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 442630805  28 DAQVKVREATSNDPWGPSAAIMSEIAELTYNVVAFSEIMQMIWKRLNDHGKNWRHVYKALILLEYLIKTGSEKVAQQCKE 107
Cdd:cd16990    1 EAEIKVREATSNDPWGPSSSLMSEIADLTYNVVAFSEIMSMIWKRLNDHGKNWRHVYKALTLLEYLIKTGSERVAQQCKE 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 442630805 108 NIFAIQTLREFVYFEE-GKDQGTHVREKAKQLVTLLKDDERLKN 150
Cdd:cd16990   81 NIFAIQTLKDFQYIDRdGKDQGVNVREKAKQLVSLLKDDERLKN 124

Ubiquitin-interacting motif; Present in proteasome subunit S5a and other ubiquitin-associated proteins.

                           10        20
                   ....*....|....*....|
gi 442630805   208 EEELQLQLAMAMSREEAEQE 227
Cdd:smart00726   1 DEDEDLQRALELSLQEAEES 20

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 442630805  28 DAQVKVREATSNDPWGPSAAIMSEIAELTYNVVAFSEIMQMIWKRLNDHGKNWRHVYKALILLEYLIKTGSEKVAQQCKE 107
Cdd:cd16990    1 EAEIKVREATSNDPWGPSSSLMSEIADLTYNVVAFSEIMSMIWKRLNDHGKNWRHVYKALTLLEYLIKTGSERVAQQCKE 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 442630805 108 NIFAIQTLREFVYFEE-GKDQGTHVREKAKQLVTLLKDDERLKN 150
Cdd:cd16990   81 NIFAIQTLKDFQYIDRdGKDQGVNVREKAKQLVSLLKDDERLKN 124

Epsin N-terminal homology (ENTH) domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442630805    27 SDAQVKVREATSNDPWGPSAAIMSEIAELTYNV-VAFSEIMQMIWKRLNDHGkNWRHVYKALILLEYLIKTGSEKVAQQC 105
Cdd:smart00273   1 SDLEVKVRKATNNDEWGPKGKHLREIIQGTHNEkSSFAEIMAVLWRRLNDTK-NWRVVYKALILLHYLLRNGSPRVILEA 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 442630805   106 KENIFAIQTLREFVYFEE-GKDQGTHVREKAKQLVTLLKDDERLKNER 152
Cdd:smart00273  80 LRNRNRILNLSDFQDIDSrGKDQGANIRTYAKYLLERLEDDRRLKEER 127

Ubiquitin-interacting motif; Present in proteasome subunit S5a and other ubiquitin-associated proteins.

                           10        20
                   ....*....|....*....|
gi 442630805   208 EEELQLQLAMAMSREEAEQE 227
Cdd:smart00726   1 DEDEDLQRALELSLQEAEES 20

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 442630805  28 DAQVKVREATSNDPWGPSAAIMSEIAELTYNVVAFSEIMQMIWKRLNDHGKNWRHVYKALILLEYLIKTGSEKVAQQCKE 107
Cdd:cd16990    1 EAEIKVREATSNDPWGPSSSLMSEIADLTYNVVAFSEIMSMIWKRLNDHGKNWRHVYKALTLLEYLIKTGSERVAQQCKE 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 442630805 108 NIFAIQTLREFVYFEE-GKDQGTHVREKAKQLVTLLKDDERLKN 150
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 442630805   26 YSDAQVKVREATSNDPWGPSAAIMSEIAELTYNVVAFSEIMQMIWKRLNDHGKNWRHVYKALILLEYLIKTGSEKVAQQC 105
Cdd:pfam01417   1 YSETELKVREATNNDPWGPSGTLMDEIARLTYNYVEFPEIMKMLWKRLNDKGKNWRHIYKALTLLEYLLKNGSERVVDDL 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 442630805  106 KENIFAIQTLREFVYFEE-GKDQGTHVREKAKQLVTLLKDDERL 148
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 442630805  29 AQVKVREATSNDPWGPSAAIMSEIAELTYNVVAFSEIMQMIWKR-LNDHGKNWRHVYKALILLEYLIKTGSEKVAQQCKE 107
Cdd:cd16989    1 IESKVREATNDDPWGPTGQLMQEIARYTFTYEQFPEVMNMLWKRmLKDNKKNWRRVYKSLLLLDYLLKNGSERVVTSARE 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 442630805 108 NIFAIQTLREFVYFEE-GKDQGTHVREKAKQLVTLLKDDERLKNERVKA 155
Cdd:cd16989   81 HIYDLRSLENYHFIDEkGKDQGINVRQKVKEIIELLQDDERLREERKKA 129

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 442630805  32 KVREATSNDPWGPSAAIMSEIAELTYNVVAFSEIMQMIWKRLND-HGKNWRHVYKALILLEYLIKTGSEKVAQQCKENIF 110
Cdd:cd16992    4 KVREATNNDPWGASSTLMQEIAQGTYNYQQFNEIMPMIYKRFTEkAGSEWRQIYKALQLLEYLIKNGSERVVDDARGHLT 83

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 442630805 111 AIQTLREFVYFEE-GKDQGTHVREKAKQLVTLLKDDER 147
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 442630805  29 AQVKVREAT-SNDPWGPSAAIMSEIAELTYNVVAFSEIMQMIWKRLNDHG-----KNWRHVYKALILLEYLIKTGSEKVA 102
Cdd:cd16994    1 TELKVKQATdDNETSGATGTLMNEISVLTYSPKTLKEITQVLKKRLSGNSkksshKNCVHILKTLTLISYLINNGSNEFI 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 442630805 103 QQCKENIFAIQTLREFVYFEEGKDQ-GTHVREKAKQLVTLLKDDE 146
Cdd:cd16994   81 AWLRSNLYLIERLKDFEVQDNRDLPmANQIRSLSQDICELINDDE 125

VHS (Vps27/Hrs/STAM) domain family; The VHS domain is present in Vps27 (Vacuolar Protein Sorting), Hrs (Hepatocyte growth factor-regulated tyrosine kinase substrate) and STAM (Signal Transducing Adaptor Molecule). It has a superhelical structure similar to that of the ARM (Armadillo) repeats and is present at the N-termini of proteins involved in intracellular membrane trafficking. There are four general groups of VHS domain containing proteins based on their association with other domains. The first group consists of proteins of the STAM/EAST/Hbp family, which has the domain composition of VHS-SH3-ITAM. The second consists of proteins with a FYVE domain C-terminal to VHS. The third consists of GGA proteins with a domain composition of VHS-GAT (GGA and TOM)-GAE (Gamma-Adaptin Ear) domain. The fourth consists of proteins with a VHS domain alone or with domains other than those mentioned above. In GGA proteins, VHS domains are involved in cargo recognition in trans-Golgi, thereby having a general membrane targeting/cargo recognition role in vesicular trafficking.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442630805  33 VREATSNDPWGPSAAIMSEIAELtYNVVAFS--EIMQMIWKRLNDhgKNWRHVYKALILLEYLIKTGSEKVAQQ-CKENI 109
Cdd:cd03561    5 VEKATSESLTEPDWALNLEICDL-VNSDPAQakDAVRALRKRLQS--KNPKVQLLALTLLETLVKNCGAPFHSEvASRDF 81

                         90       100       110
                 ....*....|....*....|....*....|
gi 442630805 110 faiqtLREFVYFEEGKDQGTHVREKAKQLV 139
Cdd:cd03561   82 -----LQELVKLVKKKKTSPEVREKALALI 106

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
                 ....*....|....*....|....*....|....*....|....*...
gi 442630805  56 TYN-VVAFSEIMQMIWKRLNDhgKNWRHVYKALILLEYLIKTGSEKVA 102
Cdd:cd16988   28 TYSsDASFGEIVRALSRRLRD--NSWTVVFKSLIVLHLMIREGETDDV 73

ANTH domain; AP180 is an endocytotic accessory proteins that has been implicated in the formation of clathrin-coated pits. The domain is involved in phosphatidylinositol 4,5-bisphosphate binding and is a universal adaptor for nucleation of clathrin coats.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442630805   28 DAQVKVREATSNDPWGPSAAIMSEIAELTYNVVAFSEIMQMIWKRLNDHgKNWRHVYKALILLEYLIKTGSEKVAQQCKE 107
Cdd:pfam07651   1 DLEVAVVKATSHDEAPPKEKHVREILVGTSSSAKLAALFWALSRRLPLT-RSWVVAFKALILVHKLLREGHPSVLQELLR 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 442630805  108 NIFAIQTLREFVYFEEGKDQGTHVREKAKQLvtllkdDERLK 149
Cdd:pfam07651  80 ARRRISSLLRISSFSLSWDYGAFIRAYAKYL------DERLD 115

hypothetical protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442630805 549 SALVNLDNLIKPIAPQ--------------TQTGNQPAYNPFSDNVVPPKT--NLFQQQQPAVPS-------------IN 599
Cdd:PLN03131 338 GSHASLDHFKAPVAPEaaapmappidlfqlPATSPAPPVDLFEIPPLDPAPaiNAYQPPQTSLPSsidlfggitqqqsIN 417

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442630805 600 QLKQQAPFSVSMNQDPWAPVMGGVSTTSQPQP-NLQVYNNAYQSSSSTNILGKSNIPTNMN-SSTSNSTIHSCYASPSPG 677
Cdd:PLN03131 418 SLDEKSPELSIPKNEGWATFDGIQPIASTPGNeNLTPFSIGPSMAGSANFDQVPSLDKGMQwPPFQNSSDEESASGPAPW 497

                 ....*....
gi 442630805 678 VDGIRNMDI 686
Cdd:PLN03131 498 LGDLHNVEA 506