxisomes play diverse roles in the cell, compartmentalising many activities related to lipid metabolism and functioning in the decomposition of toxic hydrogen peroxide. Sequence similarity was identified between two hypothetical proteins and the peroxin integral membrane protein Pex24p.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568939077   695 VYIYENQRWNPVT-GYTSRGLPTDRFMWSDvtglqECTKAGTKPPSL-----------QWTWV--SDWYVDFSVPGG--- 757
Cdd:pfam06398  254 VEIFENQRRWLLGiGWTSSLLSYERYDWTD-----EYRIALNEAPPGvdhledfeppeGWRWVdnSKWRLDLTPDGWvee 328

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 568939077   758 --------TDQEGWQYASDFPASYHGYKTMKDFVRRRCWAR 790
Cdd:pfam06398  329 rflttvnpDEDEGWVYDDNTWKEPSTEDGFSKYTRRRRWIR 369

PH domain; PH stands for pleckstrin homology.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568939077   484 VKTGALQWWCDWKPHKWVDVRVALeqftghdgaRDSILFIY---YVVHEEKKYLHVFLNEVTVLVPVLNE---AKHSFAL 557
Cdd:pfam00169    2 VKEGWLLKKGGGKKKSWKKRYFVL---------FDGSLLYYkddKSGKSKEPKGSISLSGCEVVEVVASDspkRKFCFEL 72

                           90       100       110
                   ....*....|....*....|....*....|...
gi 568939077   558 YTPERTRQRwPVRLAAATEQDMNDWLALLSLSC 590
Cdd:pfam00169   73 RTGERTGKR-TYLLQAESEEERKDWIKAIQSAI 104

Beta propeller repeats in Physarum polycephalum tectonins, Limulus lectin L-6 and animal hypothetical proteins;

                            10        20
                    ....*....|....*....|....*.
gi 568939077    943 SSWEHVSNNVRKVSVGPLDQVWVIAN 968
Cdd:smart00706    1 GSWTQVPGELVQVSVGPSDTVWAVNS 26

Tectonin beta-propeller repeat-containing protein 1 Pleckstrin homology (PH) domain, repeat 1; TECPR1 is a tethering factor involved in autophagy. It promotes the autophagosome fusion with lysosomes by associating with both the ATG5-ATG12 conjugate and phosphatidylinositol-3-phosphate (PtdIns3P) present at the surface of autophagosomes. TECPR1 is also involved in selective autophagy against bacterial pathogens, by being required for phagophore/preautophagosomal structure biogenesis and maturation. It contains 2 DysFN (Dysferlin domains of unknown function, N-terminal), 2 Hyd_WA domains that is a probably beta-propeller, a PH-like domain, a TECPR domain, and a DysFC (C-terminal). The PH domain mediates the binding to phosphatidylinositol-3-phosphate (PtdIns3P). Binding to the ATG5-ATG12 conjugate exposes the PH domain, allowing the association with PtdIns3P. 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568939077  478 VEQSVWVKTGALQWWCDWKPHKWVDVRVALEQFTGHDGARDSILFIYYVVHEEKKYLHVFLNEVTVLVPVLNEA-KHSFA 556
Cdd:cd13300     1 VERSSWVKTGALQWWSDWKPHKWADCRVALEQGTGSDGRQDSIFFVYYTYHGEKKYIQFFLSEITCVVPVNNGGeKPSFA 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 568939077  557 LYTPERTRQRWPVRLAAATEQDMNDWLALLSLSCCESRKVHG 598
Cdd:cd13300    81 IYTPKRTKQRWPIRLAANTEQELEDWLSLLSMSCCEVRGIQG 122

Tectonin domain; This entry represents proteins homologous to tectonin. This protein adopts a 6 bladed beta propeller structure.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568939077   851 GSSWLHVgtDQPFASVSIGACYQVWAVARDGSAFYRGSVSPSQPAGDCWYHIPSppkqKLTQVSVGQTSVYALDENGNLW 930
Cdd:pfam19193   60 GGSWVPV--DGSLKQVDAGGDGQVWGVNSADDIYCLNGDDASSYAGLPWTQVDG----SLKYYSCGPGGCWGVNSNDDIY 133

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568939077   931 YRAGITPSYPQGSSWEHVSNNVRKVSVGPLDQVWVIAnkvqgshglSRGTVCRRMGVQPREPKGQGWDYGIGG-GWDHIS 1009
Cdd:pfam19193  134 YRRYVGPSTCGGTGWTQVPGKLKMIEVGSDGSVFGVN---------SNGNVYQRTGISSSNPTGTGWTQIPGSlSIKHVS 204

                   .
gi 568939077  1010 V 1010
Cdd:pfam19193  205 Y 205

Dysferlin domain, C-terminal region; Domain of unknown function present in yeast peroxisomal proteins, dysferlin, myoferlin and hypothetical proteins. Due to an insertion of a dysferlin domain within a second dysferlin domain we have chosen to predict these domains in two parts: the N-terminal region and the C-terminal region.

                            10        20        30
                    ....*....|....*....|....*....|....
gi 568939077    762 GWQYASDFPASYHGYKTMKDFVRRRCWARKCKLV 795
Cdd:smart00694    1 GWQYSDNFWANYHKTEKMTDFVRRRRWVRRRRHK 34

Tectonin domain; This entry represents proteins homologous to tectonin. This protein adopts a 6 bladed beta propeller structure.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568939077   866 VSIGACyQVWAVARDGSAFYRgsvspsqpAGDCWYHIPSppkqKLTQVSVGQTSVYALDENGNLWYRagitpsypQGSSW 945
Cdd:pfam19193    5 IDAGQG-QVWGVDSAGNVYYL--------TGSSWVRVPG----RLKHVSVGPAGVWGVNSNNKIYKY--------VGGSW 63

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 568939077   946 EHVSNNVRKVSVGPLDQVWVIAnkvqgshglSRGTVCRRMGVQPREPKGQGWDYgIGGGWDHISV 1010
Cdd:pfam19193   64 VPVDGSLKQVDAGGDGQVWGVN---------SADDIYCLNGDDASSYAGLPWTQ-VDGSLKYYSC 118

Propeller; Tectonins I and II are two dominant proteins in the nuclei and nuclear matrix from plasmodia of Physarum polycephalum (Slime mold) and both proteins contain six tandem repeats that are each 33-37 amino acids in length. Homologous repeats are found in L-6, a bacterial lipopolysaccharide-binding lectin from horseshoe crab hemocytes. The repetitive sequences of the tectonins and L-6 are reminiscent of the WD repeats of the beta-subunit of G proteins, suggesting that they form beta-propeller domains. The tectonins may be lectins that function as part of a transmembrane signalling complex during phagocytosis. Tectonin beta-propeller repeat-containing protein 1 (TECPR1) has a critical function during autophagosome maturation and autophagosome-lysosome fusion.

                           10        20        30
                   ....*....|....*....|....*....|
gi 568939077   919 SVYALDENGNLWYRAGITPSYPQGSSWEHV 948
Cdd:pfam06462    1 QVWAVTSDGRVYFRTGVTPSNPTGTSWEHV 30

Propeller; Tectonins I and II are two dominant proteins in the nuclei and nuclear matrix from plasmodia of Physarum polycephalum (Slime mold) and both proteins contain six tandem repeats that are each 33-37 amino acids in length. Homologous repeats are found in L-6, a bacterial lipopolysaccharide-binding lectin from horseshoe crab hemocytes. The repetitive sequences of the tectonins and L-6 are reminiscent of the WD repeats of the beta-subunit of G proteins, suggesting that they form beta-propeller domains. The tectonins may be lectins that function as part of a transmembrane signalling complex during phagocytosis. Tectonin beta-propeller repeat-containing protein 1 (TECPR1) has a critical function during autophagosome maturation and autophagosome-lysosome fusion.

                           10        20        30
                   ....*....|....*....|....*....|
gi 568939077   828 ALWAVSDKGDVLCRLGVSELNPAGSSWLHV 857
Cdd:pfam06462    1 QVWAVTSDGRVYFRTGVTPSNPTGTSWEHV 30

Propeller; Tectonins I and II are two dominant proteins in the nuclei and nuclear matrix from plasmodia of Physarum polycephalum (Slime mold) and both proteins contain six tandem repeats that are each 33-37 amino acids in length. Homologous repeats are found in L-6, a bacterial lipopolysaccharide-binding lectin from horseshoe crab hemocytes. The repetitive sequences of the tectonins and L-6 are reminiscent of the WD repeats of the beta-subunit of G proteins, suggesting that they form beta-propeller domains. The tectonins may be lectins that function as part of a transmembrane signalling complex during phagocytosis. Tectonin beta-propeller repeat-containing protein 1 (TECPR1) has a critical function during autophagosome maturation and autophagosome-lysosome fusion.

                           10        20        30
                   ....*....|....*....|....*....|
gi 568939077   873 QVWAVARDGSAFYRGSVSPSQPAGDCWYHI 902
Cdd:pfam06462    1 QVWAVTSDGRVYFRTGVTPSNPTGTSWEHV 30

Beta propeller repeats in Physarum polycephalum tectonins, Limulus lectin L-6 and animal hypothetical proteins;

                            10        20        30
                    ....*....|....*....|....*....|....*..
gi 568939077    103 SSWSLVetPGEVVQISCGPHDLIWATLWEGQALVREG 139
Cdd:smart00706    1 GSWTQV--PGELVQVSVGPSDTVWAVNSDGNIYRRTG 35

Beta propeller repeats in Physarum polycephalum tectonins, Limulus lectin L-6 and animal hypothetical proteins;

                            10        20        30
                    ....*....|....*....|....*....|....*
gi 568939077    196 SWIEMVGEMTMVNVGLNDQVWGISCeDRAVYFRQG 230
Cdd:smart00706    2 SWTQVPGELVQVSVGPSDTVWAVNS-DGNIYRRTG 35

PH domain; PH stands for pleckstrin homology.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568939077   484 VKTGALQWWCDWKPHKWVDVRVALeqftghdgaRDSILFIY---YVVHEEKKYLHVFLNEVTVLVPVLNE---AKHSFAL 557
Cdd:pfam00169    2 VKEGWLLKKGGGKKKSWKKRYFVL---------FDGSLLYYkddKSGKSKEPKGSISLSGCEVVEVVASDspkRKFCFEL 72

                           90       100       110
                   ....*....|....*....|....*....|...
gi 568939077   558 YTPERTRQRwPVRLAAATEQDMNDWLALLSLSC 590
Cdd:pfam00169   73 RTGERTGKR-TYLLQAESEEERKDWIKAIQSAI 104

Propeller; Tectonins I and II are two dominant proteins in the nuclei and nuclear matrix from plasmodia of Physarum polycephalum (Slime mold) and both proteins contain six tandem repeats that are each 33-37 amino acids in length. Homologous repeats are found in L-6, a bacterial lipopolysaccharide-binding lectin from horseshoe crab hemocytes. The repetitive sequences of the tectonins and L-6 are reminiscent of the WD repeats of the beta-subunit of G proteins, suggesting that they form beta-propeller domains. The tectonins may be lectins that function as part of a transmembrane signalling complex during phagocytosis. Tectonin beta-propeller repeat-containing protein 1 (TECPR1) has a critical function during autophagosome maturation and autophagosome-lysosome fusion.

                           10        20        30
                   ....*....|....*....|....*....|.
gi 568939077   214 QVWGISCEDRaVYFRQGVTPSELSGKTWKAI 244
Cdd:pfam06462    1 QVWAVTSDGR-VYFRTGVTPSNPTGTSWEHV 30

Tectonin domain; This entry represents proteins homologous to tectonin. This protein adopts a 6 bladed beta propeller structure.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 568939077   910 LTQVSVGQTSVYALDENGNLWYRagitpsypQGSSWEHVSNNVRKVSVGPlDQVWVI--ANKV 970
Cdd:pfam19193    2 LKQIDAGQGQVWGVDSAGNVYYL--------TGSSWVRVPGRLKHVSVGP-AGVWGVnsNNKI 55

KIFIA and KIFIB protein pleckstrin homology (PH) domain; The kinesin-3 family motors KIFIA (Caenorhabditis elegans homolog unc-104) and KIFIB transport synaptic vesicle precursors that contain synaptic vesicle proteins, such as synaptophysin, synaptotagmin and the small GTPase RAB3A, but they do not transport organelles that contain plasma membrane proteins. They have a N-terminal motor domain, followed by a coiled-coil domain, and a C-terminal PH domain. KIF1A adopts a monomeric form in vitro, but acts as a processive dimer in vivo. KIF1B has alternatively spliced isoforms distinguished by the presence or absence of insertion sequences in the conserved amino-terminal region of the protein; this results in their different motor activities. KIF1A and KIF1B bind to RAB3 proteins through the adaptor protein mitogen-activated protein kinase (MAPK) -activating death domain (MADD; also calledDENN), which was first identified as a RAB3 guanine nucleotide exchange factor (GEF). 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.

                          10        20        30
                  ....*....|....*....|....*....|..
gi 568939077  552 KHSFALYTPERTrqrwpVRLAAATEQDMNDWL 583
Cdd:cd01233    69 PNVFAVYTPTNS-----YLLQARSEKEMQDWL 95