FERM domain C-lobe of Protein 4.1 family; The protein 4.1 family includes four well-defined members: erythroid protein 4.1 (4.1R), the best known and characterized member, 4.1G (general), 4.1N (neuronal), and 4.1 B (brain). The less well understood 4.1O/FRMD3 is not a true member of this family and is not included in this hierarchy. Besides three highly conserved domains, FERM, SAB (spectrin and actin binding domain) and CTD (C-terminal domain), the proteins from this family contain several unique domains: U1, U2 and U3. FERM domains like other members of the FERM domain superfamily have a cloverleaf architecture with three distinct lobes: (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 brain is a particularly rich source of protein 4.1 isoforms. The various 4.1R, 4.1G, 4.1N, and 4.1B mRNAs are all expressed in distinct patterns within the brain. It is likely that 4.1 proteins play important functional roles in the brain including motor coordination and spatial learning, postmitotic differentiation, and synaptic architecture and function. In addition they are found in nonerythroid, nonneuronal cells where they may play a general structural role in nuclear architecture and/or may interact with splicing factors. 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 1720388969  304 YGVDLHHAKDSEGVEIMLGVCASGLLIYRDRLRINRFAWPKVLKISYKRNNFYIKIRPGEFEQFESTIGFKLPNHRAAKR 383
Cdd:cd13184      1 YGVDLHPAKDSEGVDIMLGVCSSGLLVYRDRLRINRFAWPKVLKISYKRNNFYIKIRPGEFEQYETTIGFKLPNHRAAKR 80

                           90
                   ....*....|....
gi 1720388969  384 LWKVCVEHHTFFRL 397
Cdd:cd13184     81 LWKVCVEHHTFFRL 94

FERM adjacent (FA); This region is found adjacent to Band 4.1 / FERM domains (pfam00373) in a subset of FERM containing protein. The region has been hypothesized to play a role in regulatory adaptation, based on similarity to other protein kinase substrates.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 1720388969  406 KFLTLGSKFRYSGRTQAQTRRASALIDRPAPYFERSSSKRYTMS 449
Cdd:pfam08736    1 KFFSLGSKFRYSGRTQKQTVEDSSEILRPQPEFERSPSKRYPSR 44

FERM domain C-lobe of Protein 4.1 family; The protein 4.1 family includes four well-defined members: erythroid protein 4.1 (4.1R), the best known and characterized member, 4.1G (general), 4.1N (neuronal), and 4.1 B (brain). The less well understood 4.1O/FRMD3 is not a true member of this family and is not included in this hierarchy. Besides three highly conserved domains, FERM, SAB (spectrin and actin binding domain) and CTD (C-terminal domain), the proteins from this family contain several unique domains: U1, U2 and U3. FERM domains like other members of the FERM domain superfamily have a cloverleaf architecture with three distinct lobes: (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 brain is a particularly rich source of protein 4.1 isoforms. The various 4.1R, 4.1G, 4.1N, and 4.1B mRNAs are all expressed in distinct patterns within the brain. It is likely that 4.1 proteins play important functional roles in the brain including motor coordination and spatial learning, postmitotic differentiation, and synaptic architecture and function. In addition they are found in nonerythroid, nonneuronal cells where they may play a general structural role in nuclear architecture and/or may interact with splicing factors. 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 1720388969  304 YGVDLHHAKDSEGVEIMLGVCASGLLIYRDRLRINRFAWPKVLKISYKRNNFYIKIRPGEFEQFESTIGFKLPNHRAAKR 383
Cdd:cd13184      1 YGVDLHPAKDSEGVDIMLGVCSSGLLVYRDRLRINRFAWPKVLKISYKRNNFYIKIRPGEFEQYETTIGFKLPNHRAAKR 80

                           90
                   ....*....|....
gi 1720388969  384 LWKVCVEHHTFFRL 397
Cdd:cd13184     81 LWKVCVEHHTFFRL 94

4.1 protein C-terminal domain (CTD); At the C-terminus of all known 4.1 proteins is a sequence domain unique to these proteins, known as the C-terminal domain (CTD). Mammalian CTDs are associated with a growing number of protein-protein interactions, although such activities have yet to be associated with invertebrate CTDs. Mammalian CTDs are generally defined by sequence alignment as encoded by exons 18-21. Comparison of known vertebrate 4.1 proteins with invertebrate 4.1 proteins indicates that mammalian 4.1 exon 19 represents a vertebrate adaptation that extends the sequence of the CTD with a Ser/Thr-rich sequence. The CTD was first described as a 22/24-kDa domain by chymotryptic digestion of erythrocyte 4.1 (4.1R). CTD is thought to represent an independent folding structure which has gained function since the divergence of vertebrates from invertebrates.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720388969  979 KEVPVVHTETKTITYESSQVDPGADLEPGVLMSAQTITSETTSTTTTTHITKTVKGGISETRIEKRIVITGDADIDHDQA 1058
Cdd:pfam05902    1 KEVPIVHTETKTITYESSQVDGRGDSDPGVLVSAQTITSETQSTTTTTHITKTVKGGISETRIEKRIVITGDADIDHDQA 80

                           90       100
                   ....*....|....*....|....*..
gi 1720388969 1059 LAQAIKEAKEQHPDMSVTKVVVHKETE 1085
Cdd:pfam05902   81 LAQAIKEAKEQHPDMSVTKVVVHKETE 107

FERM C-terminal PH-like domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720388969  313 DSEGVEIMLGVCASGLLIYRDRLRI-NRFAWPKVLKISYKRNNFYIKIRpgeFEQFESTIGFKLPNHRAAKRLWKVCVEH 391
Cdd:pfam09380    1 DKEGTDLWLGVSAKGILVYEDNNKIlNLFPWREIRKISFKRKKFLIKLR---DKSSEETLGFYTESSRACKYLWKLCVEQ 77

                   ....*.
gi 1720388969  392 HTFFRL 397
Cdd:pfam09380   78 HTFFRL 83

SAB domain; This presumed domain is found in proteins containing FERM domains pfam00373. This domain is found to bind to both spectrin and actin, hence the name SAB (Spectrin and Actin Binding) domain.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1720388969  721 TEDLDKTQDELMKHQTNISELKRTFLETSTETALTNEWEKRLST-SPVR 768
Cdd:pfam04382    2 LEDLDKTQEDLLKHQASISELKRTFMEPNPEDLGPSEWEKRLSSnSPVR 50

FERM domain C-lobe of Protein 4.1 family; The protein 4.1 family includes four well-defined members: erythroid protein 4.1 (4.1R), the best known and characterized member, 4.1G (general), 4.1N (neuronal), and 4.1 B (brain). The less well understood 4.1O/FRMD3 is not a true member of this family and is not included in this hierarchy. Besides three highly conserved domains, FERM, SAB (spectrin and actin binding domain) and CTD (C-terminal domain), the proteins from this family contain several unique domains: U1, U2 and U3. FERM domains like other members of the FERM domain superfamily have a cloverleaf architecture with three distinct lobes: (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 brain is a particularly rich source of protein 4.1 isoforms. The various 4.1R, 4.1G, 4.1N, and 4.1B mRNAs are all expressed in distinct patterns within the brain. It is likely that 4.1 proteins play important functional roles in the brain including motor coordination and spatial learning, postmitotic differentiation, and synaptic architecture and function. In addition they are found in nonerythroid, nonneuronal cells where they may play a general structural role in nuclear architecture and/or may interact with splicing factors. 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 1720388969  304 YGVDLHHAKDSEGVEIMLGVCASGLLIYRDRLRINRFAWPKVLKISYKRNNFYIKIRPGEFEQFESTIGFKLPNHRAAKR 383
Cdd:cd13184      1 YGVDLHPAKDSEGVDIMLGVCSSGLLVYRDRLRINRFAWPKVLKISYKRNNFYIKIRPGEFEQYETTIGFKLPNHRAAKR 80

                           90
                   ....*....|....
gi 1720388969  384 LWKVCVEHHTFFRL 397
Cdd:cd13184     81 LWKVCVEHHTFFRL 94

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in erythrocyte membrane protein band 4.1-like proteins; The family includes erythrocyte membrane protein band 4.1-like proteins EPB41L1/4.1N, EPB41L2/4.1G, and EPB41L3/4.1B. They belong to the skeletal protein 4.1 family that is involved in cellular processes such as cell adhesion, migration and signaling. EPB41L1 is a cytoskeleton-associated protein that may serve as a tumor suppressor in solid tumors. EPB41L2 is involved in cellular processes such as cell adhesion, migration and signaling. EPB41L3 also acts as a tumor suppressor implicated in a variety of meningiomas and carcinomas. Members in this family contain 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        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720388969  117 SMQCKVTLLDGSEYGCDVDKRSRGQVLFDKVCEHLNLLEKDYFGLTYRDAENQKNWLDPAKEIKKQIRSGAWHFSFNVKF 196
Cdd:cd17106      1 SQQCKVLLLDGTEYTCEVEKRAKGQVLFDKVCEHLNLLEKDYFGLTYRDAQDQKNWLDPAKEIKKQIRSGPWLFSFNVKF 80

                   ....
gi 1720388969  197 YPPD 200
Cdd:cd17106     81 YPPD 84

4.1 protein C-terminal domain (CTD); At the C-terminus of all known 4.1 proteins is a sequence domain unique to these proteins, known as the C-terminal domain (CTD). Mammalian CTDs are associated with a growing number of protein-protein interactions, although such activities have yet to be associated with invertebrate CTDs. Mammalian CTDs are generally defined by sequence alignment as encoded by exons 18-21. Comparison of known vertebrate 4.1 proteins with invertebrate 4.1 proteins indicates that mammalian 4.1 exon 19 represents a vertebrate adaptation that extends the sequence of the CTD with a Ser/Thr-rich sequence. The CTD was first described as a 22/24-kDa domain by chymotryptic digestion of erythrocyte 4.1 (4.1R). CTD is thought to represent an independent folding structure which has gained function since the divergence of vertebrates from invertebrates.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720388969  979 KEVPVVHTETKTITYESSQVDPGADLEPGVLMSAQTITSETTSTTTTTHITKTVKGGISETRIEKRIVITGDADIDHDQA 1058
Cdd:pfam05902    1 KEVPIVHTETKTITYESSQVDGRGDSDPGVLVSAQTITSETQSTTTTTHITKTVKGGISETRIEKRIVITGDADIDHDQA 80

                           90       100
                   ....*....|....*....|....*..
gi 1720388969 1059 LAQAIKEAKEQHPDMSVTKVVVHKETE 1085
Cdd:pfam05902   81 LAQAIKEAKEQHPDMSVTKVVVHKETE 107

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        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720388969  303 MYGVDLHHAKDSEGVEIMLGVCASGLLIYRDRLRINRFAWPKVLKISYKRNNFYIKIRPGEFEQFESTIGFKLPNHRAAK 382
Cdd:cd13189      1 LYGVELHSARDSNNLELQIGVSSAGILVFQNGIRINTFPWSKIVKISFKRKQFFIQLRREPNESRDTILGFNMLSYRACK 80

                           90
                   ....*....|....*
gi 1720388969  383 RLWKVCVEHHTFFRL 397
Cdd:cd13189     81 NLWKSCVEHHTFFRL 95

FERM central domain; This domain is the central structural domain of the FERM domain.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720388969  199 PDPAQLSEDITRYYLCLQLRDDIVSGRLPCSFVTLALLGSYTVQSELGDYDPDECGNDYISEFRFAPNH------TKELE 272
Cdd:pfam00373    1 DLELLLQDEVTRHLLYLQAKDDILEGRLPCSEEEALLLAALQLQAEFGDYQPSSHTSEYLSLESFLPKQllrkmkSKELE 80

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 1720388969  273 DKVIELHKSHRGMTPAEAEMHFLENAKKLSMYGVDLH 309
Cdd:pfam00373   81 KRVLEAHKNLRGLSAEEAKLKYLQIAQSLPTYGVEFF 117

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720388969  209 TRYYLCLQLRDDIVSGRLPCSFVTLALLGSYTVQSELGDYDPDECGNDYISEFRFAPNHT------KELEDKVIELHKSH 282
Cdd:cd14473      1 TRYLLYLQVKRDILEGRLPCSEETAALLAALALQAEYGDYDPSEHKPKYLSLKRFLPKQLlkqrkpEEWEKRIVELHKKL 80

                           90
                   ....*....|....*....
gi 1720388969  283 RGMTPAEAEMHFLENAKKL 301
Cdd:cd14473     81 RGLSPAEAKLKYLKIARKL 99

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 1720388969  296 ENAKKLSMYGVDLHHAKDSEGVEIMLGVCASGLLIYRDRLRINRFAWPKVLKISYKRNNFYIKIRPGEFEQFESTIGFKL 375
Cdd:cd13193      1 ETARRCELYGIRLHPAKDREGVKLNLAVAHMGILVFQGFTKINTFSWAKIRKLSFKRKRFLIKLHPEAYGSYKDTVEFSF 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 1720388969  376 PNHRAAKRLWKVCVEHHTFFRLLLPEAPPK---KFLTLGSKF 414
Cdd:cd13193     81 ESRNECKSFWKKCIEHHAFFRCSEVPKPPSpklRLFSRGSSF 122

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in FERM, RhoGEF and pleckstrin domain-containing protein 1 (FARP1) and similar proteins; This family includes the F1 sub-domain of FERM, RhoGEF and pleckstrin domain-containing proteins FARP1, FARP2, and FERM domain-containing protein 7 (FRMD7). FARP1, also termed chondrocyte-derived ezrin-like protein (CDEP), or pleckstrin homology (PH) domain-containing family C member 2 (PLEKHC2), is a neuronal activator of the RhoA GTPase. It promotes outgrowth of developing motor neuron dendrites. It also regulates excitatory synapse formation and morphology, as well as activates the GTPase Rac1 to promote F-actin assembly. FARP2, also termed FERM domain including RhoGEF (FIR), or Pleckstrin homology (PH) domain-containing family C member 3, is a Dbl-family guanine nucleotide exchange factor (GEF) that activates Rac1 or Cdc42 in response to upstream signals, suggesting roles in regulating processes such as neuronal axon guidance and bone homeostasis. It is also a key molecule involved in the response of neuronal growth cones to class-3 semaphorins. FRMD7 plays an important role in neuronal development and is involved in the regulation of F-actin, neurofilament, and microtubule dynamics. All family members contain a FERM domain that 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).

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720388969  118 MQCKVTLLDGSEYGCDVDKRSRGQVLFDKVCEHLNLLEKDYFGLTYRDAENQKNWLDPAKEIKKQIRSgawH----FSFN 193
Cdd:cd17098      1 LHVKVQMLDDTVHIFQVQQKALGEVLFDQVCKHLNLLESDYFGLEFTDPEGNKCWLDPEKPILRQVKR---PkdvvFKFV 77

                   ....*...
gi 1720388969  194 VKFYPPDP 201
Cdd:cd17098     78 VKFYTPDP 85

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in erythrocyte membrane protein band 4.1-like 5 (EPB41L5) and similar proteins; This family includes FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in erythrocyte membrane protein band 4.1-like proteins, EPB41L5 and EPB41L4B. EPB41L5 is a mesenchymal-specific protein that is an integral component of the ARF6-based pathway. EPB41L4B is a positive regulator of keratinocyte adhesion and motility, suggesting a role in wound healing. It also promotes cancer metastasis in melanoma, prostate cancer and breast cancer. Both EPB41L5 and EPB41L4B 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 1720388969  118 MQCKVTLLDGSEYGCDVDKRSRGQVLFDKVCEHLNLLEKDYFGLTYRDAENQKNWLDPAKEIKKQIRSG-AWHFSFNVKF 196
Cdd:cd17108      1 IQCKVILLDGTDLSIELPKKAKGQELYEQVFYHLDLIEKDYFGLQFMDAAQVQHWLDPTKKIKKQVKIGpPYTLRFRVKF 80

                   .
gi 1720388969  197 Y 197
Cdd:cd17108     81 Y 81

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in erythrocyte band 4.1-like protein 4A (EPB41L4A) and similar proteins; EPB41L4A, also termed protein NBL4, is a member of the band 4.1/Nbl4 (novel band 4.1-like protein 4) group of the FERM protein superfamily. It contains 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). EPB41L4A is an important component of the beta-catenin/Tcf pathway. It may be related to determination of cell polarity or proliferation.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720388969  116 KSMQCKVTLLDGSEYGC----DVDKRSRGQVLFDKVCEHLNLLEKDYFGLTYRDAENQKNWLDPAKEIKKQIR--SGAWH 189
Cdd:cd17107      1 EEFYCEIVLLDESELILtiqqDGIKSSKGSVVLDVVFQHLNLLETDYFGLRYIDRQHQTHWLDPAKTLSEQLKliGPPYT 80

                           90
                   ....*....|.
gi 1720388969  190 FSFNVKFYPPD 200
Cdd:cd17107     81 LYFGVKFYAED 91

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in erythrocyte band 4.1-like protein 4B (EPB41L4B); EPB41L4B, also termed FERM-containing protein CG1, or expressed in high metastatic cells (Ehm2), or Lulu2, is a member of the band 4.1/Nbl4 (novel band 4.1-like protein 4) group of the FERM protein superfamily. It contains 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). EPB41L4B is a positive regulator of keratinocyte adhesion and motility, suggesting a role in wound healing. It also promotes cancer metastasis in melanoma, prostate cancer and breast cancer.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720388969  118 MQCKVTLLDGSEYGCDVDKRSRGQVLFDKVCEHLNLLEKDYFGLTYRDAENQKNWLDPAKEIKKQIRSG-AWHFSFNVKF 196
Cdd:cd17204      1 LTCRVLLLDGTDVSVELPKHAKGQDLFDQIVYHLDLVETDYFGLQFMDAAQVAHWLDHTKPIKKQIKIGpPYTLHFRIKY 80

                   .
gi 1720388969  197 Y 197
Cdd:cd17204     81 Y 81

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720388969  305 GVDLHHAKDSE--GVEIMLGVCASGLLIY--RDRLRINRFAWPKVLKISYKR-NNFYIKIRPgefEQFESTIGFKLPNhR 379
Cdd:cd00836      1 GVEFFPVKDKSkkGSPIILGVNPEGISVYdeLTGQPLVLFPWPNIKKISFSGaKKFTIVVAD---EDKQSKLLFQTPS-R 76

                           90
                   ....*....|....*..
gi 1720388969  380 AAKRLWKVCVEHHTFFR 396
Cdd:cd00836     77 QAKEIWKLIVGYHRFLL 93

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in FERM, ARH/RhoGEF and pleckstrin domain-containing protein 2 (FARP2) and similar proteins; FARP2, also termed FERM domain including RhoGEF (FIR), or Pleckstrin homology (PH) domain-containing family C member 3, is a Dbl-family guanine nucleotide exchange factor (GEF) that activates Rac1 or Cdc42 in response to upstream signals, suggesting roles in regulating processes such as neuronal axon guidance and bone homeostasis. It is also a key molecule involved in the response of neuronal growth cones to class-3 semaphorins. FARP2 contains a FERM domain, a Dbl-homology (DH) domain and two pleckstrin homology (PH) domains. 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 1720388969  118 MQCKVTLLDGSEYGCDVDKRSRGQVLFDKVCEHLNLLEKDYFGLTYRDAENQKNWLDPAKEIKKQI-RSGAWHFSFNVKF 196
Cdd:cd17190      1 LQLRVKLLDNTTEPLEIEPKADGQALLSQVFKRLNLVESDYFGLEFQNSQSNWIWLEPMKLIVKQVrRPKNTKLRLAVKF 80

                   ....*
gi 1720388969  197 YPPDP 201
Cdd:cd17190     81 FPPDP 85

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in FERM domain-containing protein 7 (FRMD7); FRMD7 plays an important role in neuronal development and is involved in the regulation of F-actin, neurofilament, and microtubule dynamics. It interacts with the Rho GTPase regulator, RhoGDIalpha, and activates the Rho subfamily member Rac1, which regulates reorganization of actin filaments and controls neuronal outgrowth. Mutations in the FRMD7 gene are responsible for the X-linked idiopathic congenital nystagmus (ICN), a disease which affects ocular motor control. FRMD7 contains a FERM domain, and a pleckstrin homology (PH) 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        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720388969  121 KVTLLDGSEYGCDVDKRSRGQVLFDKVCEHLNLLEKDYFGLTYRDAENQKNWLDPAKEIKKQI-RSGAWHFSFNVKFYPP 199
Cdd:cd17188      5 KVQFLDDSQKVFVVDQKSTGKDLFNMSCSHLNLVEKEYFGLEFRNHAGNNVWLELLKPITKQIkNPKELIFKFTVKFFPV 84

                   ..
gi 1720388969  200 DP 201
Cdd:cd17188     85 DP 86

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in FERM, ARH/RhoGEF and pleckstrin domain-containing protein 1 (FARP1); FARP1, also termed chondrocyte-derived ezrin-like protein (CDEP), or pleckstrin homology (PH) domain-containing family C member 2 (PLEKHC2), is a neuronal activator of the RhoA GTPase. It promotes outgrowth of developing motor neuron dendrites. It also regulates excitatory synapse formation and morphology, as well as activates the GTPase Rac1 to promote F-actin assembly. As a novel downstream signaling partner of Rif, FARP1 is involved in the regulation of semaphorin signaling in neurons. FARP1 contains a FERM domain, a Dbl-homology (DH) domain and two pleckstrin homology (PH) domains. 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 1720388969  121 KVTLLDGSEYGCDVDKRSRGQVLFDKVCEHLNLLEKDYFGLTYRDAENQKNWLDPAKEIKKQIRSGAwH--FSFNVKFYP 198
Cdd:cd17189      4 KVQMLDDTQEVFEVPQRAPGKVLLDAVCSHLNLVEGDYFGLEFQDHRKVMVWLDLLKPIVKQIRRPK-HvvLRFVVKFFP 82

                   ..
gi 1720388969  199 PD 200
Cdd:cd17189     83 PD 84

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in E3 ubiquitin-protein ligase MYLIP and similar proteins; MYLIP, also termed inducible degrader of the LDL-receptor (Idol), or myosin regulatory light chain interacting protein (MIR), is an E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of myosin regulatory light chain (MRLC), LDLR, VLDLR and LRP8. Its activity depends on E2 ubiquitin-conjugating enzymes of the UBE2D family, including UBE2D1, UBE2D2, UBE2D3, and UBE2D4. MYLIP stimulates clathrin-independent endocytosis and acts as a sterol-dependent inhibitor of cellular cholesterol uptake by binding directly to the cytoplasmic tail of the LDLR and promoting its ubiquitination via the UBE2D1/E1 complex. The ubiquitinated LDLR then enters the multivesicular body (MVB) protein-sorting pathway and is shuttled to the lysosome for degradation. Moreover, MYLIP has been identified as a novel ERM-like protein that affects cytoskeleton interactions regulating cell motility, such as neurite outgrowth. The ERM proteins includes ezrin, radixin, and moesin, which are cytoskeletal effector proteins linking actin to membrane-bound proteins at the cell surface. MYLIP contains a FERM-domain and a C-terminal C3HC4-type RING-HC finger. 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 1720388969  118 MQCKVTLLDGSEYGCDVDKRSRGQVLFDKVCEHLNLLEKDYFGLTYRDAENQKNWLDPAKEIKKQIRSGAWH-FSFNVKF 196
Cdd:cd17104      1 MLCLVSQPDSVVIEVEVDPKANGQECLDKVCQKLGIIEKDYFGLQYTGPKGERLWLNLRNRISRQLPGPPPYrLRLRVKF 80

                   .
gi 1720388969  197 Y 197
Cdd:cd17104     81 F 81

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        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720388969  304 YGVDLHHAKDSEGVEIMLGVCASGLLIYRDRLR-INRFAWPKVLKISYKRNNFYIKIRPGEFEqfESTIGFKLPNHRAAK 382
Cdd:cd13195      1 YGVEFFEVRNIEGQKLLIGVGPHGITICNDDFEvIERIPYTAIQMATSSGRVFTLTYLSDDGS--VKVLEFKLPSTRAAS 78

                           90
                   ....*....|....
gi 1720388969  383 RLWKVCVEHHTFFR 396
Cdd:cd13195     79 GLYRAITEKHAFYR 92

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in tyrosine-protein phosphatase non-receptors PTPN14, PTPN21, and similar proteins; This family includes tyrosine-protein phosphatase non-receptors PTPN14 and PTPN21, both of which are protein-tyrosine phosphatase (PTP). They belong 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). PTPN14 plays a role in the nucleus during cell proliferation. 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.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1720388969  121 KVTLLDGSEYGCDVDKRSRGQVLFDKVCEHLNLLEKDYFGLTYRDAENQKNWLDPAKEIKKQIRSGAWHFS--FNVKFY 197
Cdd:cd17099      7 RIQLLDNTVLECTLSPESTGQDCLEYVAQRLELREIEYFGLRYVNKKGQLRWVDLEKPLKKQLDKHAHEPLlyFGVMFY 85

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in FERM domain-containing proteins FRMD4A, FRMD4B, and similar proteins; This family includes FERM domain-containing proteins FRMD4A and FRMD4B, both of which 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). FRMD4A is a cytohesin adaptor involved in cell structure, transport and signaling. It promotes the growth of cancer cells in tongue, head and neck squamous cell carcinomas. 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).

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720388969  116 KSMQCKVTLLDGSEYGCDVDKRSRGQVLFDKVCEHLNLLEKDYFGLTYRDAENQKNWLDPAK-----EIKKQIRSGAWHF 190
Cdd:cd17103      1 EGRRCQVVLLDDRRLEILVQPKLLAGDLLDLVASHFNLKEKEYFGLAYEDETGHYNWLQLDKrvldhEFPKKWSSGPLVL 80

                   ....*..
gi 1720388969  191 SFNVKFY 197
Cdd:cd17103     81 HFAVKFY 87

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 1720388969  120 CKVTLLDGSEYGCDVDKRSRGQVLFDKVCEHLNLLEKDYFGLTYRDAENQKNWLDPAKEIKKQ---IRSGAWHFSFNVKF 196
Cdd:cd17200      5 CQVHLLDDRKLELLVQPKLLSRELLDLVASHFNLKEKEYFGITFIDDTGQSNWLQLDHRVLDHdlpKKSGPVTLYFAVRF 84

                   .
gi 1720388969  197 Y 197
Cdd:cd17200     85 Y 85

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 1720388969  303 MYGVDLHHAKDSEGVEIMLGVCASGLLIYR--DRL--RINrFAWPKVLKISYKRNNFYIKIRPGEFEQFEstigFKLPNH 378
Cdd:cd13194      1 MYGVNYFEIKNKKGTDLWLGVDALGLNIYEpdNKLtpKIG-FPWSEIRNISFNDKKFVIKPIDKKAPDFV----FYSPRL 75

                           90
                   ....*....|....*..
gi 1720388969  379 RAAKRLWKVCVEHHTFF 395
Cdd:cd13194     76 RINKRILDLCMGNHELY 92

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 1720388969  116 KSMQCKVTLLDgSEYGCDVDKRSRGQVLFDKVCEHLNLLEKDYFGLTYRDAENQKNWLD-----PAKEIKKQirsGAWHF 190
Cdd:cd17239      1 KPINVRVTTMD-AELEFAIQPNTTGKQLFDQVVKTIGLREVWYFGLQYVDNKGFPTWLKldkkvSAQEVRKE---NPLQF 76

                   ....*...
gi 1720388969  191 SFNVKFYP 198
Cdd:cd17239     77 KFRAKFYP 84

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        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720388969  121 KVTLLDGS--EYGCDVDkrSRGQVLFDKVCEHLNLLEKDYFGLTYRDAENQKNWLDPAKEIKKQIRSGAWHFS--FNVKF 196
Cdd:cd17192      7 RIQLLNNEfvEFTLSVE--STGQECLEAVAQRLELREITYFSLWYYNKQNQQRWVDLEKPLKKQLDKYALEPTvyFGVVF 84

                   ...
gi 1720388969  197 YPP 199
Cdd:cd17192     85 YVP 87

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in FERM domain-containing protein 4A (FRMD4A); FRMD4A is a cytohesin adaptor involved in cell structure, transport and signaling. It promotes the growth of cancer cells in tongue, head and neck squamous cell carcinomas. It also regulates tau secretion by activating cytohesin-Arf6 signaling through connecting cytohesin family Arf6-specific guanine-nucleotide exchange factors (GEFs) and Par-3 at primordial adherens junctions during epithelial polarization. As a genetic risk factor for late-onset Alzheimer's disease (AD), FRMD4A may play a role in amyloidogenic and tau-related pathways in AD. FRMD4A contains 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 1720388969  119 QCKVTLLDGSEYGCDVDKRSRGQVLFDKVCEHLNLLEKDYFGLTYRDAENQKNWLDPAKEIKKQ---IRSGAWHFSFNVK 195
Cdd:cd17199      4 RCQVHLLDDRKLELLVQPKLLAKELLDLVASHFNLKEKEYFGIAFTDETGHLNWLQLDRRVLEHdfpKKSGPVVLYFCVR 83

                   ..
gi 1720388969  196 FY 197
Cdd:cd17199     84 FY 85

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in tyrosine-protein phosphatase non-receptor type 14 (PTPN14) and similar proteins; PTPN14, also termed protein-tyrosine phosphatase pez, or PTPD2, or PTP36, is a widely expressed non-transmembrane cytosolic protein tyrosine phosphatase (PTP). It 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). PTPN14 plays a role in the nucleus during cell proliferation. It forms a complex with Kibra and LATS1 proteins and negatively regulates the key Hippo pathway protein Yes-associated protein (YAP) oncogenic function by controlling its localization. It specifically regulates p130 Crk-associated substrate (p130Cas) phosphorylation at tyrosine residue 128 (Y128) in colorectal cancer (CRC) cells. Moreover, PTPN14 may be a critical enzyme in regulating endothelial cell function. It plays a crucial role in organogenesis by inducing transforming growth factor beta (TGFbeta) and epithelial-mesenchymal transition (EMT). It also acts as a modifier of angiogenesis and hereditary haemorrhagic telangiectasia. It regulates the lymphatic function and choanal development through the interaction with the vascular endothelial growth factor receptor 3 (VEGFR3), a receptor tyrosine kinase essential for lymphangiogenesis. Furthermore, PTPN14 functions as a regulator of cell motility through its action on cell-cell adhesion. Beta-Catenin, a central component of adherens junctions, has been identified as a PTPN14 substrate. PTPN14 works as a novel sperm-motility biomarker and a potential mitochondrial protein.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720388969  121 KVTLLDGSEYGCDVDKRSRGQVLFDKVCEHLNLLEKDYFGLTYRDAENQKNWLDPAKEIKKQIRSGAWH--FSFNVKFYP 198
Cdd:cd17191      7 RIRLLDSNVIECTLSVESTGQECLEAVAQRLELRETHYFGLWFLSKSQQARWVELEKPLKKQLDKFANEplLFFGVMFYV 86

                   .
gi 1720388969  199 P 199
Cdd:cd17191     87 P 87