FERM domain C-lobe/F3 of the ERM family; The ERM family includes ezrin, radixin, moesin and merlin. They are composed of a N-terminal FERM (ERM) domain (also called N-ERMAD (N-terminal ERM association domain)), a coiled coil region (CRR), and a C-terminal domain CERMAD (C-terminal ERM association domain) which has an F-actin-binding site (ABD). Two actin-binding sites have been identified in the middle and N-terminal domains. Merlin is structurally similar to the ERM proteins, but instead of an actin-binding domain (ABD), it contains a C-terminal domain (CTD), just like the proteins from the 4.1 family. Activated ezrin, radixin and moesin are thought to be involved in the linking of actin filaments to CD43, CD44, ICAM1-3 cell adhesion molecules, various membrane channels and receptors, such as the Na+/H+ exchanger-3 (NHE3), cystic fibrosis transmembrane conductance regulator (CFTR), and the beta2-adrenergic receptor. The ERM proteins exist in two states, a dormant state in which the FERM domain binds to its own C-terminal tail and thereby precludes binding of some partner proteins, and an activated state, in which the FERM domain binds to one of many membrane binding proteins and the C-terminal tail binds to F-actin. The FERM domain has a cloverleaf tripart structure composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3). The C-lobe/F3 within the FERM domain of ERM is part of the PH domain family. The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs), the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326429935 205 MYGVNYFPIKNKRGTLLWLGVDALGLNIYKSNDKLTPSISFPWSEIKTVSYNDRKFVIKPLDKHAVDLVFFSTDPSVNKT 284
Cdd:cd13194    1 MYGVNYFEIKNKKGTDLWLGVDALGLNIYEPDNKLTPKIGFPWSEIRNISFNDKKFVIKPIDKKAPDFVFYSPRLRINKR 80

                         90
                 ....*....|....*..
gi 326429935 285 ILQLCIGNHELYLKRRE 301
Cdd:cd13194   81 ILDLCMGNHELYMRRRK 97

Ezrin/radixin/moesin family C terminal; This entry represents the C-terminal domain of the ERM family of proteins which consists of three closely-related proteins, ezrin, radixin and moesin. These proteins link actin filaments of cell surface structures to the plasma membrane, using a C-terminal F-actin binding segment and an N-terminal FERM domain (pfam00373), a common membrane binding module. Ezrin was first identified as a constituent of microvilli, radixin as a barbed, end-capping actin-modulating protein from isolated junctional fractions and moesin as a heparin binding protein. A tumour suppressor molecule responsible for neurofibromatosis type 2 (NF2) is highly similar to ERM proteins and has been designated merlin (moesin-ezrin-radixin-like protein). This entry represents the C-terminal actin-binding tail domain. This entry also includes Ermin proteins, oligodendrocyte-specific proteins associated with the cytoskeleton whose C-terminal domain is similar to that in ERM family.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 326429935  469 RLEAAIKNISMDLEGLQIADRKTTEDQIHEQNAATGETKYDTLSRITRGSAKSRITFFEEL 529
Cdd:pfam00769  17 RLQEQLKELKSELAQARDETKQTALDILHEENVRQGRDKYKTLRKIRQGNTKQRVDFFEEL 77

FERM domain C-lobe/F3 of the ERM family; The ERM family includes ezrin, radixin, moesin and merlin. They are composed of a N-terminal FERM (ERM) domain (also called N-ERMAD (N-terminal ERM association domain)), a coiled coil region (CRR), and a C-terminal domain CERMAD (C-terminal ERM association domain) which has an F-actin-binding site (ABD). Two actin-binding sites have been identified in the middle and N-terminal domains. Merlin is structurally similar to the ERM proteins, but instead of an actin-binding domain (ABD), it contains a C-terminal domain (CTD), just like the proteins from the 4.1 family. Activated ezrin, radixin and moesin are thought to be involved in the linking of actin filaments to CD43, CD44, ICAM1-3 cell adhesion molecules, various membrane channels and receptors, such as the Na+/H+ exchanger-3 (NHE3), cystic fibrosis transmembrane conductance regulator (CFTR), and the beta2-adrenergic receptor. The ERM proteins exist in two states, a dormant state in which the FERM domain binds to its own C-terminal tail and thereby precludes binding of some partner proteins, and an activated state, in which the FERM domain binds to one of many membrane binding proteins and the C-terminal tail binds to F-actin. The FERM domain has a cloverleaf tripart structure composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3). The C-lobe/F3 within the FERM domain of ERM is part of the PH domain family. The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs), the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326429935 205 MYGVNYFPIKNKRGTLLWLGVDALGLNIYKSNDKLTPSISFPWSEIKTVSYNDRKFVIKPLDKHAVDLVFFSTDPSVNKT 284
Cdd:cd13194    1 MYGVNYFEIKNKKGTDLWLGVDALGLNIYEPDNKLTPKIGFPWSEIRNISFNDKKFVIKPIDKKAPDFVFYSPRLRINKR 80

                         90
                 ....*....|....*..
gi 326429935 285 ILQLCIGNHELYLKRRE 301
Cdd:cd13194   81 ILDLCMGNHELYMRRRK 97

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in the ERM family proteins; The ezrin-radixin-moesin (ERM) family includes a group of closely related cytoskeletal proteins that play an essential role in microvilli formation, T-cell activation, and tumor metastasis through providing a regulated linkage between F-actin and membrane-associated proteins. These proteins may also function in signaling cascades that regulate the assembly of actin stress fibers. The ERM proteins consist of an N-terminal FERM domain, a coiled-coil (CC) domain and a C-terminal tail segment (C-tail) containing a well-defined actin-binding motif. They exist in two states, a dormant state in which the FERM domain binds to its own C-terminal tail and thereby precludes binding of some partner proteins, and an activated state, in which the FERM domain binds to one of many membrane binding proteins and the C-terminal tail binds to F-actin. The FERM domain is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N). Merlin, which is highly related to the members of the ezrin, radixin, and moesin (ERM) protein family that are directly attached to and functionally linked with NHE1, is included in this family.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326429935  10 FRVLVHTADATLEFSIQPKTTGQELFDLVVRTTGLRETWFFDLCYENTKGRMSWLKREKKVLTQDVPHIQPLPFHFKVKY 89
Cdd:cd17097    1 INVRVTTMDAELEFSIKPKAKGRELFDLVCRTIGLRETWYFGLQYENKKGRVAWLKPDKKVLTQDVSKNNTLKFFFLVKF 80

                 ...
gi 326429935  90 YPE 92
Cdd:cd17097   81 YPE 83

FERM C-terminal PH-like domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326429935  215 NKRGTLLWLGVDALGLNIYKSNDKLtpSISFPWSEIKTVSYNDRKFVIKPLDKHAVDLVFFST-DPSVNKTILQLCIGNH 293
Cdd:pfam09380   1 DKEGTDLWLGVSAKGILVYEDNNKI--LNLFPWREIRKISFKRKKFLIKLRDKSSEETLGFYTeSSRACKYLWKLCVEQH 78

                  ....*..
gi 326429935  294 ELYLKRR 300
Cdd:pfam09380  79 TFFRLRR 85

Ezrin/radixin/moesin, alpha-helical domain; The ERM family consists of three closely-related proteins, ezrin, radixin and moesin. Ezrin was first identified as a constituent of microvilli, radixin as a barbed, end-capping actin-modulating protein from isolated junctional fractions, and moesin as a heparin binding protein. A tumour suppressor molecule responsible for neurofibromatosis type 2 (NF2) is highly similar to ERM proteins and has been designated merlin (moesin-ezrin-radixin-like protein). ERM molecules contain 3 domains, an N-terminal globular domain, an extended alpha-helical domain and a charged C-terminal domain (pfam00769). Ezrin, radixin and merlin also contain a polyproline linker region between the helical and C-terminal domains. The N-terminal domain is highly conserved and is also found in merlin, band 4.1 proteins and members of the band 4.1 superfamily, designated the FERM domain. ERM proteins crosslink actin filaments with plasma membranes. They co-localize with CD44 at actin filament plasma membrane interaction sites, associating with CD44 via their N-terminal domains and with actin filaments via their C-terminal domains. This is the alpha-helical domain, which is involved in intramolecular masking of protein-protein interaction sites, regulating the activity of this proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326429935  338 AEREKDKMSIKLKRAERKAAQTKQDLSRMREAAQILSEKVEMAEVETGLLLAKAQEAETTLQQMLHEKERTEQEKQDLVR 417
Cdd:pfam20492   4 AEREKQELEERLKQYEEETKKAQEELEESEETAEELEEERRQAEEEAERLEQKRQEAEEEKERLEESAEMEAEEKEQLEA 83

                          90
                  ....*....|.
gi 326429935  418 QARDAKESAQR 428
Cdd:pfam20492  84 ELAEAQEEIAR 94

Membrane protein TolA involved in colicin uptake [Cell wall/membrane/envelope biogenesis];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326429935 333 QSRKLAEREKDKMSIKLKRAERKA----AQTKQDLSRMR-EAAQILSEKVE-MAEVETGLLLAKAQEAETTLQQMLHEKE 406
Cdd:COG3064   34 KAKEEAEEERLAELEAKRQAEEEAreakAEAEQRAAELAaEAAKKLAEAEKaAAEAEKKAAAEKAKAAKEAEAAAAAEKA 113

                         90       100
                 ....*....|....*....|..
gi 326429935 407 RTEQEKQDLVRQARDAKESAQR 428
Cdd:COG3064  114 AAAAEKEKAEEAKRKAEEEAKR 135

FERM domain C-lobe/F3 of the ERM family; The ERM family includes ezrin, radixin, moesin and merlin. They are composed of a N-terminal FERM (ERM) domain (also called N-ERMAD (N-terminal ERM association domain)), a coiled coil region (CRR), and a C-terminal domain CERMAD (C-terminal ERM association domain) which has an F-actin-binding site (ABD). Two actin-binding sites have been identified in the middle and N-terminal domains. Merlin is structurally similar to the ERM proteins, but instead of an actin-binding domain (ABD), it contains a C-terminal domain (CTD), just like the proteins from the 4.1 family. Activated ezrin, radixin and moesin are thought to be involved in the linking of actin filaments to CD43, CD44, ICAM1-3 cell adhesion molecules, various membrane channels and receptors, such as the Na+/H+ exchanger-3 (NHE3), cystic fibrosis transmembrane conductance regulator (CFTR), and the beta2-adrenergic receptor. The ERM proteins exist in two states, a dormant state in which the FERM domain binds to its own C-terminal tail and thereby precludes binding of some partner proteins, and an activated state, in which the FERM domain binds to one of many membrane binding proteins and the C-terminal tail binds to F-actin. The FERM domain has a cloverleaf tripart structure composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3). The C-lobe/F3 within the FERM domain of ERM is part of the PH domain family. The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs), the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326429935 205 MYGVNYFPIKNKRGTLLWLGVDALGLNIYKSNDKLTPSISFPWSEIKTVSYNDRKFVIKPLDKHAVDLVFFSTDPSVNKT 284
Cdd:cd13194    1 MYGVNYFEIKNKKGTDLWLGVDALGLNIYEPDNKLTPKIGFPWSEIRNISFNDKKFVIKPIDKKAPDFVFYSPRLRINKR 80

                         90
                 ....*....|....*..
gi 326429935 285 ILQLCIGNHELYLKRRE 301
Cdd:cd13194   81 ILDLCMGNHELYMRRRK 97

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in the ERM family proteins; The ezrin-radixin-moesin (ERM) family includes a group of closely related cytoskeletal proteins that play an essential role in microvilli formation, T-cell activation, and tumor metastasis through providing a regulated linkage between F-actin and membrane-associated proteins. These proteins may also function in signaling cascades that regulate the assembly of actin stress fibers. The ERM proteins consist of an N-terminal FERM domain, a coiled-coil (CC) domain and a C-terminal tail segment (C-tail) containing a well-defined actin-binding motif. They exist in two states, a dormant state in which the FERM domain binds to its own C-terminal tail and thereby precludes binding of some partner proteins, and an activated state, in which the FERM domain binds to one of many membrane binding proteins and the C-terminal tail binds to F-actin. The FERM domain is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N). Merlin, which is highly related to the members of the ezrin, radixin, and moesin (ERM) protein family that are directly attached to and functionally linked with NHE1, is included in this family.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326429935  10 FRVLVHTADATLEFSIQPKTTGQELFDLVVRTTGLRETWFFDLCYENTKGRMSWLKREKKVLTQDVPHIQPLPFHFKVKY 89
Cdd:cd17097    1 INVRVTTMDAELEFSIKPKAKGRELFDLVCRTIGLRETWYFGLQYENKKGRVAWLKPDKKVLTQDVSKNNTLKFFFLVKF 80

                 ...
gi 326429935  90 YPE 92
Cdd:cd17097   81 YPE 83

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in the ERM family proteins, Ezrin, Radixin, and Moesin; The ezrin-radixin-moesin (ERM) family includes a group of closely related cytoskeletal proteins that plays an essential role in microvilli formation, T-cell activation, and tumor metastasis through providing a regulated linkage between F-actin and membrane-associated proteins. These proteins may also function in signaling cascades that regulate the assembly of actin stress fibers. The ERM proteins consist of an N-terminal FERM domain, a coiled-coil (CC) domain and a C-terminal tail segment (C-tail) containing a well-defined actin-binding motif. They exist in two states, a dormant state in which the FERM domain binds to its own C-terminal tail and thereby precludes binding of some partner proteins, and an activated state, in which the FERM domain binds to one of many membrane binding proteins and the C-terminal tail binds to F-actin. The FERM domain is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326429935  12 VLVHTADATLEFSIQPKTTGQELFDLVVRTTGLRETWFFDLCYENTKGRMSWLKREKKVLTQDVPHIQPLPFHFKVKYYP 91
Cdd:cd17187    3 VRVTTMDAELEFAIQPNTTGKQLFDQVVKTIGLREIWFFGLQYVDSKGYSTWLKLNKKVLSQDVKKENPLQFKFRAKFYP 82

                 .
gi 326429935  92 E 92
Cdd:cd17187   83 E 83

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in Ezrin and similar proteins; Ezrin, also termed cytovillin, or villin-2, or p81, is a member of the ezrin/radixin/moesin (ERM) family of cytoskeletal proteins that plays an essential role in microvilli formation, T-cell activation, and tumor metastasis through providing a regulated linkage between F-actin and membrane-associated proteins. These proteins may also function in signaling cascades that regulate the assembly of actin stress fibers. The ERM proteins consist of an N-terminal FERM domain, a coiled-coil (CC) domain and a C-terminal tail segment (C-tail) containing a well-defined actin-binding motif. The C-terminal domain can fold back to bind to the FERM domain forming an autoinhibited conformation. The FERM domain is made up of three sub-domains, F1, F2, and F3. This family corresponds to F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N). Ezrin is a tyrosine kinase substrate that functions as a cross-linker between actin cytoskeleton and plasma membrane. It has been implicated in the regulation of the proliferation, apoptosis, adhesion, invasion, metastasis and angiogenesis of cancer cells.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326429935  12 VLVHTADATLEFSIQPKTTGQELFDLVVRTTGLRETWFFDLCYENTKGRMSWLKREKKVLTQDVPHIQPLPFHFKVKYYP 91
Cdd:cd17239    5 VRVTTMDAELEFAIQPNTTGKQLFDQVVKTIGLREVWYFGLQYVDNKGFPTWLKLDKKVSAQEVRKENPLQFKFRAKFYP 84

                 .
gi 326429935  92 E 92
Cdd:cd17239   85 E 85

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in moesin and similar proteins; Moesin, also termed membrane-organizing extension spike protein, is a member of the ezrin/radixin/moesin (ERM) family of cytoskeletal proteins that plays an essential role in microvilli formation, T-cell activation, and tumor metastasis through providing a regulated linkage between F-actin and membrane-associated proteins. These proteins may also function in signaling cascades that regulate the assembly of actin stress fibers. The ERM proteins consist of an N-terminal FERM domain, a coiled-coil (CC) domain and a C-terminal tail segment (C-tail) containing a well-defined actin-binding motif. The C-terminal domain can fold back to bind to the FERM domain forming an autoinhibited conformation. The FERM domain is made up of three sub-domains, F1, F2, and F3. This family corresponds to F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N). Moesin is involved in mitotic spindle function through stabilizing cell shape and microtubules at the cell cortex. It is required for the formation of F-actin networks that mediate endosome biogenesis or maturation and transport through the degradative pathway.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326429935  12 VLVHTADATLEFSIQPKTTGQELFDLVVRTTGLRETWFFDLCYENTKGRMSWLKREKKVLTQDVPHIQPLPFHFKVKYYP 91
Cdd:cd17237    4 VRVTTMDAELEFAIQPNTTGKQLFDQVVKTIGLREVWFFGLQYQDTKGFSTWLKLNKKVTAQDVRKESPLLFKFRAKFYP 83

                 .
gi 326429935  92 E 92
Cdd:cd17237   84 E 84

FERM C-terminal PH-like domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326429935  215 NKRGTLLWLGVDALGLNIYKSNDKLtpSISFPWSEIKTVSYNDRKFVIKPLDKHAVDLVFFST-DPSVNKTILQLCIGNH 293
Cdd:pfam09380   1 DKEGTDLWLGVSAKGILVYEDNNKI--LNLFPWREIRKISFKRKKFLIKLRDKSSEETLGFYTeSSRACKYLWKLCVEQH 78

                  ....*..
gi 326429935  294 ELYLKRR 300
Cdd:pfam09380  79 TFFRLRR 85

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F0 sub-domain and F1 sub-domain, found in FERM (Four.1/Ezrin/Radixin/Moesin) family proteins; FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain is present at the N-terminus of a large and diverse group of proteins that mediate linkage of the cytoskeleton to the plasma membrane. FERM-containing proteins are ubiquitous components of the cytocortex and are involved in cell transport, cell structure and signaling functions. The FERM domain is made up of three sub-domains, F1, F2, and F3. The family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N), which is structurally similar to ubiquitin.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 326429935  18 DATLEFSIQPKTTGQELFDLVVRTTGLRETWFFDLCYENTKGRMSWLKREKKVLTQdVPHIQPLPFHFKVKY 89
Cdd:cd01765   10 GTELTLEVSKKATGQELFDKVCEKLNLLEKDYFGLFYEDNDGQKHWLDLDKKISKQ-LKRSGPYQFYFRVKF 80

FERM N-terminal domain; This domain is the N-terminal ubiquitin-like structural domain of the FERM domain.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 326429935   14 VHTADAT-LEFSIQPKTTGQELFDLVVRTTGLRETWFFDLCYENTKGRMSWLKREKKVLTQDV 75
Cdd:pfam09379   1 VRLLDGTvLEFDVQPKATGQVLLDQVCNHLNLKEKDYFGLQFLDDNGEHRWLDLSKRLSKQAP 63

Ezrin/radixin/moesin family C terminal; This entry represents the C-terminal domain of the ERM family of proteins which consists of three closely-related proteins, ezrin, radixin and moesin. These proteins link actin filaments of cell surface structures to the plasma membrane, using a C-terminal F-actin binding segment and an N-terminal FERM domain (pfam00373), a common membrane binding module. Ezrin was first identified as a constituent of microvilli, radixin as a barbed, end-capping actin-modulating protein from isolated junctional fractions and moesin as a heparin binding protein. A tumour suppressor molecule responsible for neurofibromatosis type 2 (NF2) is highly similar to ERM proteins and has been designated merlin (moesin-ezrin-radixin-like protein). This entry represents the C-terminal actin-binding tail domain. This entry also includes Ermin proteins, oligodendrocyte-specific proteins associated with the cytoskeleton whose C-terminal domain is similar to that in ERM family.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 326429935  469 RLEAAIKNISMDLEGLQIADRKTTEDQIHEQNAATGETKYDTLSRITRGSAKSRITFFEEL 529
Cdd:pfam00769  17 RLQEQLKELKSELAQARDETKQTALDILHEENVRQGRDKYKTLRKIRQGNTKQRVDFFEEL 77

Ras-associating (RA) domain, FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F0/F1 sub-domain, structurally similar to a beta-grasp ubiquitin-like fold; RA domain-containing proteins function by interacting, directly or indirectly, with Ras proteins and are involved in several different functions ranging from tumor suppression to being oncoproteins. Ras protein is a small GTPase that is involved in cellular signal transduction. The RA domain has the beta-grasp ubiquitin-like (Ubl) fold with low sequence similarity to ubiquitin (Ub). Ub is a protein modifier in eukaryotes that is involved in various cellular processes, including transcriptional regulation, cell cycle control, and DNA repair in eukaryotes. RA-containing proteins include RalGDS, AF6, RIN, RASSF1, SNX27, CYR1, STE50, and phospholipase C epsilon. The FERM domain is present at the N-terminus of a large and diverse group of proteins that mediate linkage of the cytoskeleton to the plasma membrane. FERM-containing proteins are ubiquitous components of the cytocortex and are involved in cell transport, cell structure and signaling. The FERM domain is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain, also known as the N-terminal Ubl-like structural domain of the FERM domain (FERM_N), which is structurally similar to Ub. Some FERM domain-containing proteins contain an N-terminal region, which also has the beta-grasp Ub-like fold, precedes the FERM domain and has been referred to as the F0 domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326429935  12 VLVHTADATLEFSIQPKTTGQELFDLVVRTTGLR-----------ETWFFDLCYENTK-------------GRMSWLKRE 67
Cdd:cd01768    7 AGLASGANYKSVLATARSTARELVAEALERYGLAgspgggpgessCVDAFALCDALGRpaaagvgsgewraEHLRVLGDS 86

                         90       100
                 ....*....|....*....|...
gi 326429935  68 KKVLTQ----DVPHIQPLPFHFK 86
Cdd:cd01768   87 ERPLLVqelwRARPGWARRFELR 109

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in FERM domain-containing protein 4B (FRMD4B); FRMD4B, also termed GRP1-binding protein GRSP1, interacts with the coil-coil domain of ARF exchange factor GRP1 to form the Grsp1-Grp1 complex that co-localizes with cortical actin rich regions in response to stimulation of CHO-T cells with insulin or epidermal growth factor (EGF). FRMD4B contains a FERM protein interaction domain as well as two coiled coil domains and may therefore function as a scaffolding protein. The FERM domain is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326429935   4 KGRHQWFRVLvhtADATLEFSIQPKTTGQELFDLVVRTTGLRETWFFDLCYENTKGRMSWLKREKKVLTQDVPHIQ-PLP 82
Cdd:cd17200    1 EGRHCQVHLL---DDRKLELLVQPKLLSRELLDLVASHFNLKEKEYFGITFIDDTGQSNWLQLDHRVLDHDLPKKSgPVT 77

                         90
                 ....*....|..
gi 326429935  83 FHFKVKYYPEDV 94
Cdd:cd17200   78 LYFAVRFYIESI 89

FERM domain C-lobe of FERM domain containing 1 and 6 proteins; FRMD6 (also called willin and hEx/human expanded) is localized throughout the cytoplasm or along the plasma membrane. The Drosophilla protein Ex is a regulator of the Hippo/SWH (Sav/Wts/Hpo) signaling pathway, a signaling pathway that plays a pivotal role in organ size control and is tumor suppression by restricting proliferation and promoting apoptosis. Surprisingly, hEx is thought to function independently of the Hippo pathway. Instead it is hypothesized that hEx inhibits progression through the S phase of the cell cycle by upregulating p21(Cip1) and downregulating Cyclin A. It is also implicated in the progression of Alzheimer disease. Not much is known about FRMD1 to date. Both FRMD1 and FRMD6 contains a single FERM domain which has a cloverleaf tripart structure composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3). The C-lobe is a member of the PH superfamily. The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs) , the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326429935 214 KNKRGTL--LWLGVDALGLNIYK-SNDKLTPSISFPWSEIKTVSYNDRKFVIKPLDKHAvDLVFFSTDPSVNKTILQLCI 290
Cdd:cd13185   12 KSKKETPgsVLLGITAKGIQIYQeSDGEQQLLRTFPWSNIGKLSFDRKKFEIRPEGSLR-KLTYYTSSDEKSKYLLALCR 90

                 ....*...
gi 326429935 291 GNHELYLK 298
Cdd:cd13185   91 ETHQFSMA 98

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in tyrosine-protein phosphatase non-receptor type 13 (PTPN13) and similar proteins; This family includes tyrosine-protein phosphatase non-receptor type 13 (PTPN13), FERM and PDZ domain-containing protein 2 (FRMPD2), and FERM domain-containing proteins FRMD1 and FRMD6. All family members contain a FERM domain that is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326429935  20 TLEFSIQPKTTGQELFDLVVRTTGLRETWFFDLCYEN----------TK----GRMSWLKREKKVLTQDVPhiqPLPFHF 85
Cdd:cd17101   13 RLQVAVDVKTTVQDLFDQVCDHLGLQETELFGLAVLKdgeyffldpdTKlskyAPKGWKSEAKKGLKGGKP---VFTLYF 89

                 ....*..
gi 326429935  86 KVKYYPE 92
Cdd:cd17101   90 RVKFYVD 96

FERM domain C-lobe of FERM domain-containing protein 3 and 5 (FRMD3 and 5); FRMD3 (also called Band 4.1-like protein 4O/4.1O though it is not a true member of that family) is a novel putative tumor suppressor gene that is implicated in the origin and progression of lung cancer. In humans there are 5 isoforms that are produced by alternative splicing. Less is known about FRMD5, though there are 2 isoforms of the human protein are produced by alternative splicing. Both FRMD3 and FRMD5 contain a N-terminal FERM domain, followed by a FERM adjacent (FA) domain, and 4.1 protein C-terminal domain (CTD). The FERM domain has a cloverleaf tripart structure composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs), the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326429935 192 AKMKYLAFAQDFEMYGVNYFPIKNKRGTLLWLGVDALGLNIYKSNDKltpSISFPWSEIKTVSYNDRKF---VIKPLDKH 268
Cdd:cd13192    1 AEDNFLRKAATLETYGVDPHPVKDHRGNQLYLGFTHTGIVTFQGGKR---VHHFRWNDITKFNYEGKMFilhVMQKEEKK 77

                         90       100
                 ....*....|....*....|....*...
gi 326429935 269 AVdLVFFSTDPSVNKTILQLCIGNHELY 296
Cdd:cd13192   78 HT-LGFKCPTPAACKHLWKCAVEQQAFY 104

FERM domain C-lobe of FERM, RhoGEF and pleckstrin domain-containing protein 1 and related proteins; Members here include FARP1 (also called Chondrocyte-derived ezrin-like protein; PH domain-containing family C member 2), FARP2 (also called FIR/FERM domain including RhoGEF; FGD1-related Cdc42-GEF/FRG), and FRMD7(FERM domain containing 7). FARP1 and FARP2 are members of the Dbl family guanine nucleotide exchange factors (GEFs) which are upstream positive regulators of Rho GTPases. FARP1 has increased expression in differentiated chondrocytes. FARP2 is thought to regulate neurite remodeling by mediating the signaling pathways from membrane proteins to Rac. It is found in brain, lung, and testis, as well as embryonic hippocampal and cortical neurons. These members are composed of a N-terminal FERM domain, a proline-rich (PR) domain, Dbl-homology (DH), and two C-terminal PH domains. Other members in this family do not contain the DH domains such as the Human FERM domain containing protein 7 and Caenorhabditis elegans CFRM3, both of which have unknown functions. They contain an N-terminal FERM domain, a PH domain, followed by a FA (FERM adjacent) domain. The FERM domain has a cloverleaf tripart structure composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs), the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326429935 204 EMYGVNYFPIKNKRGTLLWLGVDALGLNIYKSNDKLTpsiSFPWSEIKTVSYNDRKFVIK------PLDKHAVDLVFFST 277
Cdd:cd13193    7 ELYGIRLHPAKDREGVKLNLAVAHMGILVFQGFTKIN---TFSWAKIRKLSFKRKRFLIKlhpeayGSYKDTVEFSFESR 83

                         90
                 ....*....|....*...
gi 326429935 278 D--PSVNKTilqlCIGNH 293
Cdd:cd13193   84 NecKSFWKK----CIEHH 97

FERM domain C-lobe of Protein tyrosine phosphatase non-receptor proteins 14 and 21 (PTPN14 and 21); This CD contains PTP members: pez/PTPN14 and PTPN21. A number of mutations in Pez have been shown to be associated with breast and colorectal cancer. The PTPN protein family belong to larger family of PTPs. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. The members are composed of a N-terminal FERM domain and a C-terminal PTP catalytic domain. The FERM domain has a cloverleaf tripart structure composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. Like most other ERM members they have a phosphoinositide-binding site in their FERM domain. The FERM C domain is the third structural domain within the FERM domain. The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs) , the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326429935 206 YGVNYFPIKNKRGTLLWLGVDALGLnIYKSNDKLTPsISFPWSEIKTVSYNDRKFVIKPLDKHAVdLVFFSTDPSVNKTI 285
Cdd:cd13188    1 YGEESFPAKDEQGNEVLIGASLEGI-FVKHDNGRPP-VFFRWEDIKNVINHKRTFSIECQNSEET-VQFQFEDAETAKYV 77

                         90
                 ....*....|.
gi 326429935 286 LQLCIGNHELY 296
Cdd:cd13188   78 WKLCVLQHKFY 88

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in tyrosine-protein phosphatase non-receptor type 21 (PTPN21) and similar proteins; PTPN21, also termed protein-tyrosine phosphatase D1 (PTPD1), is a cytosolic non-receptor protein-tyrosine phosphatase (PTP) that belongs to the FERM family of PTPs characterized by a conserved N-terminal FERM domain and a C-terminal PTP catalytic domain with an intervening sequence containing an acidic region and a putative SH3 domain-binding sequence. The FERM domain is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N). PTPN21 interacts with a Tec tyrosine kinase family member, the epithelial and endothelial tyrosine kinase (Etk, also known as Bmx), modulates Stat3 activation, and plays a role in the regulation of cell growth and differentiation. It also associates with and activates Src tyrosine kinase, and directs epidermal growth factor (EGF)/Src signaling to the nucleus through activating ERK1/2- and Elk1-dependent gene transcription. PTPD1-Src complex interacts a protein kinase A-anchoring protein AKAP121 to forms a PTPD1-Src-AKAP121 complex, which is required for efficient maintenance of mitochondrial membrane potential and ATP oxidative synthesis. As a novel component of the endocytic pathway, PTPN21 supports EGF receptor stability and mitogenic signaling in bladder cancer cells. Moreover, PTPD1 regulates focal adhesion kinase (FAK) autophosphorylation and cell migration through modulating Src-FAK signaling at adhesion sites.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 326429935  21 LEFSIQPKTTGQELFDLVVRTTGLRETWFFDLCYENTKGRMSWLKREKKVLTQ-DVPHIQPLPFHFKVKYYP 91
Cdd:cd17192   16 VEFTLSVESTGQECLEAVAQRLELREITYFSLWYYNKQNQQRWVDLEKPLKKQlDKYALEPTVYFGVVFYVP 87

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in erythrocyte membrane protein band 4.1-like protein 2 (EPB41L2) and similar proteins; EPB41L2, also termed generally expressed protein 4.1 (4.1G), belongs to the skeletal protein 4.1 family that is involved in cellular processes such as cell adhesion, migration and signaling. EPB41L2 contains a FERM domain, a spectrin and actin binding (SAB) domain, and a C-terminal domain. The FERM domain is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N).

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 326429935  22 EFS--IQPKTTGQELFDLVVRTTGLRETWFFDLCYENTKGRMSWLKREKKVLTQdvphIQPLP--FHFKVKYYPED 93
Cdd:cd17202   13 EYScdLEKRAKGQVLFDKVCEHLNLLEKDYFGLLYQVSANQKNWLDSTKEIKRQ----IRRLPwlFTFNVKFYPPD 84

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in erythrocyte membrane protein band 4.1-like protein 1 (EPB41L1) and similar proteins; EPB41L1, also termed neuronal protein 4.1 (4.1N), belongs to the skeletal protein 4.1 family that is involved in cellular processes such as cell adhesion, migration and signaling. It is a cytoskeleton-associated protein that may serve as a tumor suppressor in solid tumors. It suppresses hypoxia-induced epithelial-mesenchymal transition in epithelial ovarian cancer (EOC) cells. The down-regulation of EPB41L1 expression is a critical step for non-small cell lung cancer (NSCLC) development. Moreover, EPB41L1 functions as a linker protein between inositol 1,4,5-trisphosphate receptor type1 (IP3R1) and actin filaments in neurons. EPB41L1 contains a FERM domain, a spectrin and actin binding (SAB) domain, and a C-terminal domain. The FERM domain is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N).

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 326429935  22 EFSIQPKTTGQELFDLVVRTTGLRETWFFDLCYENTKGRMSWLKREKKVLTQdvphIQPLPFHF--KVKYYPED 93
Cdd:cd17201   15 ECEVEKHARGQVLFDTVCEHLNLLEKDYFGLTFCDTESQKNWLDPSKEIKKQ----IRSGPWHFafTVKFYPPD 84

Domain of unknown function (DUF4670); This family of proteins is found in eukaryotes. Proteins in this family are typically between 373 and 763 amino acids in length.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326429935  298 KRREPDSIEVQQMRAEAAERRERMDKDRGRLIREMQSRKLAEREKDKMSIKLKRAERKAAQTKQDLSRMREAAQILsekV 377
Cdd:pfam15709 393 KQRLEEERQRQEEEERKQRLQLQAAQERARQQQEEFRRKLQELQRKKQQEEAERAEAEKQRQKELEMQLAEEQKRL---M 469

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 326429935  378 EMAEVETGLLLAKAQEAETTLQQMLHEKERTEQEKQDLVRQarDAKESAQ 427
Cdd:pfam15709 470 EMAEEERLEYQRQKQEAEEKARLEAEERRQKEEEAARLALE--EAMKQAQ 517

FERM domain C-lobe of Protein tyrosine phosphatase non-receptor proteins 3 and 4 (PTPN4 and PTPN3); PTPN4 (also called PTPMEG, protein tyrosine phosphatase, megakaryocyte) is a cytoplasmic protein-tyrosine phosphatase (PTP) thought to play a role in cerebellar function. PTPMEG-knockout mice have impaired memory formation and cerebellar long-term depression. PTPN3/PTPH1 is a membrane-associated PTP that is implicated in regulating tyrosine phosphorylation of growth factor receptors, p97 VCP (valosin-containing protein, or Cdc48 in Saccharomyces cerevisiae), and HBV (Hepatitis B Virus) gene expression; it is mutated in a subset of colon cancers. PTPMEG and PTPN3/PTPH1 contains a N-terminal FERM domain, a middle PDZ domain, and a C-terminal phosphatase domain. PTP1/Tyrosine-protein phosphatase 1 from nematodes and a FERM_C repeat 1 from Tetraodon nigroviridis are also included in this cd. The FERM domain has a cloverleaf tripart structure composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3). The C-lobe within the FERM domain is part of the PH domain family. The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs) , the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 326429935 205 MYGVNYFPIKNKRGTLLWLGVDALGLNIYKSNDKLTpsiSFPWSEIKTVSYNDRKFVI 262
Cdd:cd13189    1 LYGVELHSARDSNNLELQIGVSSAGILVFQNGIRIN---TFPWSKIVKISFKRKQFFI 55

F-type ATP synthase, membrane subunit b; Membrane subunit b is a component of the Fo complex of FoF1-ATP synthase. The F-type ATP synthases (FoF1-ATPase) consist of two structural domains: the F1 (assembly factor one) complex containing the soluble catalytic core, and the Fo (oligomycin sensitive factor) complex containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. F1 is composed of alpha (or A), beta (B), gamma (C), delta (D) and epsilon (E) subunits with a stoichiometry of 3:3:1:1:1, while Fo consists of the three subunits a, b, and c (1:2:10-14). An oligomeric ring of 10-14 c subunits (c-ring) make up the Fo rotor. The flux of protons through the ATPase channel (Fo) drives the rotation of the c-ring, which in turn is coupled to the rotation of the F1 complex gamma subunit rotor due to the permanent binding between the gamma and epsilon subunits of F1 and the c-ring of Fo. The F-ATP synthases are primarily found in the inner membranes of eukaryotic mitochondria, in the thylakoid membranes of chloroplasts or in the plasma membranes of bacteria. The F-ATP synthases are the primary producers of ATP, using the proton gradient generated by oxidative phosphorylation (mitochondria) or photosynthesis (chloroplasts). Alternatively, under conditions of low driving force, ATP synthases function as ATPases, thus generating a transmembrane proton or Na(+) gradient at the expense of energy derived from ATP hydrolysis. This group also includes F-ATP synthase that has also been found in the archaea Candidatus Methanoperedens.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326429935 338 AEREKDKMSIKLKRAERKAAQTKQdlsrmrEAAQILSEKVEMAEVETGLLLAKAQ-EAETTLQQmlhEKERTEQEKQDLV 416
Cdd:cd06503   42 AEKAKEEAEELLAEYEEKLAEARA------EAQEIIEEARKEAEKIKEEILAEAKeEAERILEQ---AKAEIEQEKEKAL 112

                 ....*
gi 326429935 417 RQARD 421
Cdd:cd06503  113 AELRK 117

FERM domain C-lobe of E3 ubiquitin ligase myosin regulatory light chain-interacting protein (MYLIP; also called inducible degrader of the LDL receptor, IDOL); MYLIP/IDOL is a regulator of the LDL receptor (LDLR) pathway via the nuclear receptor liver X receptor (LXR). In response to cellular cholesterol loading, the activation of LXR leads to the induction of MYLIP expression. MYLIP stimulates ubiquitination of the LDLR on its cytoplasmic tail, directing its degradation. The LXR-MYLIP-LDLR pathway provides a complementary pathway to sterol regulatory element-binding proteins for the feedback inhibition of cholesterol uptake. MYLIP has an N-terminal FERM domain and in some cases a C-terminal RING domain. The FERM domain has a cloverleaf tripart structure composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs), the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 326429935 206 YGVNYFPIKNKRGTLLWLGVDALGLNIYKSNDKLTPSISFPwsEIKTVSYNDRKFVIKPL-DKHAVDLVFF 275
Cdd:cd13195    1 YGVEFFEVRNIEGQKLLIGVGPHGITICNDDFEVIERIPYT--AIQMATSSGRVFTLTYLsDDGSVKVLEF 69

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in erythrocyte membrane protein band 4.1 (EPB41) and similar proteins; EPB41, also termed protein 4.1 (P4.1), or 4.1R, or Band 4.1, or EPB4.1, belongs to the skeletal protein 4.1 family that is involved in cellular processes such as cell adhesion, migration and signaling. EPB41 is a widely expressed cytoskeletal phosphoprotein that stabilizes the spectrin-actin cytoskeleton and anchors the cytoskeleton to the cell membrane. EPB41 contains a FERM domain, a spectrin and actin binding (SAB) domain, and a C-terminal domain. The FERM domain is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N).

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 326429935  18 DATLEFSIQPKTTGQELFDLVVRTTGLRETWFFDLCYENTKGRMSWLKREKKVLTQdvPHIQPLPFHFKVKYYPED 93
Cdd:cd17105   10 DTVYECEVEKHAKGQDLFKKVCEHLNLLEEDYFGLAIWDSPTSKTWLDPAKEIKKQ--VHGGPWEFTFNVKFYPPD 83

Uncharacterized membrane protein YqiK, contains Band7/PHB/SPFH domain [Function unknown];