FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain 1, F1 sub-domain, found in Myosin-VIIa, Myosin-VIIb, and similar proteins; This family includes two nontraditional members of the myosin superfamily, myosin-VIIa and myosin-VIIb. Myosin-VIIa, also termed myosin-7a (Myo7a), has been implicated in the structural organization of hair bundles at the apex of sensory hair cells (SHCs) where it serves mechanotransduction in the process of hearing and balance. Mutations in the MYO7A gene may be associated with Usher Syndrome type 1B (USH1B) and nonsyndromic hearing loss (DFNB2, DFNA11). Myosin-VIIb, also termed myosin-7b (Myo7b), is a high duty ratio motor adapted for generating and maintaining tension. It associates with harmonin and ANKS4B to form a stable ternary complex for anchoring microvilli tip-link cadherins. Like other unconventional myosins, myosin-VII is composed of a conserved motor head, a neck region and a tail region containing two MyTH4 domains, a SH3 domain, and two FERM domains. The FERM domain is made up of three sub-domains, F1, F2, and F3. The family corresponds to the F1 sub-domain of the first FERM 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3PVL_A      263 PIMLPVTFMDGTTKTLLTDSATTARELCNALADKISLKDRFGFSLYIALFDKVSSLGSGSDHVMDAISQCEQYAKEQGAQ 342
Cdd:cd17092   1 PIMLPVTFMDGSTKTVEVDSATTARELCRQLAEKLGLKDTFGFSLYIALFDKVSSLGSGTDHVMDAISQCEQYAKEKGAQ 80

                        90
                ....*....|....*....
3PVL_A      343 ERNAPWRLFFRKEVFTPWH 361
Cdd:cd17092  81 EREAPWRLYFRKEIFAPWH 99

FERM domain C-lobe, repeat 1, of Myosin VII (MyoVII/Myo7); MyoVII, a MyTH-FERM myosin, is an actin-based motor protein essential for a variety of biological processes in the actin cytoskeleton function. Mutations in MyoVII leads to problems in sensory perception: deafness and blindness in humans (Usher Syndrome), retinal defects and deafness in mice (shaker 1), and aberrant auditory and vestibular function in zebrafish. Myosin VIIAs have plus (barbed) end-directed motor activity on actin filaments and a characteristic actin-activated ATPase activity. MyoVII consists of a conserved spectrin-like, SH3 subdomain N-terminal region, a motor/head region, a neck made of 4-5 IQ motifs, and a tail consisting of a coiled-coil domain, followed by a tandem repeat of myosin tail homology 4 (MyTH4) domains and partial FERM domains that are separated by an SH3 subdomain and are thought to mediate dimerization and binding to other proteins or cargo. Members include: MyoVIIa, MyoVIIb, and MyoVII members that do not have distinct myosin VIIA and myosin VIIB genes. 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3PVL_A      474 LLFSRFYEAYKFSGPPLPKSDVIVAVNWTGVYFVDEQEQVLLELSFPEIMAVSSSRGTKMMAPSFTLATIKGDEYTFTSS 553
Cdd:cd13198   1 LLFSRFFEATKFSGPSLPKSEVIIAVNWTGIYFVDEQEQVLLELSFPEITGVSSSRGKRDGGQSFTLTTIQGEEFVFQSP 80

                        90
                ....*....|....*....
3PVL_A      554 NAEDIRDLVVTFLEGLRKR 572
Cdd:cd13198  81 NAEDIAELVNYFLEGLRKR 99

Src Homology 3 domain of Myosin VIIa and similar proteins; Myo7A is an uncoventional myosin that is involved in organelle transport. It is required for sensory function in both Drosophila and mammals. Mutations in the Myo7A gene cause both syndromic deaf-blindness [Usher syndrome I (USH1)] and nonsyndromic (DFNB2 and DFNA11) deafness in humans. It contains an N-terminal motor domain, light chain-binding IQ motifs, a coiled-coil region for heavy chain dimerization, and a tail consisting of a pair of MyTH4-FERM tandems separated by a SH3 domain. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
3PVL_A      573 SKYVVALQDNPNPAGEeSGFLSFAKGDLIILDHDTGEQVMNSGWANGINERTKQRGDFPTDCVYV 637
Cdd:cd11881   1 SKYVVALQDYPNPSDG-SSFLSFAKGDLIILDQDTGEQVMNSGWCNGRNDRTGQRGDFPADCVYV 64

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain 1, F1 sub-domain, found in Myosin-VIIa, Myosin-VIIb, and similar proteins; This family includes two nontraditional members of the myosin superfamily, myosin-VIIa and myosin-VIIb. Myosin-VIIa, also termed myosin-7a (Myo7a), has been implicated in the structural organization of hair bundles at the apex of sensory hair cells (SHCs) where it serves mechanotransduction in the process of hearing and balance. Mutations in the MYO7A gene may be associated with Usher Syndrome type 1B (USH1B) and nonsyndromic hearing loss (DFNB2, DFNA11). Myosin-VIIb, also termed myosin-7b (Myo7b), is a high duty ratio motor adapted for generating and maintaining tension. It associates with harmonin and ANKS4B to form a stable ternary complex for anchoring microvilli tip-link cadherins. Like other unconventional myosins, myosin-VII is composed of a conserved motor head, a neck region and a tail region containing two MyTH4 domains, a SH3 domain, and two FERM domains. The FERM domain is made up of three sub-domains, F1, F2, and F3. The family corresponds to the F1 sub-domain of the first FERM 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3PVL_A      263 PIMLPVTFMDGTTKTLLTDSATTARELCNALADKISLKDRFGFSLYIALFDKVSSLGSGSDHVMDAISQCEQYAKEQGAQ 342
Cdd:cd17092   1 PIMLPVTFMDGSTKTVEVDSATTARELCRQLAEKLGLKDTFGFSLYIALFDKVSSLGSGTDHVMDAISQCEQYAKEKGAQ 80

                        90
                ....*....|....*....
3PVL_A      343 ERNAPWRLFFRKEVFTPWH 361
Cdd:cd17092  81 EREAPWRLYFRKEIFAPWH 99

FERM domain C-lobe, repeat 1, of Myosin VII (MyoVII/Myo7); MyoVII, a MyTH-FERM myosin, is an actin-based motor protein essential for a variety of biological processes in the actin cytoskeleton function. Mutations in MyoVII leads to problems in sensory perception: deafness and blindness in humans (Usher Syndrome), retinal defects and deafness in mice (shaker 1), and aberrant auditory and vestibular function in zebrafish. Myosin VIIAs have plus (barbed) end-directed motor activity on actin filaments and a characteristic actin-activated ATPase activity. MyoVII consists of a conserved spectrin-like, SH3 subdomain N-terminal region, a motor/head region, a neck made of 4-5 IQ motifs, and a tail consisting of a coiled-coil domain, followed by a tandem repeat of myosin tail homology 4 (MyTH4) domains and partial FERM domains that are separated by an SH3 subdomain and are thought to mediate dimerization and binding to other proteins or cargo. Members include: MyoVIIa, MyoVIIb, and MyoVII members that do not have distinct myosin VIIA and myosin VIIB genes. 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3PVL_A      474 LLFSRFYEAYKFSGPPLPKSDVIVAVNWTGVYFVDEQEQVLLELSFPEIMAVSSSRGTKMMAPSFTLATIKGDEYTFTSS 553
Cdd:cd13198   1 LLFSRFFEATKFSGPSLPKSEVIIAVNWTGIYFVDEQEQVLLELSFPEITGVSSSRGKRDGGQSFTLTTIQGEEFVFQSP 80

                        90
                ....*....|....*....
3PVL_A      554 NAEDIRDLVVTFLEGLRKR 572
Cdd:cd13198  81 NAEDIAELVNYFLEGLRKR 99

Band 4.1 homologues; Also known as ezrin/radixin/moesin (ERM) protein domains. Present in myosins, ezrin, radixin, moesin, protein tyrosine phosphatases. Plasma membrane-binding domain. These proteins play structural and regulatory roles in the assembly and stabilization of specialized plasmamembrane domains. Some PDZ domain containing proteins bind one or more of this family. Now includes JAKs.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3PVL_A         265 MLPVTFMDGTTKTLLTDSATTARELCNALADKISLKDRFGFSLYIALFDKVsslgsgsdhvmdaISQCEQYAKEQGAQER 344
Cdd:smart00295   1 VLKVYLLDGTTLEFEVDSSTTAEELLETVCRKLGIRESEYFGLQFEDPDED-------------LRHWLDPAKTLLDQDV 67

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3PVL_A         345 N-APWRLFFRKEVFTPWHN-PSEDNVATNLIYQQVVRGVKFGEYRCEKEdDLAELASQQYFVDYG---SEMILERLLSLV 419
Cdd:smart00295  68 KsEPLTLYFRVKFYPPDPNqLKEDPTRLNLLYLQVRNDILEGRLPCPEE-EALLLAALALQAEFGdydEELHDLRGELSL 146

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
3PVL_A         420 PTYIPDREITPLKnLEKWAQLAIAAHKKGIYaQRRTDSqKVKedVVNYARfKWPLLFSRFY 480
Cdd:smart00295 147 KRFLPKQLLDSRK-LKEWRERIVELHKELIG-LSPEEA-KLK--YLELAR-KLPTYGVELF 201

FERM domain B-lobe; The FERM domain has a cloverleaf tripart structure (FERM_N, FERM_M, FERM_C/N, alpha-, and C-lobe/A-lobe, B-lobe, C-lobe/F1, F2, F3). 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, the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the pleckstrin homology (PH) and phosphotyrosine binding (PTB) domains and consequently is capable of binding to both peptides and phospholipids at different sites.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3PVL_A      369 ATNLIYQQVVRGVKFGEYRCeKEDDLAELASQQYFVDYG--SEMILERLLSLVPTYIPDREITPLKNlEKWAQLAIAAHK 446
Cdd:cd14473   1 TRYLLYLQVKRDILEGRLPC-SEETAALLAALALQAEYGdyDPSEHKPKYLSLKRFLPKQLLKQRKP-EEWEKRIVELHK 78

                        90       100
                ....*....|....*....|...
3PVL_A      447 KgiyaQRRTDSQKVKEDVVNYAR 469
Cdd:cd14473  79 K----LRGLSPAEAKLKYLKIAR 97

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
3PVL_A         572 RSKYVVALQDNPnpaGEESGFLSFAKGDLIILDHDTgeqvmNSGWANGINERtKQRGDFPTDCV 635
Cdd:smart00326   1 EGPQVRALYDYT---AQDPDELSFKKGDIITVLEKS-----DDGWWKGRLGR-GKEGLFPSNYV 55

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain 1, F1 sub-domain, found in Myosin-VIIa, Myosin-VIIb, and similar proteins; This family includes two nontraditional members of the myosin superfamily, myosin-VIIa and myosin-VIIb. Myosin-VIIa, also termed myosin-7a (Myo7a), has been implicated in the structural organization of hair bundles at the apex of sensory hair cells (SHCs) where it serves mechanotransduction in the process of hearing and balance. Mutations in the MYO7A gene may be associated with Usher Syndrome type 1B (USH1B) and nonsyndromic hearing loss (DFNB2, DFNA11). Myosin-VIIb, also termed myosin-7b (Myo7b), is a high duty ratio motor adapted for generating and maintaining tension. It associates with harmonin and ANKS4B to form a stable ternary complex for anchoring microvilli tip-link cadherins. Like other unconventional myosins, myosin-VII is composed of a conserved motor head, a neck region and a tail region containing two MyTH4 domains, a SH3 domain, and two FERM domains. The FERM domain is made up of three sub-domains, F1, F2, and F3. The family corresponds to the F1 sub-domain of the first FERM 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3PVL_A      263 PIMLPVTFMDGTTKTLLTDSATTARELCNALADKISLKDRFGFSLYIALFDKVSSLGSGSDHVMDAISQCEQYAKEQGAQ 342
Cdd:cd17092   1 PIMLPVTFMDGSTKTVEVDSATTARELCRQLAEKLGLKDTFGFSLYIALFDKVSSLGSGTDHVMDAISQCEQYAKEKGAQ 80

                        90
                ....*....|....*....
3PVL_A      343 ERNAPWRLFFRKEVFTPWH 361
Cdd:cd17092  81 EREAPWRLYFRKEIFAPWH 99

FERM domain C-lobe, repeat 1, of Myosin VII (MyoVII/Myo7); MyoVII, a MyTH-FERM myosin, is an actin-based motor protein essential for a variety of biological processes in the actin cytoskeleton function. Mutations in MyoVII leads to problems in sensory perception: deafness and blindness in humans (Usher Syndrome), retinal defects and deafness in mice (shaker 1), and aberrant auditory and vestibular function in zebrafish. Myosin VIIAs have plus (barbed) end-directed motor activity on actin filaments and a characteristic actin-activated ATPase activity. MyoVII consists of a conserved spectrin-like, SH3 subdomain N-terminal region, a motor/head region, a neck made of 4-5 IQ motifs, and a tail consisting of a coiled-coil domain, followed by a tandem repeat of myosin tail homology 4 (MyTH4) domains and partial FERM domains that are separated by an SH3 subdomain and are thought to mediate dimerization and binding to other proteins or cargo. Members include: MyoVIIa, MyoVIIb, and MyoVII members that do not have distinct myosin VIIA and myosin VIIB genes. 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3PVL_A      474 LLFSRFYEAYKFSGPPLPKSDVIVAVNWTGVYFVDEQEQVLLELSFPEIMAVSSSRGTKMMAPSFTLATIKGDEYTFTSS 553
Cdd:cd13198   1 LLFSRFFEATKFSGPSLPKSEVIIAVNWTGIYFVDEQEQVLLELSFPEITGVSSSRGKRDGGQSFTLTTIQGEEFVFQSP 80

                        90
                ....*....|....*....
3PVL_A      554 NAEDIRDLVVTFLEGLRKR 572
Cdd:cd13198  81 NAEDIAELVNYFLEGLRKR 99

Band 4.1 homologues; Also known as ezrin/radixin/moesin (ERM) protein domains. Present in myosins, ezrin, radixin, moesin, protein tyrosine phosphatases. Plasma membrane-binding domain. These proteins play structural and regulatory roles in the assembly and stabilization of specialized plasmamembrane domains. Some PDZ domain containing proteins bind one or more of this family. Now includes JAKs.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3PVL_A         265 MLPVTFMDGTTKTLLTDSATTARELCNALADKISLKDRFGFSLYIALFDKVsslgsgsdhvmdaISQCEQYAKEQGAQER 344
Cdd:smart00295   1 VLKVYLLDGTTLEFEVDSSTTAEELLETVCRKLGIRESEYFGLQFEDPDED-------------LRHWLDPAKTLLDQDV 67

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3PVL_A         345 N-APWRLFFRKEVFTPWHN-PSEDNVATNLIYQQVVRGVKFGEYRCEKEdDLAELASQQYFVDYG---SEMILERLLSLV 419
Cdd:smart00295  68 KsEPLTLYFRVKFYPPDPNqLKEDPTRLNLLYLQVRNDILEGRLPCPEE-EALLLAALALQAEFGdydEELHDLRGELSL 146

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
3PVL_A         420 PTYIPDREITPLKnLEKWAQLAIAAHKKGIYaQRRTDSqKVKedVVNYARfKWPLLFSRFY 480
Cdd:smart00295 147 KRFLPKQLLDSRK-LKEWRERIVELHKELIG-LSPEEA-KLK--YLELAR-KLPTYGVELF 201

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in Dictyostelium discoideum Myosin-VIIa (DdMyo7) and similar proteins; DdMyo7, also termed Myosin-I heavy chain, or class VII unconventional myosin, or M7, plays a role in adhesion in Dictyostelium where it is a component of a complex of proteins that serve to link membrane receptors to the underlying actin cytoskeleton. It interacts with talinA, an actin-binding protein with a known role in cell-substrate adhesion. DdMyo7 is required for phagocytosis. It is also essential for the extension of filopodia, plasma membrane protrusions filled with parallel bundles of F-actin. Members in this family contain a myosin motor domain, two MyTH4 domains, two FERM (Band 4.1, ezrin, radixin, moesin) domains, and two Pleckstrin homology (PH) domains. Some family members contain an extra SH3 domain. Each 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3PVL_A      262 KPIMLPVTFMDGTTKTLLTDSATTARELCNALADKISLKDR-FGFSLYIALFDKVSSLGSgSDHVMDAISQCEQYAKEQG 340
Cdd:cd17208   2 RPIVARFYFLDGQFKALEFDSAATAAEVLEQLKQKIGLRSTaDGFALYEVFGGIERAILP-EEKVADVLSKWEKLQRTMA 80

                        90
                ....*....|....*..
3PVL_A      341 AQERNAPWRLFFRKEVF 357
Cdd:cd17208  81 SCAAQQAVKFVFKKRLF 97

FERM domain B-lobe; The FERM domain has a cloverleaf tripart structure (FERM_N, FERM_M, FERM_C/N, alpha-, and C-lobe/A-lobe, B-lobe, C-lobe/F1, F2, F3). 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, the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the pleckstrin homology (PH) and phosphotyrosine binding (PTB) domains and consequently is capable of binding to both peptides and phospholipids at different sites.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3PVL_A      369 ATNLIYQQVVRGVKFGEYRCeKEDDLAELASQQYFVDYG--SEMILERLLSLVPTYIPDREITPLKNlEKWAQLAIAAHK 446
Cdd:cd14473   1 TRYLLYLQVKRDILEGRLPC-SEETAALLAALALQAEYGdyDPSEHKPKYLSLKRFLPKQLLKQRKP-EEWEKRIVELHK 78

                        90       100
                ....*....|....*....|...
3PVL_A      447 KgiyaQRRTDSQKVKEDVVNYAR 469
Cdd:cd14473  79 K----LRGLSPAEAKLKYLKIAR 97

FERM domain C-lobe; 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3PVL_A      477 SRFYEAYKFSGPPlpkSDVIVAVNWTGVYFVDEQE-QVLLELSFPEIMAVSSSRGTKmmapsFTLATI---KGDEYTFTS 552
Cdd:cd00836   2 VEFFPVKDKSKKG---SPIILGVNPEGISVYDELTgQPLVLFPWPNIKKISFSGAKK-----FTIVVAdedKQSKLLFQT 73

                        90       100
                ....*....|....*....|
3PVL_A      553 SN--AEDIRDLVVTFLEGLR 570
Cdd:cd00836  74 PSrqAKEIWKLIVGYHRFLL 93

Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction domains that bind proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. Thus, they are referred to as proline-recognition domains (PRDs). SH3 domains are less selective and show more diverse specificity compared to other PRDs. They have been shown to bind peptide sequences that lack the PxxP motif; examples include the PxxDY motif of Eps8 and the RKxxYxxY sequence in SKAP55. SH3 domain containing proteins play versatile and diverse roles in the cell, including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies, among others. Many members of this superfamily are adaptor proteins that associate with a number of protein partners, facilitating complex formation and signal transduction.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
3PVL_A      575 YVVALQDNpnpAGEESGFLSFAKGDLIILDHDTgeqvmNSGWANGINERtKQRGDFPTDC 634
Cdd:cd00174   1 YARALYDY---EAQDDDELSFKKGDIITVLEKD-----DDGWWEGELNG-GREGLFPANY 51

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
3PVL_A         572 RSKYVVALQDNPnpaGEESGFLSFAKGDLIILDHDTgeqvmNSGWANGINERtKQRGDFPTDCV 635
Cdd:smart00326   1 EGPQVRALYDYT---AQDPDELSFKKGDIITVLEKS-----DDGWWKGRLGR-GKEGLFPSNYV 55

Src Homology 3 domain of the p85beta regulatory subunit of Class IA Phosphatidylinositol 3-kinases; Class I PI3Ks convert PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. They are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. Class IA PI3Ks associate with the p85 regulatory subunit family, which contains SH3, RhoGAP, and SH2 domains. The p85 subunits recruit the PI3K p110 catalytic subunit to the membrane, where p110 phosphorylates inositol lipids. Vertebrates harbor two p85 isoforms, called alpha and beta. In addition to regulating the p110 subunit, p85beta binds CD28 and may be involved in the activation and differentiation of antigen-stimulated T cells. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
3PVL_A      593 LSFAKGDLIILD-HDTGEQVMNS-GWANGINERTKQRGDFPTDCV-YVMP 639
Cdd:cd11909  25 LTVSRAALQALGvKEGGEQCPQSiGWILGLNERTKQRGDFPGTYVeFLGP 74

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in pleckstrin homology domain-containing family H member 1 (PLEKHH1); PLEKHH1 is a homolog of Caenorhabditis elegans MAX-1 that has been implicated in motor neuron axon guidance. PLEKHH1 is critical in vascular patterning in vertebrate species through acting upstream of the ephrin pathway. PLEKHH1 contains a putative alpha-helical coiled-coil segment within the N-terminal half, and two Pleckstrin homology (PH) domains, a MyTH4 domain, and a FERM (Band 4.1, ezrin, radixin, moesin) domain within the C-terminal half. The FERM domain is made up of three sub-domains, F1, F2, and F3. The family corresponds to F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N).

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3PVL_A      263 PIMLPVTFMDGTTKTLLTDSATTARELCNALADKISLK--DRFGFSLYIalfDKVSSLG-----SGSDHVMDAISQCEQY 335
Cdd:cd17178   1 PFSIPVHFMNGTYQVVGFDGSTTVDEFLQTLNQETGMRkpSHSGFALFT---DDPSGKDlehclQGSVKICDVISKWEQA 77

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3PVL_A      336 AKE--QGAQERNAPWRLFFRKEVF 357
Cdd:cd17178  78 LKElhPGKYEGTRTVRLTYKSRLY 101

Src Homology 3 domain of Insulin Receptor tyrosine kinase Substrate p53; IRSp53 is also known as BAIAP2 (Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2). It is a scaffolding protein that takes part in many signaling pathways including Cdc42-induced filopodia formation, Rac-mediated lamellipodia extension, and spine morphogenesis. IRSp53 exists as multiple splicing variants that differ mainly at the C-termini. One variant (T-form) is expressed exclusively in human breast cancer cells. The gene encoding IRSp53 is a putative susceptibility gene for Gilles de la Tourette syndrome. IRSp53 can also mediate the recruitment of effector proteins Tir and EspFu, which regulate host cell actin reorganization, to bacterial attachment sites. It contains an N-terminal IMD, a CRIB (Cdc42 and Rac interactive binding motif), an SH3 domain, and a WASP homology 2 (WH2) actin-binding motif at the C-terminus. The SH3 domain of IRSp53 has been shown to bind the proline-rich C-terminus of EspFu. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

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3PVL_A      586 AGEESGFLSFAKGDLIILDHDTGEqvmnSGWANGINERTKQRGDFP 631
Cdd:cd11915  11 AGDNSTLLSFKEGDYITLLVPEAR----DGWHYGECEKTKMRGWFP 52

Src Homology 3 domain of the p85 regulatory subunit of Class IA Phosphatidylinositol 3-kinases; Class I PI3Ks convert PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. They are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. Class IA PI3Ks associate with the p85 regulatory subunit family, which contains SH3, RhoGAP, and SH2 domains. The p85 subunits recruit the PI3K p110 catalytic subunit to the membrane, where p110 phosphorylates inositol lipids. Vertebrates harbor two p85 isoforms, called alpha and beta. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                        10
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3PVL_A      615 GWANGINERTKQRGDFP 631
Cdd:cd11776  49 GWLEGKNERTGERGDFP 65

Src Homology 3 domain of Amphiphysin and related domains; Amphiphysins function primarily in endocytosis and other membrane remodeling events. They exist in several isoforms and mammals possess two amphiphysin proteins from distinct genes. Amphiphysin I proteins, enriched in the brain and nervous system, contain domains that bind clathrin, Adaptor Protein complex 2 (AP2), dynamin, and synaptojanin. They function in synaptic vesicle endocytosis. Human autoantibodies to amphiphysin I hinder GABAergic signaling and contribute to the pathogenesis of paraneoplastic stiff-person syndrome. Some amphiphysin II isoforms, also called Bridging integrator 1 (Bin1), are localized in many different tissues and may function in intracellular vesicle trafficking. In skeletal muscle, Bin1 plays a role in the organization and maintenance of the T-tubule network. Mutations in Bin1 are associated with autosomal recessive centronuclear myopathy. Amphiphysins contain an N-terminal BAR domain with an additional N-terminal amphipathic helix (an N-BAR), a variable central domain, and a C-terminal SH3 domain. The SH3 domain of amphiphysins bind proline-rich motifs present in binding partners such as dynamin, synaptojanin, and nsP3. It also belongs to a subset of SH3 domains that bind ubiquitin in a site that overlaps with the peptide binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

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3PVL_A      587 GEESGFLSFAKGDLI-ILDHDTGEQvMNSGWANGINERTKQRGDFP 631
Cdd:cd11790  13 AEDTDELTFEKGDVIlVIPFDDPEE-QDEGWLMGVKESTGCRGVFP 57

C-terminal Src Homology 3 domain of the Nebulin family of proteins; Nebulin family proteins contain multiple nebulin repeats, and may contain an N-terminal LIM domain and/or a C-terminal SH3 domain. They have molecular weights ranging from 34 to 900 kD, depending on the number of nebulin repeats, and they all bind actin. They are involved in the regulation of actin filament architecture and function as stabilizers and scaffolds for cytoskeletal structures with which they associate, such as long actin filaments or focal adhesions. Nebulin family proteins that contain a C-terminal SH3 domain include the giant filamentous protein nebulin, nebulette, Lasp1, and Lasp2. Lasp2, also called LIM-nebulette, is an alternatively spliced variant of nebulette. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

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3PVL_A      594 SFAKGDLIIldhdtGEQVMNSGWANGINERTKQRGDFPTDcvYVMP 639
Cdd:cd11789  17 SFQEGDVII-----NVEIIDDGWMEGTVQRTGQSGMLPAN--YVEL 55