Antibiotic biosynthesis monooxygenase; This domain is found in monooxygenases involved in the biosynthesis of several antibiotics by Streptomyces species. It's occurrence as a repeat in Streptomyces coelicolor SCO1909 is suggestive that the other proteins function as multimers. There is also a conserved histidine which is likely to be an active site residue.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 530418307  244 LMAQRQVQVAEEGLQDFHRALRCYVDFTGAQSHCLHVSA-QKMLDGASFTLYEFWQDEASWRRHQQSPGSKAFQ 316
Cdd:pfam03992   1 IVVVAEIRVKPGKAEEFEEALAELVEATRNEPGCLSYELlRSLEDPDEYVVLEVWEDEAAFEAHLQSPHFKAAH 74

EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11) isozymes; PI-PLC isozymes are signaling enzymes that hydrolyze the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. This family corresponds to the four EF-hand motifs containing PI-PLC isozymes, including PI-PLC-beta (1-4), -gamma (1-2), -delta (1,3,4), -epsilon (1), -zeta (1), eta (1-2). Lower eukaryotes such as yeast and slime molds contain only delta-type isozymes. In contrast, other types of isoforms present in higher eukaryotes. This family also includes 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase 1 (PLC1) from fungi. Some homologs from plants contain only two atypical EF-hand motifs and they are not included. All PI-PLC isozymes except sperm-specific PI-PLC-zeta share a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C2 domain. PI-PLC-zeta lacks the PH domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Most of EF-hand motifs found in PI-PLCs consist of a helix-loop-helix structure, but lack residues critical to metal binding. Moreover, the EF-hand region of most of PI-PLCs may have an important regulatory function, but it has yet to be identified. However, PI-PLC-zeta is a key exception. It is responsible for Ca2+ oscillations in fertilized oocytes and exhibits a high sensitivity to Ca2+ mediated through its EF-hand domain. In addition, PI-PLC-eta2 shows a canonical EF-loop directing Ca2+-sensitivity and thus can amplify transient Ca2+ signals. Also it appears that PI-PLC-delta1 can regulate the binding of PH domain to PIP2 in a Ca2+-dependent manner through its functionally important EF-hand domains. PI-PLCs can be activated by a variety of extracellular ligands, such as growth factors, hormones, cytokines and lipids. Their activation has been implicated in tumorigenesis and/or metastasis linked to migration, proliferation, growth, inflammation, angiogenesis and actin cytoskeleton reorganization. PI-PLC-beta isozymes are activated by G-protein coupled receptor (GPCR) through different mechanisms. However, PI-PLC-gamma isozymes are activated by receptor tyrosine kinase (RTK), such as Rho and Ras GTPases. In contrast, PI-PLC-epsilon are activated by both GPCR and RTK. PI-PLC-delta1 and PLC-eta 1 are activated by GPCR-mediated calcium mobilization. The activation mechanism for PI-PLC-zeta remains unclear.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418307  45 FRRADKNDDGKLSFEEFQNYFADGVLSLGEL--QELFSGIDGHLTDNLETEKLCDYFSEhlgvyrpvLAALESLNRAvla 122
Cdd:cd16217    6 LRKADKNKDNKMSFKELKDFLKEINIEVDDDyaEKLFKECDKSKSGFLEGEEIEEFYKL--------LTKREEIDVI--- 74

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 530418307 123 amdatkleYERASKVDQFVTR-----FLL---RETVSQLQALQ 157
Cdd:cd16217   75 --------FGEYAKSDGTMSRnnllnFLQeeqREEVAPAYALS 109

Antibiotic biosynthesis monooxygenase; This domain is found in monooxygenases involved in the biosynthesis of several antibiotics by Streptomyces species. It's occurrence as a repeat in Streptomyces coelicolor SCO1909 is suggestive that the other proteins function as multimers. There is also a conserved histidine which is likely to be an active site residue.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 530418307  244 LMAQRQVQVAEEGLQDFHRALRCYVDFTGAQSHCLHVSA-QKMLDGASFTLYEFWQDEASWRRHQQSPGSKAFQ 316
Cdd:pfam03992   1 IVVVAEIRVKPGKAEEFEEALAELVEATRNEPGCLSYELlRSLEDPDEYVVLEVWEDEAAFEAHLQSPHFKAAH 74

EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to the activation or inactivation of target proteins. EF-hands tend to occur in pairs or higher copy numbers.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 530418307  41 FQDVFRRADKNDDGKLSFEEFQNYF--ADGVLSLGELQELFSGID 83
Cdd:cd00051    2 LREAFRLFDKDGDGTISADELKAALksLGEGLSEEEIDEMIREVD 46

EF hand;

                          10        20
                  ....*....|....*....|...
gi 530418307   41 FQDVFRRADKNDDGKLSFEEFQN 63
Cdd:pfam13202   1 LKDTFRQIDLNGDGKISKEELRR 23

EF-hand motif found in phosphoinositide phospholipase C delta 1 (PI-PLC-delta1); PI-PLC-delta1, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-1 (PLCD1), or phospholipase C-III (PLC-III), or phospholipase C-delta-1 (PLC-delta-1), is present in high abundancy in the brain, heart, lung, skeletal muscle and testis. It is activated by high calcium levels generated by other PI-PLC family members, and therefore functions as a calcium amplifier within the cell. PI-PLC-delta1 is required for maintenance of homeostasis in skin and metabolic tissues. Moreover, it is essential in trophoblasts for placental development. Simultaneous loss of PI-PLC-delta1 may cause placental vascular defects, leading to embryonic lethality. PI-PLC-delta1 can be positively or negatively regulated by several binding partners, including p122/Rho GTPase activating protein (RhoGAP), Gha/Transglutaminase II, RalA, and calmodulin. It is involved in Alzheimer's disease and hypertension. Furthermore, PI-PLC-delta1 regulates cell proliferation and cell-cycle progression from G1- to S-phase by control of cyclin E-CDK2 activity and p27 levels. It can be activated by alpha1-adrenoreceptors (AR) in a calcium-dependent manner and may be important for G protein-coupled receptors (GPCR) responses in vascular smooth muscle (VSM). PI-PLC-delta1 may also be involved in noradrenaline (NA)-induced phosphatidylinositol-4,5-bisphosphate (PIP2) hydrolysis and modulate sustained contraction of mesenteric small arteries. In addition, it inhibits thermogenesis and induces lipid accumulation, and therefore contributes to the development of obesity. PI-PLC-delta1 contains a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C-terminal C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. PI-PLC-delta1 can regulate the binding of PH domain to PIP2 in a Ca2+-dependent manner through its functionally important EF-hand domains. In addition, PI-PLC-delta1 possesses a classical leucine-rich nuclear export sequence (NES) located in the EF hand motifs, as well as a nuclear localization signal within its linker region, both of which may be responsible for translocating PI-PLC-delta1 into and out of the cell nucleus.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418307  45 FRRADKNDDGKLSFEEFQNYFADGVLSLGEL--QELFSGIDGHLTDNLETEKLCDYFSEhlgvyrpvLAALESLNRAvla 122
Cdd:cd16217    6 LRKADKNKDNKMSFKELKDFLKEINIEVDDDyaEKLFKECDKSKSGFLEGEEIEEFYKL--------LTKREEIDVI--- 74

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 530418307 123 amdatkleYERASKVDQFVTR-----FLL---RETVSQLQALQ 157
Cdd:cd16217   75 --------FGEYAKSDGTMSRnnllnFLQeeqREEVAPAYALS 109

Antibiotic biosynthesis monooxygenase; This domain is found in monooxygenases involved in the biosynthesis of several antibiotics by Streptomyces species. It's occurrence as a repeat in Streptomyces coelicolor SCO1909 is suggestive that the other proteins function as multimers. There is also a conserved histidine which is likely to be an active site residue.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 530418307  244 LMAQRQVQVAEEGLQDFHRALRCYVDFTGAQSHCLHVSA-QKMLDGASFTLYEFWQDEASWRRHQQSPGSKAFQ 316
Cdd:pfam03992   1 IVVVAEIRVKPGKAEEFEEALAELVEATRNEPGCLSYELlRSLEDPDEYVVLEVWEDEAAFEAHLQSPHFKAAH 74

EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to the activation or inactivation of target proteins. EF-hands tend to occur in pairs or higher copy numbers.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 530418307  41 FQDVFRRADKNDDGKLSFEEFQNYF--ADGVLSLGELQELFSGID 83
Cdd:cd00051    2 LREAFRLFDKDGDGTISADELKAALksLGEGLSEEEIDEMIREVD 46

EF hand;

                          10        20
                  ....*....|....*....|...
gi 530418307   41 FQDVFRRADKNDDGKLSFEEFQN 63
Cdd:pfam13202   1 LKDTFRQIDLNGDGKISKEELRR 23

EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in pairs. Links between disease states and genes encoding EF-hands, particularly the S100 subclass, are emerging. Each motif consists of a 12 residue loop flanked on either side by a 12 residue alpha-helix. EF-hands undergo a conformational change unpon binding calcium ions.

                           10        20
                   ....*....|....*....|.
gi 530418307    41 FQDVFRRADKNDDGKLSFEEF 61
Cdd:smart00054   2 LKEAFRLFDKDGDGKIDFEEF 22

EF-hand domain;

                          10        20
                  ....*....|....*....|....*
gi 530418307   41 FQDVFRRADKNDDGKLSFEEFQNYF 65
Cdd:pfam13405   2 LREAFKLFDKDGDGKISLEELRKAL 26

EF-hand domain pair;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 530418307   42 QDVFRRADKNDDGKLSFEEFQNYFA----DGVLSLGELQELFSGID 83
Cdd:pfam13499   5 KEAFKLLDSDGDGYLDVEELKKLLRkleeGEPLSDEEVEELFKEFD 50

EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to the activation or inactivation of target proteins. EF-hands tend to occur in pairs or higher copy numbers.

                         10        20
                 ....*....|....*....|..
gi 530418307  41 FQDVFRRADKNDDGKLSFEEFQ 62
Cdd:cd00051   38 IDEMIREVDKDGDGKIDFEEFL 59