Myosin X-like Pleckstrin homology (PH) domain, repeat 3; 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 third MyoX PH repeat. PLEKHH3/Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) member 3 is also part of this CD and like MyoX contains a FERM domain, a MyTH4 domain, and a single PH domain. Not much is known about the function of PLEKHH3. 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 1212450075  639 RSKGDTRVEGQEFIVRGWLHKEVKNSPKMSSLKLKKRWFVLTHNSLDYYKSSEKNALKLGTLVLNSLCSVVPPDEKIFKE 718
Cdd:cd13297      1 RPKGDLDEGGQDVIERGWLYKEGGKGGARGNLTKKKRWFVLTGNSLDYYKSSEKNSLKLGTLVLNSLCSVVPPDEKMAKE 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 1212450075  719 TGYWNVTVYGRKHCYRLYTKLLNEATRWSSAIQNVTDTKAPIDTPT 764
Cdd:cd13297     81 TGYWTFTVHGRKHSFRLYTKLQEEAMRWVNAIQDVIDSKPPIETPT 126

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 1212450075  473 KQGWLHKKGGGSSTLSRRNWKKRWFVLRQSKLMYFENDSE-EKLKGTVEVRTAKEIIDNTSKENGIDIILADRTFHLIAE 551
Cdd:cd13296      1 KSGWLTKKGGGSSTLSRRNWKSRWFVLRDTVLKYYENDQEgEKLLGTIDIRSAKEIVDNDPKENRLSITTEERTYHLVAE 80

                           90       100
                   ....*....|....*....|...
gi 1212450075  552 SPEDASQWFSVLSQVHSSTDQEI 574
Cdd:cd13296     81 SPEDASQWVNVLTRVISATDLEL 103

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 1212450075   807 YGDINLNLLKDKGYTtLQDEAIKIFnsLQQLESMSD-PIP-------IIQGILQTGHDLRPLRDELYCQLIKQTNKVPHP 878
Cdd:smart00139    3 KDPIKTSLLKLESDE-LQKEAVKIF--KAILKFMGDiPLPrpdshldLVQFILQKGLDHPELRDEIYCQLIKQLTDNPSR 79

                            90       100       110       120       130       140       150
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1212450075   879 GSvgNLYSWQILTCLSCTFLPSRGILKYLKFHLKRIREQFPGTEMEKYALFIYESLKKTKCREFVPSRDEIEALI 953
Cdd:smart00139   80 QS--EERGWQLLYLCTSLFPPSERLLPYLLQFLSRRADPGSEQGLAKYCLYRLERTLKNGARKQPPSRLELEAIL 152

Unconventional myosin-X coiled coil domain; This coiled coil domain is found in unconventional myosin-X and is responsible for dimerization.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1212450075  136 ENKQVEEILRLEKEIEDLQRMKERQELSLTEASLQKLQQLRDEELRRLEDE 186
Cdd:pfam16735    2 ESRQMEEILRLEREIERLQRQKEDQESSLCETSLNELQRLRDEEIQRLEKE 52

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
                   ....*....|....*....|....*....|....*....|...
gi 1212450075  439 FLYMKGGLMNSWKRRWCVLKDETFLWFRSKQEALKQGWLHKKG 481
Cdd:cd13301      8 YLVKKGHVVNNWKARWFVLKEDGLEYYKKKTDSSPKGMIPLKG 50

Myosin X-like Pleckstrin homology (PH) domain, repeat 3; 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 third MyoX PH repeat. PLEKHH3/Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) member 3 is also part of this CD and like MyoX contains a FERM domain, a MyTH4 domain, and a single PH domain. Not much is known about the function of PLEKHH3. 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 1212450075  639 RSKGDTRVEGQEFIVRGWLHKEVKNSPKMSSLKLKKRWFVLTHNSLDYYKSSEKNALKLGTLVLNSLCSVVPPDEKIFKE 718
Cdd:cd13297      1 RPKGDLDEGGQDVIERGWLYKEGGKGGARGNLTKKKRWFVLTGNSLDYYKSSEKNSLKLGTLVLNSLCSVVPPDEKMAKE 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 1212450075  719 TGYWNVTVYGRKHCYRLYTKLLNEATRWSSAIQNVTDTKAPIDTPT 764
Cdd:cd13297     81 TGYWTFTVHGRKHSFRLYTKLQEEAMRWVNAIQDVIDSKPPIETPT 126

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 1212450075  473 KQGWLHKKGGGSSTLSRRNWKKRWFVLRQSKLMYFENDSE-EKLKGTVEVRTAKEIIDNTSKENGIDIILADRTFHLIAE 551
Cdd:cd13296      1 KSGWLTKKGGGSSTLSRRNWKSRWFVLRDTVLKYYENDQEgEKLLGTIDIRSAKEIVDNDPKENRLSITTEERTYHLVAE 80

                           90       100
                   ....*....|....*....|...
gi 1212450075  552 SPEDASQWFSVLSQVHSSTDQEI 574
Cdd:cd13296     81 SPEDASQWVNVLTRVISATDLEL 103

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 1212450075   807 YGDINLNLLKDKGYTtLQDEAIKIFnsLQQLESMSD-PIP-------IIQGILQTGHDLRPLRDELYCQLIKQTNKVPHP 878
Cdd:smart00139    3 KDPIKTSLLKLESDE-LQKEAVKIF--KAILKFMGDiPLPrpdshldLVQFILQKGLDHPELRDEIYCQLIKQLTDNPSR 79

                            90       100       110       120       130       140       150
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1212450075   879 GSvgNLYSWQILTCLSCTFLPSRGILKYLKFHLKRIREQFPGTEMEKYALFIYESLKKTKCREFVPSRDEIEALI 953
Cdd:smart00139   80 QS--EERGWQLLYLCTSLFPPSERLLPYLLQFLSRRADPGSEQGLAKYCLYRLERTLKNGARKQPPSRLELEAIL 152

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 1212450075  847 IQGILQTGHDLRPLRDELYCQLIKQTNKVPHPGSvgNLYSWQILTCLSCTFLPSRGILKYLKFHLKRIREQFpGTEMEKY 926
Cdd:pfam00784    1 AQNILQKGLKRPELRDEIYCQLIKQTTNNPKPES--LLRGWQLLALCLGTFPPSKKLLKYLLKFLKRHADDP-SREVGKY 77

                           90       100
                   ....*....|....*....|....*...
gi 1212450075  927 ALFIYESLKKTK---CREFVPSRDEIEA 951
Cdd:pfam00784   78 AQFCLKRLKRTLkngGRKYPPSREEIEA 105

Unconventional myosin-X coiled coil domain; This coiled coil domain is found in unconventional myosin-X and is responsible for dimerization.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1212450075  136 ENKQVEEILRLEKEIEDLQRMKERQELSLTEASLQKLQQLRDEELRRLEDE 186
Cdd:pfam16735    2 ESRQMEEILRLEREIERLQRQKEDQESSLCETSLNELQRLRDEEIQRLEKE 52

PH domain; PH stands for pleckstrin homology.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1212450075  473 KQGWLHKKGGGSstlsRRNWKKRWFVLRQSKLMYFENDS---EEKLKGTVEVRTAK----EIIDNTSKENGIDIILAD-- 543
Cdd:pfam00169    3 KEGWLLKKGGGK----KKSWKKRYFVLFDGSLLYYKDDKsgkSKEPKGSISLSGCEvvevVASDSPKRKFCFELRTGErt 78

                           90       100
                   ....*....|....*....|....*..
gi 1212450075  544 --RTFHLIAESPEDASQWFSVLSQVHS 568
Cdd:pfam00169   79 gkRTYLLQAESEEERKDWIKAIQSAIR 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 1212450075   651 FIVRGWLHKEVKNSPKmsslKLKKRWFVLTHNSLDYYKSSEKNALK--LGTLVLNSLCSVVPPDEKIFKETGYWNVtVYG 728
Cdd:smart00233    1 VIKEGWLYKKSGGGKK----SWKKRYFVLFNSTLLYYKSKKDKKSYkpKGSIDLSGCTVREAPDPDSSKKPHCFEI-KTS 75

                            90       100
                    ....*....|....*....|....*..
gi 1212450075   729 RKHCYRLYTKLLNEATRWSSAIQNVTD 755
Cdd:smart00233   76 DRKTLLLQAESEEEREKWVEALRKAIA 102

Trichohyalin-plectin-homology domain; This family is a mixtrue of two different families of eukaryotic proteins. Trichoplein or mitostatin, was first defined as a meiosis-specific nuclear structural protein. It has since been linked with mitochondrial movement. It is associated with the mitochondrial outer membrane, and over-expression leads to reduction in mitochondrial motility whereas lack of it enhances mitochondrial movement. The activity appears to be mediated through binding the mitochondria to the actin intermediate filaments (IFs). The family is in the trichohyalin-plectin-homology domain.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1212450075   98 ADLLRAHQEAETRRQQELEALQKSQREADLTRELEKQRENKQVEEILRLEKEIEDLQRMK------ERQELSLTEASLQK 171
Cdd:pfam13868  208 AKLYQEEQERKERQKEREEAEKKARQRQELQQAREEQIELKERRLAEEAEREEEEFERMLrkqaedEEIEQEEAEKRRMK 287

                           90       100
                   ....*....|....*....|....*....
gi 1212450075  172 LQQLRDEELRRLEDEACRAAQEFLESLNF 200
Cdd:pfam13868  288 RLEHRRELEKQIEEREEQRAAEREEELEE 316

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 1212450075   94 AQREADlLRAHQEAETRRQQELEALqKSQREAD-LTRELEKQRENKQV--EEILRLEKEIEDLQRMKE--RQELSLTEAS 168
Cdd:COG1579     62 KRLELE-IEEVEARIKKYEEQLGNV-RNNKEYEaLQKEIESLKRRISDleDEILELMERIEELEEELAelEAELAELEAE 139

                           90
                   ....*....|....*...
gi 1212450075  169 LQKLQQLRDEELRRLEDE 186
Cdd:COG1579    140 LEEKKAELDEELAELEAE 157

PH domain; PH stands for pleckstrin homology.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1212450075  654 RGWLHKEVKNSPKmsslKLKKRWFVLTHNSLDYYKSS--EKNALKLGTLVLNSLCSVVPPDEKIFKETGYWNVTVY--GR 729
Cdd:pfam00169    4 EGWLLKKGGGKKK----SWKKRYFVLFDGSLLYYKDDksGKSKEPKGSISLSGCEVVEVVASDSPKRKFCFELRTGerTG 79

                           90       100
                   ....*....|....*....|....
gi 1212450075  730 KHCYRLYTKLLNEATRWSSAIQNV 753
Cdd:pfam00169   80 KRTYLLQAESEEERKDWIKAIQSA 103

Outer membrane protein (OmpH-like); This family includes outer membrane proteins such as OmpH among others. Skp (OmpH) has been characterized as a molecular chaperone that interacts with unfolded proteins as they emerge in the periplasm from the Sec translocation machinery.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1212450075   111 RQQELEALQKSQREadLTRELEKQRENKQVEEILRLEKEIEDLQR--MKERQELSlteaslQKLQQLRDEELRRLEDEAC 188
Cdd:smart00935   30 RQAELEKLEKELQK--LKEKLQKDAATLSEAAREKKEKELQKKVQefQRKQQKLQ------QDLQKRQQEELQKILDKIN 101

                            90
                    ....*....|...
gi 1212450075   189 RAAQEFLESLNFD 201
Cdd:smart00935  102 KAIKEVAKKKGYD 114

cell envelope integrity inner membrane protein TolA; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1212450075   91 RERAQREADLLRAHQEAETRRQQELEAlqksqreadltRELEKQRENKQVEEILRLEKEiedlqRMKERQELSLTEASLQ 170
Cdd:PRK09510    82 KKKEQQQAEELQQKQAAEQERLKQLEK-----------ERLAAQEQKKQAEEAAKQAAL-----KQKQAEEAAAKAAAAA 145

                           90       100
                   ....*....|....*....|...
gi 1212450075  171 KLQQlrDEELRRLEDEACRAAQE 193
Cdd:PRK09510   146 KAKA--EAEAKRAAAAAKKAAAE 166

Glutamine-rich N-terminal helical domain of HDAC9, a Class IIa histone deacetylase; This family consists of the glutamine-rich domain of histone deacetylase 9 (HDAC9). It belongs to a superfamily that consists of the glutamine-rich N-terminal helical extension to certain Class IIa histone deacetylases (HDACs), including HDAC4, HDAC5 and HDCA9; it is missing from HDAC7. This domain confers responsiveness to calcium signals and mediates interactions with transcription factors and cofactors, and it is able to repress transcription independently of the HDAC C-terminal, zinc-dependent catalytic domain. It has many intra- and inter-helical interactions which are possibly involved in reversible assembly and disassembly of proteins. HDACs regulate diverse cellular processes through enzymatic deacetylation of histone as well as non-histone proteins, in particular deacetylating N(6)-acetyl-lysine residues.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1212450075  108 ETRRQQELEALQKSQR--EADLTRELEKQREN------KQVEEILRLEKEiedLQRMKERQELSLTEASLQKLQQLRDEE 179
Cdd:cd10163      6 EKQLQQELLLIQQQQQiqKQLLIAEFQKQHENltrqhqAQLQEHLKLQQE---LLAMKQQQELLEKEQKLEQQRQEQELE 82

                   ....*..
gi 1212450075  180 LRRLEDE 186
Cdd:cd10163     83 RHRREQQ 89

Myosin X-like Pleckstrin homology (PH) domain, repeat 3; 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 third MyoX PH repeat. PLEKHH3/Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) member 3 is also part of this CD and like MyoX contains a FERM domain, a MyTH4 domain, and a single PH domain. Not much is known about the function of PLEKHH3. 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 1212450075  639 RSKGDTRVEGQEFIVRGWLHKEVKNSPKMSSLKLKKRWFVLTHNSLDYYKSSEKNALKLGTLVLNSLCSVVPPDEKIFKE 718
Cdd:cd13297      1 RPKGDLDEGGQDVIERGWLYKEGGKGGARGNLTKKKRWFVLTGNSLDYYKSSEKNSLKLGTLVLNSLCSVVPPDEKMAKE 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 1212450075  719 TGYWNVTVYGRKHCYRLYTKLLNEATRWSSAIQNVTDTKAPIDTPT 764
Cdd:cd13297     81 TGYWTFTVHGRKHSFRLYTKLQEEAMRWVNAIQDVIDSKPPIETPT 126

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 1212450075  473 KQGWLHKKGGGSSTLSRRNWKKRWFVLRQSKLMYFENDSE-EKLKGTVEVRTAKEIIDNTSKENGIDIILADRTFHLIAE 551
Cdd:cd13296      1 KSGWLTKKGGGSSTLSRRNWKSRWFVLRDTVLKYYENDQEgEKLLGTIDIRSAKEIVDNDPKENRLSITTEERTYHLVAE 80

                           90       100
                   ....*....|....*....|...
gi 1212450075  552 SPEDASQWFSVLSQVHSSTDQEI 574
Cdd:cd13296     81 SPEDASQWVNVLTRVISATDLEL 103

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 1212450075   807 YGDINLNLLKDKGYTtLQDEAIKIFnsLQQLESMSD-PIP-------IIQGILQTGHDLRPLRDELYCQLIKQTNKVPHP 878
Cdd:smart00139    3 KDPIKTSLLKLESDE-LQKEAVKIF--KAILKFMGDiPLPrpdshldLVQFILQKGLDHPELRDEIYCQLIKQLTDNPSR 79

                            90       100       110       120       130       140       150
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1212450075   879 GSvgNLYSWQILTCLSCTFLPSRGILKYLKFHLKRIREQFPGTEMEKYALFIYESLKKTKCREFVPSRDEIEALI 953
Cdd:smart00139   80 QS--EERGWQLLYLCTSLFPPSERLLPYLLQFLSRRADPGSEQGLAKYCLYRLERTLKNGARKQPPSRLELEAIL 152

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 1212450075   962 VYCHGGGSCKITINSHTTAGEVVEKLIRGLAMEDSrNMFALFEYNGQVDkaiesrtivadvLAKFEKLAATSEAGD---A 1038
Cdd:smart00295    4 VYLLDGTTLEFEVDSSTTAEELLETVCRKLGIRES-EYFGLQFEDPDED------------LRHWLDPAKTLLDQDvksE 70

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1212450075  1039 PWKFYFKLYCFLDTDSMPK-DSVEFAFMFEQAHEAVIHGHHPAPEESLQVLAALRLQYLQGDYTPHTSIPPLEEVYsvqr 1117
Cdd:smart00295   71 PLTLYFRVKFYPPDPNQLKeDPTRLNLLYLQVRNDILEGRLPCPEEEALLLAALALQAEFGDYDEELHDLRGELSL---- 146

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1212450075  1118 lrarisqstKTFTPyerlekrrtsflegtlrrsfrtgsvvrqkaeeEQMLDMWIKEEVcsaRTSIIDKWKKLQGMNQEQA 1197
Cdd:smart00295  147 ---------KRFLP--------------------------------KQLLDSRKLKEW---RERIVELHKELIGLSPEEA 182

                           250
                    ....*....|....*....
gi 1212450075  1198 MAKYMALIKEWPGYGSTLF 1216
Cdd:smart00295  183 KLKYLELARKLPTYGVELF 201

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 1212450075  847 IQGILQTGHDLRPLRDELYCQLIKQTNKVPHPGSvgNLYSWQILTCLSCTFLPSRGILKYLKFHLKRIREQFpGTEMEKY 926
Cdd:pfam00784    1 AQNILQKGLKRPELRDEIYCQLIKQTTNNPKPES--LLRGWQLLALCLGTFPPSKKLLKYLLKFLKRHADDP-SREVGKY 77

                           90       100
                   ....*....|....*....|....*...
gi 1212450075  927 ALFIYESLKKTK---CREFVPSRDEIEA 951
Cdd:pfam00784   78 AQFCLKRLKRTLkngGRKYPPSREEIEA 105

Unconventional myosin-X coiled coil domain; This coiled coil domain is found in unconventional myosin-X and is responsible for dimerization.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1212450075  136 ENKQVEEILRLEKEIEDLQRMKERQELSLTEASLQKLQQLRDEELRRLEDE 186
Cdd:pfam16735    2 ESRQMEEILRLEREIERLQRQKEDQESSLCETSLNELQRLRDEEIQRLEKE 52

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 1212450075  473 KQGWLHKKGGgsstlSRRNWKKRWFVLRQSKLMYF--ENDSEEKLKGTVEVRTAKEIIDNTSKENgIDIILADRTFHLIA 550
Cdd:cd13282      1 KAGYLTKLGG-----KVKTWKRRWFVLKNGELFYYksPNDVIRKPQGQIALDGSCEIARAEGAQT-FEIVTEKRTYYLTA 74

                           90
                   ....*....|....*.
gi 1212450075  551 ESPEDASQWFSVLSQV 566
Cdd:cd13282     75 DSENDLDEWIRVIQNV 90

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 1212450075  466 RSKQEALKQGWLHKKGGgsSTLsrRNWKKRWFVLRQSKLMYFENDSEEKLKGTVEVR----TAKEIIDNTSKENGIDIIL 541
Cdd:cd13248      2 DPNAPVVMSGWLHKQGG--SGL--KNWRKRWFVLKDNCLYYYKDPEEEKALGSILLPsytiSPAPPSDEISRKFAFKAEH 77

                           90       100
                   ....*....|....*....|....*
gi 1212450075  542 AD-RTFHLIAESPEDASQWFSVLSQ 565
Cdd:cd13248     78 ANmRTYYFAADTAEEMEQWMNAMSL 102

FERM domain C-lobe; The FERM domain has a cloverleaf tripart structure composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs), the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1212450075 1212 GSTLFDVeCKEGGFPQELWLGVSADAVSVYKRGEGKPLEVFQYEHILSFGAPLANTYKIVVD----ERELLFETS--EVV 1285
Cdd:cd00836      1 GVEFFPV-KDKSKKGSPIILGVNPEGISVYDELTGQPLVLFPWPNIKKISFSGAKKFTIVVAdedkQSKLLFQTPsrQAK 79

                           90
                   ....*....|...
gi 1212450075 1286 DVAKLMKAYISMI 1298
Cdd:cd00836     80 EIWKLIVGYHRFL 92

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 1212450075  473 KQGWLHKKGGgsstlSRRNWKKRWFVLRQSKLMYFEN-DSEEKLKgTVEVRTAKEIIDNTS--KENGIDIILADRTFHLI 549
Cdd:cd10573      5 KEGYLTKLGG-----IVKNWKTRWFVLRRNELKYFKTrGDTKPIR-VLDLRECSSVQRDYSqgKVNCFCLVFPERTFYMY 78

                           90
                   ....*....|....*
gi 1212450075  550 AESPEDASQWFSVLS 564
Cdd:cd10573     79 ANTEEEADEWVKLLK 93

Bruton's tyrosine kinase pleckstrin homology (PH) domain; Btk is a member of the Tec family of cytoplasmic protein tyrosine kinases that includes BMX, IL2-inducible T-cell kinase (Itk) and Tec. Btk plays a role in the maturation of B cells. Tec proteins general have an N-terminal PH domain, followed by a Tek homology (TH) domain, a SH3 domain, a SH2 domain and a kinase domain. The Btk PH domain binds phosphatidylinositol 3,4,5-trisphosphate and responds to signalling via phosphatidylinositol 3-kinase. The PH domain is also involved in membrane anchoring which is confirmed by the discovery of a mutation of a critical arginine residue in the BTK PH domain. This results in severe human immunodeficiency known as X-linked agammaglobulinemia (XLA) in humans and a related disorder is mice.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 1212450075  473 KQGWLHKKGGGSSTLSRRNWKKRWFVLRQSKLMYFENDSEE--KLKGTVEVRTAK--EIIDNTSKENG---IDIILADRT 545
Cdd:cd01238      1 LEGLLVKRSQGKKRFGPVNYKERWFVLTKSSLSYYEGDGEKrgKEKGSIDLSKVRcvEEVKDEAFFERkypFQVVYDDYT 80

                           90       100
                   ....*....|....*....|.
gi 1212450075  546 FHLIAESPEDASQWFSVLSQV 566
Cdd:cd01238     81 LYVFAPSEEDRDEWIAALRKV 101

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).