first ubiquitin-like (Ubl) domain located at the N-terminus of coronavirus SARS-CoV non-structural protein 3 (Nsp3) and related proteins; This ubiquitin-like (Ubl) domain (Ubl1) is found at the N-terminus of coronavirus Nsp3, a large multi-functional multi-domain protein which is an essential component of the replication/transcription complex (RTC). The functions of Ubl1 in CoVs are related to single-stranded RNA (ssRNA) binding and to interacting with the nucleocapsid (N) protein. SARS-CoV Ubl1 has been shown to bind ssRNA having AUA patterns, and since the 5'-UTR of the SARS-CoV genome has a number of AUA repeats, it may bind there. In mouse hepatitis virus (MHV), this Ubl1 domain binds the cognate N protein. Adjacent to Ubl1 is a Glu-rich acidic region (also referred to as hypervariable region, HVR); Ubl1 together with HVR has been called Nsp3a. Currently, the function of HVR in CoVs is unknown. This model corresponds to one of two Ubl domains in Nsp3; the other is located N-terminal to the papain-like protease (PLpro) and is not represented by this model.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564374324 401 RQELLCTVHCPGAGACPVSIDSHTTAGEVARELVGRLGLARSRNAFALYEQRGAQERALAGGTLVADVLTRFENLTSEev 480
Cdd:cd17207    1 RQELLCTVHCPGAGACSIAITSHTTAEEVVRELVGRLGLSDSRNIFALYEQNGQEEQAIGSSTIVADVLTRFENLAAE-- 78

                         90       100
                 ....*....|....*....|
gi 564374324 481 glEDSPDSGWRLCLRLHGPL 500
Cdd:cd17207   79 --EKEPDPQWRLCFKLYCFL 96

Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like and IRS-like PTB domains, the ran-binding domain, the EVH1 domain, a domain in neurobeachin and the third domain of FERM. All of these domains have a PH fold, but lack significant sequence similarity. They are generally involved in targeting to protein to the appropriate cellular location or interacting with a binding partner. This domain family possesses multiple functions including the ability to bind inositol phosphates and to other proteins.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564374324 661 GAARYDVlELSTepgGGAPQKLCLGLGAKAMSLSRPGESEPIHSVSYGHVAACQLIGPHTLALRV-GDSQLLLQSPQVEE 739
Cdd:cd13202    1 GCTLFEV-ECKE---GGFPKELWLGVSAEGVSLYKRGESKPLESFPYEHILSFGAPQANTYKIVVdGDRPMLFETTQVVE 76

                 ....*....
gi 564374324 740 IMELVNAYL 748
Cdd:cd13202   77 IAKLMKAYI 85

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in pleckstrin homology domain-containing family H member 3 (PLEKHH3); PLEKHH3 is an uncharacterized Pleckstrin homology (PH) domain-containing protein that shows high sequence similarity with unconventional myosin-X, 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. In addition to two PH domains, PLEKHH3 harbors a MyTH4 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 564374324 401 RQELLCTVHCPGAGACPVSIDSHTTAGEVARELVGRLGLARSRNAFALYEQRGAQERALAGGTLVADVLTRFENLTSEev 480
Cdd:cd17207    1 RQELLCTVHCPGAGACSIAITSHTTAEEVVRELVGRLGLSDSRNIFALYEQNGQEEQAIGSSTIVADVLTRFENLAAE-- 78

                         90       100
                 ....*....|....*....|
gi 564374324 481 glEDSPDSGWRLCLRLHGPL 500
Cdd:cd17207   79 --EKEPDPQWRLCFKLYCFL 96

Domain in Myosin and Kinesin Tails; Domain present twice in myosin-VIIa, and also present in 3 other myosins.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564374324   237 HTSSALYAPLLPLPYEVsapgpgyapLREEAVRLFLALQ------ALEGARRPGPLMQGVLQTCRDLPALQDELFLQLAK 310
Cdd:smart00139   1 YTKDPIKTSLLKLESDE---------LQKEAVKIFKAILkfmgdiPLPRPDSHLDLVQFILQKGLDHPELRDEIYCQLIK 71

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564374324   311 QTSGPAGPPGlpatqdpaALRYWQLLTCMSCTFRPGGAVRGHLLGHLERTEQALPDSELAEYARFIRKALGRTRGRELVP 390
Cdd:smart00139  72 QLTDNPSRQS--------EERGWQLLYLCTSLFPPSERLLPYLLQFLSRRADPGSEQGLAKYCLYRLERTLKNGARKQPP 143

                   ....*...
gi 564374324   391 SLAEISAL 398
Cdd:smart00139 144 SRLELEAI 151

FERM domain C-lobe of Myosin X (MyoX, Myo10); MyoX, a MyTH-FERM myosin, is a molecular motor that has crucial functions in the transport and/or tethering of integrins in the actin-based extensions known as filopodia, microtubule binding, and in netrin-mediated axon guidance. It functions as a dimer. MyoX walks on bundles of actin, rather than single filaments, unlike the other unconventional myosins. MyoX is present in organisms ranging from humans to choanoflagellates, but not in Drosophila and Caenorhabditis elegans.MyoX consists of a N-terminal motor/head region, a neck made of 3 IQ motifs, and a tail consisting of a coiled-coil domain, a PEST region, 3 PH domains, a myosin tail homology 4 (MyTH4), and a FERM domain at its very C-terminus. The MyoX FERM domain binds to the NPXY motif of several beta-integrins, a key family of cell surface receptors that are involved in cell adhesion and migration. In addition the FERM domain binds to the cytoplasmic domains of the netrin receptors DCC (deleted in colorectal cancer) and neogenin. The FERM domain also forms a supramodule with its MyTH4 domain which binds to the negatively charged E-hook region in the tails of alpha- and beta-tubulin forming a proposed motorized link between actin filaments and microtubules. 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 564374324 661 GAARYDVlELSTepgGGAPQKLCLGLGAKAMSLSRPGESEPIHSVSYGHVAACQLIGPHTLALRV-GDSQLLLQSPQVEE 739
Cdd:cd13202    1 GCTLFEV-ECKE---GGFPKELWLGVSAEGVSLYKRGESKPLESFPYEHILSFGAPQANTYKIVVdGDRPMLFETTQVVE 76

                 ....*....
gi 564374324 740 IMELVNAYL 748
Cdd:cd13202   77 IAKLMKAYI 85

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564374324    96 VIVKGWLYRePRGGGARPWllpRRAWFVLTRDSLD--QFSSSGKGARRLGSLVLTSL-CSVTGPERRPKETGLWSVTVSG 172
Cdd:smart00233   1 VIKEGWLYK-KSGGGKKSW---KKRYFVLFNSTLLyyKSKKDKKSYKPKGSIDLSGCtVREAPDPDSSKKPHCFEIKTSD 76

                           90       100
                   ....*....|....*....|....*..
gi 564374324   173 RKhSIRLCSPRQAEAERWGVALREVIA 199
Cdd:smart00233  77 RK-TLLLQAESEEEREKWVEALRKAIA 102

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

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 564374324  514 FLFEQAHALLLRGRPPPPDDTLRALAALRLQSLHRDFSP 552
Cdd:pfam00373  14 LLYLQAKDDILEGRLPCSEEEALLLAALQLQAEFGDYQP 52

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in pleckstrin homology domain-containing family H member 3 (PLEKHH3); PLEKHH3 is an uncharacterized Pleckstrin homology (PH) domain-containing protein that shows high sequence similarity with unconventional myosin-X, 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. In addition to two PH domains, PLEKHH3 harbors a MyTH4 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 564374324 401 RQELLCTVHCPGAGACPVSIDSHTTAGEVARELVGRLGLARSRNAFALYEQRGAQERALAGGTLVADVLTRFENLTSEev 480
Cdd:cd17207    1 RQELLCTVHCPGAGACSIAITSHTTAEEVVRELVGRLGLSDSRNIFALYEQNGQEEQAIGSSTIVADVLTRFENLAAE-- 78

                         90       100
                 ....*....|....*....|
gi 564374324 481 glEDSPDSGWRLCLRLHGPL 500
Cdd:cd17207   79 --EKEPDPQWRLCFKLYCFL 96

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in unconventional myosin-X; 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).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564374324 401 RQELLCTVHCPGAGACPVSIDSHTTAGEVARELVGRLGLARSRNAFALYEQRGAQERALAGGTLVADVLTRFENLTSEEV 480
Cdd:cd17206    1 RREMTATVYCYGGGSCKITINSHTTAGEVVEKLIRGLALEDSRNMFALFEHNGTTDKAIESRTVVADVLAKFEKLAAEGE 80

                         90
                 ....*....|....*..
gi 564374324 481 GLEDSPdsgWRLCLRLH 497
Cdd:cd17206   81 MEGGLP---WKLYFKLF 94

Domain in Myosin and Kinesin Tails; Domain present twice in myosin-VIIa, and also present in 3 other myosins.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564374324   237 HTSSALYAPLLPLPYEVsapgpgyapLREEAVRLFLALQ------ALEGARRPGPLMQGVLQTCRDLPALQDELFLQLAK 310
Cdd:smart00139   1 YTKDPIKTSLLKLESDE---------LQKEAVKIFKAILkfmgdiPLPRPDSHLDLVQFILQKGLDHPELRDEIYCQLIK 71

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564374324   311 QTSGPAGPPGlpatqdpaALRYWQLLTCMSCTFRPGGAVRGHLLGHLERTEQALPDSELAEYARFIRKALGRTRGRELVP 390
Cdd:smart00139  72 QLTDNPSRQS--------EERGWQLLYLCTSLFPPSERLLPYLLQFLSRRADPGSEQGLAKYCLYRLERTLKNGARKQPP 143

                   ....*...
gi 564374324   391 SLAEISAL 398
Cdd:smart00139 144 SRLELEAI 151

Myosin X Pleckstrin homology (PH) domain, repeat 2; MyoX, a MyTH-FERM myosin, is a molecular motor that has crucial functions in the transport and/or tethering of integrins in the actin-based extensions known as filopodia, microtubule binding, and in netrin-mediated axon guidance. It functions as a dimer. MyoX walks on bundles of actin, rather than single filaments, unlike the other unconventional myosins. MyoX is present in organisms ranging from humans to choanoflagellates, but not in Drosophila and Caenorhabditis elegans.MyoX consists of a N-terminal motor/head region, a neck made of 3 IQ motifs, and a tail consisting of a coiled-coil domain, a PEST region, 3 PH domains, a myosin tail homology 4 (MyTH4), and a FERM domain at its very C-terminus. The first PH domain in the MyoX tail is a split-PH domain, interupted by the second PH domain such that PH 1a and PH 1b flanks PH 2. The third PH domain (PH 3) follows the PH 1b domain. This cd contains the second PH repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564374324 100 GWLYRepRGGGA-----RPWllpRRAWFVLTRDSLDQFSSSGKGARRLGSL-VLTSLCSVtgpERRPKETGLwSVTVSGR 173
Cdd:cd13296    3 GWLTK--KGGGSstlsrRNW---KSRWFVLRDTVLKYYENDQEGEKLLGTIdIRSAKEIV---DNDPKENRL-SITTEER 73

                         90       100
                 ....*....|....*....|....*....
gi 564374324 174 KHSIRLCSPrqAEAERWGVALREVIASKA 202
Cdd:cd13296   74 TYHLVAESP--EDASQWVNVLTRVISATD 100

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in Dictyostelium discoideum Myosin-VIIa (DdMyo7) and similar proteins; DdMyo7, also termed Myosin-I heavy chain, or class VII unconventional myosin, or M7, plays a role in adhesion in Dictyostelium where it is a component of a complex of proteins that serve to link membrane receptors to the underlying actin cytoskeleton. It interacts with talinA, an actin-binding protein with a known role in cell-substrate adhesion. DdMyo7 is required for phagocytosis. It is also essential for the extension of filopodia, plasma membrane protrusions filled with parallel bundles of F-actin. Members in this family contain a myosin motor domain, two MyTH4 domains, two FERM (Band 4.1, ezrin, radixin, moesin) domains, and two Pleckstrin homology (PH) domains. Some family members contain an extra SH3 domain. Each FERM domain is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N).

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 564374324 418 VSIDSHTTAGEVARELVGRLGLARSRNAFALYEQRGAQERALAGGTLVADVLTRFENL 475
Cdd:cd17208   18 LEFDSAATAAEVLEQLKQKIGLRSTADGFALYEVFGGIERAILPEEKVADVLSKWEKL 75

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564374324    96 VIVKGWLYRePRGGGARPWllpRRAWFVLTRDSLD--QFSSSGKGARRLGSLVLTSL-CSVTGPERRPKETGLWSVTVSG 172
Cdd:smart00233   1 VIKEGWLYK-KSGGGKKSW---KKRYFVLFNSTLLyyKSKKDKKSYKPKGSIDLSGCtVREAPDPDSSKKPHCFEIKTSD 76

                           90       100
                   ....*....|....*....|....*..
gi 564374324   173 RKhSIRLCSPRQAEAERWGVALREVIA 199
Cdd:smart00233  77 RK-TLLLQAESEEEREKWVEALRKAIA 102

Phosphoinositol 3-phosphate binding proteins 1, 2, and 3 pleckstrin homology (PH) domain; PEPP1 (also called PLEKHA4/PH domain-containing family A member 4 and RHOXF1/Rhox homeobox family member 1), and related homologs PEPP2 (also called PLEKHA5/PH domain-containing family A member 5) and PEPP3 (also called PLEKHA6/PH domain-containing family A member 6), have PH domains that interact specifically with PtdIns(3,4)P3. Other proteins that bind PtdIns(3,4)P3 specifically are: TAPP1 (tandem PH-domain-containing protein-1) and TAPP2], PtdIns3P AtPH1, and Ptd- Ins(3,5)P2 (centaurin-beta2). All of these proteins contain at least 5 of the 6 conserved amino acids that make up the putative phosphatidylinositol 3,4,5- trisphosphate-binding motif (PPBM) located at their N-terminus. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564374324  95 DVIVKGWLYRePRGGGARPWllpRRAWFVLTRDSLDQFSSSgKGARRLGSLVLTSLC-SVTGPERRpketglwsvtvSGR 173
Cdd:cd13248    6 PVVMSGWLHK-QGGSGLKNW---RKRWFVLKDNCLYYYKDP-EEEKALGSILLPSYTiSPAPPSDE-----------ISR 69

                         90       100       110
                 ....*....|....*....|....*....|...
gi 564374324 174 KHSIR----------LCSPRQAEAERWGVALRE 196
Cdd:cd13248   70 KFAFKaehanmrtyyFAADTAEEMEQWMNAMSL 102

Ras-associating (RA) domain found in Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing proteins ARAP1, ARAP2, ARAP3, and similar proteins; ARAPs are phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P(3))-dependent Arf Rap-activated guanosine triphosphatase (GTPase)-activating proteins (GAPs). They contain multiple functional domains, including ArfGAP and RhoGAP domains, as well as a sterile alpha motif (Sam) domain, five PH domains, and a RA domain. The RA domain has the beta-grasp ubiquitin-like 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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 564374324 418 VSIDSHTTAGEVARELVGRLGLARSRNAFALYEQ--RGAQERALAGGTLVADVLTRFENLTSEE 479
Cdd:cd17113   20 IKVTPTMTAEEVVEQALNKKNLGGPEGNWALFEVieDGGLERPLHESEKVLDVVLRWSQWPRKS 83