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Conserved domains on  [gi|189163489|ref|NP_001099562|]
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vacuolar protein-sorting-associated protein 36 [Rattus norvegicus]

Protein Classification

EAP30/Vps36 family protein( domain architecture ID 10192393)

EAP30/Vps36 family protein such as Vps36 that is involved in Golgi to endosome trafficking

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
PH-GRAM-like_Eap45 cd13226
Pleckstrin homology-like domain or GLUE (GRAM-like ubiquitin-binding in Eap45) domain of Eap45; ...
1-128 2.25e-79

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.


:

Pssm-ID: 275408 [Multi-domain]  Cd Length: 129  Bit Score: 239.93  E-value: 2.25e-79
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 189163489   1 MDRFVWTSGLLEINETLVIQQRGVRVYDGEEKIKFDAGTLLLSTHRLIWRDQKNNECCMAIPLSQIVFIEEQAAG-IGKS 79
Cdd:cd13226    1 MDRFMWCDGLLFPNETLVIQQRGVRIYDGDEKTKFDSGELVLTSHRLIWRDQKQIERCLSLPLSLIVFIEEEESGgFGKS 80
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 189163489  80 AKIVVHLHPAPPNKEPGPFQSSKNSYIKLSFKEHGQIEFYRRLSEEMTQ 128
Cdd:cd13226   81 AKIVVHLHPAPPNKEPGPKQSSPYNYIKLSFKEGGQSEFYRALSEELTR 129
EAP30 pfam04157
EAP30/Vps36 family; This family includes EAP30 as well as the Vps36 protein. Vps36 is involved ...
154-370 5.91e-73

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.


:

Pssm-ID: 461201  Cd Length: 210  Bit Score: 226.34  E-value: 5.91e-73
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 189163489  154 VGIVGIERKLEEKRKETDKNISEAFEDLSKLMIKAKEMVELSKSIANKIKEKQGDVTEdetirFKSYLLSMGIaNPVTRE 233
Cdd:pfam04157   1 VGIAALEQRQEQQQEQYEELLSSAFEDLEALMEKFKELVEFAEKHKKKIKKNPEFRAQ-----FQSMCASLGV-DPLTFW 74
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 189163489  234 TY--GSGTQYHMQLAKQLAGILQAPLEERGGIMSLTEVYCLVNRARGMELLSPEDLVNACKMLEgLKLPVRLRVFDSGVM 311
Cdd:pfam04157  75 WMslLGVGDFYYELAVQIVEVCLATRDENGGLISLDDLYARVNRARGVELISPDDLLRAIKLLE-LVLGSRLRKFKSGLL 153
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 189163489  312 VIELQTHKEEEMVASALetVSERGSLTSEEFAKLVGMSVLLAKERLLLAEKMGHLCRDD 370
Cdd:pfam04157 154 VVQLELNTDQTEVASRL--GGLGGYVTASELADNLGWSVARAKEVLEDLEREGLLWRDE 210
 
Name Accession Description Interval E-value
PH-GRAM-like_Eap45 cd13226
Pleckstrin homology-like domain or GLUE (GRAM-like ubiquitin-binding in Eap45) domain of Eap45; ...
1-128 2.25e-79

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.


Pssm-ID: 275408 [Multi-domain]  Cd Length: 129  Bit Score: 239.93  E-value: 2.25e-79
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 189163489   1 MDRFVWTSGLLEINETLVIQQRGVRVYDGEEKIKFDAGTLLLSTHRLIWRDQKNNECCMAIPLSQIVFIEEQAAG-IGKS 79
Cdd:cd13226    1 MDRFMWCDGLLFPNETLVIQQRGVRIYDGDEKTKFDSGELVLTSHRLIWRDQKQIERCLSLPLSLIVFIEEEESGgFGKS 80
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 189163489  80 AKIVVHLHPAPPNKEPGPFQSSKNSYIKLSFKEHGQIEFYRRLSEEMTQ 128
Cdd:cd13226   81 AKIVVHLHPAPPNKEPGPKQSSPYNYIKLSFKEGGQSEFYRALSEELTR 129
EAP30 pfam04157
EAP30/Vps36 family; This family includes EAP30 as well as the Vps36 protein. Vps36 is involved ...
154-370 5.91e-73

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.


Pssm-ID: 461201  Cd Length: 210  Bit Score: 226.34  E-value: 5.91e-73
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 189163489  154 VGIVGIERKLEEKRKETDKNISEAFEDLSKLMIKAKEMVELSKSIANKIKEKQGDVTEdetirFKSYLLSMGIaNPVTRE 233
Cdd:pfam04157   1 VGIAALEQRQEQQQEQYEELLSSAFEDLEALMEKFKELVEFAEKHKKKIKKNPEFRAQ-----FQSMCASLGV-DPLTFW 74
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 189163489  234 TY--GSGTQYHMQLAKQLAGILQAPLEERGGIMSLTEVYCLVNRARGMELLSPEDLVNACKMLEgLKLPVRLRVFDSGVM 311
Cdd:pfam04157  75 WMslLGVGDFYYELAVQIVEVCLATRDENGGLISLDDLYARVNRARGVELISPDDLLRAIKLLE-LVLGSRLRKFKSGLL 153
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 189163489  312 VIELQTHKEEEMVASALetVSERGSLTSEEFAKLVGMSVLLAKERLLLAEKMGHLCRDD 370
Cdd:pfam04157 154 VVQLELNTDQTEVASRL--GGLGGYVTASELADNLGWSVARAKEVLEDLEREGLLWRDE 210
Vps36_ESCRT-II pfam11605
Vacuolar protein sorting protein 36 Vps36; Vps36 is a subunit of ESCRT-II, a protein involved ...
3-88 1.08e-13

Vacuolar protein sorting protein 36 Vps36; Vps36 is a subunit of ESCRT-II, a protein involved in driving protein sorting from endosomes to lysosomes. The GLUE domain of Vps36 allows for a tight interaction to occur between the protein and Vps28, a subunit of ESCRT-I. This interaction is critical for ubiquitinated cargo progression from early to late endosomes.


Pssm-ID: 402964  Cd Length: 92  Bit Score: 66.18  E-value: 1.08e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 189163489    3 RFVWTSGLLEINETLVIQQRGVRVYDGEEKIK-FDAGTLLLSTHRLIWRDQ---KNNECCMAIPLSQIVFIEEQAAGIGK 78
Cdd:pfam11605   2 RNTSGRPVLRENEVDIYVQDNVGLYQGDQKILnRQNGRLYLTTHRIIYVDSadpKKVSLSLPLKLVYSISEKEYSSGFLR 81
                          90
                  ....*....|.
gi 189163489   79 -SAKIVVHLHP 88
Cdd:pfam11605  82 sSPKIILFLKP 92
 
Name Accession Description Interval E-value
PH-GRAM-like_Eap45 cd13226
Pleckstrin homology-like domain or GLUE (GRAM-like ubiquitin-binding in Eap45) domain of Eap45; ...
1-128 2.25e-79

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.


Pssm-ID: 275408 [Multi-domain]  Cd Length: 129  Bit Score: 239.93  E-value: 2.25e-79
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 189163489   1 MDRFVWTSGLLEINETLVIQQRGVRVYDGEEKIKFDAGTLLLSTHRLIWRDQKNNECCMAIPLSQIVFIEEQAAG-IGKS 79
Cdd:cd13226    1 MDRFMWCDGLLFPNETLVIQQRGVRIYDGDEKTKFDSGELVLTSHRLIWRDQKQIERCLSLPLSLIVFIEEEESGgFGKS 80
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 189163489  80 AKIVVHLHPAPPNKEPGPFQSSKNSYIKLSFKEHGQIEFYRRLSEEMTQ 128
Cdd:cd13226   81 AKIVVHLHPAPPNKEPGPKQSSPYNYIKLSFKEGGQSEFYRALSEELTR 129
EAP30 pfam04157
EAP30/Vps36 family; This family includes EAP30 as well as the Vps36 protein. Vps36 is involved ...
154-370 5.91e-73

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.


Pssm-ID: 461201  Cd Length: 210  Bit Score: 226.34  E-value: 5.91e-73
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 189163489  154 VGIVGIERKLEEKRKETDKNISEAFEDLSKLMIKAKEMVELSKSIANKIKEKQGDVTEdetirFKSYLLSMGIaNPVTRE 233
Cdd:pfam04157   1 VGIAALEQRQEQQQEQYEELLSSAFEDLEALMEKFKELVEFAEKHKKKIKKNPEFRAQ-----FQSMCASLGV-DPLTFW 74
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 189163489  234 TY--GSGTQYHMQLAKQLAGILQAPLEERGGIMSLTEVYCLVNRARGMELLSPEDLVNACKMLEgLKLPVRLRVFDSGVM 311
Cdd:pfam04157  75 WMslLGVGDFYYELAVQIVEVCLATRDENGGLISLDDLYARVNRARGVELISPDDLLRAIKLLE-LVLGSRLRKFKSGLL 153
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 189163489  312 VIELQTHKEEEMVASALetVSERGSLTSEEFAKLVGMSVLLAKERLLLAEKMGHLCRDD 370
Cdd:pfam04157 154 VVQLELNTDQTEVASRL--GGLGGYVTASELADNLGWSVARAKEVLEDLEREGLLWRDE 210
Vps36_ESCRT-II pfam11605
Vacuolar protein sorting protein 36 Vps36; Vps36 is a subunit of ESCRT-II, a protein involved ...
3-88 1.08e-13

Vacuolar protein sorting protein 36 Vps36; Vps36 is a subunit of ESCRT-II, a protein involved in driving protein sorting from endosomes to lysosomes. The GLUE domain of Vps36 allows for a tight interaction to occur between the protein and Vps28, a subunit of ESCRT-I. This interaction is critical for ubiquitinated cargo progression from early to late endosomes.


Pssm-ID: 402964  Cd Length: 92  Bit Score: 66.18  E-value: 1.08e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 189163489    3 RFVWTSGLLEINETLVIQQRGVRVYDGEEKIK-FDAGTLLLSTHRLIWRDQ---KNNECCMAIPLSQIVFIEEQAAGIGK 78
Cdd:pfam11605   2 RNTSGRPVLRENEVDIYVQDNVGLYQGDQKILnRQNGRLYLTTHRIIYVDSadpKKVSLSLPLKLVYSISEKEYSSGFLR 81
                          90
                  ....*....|.
gi 189163489   79 -SAKIVVHLHP 88
Cdd:pfam11605  82 sSPKIILFLKP 92
PH-GRAM cd10570
Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins ...
19-122 3.95e-12

Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins (PH-GRAM) domain; Myotubularin-related proteins are a subfamily of protein tyrosine phosphatases (PTPs) that dephosphorylate D3-phosphorylated inositol lipids. Mutations in this family cause the human neuromuscular disorders myotubular myopathy and type 4B Charcot-Marie-Tooth syndrome. 6 of the 13 MTMRs (MTMRs 5, 9-13) contain naturally occurring substitutions of residues required for catalysis by PTP family enzymes. Although these proteins are predicted to be enzymatically inactive, they are thought to function as antagonists of endogenous phosphatase activity or interaction modules. Most MTMRs contain a N-terminal PH-GRAM domain, a Rac-induced recruitment domain (RID) domain, a PTP domain (which may be active or inactive), a SET-interaction domain, and a C-terminal coiled-coil region. In addition some members contain DENN domain N-terminal to the PH-GRAM domain and FYVE, PDZ, and PH domains C-terminal to the coiled-coil region. The GRAM domain, found in myotubularins, glucosyltransferases, and other putative membrane-associated proteins, is part of a larger motif with a pleckstrin homology (PH) domain fold.


Pssm-ID: 275393  Cd Length: 94  Bit Score: 62.01  E-value: 3.95e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 189163489  19 IQQRGVRVYDGEEKIKFDA-GTLLLSTHRLIWRDQKN-NECCMAIPLSQIVFIEEQAAGIGKSAKIVVHLHPappnkepg 96
Cdd:cd10570    1 IEKLGVRFCCALRPRKLPLeGTLYLSTYRLIFSSKADgDETKLVIPLVDITDVEKIAGASFLPSGLIITCKD-------- 72
                         90       100
                 ....*....|....*....|....*...
gi 189163489  97 pfqsskNSYIKLSFKE--HGQIEFYRRL 122
Cdd:cd10570   73 ------FRTIKFSFDSedEAVKVIARVL 94
PH-like cd00900
Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like ...
19-122 1.03e-10

Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like and IRS-like PTB domains, the ran-binding domain, the EVH1 domain, a domain in neurobeachin and the third domain of FERM. All of these domains have a PH fold, but lack significant sequence similarity. They are generally involved in targeting to protein to the appropriate cellular location or interacting with a binding partner. This domain family possesses multiple functions including the ability to bind inositol phosphates and to other proteins.


Pssm-ID: 275390  Cd Length: 89  Bit Score: 57.79  E-value: 1.03e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 189163489  19 IQQRGVRVYDgeEKIKFDAGTLLLSTHRLIWRDQKNNECCMAIPLSQIVFIEEQAAGIgKSAKIVVHLHPappnkepgpf 98
Cdd:cd00900    1 LKFRAVRVYR--EPTKRVEGTLYITSDRLILRDKNDGGLELSIPISDIVNVNVSPQGP-SSRYLVLVLKD---------- 67
                         90       100
                 ....*....|....*....|....*
gi 189163489  99 qssKNSYIKLSF-KEHGQIEFYRRL 122
Cdd:cd00900   68 ---RGEFVGFSFpKEEDAIEISDAL 89
PH-GRAM-like_Vps36 cd13227
Pleckstrin homology-like domain or GLUE (GRAM-like ubiquitin-binding in Eap45) domain of Vps36; ...
7-91 1.30e-04

Pleckstrin homology-like domain or GLUE (GRAM-like ubiquitin-binding in Eap45) domain of Vps36; ESCRT complexes form the main machinery driving protein sorting from endosomes to lysosomes. Yeast/human ESCRT-I consists of Vps23/Tsg101, Vps28/Vps28, and Vps37/Vps37 homolog. Yeast/human ESCRT-II is composed of Vps25/EAP20, Vps22/EAP30, and Vps36/EAP45. 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 itself. The yeast Vps36 GLUE has a complete PH domain, wherease Eap45 GLUE only has a PH-like fold since it lacks the secondary structure element corresponding to the 4 strand. ESCRT-II also interacts with ESCRT-III via a Vps25(EAP20)/Vps20(CHMP6) interaction. Structure 2CAY is missing this insertion that contains 2 NZF zinc fingers. It is a split PH domain, with a noncanonical lipid binding pocket that binds PI(3)P. 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.


Pssm-ID: 275409 [Multi-domain]  Cd Length: 119  Bit Score: 41.16  E-value: 1.30e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 189163489   7 TSG--LLEINETLVIQQRGVRVYDGEEKIK-FDAGTLLLSTHRLIWRD----QKNNeccMAIPLSQIVFIEEQAAGIGKS 79
Cdd:cd13227    8 RSGqpILRENEKDIYVDDNVGLYHGKSKILnRQNGRIYLTSQRIIYVDdddpKKNS---VALELDDIKSVEYSSGFLKRS 84
                         90
                 ....*....|..
gi 189163489  80 AKIVVHLHPAPP 91
Cdd:cd13227   85 PKIILFLKDESQ 96
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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