EAP30/Vps36 family; This family includes EAP30 as well as the Vps36 protein. Vps36 is involved in Golgi to endosome trafficking. EAP30 is a subunit of the ELL complex. The ELL is an 80-kDa RNA polymerase II transcription factor. ELL interacts with three other proteins to form the complex known as ELL complex. The ELL complex is capable of increasing that catalytic rate of transcription elongation, but is unable to repress initiation of transcription by RNA polymerase II as is the case of ELL. EAP30 is thought to lead to the derepression of ELL's transcriptional inhibitory activity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1032275741 174 VGLAGILRKEQEQWESTDKSLQDAFQDLNALMSKAKEMVSLAEKMRQKLLSAPSSQNgstddeemgskeEMQQWMLSVGI 253
Cdd:pfam04157   1 VGIAALEQRQEQQQEQYEELLSSAFEDLEALMEKFKELVEFAEKHKKKIKKNPEFRA------------QFQSMCASLGV 68

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1032275741 254 iSPVTKES----AGALYHQELSRQLADFVRIPLEKAGGMISLTDMYYHFNRARGTELISPDDLWQACTLWEKfDVPVMLR 329
Cdd:pfam04157  69 -DPLTFWWmsllGVGDFYYELAVQIVEVCLATRDENGGLISLDDLYARVNRARGVELISPDDLLRAIKLLEL-VLGSRLR 146

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1032275741 330 KFDSGVMVIQNKSHSDEEVmsrirmLVTKTETLRVGVTASDAALTLKIAPAMAKEHLLSAETKGLLCRD 398
Cdd:pfam04157 147 KFKSGLLVVQLELNTDQTE------VASRLGGLGGYVTASELADNLGWSVARAKEVLEDLEREGLLWRD 209

EAP30/Vps36 family; This family includes EAP30 as well as the Vps36 protein. Vps36 is involved in Golgi to endosome trafficking. EAP30 is a subunit of the ELL complex. The ELL is an 80-kDa RNA polymerase II transcription factor. ELL interacts with three other proteins to form the complex known as ELL complex. The ELL complex is capable of increasing that catalytic rate of transcription elongation, but is unable to repress initiation of transcription by RNA polymerase II as is the case of ELL. EAP30 is thought to lead to the derepression of ELL's transcriptional inhibitory activity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1032275741 174 VGLAGILRKEQEQWESTDKSLQDAFQDLNALMSKAKEMVSLAEKMRQKLLSAPSSQNgstddeemgskeEMQQWMLSVGI 253
Cdd:pfam04157   1 VGIAALEQRQEQQQEQYEELLSSAFEDLEALMEKFKELVEFAEKHKKKIKKNPEFRA------------QFQSMCASLGV 68

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1032275741 254 iSPVTKES----AGALYHQELSRQLADFVRIPLEKAGGMISLTDMYYHFNRARGTELISPDDLWQACTLWEKfDVPVMLR 329
Cdd:pfam04157  69 -DPLTFWWmsllGVGDFYYELAVQIVEVCLATRDENGGLISLDDLYARVNRARGVELISPDDLLRAIKLLEL-VLGSRLR 146

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1032275741 330 KFDSGVMVIQNKSHSDEEVmsrirmLVTKTETLRVGVTASDAALTLKIAPAMAKEHLLSAETKGLLCRD 398
Cdd:pfam04157 147 KFKSGLLVVQLELNTDQTE------VASRLGGLGGYVTASELADNLGWSVARAKEVLEDLEREGLLWRD 209

Pleckstrin homology-like domain or GLUE (GRAM-like ubiquitin-binding in Eap45) domain of Eap45; ESCRT complexes form the main machinery driving protein sorting from endosomes to lysosomes. Human/yeast ESCRT-I consists of Tsg101/Vps23, Vps28/Vps28, and a Vps37 homolog/Vps37. Human/yeast ESCRT-II is composed of EAP20/Vps25, EAP30/Vps22, and EAP45/Vps36. Yeast ESCRT-III consists Vps2, Vps20, Vps24, and Snf7 subunits. In contrast, there are three Human paralogs of Snf7 (hSnf7-1/CHMP4A, hSnf7-2/CHMP4B, and hSnf7-3/CHMP4C) and two paralogs of Vps2 (CHMP2A and CHMP2B). Yeast ESCRT-I links directly to ESCRT-II, through a tight interaction of Vps28 (ESCRT-I) with the yeast-specific zinc-finger insertion within the GLUE domain of Vps36. The Vps36 subunit (ESCRT-II) binds ubiquitin using one of its two NZF zinc fingers in its N-terminal region. Human Vps36, EAP45, also binds ubiquitin despite having no NZF domain. Instead, mammalian ESCRT-II interacts with Ub through the Eap45 GLUE domain directly. While yeast Vps36 GLUE shows a preference for the singly phosphorylated PI(3)P, while Eap45 GLUE preferentially binds the triply phosphorylated phosphatidylinositol PI(3,4,5)P3. Structurally, Eap45 GLUE only has a PH-like fold since it lacks the secondary structure element corresponding to the 4 strand, unlike that of yeast Vps36 GLUE. ESCRT-II also interacts with ESCRT-III via a EAP20(Vps25)/CHMP6(Vps20) interaction. The interactions of ESCRT-II GLUE domain with membranes, ESCRT-I, and ubiquitin are critical for ubiquitinated cargo progression from early to late endosomes. 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
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1032275741  52 TALRSGNLILTTHRLIWIpSQSNESVPSSIPLSAVthIYSHKKSIKSMFHSPRI 105
Cdd:cd13226    33 TKFDSGELVLTSHRLIWR-DQKQIERCLSLPLSLI--VFIEEEESGGFGKSAKI 83

EAP30/Vps36 family; This family includes EAP30 as well as the Vps36 protein. Vps36 is involved in Golgi to endosome trafficking. EAP30 is a subunit of the ELL complex. The ELL is an 80-kDa RNA polymerase II transcription factor. ELL interacts with three other proteins to form the complex known as ELL complex. The ELL complex is capable of increasing that catalytic rate of transcription elongation, but is unable to repress initiation of transcription by RNA polymerase II as is the case of ELL. EAP30 is thought to lead to the derepression of ELL's transcriptional inhibitory activity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1032275741 174 VGLAGILRKEQEQWESTDKSLQDAFQDLNALMSKAKEMVSLAEKMRQKLLSAPSSQNgstddeemgskeEMQQWMLSVGI 253
Cdd:pfam04157   1 VGIAALEQRQEQQQEQYEELLSSAFEDLEALMEKFKELVEFAEKHKKKIKKNPEFRA------------QFQSMCASLGV 68

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1032275741 254 iSPVTKES----AGALYHQELSRQLADFVRIPLEKAGGMISLTDMYYHFNRARGTELISPDDLWQACTLWEKfDVPVMLR 329
Cdd:pfam04157  69 -DPLTFWWmsllGVGDFYYELAVQIVEVCLATRDENGGLISLDDLYARVNRARGVELISPDDLLRAIKLLEL-VLGSRLR 146

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1032275741 330 KFDSGVMVIQNKSHSDEEVmsrirmLVTKTETLRVGVTASDAALTLKIAPAMAKEHLLSAETKGLLCRD 398
Cdd:pfam04157 147 KFKSGLLVVQLELNTDQTE------VASRLGGLGGYVTASELADNLGWSVARAKEVLEDLEREGLLWRD 209

Pleckstrin homology-like domain or GLUE (GRAM-like ubiquitin-binding in Eap45) domain of Eap45; ESCRT complexes form the main machinery driving protein sorting from endosomes to lysosomes. Human/yeast ESCRT-I consists of Tsg101/Vps23, Vps28/Vps28, and a Vps37 homolog/Vps37. Human/yeast ESCRT-II is composed of EAP20/Vps25, EAP30/Vps22, and EAP45/Vps36. Yeast ESCRT-III consists Vps2, Vps20, Vps24, and Snf7 subunits. In contrast, there are three Human paralogs of Snf7 (hSnf7-1/CHMP4A, hSnf7-2/CHMP4B, and hSnf7-3/CHMP4C) and two paralogs of Vps2 (CHMP2A and CHMP2B). Yeast ESCRT-I links directly to ESCRT-II, through a tight interaction of Vps28 (ESCRT-I) with the yeast-specific zinc-finger insertion within the GLUE domain of Vps36. The Vps36 subunit (ESCRT-II) binds ubiquitin using one of its two NZF zinc fingers in its N-terminal region. Human Vps36, EAP45, also binds ubiquitin despite having no NZF domain. Instead, mammalian ESCRT-II interacts with Ub through the Eap45 GLUE domain directly. While yeast Vps36 GLUE shows a preference for the singly phosphorylated PI(3)P, while Eap45 GLUE preferentially binds the triply phosphorylated phosphatidylinositol PI(3,4,5)P3. Structurally, Eap45 GLUE only has a PH-like fold since it lacks the secondary structure element corresponding to the 4 strand, unlike that of yeast Vps36 GLUE. ESCRT-II also interacts with ESCRT-III via a EAP20(Vps25)/CHMP6(Vps20) interaction. The interactions of ESCRT-II GLUE domain with membranes, ESCRT-I, and ubiquitin are critical for ubiquitinated cargo progression from early to late endosomes. 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
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1032275741  52 TALRSGNLILTTHRLIWIpSQSNESVPSSIPLSAVthIYSHKKSIKSMFHSPRI 105
Cdd:cd13226    33 TKFDSGELVLTSHRLIWR-DQKQIERCLSLPLSLI--VFIEEEESGGFGKSAKI 83