Epsin N-Terminal Homology (ENTH) domain of Epsin family; Members of the epsin family play an important role as accessory proteins in clathrin-mediated endocytosis. They are important factors in clathrin-coated vesicle (CCV) generation. They contribute to membrane deformation and play a key function as adaptor proteins, coupling various components of clathrin-mediated uptake. They also have an important role in selecting and recognizing cargo. Three isoforms have been identified in mammals, epsin-1 to -3, and these are conserved in vertebrates. Epsin-1 is highly enriched and represents the dominant isoform in the brain. It is required for proper synaptic vesicle retrieval and modulates the endocytic capacity of synaptic vesicles. Epsins contain an Epsin N-Terminal Homology (ENTH) domain, an evolutionarily conserved protein module found primarily in proteins that participate in clathrin-mediated endocytosis. The ENTH domain is highly similar to the N-terminal region of the AP180 N-Terminal Homology (ANTH_N) domain. ENTH and ANTH_N domains are structurally similar to the VHS domain and are composed of a superhelix of eight alpha helices. ENTH domains bind both, inositol phospholipids with preference for PtdIns(4,5)P2, and proteins, and contribute to the nucleation and formation of clathrin coats on membranes. ENTH domains also function in the development of membrane curvature through lipid remodeling during the formation of CCVs. ENTH and ANTH (E/ANTH)-containing proteins have recently been shown to function with adaptor protein-1 and GGA adaptors at the Trans-Golgi Network, which suggests that E/ANTH domains are universal components of the machinery for clathrin-mediated membrane budding.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17569583  19 DAQVKVREATSNDPWGPSTALMSEIADLTHNPMAFTEIMSIVWKRLNDSGKNWRHVYKSLVLLDFLIKCGHEKVAQQCRE 98
Cdd:cd16990   1 EAEIKVREATSNDPWGPSSSLMSEIADLTYNVVAFSEIMSMIWKRLNDHGKNWRHVYKALTLLEYLIKTGSERVAQQCKE 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 17569583  99 NVFTIETLKDFQHVE-DNRDQGLNIREKAKQITSLLSDDERLKN 141
Cdd:cd16990  81 NIFAIQTLKDFQYIDrDGKDQGVNVREKAKQLVSLLKDDERLKN 124

Epsin N-Terminal Homology (ENTH) domain of Epsin family; Members of the epsin family play an important role as accessory proteins in clathrin-mediated endocytosis. They are important factors in clathrin-coated vesicle (CCV) generation. They contribute to membrane deformation and play a key function as adaptor proteins, coupling various components of clathrin-mediated uptake. They also have an important role in selecting and recognizing cargo. Three isoforms have been identified in mammals, epsin-1 to -3, and these are conserved in vertebrates. Epsin-1 is highly enriched and represents the dominant isoform in the brain. It is required for proper synaptic vesicle retrieval and modulates the endocytic capacity of synaptic vesicles. Epsins contain an Epsin N-Terminal Homology (ENTH) domain, an evolutionarily conserved protein module found primarily in proteins that participate in clathrin-mediated endocytosis. The ENTH domain is highly similar to the N-terminal region of the AP180 N-Terminal Homology (ANTH_N) domain. ENTH and ANTH_N domains are structurally similar to the VHS domain and are composed of a superhelix of eight alpha helices. ENTH domains bind both, inositol phospholipids with preference for PtdIns(4,5)P2, and proteins, and contribute to the nucleation and formation of clathrin coats on membranes. ENTH domains also function in the development of membrane curvature through lipid remodeling during the formation of CCVs. ENTH and ANTH (E/ANTH)-containing proteins have recently been shown to function with adaptor protein-1 and GGA adaptors at the Trans-Golgi Network, which suggests that E/ANTH domains are universal components of the machinery for clathrin-mediated membrane budding.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17569583  19 DAQVKVREATSNDPWGPSTALMSEIADLTHNPMAFTEIMSIVWKRLNDSGKNWRHVYKSLVLLDFLIKCGHEKVAQQCRE 98
Cdd:cd16990   1 EAEIKVREATSNDPWGPSSSLMSEIADLTYNVVAFSEIMSMIWKRLNDHGKNWRHVYKALTLLEYLIKTGSERVAQQCKE 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 17569583  99 NVFTIETLKDFQHVE-DNRDQGLNIREKAKQITSLLSDDERLKN 141
Cdd:cd16990  81 NIFAIQTLKDFQYIDrDGKDQGVNVREKAKQLVSLLKDDERLKN 124

Epsin N-terminal homology (ENTH) domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17569583     18 SDAQVKVREATSNDPWGPSTALMSEIADLTHN-PMAFTEIMSIVWKRLNDSGkNWRHVYKSLVLLDFLIKCGHEKVAQQC 96
Cdd:smart00273   1 SDLEVKVRKATNNDEWGPKGKHLREIIQGTHNeKSSFAEIMAVLWRRLNDTK-NWRVVYKALILLHYLLRNGSPRVILEA 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 17569583     97 RENVFTIETLKDFQHV-EDNRDQGLNIREKAKQITSLLSDDERLKNER 143
Cdd:smart00273  80 LRNRNRILNLSDFQDIdSRGKDQGANIRTYAKYLLERLEDDRRLKEER 127

Epsin N-Terminal Homology (ENTH) domain of Epsin family; Members of the epsin family play an important role as accessory proteins in clathrin-mediated endocytosis. They are important factors in clathrin-coated vesicle (CCV) generation. They contribute to membrane deformation and play a key function as adaptor proteins, coupling various components of clathrin-mediated uptake. They also have an important role in selecting and recognizing cargo. Three isoforms have been identified in mammals, epsin-1 to -3, and these are conserved in vertebrates. Epsin-1 is highly enriched and represents the dominant isoform in the brain. It is required for proper synaptic vesicle retrieval and modulates the endocytic capacity of synaptic vesicles. Epsins contain an Epsin N-Terminal Homology (ENTH) domain, an evolutionarily conserved protein module found primarily in proteins that participate in clathrin-mediated endocytosis. The ENTH domain is highly similar to the N-terminal region of the AP180 N-Terminal Homology (ANTH_N) domain. ENTH and ANTH_N domains are structurally similar to the VHS domain and are composed of a superhelix of eight alpha helices. ENTH domains bind both, inositol phospholipids with preference for PtdIns(4,5)P2, and proteins, and contribute to the nucleation and formation of clathrin coats on membranes. ENTH domains also function in the development of membrane curvature through lipid remodeling during the formation of CCVs. ENTH and ANTH (E/ANTH)-containing proteins have recently been shown to function with adaptor protein-1 and GGA adaptors at the Trans-Golgi Network, which suggests that E/ANTH domains are universal components of the machinery for clathrin-mediated membrane budding.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17569583  19 DAQVKVREATSNDPWGPSTALMSEIADLTHNPMAFTEIMSIVWKRLNDSGKNWRHVYKSLVLLDFLIKCGHEKVAQQCRE 98
Cdd:cd16990   1 EAEIKVREATSNDPWGPSSSLMSEIADLTYNVVAFSEIMSMIWKRLNDHGKNWRHVYKALTLLEYLIKTGSERVAQQCKE 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 17569583  99 NVFTIETLKDFQHVE-DNRDQGLNIREKAKQITSLLSDDERLKN 141
Cdd:cd16990  81 NIFAIQTLKDFQYIDrDGKDQGVNVREKAKQLVSLLKDDERLKN 124

ENTH domain; The ENTH (Epsin N-terminal homology) domain is found in proteins involved in endocytosis and cytoskeletal machinery. The function of the ENTH domain is unknown.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17569583    17 FSDAQVKVREATSNDPWGPSTALMSEIADLTHNPMAFTEIMSIVWKRLNDSGKNWRHVYKSLVLLDFLIKCGHEKVAQQC 96
Cdd:pfam01417   1 YSETELKVREATNNDPWGPSGTLMDEIARLTYNYVEFPEIMKMLWKRLNDKGKNWRHIYKALTLLEYLLKNGSERVVDDL 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 17569583    97 RENVFTIETLKDFQHV-EDNRDQGLNIREKAKQITSLLSDDERL 139
Cdd:pfam01417  81 RENIYIIRTLTDFHYIdENGKDQGINVRKKAKEILNLLEDDELL 124

Epsin N-Terminal Homology (ENTH) domain of Epsin-related protein; Epsin-related protein (EpsinR) is also called clathrin interactor 1 (Clint), enthoprotin, or epsin-4. It is a clathrin-coated vesicle (CCV) protein that binds to membranes enriched in phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2), clathrin, and the gamma appendage domain of the adaptor protein complex 1 (AP1). It contains an Epsin N-Terminal Homology (ENTH) domain, an evolutionarily conserved protein module found primarily in proteins that participate in clathrin-mediated endocytosis. The ENTH domain is highly similar to the N-terminal region of the AP180 N-Terminal Homology (ANTH_N) domain. ENTH and ANTH_N domains are structurally similar to the VHS domain and are composed of a superhelix of eight alpha helices. ENTH domains bind both, inositol phospholipids with preference for PtdIns(4,5)P2, and proteins, and contribute to the nucleation and formation of clathrin coats on membranes. ENTH domains also function in the development of membrane curvature through lipid remodeling during the formation of clathrin-coated vesicles. The ENTH domain of human epsinR binds directly to the helical bundle domain of the mouse SNARE Vti1b; soluble NSF attachment protein receptors (SNAREs) are type II transmembrane proteins that have critical roles in providing the specificity and energy for transport-vesicle fusion. Specific ENTH domains may also function as protein cargo selection/recognition modules. ENTH and ANTH (E/ANTH)-containing proteins have recently been shown to function with adaptor protein-1 and GGA adaptors at the Trans-Golgi Network, which suggests that E/ANTH domains are universal components of the machinery for clathrin-mediated membrane budding.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17569583  20 AQVKVREATSNDPWGPSTALMSEIADLTHNPMAFTEIMSIVWKR-LNDSGKNWRHVYKSLVLLDFLIKCGHEKVAQQCRE 98
Cdd:cd16989   1 IESKVREATNDDPWGPTGQLMQEIARYTFTYEQFPEVMNMLWKRmLKDNKKNWRRVYKSLLLLDYLLKNGSERVVTSARE 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 17569583  99 NVFTIETLKDFQHVEDN-RDQGLNIREKAKQITSLLSDDERLKNER 143
Cdd:cd16989  81 HIYDLRSLENYHFIDEKgKDQGINVRQKVKEIIELLQDDERLREER 126

Epsin N-Terminal Homology (ENTH) domain of Yeast Ent3 and similar proteins; This subfamily is composed of one of two epsinR orthologs present in Saccharomyces cerevisiae, Epsin-3 (Ent3 or Ent3p), and similar proteins. Ent3 is an adaptor proteins at the Trans-Golgi Network (TGN); it cooperates with yeast SNARE Vti1p to regulate transport from the TGN to the prevacuolar endosome. Ent3 facilitates the interaction between Gga2p with both the endosomal syntaxin Pep12p and clathrin in the GGA-dependent transport to the late endosome. Yeast epsins contain an Epsin N-Terminal Homology (ENTH) domain, an evolutionarily conserved protein module found primarily in proteins that participate in clathrin-mediated endocytosis. ENTH domain is highly similar to the N-terminal region of the AP180 N-Terminal Homology (ANTH_N) domain. ENTH and ANTH_N domains are structurally similar to the VHS domain and are composed of a superhelix of eight alpha helices. ENTH domains bind both, inositol phospholipids with preference for PtdIns(4,5)P2, and proteins, and contribute to the nucleation and formation of clathrin coats on membranes. ENTH domains also function in the development of membrane curvature through lipid remodeling during the formation of clathrin-coated vesicles. Similar to mammalian epsinR, The ENTH domain of Ent3 binds to the yeast SNARE Vti1p; soluble NSF attachment protein receptors (SNAREs) are type II transmembrane proteins that have critical roles in providing the specificity and energy for transport-vesicle fusion. Specific ENTH domains may also function as protein cargo selection/recognition modules. ENTH and ANTH (E/ANTH)-containing proteins have recently been shown to function with adaptor protein-1 and GGA adaptors at the Trans-Golgi Network, which suggests that E/ANTH domains are universal components of the machinery for clathrin-mediated membrane budding.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17569583  23 KVREATSNDPWGPSTALMSEIADLTHNPMAFTEIMSIVWKRLND-SGKNWRHVYKSLVLLDFLIKCGHEKVAQQCRENVF 101
Cdd:cd16992   4 KVREATNNDPWGASSTLMQEIAQGTYNYQQFNEIMPMIYKRFTEkAGSEWRQIYKALQLLEYLIKNGSERVVDDARGHLT 83

                        90       100       110
                ....*....|....*....|....*....|....*...
gi 17569583 102 TIETLKDFQHVEDN-RDQGLNIREKAKQITSLLSDDER 138
Cdd:cd16992  84 LIKMLRSFHYIDDKgKDQGINVRNRAKELIELLSDDEK 121

Epsin N-Terminal Homology (ENTH) domain of Yeast Ent4 and similar proteins; Yeast Epsin-4 (Ent4 or Ent4p) has been reported to be involved in the Trans-Golgi Network (TGN)-to-vacuole sorting of Arn1p, a transporter for the uptake of ferrichrome, an important nutritional source of iron. Yeast epsins contain an Epsin N-Terminal Homology (ENTH) domain, an evolutionarily conserved protein module found primarily in proteins that participate in clathrin-mediated endocytosis. ENTH domain is highly similar to the N-terminal region of the AP180 N-Terminal Homology (ANTH_N) domain. ENTH and ANTH_N domains are structurally similar to the VHS domain and are composed of a superhelix of eight alpha helices. ENTH domains bind both, inositol phospholipids with preference for PtdIns(4,5)P2, and proteins, and contribute to the nucleation and formation of clathrin coats on membranes. ENTH domains also function in the development of membrane curvature through lipid remodeling during the formation of clathrin-coated vesicles. ENTH and ANTH (E/ANTH)-containing proteins have recently been shown to function with adaptor protein-1 and GGA adaptors at the Trans-Golgi Network, which suggests that E/ANTH domains are universal components of the machinery for clathrin-mediated membrane budding.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17569583  20 AQVKVREAT-SNDPWGPSTALMSEIADLTHNPMAFTEIMSIVWKRLN-----DSGKNWRHVYKSLVLLDFLIKCGHEKVA 93
Cdd:cd16994   1 TELKVKQATdDNETSGATGTLMNEISVLTYSPKTLKEITQVLKKRLSgnskkSSHKNCVHILKTLTLISYLINNGSNEFI 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 17569583  94 QQCRENVFTIETLKDFqHVEDNRDQGL--NIREKAKQITSLLSDDE 137
Cdd:cd16994  81 AWLRSNLYLIERLKDF-EVQDNRDLPManQIRSLSQDICELINDDE 125

Epsin N-Terminal Homology (ENTH) domain of Yeast Ent5 and similar proteins; This subfamily is composed of one of two epsinR orthologs present in Saccharomyces cerevisiae, Epsin-5 (Ent5 or Ent5p), and similar proteins. Ent5 is required, together with Ent3 and Vps27p for ubiquitin-dependent protein sorting into the multivesicular body. It is also required for protein transport from the Trans-Golgi Network (TGN) to the vacuole. Yeast epsins contain an Epsin N-Terminal Homology (ENTH) domain, an evolutionarily conserved protein module found primarily in proteins that participate in clathrin-mediated endocytosis. ENTH domain is highly similar to the N-terminal region of the AP180 N-Terminal Homology (ANTH_N) domain. ENTH and ANTH_N domains are structurally similar to the VHS domain and are composed of a superhelix of eight alpha helices. ENTH domains bind both, inositol phospholipids with preference for PtdIns(4,5)P2, and proteins, and contribute to the nucleation and formation of clathrin coats on membranes. ENTH domains also function in the development of membrane curvature through lipid remodeling during the formation of clathrin-coated vesicles. ENTH and ANTH (E/ANTH)-containing proteins have recently been shown to function with adaptor protein-1 and GGA adaptors at the Trans-Golgi Network, which suggests that E/ANTH domains are universal components of the machinery for clathrin-mediated membrane budding.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17569583  21 QVKVREATSNDPWGPSTA-LMSEIADLTHNPMAFteIMSIVWKRLNDS-------------------GKNWRHVYKSLVL 80
Cdd:cd16993   2 QIDIRRATNTDAWGPTPKhLAKVLRNRYQVPLYL--MTEYTLKRLVDHiatrpknlyekarkdyvnyGSEWRVVLKCLIV 79

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 17569583  81 LDFLI---KCGHE-KVAQQCREN---VFTIETLK-DFQHVEDNRDQ--GLNIREKAKQITSLLSDDERLKNERTRFI 147
Cdd:cd16993  80 IEFLLlnvDTGDElNQVLSCLLNhkhIFTREIAQyKVKFSNDGKMEihERGIQKKCELILQLIEDSDFLRQERAKNK 156

ANTH (AP180 N-Terminal Homology) domain, N-terminal region, of yeast clathrin coat assembly protein AP180 (YAP180) and similar proteins; This subfamily includes yeast clathrin coat assembly protein AP180 (YAP180) and similar proteins. There are two YAP180 proteins in Saccharomyces cerevisiae, AP180A (yAP180A or YAP1801) and AP180B (yAP180B or YAP1802). They are involved in endocytosis and clathrin cage assembly. ANTH domains bind both inositol phospholipids and proteins, and contribute to the nucleation and formation of clathrin coats on membranes. The ANTH domain is a unique module whose N-terminal half is structurally similar to the Epsin N-Terminal Homology (ENTH) and Vps27/Hrs/STAM (VHS) domains, containing a superhelix of eight alpha helices. In addition, it contains a coiled-coil C-terminal half with strutural similarity to spectrin repeats. It binds phosphoinositide PtdIns(4,5)P2 at a short conserved motif K[X]9[K/R][H/Y] between helices 1 and 2. This model describes the N-terminal region of ANTH domains of plant clathrin coat assembly protein AP180 and similar proteins.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17569583  43 IADLTHNPMAFTEIMSIVWKRLNDSgkNWRHVYKSLVLLDFLIKCGHEKVAQQC---RENVFTIETLKDFQHveDNRDQG 119
Cdd:cd16988  25 LLATYSSDASFGEIVRALSRRLRDN--SWTVVFKSLIVLHLMIREGETDDVLLYylsRPDFLDLRKIRNGSS--AGSGQL 100

                ....
gi 17569583 120 LNIR 123
Cdd:cd16988 101 QNIQ 104