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Conserved domains on  [gi|663071182|ref|NP_001284697|]
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centrin-3 isoform 3 [Homo sapiens]

Protein Classification

EF-hand domain-containing protein( domain architecture ID 1001355)

EF-hand (EFh) domain-containing protein may be involved in binding intracellular calcium and in calcium signal transduction

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
PTZ00183 super family cl33171
centrin; Provisional
 15-115 4.92e-33

centrin; Provisional


The actual alignment was detected with superfamily member PTZ00183:

Pssm-ID: 185503 [Multi-domain]  Cd Length: 158  Bit Score: 114.40  E-value: 4.92e-33
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 663071182  15 KRKKRRELSEEQKQEIKDAFELFDTDKDEAIDYHELKVAMRALGFDVKKADVLKILKDYDREATGKITFEDFNEVVTDWI 94
Cdd:PTZ00183   4 RRSERPGLTEDQKKEIREAFDLFDTDGSGTIDPKELKVAMRSLGFEPKKEEIKQMIADVDKDGSGKIDFEEFLDIMTKKL 83

                         90       100
                 ....*....|....*....|.
gi 663071182  95 LERDPHEEILKAFKLFDDDDS 115
Cdd:PTZ00183  84 GERDPREEILKAFRLFDDDKT 104
 
Name Accession Description Interval E-value
PTZ00183 PTZ00183
centrin; Provisional
 15-115 4.92e-33

centrin; Provisional


Pssm-ID: 185503 [Multi-domain]  Cd Length: 158  Bit Score: 114.40  E-value: 4.92e-33
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 663071182  15 KRKKRRELSEEQKQEIKDAFELFDTDKDEAIDYHELKVAMRALGFDVKKADVLKILKDYDREATGKITFEDFNEVVTDWI 94
Cdd:PTZ00183   4 RRSERPGLTEDQKKEIREAFDLFDTDGSGTIDPKELKVAMRSLGFEPKKEEIKQMIADVDKDGSGKIDFEEFLDIMTKKL 83

                         90       100
                 ....*....|....*....|.
gi 663071182  95 LERDPHEEILKAFKLFDDDDS 115
Cdd:PTZ00183  84 GERDPREEILKAFRLFDDDKT 104
EFh cd00051
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...
 29-91 2.10e-11

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.


Pssm-ID: 238008 [Multi-domain]  Cd Length: 63  Bit Score: 56.02  E-value: 2.10e-11
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 663071182  29 EIKDAFELFDTDKDEAIDYHELKVAMRALGFDVKKADVLKILKDYDREATGKITFEDFNEVVT 91
Cdd:cd00051    1 ELREAFRLFDKDGDGTISADELKAALKSLGEGLSEEEIDEMIREVDKDGDGKIDFEEFLELMA 63
EF-hand_7 pfam13499
EF-hand domain pair;
27-91 3.21e-07

EF-hand domain pair;


Pssm-ID: 463900 [Multi-domain]  Cd Length: 67  Bit Score: 44.94  E-value: 3.21e-07
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 663071182   27 KQEIKDAFELFDTDKDEAIDYHELKVAMRAL--GFDVKKADVLKILKDYDREATGKITFEDFNEVVT 91
Cdd:pfam13499   1 EEKLKEAFKLLDSDGDGYLDVEELKKLLRKLeeGEPLSDEEVEELFKEFDLDKDGRISFEEFLELYS 67
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
24-93 1.95e-06

Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 44.78  E-value: 1.95e-06
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 663071182  24 EEQKQEIKDAFELFDTDKDEAIDYHELKVAMRALGFDvkKADVLKILKDYDREATGKITFEDFNEVVTDW 93
Cdd:COG5126   65 ATVEPFARAAFDLLDTDGDGKISADEFRRLLTALGVS--EEEADELFARLDTDGDGKISFEEFVAAVRDY 132
EFh smart00054
EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in ...
 29-57 4.36e-04

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.


Pssm-ID: 197492 [Multi-domain]  Cd Length: 29  Bit Score: 35.82  E-value: 4.36e-04
                           10        20
                   ....*....|....*....|....*....
gi 663071182    29 EIKDAFELFDTDKDEAIDYHELKVAMRAL 57
Cdd:smart00054   1 ELKEAFRLFDKDGDGKIDFEEFKDLLKAL 29
 
Name Accession Description Interval E-value
PTZ00183 PTZ00183
centrin; Provisional
 15-115 4.92e-33

centrin; Provisional


Pssm-ID: 185503 [Multi-domain]  Cd Length: 158  Bit Score: 114.40  E-value: 4.92e-33
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 663071182  15 KRKKRRELSEEQKQEIKDAFELFDTDKDEAIDYHELKVAMRALGFDVKKADVLKILKDYDREATGKITFEDFNEVVTDWI 94
Cdd:PTZ00183   4 RRSERPGLTEDQKKEIREAFDLFDTDGSGTIDPKELKVAMRSLGFEPKKEEIKQMIADVDKDGSGKIDFEEFLDIMTKKL 83

                         90       100
                 ....*....|....*....|.
gi 663071182  95 LERDPHEEILKAFKLFDDDDS 115
Cdd:PTZ00183  84 GERDPREEILKAFRLFDDDKT 104
PTZ00184 PTZ00184
calmodulin; Provisional
 21-113 8.90e-15

calmodulin; Provisional


Pssm-ID: 185504 [Multi-domain]  Cd Length: 149  Bit Score: 67.09  E-value: 8.90e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 663071182  21 ELSEEQKQEIKDAFELFDTDKDEAIDYHELKVAMRALGFDVKKADVLKILKDYDREATGKITFEDFNEVVTDWILERDPH 100
Cdd:PTZ00184   4 QLTEEQIAEFKEAFSLFDKDGDGTITTKELGTVMRSLGQNPTEAELQDMINEVDADGNGTIDFPEFLTLMARKMKDTDSE 83

                         90
                 ....*....|...
gi 663071182 101 EEILKAFKLFDDD 113
Cdd:PTZ00184  84 EEIKEAFKVFDRD 96
EFh cd00051
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...
 29-91 2.10e-11

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.


Pssm-ID: 238008 [Multi-domain]  Cd Length: 63  Bit Score: 56.02  E-value: 2.10e-11
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 663071182  29 EIKDAFELFDTDKDEAIDYHELKVAMRALGFDVKKADVLKILKDYDREATGKITFEDFNEVVT 91
Cdd:cd00051    1 ELREAFRLFDKDGDGTISADELKAALKSLGEGLSEEEIDEMIREVDKDGDGKIDFEEFLELMA 63
EFh_PEF_Group_I cd16180
Penta-EF hand, calcium binding motifs, found in Group I PEF proteins; The family corresponds ...
 31-113 1.15e-09

Penta-EF hand, calcium binding motifs, found in Group I PEF proteins; The family corresponds to Group I PEF proteins that have been found not only in higher animals but also in lower animals, plants, fungi and protists. Group I PEF proteins include apoptosis-linked gene 2 protein (ALG-2), peflin and similar proteins. ALG-2, also termed programmed cell death protein 6 (PDCD6), is a widely expressed calcium-binding modulator protein associated with cell proliferation and death, as well as cell survival. It forms a homodimer in the cell or a heterodimer with its closest paralog peflin. Among the PEF proteins, ALG-2 can bind three Ca2+ ions through its EF1, EF3, and EF5 hands, where it is unique in that its EF5 hand binds Ca2+ ion in a canonical coordination. Peflin is a ubiquitously expressed 30-kD PEF protein containing five EF-hand motifs in its C-terminal domain and a longer N-terminal hydrophobic domain (NHB domain) than any other member of the PEF family. The NHB domain harbors nine repeats of a nonapeptide (A/PPGGPYGGP). Peflin may modulate the function of ALG-2 in Ca2+ signaling. It exists only as a heterodimer with ALG-2, and binds two Ca2+ ions through its EF1 and EF3 hands. Its additional EF5 hand is unpaired and does not bind Ca2+ ion but mediates the heterodimerization with ALG-2. The dissociation of heterodimer occurs in the presence of Ca2+.


Pssm-ID: 320055 [Multi-domain]  Cd Length: 164  Bit Score: 53.69  E-value: 1.15e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 663071182  31 KDAFELFDTDKDEAIDYHELKVAMRALGFDVKKADVLKILKDYDREATGKITFEDFNEVVTdwILERdpheeILKAFKLF 110
Cdd:cd16180   70 RRLFRRFDRDRSGSIDFNELQNALSSFGYRLSPQFVQLLVRKFDRRRRGSISFDDFVEACV--TLKR-----LTDAFRKY 142


                 ...
gi 663071182 111 DDD 113
Cdd:cd16180  143 DTN 145
EFh_PEF_Group_II_sorcin_like cd16181
Penta-EF hand, calcium binding motifs, found in sorcin, grancalcin, and similar proteins; The ...
 31-112 5.08e-08

Penta-EF hand, calcium binding motifs, found in sorcin, grancalcin, and similar proteins; The family corresponds to the second group of penta-EF hand (PEF) proteins that includes sorcin, grancalcin, and similar proteins. Sorcin, also termed 22 kDa Ca2+-binding protein, CP-22, or V19, is a soluble resistance-related calcium-binding protein that is expressed in normal mammalian tissues, such as the liver, lungs and heart. It contains a flexible glycine and proline-rich N-terminal extension and five EF-hand motifs that associate with membranes in a calcium-dependent manner. It may harbor three potential Ca2+ binding sites through its EF1, EF2 and EF3 hands. However, binding of only two Ca2+/monomer suffices to trigger the conformational change that exposes hydrophobic regions and leads to interaction with the respective targets. Sorcin forms homodimers through the association of the unpaired EF5 hand. Among the PEF proteins, sorcin is unique in that it contains potential phosphorylation sites by cAMP-dependent protein kinase (PKA), and it can form a tetramer at slightly acid pH values although remaining a stable dimer at neutral pH. Grancalcin (GCA) is a cytosolic Ca2+-binding protein specifically expressed in neutrophils and monocytes/macrophages. It can strongly interact with sorcin to form a heterodimer and further modulate the function of sorcin. GCA exists as homodimers in solution. It contains five EF-hand motifs attached to an N-terminal region of an approximately 50 residue-long segment rich in glycines and prolines. In contrast with sorcin, GCA binds two Ca2+ ions through its EF1 and EF3 hands.


Pssm-ID: 320056 [Multi-domain]  Cd Length: 165  Bit Score: 49.29  E-value: 5.08e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 663071182  31 KDAFELFDTDKDEAIDYHELKVAMRALGFDVKKADVLKILKDYDreATGKITFEDFNEV------VTDWILERDPHEEIL 104
Cdd:cd16181   73 KTTFMQYDRDRSGTVEPQELQQAIRSFGYNLSPQALNVIVKRYS--KNGRITFDDFVACavrlraLTDRFRRRDTQQNGT 150


                 ....*...
gi 663071182 105 KAFKlFDD 112
Cdd:cd16181  151 ATFQ-YDD 157
EF-hand_7 pfam13499
EF-hand domain pair;
27-91 3.21e-07

EF-hand domain pair;


Pssm-ID: 463900 [Multi-domain]  Cd Length: 67  Bit Score: 44.94  E-value: 3.21e-07
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 663071182   27 KQEIKDAFELFDTDKDEAIDYHELKVAMRAL--GFDVKKADVLKILKDYDREATGKITFEDFNEVVT 91
Cdd:pfam13499   1 EEKLKEAFKLLDSDGDGYLDVEELKKLLRKLeeGEPLSDEEVEELFKEFDLDKDGRISFEEFLELYS 67
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
24-93 1.95e-06

Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 44.78  E-value: 1.95e-06
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 663071182  24 EEQKQEIKDAFELFDTDKDEAIDYHELKVAMRALGFDvkKADVLKILKDYDREATGKITFEDFNEVVTDW 93
Cdd:COG5126   65 ATVEPFARAAFDLLDTDGDGKISADEFRRLLTALGVS--EEEADELFARLDTDGDGKISFEEFVAAVRDY 132
EFh_PEF_peflin cd16184
EF-hand, calcium binding motif, found in peflin and similar proteins; Peflin, also termed ...
 28-86 7.21e-06

EF-hand, calcium binding motif, found in peflin and similar proteins; Peflin, also termed penta-EF hand (PEF) protein with a long N-terminal hydrophobic domain, or penta-EF hand domain-containing protein 1, is a ubiquitously expressed 30-kD PEF protein containing five EF-hand motifs in its C-terminal domain and a longer N-terminal hydrophobic domain (NHB domain) than any other member of the PEF family. The NHB domain harbors nine repeats of a nonapeptide (A/PPGGPYGGP). Peflin may modulate the function of ALG-2 in Ca2+ signaling. It exists only as a heterodimer with ALG-2, and binds two Ca2+ ions through its EF1 and EF3 hands. Its additional EF5 hand is unpaired and does not bind Ca2+ ion but mediates the heterodimerization with ALG-2. The dissociation of heterodimer occurs in the presence of Ca2+. In lower vertebrates, peflin may interact with transient receptor potential N (TRPN1), suggesting a potential role of peflin in fast transducer channel adaptation.


Pssm-ID: 320059 [Multi-domain]  Cd Length: 165  Bit Score: 43.41  E-value: 7.21e-06
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 663071182  28 QEIKDAFELFDTDKDEAIDYHELKVAMRALGFDVKKADVLKILKDYDREATGKITFEDF 86
Cdd:cd16184   67 QQWKQVFQQFDRDRSGSIDENELHQALSQMGYRLSPQFVQFLVSKYDPRARRSLTLDQF 125
EFh_PEF_sorcin cd16187
Penta-EF hand, calcium binding motifs, found in sorcin; Sorcin, also termed 22 kDa Ca2 ...
 31-112 9.25e-06

Penta-EF hand, calcium binding motifs, found in sorcin; Sorcin, also termed 22 kDa Ca2+-binding protein, CP-22, or V19, is a soluble resistance-related calcium-binding protein that is expressed in normal mammalian tissues, such as the liver, lungs and heart. The up-regulation of sorcin is correlated with a number of cancer types, including colorectal, gastric and breast cancer. It may represent a therapeutic target for reversing tumor multidrug resistance (MDR). Sorcin participates in the regulation of calcium homeostasis in cells and is necessary for the activation of mitosis and cytokinesis. It enhances metastasis and promotes epithelial-to-mesenchymal transition of colorectal cancer. Moreover, sorcin has been implicated in the regulation of intracellular Ca2+ cycling and cardiac excitation-contraction coupling. It displays the anti-apoptotic properties via the modulation of mitochondrial Ca2+ handling in cardiac myocytes. It can target and activate the sarcolemmal Na+/Ca2+ exchanger (NCX1) in cardiac muscle. Meanwhile, sorcin modulates cardiac L-type Ca2+ current by functional interaction with the alpha1C subunit. It also associates with calcium/calmodulin-dependent protein kinase IIdeltaC (CaMKIIdelta(C)) and further modulates ryanodine receptor (RyR) function in cardiac myocytes. Furthermore, sorcin may act as a Ca2+ sensor for glucose-induced nuclear translocation and the activation of carbohydrate-responsive element-binding protein (ChREBP)-dependent genes. As a mitochondrial chaperone TRAP1 interactor, sorcin involves in mitochondrial metabolism through the TRAP1 pathway. In addition, sorcin may regulate the inhibition of type I interferon response in cells through interacting with foot-and-mouth disease virus (FMDV) VP1. Sorcin contains a flexible glycine and proline-rich N-terminal extension and five EF-hand motifs that associate with membranes in a calcium-dependent manner. It may harbor three potential Ca2+ binding sites through its EF1, EF2 and EF3 hands. However, binding of only two Ca2+/monomer suffices to trigger the conformational change that exposes hydrophobic regions and leads to interaction with the respective targets. Sorcin forms homodimers through the association of the unpaired EF5 hand. Among the PEF proteins, sorcin is unique in that it contains potential phosphorylation sites by cAMP-dependent protein kinase (PKA), and it can form a tetramer at slightly acid pH values although remaining a stable dimer at neutral pH.


Pssm-ID: 320062 [Multi-domain]  Cd Length: 165  Bit Score: 43.36  E-value: 9.25e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 663071182  31 KDAFELFDTDKDEAIDYHELKVAMRALGFDVKKADVLKILKDYdrEATGKITFEDFN------EVVTDWILERDPHEEIL 104
Cdd:cd16187   73 RQHFISFDSDRSGTVDPQELQKALTTMGFRLSPQAVNSIAKRY--STNGKITFDDYIaccvklRALTDSFRRRDTSQQGV 150


                 ....*...
gi 663071182 105 KAFKlFDD 112
Cdd:cd16187  151 VNFP-YDD 157
EFh_PI-PLC cd15898
EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4. ...
 30-86 1.26e-05

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.


Pssm-ID: 320029 [Multi-domain]  Cd Length: 137  Bit Score: 42.27  E-value: 1.26e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 663071182  30 IKDAFELFDTDKDEAIDYHELKVAMRALGFDVKKADVLKILKDYDREATGKITFEDF 86
Cdd:cd15898    2 LRRQWIKADKDGDGKLSLKEIKKLLKRLNIRVSEKELKKLFKEVDTNGDGTLTFDEF 58
EFh_PEF_ALG-2 cd16183
EF-hand, calcium binding motif, found in apoptosis-linked gene 2 protein (ALG-2) and similar ...
 28-86 5.46e-05

EF-hand, calcium binding motif, found in apoptosis-linked gene 2 protein (ALG-2) and similar proteins; ALG-2, also termed programmed cell death protein 6 (PDCD6), or probable calcium-binding protein ALG-2, is one of the prototypic members of the penta EF-hand protein family. It is a widely expressed calcium-binding modulator protein associated with cell proliferation and death, as well as cell survival. ALG-2 acts as a pro-apoptotic factor participating in T cell receptor-, Fas-, and glucocorticoid-induced programmed cell death, and also serves as a useful molecular marker for the prognosis of cancers. Moreover, ALG-2 functions as a calcium ion sensor at endoplasmic reticulum (ER) exit sites, and modulates ER-stress-stimulated cell death and neuronal apoptosis during organ formation. Furthermore, ALG-2 can mediate the pro-apoptotic activity of cisplatin or tumor necrosis factor alpha (TNFalpha) through the down-regulation of nuclear factor-kappaB (NF-kappaB) expression. It also inhibits angiogenesis through PI3K/mTOR/p70S6K pathway by interacting of vascular endothelial growth factor receptor-2 (VEGFR-2). In addition, nuclear ALG-2 may participate in the post-transcriptional regulation of Inositol Trisphosphate Receptor Type 1 (IP3R1) pre-mRNA at least in part by interacting with CHERP (Ca2+ homeostasis endoplasmic reticulum protein) calcium-dependently. ALG-2 contains five serially repeated EF-hand motifs and interacts with various proteins, including ALG-2-interacting protein X (Alix), Fas, annexin XI, death-associated protein kinase 1 (DAPk1), Tumor susceptibility gene 101 (TSG101), Sec31A, phospholipid scramblase 3 (PLSCR3), the P-body component PATL1, and endosomal sorting complex required for transport (ESCRT)-III-related protein IST1, in a calcium-dependent manner. It forms a homodimer in the cell or a heterodimer with its closest paralog peflin. Among the PEF proteins, ALG-2 can bind three Ca2+ ions through its EF1, EF3, and EF5 hands, where it is unique in that its EF5 hand binds Ca2+ ion in a canonical coordination.


Pssm-ID: 320058 [Multi-domain]  Cd Length: 165  Bit Score: 41.09  E-value: 5.46e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 663071182  28 QEIKDAFELFDTDKDEAIDYHELKVAMRALGFDVKKADVLKILKDYDREATGKITFEDF 86
Cdd:cd16183   67 TDWQNCFRSFDRDNSGNIDKNELKQALTSFGYRLSDQFYDILVRKFDRQGRGTIAFDDF 125
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
24-115 1.06e-04

Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 39.78  E-value: 1.06e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 663071182  24 EEQKQEIKDAFELFDTDKDEAIDYHELKVAMRALgfdvkkadVLKILKDYDREATGKITFEDFNEVVTDWiLERDPHEEI 103
Cdd:COG5126    1 DLQRRKLDRRFDLLDADGDGVLERDDFEALFRRL--------WATLFSEADTDGDGRISREEFVAGMESL-FEATVEPFA 71

                         90
                 ....*....|..
gi 663071182 104 LKAFKLFDDDDS 115
Cdd:COG5126   72 RAAFDLLDTDGD 83
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
19-115 1.30e-04

Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 39.78  E-value: 1.30e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 663071182  19 RRELSEEQKQEIKDAFELFDTDKDEAIDYHELKVAMRALGFDVKKADVLKILKDYDREATGKITFEDFNEVVTDWILERD 98
Cdd:COG5126   24 RDDFEALFRRLWATLFSEADTDGDGRISREEFVAGMESLFEATVEPFARAAFDLLDTDGDGKISADEFRRLLTALGVSEE 103

                         90
                 ....*....|....*..
gi 663071182  99 PHEEilkAFKLFDDDDS 115
Cdd:COG5126  104 EADE---LFARLDTDGD 117
EFh_PEF_grancalcin cd16186
Penta-EF hand, calcium binding motifs, found in grancalcin; Grancalcin (GCA) is a cytosolic ...
 31-112 1.50e-04

Penta-EF hand, calcium binding motifs, found in grancalcin; Grancalcin (GCA) is a cytosolic Ca2+-binding protein specifically expressed in neutrophils and monocytes/macrophages. It displays a Ca2+-dependent translocation to granules and plasma membrane upon neutrophil activation, suggesting roles in granule-membrane fusion and degranulation of neutrophils. It may also play a role in the regulation of vesicle/granule exocytosis through the reversible binding of secretory vesicles and plasma membranes upon the presence of calcium. Moreover, GCA is involved in inflammation, as well as in the process of adhesion of neutrophils to fibronectin. It plays a key role in leukocyte-specific functions that are responsible for host defense, and affects the function of integrin receptors on immune cells through binding to L-plastin in the absence of calcium. Furthermore, GCA can strongly interact with sorcin to form a heterodimer, and further modulate the function of sorcin. GCA exists as homodimers in solution. It contains five EF-hand motifs attached to an N-terminal region of an approximately 50 residue-long segment rich in glycines and prolines. GCA binds two Ca2+ ions through its EF1 and EF3 hands.


Pssm-ID: 320061 [Multi-domain]  Cd Length: 165  Bit Score: 39.85  E-value: 1.50e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 663071182  31 KDAFELFDTDKDEAIDYHELKVAMRALGFDVKKADVLKILKDYDReaTGKITFEDFN------EVVTDWILERDPHEEIL 104
Cdd:cd16186   73 KQNFMTVDQDRSGTVEPHELRQAIGAMGYRLSPQTLTTIVKRYSK--NGRIYFDDYVaccvklRALTDFFRRRDHMQQGS 150


                 ....*...
gi 663071182 105 KAFkLFDD 112
Cdd:cd16186  151 VNF-IYDD 157
PTZ00184 PTZ00184
calmodulin; Provisional
 16-86 2.62e-04

calmodulin; Provisional


Pssm-ID: 185504 [Multi-domain]  Cd Length: 149  Bit Score: 38.97  E-value: 2.62e-04
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 663071182  16 RKKRRELSEEqkqEIKDAFELFDTDKDEAIDYHELKVAMRALGFDVKKADVLKILKDYDREATGKITFEDF 86
Cdd:PTZ00184  75 RKMKDTDSEE---EIKEAFKVFDRDGNGFISAAELRHVMTNLGEKLTDEEVDEMIREADVDGDGQINYEEF 142
EF-hand_6 pfam13405
EF-hand domain;
29-58 3.86e-04

EF-hand domain;


Pssm-ID: 463869 [Multi-domain]  Cd Length: 30  Bit Score: 36.00  E-value: 3.86e-04
                          10        20        30
                  ....*....|....*....|....*....|
gi 663071182   29 EIKDAFELFDTDKDEAIDYHELKVAMRALG 58
Cdd:pfam13405   1 ELREAFKLFDKDGDGKISLEELRKALRSLG 30
EFh smart00054
EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in ...
 29-57 4.36e-04

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.


Pssm-ID: 197492 [Multi-domain]  Cd Length: 29  Bit Score: 35.82  E-value: 4.36e-04
                           10        20
                   ....*....|....*....|....*....
gi 663071182    29 EIKDAFELFDTDKDEAIDYHELKVAMRAL 57
Cdd:smart00054   1 ELKEAFRLFDKDGDGKIDFEEFKDLLKAL 29
EF-hand_1 pfam00036
EF hand; The EF-hands can be divided into two classes: signalling proteins and buffering ...
 29-57 1.04e-03

EF hand; The EF-hands can be divided into two classes: signalling proteins and buffering/transport proteins. The first group is the largest and includes the most well-known members of the family such as calmodulin, troponin C and S100B. These proteins typically undergo a calcium-dependent conformational change which opens a target binding site. The latter group is represented by calbindin D9k and do not undergo calcium dependent conformational changes.


Pssm-ID: 425435 [Multi-domain]  Cd Length: 29  Bit Score: 34.68  E-value: 1.04e-03
                          10        20
                  ....*....|....*....|....*....
gi 663071182   29 EIKDAFELFDTDKDEAIDYHELKVAMRAL 57
Cdd:pfam00036   1 ELKEIFRLFDKDGDGKIDFEEFKELLKKL 29
EFh_PEF cd15897
The penta-EF hand (PEF) family; The penta-EF hand (PEF) family contains a group of five ...
 31-86 1.14e-03

The penta-EF hand (PEF) family; The penta-EF hand (PEF) family contains a group of five EF-hand calcium-binding proteins, including several classical calpain large catalytic subunits (CAPN1, 2, 3, 8, 9, 11, 12, 13, 14), two calpain small subunits (CAPNS1 and CAPNS2), as well as non-calpain PEF proteins, ALG-2 (apoptosis-linked gene 2, also termed programmed cell death protein 6, PDCD6), peflin, sorcin, and grancalcin. Based on the sequence similarity of EF1 hand, ALG-2 and peflin have been classified into group I PEF proteins. Calcium-dependent protease calpain subfamily members, sorcin and grancalcin, are group II PEF proteins. Calpains (EC 3.4.22.17) are calcium-activated intracellular cysteine proteases that play important roles in the degradation or functional modulation in a variety of substrates. They have been implicated in a number of physiological processes such as cell cycle progression, remodeling of cytoskeletal-cell membrane attachments, signal transduction, gene expression and apoptosis. ALG-2 is a pro-apoptotic factor that forms a homodimer in the cell or a heterodimer with its closest paralog peflin through their EF5s. Peflin is a 30-kD PEF protein with a longer N-terminal hydrophobic domain than any other member of the PEF family, and it contains nine nonapeptide (A/PPGGPYGGP) repeats. It exists only as a heterodimer with ALG-2. The dissociation of heterodimer occurs in the presence of Ca2+. ALG-2 interacts with various proteins in a Ca2+-dependent manner. Sorcin (for soluble resistance-related calcium binding protein) is a soluble resistance-related calcium-binding protein that participates in the regulation of calcium homeostasis in cells. Grancalcin is a cytosolic Ca2+-binding protein specifically expressed in neutrophils and monocytes/macrophages. It plays a key role in leukocyte-specific functions that are responsible for host defense. Grancalcin can form a heterodimer together with sorcin. Members in this family contain five EF-hand motifs attached to an N-terminal region of variable length containing one or more short Gly/Pro-rich sequences. These proteins form homodimers or heterodimers through pairing between the 5th EF-hands from the two molecules. Unlike calmodulin, the PEF domains do not undergo major conformational changes upon binding Ca2+.


Pssm-ID: 320054 [Multi-domain]  Cd Length: 165  Bit Score: 37.41  E-value: 1.14e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 663071182  31 KDAFELFDTDKDEAIDYHELKVAMRALGFDVKKADVLKILKDYDREaTGKITFEDF 86
Cdd:cd15897   73 QEIFRTYDTDGSGTIDSNELRQALSGAGYRLSEQTYDIIIRRYDRG-RGNIDFDDF 127
EFh_PEF_ALG-2_like cd16185
EF-hand, calcium binding motif, found in homologs of mammalian apoptosis-linked gene 2 protein ...
 28-86 1.83e-03

EF-hand, calcium binding motif, found in homologs of mammalian apoptosis-linked gene 2 protein (ALG-2); The family includes some homologs of mammalian apoptosis-linked gene 2 protein (ALG-2) mainly found in lower eukaryotes, such as a parasitic protist Leishmarua major and a cellular slime mold Dictyostelium discoideum. These homologs contains five EF-hand motifs. Due to the presence of unfavorable residues at the Ca2+-coordinating positions, their non-canonical EF4 and EF5 hands may not bind Ca2+. Two Dictyostelium PEF proteins are the prototypes of this family. They may bind to cytoskeletal proteins and/or signal-transducing proteins localized to detergent-resistant membranes named lipid rafts, and occur as monomers or weak homo- or heterodimers like ALG-2. They can serve as a mediator for Ca2+ signaling-related Dictyostehum programmed cell death (PCD).


Pssm-ID: 320060 [Multi-domain]  Cd Length: 163  Bit Score: 36.81  E-value: 1.83e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 663071182  28 QEIKDAFELFDTDKDEAIDYHELKVAMRALGFDVKKADVLKILKDYDREATGKITFEDF 86
Cdd:cd16185   66 SNMQNGFEQRDTSRSGRLDANEVHEALAASGFQLDPPAFQALFRKFDPDRGGSLGFDDY 124
ELC_N cd22949
N-terminal domain of Myosin essential light chain ELC; ELC is part of the apicomplexan ...
 28-99 1.89e-03

N-terminal domain of Myosin essential light chain ELC; ELC is part of the apicomplexan membrane-associated protein complex called the glideosome, which is essential for parasite motility. The glideosome is composed of six proteins: myosin A (MyoA), essential light chain ELC, myosin light chain MLC1 (also called MTIP), and the glideosome-associated proteins GAP40, GAP45, and GAP50. MyoA is a Class XIV myosin implicated in gliding motility, as well as host cell and tissue invasion by parasites. ELC binds to the MyoA neck region adjacent to the MLC1-binding site, and both myosin light chains co-located to the glideosome. Although ELCs bind to a conserved MyoA sequence, P. falciparum ELC adopts a distinct structure in the free and MyoA-bound state. Therefore ELCs enhance MyoA performance by inducing alpha helical structure formation in MyoA and thus stiffening its lever arm. It has been shown that disruption of MyoA, MLC1, or ELC have dramatic effects on parasite motility but do not affect parasite shape or replication. The ELC N-terminal domain is part of the EF-hand calcium binding motif superfamily. Calcium binding has no effect on the structure of ELCs.


Pssm-ID: 439385 [Multi-domain]  Cd Length: 66  Bit Score: 35.02  E-value: 1.89e-03
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 663071182  28 QEIKDAFELFDTDKDEAIDYHELKVAMRALGFDVkKADVLKILKDydreatgKITFEDFNEVVTDWILERDP 99
Cdd:cd22949    3 EKFREAFILFDRDGDGELTMYEAVLAMRSCGIPL-TNDEKDALPA-------SMNWDQFENWAKKKLAYSDP 66
EFh_PEF_CalpA_B cd16196
Penta-EF hand, calcium binding motifs, found in Drosophila melanogaster calpain-A (CalpA), ...
 31-86 5.51e-03

Penta-EF hand, calcium binding motifs, found in Drosophila melanogaster calpain-A (CalpA), calpain-B (CalpB), and similar proteins; The family contains two calpains that have been found in Drosophila, CalpA and CalpB. CalpA, also termed calcium-activated neutral proteinase A (CANP A), or calpain-A catalytic subunit, is a Drosophila calpain homolog specifically expressed in a few neurons in the central nervous system, in scattered endocrine cells in the midgut, and in blood cells. CalpB, also termed calcium-activated neutral proteinase B (CANP B), contains calpain-B catalytic subunit 1 and calpain-B catalytic subunit 2. Both CalpA and CalpB are closely related to that of vertebrate calpains, and they share similar domain architecture, which consists of four domains: the N-terminal domain I, the catalytic domain II carrying the three active site residues, Cys, His and Asn, the Ca2+-regulated phospholipid-binding domain III, and penta-EF-hand Ca2+-binding domain IV. Besides, CalpA and CalpB display some distinguishing structural features that are not found in mammalian typical calpains. CalpA harbors a 76 amino acid long hydrophobic stretch inserted in domain IV, which may be involved in membrane attachment of this enzyme. CalpB has an unusually long N-terminal tail of 224 amino acids, which belongs to the class of intrinsically unstructured proteins (IUP) and may become ordered upon binding to target protein(s). Moreover, they do not need small regulatory subunits for their catalytic activity, and their proteolytic function is not regulated by an intrinsic inhibitor as the Drosophila genome contains neither regulatory subunit nor calpastatin orthologs. As a result, they may exist as a monomer or perhaps as a homo- or heterodimer together with a second large subunit. Furthermore, both CalpA and CalpB are dispensable for viability and fertility and do not share vital functions during Drosophila development. Phosphatidylinositol 4,5-diphosphate, phosphatidylinositol 4-monophosphate, phosphatidylinositol, and phosphatidic acid can stimulate the activity and the rate of activation of CalpA, but not CalpB. Calpain A modulates Toll responses by limited Cactus/IkappaB proteolysis. CalpB directly interacts with talin, an important component of the focal adhesion complex, and functions as an important modulator in border cell migration within egg chambers, which may act via the digestion of talin. CalpB can be phosphorylated by cAMP-dependent protein kinase (protein kinase A, PKA; EC 2.7.11.11) at Ser240 and Ser845, as well as by mitogen-activated protein kinase (ERK1 and ERK2; EC 2.7.11.24) at Thr747. The activation of the ERK pathway by extracellular signals results in the phosphorylation and activation of calpain B. In Schneider cells (S2), calpain B was mainly in the cytoplasm and upon a rise in Ca2+ the enzyme adhered to intracellular membranes.


Pssm-ID: 320071 [Multi-domain]  Cd Length: 167  Bit Score: 35.26  E-value: 5.51e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 663071182  31 KDAFELFDTDKDEAIDYHELKVAMRALGFDVKKADVLKILKDY-DREatGKITFEDF 86
Cdd:cd16196   74 KRVFKLFDTDGSGSFSSFELRNALNSAGFRLSNATLNALVLRYsNKD--GRISFDDF 128
EFh_PEF_Group_I cd16180
Penta-EF hand, calcium binding motifs, found in Group I PEF proteins; The family corresponds ...
 29-115 8.88e-03

Penta-EF hand, calcium binding motifs, found in Group I PEF proteins; The family corresponds to Group I PEF proteins that have been found not only in higher animals but also in lower animals, plants, fungi and protists. Group I PEF proteins include apoptosis-linked gene 2 protein (ALG-2), peflin and similar proteins. ALG-2, also termed programmed cell death protein 6 (PDCD6), is a widely expressed calcium-binding modulator protein associated with cell proliferation and death, as well as cell survival. It forms a homodimer in the cell or a heterodimer with its closest paralog peflin. Among the PEF proteins, ALG-2 can bind three Ca2+ ions through its EF1, EF3, and EF5 hands, where it is unique in that its EF5 hand binds Ca2+ ion in a canonical coordination. Peflin is a ubiquitously expressed 30-kD PEF protein containing five EF-hand motifs in its C-terminal domain and a longer N-terminal hydrophobic domain (NHB domain) than any other member of the PEF family. The NHB domain harbors nine repeats of a nonapeptide (A/PPGGPYGGP). Peflin may modulate the function of ALG-2 in Ca2+ signaling. It exists only as a heterodimer with ALG-2, and binds two Ca2+ ions through its EF1 and EF3 hands. Its additional EF5 hand is unpaired and does not bind Ca2+ ion but mediates the heterodimerization with ALG-2. The dissociation of heterodimer occurs in the presence of Ca2+.


Pssm-ID: 320055 [Multi-domain]  Cd Length: 164  Bit Score: 34.81  E-value: 8.88e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 663071182  29 EIKDAFELFDTDKDEAIDYHELKVAMRALGFDVKKADVLKIL-KDYDREATGKITFEDFNEV---VTDWilerdpheeiL 104
Cdd:cd16180    1 ELRRIFQAVDRDRSGRISAKELQRALSNGDWTPFSIETVRLMiNMFDRDRSGTINFDEFVGLwkyIQDW----------R 70

                         90
                 ....*....|.
gi 663071182 105 KAFKLFDDDDS 115
Cdd:cd16180   71 RLFRRFDRDRS 81
EFh_PEF_CAPN13_14 cd16195
Penta-EF hand, calcium binding motifs, found in calpain-13 (CAPN13), calpain-14 (CAPN14), and ...
 31-86 9.35e-03

Penta-EF hand, calcium binding motifs, found in calpain-13 (CAPN13), calpain-14 (CAPN14), and similar proteins; CAPN13, also termed calcium-activated neutral proteinase 13 (CANP 13), a 63.6 kDa calpain large subunit that exhibits a restricted tissue distribution with low levels of expression detected only in human testis and lung. In calpain family, CAPN13 is most closely related to calpain-14 (CAPN14). CAPN14, also termed calcium-activated neutral proteinase 14 (CANP 14), is a 76.7 kDa calpain large subunit that is most highly expressed in the oesophagus. Its expression and calpain activity can be induced by IL-13. Both CAPN13 and CAPN14 contain a calpain cysteine protease (CysPc) domain, a C2-domain-like (C2L) domain, and a C-terminal Ca2+-binding penta-EF-hand (PEF) domain.


Pssm-ID: 320070 [Multi-domain]  Cd Length: 168  Bit Score: 34.87  E-value: 9.35e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 663071182  31 KDAFELFDTDKDEAIDYHELKVAMRALGFDVKKaDVLKILKDYDREATGKITFEDF 86
Cdd:cd16195   76 KDIFQKADVSKSGFLSLSELRNAIQAAGIRVSD-DLLNLMALRYGDSSGRISFESF 130
EFh_calglandulin_like cd16252
EF-hand, calcium binding motif, found in uncharacterized calglandulin-like proteins; The ...
 23-91 9.48e-03

EF-hand, calcium binding motif, found in uncharacterized calglandulin-like proteins; The family corresponds to a group of uncharacterized calglandulin-like proteins. Although their biological function remain unclear, they show high sequence similarity with human calglandulin-like protein GAGLP, which is an ortholog of calglandulin from the venom glands of Bothrops insularis snake. Both GAGLP and calglandulin are putative Ca2+-binding proteins with four EF-hand motifs. However, members in this family contain only three EF-hand motifs. In this point, they may belong to the parvalbumin-like EF-hand family, which is characterized by the presence of three consecutive EF-hand motifs (helix-loop-helix).


Pssm-ID: 319995 [Multi-domain]  Cd Length: 106  Bit Score: 34.04  E-value: 9.48e-03
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 663071182  23 SEEQKQEIKDAFELFDTDKDEAIDYHELK-------VAMRALGFDVKKADVlkILKDYDREATGKITFEDFNEVVT 91
Cdd:cd16252   32 SEQQEEAIRKAFQMLDKDKSGFIEWNEIKyilstvpSSMPVAPLSDEEAEA--MIQAADTDGDGRIDFQEFSDMVK 105
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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