Pleckstrin homology-like domain-containing family B member 2 pleckstrin homology (PH) domain; PHLDB2 (also called LL5beta) and PHLDB1 (also called LL5alpha) are cytoskeleton- and membrane-associated proteins. PHLDB2 has been identified as a key component of the synaptic podosomes that play an important role in in postsynaptic maturation. Both are large proteins containing an N-terminal pleckstrin (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 2024344744 1209 TEKTCRGFLIKMGGKIKTWKKRWFVFDRNKRTFTYYADKHETKLKGVIYFQAIEEVYYDHLKNAYKSPNPLLTFSVKTHD 1288
Cdd:cd14673      1 SSKRCRGFLTKMGGKIKTWKKRWFVFDRNKRTLSYYVDKHEKKLKGVIYFQAIEEVYYDHLRSAAKSPNPALTFCVKTHD 80

                           90       100
                   ....*....|....*....|....*
gi 2024344744 1289 RIYYMVAPTPEAMRIWMDVIVTGAE 1313
Cdd:cd14673     81 RLYYMVAPSPEAMRIWMDVIVTGAE 105

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 2024344744 1101 RIEEMERLLKQAHAEKtRLLESREREMEAKKRALEEEKRR----REQLEKRLEEETSQRQKLI-EKEVKIREKQRAQAR 1174
Cdd:pfam20492   35 TAEELEEERRQAEEEA-ERLEQKRQEAEEEKERLEESAEMeaeeKEQLEAELAEAQEEIARLEeEVERKEEEARRLQEE 112

Pleckstrin homology-like domain-containing family B member 2 pleckstrin homology (PH) domain; PHLDB2 (also called LL5beta) and PHLDB1 (also called LL5alpha) are cytoskeleton- and membrane-associated proteins. PHLDB2 has been identified as a key component of the synaptic podosomes that play an important role in in postsynaptic maturation. Both are large proteins containing an N-terminal pleckstrin (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 2024344744 1209 TEKTCRGFLIKMGGKIKTWKKRWFVFDRNKRTFTYYADKHETKLKGVIYFQAIEEVYYDHLKNAYKSPNPLLTFSVKTHD 1288
Cdd:cd14673      1 SSKRCRGFLTKMGGKIKTWKKRWFVFDRNKRTLSYYVDKHEKKLKGVIYFQAIEEVYYDHLRSAAKSPNPALTFCVKTHD 80

                           90       100
                   ....*....|....*....|....*
gi 2024344744 1289 RIYYMVAPTPEAMRIWMDVIVTGAE 1313
Cdd:cd14673     81 RLYYMVAPSPEAMRIWMDVIVTGAE 105

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344744  590 QRGQELTRLEEERIVILNNLEELEQKIKDLNDQMDESSRELdmecALLDGEQKSETTELLKEKEILDHLNRKIAELERNv 669
Cdd:COG1196    292 ELLAELARLEQDIARLEERRRELEERLEELEEELAELEEEL----EELEEELEELEEELEEAEEELEEAEAELAEAEEA- 366

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344744  670 igEKAKEKLKLDAEREKLERLQELYSEQKTQLDNcpESMREQLQQQLKRDADLLDIESKHFEDLEFQQLEHESRLDEEKE 749
Cdd:COG1196    367 --LLEAEAELAEAEEELEELAEELLEALRAAAEL--AAQLEELEEAEEALLERLERLEEELEELEEALAELEEEEEEEEE 442

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2024344744  750 NLtQQLLREVAEYQRSIVSRKEKISALKKQANHIVQQAQREQDHFVKEKNNLIMMLQREKE 810
Cdd:COG1196    443 AL-EEAAEEEAELEEEEEALLELLAELLEEAALLEAALAELLEELAEAAARLLLLLEAEAD 502

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344744  608 NLEELEQKIKDLNDQMDESSRELDMEC---ALLDGEQKSETTELLKEKEILD----HLNRKIAELERnvigEKAKEKLKL 680
Cdd:TIGR02169  185 NIERLDLIIDEKRQQLERLRREREKAEryqALLKEKREYEGYELLKEKEALErqkeAIERQLASLEE----ELEKLTEEI 260

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344744  681 DAEREKLERLQELYSEQKTQLDncPESMREQLQQQlkrdADLLDIESK-------------HFEDLEFQQLEHESRLDEE 747
Cdd:TIGR02169  261 SELEKRLEEIEQLLEELNKKIK--DLGEEEQLRVK----EKIGELEAEiaslersiaekerELEDAEERLAKLEAEIDKL 334

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2024344744  748 KENLTqQLLREVAEYQRSIVSRKEKISALKKQANHIVQQAQREQDHF------VKEKNNLIMMLQREKENL 812
Cdd:TIGR02169  335 LAEIE-ELEREIEEERKRRDKLTEEYAELKEELEDLRAELEEVDKEFaetrdeLKDYREKLEKLKREINEL 404

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 2024344744 1101 RIEEMERLLKQAHAEKtRLLESREREMEAKKRALEEEKRR----REQLEKRLEEETSQRQKLI-EKEVKIREKQRAQAR 1174
Cdd:pfam20492   35 TAEELEEERRQAEEEA-ERLEQKRQEAEEEKERLEESAEMeaeeKEQLEAELAEAQEEIARLEeEVERKEEEARRLQEE 112

Coiled-coil domain-containing protein 158; CCDC158 is a family of proteins found in eukaryotes. The function is not known.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344744  584 ECTSDDQRGQELTRLEEERIVILNN---LEELEQKIKDLNDQMDESSRELDMECALLDGEQKSETTELLKEKEI-LDHLN 659
Cdd:pfam15921  158 KCLKEDMLEDSNTQIEQLRKMMLSHegvLQEIRSILVDFEEASGKKIYEHDSMSTMHFRSLGSAISKILRELDTeISYLK 237

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344744  660 RKIAELERNVIGEKAKEKLKLDAE-REKLERLQELYSEQKTQLDNCPE---SMREQ---LQQQLkrdaDLLDIESKHFED 732
Cdd:pfam15921  238 GRIFPVEDQLEALKSESQNKIELLlQQHQDRIEQLISEHEVEITGLTEkasSARSQansIQSQL----EIIQEQARNQNS 313

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344744  733 LEFQQLEhesrldeEKENLTQQLLREVAEYQRSIvsrKEKISALKKQ---ANHIVQQAQREQDHFVKEKNNLIMMLQREK 809
Cdd:pfam15921  314 MYMRQLS-------DLESTVSQLRSELREAKRMY---EDKIEELEKQlvlANSELTEARTERDQFSQESGNLDDQLQKLL 383

                          250
                   ....*....|.
gi 2024344744  810 ENLCNLEKKYS 820
Cdd:pfam15921  384 ADLHKREKELS 394

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344744 1100 ARIEEMERLLKQAHAEKTRllesREREMEAKKRALEEEKRRREQLEKRLE----EETSQRQKLIEKEVKIREKQRA 1171
Cdd:TIGR02169  681 ERLEGLKRELSSLQSELRR----IENRLDELSQELSDASRKIGEIEKEIEqleqEEEKLKERLEELEEDLSSLEQE 752

phosphodiesterase; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344744 1103 EEMERLLKQAHAE-----KTRLLESRErEMEAKKRALEEEKRRREQLEKRLEEETSQRQKLIEKEVKIREKQRAQARPLT 1177
Cdd:PRK12704    38 EEAKRILEEAKKEaeaikKEALLEAKE-EIHKLRNEFEKELRERRNELQKLEKRLLQKEENLDRKLELLEKREEELEKKE 116

                           90
                   ....*....|...
gi 2024344744 1178 RYLPIRKEDFDLR 1190
Cdd:PRK12704   117 KELEQKQQELEKK 129

Pleckstrin homology-like domain-containing family B member 2 pleckstrin homology (PH) domain; PHLDB2 (also called LL5beta) and PHLDB1 (also called LL5alpha) are cytoskeleton- and membrane-associated proteins. PHLDB2 has been identified as a key component of the synaptic podosomes that play an important role in in postsynaptic maturation. Both are large proteins containing an N-terminal pleckstrin (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 2024344744 1209 TEKTCRGFLIKMGGKIKTWKKRWFVFDRNKRTFTYYADKHETKLKGVIYFQAIEEVYYDHLKNAYKSPNPLLTFSVKTHD 1288
Cdd:cd14673      1 SSKRCRGFLTKMGGKIKTWKKRWFVFDRNKRTLSYYVDKHEKKLKGVIYFQAIEEVYYDHLRSAAKSPNPALTFCVKTHD 80

                           90       100
                   ....*....|....*....|....*
gi 2024344744 1289 RIYYMVAPTPEAMRIWMDVIVTGAE 1313
Cdd:cd14673     81 RLYYMVAPSPEAMRIWMDVIVTGAE 105

Grb2-associated binding protein family Pleckstrin homology (PH) domain; Gab proteins 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. There are 3 families: Gab1, Gab2, and Gab3. 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 2024344744 1213 CRGFLIKM--GGKIKT--WKKRWFVFDRNKRT-----FTYYADKHETKLKGVIYFQAIEEVyyDH-LKNAYKSPNPLLTF 1282
Cdd:cd13324      3 YEGWLTKSppEKKIWRaaWRRRWFVLRSGRLSggqdvLEYYTDDHCKKLKGIIDLDQCEQV--DAgLTFEKKKFKNQFIF 80

                           90       100
                   ....*....|....*....|....*.
gi 2024344744 1283 SVKTHDRIYYMVAPTPEAMRIWMDVI 1308
Cdd:cd13324     81 DIRTPKRTYYLVAETEEEMNKWVRCI 106

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 2024344744 1215 GFLIKMGGKIKTWKKRWFVFDRNKrtFTYYADKHETKLKGVIYFQAIEEVYYDHlknaykSPNPLLTFSVKTHDRIYYMV 1294
Cdd:cd10573      7 GYLTKLGGIVKNWKTRWFVLRRNE--LKYFKTRGDTKPIRVLDLRECSSVQRDY------SQGKVNCFCLVFPERTFYMY 78

                           90
                   ....*....|....
gi 2024344744 1295 APTPEAMRIWMDVI 1308
Cdd:cd10573     79 ANTEEEADEWVKLL 92

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 2024344744 1215 GFLIKMGGKI-----KTWKKRWFVFDRNKrtFTYYADKHET-KLKGVIYFQAIEEVYYDHLKnayksPNpllTFSVKTHD 1288
Cdd:cd13296      3 GWLTKKGGGSstlsrRNWKSRWFVLRDTV--LKYYENDQEGeKLLGTIDIRSAKEIVDNDPK-----EN---RLSITTEE 72

                           90       100
                   ....*....|....*....|
gi 2024344744 1289 RIYYMVAPTPEAMRIWMDVI 1308
Cdd:cd13296     73 RTYHLVAESPEDASQWVNVL 92

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344744  590 QRGQELTRLEEERIVILNNLEELEQKIKDLNDQMDESSRELdmecALLDGEQKSETTELLKEKEILDHLNRKIAELERNv 669
Cdd:COG1196    292 ELLAELARLEQDIARLEERRRELEERLEELEEELAELEEEL----EELEEELEELEEELEEAEEELEEAEAELAEAEEA- 366

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344744  670 igEKAKEKLKLDAEREKLERLQELYSEQKTQLDNcpESMREQLQQQLKRDADLLDIESKHFEDLEFQQLEHESRLDEEKE 749
Cdd:COG1196    367 --LLEAEAELAEAEEELEELAEELLEALRAAAEL--AAQLEELEEAEEALLERLERLEEELEELEEALAELEEEEEEEEE 442

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2024344744  750 NLtQQLLREVAEYQRSIVSRKEKISALKKQANHIVQQAQREQDHFVKEKNNLIMMLQREKE 810
Cdd:COG1196    443 AL-EEAAEEEAELEEEEEALLELLAELLEEAALLEAALAELLEELAEAAARLLLLLEAEAD 502

General Receptor for Phosphoinositides-1-like Pleckstrin homology (PH) domain; GRP1/cytohesin3 and the related proteins ARNO (ARF nucleotide-binding site opener)/cytohesin-2 and cytohesin-1 are ARF exchange factors that contain a pleckstrin homology (PH) domain thought to target these proteins to cell membranes through binding polyphosphoinositides. The PH domains of all three proteins exhibit relatively high affinity for PtdIns(3,4,5)P3. Within the Grp1 family, diglycine (2G) and triglycine (3G) splice variants, differing only in the number of glycine residues in the PH domain, strongly influence the affinity and specificity for phosphoinositides. The 2G variants selectively bind PtdIns(3,4,5)P3 with high affinity,the 3G variants bind PtdIns(3,4,5)P3 with about 30-fold lower affinity and require the polybasic region for plasma membrane targeting. These ARF-GEFs share a common, tripartite structure consisting of an N-terminal coiled-coil domain, a central domain with homology to the yeast protein Sec7, a PH domain, and a C-terminal polybasic region. The Sec7 domain is autoinhibited by conserved elements proximal to the PH domain. GRP1 binds to the DNA binding domain of certain nuclear receptors (TRalpha, TRbeta, AR, ER, but not RXR), and can repress thyroid hormone receptor (TR)-mediated transactivation by decreasing TR-complex formation on thyroid hormone response elements. ARNO promotes sequential activation of Arf6, Cdc42 and Rac1 and insulin secretion. Cytohesin acts as a PI 3-kinase effector mediating biological responses including cell spreading and adhesion, chemotaxis, protein trafficking, and cytoskeletal rearrangements, only some of which appear to depend on their ability to activate ARFs. 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 2024344744 1215 GFLIKMGGKIKTWKKRWFVFDRNKRTFTYYADKHETklKGVIYFQAIeEVYYDHLKNA------YKSPNPLLTFSVKT-- 1286
Cdd:cd01252      7 GWLLKLGGRVKSWKRRWFILTDNCLYYFEYTTDKEP--RGIIPLENL-SVREVEDKKKpfcfelYSPSNGQVIKACKTds 83

                           90       100       110
                   ....*....|....*....|....*....|
gi 2024344744 1287 --------HDrIYYMVAPTPEAMRIWMDVI 1308
Cdd:cd01252     84 dgkvvegnHT-VYRISAASEEERDEWIKSI 112

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 2024344744 1215 GFLIKMGGKIKTWKKRWFVFdRNKRtFTYYADKHETKLKGVIYFQAIEEVYYDHLKnayKSPNpllTFSVKTHDRIYYMV 1294
Cdd:cd13255     10 GYLEKKGERRKTWKKRWFVL-RPTK-LAYYKNDKEYRLLRLIDLTDIHTCTEVQLK---KHDN---TFGIVTPARTFYVQ 81

                           90
                   ....*....|....
gi 2024344744 1295 APTPEAMRIWMDVI 1308
Cdd:cd13255     82 ADSKAEMESWISAI 95

PH domain; PH stands for pleckstrin homology.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344744 1212 TCRGFLIKMGGKIK-TWKKRWFVFDRNkrTFTYYADK---HETKLKGVIYFQAIEEVYYDHLKNAyKSPNPL-LTFSVKT 1286
Cdd:pfam00169    2 VKEGWLLKKGGGKKkSWKKRYFVLFDG--SLLYYKDDksgKSKEPKGSISLSGCEVVEVVASDSP-KRKFCFeLRTGERT 78

                           90       100
                   ....*....|....*....|..
gi 2024344744 1287 HDRIYYMVAPTPEAMRIWMDVI 1308
Cdd:pfam00169   79 GKRTYLLQAESEEERKDWIKAI 100

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 2024344744 1215 GFLIKMGGK-IKTWKKRWFVFDRNKRTFTYYADKHETKLKGVIYFQAIEEVYYDHLKnayKSPNpllTFSVKT-HDRIYY 1292
Cdd:cd00821      3 GYLLKRGGGgLKSWKKRWFVLFEGVLLYYKSKKDSSYKPKGSIPLSGILEVEEVSPK---ERPH---CFELVTpDGRTYY 76

                           90
                   ....*....|....*.
gi 2024344744 1293 MVAPTPEAMRIWMDVI 1308
Cdd:cd00821     77 LQADSEEERQEWLKAL 92

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344744  589 DQRGQELTRLEEER------------------IVILNNLEELEQKIKDLNDQMDESSRELDMECALLDgEQKSETTELLK 650
Cdd:TIGR02169  194 DEKRQQLERLRRERekaeryqallkekreyegYELLKEKEALERQKEAIERQLASLEEELEKLTEEIS-ELEKRLEEIEQ 272

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344744  651 EkeiLDHLNRKIAELERNVIGEKAKEKLKLDAEREKLERLQELYSEQKTQLDNcpesmrEQLQQQLKRDADLLDIESKHf 730
Cdd:TIGR02169  273 L---LEELNKKIKDLGEEEQLRVKEKIGELEAEIASLERSIAEKERELEDAEE------RLAKLEAEIDKLLAEIEELE- 342

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344744  731 EDLEFQQLEHESRLDE-----EKENLTQQLLREV----AEYQRSIVSRKEKISALKKQANHIvqqaQREQDHFVKEKNNL 801
Cdd:TIGR02169  343 REIEEERKRRDKLTEEyaelkEELEDLRAELEEVdkefAETRDELKDYREKLEKLKREINEL----KRELDRLQEELQRL 418

                          250
                   ....*....|....*..
gi 2024344744  802 IMMLQREKENLCNLEKK 818
Cdd:TIGR02169  419 SEELADLNAAIAGIEAK 435

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344744  589 DQRGQELTRLEEERIVILNNLEELEQKIKDLNDQMDESSRELDMECALLDGEQKSETTELLKEKEILDHLNRKIAELERN 668
Cdd:COG1196    333 EELEEELEELEEELEEAEEELEEAEAELAEAEEALLEAEAELAEAEEELEELAEELLEALRAAAELAAQLEELEEAEEAL 412

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344744  669 VIGEKAKEKLKLDAEREKLERLQELYSEQKTQLdncpESMREQLQQQLKRDADLLDIESKHFEDLEFQQLEHESRLDEEK 748
Cdd:COG1196    413 LERLERLEEELEELEEALAELEEEEEEEEEALE----EAAEEEAELEEEEEALLELLAELLEEAALLEAALAELLEELAE 488

                          170
                   ....*....|...
gi 2024344744  749 ENLTQQLLREVAE 761
Cdd:COG1196    489 AAARLLLLLEAEA 501

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344744  590 QRGQEL-TRLEE-ERIVILNNLEELEQKIKDLNDQMDESSRELDmecalldgeqksETTELLKEKEI-LDHLNRKIAELE 666
Cdd:TIGR02168  213 ERYKELkAELRElELALLVLRLEELREELEELQEELKEAEEELE------------ELTAELQELEEkLEELRLEVSELE 280

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344744  667 RNvIGEKAKEKLKLDAEREKLERLQELYSEQKTQLDNCPESM---REQLQQQLKRDADLLDIESKHFEDLEFQQLEHESR 743
Cdd:TIGR02168  281 EE-IEELQKELYALANEISRLEQQKQILRERLANLERQLEELeaqLEELESKLDELAEELAELEEKLEELKEELESLEAE 359

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2024344744  744 LDE---EKENLTQQL--LREVAEYQRS-IVSRKEKISALKKQANHI---VQQAQREQDHFVKEKNNLIMMLQR 807
Cdd:TIGR02168  360 LEEleaELEELESRLeeLEEQLETLRSkVAQLELQIASLNNEIERLearLERLEDRRERLQQEIEELLKKLEE 432

Septal ring factor EnvC, activator of murein hydrolases AmiA and AmiB [Cell cycle control, cell division, chromosome partitioning];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344744  589 DQRGQELTRLEEERIVILNNLEELEQKIKDLNDQMDESSRELdmecALLDGEQKSETTELLKEKEILDHLNRKIAELERN 668
Cdd:COG4942     37 AELEKELAALKKEEKALLKQLAALERRIAALARRIRALEQEL----AALEAELAELEKEIAELRAELEAQKEELAELLRA 112

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344744  669 V--IGEKAKEKLKLDAER-EKLERLQELYSEQKTQLDNCPESMREQlQQQLKRDADLLDIESKHFEDLEFQQLEHESRLD 745
Cdd:COG4942    113 LyrLGRQPPLALLLSPEDfLDAVRRLQYLKYLAPARREQAEELRAD-LAELAALRAELEAERAELEALLAELEEERAALE 191

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2024344744  746 ---EEKENLTQQLLREVAEYQRSIVSRKEKISALKKQANHIVQQAQREQ-----DHFVKEKNNLIM 803
Cdd:COG4942    192 alkAERQKLLARLEKELAELAAELAELQQEAEELEALIARLEAEAAAAAertpaAGFAALKGKLPW 257

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 2024344744 1207 SLTEKTCRGFLIKMGGK-IKTWKKRWFVFdrNKRTFTYYADKHETKLKGVIY---FQAIEEVYYDHLKNAYkspnpllTF 1282
Cdd:cd13248      3 PNAPVVMSGWLHKQGGSgLKNWRKRWFVL--KDNCLYYYKDPEEEKALGSILlpsYTISPAPPSDEISRKF-------AF 73

                           90       100
                   ....*....|....*....|....*..
gi 2024344744 1283 SV-KTHDRIYYMVAPTPEAMRIWMDVI 1308
Cdd:cd13248     74 KAeHANMRTYYFAADTAEEMEQWMNAM 100

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344744  589 DQRGQELTRLEEERIVILNNLEEL-------EQKIKDLNDQMDESSRELdmecalldgeqKSETTELLKEKEILDHLNRK 661
Cdd:TIGR02168  750 AQLSKELTELEAEIEELEERLEEAeeelaeaEAEIEELEAQIEQLKEEL-----------KALREALDELRAELTLLNEE 818

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024344744  662 IAELE------RNVIGEKAKEKLKLDAEREKLERLQELYSEQKTQLDNCPESMREQLQQQLKRDADL---LDIESKHFED 732
Cdd:TIGR02168  819 AANLRerleslERRIAATERRLEDLEEQIEELSEDIESLAAEIEELEELIEELESELEALLNERASLeeaLALLRSELEE 898