Atypical FERM-like domain C-lobe of Sorting nexin 27; SNX27 is localized to early endosomes and known to regulate the intracellular trafficking of ion channels and receptors. SNX27 contain a N-terminal PDZ domain, a PX domain, and a FERM-like domain. SNX27 regulates trafficking of a PAK interacting exchange factor-G protein-coupled receptor kinase interacting protein complex via its PDZ domain interaction. Sorting nexin 27 interacts with multidrug resistance-associated protein 4 (MRP4). SNX27 binds Ras GTPase through its FERM-like domains. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. These interactions place the PX-FERM-like proteins at a hub of endosomal sorting and signaling processes. These proteins participate in a network of interactions that will impact on both endosomal protein trafficking and compartment specific Ras signaling cascades. The typical 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. FERM domains are found in 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 767910545 304 NEIIFPHCACDSRRKGHVITAISITHFKLHACTEEGQLENQVIAFEWDEMQRWDTDEEGMAFCFEYARGEKKPRWVKIFT 383
Cdd:cd13338    1 NEVVFPHCACDSRKEGHVIPSVSMKAFKLHACTEDGELENQEIEFEWDEIQRWETDEEGMAFCFEYSRPGKKPRWVKVFT 80

                         90       100
                 ....*....|....*....|..
gi 767910545 384 PYFNYMHECFERVFCELKWRKE 405
Cdd:cd13338   81 PYYEYMHECFERVQEERKWRKE 102

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in sorting nexin protein 27 (SNX27); SNX27 is a member of the family of cytoplasmic sorting nexin adaptor proteins that regulate endosomal trafficking of cell surface proteins. In addition to a PX (Phox homology) domain that regulates its endosomal localization, SNX27 has a unique PDZ (Psd-95/Dlg/ZO1) domain and an atypical FERM (4.1, ezrin, radixin, moesin) domain that both function to bind short peptide sequence motifs in the cytoplasmic domains of the cargo receptors. 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 767910545 152 SDVELRVALPDGTTVTVRVKKNSTTDQVYQAIAAKVGMDSTTVNYFALFEVISHSFVRKLAPNEFPHKLYIQNYTSAVpG 231
Cdd:cd01777    1 SDVELKVLLPDRTTVTVSVKKNSNTDQVYQALVEKLGMDSETANYFALFEIIEYNFERKLQPNEFPHNLYIQNYSTAS-A 79

                         90
                 ....*....|...
gi 767910545 232 TCLTIRKWLFTTE 244
Cdd:cd01777   80 TCITLRKWLFTLA 92

Atypical FERM-like domain C-lobe of Sorting nexin 27; SNX27 is localized to early endosomes and known to regulate the intracellular trafficking of ion channels and receptors. SNX27 contain a N-terminal PDZ domain, a PX domain, and a FERM-like domain. SNX27 regulates trafficking of a PAK interacting exchange factor-G protein-coupled receptor kinase interacting protein complex via its PDZ domain interaction. Sorting nexin 27 interacts with multidrug resistance-associated protein 4 (MRP4). SNX27 binds Ras GTPase through its FERM-like domains. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. These interactions place the PX-FERM-like proteins at a hub of endosomal sorting and signaling processes. These proteins participate in a network of interactions that will impact on both endosomal protein trafficking and compartment specific Ras signaling cascades. The typical 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. FERM domains are found in 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 767910545 304 NEIIFPHCACDSRRKGHVITAISITHFKLHACTEEGQLENQVIAFEWDEMQRWDTDEEGMAFCFEYARGEKKPRWVKIFT 383
Cdd:cd13338    1 NEVVFPHCACDSRKEGHVIPSVSMKAFKLHACTEDGELENQEIEFEWDEIQRWETDEEGMAFCFEYSRPGKKPRWVKVFT 80

                         90       100
                 ....*....|....*....|..
gi 767910545 384 PYFNYMHECFERVFCELKWRKE 405
Cdd:cd13338   81 PYYEYMHECFERVQEERKWRKE 102

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in sorting nexin protein 27 (SNX27); SNX27 is a member of the family of cytoplasmic sorting nexin adaptor proteins that regulate endosomal trafficking of cell surface proteins. In addition to a PX (Phox homology) domain that regulates its endosomal localization, SNX27 has a unique PDZ (Psd-95/Dlg/ZO1) domain and an atypical FERM (4.1, ezrin, radixin, moesin) domain that both function to bind short peptide sequence motifs in the cytoplasmic domains of the cargo receptors. 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 767910545 152 SDVELRVALPDGTTVTVRVKKNSTTDQVYQAIAAKVGMDSTTVNYFALFEVISHSFVRKLAPNEFPHKLYIQNYTSAVpG 231
Cdd:cd01777    1 SDVELKVLLPDRTTVTVSVKKNSNTDQVYQALVEKLGMDSETANYFALFEIIEYNFERKLQPNEFPHNLYIQNYSTAS-A 79

                         90
                 ....*....|...
gi 767910545 232 TCLTIRKWLFTTE 244
Cdd:cd01777   80 TCITLRKWLFTLA 92

Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); putative RasGTP effectors in other cases. Recent evidence (not yet in MEDLINE) shows that some RA domains do NOT bind RasGTP. Predicted structure similar to that determined, and that of the RasGTP-binding domain of Raf kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767910545  152 SDVELRVALPDG----TTVTVRVKKNSTTDQVYQAIAAKVGMDSTTvNYFALFEVI-SHSFVRKLAPNEFPHKLYIQNYT 226
Cdd:pfam00788   1 DDGVLKVYTEDGkpgtTYKTILVSSSTTAEEVIEALLEKFGLEDDP-RDYVLVEVLeRGGGERRLPDDECPLQIQLQWPR 79

                          90
                  ....*....|....*
gi 767910545  227 SAvPGTCLTIRKWLF 241
Cdd:pfam00788  80 DA-SDSRFLLRKRDD 93

PDZ domain of sorting nexin-27 (SNX27), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of SNX27, and related domains. SNX27 is involved in retrograde transport from endosome to plasma membrane. The PDZ domain of SNX27 links cargo identification to retromer-mediated transport. SNX27 binds to the retromer complex (vacuolar protein sorting 26(VPS26)-VPS29-VPS35), via its PDZ domain binding to VPS26. The SNX27 PDZ domain also binds to cargo including the G-protein-coupled receptors (GPCRs): beta2-adrenergic receptor (beta2AR), beta1AR, parathyroid hormone receptor (PTHR), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs), NMDA receptors, 5-hydroxytryptamine 4a receptors, frizzled receptors, and somatostatin receptor subtype 5 (SSTR5). Additional binding partners of the SNX27 PDZ domain include G protein-gated inwardly rectifying potassium (Kir3) channels, angiotensin-converting enzyme 2 (ACE2), and PTEN (phosphatase and tensin homolog deleted on chromosome 10); PTEN binding to SNX27 prevents SNX27's association with the retromer complex. SNX27 has been reported to be a host factor needed for efficient entry of an engineered SARS-CoV-2 variant, the spike protein of which contains a deletion at the S1/S2 subunit cleavage site; the PDZ domain of SNX27 binds angiotensin-converting enzyme 2 (ACE2), and may be involved in recycling ACE2 to the plasma membrane, thereby promoting viral entry. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This SNX27-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                         10        20
                 ....*....|....*....|
gi 767910545  42 RVVRIVKSESGYGFNVRGQV 61
Cdd:cd23070    1 RVVTIVKSETGFGFNVRGQV 20

Sorting Nexin 17 FERM C-terminal domain; This is the C-terminal domain of sorting nexin 17 (SNX17) present in Homo sapiens. SNX17 localizes to early endosomes where it directly binds NPX(Y/F) motifs in the target receptors to mediate their rates of endocytic internalization, recycling, or degradation. The domain is known as terminal band 4.1/ezrin/radixin/moesin (FERM) domain. The FERM domain binds directly to the common motif, NPX(Y/F), in the cytoplasmic region of its target proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767910545  302 GYneIIFPHCACDSRRKGHVITaISITHFKLHAC--TEEGQLENqvIAFEWDEMQRW------------DTDEEGMAFCF 367
Cdd:pfam18116   1 GY--IQFDPCTCDYPEPDSRVT-VSVGNNELNCCitLPEKETEE--AAFKVTRMRCWrvtaldnksmspQDNEQGLELSF 75

                          90       100       110
                  ....*....|....*....|....*....|...
gi 767910545  368 EYARGEKKPRWVKIFTPYFNYMHECFERVFCEL 400
Cdd:pfam18116  76 EYLFSKDELKWITIASEQAILLSMCLQSMVDEL 108

Atypical FERM-like domain C-lobe of Sorting nexin 27; SNX27 is localized to early endosomes and known to regulate the intracellular trafficking of ion channels and receptors. SNX27 contain a N-terminal PDZ domain, a PX domain, and a FERM-like domain. SNX27 regulates trafficking of a PAK interacting exchange factor-G protein-coupled receptor kinase interacting protein complex via its PDZ domain interaction. Sorting nexin 27 interacts with multidrug resistance-associated protein 4 (MRP4). SNX27 binds Ras GTPase through its FERM-like domains. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. These interactions place the PX-FERM-like proteins at a hub of endosomal sorting and signaling processes. These proteins participate in a network of interactions that will impact on both endosomal protein trafficking and compartment specific Ras signaling cascades. The typical 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. FERM domains are found in 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 767910545 304 NEIIFPHCACDSRRKGHVITAISITHFKLHACTEEGQLENQVIAFEWDEMQRWDTDEEGMAFCFEYARGEKKPRWVKIFT 383
Cdd:cd13338    1 NEVVFPHCACDSRKEGHVIPSVSMKAFKLHACTEDGELENQEIEFEWDEIQRWETDEEGMAFCFEYSRPGKKPRWVKVFT 80

                         90       100
                 ....*....|....*....|..
gi 767910545 384 PYFNYMHECFERVFCELKWRKE 405
Cdd:cd13338   81 PYYEYMHECFERVQEERKWRKE 102

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in sorting nexin protein 27 (SNX27); SNX27 is a member of the family of cytoplasmic sorting nexin adaptor proteins that regulate endosomal trafficking of cell surface proteins. In addition to a PX (Phox homology) domain that regulates its endosomal localization, SNX27 has a unique PDZ (Psd-95/Dlg/ZO1) domain and an atypical FERM (4.1, ezrin, radixin, moesin) domain that both function to bind short peptide sequence motifs in the cytoplasmic domains of the cargo receptors. 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 767910545 152 SDVELRVALPDGTTVTVRVKKNSTTDQVYQAIAAKVGMDSTTVNYFALFEVISHSFVRKLAPNEFPHKLYIQNYTSAVpG 231
Cdd:cd01777    1 SDVELKVLLPDRTTVTVSVKKNSNTDQVYQALVEKLGMDSETANYFALFEIIEYNFERKLQPNEFPHNLYIQNYSTAS-A 79

                         90
                 ....*....|...
gi 767910545 232 TCLTIRKWLFTTE 244
Cdd:cd01777   80 TCITLRKWLFTLA 92

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in PX-FERM family sorting nexin proteins; This family includes three endosome-associated PX (Phox homology) and FERM (Band 4.1, ezrin, radixin, moesin) domain-containing proteins called sorting nexin (SNX) 17, SNX27, and SNX31, which are modular peripheral membrane proteins acting as central scaffolds mediating protein-lipid interactions, cargo binding, and regulatory protein recruitment. They are key regulators of endosomal recycling and bind conserved NPX(Y/F) peptide sorting motifs in transmembrane cargos via an atypical FERM 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 767910545 152 SDVELRVALPDGTTVTVRVKKNSTTDQVYQAIAAKVGMDSTTVNYFALFEVISH-----SFVRKLAPNEFPHKLYIQNYT 226
Cdd:cd17109    1 SDVELRVALPNGQTVTVRVKTSDTTEQVLEAVAAKVGLDSTLVGYFALFLVRSHsegklSFVRKLAPFELPYVSYISNYT 80

                         90
                 ....*....|....*.
gi 767910545 227 savPGTCLTIRKWLFT 242
Cdd:cd17109   81 ---PGTKLTLRKWYFT 93

The Phox Homology domain, a phosphoinositide binding module; The PX domain is a phosphoinositide (PI) binding module involved in targeting proteins to membranes. Proteins containing PX domains interact with PIs and have been implicated in highly diverse functions such as cell signaling, vesicular trafficking, protein sorting, lipid modification, cell polarity and division, activation of T and B cells, and cell survival. Many members of this superfamily bind phosphatidylinositol-3-phosphate (PI3P) but in some cases, other PIs such as PI4P or PI(3,4)P2, among others, are the preferred substrates. In addition to protein-lipid interaction, the PX domain may also be involved in protein-protein interaction, as in the cases of p40phox, p47phox, and some sorting nexins (SNXs). The PX domain is conserved from yeast to humans and is found in more than 100 proteins. The majority of PX domain-containing proteins are SNXs, which play important roles in endosomal sorting.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 767910545  72 CSKRYREFAILHQNLKREFANFTFPRLPGK-WPFSLSEQQLDARRRGLEEYLEKVCSIRVIGESDIMQEFLS 142
Cdd:cd06093   34 VYRRYSDFEELHEKLKKKFPGVILPPLPPKkLFGNLDPEFIEERRKQLEQYLQSLLNHPELRNSEELKEFLE 105

Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); putative RasGTP effectors in other cases. Recent evidence (not yet in MEDLINE) shows that some RA domains do NOT bind RasGTP. Predicted structure similar to that determined, and that of the RasGTP-binding domain of Raf kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767910545  152 SDVELRVALPDG----TTVTVRVKKNSTTDQVYQAIAAKVGMDSTTvNYFALFEVI-SHSFVRKLAPNEFPHKLYIQNYT 226
Cdd:pfam00788   1 DDGVLKVYTEDGkpgtTYKTILVSSSTTAEEVIEALLEKFGLEDDP-RDYVLVEVLeRGGGERRLPDDECPLQIQLQWPR 79

                          90
                  ....*....|....*
gi 767910545  227 SAvPGTCLTIRKWLF 241
Cdd:pfam00788  80 DA-SDSRFLLRKRDD 93

The phosphoinositide binding Phox Homology domain of yeast MDM1p; The PX domain is a phosphoinositide binding (PI) module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Yeast MDM1p is a filament-like protein localized in punctate structures distributed throughout the cytoplasm. It plays an important role in nuclear and mitochondrial transmission to daughter buds. Members of this subfamily show similar domain architectures as some sorting nexins (SNXs). Some members are similar to SNX19 in that they contain an N-terminal PXA domain, a central PX domain, and a C-terminal domain that is conserved in some SNXs. Others are similar to SNX13 and SNX14, which also harbor these three domains as well as a regulator of G protein signaling (RGS) domain in between the PXA and PX domains. SNXs make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 767910545  73 SKRYREFAILHQNLKREFANFTFPRLPGKWPFSLSEQQ---LDARRRGLEEYLEKVCSIRVIGESDIMQEFLS 142
Cdd:cd06876   60 ARRYSEFLELHKYLKKRYPGVLKLDFPQKRKISLKYSKtllVEERRKALEKYLQELLKIPEVCEDEEFRKFLS 132

The phosphoinositide binding Phox Homology domain of the fungal protein YPT35; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. This subfamily is composed of YPT35 proteins from the fungal subkingdom Dikarya. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction. The PX domain of YPT35 binds to phosphatidylinositol 3-phosphate (PI3P). It also serves as a protein interaction domain, binding to members of the Yip1p protein family, which localize to the ER and Golgi. YPT35 is mainly associated with endosomes and together with Yip1p proteins, may be involved in a specific function in the endocytic pathway.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 767910545  74 KRYREFAILHQNLKREFANFTF---PRLPGKWPFSLSEQQ-----LDARRRGLEEYLEKVCSIRVIGESDIMQEFL 141
Cdd:cd07280   43 KRYSEFVQLREALLDEFPRHKRneiPQLPPKVPWYDSRVNlnkawLEKRRRGLQYFLNCVLLNPVFGGSPVVKEFL 118

The phosphoinositide binding Phox Homology domain of Sorting Nexins 20 and 21; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. This subfamily consists of SNX20, SNX21, and similar proteins. SNX20 interacts with P-Selectin glycoprotein ligand-1 (PSGL-1), a surface-expressed mucin that acts as a ligand for the selectin family of adhesion proteins. It may function in the sorting and cycling of PSGL-1 into endosomes. SNX21, also called SNX-L, is distinctly and highly-expressed in fetal liver and may be involved in protein sorting and degradation during embryonic liver development.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 767910545  73 SKRYREFAILHQNLKREF----ANFTFPR--LPGkwpfSLSEQQLDARRRGLEEYLEKVCSIRVIGESDIMQEFL 141
Cdd:cd07279   39 ERRYSDFLKLYKALRKQHpqlmAKVSFPRkvLMG----NFSSELIAERSRAFEQFLGHILSIPNLRDSKAFLDFL 109

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in sorting nexin protein 31 (SNX31); SNX31 is a member of the family of cytoplasmic sorting nexin adaptor proteins that regulate endosomal trafficking of cell surface proteins. It is a novel sorting nexin associated with the uroplakin-degrading multivesicular bodies in terminally differentiated urothelial cells. SNX31 binds multiple beta integrin cytoplasmic domains and regulates beta1 integrin surface levels and stability. SNX31 contains a PX (Phox homology) domain and a FERM (Band 4.1, ezrin, radixin, moesin) 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 767910545 156 LRVALPDGTTVTVRVKKNSTTDQVYQAIAAKVGMDSTTVNYFALFEVISH-----SFVRKLAPNEFPhklYIQNYTSAVP 230
Cdd:cd16122    8 LDVYLPDGRSVRIDVKTSDTAERVLEVVLDRIGLSRELRGYFSLFLVKGKgkgdfSVVKKLAPFELP---YVTLESGEME 84

                 ....*....
gi 767910545 231 GTCLTIRKW 239
Cdd:cd16122   85 RCKLGIRKW 93

PDZ domain of sorting nexin-27 (SNX27), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of SNX27, and related domains. SNX27 is involved in retrograde transport from endosome to plasma membrane. The PDZ domain of SNX27 links cargo identification to retromer-mediated transport. SNX27 binds to the retromer complex (vacuolar protein sorting 26(VPS26)-VPS29-VPS35), via its PDZ domain binding to VPS26. The SNX27 PDZ domain also binds to cargo including the G-protein-coupled receptors (GPCRs): beta2-adrenergic receptor (beta2AR), beta1AR, parathyroid hormone receptor (PTHR), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs), NMDA receptors, 5-hydroxytryptamine 4a receptors, frizzled receptors, and somatostatin receptor subtype 5 (SSTR5). Additional binding partners of the SNX27 PDZ domain include G protein-gated inwardly rectifying potassium (Kir3) channels, angiotensin-converting enzyme 2 (ACE2), and PTEN (phosphatase and tensin homolog deleted on chromosome 10); PTEN binding to SNX27 prevents SNX27's association with the retromer complex. SNX27 has been reported to be a host factor needed for efficient entry of an engineered SARS-CoV-2 variant, the spike protein of which contains a deletion at the S1/S2 subunit cleavage site; the PDZ domain of SNX27 binds angiotensin-converting enzyme 2 (ACE2), and may be involved in recycling ACE2 to the plasma membrane, thereby promoting viral entry. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This SNX27-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                         10        20
                 ....*....|....*....|
gi 767910545  42 RVVRIVKSESGYGFNVRGQV 61
Cdd:cd23070    1 RVVTIVKSETGFGFNVRGQV 20

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 767910545 154 VELRVALPDGTTVTVRVKKNSTTDQVYQAIAAKVGMDSttVNYFALFEVISHSFVRKLAPNE 215
Cdd:cd01765    1 ISCRVRLLDGTELTLEVSKKATGQELFDKVCEKLNLLE--KDYFGLFYEDNDGQKHWLDLDK 60

The phosphoinositide binding Phox Homology domain of uncharacterized fungal proteins; The PX domain is a phosphoinositide (PI) binding module involved in targeting proteins to PI-enriched membranes. Members in this subfamily are uncharacterized fungal proteins containing a PX domain. PX domain harboring proteins have been implicated in highly diverse functions such as cell signaling, vesicular trafficking, protein sorting, lipid modification, cell polarity and division, activation of T and B cells, and cell survival. In addition to protein-lipid interaction, the PX domain may also be involved in protein-protein interaction.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 767910545  72 CSKRYREFAILHQNLKREFANFTFPRLPGKwpFSLSEQQLdarRRGLEEYLEKVCSIRVIGESDIMQEFLSES 144
Cdd:cd06869   52 VARRYSDFKKLHHDLKKEFPGKKLPKLPHK--DKLPREKL---RLSLRQYLRSLLKDPEVAHSSILQEFLTSD 119

The phosphoinositide binding Phox Homology domain of SNARE proteins from fungi; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. This subfamily is composed of fungal proteins similar to Saccharomyces cerevisiae Vam7p. They contain an N-terminal PX domain and a C-terminal SNARE domain. The SNARE (Soluble NSF attachment protein receptor) family of proteins are integral membrane proteins that serve as key factors for vesicular trafficking. Vam7p is anchored at the vacuolar membrane through the specific interaction of its PX domain with phosphatidylinositol-3-phosphate (PI3P) present in bilayers. It plays an essential role in vacuole fusion. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 767910545  72 CSKRYREFAILHQNLKREFANFTFPRLPGK---WPFSLSEQQLDARRRGLEEYL-----EKVCSIRvigESDIMQEFLS 142
Cdd:cd06897   31 VSRRYSEFVALHKQLESEVGIEPPYPLPPKswfLSTSSNPKLVEERRVGLEAFLrallnDEDSRWR---NSPAVKEFLN 106

The phosphoinositide binding Phox Homology Domain of the Gamma Isoform of Class II Phosphoinositide 3-Kinases; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The Phosphoinositide 3-Kinase (PI3K) family of enzymes catalyzes the phosphorylation of the 3-hydroxyl group of the inositol ring of phosphatidylinositol. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. PI3Ks are divided into three main classes (I, II, and III) based on their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PI as a substrate to produce PI3P, but can also phosphorylate PI4P to produce PI(3,4)P2. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a PX domain, and a second C2 domain at the C-terminus. The class II gamma isoform, PI3K-C2gamma, is expressed in the liver, breast, and prostate. It's biological function remains unknown. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 767910545  69 RQLCSKRYREFAILHQNLKREFANFTFPRLPGKW--PFSLSEQQldaRRRGLEEYLEKVCSI-RVIGESD-IMQEFLSE 143
Cdd:cd06896   26 VSLTEKSFEQFSELHSQLQKQFPSLALPEFPHWWhlPFTDSDHK---RVRDLNHYLEQLLSGsREVANSDcVLSFFLSE 101

The phosphoinositide binding Phox Homology domain of Sorting Nexin 14; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX14 may be involved in recruiting other proteins to the membrane via protein-protein and protein-ligand interaction. It is expressed in the embryonic nervous system of mice, and is co-expressed in the motoneurons and the anterior pituary with Islet-1. SNX14 shows a similar domain architecture as SNX13, containing an N-terminal PXA domain, a regulator of G protein signaling (RGS) domain, a PX domain, and a C-terminal domain that is conserved in some SNXs.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 767910545  74 KRYREFAILHQNLkREF-ANFTFPRLPGKWPF-SLSEQQLDARRRGLEEYLEKVCSIRVIGESDIMQEFLS 142
Cdd:cd06877   48 RRYNEFYVLESKL-TEFhGEFPDAPLPSRRIFgPKSYEFLESKREIFEEFLQKLLQKPELRGSELLYDFLS 117

Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); putative RasGTP effectors in other cases. Kalhammer et al. have shown that not all RA domains bind RasGTP. Predicted structure similar to that determined, and that of the RasGTP-binding domain of Raf kinase. Predicted RA domains in PLC210 and nore1 found to bind RasGTP. Included outliers (Grb7, Grb14, adenylyl cyclases etc.)

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 767910545   155 ELRVA---LPDGTTVTVRVKKNSTTDQVYQAIAAKVGMDSTtVNYFALFEVISHSFVRKLAPNEFPHKL 220
Cdd:smart00314   4 VLRVYvddLPGGTYKTLRVSSRTTARDVIQQLLEKFHLTDD-PEEYVLVEVLPDGKERVLPDDENPLQL 71

The phosphoinositide binding Phox Homology domain of Sorting Nexin 13; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX13, also called RGS-PX1, contains an N-terminal PXA domain, a regulator of G protein signaling (RGS) domain, a PX domain, and a C-terminal domain that is conserved in some SNXs. It specifically binds to the stimulatory subunit of the heterotrimeric G protein G(alpha)s, serving as its GTPase activating protein, through the RGS domain. It preferentially binds phosphatidylinositol-3-phosphate (PI3P) through the PX domain and is localized in early endosomes. SNX13 is involved in endosomal sorting of EGFR into multivesicular bodies (MVB) for delivery to the lysosome.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767910545  60 QVYNVYMAGRQLC---SKRYREFAILHQNLKREFANFTFPRLPGKWPF-SLSEQQLDARRRGLEEYLEKVCSIRVIGESD 135
Cdd:cd06873   28 SVTRIYPNGQEESwhvYRRYSDFHDLHMRLKEKFPNLSKLSFPGKKTFnNLDRAFLEKRRKMLNQYLQSLLNPEVLDANP 107

                 ....*.
gi 767910545 136 IMQEFL 141
Cdd:cd06873  108 GLQEIV 113

The phosphoinositide binding Phox Homology domain of SNX-like proteins; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. Some SNXs are localized in early endosome structures such as clathrin-coated pits, while others are located in late structures of the endocytic pathway. This subfamily is composed of uncharacterized proteins, predominantly from plants, with similarity to sorting nexins. A few members show a similar domain architecture as a subfamily of sorting nexins, containing a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain. The PX-BAR structural unit is known to determine specific membrane localization.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767910545  74 KRYREFAILHQNLKREFANFTFPRLPGKWPFSLSEQQLDA----RRRGLEEYLEKVCSIRVIGESDIMQEFLSE 143
Cdd:cd06865   46 RRFRDVVALADRLAEAYRGAFVPPRPDKSVVESQVMQSAEfieqRRVALEKYLNRLAAHPVIGLSDELRVFLTL 119

The phosphoinositide binding Phox Homology domain of fungal Sorting Nexins 41 and 42; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. Some SNXs are localized in early endosome structures such as clathrin-coated pits, while others are located in late structures of the endocytic pathway. SNX41 and SNX42 (also called Atg20p) form dimers with SNX4, and are required in protein recycling from the sorting endosome (post-Golgi endosome) back to the late Golgi in yeast.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767910545  75 RYREFAILHQNLKREFANFTFPRLPGKWPF-SLSEQQLDA---------RRRGLEEYLEKVCSIRVIGESDIMQEFLS 142
Cdd:cd06867   33 RYSEFESLRKNLTRLYPTLIIPPIPEKHSLkDYAKKPSKAkndakiierRKRMLQRFLNRCLQHPILRNDIVFQKFLD 110

Sorting Nexin 17 FERM C-terminal domain; This is the C-terminal domain of sorting nexin 17 (SNX17) present in Homo sapiens. SNX17 localizes to early endosomes where it directly binds NPX(Y/F) motifs in the target receptors to mediate their rates of endocytic internalization, recycling, or degradation. The domain is known as terminal band 4.1/ezrin/radixin/moesin (FERM) domain. The FERM domain binds directly to the common motif, NPX(Y/F), in the cytoplasmic region of its target proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767910545  302 GYneIIFPHCACDSRRKGHVITaISITHFKLHAC--TEEGQLENqvIAFEWDEMQRW------------DTDEEGMAFCF 367
Cdd:pfam18116   1 GY--IQFDPCTCDYPEPDSRVT-VSVGNNELNCCitLPEKETEE--AAFKVTRMRCWrvtaldnksmspQDNEQGLELSF 75

                          90       100       110
                  ....*....|....*....|....*....|...
gi 767910545  368 EYARGEKKPRWVKIFTPYFNYMHECFERVFCEL 400
Cdd:pfam18116  76 EYLFSKDELKWITIASEQAILLSMCLQSMVDEL 108

The phosphoinositide binding Phox Homology domain of Sorting Nexin 9; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX9, also known as SH3PX1, is a cytosolic protein that interacts with proteins associated with clathrin-coated pits such as Cdc-42-associated tyrosine kinase 2 (ACK2). It contains an N-terminal Src Homology 3 (SH3) domain, a PX domain, and a C-terminal Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature. The PX-BAR structural unit helps determine specific membrane localization. Through its SH3 domain, SNX9 binds class I polyproline sequences found in dynamin 1/2 and the WASP/N-WASP actin regulators. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis. Its array of interacting partners suggests that SNX9 functions at the interface between endocytosis and actin cytoskeletal organization.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767910545  75 RYREFAILHQNLKREFA-NFTFPRLPGKWPFSLSEQQ-LDARRRGLEEYLEKVCSIRVIGESDIMQEFLSESDE 146
Cdd:cd07285   37 RYKHFDWLYERLLVKFGlAIPIPSLPDKQVTGRFEEEfIKMRMERLQAWMTRMCRHPVISESEVFQQFLNFRDE 110

The phosphoinositide binding Phox Homology domain of Sorting Nexins 1 and 2; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. This subfamily consists of SNX1, SNX2, and similar proteins. They harbor a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain. Both domains have been shown to determine the specific membrane-targeting of SNX1. SNX1 and SNX2 are components of the retromer complex, a membrane coat multimeric complex required for endosomal retrieval of lysosomal hydrolase receptors to the Golgi. The retromer consists of a cargo-recognition subcomplex and a subcomplex formed by a dimer of sorting nexins (SNX1 and/or SNX2), which ensures effcient cargo sorting by facilitating proper membrane localization of the cargo-recognition subcomplex.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 767910545  72 CSKRYREFAILHQNLKREFANFTFPRLPGKWPFSLSEQQLD---ARRRGLEEYLEKVCSIRVIGESDIMQEFLsESD 145
Cdd:cd06859   39 VLRRYSDFLWLYERLVEKYPGRIVPPPPEKQAVGRFKVKFEfieKRRAALERFLRRIAAHPVLRKDPDFRLFL-ESD 114

Ras-associating (RA) domain 1 found in Afadin; Afadin, also termed ALL1-fused gene from chromosome 6 protein (AF-6), or canoe, is involved in many fundamental signaling cascades in cells. In addition, it is involved in oncogenesis and metastasis. Afadin has multiple domains: from the N-terminus to the C-terminus it has two Ras-associated (RA) domains, a forkhead-associated domain, a dilute domain, a PDZ domain, three proline-rich domains, and an F-actin-binding domain. RA domain-containing proteins function by interacting with Ras proteins directly or indirectly and are involved in several different functions ranging from tumor suppression to being oncoproteins. Ras proteins are small GTPases that are involved in cellular signal transduction. The RA domain has a 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. Afadin is abundant at cadherin-based adherens junctions in epithelial cells, endothelial cells, and fibroblasts. This family corresponds to the first RA domain of afadin, which mediates its self-association.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767910545 141 LSESDEN--YNGVsdveLRVALPDGT----TVTVRVKKNSTTDQVYQAIAAKV--GMDSTTVNYFALFEVISHSFVRKLA 212
Cdd:cd01782   11 LSQPNEDleFHGV----MRFYFQDGGakvaTKCIRVSSTATTQDVIETLIEKFrpDMRMLSNPRYSLYEVHPNGEERKLD 86

                         90
                 ....*....|.
gi 767910545 213 PNEFPhkLYIQ 223
Cdd:cd01782   87 DDEKP--LVVQ 95

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in unconventional myosin-X and similar proteins; Myosin-X, also termed myosin-10 (Myo10), is an untraditional member of myosin superfamily. It is an actin-based motor protein that plays a critical role in diverse cellular motile events, such as filopodia formation/extension, phagocytosis, cell migration, and mitotic spindle maintenance, as well as a number of disease states including cancer metastasis and pathogen infection. Myosin-X functions as an important regulator of cytoskeleton that modulates cell motilities in many different cellular contexts. It regulates neuronal radial migration through interacting with N-cadherin. Like other unconventional myosins, Myosin-X is composed of a conserved motor head, a neck region and a variable tail. The neck region consists of three IQ motifs (light chain-binding sites), and a predicted stalk of coiled coil. The tail contains three PEST regions, three PH domains, a MyTH4 domain, and a FERM 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). Amoebozoan Dictyostelium discoideum myosin VII (DdMyo7) and uncharacterized pleckstrin homology domain-containing family H member 3 (PLEKHH3) are also included in this family. Like metazoan Myo10, DdMyo7 is essential for the extension of filopodia, plasma membrane protrusions filled with parallel bundles of F-actin.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 767910545 152 SDVELRVALPDGTTVTVRVKKNSTTDQVYQAIAAKVGMDSTTvNYFALFE 201
Cdd:cd17110    2 QELTVTVTCQGGRTCKVAIDSWTTCGEVSKDLARRLGLERSR-NGFALFE 50

The phosphoinositide binding Phox Homology domain of the Imidazoline Receptor Antisera-Selected; The PX domain is a phosphoinositide binding (PI) module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Imidazoline Receptor Antisera-Selected (IRAS), also called nischarin, contains an N-terminal PX domain, leucine rich repeats, and a predicted coiled coil domain. The PX domain of IRAS binds to phosphatidylinositol-3-phosphate in membranes. Together with the coiled coil domain, it is essential for the localization of IRAS to endosomes. IRAS has been shown to interact with integrin and inhibit cell migration. Its interaction with alpha5 integrin causes a redistribution of the receptor from the cell surface to endosomal structures, suggesting that IRAS may function as a sorting nexin (SNX) which regulates the endosomal trafficking of integrin. SNXs make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767910545  41 PRVVRIVKSESGYGFNVrgQVYNVYMAGRQ-LCSKRYREFAILHQNLKREFaNFTFPRLPGKWPF-SLSEQQLDARRRGL 118
Cdd:cd06875    3 ETKIRIPSAETVEGYTV--YIIEVKVGSVEwTVKHRYSDFAELHDKLVAEH-KVDKDLLPPKKLIgNKSPSFVEKRRKEL 79

                 ....*..
gi 767910545 119 EEYLEKV 125
Cdd:cd06875   80 EIYLQTL 86