ANTH (AP180 N-Terminal Homology) domain family, N-terminal region; The ANTH (AP180 N-Terminal Homology) domain family is composed of Adaptor Protein 180 (AP180), Clathrin Assembly Lymphoid Myeloid Leukemia protein (CALM), and similar proteins. ANTH domains bind both inositol phospholipids and proteins, and contribute to the nucleation and formation of clathrin coats on membranes. ANTH-bearing proteins have recently been shown to function with adaptor protein-1 and GGA adaptors at the Trans-Golgi Network, which suggests that the ANTH domain is a universal component of the machinery for clathrin-mediated membrane budding. 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063683454  32 LDVAIVKATNHVECPPKDRHLRKIFLATSAIRPRADVAYCIHALSRRLHKtRNWTVALKALLVIHRLLRDGDPTFREELL 111
Cdd:cd03564     1 LDVAVVKATNHDEVPPKEKHVRKLLLATSNGGGRADVAYIVHALAKRLHK-KNWIVVLKTLIVIHRLLREGSPSFLEELL 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1063683454 112 NFSQkgRIMQISNFKDDSSP-----VGWVRTYALFLEERLECF 149
Cdd:cd03564    80 RYSG--HIFNLSNFKDDSSPeawdlSAFIRRYARYLEERLECF 120

ANTH (AP180 N-Terminal Homology) domain family, N-terminal region; The ANTH (AP180 N-Terminal Homology) domain family is composed of Adaptor Protein 180 (AP180), Clathrin Assembly Lymphoid Myeloid Leukemia protein (CALM), and similar proteins. ANTH domains bind both inositol phospholipids and proteins, and contribute to the nucleation and formation of clathrin coats on membranes. ANTH-bearing proteins have recently been shown to function with adaptor protein-1 and GGA adaptors at the Trans-Golgi Network, which suggests that the ANTH domain is a universal component of the machinery for clathrin-mediated membrane budding. 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063683454  32 LDVAIVKATNHVECPPKDRHLRKIFLATSAIRPRADVAYCIHALSRRLHKtRNWTVALKALLVIHRLLRDGDPTFREELL 111
Cdd:cd03564     1 LDVAVVKATNHDEVPPKEKHVRKLLLATSNGGGRADVAYIVHALAKRLHK-KNWIVVLKTLIVIHRLLREGSPSFLEELL 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1063683454 112 NFSQkgRIMQISNFKDDSSP-----VGWVRTYALFLEERLECF 149
Cdd:cd03564    80 RYSG--HIFNLSNFKDDSSPeawdlSAFIRRYARYLEERLECF 120

Epsin N-terminal homology (ENTH) domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063683454   31 ELDVAIVKATNHVECPPKDRHLRKIFLATSaiRPRADVAYCIHALSRRLHKTRNWTVALKALLVIHRLLRDGDPtfrEEL 110
Cdd:smart00273   2 DLEVKVRKATNNDEWGPKGKHLREIIQGTH--NEKSSFAEIMAVLWRRLNDTKNWRVVYKALILLHYLLRNGSP---RVI 76

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1063683454  111 LNFSQKG-RIMQISNFKDDSSpVGW-----VRTYALFLEERLECFRVLKYD 155
Cdd:smart00273  77 LEALRNRnRILNLSDFQDIDS-RGKdqganIRTYAKYLLERLEDDRRLKEE 126

ANTH (AP180 N-Terminal Homology) domain, N-terminal region, of Sla2p/HIP1/HIP1R subfamily; Members of the Sla2p/HIP1/HIP1R subfamily share a common domain architecture, containing an N-terminal ANTH, a central clathrin-binding colied-coil, and a C-terminal actin-binding talin-like (also called I/LWEQ) domains. HIP1 was identified in 1997 as an interactor of huntingtin; when mutated, it is involved in the neurodegenerative disorder Huntington's disease. Both HIP1 and HIP1R promote clathrin assembly in vitro. Yeast Sla2p, is a regulator of membrane cytoskeleton 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. While the ANTH domain of Sla2p preferentially binds PtdIns(4,5)P2, which is considered to be an interaction hub in the clathrin interactome, mammalian HIP1 and HIP1R were found to preferentially bind PtdIns(3,4)P2 and PtdIns(3,5)P2, respectively. This model describes the N-terminal region of ANTH domains of the Sla2p/HIP1/HIP1R subfamily.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063683454  34 VAIVKATNHVECPPKDRHLRKIFLATSAirpRADVAYCIHALSRRLHKTrNWTVALKALLVIHRLLRDGDPtfREELLNF 113
Cdd:cd16986     3 KAVNKATNKTDSPPKPKHVRTIIVKSWT---HQKGPQFYEELSKRLLLN-NPVVQFKALVTLHKVLRDGPP--ELSLLGG 76

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1063683454 114 SQKGRIMQISNFKDDSSPV-----GWVRTYALFLEERLE 147
Cdd:cd16986    77 YLDAWLPELVRVKNTQQSLsefysQLIKKYVRYLELKVV 115

ANTH (AP180 N-Terminal Homology) domain, N-terminal region, of Sla2p and similar proteins; This subfamily is composed of Saccharomyces cerevisiae Sla2 protein (Sla2p, also called transmembrane protein MOP2), Schizosaccharomyces pombe endocytosis protein End4 (End4p, also called Sla2 protein homolog), and similar proteins. In yeast, cells lacking Sla2p have severe defects in actin organization, cell morphology, and endocytosis, suggesting roles in these processes. Sla2p regulates the Eps15-like Arp2/3 complex activator, Pan1p, controlling actin polymerization during endocytosis. In fission yeast, End4p has been implicated in cellular morphogenesis. Sla2p contains an N-terminal ANTH, a central colied-coil, and a C-terminal actin-binding talin-like (also called I/LWEQ) domains. 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. The ANTH domain of Sla2p preferentially binds PtdIns(4,5)P2, which is considered to be an interaction hub in the clathrin interactome. This model describes the N-terminal region of ANTH domains f Sla2p and similar proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063683454  32 LDVAIVKATNHVECPPKDRHLRKIFLATSAIRPRADVAYCIhalsRRLHKTRNWTVALKALLVIHRLLRDGDPTFREEll 111
Cdd:cd17007     1 LQVAIKKACSSDETAPKRKHVRACIVYTWDHKSSKPFWNAL----KTQPLLSDEVQCFKALITIHKVLQEGHPSALKE-- 74

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1063683454 112 NFSQKGRIMQISNFKDDSSPVGW---VRTYALFLEERLE 147
Cdd:cd17007    75 AIRNIEWLESLGRQSSGSGAKGYgrlIKEYVRYLLDKLA 113

Epsin N-Terminal Homology (ENTH) domain family; The Epsin N-Terminal Homology (ENTH) domain is 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, contributing 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 1063683454  39 ATNHVECPPKDRHLRKIFLATSAIRPRADVaycIHALSRRL-HKTRNWTVALKALLVIHRLLRDGDPTFREELLNfsQKG 117
Cdd:cd03571     8 ATSNEPWGPTGSQLAEIAQATFDYDDYQRI---MKVLWKRLnDKGKNWRHVYKALTLLEYLLKNGSERVVDEFRD--NLY 82

                  ....*....
gi 1063683454 118 RIMQISNFK 126
Cdd:cd03571    83 LIRTLQDFQ 91

ANTH (AP180 N-Terminal Homology) domain, N-terminal region, of Huntingtin-interacting protein 1-related protein; Huntingtin-interacting protein 1-related protein (HIP1R), also called HIP12, promotes clathrin assembly in vitro. It is an endocytic protein involved in receptor trafficking, including regulating cell surface expression of receptor tyrosine kinases. Low HIP1R protein expression is associated with worse survival in diffuse large B-cell lymphoma (DLBCL) patients; it is preferentially expressed in germinal center B-cell (GCB)-like DLBCL, and may be potentially useful in subtyping DLBCL cases. HIP1R contains an N-terminal ANTH, a central clathrin-binding colied-coil, and a C-terminal actin-binding talin-like (also called I/LWEQ) domain. 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. The ANTH domain of mammalian HIP1R was found to preferentially bind PtdIns(3,5)P2 instead of PtdIns(4,5)P2, which is considered to be an interaction hub in the clathrin interactome. This model describes the N-terminal region of ANTH domain of Huntingtin-interacting protein 1-related protein.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1063683454  34 VAIVKATNHVECPPKDRHLRKIFLATSairpRADVAYCIHALSRRLHKTRNWTVALKALLVIHRLLRDGDP 104
Cdd:cd17014     3 ISISKAINTQEAPVKEKHARRIILGTH----HEKGAFTFWSYAIGLPLPSSSILSWKFCHVLHKVLRDGHP 69