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 55741447  996 PFSIPVHFTNGTYHVVGFDGSSTVDEFLQRLNQEIGMRKPSHSGFALFTDDPSGRDLEHCLQGSVKICDAISKWEQAMKE 1075
Cdd:cd17178    1 PFSIPVHFMNGTYQVVGFDGSTTVDEFLQTLNQETGMRKPSHSGFALFTDDPSGKDLEHCLQGSVKICDVISKWEQALKE 80

                         90       100
                 ....*....|....*....|....*..
gi 55741447 1076 LHPGKSEgGTRVVKLMYKNRLYFRSQV 1102
Cdd:cd17178   81 LHPGKYE-GTRTVRLTYKSRLYFRAQA 106

Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 (PLEKHH1) PH domain, repeat 1; PLEKHH1 and PLEKHH2 (also called PLEKHH1L) are thought to function in phospholipid binding and signal transduction. There are 3 Human PLEKHH genes: PLEKHH1, PLEKHH2, and PLEKHH3. There are many isoforms, the longest of which contain a FERM domain, a MyTH4 domain, two PH domains, a peroximal domain, a vacuolar domain, and a coiled coil stretch. 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 C-lobe/F3 within the FERM domain is part of the PH domain family. 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 55741447  581 KSGYLLKMGSQVKTWKRRWFVLRQGQIMYYKSPSDVIRKPQGQVDLNSRCQIVRGEGSQTFQLISEKKTYYLTADSPSLL 660
Cdd:cd13282    1 KAGYLTKLGGKVKTWKRRWFVLKNGELFYYKSPNDVIRKPQGQIALDGSCEIARAEGAQTFEIVTEKRTYYLTADSENDL 80

                         90
                 ....*....|....*.
gi 55741447  661 EEWIRVLQSLLKVQAT 676
Cdd:cd13282   81 DEWIRVIQNVLRRQAS 96

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

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55741447     999 IPVHFTNGTYHVVGFDGSSTVDEFLQRLNQEIGMRkpSHSGFALFTDDPSGrDLEHCLQGSVKICDAISKWEQAmkelhp 1078
Cdd:smart00295    2 LKVYLLDGTTLEFEVDSSTTAEELLETVCRKLGIR--ESEYFGLQFEDPDE-DLRHWLDPAKTLLDQDVKSEPL------ 72

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55741447    1079 gkseggtrvvKLMYKNRLYFRSQVKGETDRERL-LLASQTSREIVAGRFPINKELALEMAALMAQVEYGDlekpalpgpg 1157
Cdd:smart00295   73 ----------TLYFRVKFYPPDPNQLKEDPTRLnLLYLQVRNDILEGRLPCPEEEALLLAALALQAEFGD---------- 132

                           170       180       190       200       210       220       230
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 55741447    1158 gTSPAKAQHLLQQVLDRFHPRRYRHGAPAEQLRhlaDMLTTKWATLQGCSPPECIRIYLTVARKWPFFGAKLF 1230
Cdd:smart00295  133 -YDEELHDLRGELSLKRFLPKQLLDSRKLKEWR---ERIVELHKELIGLSPEEAKLKYLELARKLPTYGVELF 201

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 55741447     688 PTVKGWLTKVKHGHSKV---VWCALVGKIFYYYRSHEDK---RPLGCLPVRDAHIEEVDRSCDSDEDyeaggtrrllssH 761
Cdd:smart00233    1 VIKEGWLYKKSGGGKKSwkkRYFVLFNSTLLYYKSKKDKksyKPKGSIDLSGCTVREAPDPDSSKKP------------H 68

                            90       100       110
                    ....*....|....*....|....*....|.
gi 55741447     762 CTLVIHPTEHspTYLLIG-TKHEKDTWLYHL 791
Cdd:smart00233   69 CFEIKTSDRK--TLLLQAeSEEEREKWVEAL 97

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55741447  996 PFSIPVHFTNGTYHVVGFDGSSTVDEFLQRLNQEIGMRKPSHSGFALFTDDPSGRDLEHCLQGSVKICDAISKWEQAMKE 1075
Cdd:cd17178    1 PFSIPVHFMNGTYQVVGFDGSTTVDEFLQTLNQETGMRKPSHSGFALFTDDPSGKDLEHCLQGSVKICDVISKWEQALKE 80

                         90       100
                 ....*....|....*....|....*..
gi 55741447 1076 LHPGKSEgGTRVVKLMYKNRLYFRSQV 1102
Cdd:cd17178   81 LHPGKYE-GTRTVRLTYKSRLYFRAQA 106

Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 (PLEKHH1) PH domain, repeat 1; PLEKHH1 and PLEKHH2 (also called PLEKHH1L) are thought to function in phospholipid binding and signal transduction. There are 3 Human PLEKHH genes: PLEKHH1, PLEKHH2, and PLEKHH3. There are many isoforms, the longest of which contain a FERM domain, a MyTH4 domain, two PH domains, a peroximal domain, a vacuolar domain, and a coiled coil stretch. 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 C-lobe/F3 within the FERM domain is part of the PH domain family. 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 55741447  581 KSGYLLKMGSQVKTWKRRWFVLRQGQIMYYKSPSDVIRKPQGQVDLNSRCQIVRGEGSQTFQLISEKKTYYLTADSPSLL 660
Cdd:cd13282    1 KAGYLTKLGGKVKTWKRRWFVLKNGELFYYKSPNDVIRKPQGQIALDGSCEIARAEGAQTFEIVTEKRTYYLTADSENDL 80

                         90
                 ....*....|....*.
gi 55741447  661 EEWIRVLQSLLKVQAT 676
Cdd:cd13282   81 DEWIRVIQNVLRRQAS 96

MyTH4 domain; Domain in myosin and kinesin tails, present twice in myosin-VIIa, and also present in 3 other myosins.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55741447    880 AQTALQVCLVHPELQSEIYCQLMKQTScRPPQKYSLMQCWQLLALCAPLFLPQHHFLWYVKQQLQRHADPRS-ETGQYAT 958
Cdd:pfam00784    1 AQNILQKGLKRPELRDEIYCQLIKQTT-NNPKPESLLRGWQLLALCLGTFPPSKKLLKYLLKFLKRHADDPSrEVGKYAQ 79

                           90       100
                   ....*....|....*....|....*.
gi 55741447    959 YCQRAVERTLRTGEREARPSRMEVVS 984
Cdd:pfam00784   80 FCLKRLKRTLKNGGRKYPPSREEIEA 105

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 55741447     579 LEKSGYLLKMGSQV-KTWKRRWFVLRQGQIMYYKSPSDV-IRKPQGQVDLNSrCQIVRGEGSQ------TFQLIS-EKKT 649
Cdd:smart00233    1 VIKEGWLYKKSGGGkKSWKKRYFVLFNSTLLYYKSKKDKkSYKPKGSIDLSG-CTVREAPDPDsskkphCFEIKTsDRKT 79

                            90       100
                    ....*....|....*....|...
gi 55741447     650 YYLTADSPSLLEEWIRVLQSLLK 672
Cdd:smart00233   80 LLLQAESEEEREKWVEALRKAIA 102

PH domain; PH stands for pleckstrin homology.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55741447    579 LEKSGYLLKMGSQVK-TWKRRWFVLRQGQIMYYKSPSDVI-RKPQGQVDLNSrCQIVR------GEGSQTFQLI----SE 646
Cdd:pfam00169    1 VVKEGWLLKKGGGKKkSWKKRYFVLFDGSLLYYKDDKSGKsKEPKGSISLSG-CEVVEvvasdsPKRKFCFELRtgerTG 79

                           90       100
                   ....*....|....*....|....*.
gi 55741447    647 KKTYYLTADSPSLLEEWIRVLQSLLK 672
Cdd:pfam00169   80 KRTYLLQAESEEERKDWIKAIQSAIR 105

Predicted nucleic acid-binding protein DR0291, contains C4-type Zn-ribbon domain [General function prediction only];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55741447   20 TLETQLFRFRlqasKIRELLADKMQELEQRLLEAEQRAENAETQVGVMEEKVKLSNLKnVDSEGSLHRKYQELLKAIKGK 99
Cdd:COG1579   14 ELDSELDRLE----HRLKELPAELAELEDELAALEARLEAAKTELEDLEKEIKRLELE-IEEVEARIKKYEEQLGNVRNN 88

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 55741447  100 DE---LISQLEAqLEKQKQMRAEEAKTVQEKAAKIKEWVTLKLAKLEMENQHLKSHNQRLVEQVGSLQDALEAIQ 171
Cdd:COG1579   89 KEyeaLQKEIES-LKRRISDLEDEILELMERIEELEEELAELEAELAELEAELEEKKAELDEELAELEAELEELE 162

DNA double-strand break repair ATPase Rad50;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55741447    33 SKIRELLADKMQELEQRLLEAEQRAENAETQVGVMEEKV-KLSNLKNVDSEgsLHRKYQELLKAIKgKDELISQLEAQLE 111
Cdd:PRK03918  299 SEFYEEYLDELREIEKRLSRLEEEINGIEERIKELEEKEeRLEELKKKLKE--LEKRLEELEERHE-LYEEAKAKKEELE 375

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 55741447   112 KQKQMRA----EEAKTVQEKAAKIKEWVTLKLAKLEMENQHLKShnqrlveQVGSLQDALEAIQIA 173
Cdd:PRK03918  376 RLKKRLTgltpEKLEKELEELEKAKEEIEEEISKITARIGELKK-------EIKELKKAIEELKKA 434

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 55741447     688 PTVKGWLTKVKHGHSKV---VWCALVGKIFYYYRSHEDK---RPLGCLPVRDAHIEEVDRSCDSDEDyeaggtrrllssH 761
Cdd:smart00233    1 VIKEGWLYKKSGGGKKSwkkRYFVLFNSTLLYYKSKKDKksyKPKGSIDLSGCTVREAPDPDSSKKP------------H 68

                            90       100       110
                    ....*....|....*....|....*....|.
gi 55741447     762 CTLVIHPTEHspTYLLIG-TKHEKDTWLYHL 791
Cdd:smart00233   69 CFEIKTSDRK--TLLLQAeSEEEREKWVEAL 97

Bacillus thuringiensis crystal 6Aa (Cry6Aa) toxin, and similar proteins; This model includes pesticidal Cry6Aa toxin from Bacillus thuringiensis, one of the many parasporal crystal (Cry) toxins produced during the sporulation phase of growth. Many of these proteins are toxic to numerous insect species and have been effectively used as proteinaceous insecticides to directly kill insect pests; some have been used to control insect growth on transgenic agricultural plants. Cry6Aa exists as a protoxin, which is activated by cleavage using trypsin. Structure studies for Cry6Aa support a mechanism of action by pore formation, similar to cytolysin A (ClyA)-type alpha pore-forming toxins (alpha-PFTs) such as HblB, and bioassay and mutation studies show that Cry6Aa is an active pore-forming toxin. Cry6Aa shows atypical features compared to other members of alpha-PFTs, including internal repeat sequences and small loop regions within major alpha helices.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55741447   48 QRLLEAEQR-AENAETQVGVMEEKVK--LSNLKNVDSE-GSLHRKYQELLKAIKGKDEL--ISQLEAQLEKQKQMRAEEA 121
Cdd:cd22656  120 KALLDDLLKeAKKYQDKAAKVVDKLTdfENQTEKDQTAlETLEKALKDLLTDEGGAIARkeIKDLQKELEKLNEEYAAKL 199

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 55741447  122 K-TVQEKAAKIKEWvTLKLAKLEMENQHLKSHNQRLVEQVGSLQDALEAIQ 171
Cdd:cd22656  200 KaKIDELKALIADD-EAKLAAALRLIADLTAADTDLDNLLALIGPAIPALE 249

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55741447  996 PFSIPVHFTNGTYHVVGFDGSSTVDEFLQRLNQEIGMRKPSHSGFALFTDDPSGRDLEHCLQGSVKICDAISKWEQAMKE 1075
Cdd:cd17178    1 PFSIPVHFMNGTYQVVGFDGSTTVDEFLQTLNQETGMRKPSHSGFALFTDDPSGKDLEHCLQGSVKICDVISKWEQALKE 80

                         90       100
                 ....*....|....*....|....*..
gi 55741447 1076 LHPGKSEgGTRVVKLMYKNRLYFRSQV 1102
Cdd:cd17178   81 LHPGKYE-GTRTVRLTYKSRLYFRAQA 106

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in pleckstrin homology domain-containing family H member 2 (PLEKHH2); PLEKHH2 is a novel podocyte protein downregulated in human focal segmental glomerulosclerosis. It is highly enriched in renal glomerular podocytes, and acts as a novel, important component of the podocyte foot processes. PLEKHH2 contains a putative alpha-helical coiled-coil segment within the N-terminal half, and two Pleckstrin homology (PH) domains, a MyTH4 domain, and a FERM (Band 4.1, ezrin, radixin, moesin) domain within the C-terminal half. The FERM domain is made up of three sub-domains, F1, F2, and F3. The family corresponds to F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N). PLEKHH2 is involved in matrix adhesion and actin dynamics. It directly interacts through its FERM domain with the focal adhesion protein Hic-5 and actin.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55741447  996 PFSIPVHFTNGTYHVVGFDGSSTVDEFLQRLNQEIGMRKPSHSGFALFTDDPSGRDLEHCLQGSVKICDAISKWEQAMKE 1075
Cdd:cd17179    1 PFSIPVHFMNGTYQVVGFDASTTVEEFLNTLNQDTGMRKPGQSGFALFTDDPSGKDLEHCLQGNIKICDIISKWEQASKE 80

                         90       100
                 ....*....|....*....|...
gi 55741447 1076 LHPGKSEgGTRVVKLMYKNRLYF 1098
Cdd:cd17179   81 QHPGKCE-GTRTVRLTYKNRLYF 102

Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 (PLEKHH1) PH domain, repeat 1; PLEKHH1 and PLEKHH2 (also called PLEKHH1L) are thought to function in phospholipid binding and signal transduction. There are 3 Human PLEKHH genes: PLEKHH1, PLEKHH2, and PLEKHH3. There are many isoforms, the longest of which contain a FERM domain, a MyTH4 domain, two PH domains, a peroximal domain, a vacuolar domain, and a coiled coil stretch. 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 C-lobe/F3 within the FERM domain is part of the PH domain family. 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 55741447  581 KSGYLLKMGSQVKTWKRRWFVLRQGQIMYYKSPSDVIRKPQGQVDLNSRCQIVRGEGSQTFQLISEKKTYYLTADSPSLL 660
Cdd:cd13282    1 KAGYLTKLGGKVKTWKRRWFVLKNGELFYYKSPNDVIRKPQGQIALDGSCEIARAEGAQTFEIVTEKRTYYLTADSENDL 80

                         90
                 ....*....|....*.
gi 55741447  661 EEWIRVLQSLLKVQAT 676
Cdd:cd13282   81 DEWIRVIQNVLRRQAS 96

MyTH4 domain; Domain in myosin and kinesin tails, present twice in myosin-VIIa, and also present in 3 other myosins.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 55741447    880 AQTALQVCLVHPELQSEIYCQLMKQTScRPPQKYSLMQCWQLLALCAPLFLPQHHFLWYVKQQLQRHADPRS-ETGQYAT 958
Cdd:pfam00784    1 AQNILQKGLKRPELRDEIYCQLIKQTT-NNPKPESLLRGWQLLALCLGTFPPSKKLLKYLLKFLKRHADDPSrEVGKYAQ 79

                           90       100
                   ....*....|....*....|....*.
gi 55741447    959 YCQRAVERTLRTGEREARPSRMEVVS 984
Cdd:pfam00784   80 FCLKRLKRTLKNGGRKYPPSREEIEA 105

Pleckstrin homology (PH) domain; 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 55741447  581 KSGYLLKMGS-QVKTWKRRWFVLRQGQIMYYKSPSDVIRKPQGQVDLNSRCQIV---RGEGSQTFQLI-SEKKTYYLTAD 655
Cdd:cd00821    1 KEGYLLKRGGgGLKSWKKRWFVLFEGVLLYYKSKKDSSYKPKGSIPLSGILEVEevsPKERPHCFELVtPDGRTYYLQAD 80

                         90
                 ....*....|..
gi 55741447  656 SPSLLEEWIRVL 667
Cdd:cd00821   81 SEEERQEWLKAL 92

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 55741447     579 LEKSGYLLKMGSQV-KTWKRRWFVLRQGQIMYYKSPSDV-IRKPQGQVDLNSrCQIVRGEGSQ------TFQLIS-EKKT 649
Cdd:smart00233    1 VIKEGWLYKKSGGGkKSWKKRYFVLFNSTLLYYKSKKDKkSYKPKGSIDLSG-CTVREAPDPDsskkphCFEIKTsDRKT 79

                            90       100
                    ....*....|....*....|...
gi 55741447     650 YYLTADSPSLLEEWIRVLQSLLK 672
Cdd:smart00233   80 LLLQAESEEEREKWVEALRKAIA 102

Dual Adaptor for Phosphotyrosine and 3-Phosphoinositides Pleckstrin homology (PH) domain; DAPP1 (also known as PHISH/3' phosphoinositide-interacting SH2 domain-containing protein or Bam32) plays a role in B-cell activation and has potential roles in T-cell and mast cell function. DAPP1 promotes B cell receptor (BCR) induced activation of Rho GTPases Rac1 and Cdc42, which feed into mitogen-activated protein kinases (MAPK) activation pathways and affect cytoskeletal rearrangement. DAPP1can also regulate BCR-induced activation of extracellular signal-regulated kinase (ERK), and c-jun NH2-terminal kinase (JNK). DAPP1 contains an N-terminal SH2 domain and a C-terminal pleckstrin homology (PH) domain with a single tyrosine phosphorylation site located centrally. DAPP1 binds strongly to both PtdIns(3,4,5)P3 and PtdIns(3,4)P2. The PH domain is essential for plasma membrane recruitment of PI3K upon cell activation. 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 55741447  581 KSGYLLKMGSQVKTWKRRWFVLRQGQIMYYKSPSDVirKPQGQVDLNsRCQIVRGEGSQ----TFQLISEKKTYYLTADS 656
Cdd:cd10573    5 KEGYLTKLGGIVKNWKTRWFVLRRNELKYFKTRGDT--KPIRVLDLR-ECSSVQRDYSQgkvnCFCLVFPERTFYMYANT 81

                         90
                 ....*....|....*
gi 55741447  657 PSLLEEWIRVLQSLL 671
Cdd:cd10573   82 EEEADEWVKLLKWKL 96

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 55741447  581 KSGYLLKMGSQV-----KTWKRRWFVLRQGQIMYYKSPSDViRKPQGQVDLNSRCQIV-RGEGSQTFQLISEKKTYYLTA 654
Cdd:cd13296    1 KSGWLTKKGGGSstlsrRNWKSRWFVLRDTVLKYYENDQEG-EKLLGTIDIRSAKEIVdNDPKENRLSITTEERTYHLVA 79

                         90
                 ....*....|....*
gi 55741447  655 DSPSLLEEWIRVLQS 669
Cdd:cd13296   80 ESPEDASQWVNVLTR 94

Switch-associated protein-70 Pleckstrin homology (PH) domain; SWAP-70 (also called Differentially expressed in FDCP 6/DEF-6 or IRF4-binding protein) functions in cellular signal transduction pathways (in conjunction with Rac), regulates cell motility through actin rearrangement, and contributes to the transformation and invasion activity of mouse embryo fibroblasts. Metazoan SWAP-70 is found in B lymphocytes, mast cells, and in a variety of organs. Metazoan SWAP-70 contains an N-terminal EF-hand motif, a centrally located PH domain, and a C-terminal coiled-coil domain. The PH domain of Metazoan SWAP-70 contains a phosphoinositide-binding site and a nuclear localization signal (NLS), which localize SWAP-70 to the plasma membrane and nucleus, respectively. The NLS is a sequence of four Lys residues located at the N-terminus of the C-terminal a-helix; this is a unique characteristic of the Metazoan SWAP-70 PH domain. The SWAP-70 PH domain binds PtdIns(3,4,5)P3 and PtdIns(4,5)P2 embedded in lipid bilayer vesicles. There are additional plant SWAP70 proteins, but these are not included in this hierarchy. Rice SWAP70 (OsSWAP70) exhibits GEF activity toward the its Rho GTPase, OsRac1, and regulates chitin-induced production of reactive oxygen species and defense gene expression in rice. Arabidopsis SWAP70 (AtSWAP70) plays a role in both PAMP- and effector-triggered immunity. Plant SWAP70 contains both DH and PH domains, but their arrangement is the reverse of that in typical DH-PH-type Rho GEFs, wherein the DH domain is flanked by a C-terminal PH domain. 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 55741447  581 KSGYLLKMGSQVKTWKRRWFVLRQGQIMYYKSPSDviRKPQGQVDLNSRCQI----VRGEGSQTFQLISEKKTYYLTADS 656
Cdd:cd13273   10 KKGYLWKKGHLLPTWTERWFVLKPNSLSYYKSEDL--KEKKGEIALDSNCCVeslpDREGKKCRFLVKTPDKTYELSASD 87

                         90       100
                 ....*....|....*....|.
gi 55741447  657 PSLLEEWIRVLQSLLKVQATG 677
Cdd:cd13273   88 HKTRQEWIAAIQTAIRLSQEG 108

Autophagy-related protein 26/Sterol 3-beta-glucosyltransferase Pleckstrin homology (PH) domain, repeat 1; ATG26 (also called UGT51/UDP-glycosyltransferase 51), a member of the glycosyltransferase 28 family, resulting in the biosynthesis of sterol glucoside. ATG26 in decane metabolism and autophagy. There are 32 known autophagy-related (ATG) proteins, 17 are components of the core autophagic machinery essential for all autophagy-related pathways and 15 are the additional components required only for certain pathways or species. The core autophagic machinery includes 1) the ATG9 cycling system (ATG1, ATG2, ATG9, ATG13, ATG18, and ATG27), 2) the phosphatidylinositol 3-kinase complex (ATG6/VPS30, ATG14, VPS15, and ATG34), and 3) the ubiquitin-like protein system (ATG3, ATG4, ATG5, ATG7, ATG8, ATG10, ATG12, and ATG16). Less is known about how the core machinery is adapted or modulated with additional components to accommodate the nonselective sequestration of bulk cytosol (autophagosome formation) or selective sequestration of specific cargos (Cvt vesicle, pexophagosome, or bacteria-containing autophagosome formation). The pexophagosome-specific additions include the ATG30-ATG11-ATG17 receptor-adaptors complex, the coiled-coil protein ATG25, and the sterol glucosyltransferase ATG26. ATG26 is necessary for the degradation of medium peroxisomes. It contains 2 GRAM domains and a single PH domain. PH domains are only found in eukaryotes. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. PH domains also have diverse functions. They are often involved in targeting proteins to the plasma membrane, but 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 55741447  581 KSGYLLKMGSQVKTWKRRWFVLRQGQIMYYKSPSDvIRKPQGQVDLN--SRCQIVRGEGSQT--FQLISEKKTYYLTADS 656
Cdd:cd13215   23 KSGYLSKRSKRTLRYTRYWFVLKGDTLSWYNSSTD-LYFPAGTIDLRyaTSIELSKSNGEATtsFKIVTNSRTYKFKADS 101

                         90
                 ....*....|....*...
gi 55741447  657 PSLLEEWIRVLQsllKVQ 674
Cdd:cd13215  102 ETSADEWVKALK---KQI 116

Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal proteins are unknown, but they all contain 2 PH domains. This cd represents the first 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 55741447  581 KSGYLLKMGSQVKTWKRRWFVLRQGQIMYYKSPSDviRKPQGQVDLN--SRCQIVRGEGSQ-TFQLISEKKTYYLTADSP 657
Cdd:cd13298    8 KSGYLLKRSRKTKNWKKRWVVLRPCQLSYYKDEKE--YKLRRVINLSelLAVAPLKDKKRKnVFGIYTPSKNLHFRATSE 85

                         90
                 ....*....|...
gi 55741447  658 SLLEEWIRVLQSL 670
Cdd:cd13298   86 KDANEWVEALREE 98

Arabidopsis thaliana Pleckstrin homolog (PH) 1 (AtPH1) PH domain; AtPH1 is expressed in all plant tissue and is proposed to be the plant homolog of human pleckstrin. Pleckstrin consists of two PH domains separated by a linker region, while AtPH has a single PH domain with a short N-terminal extension. AtPH1 binds PtdIns3P specifically and is thought to be an adaptor molecule since it has no obvious catalytic functions. 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 55741447  581 KSGYLLKMGSQVKTWKRRWFVLRQGQIMYYKSPsDVIR--KPQGQVDLNSrCQIVRGEGSQT-----FQLISEKKTYYLT 653
Cdd:cd13276    1 KAGWLEKQGEFIKTWRRRWFVLKQGKLFWFKEP-DVTPysKPRGVIDLSK-CLTVKSAEDATnkenaFELSTPEETFYFI 78

                         90
                 ....*....|.
gi 55741447  654 ADSPSLLEEWI 664
Cdd:cd13276   79 ADNEKEKEEWI 89

Set binding factor 1 (also called Human MTMR5) Pleckstrin Homology (PH) domain; Sbf1 is a myotubularin-related pseudo-phosphatase. Both Sbf1 and myotubularin interact with the SET domains of Hrx and other epigenetic regulatory proteins, but Sbf1 lacks phosphatase activity due to several amino acid changes in its structurally preserved catalytic pocket. It contains pleckstrin (PH), GEF, and myotubularin homology domains that are thought to be responsible for signaling and growth control. Sbf1 functions as an inhibitor of cellular growth. The N-terminal GEF homology domain serves to inhibit the transforming effects of Sbf1. 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 55741447  583 GYLLKMGSQVKTWKRRWFVL--RQGQIMYYKSPSDviRKPQGQVDLN--SRCQIV--------RGEGSQTFQLISEKKTY 650
Cdd:cd01235    7 GYLYKRGALLKGWKQRWFVLdsTKHQLRYYESRED--TKCKGFIDLAevESVTPAtpiigapkRADEGAFFDLKTNKRVY 84

                         90       100
                 ....*....|....*....|..
gi 55741447  651 YLTADSPSLLEEWIRVLQSLLK 672
Cdd:cd01235   85 NFCAFDAESAQQWIEKIQSCLS 106

TBC1 domain family member 2A pleckstrin homology (PH) domain; TBC1D2A (also called PARIS-1/Prostate antigen recognized and identified by SEREX 1 and ARMUS) contains a PH domain and a TBC-type GTPase catalytic domain. TBC1D2A integrates signaling between Arf6, Rac1, and Rab7 during junction disassembly. Activated Rac1 recruits TBC1D2A to locally inactivate Rab7 via its C-terminal TBC/RabGAP domain and facilitate E-cadherin degradation in lysosomes. The TBC1D2A PH domain mediates localization at cell-cell contacts and coprecipitates with cadherin complexes. 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 55741447  582 SGYLLKM---GSQVKTWKRRWFVL--RQGQIMYYKSPSDVirKPQGQVDLNSRC---QIVRGEGsqTFQLISEKKTYYLT 653
Cdd:cd01265    3 CGYLNKLetrGLGLKGWKRRWFVLdeSKCQLYYYRSPQDA--TPLGSIDLSGAAfsyDPEAEPG--QFEIHTPGRVHILK 78

                         90
                 ....*....|....*.
gi 55741447  654 ADSPSLLEEWIRVLQS 669
Cdd:cd01265   79 ASTRQAMLYWLQALQS 94