Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344746  600 DDQRGQELTRLEEERIVILNNLEELEQKIKDLNDQMDESSRELDMECALLDGEQKSE---TTELLKEKEILDHLNRKIAE 676
Cdd:COG1196    234 LRELEAELEELEAELEELEAELEELEAELAELEAELEELRLELEELELELEEAQAEEyelLAELARLEQDIARLEERRRE 313

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344746  677 LERNvigEKAKDADLLDIESKHfEDLEFQQLEHESRLDEEKENL--TQQLLREVAEYQRSIVSRKEKISALKKQANHIVQ 754
Cdd:COG1196    314 LEER---LEELEEELAELEEEL-EELEEELEELEEELEEAEEELeeAEAELAEAEEALLEAEAELAEAEEELEELAEELL 389

                          170       180       190
                   ....*....|....*....|....*....|....*..
gi 2024344746  755 QAQREQDHFVKEKNNLIMMLQREKENLCNLEKKYSSL 791
Cdd:COG1196    390 EALRAAAELAAQLEELEEAEEALLERLERLEEELEEL 426

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 2024344746  1181 TCRGFLIKMG-GKIKTWKKRWFVFDRNkrTFTYYADKHE---TKLKGVIYFQAIeEVYYDHLKNAYKSPNpllTFSVKTH 1256
Cdd:smart00233    2 IKEGWLYKKSgGGKKSWKKRYFVLFNS--TLLYYKSKKDkksYKPKGSIDLSGC-TVREAPDPDSSKKPH---CFEIKTS 75

                            90       100
                    ....*....|....*....|..
gi 2024344746  1257 DR-IYYMVAPTPEAMRIWMDVI 1277
Cdd:smart00233   76 DRkTLLLQAESEEEREKWVEAL 97

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344746  600 DDQRGQELTRLEEERIVILNNLEELEQKIKDLNDQMDESSRELDMECALLDGEQKSE---TTELLKEKEILDHLNRKIAE 676
Cdd:COG1196    234 LRELEAELEELEAELEELEAELEELEAELAELEAELEELRLELEELELELEEAQAEEyelLAELARLEQDIARLEERRRE 313

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344746  677 LERNvigEKAKDADLLDIESKHfEDLEFQQLEHESRLDEEKENL--TQQLLREVAEYQRSIVSRKEKISALKKQANHIVQ 754
Cdd:COG1196    314 LEER---LEELEEELAELEEEL-EELEEELEELEEELEEAEEELeeAEAELAEAEEALLEAEAELAEAEEELEELAEELL 389

                          170       180       190
                   ....*....|....*....|....*....|....*..
gi 2024344746  755 QAQREQDHFVKEKNNLIMMLQREKENLCNLEKKYSSL 791
Cdd:COG1196    390 EALRAAAELAAQLEELEEAEEALLERLERLEEELEEL 426

Ezrin/radixin/moesin, alpha-helical domain; The ERM family consists of three closely-related proteins, ezrin, radixin and moesin. Ezrin was first identified as a constituent of microvilli, radixin as a barbed, end-capping actin-modulating protein from isolated junctional fractions, and moesin as a heparin binding protein. A tumour suppressor molecule responsible for neurofibromatosis type 2 (NF2) is highly similar to ERM proteins and has been designated merlin (moesin-ezrin-radixin-like protein). ERM molecules contain 3 domains, an N-terminal globular domain, an extended alpha-helical domain and a charged C-terminal domain (pfam00769). Ezrin, radixin and merlin also contain a polyproline linker region between the helical and C-terminal domains. The N-terminal domain is highly conserved and is also found in merlin, band 4.1 proteins and members of the band 4.1 superfamily, designated the FERM domain. ERM proteins crosslink actin filaments with plasma membranes. They co-localize with CD44 at actin filament plasma membrane interaction sites, associating with CD44 via their N-terminal domains and with actin filaments via their C-terminal domains. This is the alpha-helical domain, which is involved in intramolecular masking of protein-protein interaction sites, regulating the activity of this proteins.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2024344746 1070 RIEEMERLLKQAHAEKtRLLESREREMEAKKRALEEEKRR----REQLEKRLEEETSQRQKLI-EKEVKIREKQRAQAR 1143
Cdd:pfam20492   35 TAEELEEERRQAEEEA-ERLEQKRQEAEEEKERLEESAEMeaeeKEQLEAELAEAQEEIARLEeEVERKEEEARRLQEE 112

Myosin tail; The myosin molecule is a multi-subunit complex made up of two heavy chains and four light chains it is a fundamental contractile protein found in all eukaryote cell types. This family consists of the coiled-coil myosin heavy chain tail region. The coiled-coil is composed of the tail from two molecules of myosin. These can then assemble into the macromolecular thick filament. The coiled-coil region provides the structural backbone the thick filament.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344746  603 RGQEL--------TRLEEE--RIVIL-NNLEELEQKIKDLNDQMDE---SSRELDMECALLDGEQKS----------ETT 658
Cdd:pfam01576   69 RKQELeeilheleSRLEEEeeRSQQLqNEKKKMQQHIQDLEEQLDEeeaARQKLQLEKVTTEAKIKKleedillledQNS 148

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344746  659 ELLKEKEILDhlnRKIAELERNVIGEKAKDADLLDIESKH---FEDLEfQQLEHESRLDEEKENLTQQLLREVAEYQRSI 735
Cdd:pfam01576  149 KLSKERKLLE---ERISEFTSNLAEEEEKAKSLSKLKNKHeamISDLE-ERLKKEEKGRQELEKAKRKLEGESTDLQEQI 224

                          170
                   ....*....|...
gi 2024344746  736 VSRKEKISALKKQ 748
Cdd:pfam01576  225 AELQAQIAELRAQ 237

MAEBL; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344746 1075 ERLLKQAHAEKTRLLESREREMEAKKRA-----LEEEKRRREQLEKRLEEETSQRQKLIEKE----VKIREKQRAQARPL 1145
Cdd:PTZ00121  1664 AEEAKKAEEDKKKAEEAKKAEEDEKKAAealkkEAEEAKKAEELKKKEAEEKKKAEELKKAEeenkIKAEEAKKEAEEDK 1743

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344746 1146 TRYLPIRKEDFDlRSHIETAGHNIETCYHVSLTEKTCrgfLIKMGGKIKTWKKRWFVFDRNKRTFTYYADKHETKLKGVI 1225
Cdd:PTZ00121  1744 KKAEEAKKDEEE-KKKIAHLKKEEEKKAEEIRKEKEA---VIEEELDEEDEKRRMEVDKKIKDIFDNFANIIEGGKEGNL 1819

                          170       180
                   ....*....|....*....|....
gi 2024344746 1226 YFQAIEEVYYDHLKNAYKSPNPLL 1249
Cdd:PTZ00121  1820 VINDSKEMEDSAIKEVADSKNMQL 1843

Uncharacterized family; SPFH (stomatin, prohibitin, flotillin, and HflK/C) superfamily; This model summarizes an uncharacterized family of proteins similar to stomatin, prohibitin, flotillin, HflK/C (SPFH) and podocin. The conserved domain common to the SPFH superfamily has also been referred to as the Band 7 domain. Many superfamily members are associated with lipid rafts. Individual proteins of the SPFH superfamily may cluster to form membrane microdomains which may in turn recruit multiprotein complexes. Microdomains formed from flotillin proteins may in addition be dynamic units with their own regulatory functions. Flotillins have been implicated in signal transduction, vesicle trafficking, cytoskeleton rearrangement and are known to interact with a variety of proteins. Stomatin interacts with and regulates members of the degenerin/epithelia Na+ channel family in mechanosensory cells of Caenorhabditis elegans and vertebrate neurons and participates in trafficking of Glut1 glucose transporters. Prohibitin may act as a chaperone for the stabilization of mitochondrial proteins. Prokaryotic HflK/C plays a role in the decision between lysogenic and lytic cycle growth during lambda phage infection. Flotillins have been implicated in the progression of prion disease, in the pathogenesis of neurodegenerative diseases such as Parkinson's and Alzheimer's disease and, in cancer invasion and metastasis. Mutations in the podocin gene give rise to autosomal recessive steroid resistant nephritic syndrome.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344746 1072 EEMErllkqahAEKTRLLESRER--------EMEAKKRALEEEKRR---REQLEKRLEE-ETSQRQKLIEKEVKI-REKQ 1138
Cdd:cd03406    169 EAME-------AEKTKLLIAEQHqkvvekeaETERKRAVIEAEKDAevaKIQMQQKIMEkEAEKKISEIEDEMHLaREKA 241

                   ....
gi 2024344746 1139 RAQA 1142
Cdd:cd03406    242 RADA 245

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 2024344746 1184 GFLIKMGGKIKTWKKRWFVFDRNKRTFTYYADKHETKLKGVIYFQAIEEVY-YDHLKNAYKSPNPLLTFSVKTHDRIYYM 1262
Cdd:cd01235      7 GYLYKRGALLKGWKQRWFVLDSTKHQLRYYESREDTKCKGFIDLAEVESVTpATPIIGAPKRADEGAFFDLKTNKRVYNF 86

                           90
                   ....*....|....*
gi 2024344746 1263 VAPTPEAMRIWMDVI 1277
Cdd:cd01235     87 CAFDAESAQQWIEKI 101

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 2024344746 1184 GFLIKMGGKIKTWKKRWFVFdRNKRTFtYYADKHET--KLKGVIYFQAIEEVyydhlknayKSPNPLLTFSVKTHDRIYY 1261
Cdd:cd13282      3 GYLTKLGGKVKTWKRRWFVL-KNGELF-YYKSPNDVirKPQGQIALDGSCEI---------ARAEGAQTFEIVTEKRTYY 71

                           90       100
                   ....*....|....*....|....
gi 2024344746 1262 MVAPTPEAMRIWMDVIVTGAEGYT 1285
Cdd:cd13282     72 LTADSENDLDEWIRVIQNVLRRQA 95

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 2024344746 1182 CRGFLIKMGGKIKTWKKRWFVFDRNKrtFTYYADKHETKLKGVIYFQAIEEVYYdhLKNAyKSPNpllTFSVKTHDRIYY 1261
Cdd:cd13298      8 KSGYLLKRSRKTKNWKKRWVVLRPCQ--LSYYKDEKEYKLRRVINLSELLAVAP--LKDK-KRKN---VFGIYTPSKNLH 79

                           90
                   ....*....|....*.
gi 2024344746 1262 MVAPTPEAMRIWMDVI 1277
Cdd:cd13298     80 FRATSEKDANEWVEAL 95

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 2024344746 1184 GFLIKMGGKI-----KTWKKRWFVFDRNKrtFTYYADKHET-KLKGVIYFQAIEEVYYDHLKnayksPNpllTFSVKTHD 1257
Cdd:cd13296      3 GWLTKKGGGSstlsrRNWKSRWFVLRDTV--LKYYENDQEGeKLLGTIDIRSAKEIVDNDPK-----EN---RLSITTEE 72

                           90       100
                   ....*....|....*....|
gi 2024344746 1258 RIYYMVAPTPEAMRIWMDVI 1277
Cdd:cd13296     73 RTYHLVAESPEDASQWVNVL 92

Tandem PH-domain-containing protein 2 Pleckstrin homology (PH) domain; The binding of TAPP2 (also called PLEKHA2) adaptors to PtdIns(3,4)P(2), but not PI(3,4, 5)P3, function as negative regulators of insulin and PI3K signalling pathways (i.e. TAPP/utrophin/syntrophin complex). TAPP2 contains two sequential PH domains in which the C-terminal PH domain specifically binds PtdIns(3,4)P2 with high affinity. The N-terminal PH domain does not interact with any phosphoinositide tested. They also contain a C-terminal PDZ-binding motif that interacts with several PDZ-binding proteins, including PTPN13 (known previously as PTPL1 or FAP-1) as well as the scaffolding proteins MUPP1 (multiple PDZ-domain-containing protein 1), syntrophin and utrophin. The members here are most sequence similar to TAPP2 proteins, but may not be actual TAPP2 proteins. 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 2024344746 1184 GFLIKMGGKIKTWKKRWFVFdRNKRtFTYYADKHETKLKGVIYFQAIEEVYYDHLKnayKSPNpllTFSVKTHDRIYYMV 1263
Cdd:cd13255     10 GYLEKKGERRKTWKKRWFVL-RPTK-LAYYKNDKEYRLLRLIDLTDIHTCTEVQLK---KHDN---TFGIVTPARTFYVQ 81

                           90
                   ....*....|....
gi 2024344746 1264 APTPEAMRIWMDVI 1277
Cdd:cd13255     82 ADSKAEMESWISAI 95

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 2024344746 1184 GFLIKMGGK-IKTWKKRWFVFDRNKRTFTYYADKHETKLKGVIYFQAIEEVYYDHLKnayKSPNpllTFSVKT-HDRIYY 1261
Cdd:cd00821      3 GYLLKRGGGgLKSWKKRWFVLFEGVLLYYKSKKDSSYKPKGSIPLSGILEVEEVSPK---ERPH---CFELVTpDGRTYY 76

                           90
                   ....*....|....*.
gi 2024344746 1262 MVAPTPEAMRIWMDVI 1277
Cdd:cd00821     77 LQADSEEERQEWLKAL 92

Grb2-associated binding protein family pleckstrin homology (PH) domain; The Gab subfamily includes several Gab proteins, Drosophila DOS and C. elegans SOC-1. They are scaffolding adaptor proteins, which possess N-terminal PH domains and a C-terminus with proline-rich regions and multiple phosphorylation sites. Following activation of growth factor receptors, Gab proteins are tyrosine phosphorylated and activate PI3K, which generates 3-phosphoinositide lipids. By binding to these lipids via the PH domain, Gab proteins remain in proximity to the receptor, leading to further signaling. While not all Gab proteins depend on the PH domain for recruitment, it is required for Gab activity. Members here include insect, nematodes, and crustacean Gab2s. 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 2024344746 1196 WKKRWFVFDRNK---RTF-TYYADKHETKLKGVIYFQAIEEV----YYDHLKNAYKSpnplLTFSVKTHDRIYYMVAPTP 1267
Cdd:cd13384     23 WRRRYFVLRQSEipgQYFlEYYTDRTCRKLKGSIDLDQCEQVdaglTFETKNKLKDQ----HIFDIRTPKRTYYLVADTE 98

                           90
                   ....*....|..
gi 2024344746 1268 EAMRIWMDVIVT 1279
Cdd:cd13384     99 DEMNKWVNCICT 110

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 2024344746 1176 SLTEKTCRGFLIKMGGK-IKTWKKRWFVFdrNKRTFTYYADKHETKLKGVIY---FQAIEEVYYDHLKNAYkspnpllTF 1251
Cdd:cd13248      3 PNAPVVMSGWLHKQGGSgLKNWRKRWFVL--KDNCLYYYKDPEEEKALGSILlpsYTISPAPPSDEISRKF-------AF 73

                           90       100
                   ....*....|....*....|....*..
gi 2024344746 1252 SV-KTHDRIYYMVAPTPEAMRIWMDVI 1277
Cdd:cd13248     74 KAeHANMRTYYFAADTAEEMEQWMNAM 100

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344746  601 DQRGQELTRLEEERIVILNNLEELEQKIKDLNDQMDESSRELDMECALLDGEQKSETTELLKEKEILDHLNRKIAELERN 680
Cdd:COG1196    333 EELEEELEELEEELEEAEEELEEAEAELAEAEEALLEAEAELAEAEEELEELAEELLEALRAAAELAAQLEELEEAEEAL 412

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344746  681 V-----IGEKAKDADLLDIESKHFEDLEFQQLEHESRLDEEKENLTQQLLREVAEYQRSIVSRKEKISALKKQANHIVQQ 755
Cdd:COG1196    413 LerlerLEEELEELEEALAELEEEEEEEEEALEEAAEEEAELEEEEEALLELLAELLEEAALLEAALAELLEELAEAAAR 492

                   ....*.
gi 2024344746  756 AQREQD 761
Cdd:COG1196    493 LLLLLE 498

Grb2-associated binding protein 3 pleckstrin homology (PH) domain; The Gab subfamily includes several Gab proteins, Drosophila DOS and C. elegans SOC-1. They are scaffolding adaptor proteins, which possess N-terminal PH domains and a C-terminus with proline-rich regions and multiple phosphorylation sites. Following activation of growth factor receptors, Gab proteins are tyrosine phosphorylated and activate PI3K, which generates 3-phosphoinositide lipids. By binding to these lipids via the PH domain, Gab proteins remain in proximity to the receptor, leading to further signaling. While not all Gab proteins depend on the PH domain for recruitment, it is required for Gab activity. The members in this cd include the Gab1, Gab2, and Gab3 proteins. 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 2024344746 1182 CRGFLIKMGGKIK----TWKKRWFVFDR-----NKRTFTYYADKHETKLKGVIYFQAIEEVYY---DHLKNAYKSPnplL 1249
Cdd:cd13385      8 CTGWLIKSPPERKlkryAWRKRWFVLRRgrmsgNPDVLEYYRNNHSKKPIRVIDLSECEVLKHsgpNFIRKEFQNN---F 84

                           90       100
                   ....*....|....*....|....*...
gi 2024344746 1250 TFSVKTHDRIYYMVAPTPEAMRIWMDVI 1277
Cdd:cd13385     85 VFIVKTTYRTFYLVAKTEEEMQVWVHNI 112

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344746  602 QRGQELTRLEEERIVILNNLEELEQKIKDLNDQMDESSRELDM-----ECALLDGEQKSETTELLKEKEILDHLNRKIAE 676
Cdd:COG4717     78 EELKEAEEKEEEYAELQEELEELEEELEELEAELEELREELEKlekllQLLPLYQELEALEAELAELPERLEELEERLEE 157

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344746  677 LERNVIGEKAKDADLLDIESKHFEDLEFQQLEHESRLDEEKENLtQQLLREVAEYQRSIVSRKEKISALKKQANHIVQQA 756
Cdd:COG4717    158 LRELEEELEELEAELAELQEELEELLEQLSLATEEELQDLAEEL-EELQQRLAELEEELEEAQEELEELEEELEQLENEL 236

                   ....*
gi 2024344746  757 QREQD 761
Cdd:COG4717    237 EAAAL 241

RAS p21 protein activator (GTPase activating protein) 1 Pleckstrin homology (PH) domain; RASA1 (also called RasGap1 or p120) is a member of the RasGAP family of GTPase-activating proteins. RASA1 contains N-terminal SH2-SH3-SH2 domains, followed by two C2 domains, a PH domain, a RasGAP domain, and a BTK domain. Splice variants lack the N-terminal domains. It is a cytosolic vertebrate protein that acts as a suppressor of RAS via its C-terminal GAP domain function, enhancing the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS, allowing control of cellular proliferation and differentiation. Additionally, it is involved in mitogenic signal transmission towards downstream interacting partners through its N-terminal SH2-SH3-SH2 domains. RASA1 interacts with a number of proteins including: G3BP1, SOCS3, ANXA6, Huntingtin, KHDRBS1, Src, EPHB3, EPH receptor B2, Insulin-like growth factor 1 receptor, PTK2B, DOK1, PDGFRB, HCK, Caveolin 2, DNAJA3, HRAS, GNB2L1 and NCK1. 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 2024344746 1183 RGFLIKMGGKIKTWKKRWFVFDRNKRTFTYYADKHETKLKGVI-----YFQAIEEVYYDHlknayksPNPL-LTFSVKTH 1256
Cdd:cd13260      6 KGYLLKKGGKNKKWKNLYFVLEGKEQHLYFFDNEKRTKPKGLIdlsycSLYPVHDSLFGR-------PNCFqIVVRALNE 78

                           90
                   ....*....|....*....
gi 2024344746 1257 DRIYYMVAPTPEAMRIWMD 1275
Cdd:cd13260     79 STITYLCADTAELAQEWMR 97

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344746  605 QELTRLEEERIVILNNLEELEQKIKDLNDQMDESSRELDMECALLDGEQKSETTELLKEKEILDHLNRKIAELERNVIGE 684
Cdd:COG1196    309 ERRRELEERLEELEEELAELEEELEELEEELEELEEELEEAEEELEEAEAELAEAEEALLEAEAELAEAEEELEELAEEL 388

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2024344746  685 KAKDADLLDIESK--HFEDLEFQQLEHESRLDEEKENLTQQLLREVAEYQRSIVSRKEKISALKKQANHIVQQAQREQD 761
Cdd:COG1196    389 LEALRAAAELAAQleELEEAEEALLERLERLEEELEELEEALAELEEEEEEEEEALEEAAEEEAELEEEEEALLELLAE 467

Uncharacterized coiled-coil protein, contains DUF342 domain [Function unknown];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344746  606 ELTRLEEERIVILNNLEELEQKIKDLNDQMDESSRELDmecaLLDGEQKSETTELLKEKEILDHLNRKIAEL--ERNVIG 683
Cdd:COG1340      9 SLEELEEKIEELREEIEELKEKRDELNEELKELAEKRD----ELNAQVKELREEAQELREKRDELNEKVKELkeERDELN 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344746  684 EKAKD----------------ADLLDIE--SKHFEDLEFQQ------LEHESRLDEEKENLTQQL--LREVAEYQRSIVS 737
Cdd:COG1340     85 EKLNElreeldelrkelaelnKAGGSIDklRKEIERLEWRQqtevlsPEEEKELVEKIKELEKELekAKKALEKNEKLKE 164

                          170
                   ....*....|....*...
gi 2024344746  738 RKEKISALKKQANHIVQQ 755
Cdd:COG1340    165 LRAELKELRKEAEEIHKK 182

Ezrin/radixin/moesin, alpha-helical domain; The ERM family consists of three closely-related proteins, ezrin, radixin and moesin. Ezrin was first identified as a constituent of microvilli, radixin as a barbed, end-capping actin-modulating protein from isolated junctional fractions, and moesin as a heparin binding protein. A tumour suppressor molecule responsible for neurofibromatosis type 2 (NF2) is highly similar to ERM proteins and has been designated merlin (moesin-ezrin-radixin-like protein). ERM molecules contain 3 domains, an N-terminal globular domain, an extended alpha-helical domain and a charged C-terminal domain (pfam00769). Ezrin, radixin and merlin also contain a polyproline linker region between the helical and C-terminal domains. The N-terminal domain is highly conserved and is also found in merlin, band 4.1 proteins and members of the band 4.1 superfamily, designated the FERM domain. ERM proteins crosslink actin filaments with plasma membranes. They co-localize with CD44 at actin filament plasma membrane interaction sites, associating with CD44 via their N-terminal domains and with actin filaments via their C-terminal domains. This is the alpha-helical domain, which is involved in intramolecular masking of protein-protein interaction sites, regulating the activity of this proteins.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2024344746 1070 RIEEMERLLKQAHAEKtRLLESREREMEAKKRALEEEKRR----REQLEKRLEEETSQRQKLI-EKEVKIREKQRAQAR 1143
Cdd:pfam20492   35 TAEELEEERRQAEEEA-ERLEQKRQEAEEEKERLEESAEMeaeeKEQLEAELAEAQEEIARLEeEVERKEEEARRLQEE 112

ArfGAP with dual PH domains Pleckstrin homology (PH) domain, repeat 2; ADAP (also called centaurin alpha) is a phophatidlyinositide binding protein consisting of an N-terminal ArfGAP domain and two PH domains. In response to growth factor activation, PI3K phosphorylates phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol 3,4,5-trisphosphate. Centaurin alpha 1 is recruited to the plasma membrane following growth factor stimulation by specific binding of its PH domain to phosphatidylinositol 3,4,5-trisphosphate. Centaurin alpha 2 is constitutively bound to the plasma membrane since it binds phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate with equal affinity. This cd contains the second PH domain 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 2024344746 1184 GFLIKMGGKIKT-WKKRWFVFDRnkRTFTYYADKHETKLKGVIYFQAIEEVYY------DHLKNAYKSPnplltFSVKTH 1256
Cdd:cd01251      6 GYLEKTGPKQTDgFRKRWFTLDD--RRLMYFKDPLDAFPKGEIFIGSKEEGYSvreglpPGIKGHWGFG-----FTLVTP 78

                           90       100
                   ....*....|....*....|.
gi 2024344746 1257 DRIYYMVAPTPEAMRIWMDVI 1277
Cdd:cd01251     79 DRTFLLSAETEEERREWITAI 99

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 2024344746  605 QELTRLEEERIVILNNLEELEQKIKDLNDQMDESSRELDMECALLDgEQKSETTELLKEKEiLDHLNRKIAELERNVigE 684
Cdd:COG1579     31 AELAELEDELAALEARLEAAKTELEDLEKEIKRLELEIEEVEARIK-KYEEQLGNVRNNKE-YEALQKEIESLKRRI--S 106

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2024344746  685 KAKDaDLLDIESKHfEDLEFQQLEHESRLDEEKENL---TQQLLREVAEYQRSIVSRKEKISALKKQ 748
Cdd:COG1579    107 DLED-EILELMERI-EELEEELAELEAELAELEAELeekKAELDEELAELEAELEELEAEREELAAK 171