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Conserved domains on  [gi|4507615|ref|NP_003271|]
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troponin C, slow skeletal and cardiac muscles [Homo sapiens]

Protein Classification

EF-hand domain-containing protein( domain architecture ID 1000080)

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
PTZ00184 super family cl33172
calmodulin; Provisional
9-157 1.90e-42

calmodulin; Provisional


The actual alignment was detected with superfamily member PTZ00184:

Pssm-ID: 185504 [Multi-domain]  Cd Length: 149  Bit Score: 138.36  E-value: 1.90e-42
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4507615     9 VEQLTEEQKNEFKAAFDIFVLGAeDGCISTKELGKVMRMLGQNPTPEELQEMIDEVDEDGSGTVDFDEFLVMMVRCMKDd 88
Cdd:PTZ00184   2 ADQLTEEQIAEFKEAFSLFDKDG-DGTITTKELGTVMRSLGQNPTEAELQDMINEVDADGNGTIDFPEFLTLMARKMKD- 79
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 4507615    89 skGKSEEELSDLFRMFDKNADGYIDLDELKIMLQATGETITEDDIEELMKDGDKNNDGRIDYDEFLEFM 157
Cdd:PTZ00184  80 --TDSEEEIKEAFKVFDRDGNGFISAAELRHVMTNLGEKLTDEEVDEMIREADVDGDGQINYEEFVKMM 146
 
Name Accession Description Interval E-value
PTZ00184 PTZ00184
calmodulin; Provisional
9-157 1.90e-42

calmodulin; Provisional


Pssm-ID: 185504 [Multi-domain]  Cd Length: 149  Bit Score: 138.36  E-value: 1.90e-42
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4507615     9 VEQLTEEQKNEFKAAFDIFVLGAeDGCISTKELGKVMRMLGQNPTPEELQEMIDEVDEDGSGTVDFDEFLVMMVRCMKDd 88
Cdd:PTZ00184   2 ADQLTEEQIAEFKEAFSLFDKDG-DGTITTKELGTVMRSLGQNPTEAELQDMINEVDADGNGTIDFPEFLTLMARKMKD- 79
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 4507615    89 skGKSEEELSDLFRMFDKNADGYIDLDELKIMLQATGETITEDDIEELMKDGDKNNDGRIDYDEFLEFM 157
Cdd:PTZ00184  80 --TDSEEEIKEAFKVFDRDGNGFISAAELRHVMTNLGEKLTDEEVDEMIREADVDGDGQINYEEFVKMM 146
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
33-159 1.78e-18

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


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 76.37  E-value: 1.78e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4507615   33 DGCISTKELGKVMRMLgqnptpeeLQEMIDEVDEDGSGTVDFDEFLVMMVRCMKDDSkgksEEELSDLFRMFDKNADGYI 112
Cdd:COG5126  19 DGVLERDDFEALFRRL--------WATLFSEADTDGDGRISREEFVAGMESLFEATV----EPFARAAFDLLDTDGDGKI 86
                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 4507615  113 DLDELKIMLQATGetITEDDIEELMKDGDKNNDGRIDYDEFLEFMKG 159
Cdd:COG5126  87 SADEFRRLLTALG--VSEEEADELFARLDTDGDGKISFEEFVAAVRD 131
EFh cd00051
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...
96-158 2.25e-17

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: 71.42  E-value: 2.25e-17
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 4507615   96 ELSDLFRMFDKNADGYIDLDELKIMLQATGETITEDDIEELMKDGDKNNDGRIDYDEFLEFMK 158
Cdd:cd00051   1 ELREAFRLFDKDGDGTISADELKAALKSLGEGLSEEEIDEMIREVDKDGDGKIDFEEFLELMA 63
EF-hand_7 pfam13499
EF-hand domain pair;
94-158 2.19e-12

EF-hand domain pair;


Pssm-ID: 463900 [Multi-domain]  Cd Length: 67  Bit Score: 58.80  E-value: 2.19e-12
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 4507615     94 EEELSDLFRMFDKNADGYIDLDELKIMLQA--TGETITEDDIEELMKDGDKNNDGRIDYDEFLEFMK 158
Cdd:pfam13499   1 EEKLKEAFKLLDSDGDGYLDVEELKKLLRKleEGEPLSDEEVEELFKEFDLDKDGRISFEEFLELYS 67
XopAW NF041410
XopAW family type III secretion system calcium-binding effector;
33-153 5.95e-10

XopAW family type III secretion system calcium-binding effector;


Pssm-ID: 469301 [Multi-domain]  Cd Length: 227  Bit Score: 55.84  E-value: 5.95e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4507615    33 DGCISTKELGKvmrMLGQNP---TPEELQEMIDEVDEDGSGTVDFDEFLVMMVRCMKDDSKGKSEEELSDLFRMFDKNAD 109
Cdd:NF041410  41 DGSVSQDELSS---ALSSKSddgSLIDLSELFSDLDSDGDGSLSSDELAAAAPPPPPPPDQAPSTELADDLLSALDTDGD 117
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 4507615   110 GYIDLDELKIMLQATGETiteDDIEELMKDGDKNNDGRIDYDEF 153
Cdd:NF041410 118 GSISSDELSAGLTSAGSS---ADSSQLFSALDSDGDGSVSSDEL 158
XopAW NF041410
XopAW family type III secretion system calcium-binding effector;
57-153 2.42e-09

XopAW family type III secretion system calcium-binding effector;


Pssm-ID: 469301 [Multi-domain]  Cd Length: 227  Bit Score: 53.92  E-value: 2.42e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4507615    57 LQEMIDEVDEDGSGTVDFDEFLVMMVrcmkDDSKGKSEEELSDLFRMFDKNADGYIDLDELKIML----QATGETITEDD 132
Cdd:NF041410  29 QKQLFAKLDSDGDGSVSQDELSSALS----SKSDDGSLIDLSELFSDLDSDGDGSLSSDELAAAAppppPPPDQAPSTEL 104
                         90       100
                 ....*....|....*....|.
gi 4507615   133 IEELMKDGDKNNDGRIDYDEF 153
Cdd:NF041410 105 ADDLLSALDTDGDGSISSDEL 125
XopAW NF041410
XopAW family type III secretion system calcium-binding effector;
32-123 1.36e-07

XopAW family type III secretion system calcium-binding effector;


Pssm-ID: 469301 [Multi-domain]  Cd Length: 227  Bit Score: 49.29  E-value: 1.36e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4507615    32 EDGCISTKELGKVMRM----LGQNPTPEELQEMIDEVDEDGSGTVDFDEFLVMMvrcmkddSKGKSEEELSDLFRMFDKN 107
Cdd:NF041410  76 GDGSLSSDELAAAAPPppppPDQAPSTELADDLLSALDTDGDGSISSDELSAGL-------TSAGSSADSSQLFSALDSD 148
                         90
                 ....*....|....*.
gi 4507615   108 ADGYIDLDELKIMLQA 123
Cdd:NF041410 149 GDGSVSSDELAAALQP 164
XopAW NF041410
XopAW family type III secretion system calcium-binding effector;
89-158 1.90e-07

XopAW family type III secretion system calcium-binding effector;


Pssm-ID: 469301 [Multi-domain]  Cd Length: 227  Bit Score: 48.52  E-value: 1.90e-07
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4507615    89 SKGKSEEELSDLFRMFDKNADGYIDLDELKIMLQATGETITEDDIEELMKDGDKNNDGRIDYDEFLEFMK 158
Cdd:NF041410  21 SSARSQQFQKQLFAKLDSDGDGSVSQDELSSALSSKSDDGSLIDLSELFSDLDSDGDGSLSSDELAAAAP 90
EFh smart00054
EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in ...
56-81 2.38e-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: 36.59  E-value: 2.38e-04
                           10        20
                   ....*....|....*....|....*.
gi 4507615      56 ELQEMIDEVDEDGSGTVDFDEFLVMM 81
Cdd:smart00054   1 ELKEAFRLFDKDGDGKIDFEEFKDLL 26
 
Name Accession Description Interval E-value
PTZ00184 PTZ00184
calmodulin; Provisional
9-157 1.90e-42

calmodulin; Provisional


Pssm-ID: 185504 [Multi-domain]  Cd Length: 149  Bit Score: 138.36  E-value: 1.90e-42
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4507615     9 VEQLTEEQKNEFKAAFDIFVLGAeDGCISTKELGKVMRMLGQNPTPEELQEMIDEVDEDGSGTVDFDEFLVMMVRCMKDd 88
Cdd:PTZ00184   2 ADQLTEEQIAEFKEAFSLFDKDG-DGTITTKELGTVMRSLGQNPTEAELQDMINEVDADGNGTIDFPEFLTLMARKMKD- 79
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 4507615    89 skGKSEEELSDLFRMFDKNADGYIDLDELKIMLQATGETITEDDIEELMKDGDKNNDGRIDYDEFLEFM 157
Cdd:PTZ00184  80 --TDSEEEIKEAFKVFDRDGNGFISAAELRHVMTNLGEKLTDEEVDEMIREADVDGDGQINYEEFVKMM 146
PTZ00183 PTZ00183
centrin; Provisional
11-158 4.07e-28

centrin; Provisional


Pssm-ID: 185503 [Multi-domain]  Cd Length: 158  Bit Score: 102.07  E-value: 4.07e-28
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4507615    11 QLTEEQKNEFKAAFDIFVLGAEdGCISTKELGKVMRMLGQNPTPEELQEMIDEVDEDGSGTVDFDEFLVMMVRCMkddSK 90
Cdd:PTZ00183  10 GLTEDQKKEIREAFDLFDTDGS-GTIDPKELKVAMRSLGFEPKKEEIKQMIADVDKDGSGKIDFEEFLDIMTKKL---GE 85
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 4507615    91 GKSEEELSDLFRMFDKNADGYIDLDELKIMLQATGETITEDDIEELMKDGDKNNDGRIDYDEFLEFMK 158
Cdd:PTZ00183  86 RDPREEILKAFRLFDDDKTGKISLKNLKRVAKELGETITDEELQEMIDEADRNGDGEISEEEFYRIMK 153
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
33-159 1.78e-18

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


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 76.37  E-value: 1.78e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4507615   33 DGCISTKELGKVMRMLgqnptpeeLQEMIDEVDEDGSGTVDFDEFLVMMVRCMKDDSkgksEEELSDLFRMFDKNADGYI 112
Cdd:COG5126  19 DGVLERDDFEALFRRL--------WATLFSEADTDGDGRISREEFVAGMESLFEATV----EPFARAAFDLLDTDGDGKI 86
                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 4507615  113 DLDELKIMLQATGetITEDDIEELMKDGDKNNDGRIDYDEFLEFMKG 159
Cdd:COG5126  87 SADEFRRLLTALG--VSEEEADELFARLDTDGDGKISFEEFVAAVRD 131
EFh cd00051
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...
96-158 2.25e-17

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: 71.42  E-value: 2.25e-17
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 4507615   96 ELSDLFRMFDKNADGYIDLDELKIMLQATGETITEDDIEELMKDGDKNNDGRIDYDEFLEFMK 158
Cdd:cd00051   1 ELREAFRLFDKDGDGTISADELKAALKSLGEGLSEEEIDEMIREVDKDGDGKIDFEEFLELMA 63
EF-hand_7 pfam13499
EF-hand domain pair;
94-158 2.19e-12

EF-hand domain pair;


Pssm-ID: 463900 [Multi-domain]  Cd Length: 67  Bit Score: 58.80  E-value: 2.19e-12
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 4507615     94 EEELSDLFRMFDKNADGYIDLDELKIMLQA--TGETITEDDIEELMKDGDKNNDGRIDYDEFLEFMK 158
Cdd:pfam13499   1 EEKLKEAFKLLDSDGDGYLDVEELKKLLRKleEGEPLSDEEVEELFKEFDLDKDGRISFEEFLELYS 67
EFh cd00051
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...
19-81 3.24e-12

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: 58.33  E-value: 3.24e-12
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 4507615   19 EFKAAFDIFVLGaEDGCISTKELGKVMRMLGQNPTPEELQEMIDEVDEDGSGTVDFDEFLVMM 81
Cdd:cd00051   1 ELREAFRLFDKD-GDGTISADELKAALKSLGEGLSEEEIDEMIREVDKDGDGKIDFEEFLELM 62
EFh_PI-PLC cd15898
EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4. ...
33-157 1.63e-11

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: 58.45  E-value: 1.63e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4507615   33 DGCISTKELGKVMRMLGQNPTPEELQEMIDEVDEDGSGTVDFDEFLVMMVRCMkddskgkSEEELSDLFRMFDKNADGYI 112
Cdd:cd15898  14 DGKLSLKEIKKLLKRLNIRVSEKELKKLFKEVDTNGDGTLTFDEFEELYKSLT-------ERPELEPIFKKYAGTNRDYM 86
                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 4507615  113 DLDELKIMLQAT-GETITEDDIEELMKD-GDKNNDGRIDYDEFLEFM 157
Cdd:cd15898  87 TLEEFIRFLREEqGENVSEEECEELIEKyEPERENRQLSFEGFTNFL 133
EFh_PEF_Group_I cd16180
Penta-EF hand, calcium binding motifs, found in Group I PEF proteins; The family corresponds ...
34-155 2.74e-11

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: 58.31  E-value: 2.74e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4507615   34 GCISTKELGKVMRMLGQNP-TPEELQEMIDEVDEDGSGTVDFDEFLVMMvrcmkddskgKSEEELSDLFRMFDKNADGYI 112
Cdd:cd16180  15 GRISAKELQRALSNGDWTPfSIETVRLMINMFDRDRSGTINFDEFVGLW----------KYIQDWRRLFRRFDRDRSGSI 84
                        90       100       110       120
                ....*....|....*....|....*....|....*....|...
gi 4507615  113 DLDELKIMLQATGETITEDDIEELMKDGDKNNDGRIDYDEFLE 155
Cdd:cd16180  85 DFNELQNALSSFGYRLSPQFVQLLVRKFDRRRRGSISFDDFVE 127
EFh_PEF_ALG-2_like cd16185
EF-hand, calcium binding motif, found in homologs of mammalian apoptosis-linked gene 2 protein ...
34-156 2.88e-10

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: 55.68  E-value: 2.88e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4507615   34 GCISTKELGKVMRMLGQNPTPEELQEMIDEVDEDGSGTVDFDEFLVMmvrcmkddskgksEEELSDL---FRMFDKNADG 110
Cdd:cd16185  15 GSIDVNELQKALAGGGLLFSLATAEKLIRMFDRDGNGTIDFEEFAAL-------------HQFLSNMqngFEQRDTSRSG 81
                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 4507615  111 YIDLDELKIMLQATGETITEDDIEELMKDGDKNNDGRIDYDEFLEF 156
Cdd:cd16185  82 RLDANEVHEALAASGFQLDPPAFQALFRKFDPDRGGSLGFDDYIEL 127
XopAW NF041410
XopAW family type III secretion system calcium-binding effector;
33-153 5.95e-10

XopAW family type III secretion system calcium-binding effector;


Pssm-ID: 469301 [Multi-domain]  Cd Length: 227  Bit Score: 55.84  E-value: 5.95e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4507615    33 DGCISTKELGKvmrMLGQNP---TPEELQEMIDEVDEDGSGTVDFDEFLVMMVRCMKDDSKGKSEEELSDLFRMFDKNAD 109
Cdd:NF041410  41 DGSVSQDELSS---ALSSKSddgSLIDLSELFSDLDSDGDGSLSSDELAAAAPPPPPPPDQAPSTELADDLLSALDTDGD 117
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 4507615   110 GYIDLDELKIMLQATGETiteDDIEELMKDGDKNNDGRIDYDEF 153
Cdd:NF041410 118 GSISSDELSAGLTSAGSS---ADSSQLFSALDSDGDGSVSSDEL 158
EFh_parvalbumin_like cd16251
EF-hand, calcium binding motif, found in parvalbumin-like EF-hand family; The family includes ...
70-159 1.17e-09

EF-hand, calcium binding motif, found in parvalbumin-like EF-hand family; The family includes alpha- and beta-parvalbumins, and a group of uncharacterized calglandulin-like proteins. Parvalbumins are small, acidic, cytosolic EF-hand-containing Ca2+-buffer and Ca2+ transporter/shuttle proteins belonging to EF-hand superfamily. They are expressed by vertebrates in fast-twitch muscle cells, specific neurons of the central and peripheral nervous system, sensory cells of the mammalian auditory organ (Corti's cell), and some other cells, and characterized by the presence of three consecutive EF-hand motifs (helix-loop-helix) called AB, CD, and EF, but only CD and EF can chelate metal ions, such as Ca2+ and Mg2+. Thus, they may play an additional role in Mg2+ handling. Moreover, parvalbumins represent one of the major animal allergens. In metal-bound states, parvalbumins possess a rigid and stable tertiary structure and display strong allergenicity. In contrast, the metal-free parvalbumins are intrinsically disordered, and the loss of metal ions results in a conformational change that decreases their IgE binding capacity. Furthermore, parvalbumins have been widely used as a neuronal marker for a variety of functional brain systems. They also function as a Ca2+ shuttle transporting Ca2+ from troponin-C (TnC) to the sarcoplasmic reticulum (SR) Ca2+ pump during muscle relaxation. Thus they may facilitate myocardial relaxation and play important roles in cardiac diastolic dysfunction. Parvalbumins consists of alpha- and beta- sublineages, which can be distinguished on the basis of isoelectric point (pI > 5 for alpha; pI


Pssm-ID: 319994 [Multi-domain]  Cd Length: 101  Bit Score: 52.54  E-value: 1.17e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4507615   70 GTVDFDEFLVMMvrcmkdDSKGKSEEELSDLFRMFDKNADGYIDLDELKIMLQ---ATGETITEDDIEELMKDGDKNNDG 146
Cdd:cd16251  15 GSFNYKKFFEHV------GLKQKSEDQIKKVFQILDKDKSGFIEEEELKYILKgfsIAGRDLTDEETKALLAAGDTDGDG 88
                        90
                ....*....|...
gi 4507615  147 RIDYDEFLEFMKG 159
Cdd:cd16251  89 KIGVEEFATLVAG 101
XopAW NF041410
XopAW family type III secretion system calcium-binding effector;
57-153 2.42e-09

XopAW family type III secretion system calcium-binding effector;


Pssm-ID: 469301 [Multi-domain]  Cd Length: 227  Bit Score: 53.92  E-value: 2.42e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4507615    57 LQEMIDEVDEDGSGTVDFDEFLVMMVrcmkDDSKGKSEEELSDLFRMFDKNADGYIDLDELKIML----QATGETITEDD 132
Cdd:NF041410  29 QKQLFAKLDSDGDGSVSQDELSSALS----SKSDDGSLIDLSELFSDLDSDGDGSLSSDELAAAAppppPPPDQAPSTEL 104
                         90       100
                 ....*....|....*....|.
gi 4507615   133 IEELMKDGDKNNDGRIDYDEF 153
Cdd:NF041410 105 ADDLLSALDTDGDGSISSDEL 125
EFh_parvalbumin_beta cd16255
EF-hand, calcium binding motif, found in beta-parvalbumin; Beta-parvalbumin, also termed ...
91-158 2.83e-09

EF-hand, calcium binding motif, found in beta-parvalbumin; Beta-parvalbumin, also termed Oncomodulin-1 (OM), is a small calcium-binding protein that is expressed in hepatomas, as well as in the blastocyst and the cytotrophoblasts of the placenta. It is also found to be expressed in the cochlear outer hair cells of the organ of Corti and frequently expressed in neoplasms. Mammalian beta-parvalbumin is secreted by activated macrophages and neutrophils. It may function as a tissue-specific Ca2+-dependent regulatory protein, and may also serve as a specialized cytosolic Ca2+ buffer. Beta-parvalbumin acts as a potent growth-promoting signal between the innate immune system and neurons in vivo. It has high and specific affinity for its receptor on retinal ganglion cells (RGC) and functions as the principal mediator of optic nerve regeneration. It exerts its effects in a cyclic adenosine monophosphate (cAMP)-dependent manner and can further elevate intracellular cAMP levels. Moreover, beta-parvalbumin is associated with efferent function and outer hair cell electromotility, and can identify different hair cell types in the mammalian inner ear. Beta-parvalbumin is characterized by the presence of three consecutive EF-hand motifs (helix-loop-helix) called AB, CD, and EF, but only CD and EF can chelate metal ions, such as Ca2+ and Mg2+. The EF site displays a high-affinity for Ca2+/Mg2+, and the CD site is a low-affinity Ca2+-specific site. In addition, beta-parvalbumin is distinguished from other parvalbumins by its unusually low isoelectric point (pI = 3.1) and sequence eccentricities (e.g., Y57-L58-D59 instead of F57-I58-E59).


Pssm-ID: 319998 [Multi-domain]  Cd Length: 101  Bit Score: 51.66  E-value: 2.83e-09
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 4507615   91 GKSEEELSDLFRMFDKNADGYIDLDELKIMLQ---ATGETITEDDIEELMKDGDKNNDGRIDYDEFLEFMK 158
Cdd:cd16255  30 KKSADDVKKVFEIIDQDKSGFIEEEELKLFLQnfsSGARELTDAETKAFLKAGDSDGDGKIGVEEFQALVK 100
EFh cd00051
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...
56-122 2.88e-09

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: 50.62  E-value: 2.88e-09
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 4507615   56 ELQEMIDEVDEDGSGTVDFDEFLvmmvRCMKDDSKGKSEEELSDLFRMFDKNADGYIDLDELKIMLQ 122
Cdd:cd00051   1 ELREAFRLFDKDGDGTISADELK----AALKSLGEGLSEEEIDEMIREVDKDGDGKIDFEEFLELMA 63
EFh_PEF_ALG-2 cd16183
EF-hand, calcium binding motif, found in apoptosis-linked gene 2 protein (ALG-2) and similar ...
34-155 3.65e-09

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: 52.64  E-value: 3.65e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4507615   34 GCISTKELGKVMRMLGQNP-TPEELQEMIDEVDEDGSGTVDFDEFLvmmvrcmkddSKGKSEEELSDLFRMFDKNADGYI 112
Cdd:cd16183  15 GQISATELQQALSNGTWTPfNPETVRLMIGMFDRDNSGTINFQEFA----------ALWKYITDWQNCFRSFDRDNSGNI 84
                        90       100       110       120
                ....*....|....*....|....*....|....*....|...
gi 4507615  113 DLDELKIMLQATGETITEDDIEELMKDGDKNNDGRIDYDEFLE 155
Cdd:cd16183  85 DKNELKQALTSFGYRLSDQFYDILVRKFDRQGRGTIAFDDFIQ 127
EFh_parvalbumin_alpha cd16254
EF-hand, calcium binding motif, found in alpha-parvalbumin; Alpha-parvalbumin is cytosolic Ca2 ...
90-153 4.68e-09

EF-hand, calcium binding motif, found in alpha-parvalbumin; Alpha-parvalbumin is cytosolic Ca2+/Mg2+-binding protein expressed mainly in fast-twitch skeletal myofibrils, where it may act as a soluble relaxing factor facilitating the Ca2+-mediated relaxation phase. It is also expressed in rapidly firing neurons, particularly GABA-ergic neurons, and thus may confer protection against Ca2+ toxicity. The major role of alpha-parvalbumin is metal buffering and transport of Ca2+. It binds different metal cations, and exhibits very high affinity for Ca2+ and physiologically significant affinity for Mg2+. Alpha-parvalbumin is characterized by the presence of three consecutive EF-hand motifs (helix-loop-helix) called AB, CD, and EF, but only CD and EF can chelate metal ions, such as Ca2+ and Mg2+. Both metal ion-binding sites in alpha-parvalbumin are high-affinity sites. Additionally, in contrast to beta-parvalbumin, alpha-parvalbumin is less acidic and has an additional residue in the C-terminal helix.


Pssm-ID: 319997 [Multi-domain]  Cd Length: 101  Bit Score: 50.98  E-value: 4.68e-09
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 4507615   90 KGKSEEELSDLFRMFDKNADGYIDLDELKIMLQ---ATGETITEDDIEELMKDGDKNNDGRIDYDEF 153
Cdd:cd16254  29 KKKSADDVKKVFHILDKDKSGFIEEDELKFVLKgfsPDGRDLSDKETKALLAAGDKDGDGKIGIDEF 95
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
55-161 6.68e-09

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


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 51.33  E-value: 6.68e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4507615   55 EELQEMIDEVDEDGSGTVDFDEFLVMMVRcmkddskgkseeELSDLFRMFDKNADGYIDLDELKIMLQATGETITEDDIE 134
Cdd:COG5126   5 RKLDRRFDLLDADGDGVLERDDFEALFRR------------LWATLFSEADTDGDGRISREEFVAGMESLFEATVEPFAR 72
                        90       100
                ....*....|....*....|....*..
gi 4507615  135 ELMKDGDKNNDGRIDYDEFLEFMKGVE 161
Cdd:COG5126  73 AAFDLLDTDGDGKISADEFRRLLTALG 99
EFh_PI-PLC cd15898
EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4. ...
97-158 5.77e-08

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: 48.82  E-value: 5.77e-08
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 4507615   97 LSDLFRMFDKNADGYIDLDELKIMLQATGETITEDDIEELMKDGDKNNDGRIDYDEFLEFMK 158
Cdd:cd15898   2 LRRQWIKADKDGDGKLSLKEIKKLLKRLNIRVSEKELKKLFKEVDTNGDGTLTFDEFEELYK 63
XopAW NF041410
XopAW family type III secretion system calcium-binding effector;
32-123 1.36e-07

XopAW family type III secretion system calcium-binding effector;


Pssm-ID: 469301 [Multi-domain]  Cd Length: 227  Bit Score: 49.29  E-value: 1.36e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4507615    32 EDGCISTKELGKVMRM----LGQNPTPEELQEMIDEVDEDGSGTVDFDEFLVMMvrcmkddSKGKSEEELSDLFRMFDKN 107
Cdd:NF041410  76 GDGSLSSDELAAAAPPppppPDQAPSTELADDLLSALDTDGDGSISSDELSAGL-------TSAGSSADSSQLFSALDSD 148
                         90
                 ....*....|....*.
gi 4507615   108 ADGYIDLDELKIMLQA 123
Cdd:NF041410 149 GDGSVSSDELAAALQP 164
XopAW NF041410
XopAW family type III secretion system calcium-binding effector;
89-158 1.90e-07

XopAW family type III secretion system calcium-binding effector;


Pssm-ID: 469301 [Multi-domain]  Cd Length: 227  Bit Score: 48.52  E-value: 1.90e-07
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4507615    89 SKGKSEEELSDLFRMFDKNADGYIDLDELKIMLQATGETITEDDIEELMKDGDKNNDGRIDYDEFLEFMK 158
Cdd:NF041410  21 SSARSQQFQKQLFAKLDSDGDGSVSQDELSSALSSKSDDGSLIDLSELFSDLDSDGDGSLSSDELAAAAP 90
EFh_PEF cd15897
The penta-EF hand (PEF) family; The penta-EF hand (PEF) family contains a group of five ...
33-155 4.75e-07

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: 47.04  E-value: 4.75e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4507615   33 DGCISTKELGKVMRMLGQNP-----TPEELQEMIDEVDEDGSGTVDFDEF--LVMMVRCMKddskgkseeelsDLFRMFD 105
Cdd:cd15897  13 DGEISATELQQALSNVGWTHfdlgfSLETCRSMIAMMDRDHSGKLNFSEFkgLWNYIKAWQ------------EIFRTYD 80
                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|
gi 4507615  106 KNADGYIDLDELKIMLQATGETITEDDIEELMKDGDKNNdGRIDYDEFLE 155
Cdd:cd15897  81 TDGSGTIDSNELRQALSGAGYRLSEQTYDIIIRRYDRGR-GNIDFDDFIQ 129
EF-hand_8 pfam13833
EF-hand domain pair;
32-84 1.06e-06

EF-hand domain pair;


Pssm-ID: 404678 [Multi-domain]  Cd Length: 54  Bit Score: 43.46  E-value: 1.06e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 4507615     32 EDGCISTKELGKVMRMLG-QNPTPEELQEMIDEVDEDGSGTVDFDEFLVMMVRC 84
Cdd:pfam13833   1 EKGVITREELKRALALLGlKDLSEDEVDILFREFDTDGDGYISFDEFCVLLERR 54
EFh_calglandulin_like cd16252
EF-hand, calcium binding motif, found in uncharacterized calglandulin-like proteins; The ...
70-159 1.18e-06

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: 44.83  E-value: 1.18e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4507615   70 GTVDFDEFLVMMVRCMKddsKGKSEEELSDLFRMFDKNADGYIDLDELKIMLQATGET-----ITEDDIEELMKDGDKNN 144
Cdd:cd16252  15 GSFNYSKFFEYMQKFQT---SEQQEEAIRKAFQMLDKDKSGFIEWNEIKYILSTVPSSmpvapLSDEEAEAMIQAADTDG 91
                        90
                ....*....|....*
gi 4507615  145 DGRIDYDEFLEFMKG 159
Cdd:cd16252  92 DGRIDFQEFSDMVKK 106
EFh_CREC_Calumenin_like cd16226
EF-hand, calcium binding motif, found in calumenin, reticulocalbin-1 (RCN-1), reticulocalbin-3 ...
58-155 1.37e-06

EF-hand, calcium binding motif, found in calumenin, reticulocalbin-1 (RCN-1), reticulocalbin-3 (RCN-3), and similar proteins; The family corresponds to a group of six EF-hand Ca2+-binding proteins, including calumenin (also known as crocalbin or CBP-50), reticulocalbin-1 (RCN-1), reticulocalbin-3 (RCN-3), and similar proteins. Calumenin is an endo/sarcoplasmic reticulum (ER/SR) resident low-affinity Ca2+-binding protein that contains six EF-hand domains and a C-terminal SR retention signal His-Asp-Glu-Phe (HDEF) tetrapeptide. It functions as a novel regulator of SERCA2, and its expressional changes are tightly coupled with Ca2+-cycling of cardiomyocytes. It is also broadly involved in haemostasis and in the pathophysiology of thrombosis. Moreover, the extracellular calumenin acts as a suppressor of cell migration and tumor metastasis. RCN-1 is an endoplasmic reticulum resident Ca2+-binding protein with a carboxyl-terminal His-Asp-Glu-Leu (HDEL) tetrapeptide signal. It acts as a potential negative regulator of B-RAF activation and can negatively modulate cardiomyocyte hypertrophy by inhibition of the mitogen-activated protein kinase signalling cascade. It also plays a key role in the development of doxorubicin-associated resistance. RCN-3 is a putative six EF-hand Ca2+-binding protein that contains five RXXR (X is any amino acid) motifs and a C-terminal ER retrieval signal HDEL tetrapeptide. The RXXR motif represents the target sequence of subtilisin-like proprotein convertases (SPCs). RCN-3 is specifically bound to the paired basic amino-acid-cleaving enzyme-4 (PACE4) precursor protein and plays an important role in the biosynthesis of PACE4.


Pssm-ID: 320024 [Multi-domain]  Cd Length: 264  Bit Score: 46.42  E-value: 1.37e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4507615   58 QEMIDEVDEDGSGTVDFDEFLVMMVRC---MKDDSKGKSEEELSDLFRmfDKNADGYIDLDELKIMLQATGETITEDDIE 134
Cdd:cd16226 159 QETLEDIDKNKDGFISLEEYIGDMYRDddeEEDPDWVKSEREQFKEFR--DKNKDGKMDREEVKDWILPEDYDHAEAEAK 236
                        90       100
                ....*....|....*....|.
gi 4507615  135 ELMKDGDKNNDGRIDYDEFLE 155
Cdd:cd16226 237 HLIYEADDDKDGKLTKEEILD 257
PTZ00184 PTZ00184
calmodulin; Provisional
19-83 1.44e-06

calmodulin; Provisional


Pssm-ID: 185504 [Multi-domain]  Cd Length: 149  Bit Score: 45.52  E-value: 1.44e-06
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 4507615    19 EFKAAFDIFVLGAeDGCISTKELGKVMRMLGQNPTPEELQEMIDEVDEDGSGTVDFDEFLVMMVR 83
Cdd:PTZ00184  85 EIKEAFKVFDRDG-NGFISAAELRHVMTNLGEKLTDEEVDEMIREADVDGDGQINYEEFVKMMMS 148
EFh_CREC_RCN2_like cd16227
EF-hand, calcium binding motif, found in reticulocalbin-2 (RCN2) mainly from protostomes; This ...
32-154 1.66e-06

EF-hand, calcium binding motif, found in reticulocalbin-2 (RCN2) mainly from protostomes; This family corresponds to a group of uncharacterized RCN2-like proteins, which are mainly found in protostomes. Although their biological function remains unclear, they show high sequence similarity with RCN2 (also known as E6BP or TCBP-49), which is an endoplasmic reticulum resident low-affinity Ca2+-binding protein that has been implicated in immunity, redox homeostasis, cell cycle regulation and coagulation. Members in this family contain six copies of the EF-hand Ca2+-binding motif, but may lack a C-terminal His-Asp-Glu-Leu (HDEL) tetrapeptide that is required for retention of RCN2 in the endoplasmic reticulum (ER).


Pssm-ID: 320025 [Multi-domain]  Cd Length: 263  Bit Score: 46.16  E-value: 1.66e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4507615   32 EDGCISTKELGKVMRMLGQNPTPEELQEMIDEVDEDGSGTVDFDEFLVMMVRCMKDDSKGKSEEELSDLFRMF------- 104
Cdd:cd16227  49 DDGFIDRKELKAWILRSFKMLDEEEANERFEEADEDGDGKVTWEEYLADSFGYDDEDNEEMIKDSTEDDLKLLeddkemf 128
                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....
gi 4507615  105 ---DKNADGYIDLDELKIMLQATG-ETITEDDIEELMKDGDKNNDGRIDYDEFL 154
Cdd:cd16227 129 eaaDLNKDGKLDKTEFSAFQHPEEyPHMHPVLIEQTLRDKDKDNDGFISFQEFL 182
EFh_PI-PLCdelta cd16202
EF-hand motif found in phosphoinositide phospholipase C delta (PI-PLC-delta); PI-PLC-delta ...
97-156 1.70e-06

EF-hand motif found in phosphoinositide phospholipase C delta (PI-PLC-delta); PI-PLC-delta isozymes represent a class of metazoan PI-PLCs that are some of the most sensitive to calcium among all PLCs. Their activation is modulated by intracellular calcium ion concentration, phospholipids, polyamines, and other proteins, such as RhoAGAP. Like other PI-PLC isozymes, PI-PLC-delta isozymes contain 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. There are three PI-PLC-delta isozymes (1, 3 and 4). PI-PLC-delta1 is relatively well characterized. It is activated by high calcium levels generated by other PI-PLC family members, and therefore functions as a calcium amplifier within the cell. Different PI-PLC-delta isozymes have different tissue distribution and different subcellular locations. PI-PLC-delta1 is mostly a cytoplasmic protein, PI-PLC-delta3 is located in the membrane, and PI-PLC-delta4 is predominantly detected in the cell nucleus. PI-PLC-delta isozymes is evolutionarily conserved even in non-mammalian species, such as yeast, slime molds and plants.


Pssm-ID: 320032 [Multi-domain]  Cd Length: 140  Bit Score: 44.91  E-value: 1.70e-06
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 4507615   97 LSDLFRMFDKNADGYIDLDELKIMLQATGETITEDDIEELMKDGDKNNDGRIDYDEFLEF 156
Cdd:cd16202   2 LKDQFRKADKNGDGKLSFKECKKLLKKLNVKVDKDYAKKLFQEADTSGEDVLDEEEFVQF 61
EFh_PEF_Group_II_CAPN_like cd16182
Penta-EF hand, calcium binding motifs, found in PEF calpain family; The PEF calpain family ...
32-157 1.83e-06

Penta-EF hand, calcium binding motifs, found in PEF calpain family; The PEF calpain family belongs to the second group of penta-EF hand (PEF) proteins. It includes classical (also called conventional or typical) calpain (referring to a calcium-dependent papain-like enzymes, EC 3.4.22.17) large catalytic subunits (CAPN1, 2, 3, 8, 9, 11, 12, 13, 14) and two calpain small subunits (CAPNS1 and CAPNS2), which are largely confined to animals (metazoans). These PEF-containing are nonlysosomal intracellular calcium-activated intracellular cysteine proteases that play important roles in the degradation or functional modulation in a variety of substrates in response to calcium signalling. The classical mu- and m-calpains are heterodimers consisting of homologous but a distinct (large) L-subunit/chain (CAPN1 or CAPN2) and a common (small) S-subunit/chain (CAPNS1 or CAPNS2). These L-subunits (CAPN1 and CAPN2) and S-subunit CAPNS1 are ubiquitously found in all tissues. Other calpains likely consist of an isolated L-subunit/chain alone. Many of them, such as CAPNS2, CAPN3 (in skeletal muscle, or lens), CAPN8 (in stomach), CAPN9 (in digestive tracts), CAPN11 (in testis), CAPN12 (in follicles), are tissue-specific and have specific functions in distinct organs. The L-subunits of similar structure (called CALPA and B) also have been found in Drosophila melanogaster. The S-subunit seems to have a chaperone-like function for proper folding of the L-subunit. The catalytic L-subunits contain a short N-terminal anchor helix, followed by a calpain cysteine protease (CysPc) domain, a C2-domain-like (C2L) domain, and a C-terminal Ca2+-binding penta-EF-hand (PEF) domain. The S-subunits only have the PEF domain following an N-terminal Gly-rich hydrophobic domain. The calpains undergo a rearrangement of the protein backbone upon Ca2+-binding.


Pssm-ID: 320057 [Multi-domain]  Cd Length: 167  Bit Score: 45.29  E-value: 1.83e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4507615   32 EDGCISTKELGKVM------RMLGQNPTPEEL-QEMIDEVDEDGSGTVDFDEFLVMMVRCmkddskgkseEELSDLFRMF 104
Cdd:cd16182  12 EDEEIDAVELQKLLnasllkDMPKFDGFSLETcRSLIALMDTNGSGRLDLEEFKTLWSDL----------KKWQAIFKKF 81
                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....
gi 4507615  105 DKNADGYIDLDELKIMLQATGETITEDDIEELM-KDGDKNndGRIDYDEFLEFM 157
Cdd:cd16182  82 DTDRSGTLSSYELRKALESAGFHLSNKVLQALVlRYADST--GRITFEDFVSCL 133
EFh_CREC_Calumenin_like cd16226
EF-hand, calcium binding motif, found in calumenin, reticulocalbin-1 (RCN-1), reticulocalbin-3 ...
93-161 1.90e-06

EF-hand, calcium binding motif, found in calumenin, reticulocalbin-1 (RCN-1), reticulocalbin-3 (RCN-3), and similar proteins; The family corresponds to a group of six EF-hand Ca2+-binding proteins, including calumenin (also known as crocalbin or CBP-50), reticulocalbin-1 (RCN-1), reticulocalbin-3 (RCN-3), and similar proteins. Calumenin is an endo/sarcoplasmic reticulum (ER/SR) resident low-affinity Ca2+-binding protein that contains six EF-hand domains and a C-terminal SR retention signal His-Asp-Glu-Phe (HDEF) tetrapeptide. It functions as a novel regulator of SERCA2, and its expressional changes are tightly coupled with Ca2+-cycling of cardiomyocytes. It is also broadly involved in haemostasis and in the pathophysiology of thrombosis. Moreover, the extracellular calumenin acts as a suppressor of cell migration and tumor metastasis. RCN-1 is an endoplasmic reticulum resident Ca2+-binding protein with a carboxyl-terminal His-Asp-Glu-Leu (HDEL) tetrapeptide signal. It acts as a potential negative regulator of B-RAF activation and can negatively modulate cardiomyocyte hypertrophy by inhibition of the mitogen-activated protein kinase signalling cascade. It also plays a key role in the development of doxorubicin-associated resistance. RCN-3 is a putative six EF-hand Ca2+-binding protein that contains five RXXR (X is any amino acid) motifs and a C-terminal ER retrieval signal HDEL tetrapeptide. The RXXR motif represents the target sequence of subtilisin-like proprotein convertases (SPCs). RCN-3 is specifically bound to the paired basic amino-acid-cleaving enzyme-4 (PACE4) precursor protein and plays an important role in the biosynthesis of PACE4.


Pssm-ID: 320024 [Multi-domain]  Cd Length: 264  Bit Score: 46.04  E-value: 1.90e-06
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 4507615   93 SEEELSDLFRMFDKNADGYIDLDELKIMLQATGETITEDDIEELMKDGDKNNDGRIDYDEFLEFMKGVE 161
Cdd:cd16226  33 SKERLGIIVDKIDKNGDGFVTEEELKDWIKYVQKKYIREDVDRQWKEYDPNKDGKLSWEEYKKATYGFL 101
EFh_parvalbumins cd16253
EF-hand, calcium binding motif, found in parvalbumins; Parvalbumins are small, acidic, ...
90-158 2.27e-06

EF-hand, calcium binding motif, found in parvalbumins; Parvalbumins are small, acidic, cytosolic EF-hand-containing Ca2+-buffer and Ca2+ transporter/shuttle proteins belonging to EF-hand superfamily. They are expressed by vertebrates in fast-twitch muscle cells, specific neurons of the central and peripheral nervous system, sensory cells of the mammalian auditory organ (Corti's cell), and some other cells, and characterized by the presence of three consecutive EF-hand motifs (helix-loop-helix) called AB, CD, and EF, but only CD and EF can chelate metal ions, such as Ca2+ and Mg2+. Thus, they may play an additional role in Mg2+ handling. Moreover, parvalbumins represent one of the major animal allergens. In metal-bound states, parvalbumins possess a rigid and stable tertiary structure and display strong allergenicity. In contrast, the metal-free parvalbumins are intrinsically disordered, and the loss of metal ions results in a conformational change that decreases their IgE binding capacity. Furthermore, parvalbumins have been widely used as a neuronal marker for a variety of functional brain systems. They also function as a Ca2+ shuttle transporting Ca2+ from troponin-C (TnC) to the sarcoplasmic reticulum (SR) Ca2+ pump during muscle relaxation. Thus they may facilitate myocardial relaxation and play important roles in cardiac diastolic dysfunction. Parvalbumins consists of alpha- and beta- sublineages, which can be distinguished on the basis of isoelectric point (pI > 5 for alpha; pI


Pssm-ID: 319996 [Multi-domain]  Cd Length: 101  Bit Score: 43.70  E-value: 2.27e-06
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 4507615   90 KGKSEEELSDLFRMFDKNADGYIDLDELKIMLQ---ATGETITEDDIEELMKDGDKNNDGRIDYDEFLEFMK 158
Cdd:cd16253  29 SKKSPADIKKVFNILDQDKSGFIEEEELKLFLKnfsDGARVLSDKETKNFLAAGDSDGDGKIGVDEFKSMVK 100
EFh_PI-PLC cd15898
EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4. ...
57-160 2.43e-06

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: 44.58  E-value: 2.43e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4507615   57 LQEMIDEVDEDGSGTVDFDEFLVMMVRcmkdDSKGKSEEELSDLFRMFDKNADGYIDLDEL-KIMLQATgetiTEDDIEE 135
Cdd:cd15898   2 LRRQWIKADKDGDGKLSLKEIKKLLKR----LNIRVSEKELKKLFKEVDTNGDGTLTFDEFeELYKSLT----ERPELEP 73
                        90       100
                ....*....|....*....|....*
gi 4507615  136 LMKDGDKNNDGRIDYDEFLEFMKGV 160
Cdd:cd15898  74 IFKKYAGTNRDYMTLEEFIRFLREE 98
EF-hand_7 pfam13499
EF-hand domain pair;
55-122 3.02e-06

EF-hand domain pair;


Pssm-ID: 463900 [Multi-domain]  Cd Length: 67  Bit Score: 42.63  E-value: 3.02e-06
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 4507615     55 EELQEMIDEVDEDGSGTVDFDEFLVMMVRCMKDDSKgkSEEELSDLFRMFDKNADGYIDLDELKIMLQ 122
Cdd:pfam13499   2 EKLKEAFKLLDSDGDGYLDVEELKKLLRKLEEGEPL--SDEEVEELFKEFDLDKDGRISFEEFLELYS 67
EFh_PEF_CAPN13_14 cd16195
Penta-EF hand, calcium binding motifs, found in calpain-13 (CAPN13), calpain-14 (CAPN14), and ...
55-157 3.03e-06

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: 44.89  E-value: 3.03e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4507615   55 EELQEMIDEVDEDGSGTVDFDEFLVMMvrcmkddskgKSEEELSDLFRMFDKNADGYIDLDELKIMLQATGETITeDDIE 134
Cdd:cd16195  43 DACRSMVALMDLSVNGRLSLEEFSRLW----------KKLRKYKDIFQKADVSKSGFLSLSELRNAIQAAGIRVS-DDLL 111
                        90       100
                ....*....|....*....|....*
gi 4507615  135 ELM--KDGDKnnDGRIDYDEFLEFM 157
Cdd:cd16195 112 NLMalRYGDS--SGRISFESFICLM 134
EFh_ScPlc1p_like cd16207
EF-hand motif found in Saccharomyces cerevisiae phospholipase C-1 (ScPlc1p) and similar ...
46-157 3.45e-06

EF-hand motif found in Saccharomyces cerevisiae phospholipase C-1 (ScPlc1p) and similar proteins; This family represents a group of putative phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11) encoded by PLC1 genes from yeasts, which are homologs of the delta isoforms of mammalian PI-PLC in terms of overall sequence similarity and domain organization. Mammalian PI-PLC is a signaling enzyme that hydrolyzes 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 then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. The prototype of this family is protein Plc1p (also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase 1) encoded by PLC1 genes from Saccharomyces cerevisiae. ScPlc1p contains both highly conserved X- and Y- regions of PLC catalytic core domain, as well as a presumptive EF-hand like calcium binding motif. Experiments show that ScPlc1p displays calcium dependent catalytic properties with high similarity to those of the mammalian PLCs, and plays multiple roles in modulating the membrane/protein interactions in filamentation control. CaPlc1p encoded by CAPLC1 from the closely related yeast Candida albicans, an orthologue of S. cerevisiae Plc1p, is also included in this group. Like SCPlc1p, CaPlc1p has conserved presumptive catalytic domain, shows PLC activity when expressed in E. coli, and is involved in multiple cellular processes. There are two other gene copies of CAPLC1 in C. albicans, CAPLC2 (also named as PIPLC) and CAPLC3. Experiments show CaPlc1p is the only enzyme in C. albicans which functions as PLC. The biological functions of CAPLC2 and CAPLC3 gene products must be clearly different from CaPlc1p, but their exact roles remain unclear. Moreover, CAPLC2 and CAPLC3 gene products are more similar to extracellular bacterial PI-PLC than to the eukaryotic PI-PLC, and they are not included in this subfamily.


Pssm-ID: 320037 [Multi-domain]  Cd Length: 142  Bit Score: 44.16  E-value: 3.45e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4507615   46 RMLGQNPTPEELQEMIDEVDEDGSGTVDFDEFLVmMVRCMKDdskgksEEELSDLFRMFDKNADGYIDLDE-LKIMLQAT 124
Cdd:cd16207  29 RRLHINCSESYLRELFDKADTDKKGYLNFEEFQE-FVKLLKR------RKDIKAIFKQLTKPGSDGLTLEEfLKFLRDVQ 101
                        90       100       110
                ....*....|....*....|....*....|....*..
gi 4507615  125 GETITEDDIEELM----KDGDKNNDGRIDYDEFLEFM 157
Cdd:cd16207 102 KEDVDRETWEKIFekfaRRIDDSDSLTMTLEGFTSFL 138
EFh_PEF_Group_I cd16180
Penta-EF hand, calcium binding motifs, found in Group I PEF proteins; The family corresponds ...
33-112 5.24e-06

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: 44.06  E-value: 5.24e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4507615   33 DGCISTKELGKVMRMLGQNPTPEELQEMIDEVDEDGSGTVDFDEFLVMMVrCMKddskgkseeELSDLFRMFDKNADGYI 112
Cdd:cd16180  81 SGSIDFNELQNALSSFGYRLSPQFVQLLVRKFDRRRRGSISFDDFVEACV-TLK---------RLTDAFRKYDTNRTGYA 150
EFh_CREC_RCN2_like cd16227
EF-hand, calcium binding motif, found in reticulocalbin-2 (RCN2) mainly from protostomes; This ...
1-155 5.53e-06

EF-hand, calcium binding motif, found in reticulocalbin-2 (RCN2) mainly from protostomes; This family corresponds to a group of uncharacterized RCN2-like proteins, which are mainly found in protostomes. Although their biological function remains unclear, they show high sequence similarity with RCN2 (also known as E6BP or TCBP-49), which is an endoplasmic reticulum resident low-affinity Ca2+-binding protein that has been implicated in immunity, redox homeostasis, cell cycle regulation and coagulation. Members in this family contain six copies of the EF-hand Ca2+-binding motif, but may lack a C-terminal His-Asp-Glu-Leu (HDEL) tetrapeptide that is required for retention of RCN2 in the endoplasmic reticulum (ER).


Pssm-ID: 320025 [Multi-domain]  Cd Length: 263  Bit Score: 44.62  E-value: 5.53e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4507615    1 MDDIYKAAVEQLTEEQKNEFKAAfDIfvlgAEDGCISTKELGKVmrmlgQNPT------PEELQEMIDEVDEDGSGTVDF 74
Cdd:cd16227 109 MIKDSTEDDLKLLEDDKEMFEAA-DL----NKDGKLDKTEFSAF-----QHPEeyphmhPVLIEQTLRDKDKDNDGFISF 178
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4507615   75 DEFLVMMVrcmKDDSKGKSEEELSDLFRMFDKNADGYIDLDELKIMLQATGETITEDDIEELMKDGDKNNDGRIDYDEFL 154
Cdd:cd16227 179 QEFLGDRA---GHEDKEWLLVEKDRFDEDYDKDGDGKLDGEEILSWLVPDNEEIAEEEVDHLFASADDDHDDRLSFDEIL 255

                .
gi 4507615  155 E 155
Cdd:cd16227 256 D 256
EFh_CREC cd15899
EF-hand, calcium binding motif, found in CREC-EF hand family; The CREC (Cab45/reticulocalbin ...
10-159 2.71e-05

EF-hand, calcium binding motif, found in CREC-EF hand family; The CREC (Cab45/reticulocalbin/ERC45/calumenin)-EF hand family contains a group of six EF-hand, low-affinity Ca2+-binding proteins, including reticulocalbin (RCN-1), ER Ca2+-binding protein of 55 kDa (ERC-55, also known as TCBP-49 or E6BP), reticulocalbin-3 (RCN-3), Ca2+-binding protein of 45 kDa (Cab45 and its splice variant Cab45b), and calumenin ( also known as crocalbin or CBP-50). The proteins are not only localized in various parts of the secretory pathway, but also found in the cytosolic compartment and at the cell surface. They interact with different ligands or proteins and have been implicated in the secretory process, chaperone activity, signal transduction as well as in a large variety of disease processes.


Pssm-ID: 320021 [Multi-domain]  Cd Length: 267  Bit Score: 42.81  E-value: 2.71e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4507615   10 EQLT-EEQKNEFKAAFDIfVLGAEDGCISTKELGKVMRMLGQNPTPEELQEMIDEVDEDGSGTVDFDEFLVMM------- 81
Cdd:cd15899  26 DQLTpEESKRRLGVIVSK-MDVDKDGFISAKELHSWILESFKRHAMEESKEQFRAVDPDEDGHVSWDEYKNDTygsvgdd 104
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4507615   82 -----VRCMKDDSKGKSEEELSDLFRMFDKNADGYIDLDELKIMLQAT-GETITEDDIEELMKDGDKNNDGRIDYDEFLE 155
Cdd:cd15899 105 eenvaDNIKEDEEYKKLLLKDKKRFEAADQDGDLILTLEEFLAFLHPEeSPYMLDFVIKETLEDLDKNGDGFISLEEFIS 184

                ....
gi 4507615  156 FMKG 159
Cdd:cd15899 185 DPYS 188
EFh_PEF_CalpA_B cd16196
Penta-EF hand, calcium binding motifs, found in Drosophila melanogaster calpain-A (CalpA), ...
60-157 2.75e-05

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: 42.19  E-value: 2.75e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4507615   60 MIDEVDEDGSGTVDFDEF--LVMMVRCMKDdskgkseeelsdLFRMFDKNADGYIDLDELKIMLQATGETITEDDIEEL- 136
Cdd:cd16196  46 MVAMMDVDRSGKLGFEEFkkLWEDLRSWKR------------VFKLFDTDGSGSFSSFELRNALNSAGFRLSNATLNALv 113
                        90       100
                ....*....|....*....|.
gi 4507615  137 MKDGDKnnDGRIDYDEFLEFM 157
Cdd:cd16196 114 LRYSNK--DGRISFDDFIMCA 132
EFh_PEF_ALG-2_like cd16185
EF-hand, calcium binding motif, found in homologs of mammalian apoptosis-linked gene 2 protein ...
96-156 3.42e-05

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: 41.82  E-value: 3.42e-05
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 4507615   96 ELSDLFRMFDKNADGYIDLDELKIMLQATGETITEDDIEELMKDGDKNNDGRIDYDEFLEF 156
Cdd:cd16185   1 ELRQWFRAVDRDRSGSIDVNELQKALAGGGLLFSLATAEKLIRMFDRDGNGTIDFEEFAAL 61
EFh_HEF cd15902
EF-hand, calcium binding motif, found in the hexa-EF hand proteins family; The hexa-EF hand ...
54-153 3.93e-05

EF-hand, calcium binding motif, found in the hexa-EF hand proteins family; The hexa-EF hand proteins family, also named the calbindin sub-family, contains a group of six EF-hand Ca2+-binding proteins, including calretinin (CR, also termed 29 kDa calbindin), calbindin D28K (CB, also termed vitamin D-dependent calcium-binding protein, avian-type), and secretagogin (SCGN). CR is a cytosolic hexa-EF-hand calcium-binding protein predominantly expressed in a variety of normal and tumorigenic t-specific neurons of the central and peripheral nervous system. It is a multifunctional protein implicated in many biological processes, including cell proliferation, differentiation, and cell death. CB is highly expressed in brain tissue. It is a strong calcium-binding and buffering protein responsible for preventing a neuronal death as well as maintaining and controlling calcium homeostasis. SCGN is a six EF-hand calcium-binding protein expressed in neuroendocrine, pancreatic endocrine and retinal cells. It plays a crucial role in cell apoptosis, receptor signaling and differentiation. It is also involved in vesicle secretion through binding to various proteins, including interacts with SNAP25, SNAP23, DOC2alpha, ARFGAP2, rootletin, KIF5B, beta-tubulin, DDAH-2, ATP-synthase and myeloid leukemia factor 2. SCGN functions as a Ca2+ sensor/coincidence detector modulating vesicular exocytosis of neurotransmitters, neuropeptides or hormones. Although the family members share a significant amount of secondary sequence homology, they display altered structural and biochemical characteristics, and operate in distinct fashions. CB contains six EF-hand motifs in a single globular domain, where EF-hands 1, 3, 4, 5 bind four calcium ions. CR contains six EF-hand motifs within two independent domains, CR I-II and CR III-VI. They harbor two and four EF-hand motifs, respectively. The first 5 EF-hand motifs are capable of binding calcium ions, while the EF-hand 6 is inactive. SCGN consists of the three globular domains each of which contains a pair of EF-hand motifs. Human SCGN simultaneously binds four calcium ions through its EF-hands 3, 4, 5 and 6 in one high affinity and three low affinity calcium-binding sites. In contrast, SCGNs in other lower eukaryotes, such as D. rerio, X. laevis, M. domestica, G. gallus, O. anatinus, are fully competent in terms of six calcium-binding.


Pssm-ID: 320075 [Multi-domain]  Cd Length: 254  Bit Score: 42.34  E-value: 3.93e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4507615   54 PEELQEMIDEVDEDGSGTVDFDEFLVMMV------RCMKDDSKGKSEEELSDLFRMFDKNADGYIDLDELKIMLQ----- 122
Cdd:cd15902  43 AEKKKEFMEKYDENEDGKIEIRELANILPteenflLLFRREQPLISSVEFMKIWRKYDTDGSGFIEAKELKGFLKdlllk 122
                        90       100       110
                ....*....|....*....|....*....|....
gi 4507615  123 ---ATGETITEDDIEELMKDGDKNNDGRIDYDEF 153
Cdd:cd15902 123 nkkHVSPPKLDEYTKLILKEFDANKDGKLELDEM 156
EFh_PEF_Group_I cd16180
Penta-EF hand, calcium binding motifs, found in Group I PEF proteins; The family corresponds ...
96-153 7.86e-05

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: 40.59  E-value: 7.86e-05
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 4507615   96 ELSDLFRMFDKNADGYIDLDEL-KIMLQATGETITEDDIEELMKDGDKNNDGRIDYDEF 153
Cdd:cd16180   1 ELRRIFQAVDRDRSGRISAKELqRALSNGDWTPFSIETVRLMINMFDRDRSGTINFDEF 59
S-100 cd00213
S-100: S-100 domain, which represents the largest family within the superfamily of proteins ...
109-160 1.12e-04

S-100: S-100 domain, which represents the largest family within the superfamily of proteins carrying the Ca-binding EF-hand motif. Note that this S-100 hierarchy contains only S-100 EF-hand domains, other EF-hands have been modeled separately. S100 proteins are expressed exclusively in vertebrates, and are implicated in intracellular and extracellular regulatory activities. Intracellularly, S100 proteins act as Ca-signaling or Ca-buffering proteins. The most unusual characteristic of certain S100 proteins is their occurrence in extracellular space, where they act in a cytokine-like manner through RAGE, the receptor for advanced glycation products. Structural data suggest that many S100 members exist within cells as homo- or heterodimers and even oligomers; oligomerization contributes to their functional diversification. Upon binding calcium, most S100 proteins change conformation to a more open structure exposing a hydrophobic cleft. This hydrophobic surface represents the interaction site of S100 proteins with their target proteins. There is experimental evidence showing that many S100 proteins have multiple binding partners with diverse mode of interaction with different targets. In addition to S100 proteins (such as S100A1,-3,-4,-6,-7,-10,-11,and -13), this group includes the ''fused'' gene family, a group of calcium binding S100-related proteins. The ''fused'' gene family includes multifunctional epidermal differentiation proteins - profilaggrin, trichohyalin, repetin, hornerin, and cornulin; functionally these proteins are associated with keratin intermediate filaments and partially crosslinked to the cell envelope. These ''fused'' gene proteins contain N-terminal sequence with two Ca-binding EF-hands motif, which may be associated with calcium signaling in epidermal cells and autoprocessing in a calcium-dependent manner. In contrast to S100 proteins, "fused" gene family proteins contain an extraordinary high number of almost perfect peptide repeats with regular array of polar and charged residues similar to many known cell envelope proteins.


Pssm-ID: 238131 [Multi-domain]  Cd Length: 88  Bit Score: 39.01  E-value: 1.12e-04
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 4507615  109 DGYIDLDELKIMLQA-----TGETITEDDIEELMKDGDKNNDGRIDYDEFLEFMKGV 160
Cdd:cd00213  24 KDTLSKKELKELLETelpnfLKNQKDPEAVDKIMKDLDVNKDGKVDFQEFLVLIGKL 80
EFh_CREC_RCN2 cd16224
EF-hand, calcium binding motif, found in reticulocalbin-2 (RCN2); RCN2, also termed ...
57-155 1.21e-04

EF-hand, calcium binding motif, found in reticulocalbin-2 (RCN2); RCN2, also termed calcium-binding protein ERC-55, or E6-binding protein (E6BP), or TCBP-49, is an endoplasmic reticulum resident low-affinity Ca2+-binding protein that has been implicated in immunity, redox homeostasis, cell cycle regulation and coagulation. It is associated with tumorigenesis, in particular with transformation of cells of the cervix induced by human papillomavirus (HPV), through binding to human papillomavirus (HPV) E6 oncogenic protein. It specifically interacts with vitamin D receptor among nuclear receptors. RCN2 contains an N-terminal signal sequence followed by six copies of the EF-hand Ca2+-binding motif, and a C-terminal His-Asp-Glu-Leu (HDEL) tetrapeptide that is required for retention of RCN2 in the endoplasmic reticulum (ER).


Pssm-ID: 320022 [Multi-domain]  Cd Length: 268  Bit Score: 40.88  E-value: 1.21e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4507615   57 LQEMIDEVDEDGSGTVDFDEFLVMMVRCMKDDSKGKSEEELSDLFR-MFDKNADGYIDLDELKIMLQATGETITEDDIEE 135
Cdd:cd16224 163 IQEALEEHDKDGDGFISLEEFLGDYRKDPTANEDPEWIIVEKDRFVnDYDKDNDGKLDPQELLPWVVPNNYGIAQEEALH 242
                        90       100
                ....*....|....*....|
gi 4507615  136 LMKDGDKNNDGRIDYDEFLE 155
Cdd:cd16224 243 LIDEMDLNGDGRLSEEEILE 262
EFh_CREC cd15899
EF-hand, calcium binding motif, found in CREC-EF hand family; The CREC (Cab45/reticulocalbin ...
57-155 1.29e-04

EF-hand, calcium binding motif, found in CREC-EF hand family; The CREC (Cab45/reticulocalbin/ERC45/calumenin)-EF hand family contains a group of six EF-hand, low-affinity Ca2+-binding proteins, including reticulocalbin (RCN-1), ER Ca2+-binding protein of 55 kDa (ERC-55, also known as TCBP-49 or E6BP), reticulocalbin-3 (RCN-3), Ca2+-binding protein of 45 kDa (Cab45 and its splice variant Cab45b), and calumenin ( also known as crocalbin or CBP-50). The proteins are not only localized in various parts of the secretory pathway, but also found in the cytosolic compartment and at the cell surface. They interact with different ligands or proteins and have been implicated in the secretory process, chaperone activity, signal transduction as well as in a large variety of disease processes.


Pssm-ID: 320021 [Multi-domain]  Cd Length: 267  Bit Score: 40.89  E-value: 1.29e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4507615   57 LQEMIDEVDEDGSGTVDFDEFLVMMVRCMKDDSKGKSEEELSDLFR-MFDKNADGYIDLDELKIMLQATGETITEDDIEE 135
Cdd:cd15899 162 IKETLEDLDKNGDGFISLEEFISDPYSADENEEEPEWVKVEKERFVeLRDKDKDGKLDGEELLSWVDPSNQEIALEEAKH 241
                        90       100
                ....*....|....*....|
gi 4507615  136 LMKDGDKNNDGRIDYDEFLE 155
Cdd:cd15899 242 LIAESDENKDGKLSPEEILD 261
EFh_HEF cd15902
EF-hand, calcium binding motif, found in the hexa-EF hand proteins family; The hexa-EF hand ...
32-158 1.83e-04

EF-hand, calcium binding motif, found in the hexa-EF hand proteins family; The hexa-EF hand proteins family, also named the calbindin sub-family, contains a group of six EF-hand Ca2+-binding proteins, including calretinin (CR, also termed 29 kDa calbindin), calbindin D28K (CB, also termed vitamin D-dependent calcium-binding protein, avian-type), and secretagogin (SCGN). CR is a cytosolic hexa-EF-hand calcium-binding protein predominantly expressed in a variety of normal and tumorigenic t-specific neurons of the central and peripheral nervous system. It is a multifunctional protein implicated in many biological processes, including cell proliferation, differentiation, and cell death. CB is highly expressed in brain tissue. It is a strong calcium-binding and buffering protein responsible for preventing a neuronal death as well as maintaining and controlling calcium homeostasis. SCGN is a six EF-hand calcium-binding protein expressed in neuroendocrine, pancreatic endocrine and retinal cells. It plays a crucial role in cell apoptosis, receptor signaling and differentiation. It is also involved in vesicle secretion through binding to various proteins, including interacts with SNAP25, SNAP23, DOC2alpha, ARFGAP2, rootletin, KIF5B, beta-tubulin, DDAH-2, ATP-synthase and myeloid leukemia factor 2. SCGN functions as a Ca2+ sensor/coincidence detector modulating vesicular exocytosis of neurotransmitters, neuropeptides or hormones. Although the family members share a significant amount of secondary sequence homology, they display altered structural and biochemical characteristics, and operate in distinct fashions. CB contains six EF-hand motifs in a single globular domain, where EF-hands 1, 3, 4, 5 bind four calcium ions. CR contains six EF-hand motifs within two independent domains, CR I-II and CR III-VI. They harbor two and four EF-hand motifs, respectively. The first 5 EF-hand motifs are capable of binding calcium ions, while the EF-hand 6 is inactive. SCGN consists of the three globular domains each of which contains a pair of EF-hand motifs. Human SCGN simultaneously binds four calcium ions through its EF-hands 3, 4, 5 and 6 in one high affinity and three low affinity calcium-binding sites. In contrast, SCGNs in other lower eukaryotes, such as D. rerio, X. laevis, M. domestica, G. gallus, O. anatinus, are fully competent in terms of six calcium-binding.


Pssm-ID: 320075 [Multi-domain]  Cd Length: 254  Bit Score: 40.41  E-value: 1.83e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4507615   32 EDGCISTKELGKVMRMLGQN------PTPEELQEMIDEV----DEDGSGTVDFDEFlvmmVRCMKD--------DSKGKS 93
Cdd:cd15902  57 EDGKIEIRELANILPTEENFlllfrrEQPLISSVEFMKIwrkyDTDGSGFIEAKEL----KGFLKDlllknkkhVSPPKL 132
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 4507615   94 EEELSDLFRMFDKNADGYIDLDELKIML-----------QATGETITEDDIEELMKDGDKNNDGRIDYDEFLEFMK 158
Cdd:cd15902 133 DEYTKLILKEFDANKDGKLELDEMAKLLpvqenfllkfqILGAMDLTKEDFEKVFEHYDKDNNGVIEGNELDALLK 208
EF-hand_8 pfam13833
EF-hand domain pair;
109-158 1.85e-04

EF-hand domain pair;


Pssm-ID: 404678 [Multi-domain]  Cd Length: 54  Bit Score: 37.68  E-value: 1.85e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 4507615    109 DGYIDLDELKIMLQATG-ETITEDDIEELMKDGDKNNDGRIDYDEFLEFMK 158
Cdd:pfam13833   2 KGVITREELKRALALLGlKDLSEDEVDILFREFDTDGDGYISFDEFCVLLE 52
PLN02964 PLN02964
phosphatidylserine decarboxylase
54-152 2.08e-04

phosphatidylserine decarboxylase


Pssm-ID: 215520 [Multi-domain]  Cd Length: 644  Bit Score: 40.61  E-value: 2.08e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4507615    54 PEELQEMIDEVDEDGSGTVdfdeFLVMMVRCMKDDSKGKSEEELSDLFRMFDKNADGYIDLDELKIMLQATGETITEDDI 133
Cdd:PLN02964 142 PESACESFDLLDPSSSNKV----VGSIFVSCSIEDPVETERSFARRILAIVDYDEDGQLSFSEFSDLIKAFGNLVAANKK 217
                         90
                 ....*....|....*....
gi 4507615   134 EELMKDGDKNNDGRIDYDE 152
Cdd:PLN02964 218 EELFKAADLNGDGVVTIDE 236
EFh smart00054
EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in ...
56-81 2.38e-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: 36.59  E-value: 2.38e-04
                           10        20
                   ....*....|....*....|....*.
gi 4507615      56 ELQEMIDEVDEDGSGTVDFDEFLVMM 81
Cdd:smart00054   1 ELKEAFRLFDKDGDGKIDFEEFKDLL 26
EF-hand_6 pfam13405
EF-hand domain;
96-125 2.40e-04

EF-hand domain;


Pssm-ID: 463869 [Multi-domain]  Cd Length: 30  Bit Score: 36.77  E-value: 2.40e-04
                          10        20        30
                  ....*....|....*....|....*....|
gi 4507615     96 ELSDLFRMFDKNADGYIDLDELKIMLQATG 125
Cdd:pfam13405   1 ELREAFKLFDKDGDGKISLEELRKALRSLG 30
EFh_HEF_CBN cd16179
EF-hand, calcium binding motif, found in Drosophila melanogaster calbindin-32 (CBN) and ...
10-158 3.96e-04

EF-hand, calcium binding motif, found in Drosophila melanogaster calbindin-32 (CBN) and similar proteins; CBN, the product of the cbn gene, is a Drosophila homolog to vertebrate neuronal six EF-hand calcium binding proteins. It is expressed through most of ontogenesis with a selective distribution in the nervous system and in a few small adult thoracic muscles. Its precise biological role remains unclear. CBN contains six EF-hand motifs, but some of them may not bind calcium ions due to the lack of key residues.


Pssm-ID: 320079 [Multi-domain]  Cd Length: 261  Bit Score: 39.31  E-value: 3.96e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4507615   10 EQLTEEQKNEFKAAFDifvlGAEDGCISTKELGKVMRM------LGQNPTP----EELQEMIDEVDEDGSGTVDFDE--- 76
Cdd:cd16179  44 ETALEELKEEFMEAYD----ENQDGRIDIRELAQLLPTeenfllLFRRDNPldssVEFMKVWREYDKDNSGYIEADElkn 119
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4507615   77 FLVMMVRCMK---DDSKGKSEEELSDLFRMFDKNADGYIDLDELKIMLQA-----------TGETITEDDIEELMKDGDK 142
Cdd:cd16179 120 FLKHLLKEAKrdnDVSEDKLIEYTDTILQLFDRNKDGKLQLSEMARLLPVkenflcrpifkGAGKLTREDIDRVFALYDR 199
                       170
                ....*....|....*.
gi 4507615  143 NNDGRIDYDEFLEFMK 158
Cdd:cd16179 200 DNNGTIENEELTGFLK 215
ELC_N cd22949
N-terminal domain of Myosin essential light chain ELC; ELC is part of the apicomplexan ...
93-158 4.06e-04

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: 36.94  E-value: 4.06e-04
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 4507615   93 SEEELSDLFRMFDKNADGYIDLDELKIMLQATGETITEDDIEELmkdgdknnDGRIDYDEFLEFMK 158
Cdd:cd22949   1 MEEKFREAFILFDRDGDGELTMYEAVLAMRSCGIPLTNDEKDAL--------PASMNWDQFENWAK 58
EFh_CREC_RCN3 cd16230
EF-hand, calcium binding motif, found in reticulocalbin-3 (RCN-3); RCN-3, also termed EF-hand ...
30-154 4.14e-04

EF-hand, calcium binding motif, found in reticulocalbin-3 (RCN-3); RCN-3, also termed EF-hand calcium-binding protein RLP49, is a putative six EF-hand Ca2+-binding protein that contains five RXXR (X is any amino acid) motifs and a C-terminal ER retrieval signal His-Asp-Glu-Leu (HDEL) tetrapeptide. The RXXR motif represents the target sequence of subtilisin-like proprotein convertases (SPCs). RCN-3 is specifically bound to the paired basic amino-acid-cleaving enzyme-4 (PACE4) precursor protein and plays an important role in the biosynthesis of PACE4.


Pssm-ID: 320028 [Multi-domain]  Cd Length: 268  Bit Score: 39.19  E-value: 4.14e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4507615   30 GAEDGCISTKELGKVMRMLGQNPTPEELQEMIDEVDEDGSGTVDFDEFLVMMVRCMKDDSKGKSEEELSDL--------- 100
Cdd:cd16230  48 GDGDGWVSLAELRAWIAHTQQRHIRDSVSAAWQTYDTDRDGRVGWEELRNATYGHYEPGEEFHDVEDAETYkkmlarder 127
                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 4507615  101 -FRMFDKNADGYIDLDELKIMLQATG-ETITEDDIEELMKDGDKNNDGRIDYDEFL 154
Cdd:cd16230 128 rFRVADQDGDSMATREELTAFLHPEEfPHMRDIVVAETLEDLDKNKDGYVQVEEYI 183
EFh_PEF_peflin cd16184
EF-hand, calcium binding motif, found in peflin and similar proteins; Peflin, also termed ...
60-153 7.22e-04

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: 38.01  E-value: 7.22e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4507615   60 MIDEVDEDGSGTVDFDEF--LVMMVRCMKddskgkseeelsDLFRMFDKNADGYIDLDELKIMLQATGETITEDDIEELM 137
Cdd:cd16184  42 MIGMFDKDKSGTIDIYEFqaLWNYIQQWK------------QVFQQFDRDRSGSIDENELHQALSQMGYRLSPQFVQFLV 109
                        90
                ....*....|....*.
gi 4507615  138 KDGDKNNDGRIDYDEF 153
Cdd:cd16184 110 SKYDPRARRSLTLDQF 125
EFh_CREC_RCN2_like cd16227
EF-hand, calcium binding motif, found in reticulocalbin-2 (RCN2) mainly from protostomes; This ...
89-154 1.11e-03

EF-hand, calcium binding motif, found in reticulocalbin-2 (RCN2) mainly from protostomes; This family corresponds to a group of uncharacterized RCN2-like proteins, which are mainly found in protostomes. Although their biological function remains unclear, they show high sequence similarity with RCN2 (also known as E6BP or TCBP-49), which is an endoplasmic reticulum resident low-affinity Ca2+-binding protein that has been implicated in immunity, redox homeostasis, cell cycle regulation and coagulation. Members in this family contain six copies of the EF-hand Ca2+-binding motif, but may lack a C-terminal His-Asp-Glu-Leu (HDEL) tetrapeptide that is required for retention of RCN2 in the endoplasmic reticulum (ER).


Pssm-ID: 320025 [Multi-domain]  Cd Length: 263  Bit Score: 38.07  E-value: 1.11e-03
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 4507615   89 SKGKSEEELSDLFRMFDKNADGYIDLDELKIMLQATGETITEDDIEELMKDGDKNNDGRIDYDEFL 154
Cdd:cd16227  30 PPEEAKRRLAVLAKKMDLNDDGFIDRKELKAWILRSFKMLDEEEANERFEEADEDGDGKVTWEEYL 95
PLN02964 PLN02964
phosphatidylserine decarboxylase
64-121 1.29e-03

phosphatidylserine decarboxylase


Pssm-ID: 215520 [Multi-domain]  Cd Length: 644  Bit Score: 38.30  E-value: 1.29e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 4507615    64 VDEDGSGTVDFDEFLVMMvrcmKDDSKGKSEEELSDLFRMFDKNADGYIDLDELKIML 121
Cdd:PLN02964 188 VDYDEDGQLSFSEFSDLI----KAFGNLVAANKKEELFKAADLNGDGVVTIDELAALL 241
EFh_CREC_Calumenin cd16228
EF-hand, calcium binding motif, found in calumenin; Calumenin, also termed crocalbin, or IEF ...
57-155 1.84e-03

EF-hand, calcium binding motif, found in calumenin; Calumenin, also termed crocalbin, or IEF SSP 9302, is an endo/sarcoplasmic reticulum (ER/SR) resident low-affinity Ca2+-binding protein that contains six EF-hand domains and a C-terminal SR retention signal His-Asp-Glu-Phe (HDEF) tetrapeptide. It is highly expressed in various brain regions. Thus it plays an important role in migration and differentiation of neurons, and/or in Ca2+ signaling between glial cells and neurons. Calumenin is involved in Ca2+ homeostasis through interacting with ryanodine receptor RyR2 and SERCA2. It acts as a novel regulator of SERCA2, and its expressional changes are tightly coupled with Ca2+-cycling of cardiomyocytes. Calumenin also forms a Ca2+-dependent complex with thrombospondin-1, which is broadly involved in haemostasis and thrombosis. Moreover, calumenin is a molecular chaperone that endogenously regulates the vitamin K-dependent gamma-carboxylation of several proteins, including blood coagulation factors (such as FII, FVII, FIX, FX, and proteins C, S and Z), cell survival factors (Gas6) and bone metabolism proteins (such as matrix Gla protein or MGP, osteocalcin and periostin), through targeting the gamma-glutamyl carboxylase. It also functions as a charged F508del-cystic fibrosis transmembrane regulator (CFTR) folding modulator, as well as a G551D-CFTR associated protein. Furthermore, the extracellular calumenin acts as a suppressor of cell migration and tumor metastasis. It binds to and stabilizes fibulin-1, and further inactivates extracellular signal-regulated kinases 1 and 2 (ERK1/2) signaling.


Pssm-ID: 320026 [Multi-domain]  Cd Length: 263  Bit Score: 37.23  E-value: 1.84e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4507615   57 LQEMIDEVDEDGSGTVDFDEFLVMMVRCMKDDSKG---KSEEELSDLFRmfDKNADGYIDLDELKIMLQATGETITEDDI 133
Cdd:cd16228 157 VLETMEDIDKNGDGFIDLEEYIGDMYSQDGDADEPewvKTEREQFTEFR--DKNKDGKMDKEETKDWILPSDYDHAEAEA 234
                        90       100
                ....*....|....*....|..
gi 4507615  134 EELMKDGDKNNDGRIDYDEFLE 155
Cdd:cd16228 235 RHLVYESDQNKDGKLTKEEIVD 256
EFh smart00054
EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in ...
132-158 1.84e-03

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: 34.28  E-value: 1.84e-03
                           10        20
                   ....*....|....*....|....*..
gi 4507615     132 DIEELMKDGDKNNDGRIDYDEFLEFMK 158
Cdd:smart00054   1 ELKEAFRLFDKDGDGKIDFEEFKDLLK 27
EF-hand_1 pfam00036
EF hand; The EF-hands can be divided into two classes: signalling proteins and buffering ...
56-81 1.99e-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: 34.30  E-value: 1.99e-03
                          10        20
                  ....*....|....*....|....*.
gi 4507615     56 ELQEMIDEVDEDGSGTVDFDEFLVMM 81
Cdd:pfam00036   1 ELKEIFRLFDKDGDGKIDFEEFKELL 26
EFh_parvalbumins cd16253
EF-hand, calcium binding motif, found in parvalbumins; Parvalbumins are small, acidic, ...
53-123 2.01e-03

EF-hand, calcium binding motif, found in parvalbumins; Parvalbumins are small, acidic, cytosolic EF-hand-containing Ca2+-buffer and Ca2+ transporter/shuttle proteins belonging to EF-hand superfamily. They are expressed by vertebrates in fast-twitch muscle cells, specific neurons of the central and peripheral nervous system, sensory cells of the mammalian auditory organ (Corti's cell), and some other cells, and characterized by the presence of three consecutive EF-hand motifs (helix-loop-helix) called AB, CD, and EF, but only CD and EF can chelate metal ions, such as Ca2+ and Mg2+. Thus, they may play an additional role in Mg2+ handling. Moreover, parvalbumins represent one of the major animal allergens. In metal-bound states, parvalbumins possess a rigid and stable tertiary structure and display strong allergenicity. In contrast, the metal-free parvalbumins are intrinsically disordered, and the loss of metal ions results in a conformational change that decreases their IgE binding capacity. Furthermore, parvalbumins have been widely used as a neuronal marker for a variety of functional brain systems. They also function as a Ca2+ shuttle transporting Ca2+ from troponin-C (TnC) to the sarcoplasmic reticulum (SR) Ca2+ pump during muscle relaxation. Thus they may facilitate myocardial relaxation and play important roles in cardiac diastolic dysfunction. Parvalbumins consists of alpha- and beta- sublineages, which can be distinguished on the basis of isoelectric point (pI > 5 for alpha; pI


Pssm-ID: 319996 [Multi-domain]  Cd Length: 101  Bit Score: 36.00  E-value: 2.01e-03
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 4507615   53 TPEELQEMIDEVDEDGSGTVDFDEfLVMMVRCMKDDSKGKSEEELSDLFRMFDKNADGYIDLDELKIMLQA 123
Cdd:cd16253  32 SPADIKKVFNILDQDKSGFIEEEE-LKLFLKNFSDGARVLSDKETKNFLAAGDSDGDGKIGVDEFKSMVKA 101
EFh_HEF cd15902
EF-hand, calcium binding motif, found in the hexa-EF hand proteins family; The hexa-EF hand ...
99-157 2.03e-03

EF-hand, calcium binding motif, found in the hexa-EF hand proteins family; The hexa-EF hand proteins family, also named the calbindin sub-family, contains a group of six EF-hand Ca2+-binding proteins, including calretinin (CR, also termed 29 kDa calbindin), calbindin D28K (CB, also termed vitamin D-dependent calcium-binding protein, avian-type), and secretagogin (SCGN). CR is a cytosolic hexa-EF-hand calcium-binding protein predominantly expressed in a variety of normal and tumorigenic t-specific neurons of the central and peripheral nervous system. It is a multifunctional protein implicated in many biological processes, including cell proliferation, differentiation, and cell death. CB is highly expressed in brain tissue. It is a strong calcium-binding and buffering protein responsible for preventing a neuronal death as well as maintaining and controlling calcium homeostasis. SCGN is a six EF-hand calcium-binding protein expressed in neuroendocrine, pancreatic endocrine and retinal cells. It plays a crucial role in cell apoptosis, receptor signaling and differentiation. It is also involved in vesicle secretion through binding to various proteins, including interacts with SNAP25, SNAP23, DOC2alpha, ARFGAP2, rootletin, KIF5B, beta-tubulin, DDAH-2, ATP-synthase and myeloid leukemia factor 2. SCGN functions as a Ca2+ sensor/coincidence detector modulating vesicular exocytosis of neurotransmitters, neuropeptides or hormones. Although the family members share a significant amount of secondary sequence homology, they display altered structural and biochemical characteristics, and operate in distinct fashions. CB contains six EF-hand motifs in a single globular domain, where EF-hands 1, 3, 4, 5 bind four calcium ions. CR contains six EF-hand motifs within two independent domains, CR I-II and CR III-VI. They harbor two and four EF-hand motifs, respectively. The first 5 EF-hand motifs are capable of binding calcium ions, while the EF-hand 6 is inactive. SCGN consists of the three globular domains each of which contains a pair of EF-hand motifs. Human SCGN simultaneously binds four calcium ions through its EF-hands 3, 4, 5 and 6 in one high affinity and three low affinity calcium-binding sites. In contrast, SCGNs in other lower eukaryotes, such as D. rerio, X. laevis, M. domestica, G. gallus, O. anatinus, are fully competent in terms of six calcium-binding.


Pssm-ID: 320075 [Multi-domain]  Cd Length: 254  Bit Score: 37.33  E-value: 2.03e-03
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 4507615   99 DLFRMFDKNADGYIDLDELKIMLQAT-----GETITEDDIEELMKD----GDKNNDGRIDYDEFLEFM 157
Cdd:cd15902   3 EVWMHFDADGNGYIEGKELDSFLRELlkalnGKDKTDDEVAEKKKEfmekYDENEDGKIEIRELANIL 70
EFh smart00054
EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in ...
96-124 2.35e-03

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: 33.89  E-value: 2.35e-03
                           10        20
                   ....*....|....*....|....*....
gi 4507615      96 ELSDLFRMFDKNADGYIDLDELKIMLQAT 124
Cdd:smart00054   1 ELKEAFRLFDKDGDGKIDFEEFKDLLKAL 29
EFh_PEF_CAPN12 cd16194
Penta-EF hand, calcium binding motifs, found in calpain-12 (CAPN12); CAPN12, also termed ...
29-154 3.86e-03

Penta-EF hand, calcium binding motifs, found in calpain-12 (CAPN12); CAPN12, also termed calcium-activated neutral proteinase 12 (CANP 12), is a calpain large subunit mainly expressed in the cortex of the hair follicle. It may affect apoptosis regulation. CAPN12 contains a short N-terminal anchor helix, followed by 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: 320069 [Multi-domain]  Cd Length: 169  Bit Score: 36.01  E-value: 3.86e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4507615   29 LGAEDGCISTKELGKVMRML---GQNPTPEELQ-----EMIDEVDEDGSGTVDFDEFLVMMVRCMkddskgkseeELSDL 100
Cdd:cd16194   9 LAGEDEEINASELQKILSIAlerAHTSKPREFGlrtcrQLIQCFDHGQNGKLALEEFQQLWGYLL----------EWQAI 78
                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....
gi 4507615  101 FRMFDKNADGYIDLDELKIMLQATGETITeDDIEELMKDGDKNNDGRIDYDEFL 154
Cdd:cd16194  79 FTKFDEDTSGTMDSYELRLALNAAGFHLN-NQLTETLTSRYRDSRLRVDFESFL 131
EF-hand_1 pfam00036
EF hand; The EF-hands can be divided into two classes: signalling proteins and buffering ...
132-158 4.09e-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: 33.14  E-value: 4.09e-03
                          10        20
                  ....*....|....*....|....*..
gi 4507615    132 DIEELMKDGDKNNDGRIDYDEFLEFMK 158
Cdd:pfam00036   1 ELKEIFRLFDKDGDGKIDFEEFKELLK 27
EFh_CREC_Calumenin_like cd16226
EF-hand, calcium binding motif, found in calumenin, reticulocalbin-1 (RCN-1), reticulocalbin-3 ...
53-157 4.14e-03

EF-hand, calcium binding motif, found in calumenin, reticulocalbin-1 (RCN-1), reticulocalbin-3 (RCN-3), and similar proteins; The family corresponds to a group of six EF-hand Ca2+-binding proteins, including calumenin (also known as crocalbin or CBP-50), reticulocalbin-1 (RCN-1), reticulocalbin-3 (RCN-3), and similar proteins. Calumenin is an endo/sarcoplasmic reticulum (ER/SR) resident low-affinity Ca2+-binding protein that contains six EF-hand domains and a C-terminal SR retention signal His-Asp-Glu-Phe (HDEF) tetrapeptide. It functions as a novel regulator of SERCA2, and its expressional changes are tightly coupled with Ca2+-cycling of cardiomyocytes. It is also broadly involved in haemostasis and in the pathophysiology of thrombosis. Moreover, the extracellular calumenin acts as a suppressor of cell migration and tumor metastasis. RCN-1 is an endoplasmic reticulum resident Ca2+-binding protein with a carboxyl-terminal His-Asp-Glu-Leu (HDEL) tetrapeptide signal. It acts as a potential negative regulator of B-RAF activation and can negatively modulate cardiomyocyte hypertrophy by inhibition of the mitogen-activated protein kinase signalling cascade. It also plays a key role in the development of doxorubicin-associated resistance. RCN-3 is a putative six EF-hand Ca2+-binding protein that contains five RXXR (X is any amino acid) motifs and a C-terminal ER retrieval signal HDEL tetrapeptide. The RXXR motif represents the target sequence of subtilisin-like proprotein convertases (SPCs). RCN-3 is specifically bound to the paired basic amino-acid-cleaving enzyme-4 (PACE4) precursor protein and plays an important role in the biosynthesis of PACE4.


Pssm-ID: 320024 [Multi-domain]  Cd Length: 264  Bit Score: 36.41  E-value: 4.14e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4507615   53 TPEE----LQEMIDEVDEDGSGTVDFDEflvmMVRCMKDDSKGKSEEELSDLFRMFDKNADGYIDLDELKIMLQATGETI 128
Cdd:cd16226  29 TPEEskerLGIIVDKIDKNGDGFVTEEE----LKDWIKYVQKKYIREDVDRQWKEYDPNKDGKLSWEEYKKATYGFLDDE 104
                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 4507615  129 TEDDIEELM------------KDGDKNNDGRIDYDEFLEFM 157
Cdd:cd16226 105 EEDDDLHESykkmirrderrwKAADQDGDGKLTKEEFTAFL 145
EFh_CREC_cab45 cd16225
EF-hand, calcium binding motif, found in 45 kDa calcium-binding protein (Cab45); Cab45, also ...
58-155 4.51e-03

EF-hand, calcium binding motif, found in 45 kDa calcium-binding protein (Cab45); Cab45, also termed stromal cell-derived factor 4 (SDF-4), is a soluble, lumenal Golgi resident low-affinity Ca2+-binding protein that contains six copies of the EF-hand Ca2+-binding motif. It is required for secretory pathway calcium ATPase1 (SPCA1)-dependent Ca2+ import into the trans-Golgi network (TGN) and plays an essential role in Ca2+-dependent secretory cargo sorting at the TGN.


Pssm-ID: 320023 [Multi-domain]  Cd Length: 278  Bit Score: 36.12  E-value: 4.51e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4507615   58 QEMIDEVDEDGSGTVDFDEFLVMMVRCMKDDSKGKSEEELSDLFRMF----DKNADGYIDLDELKIMLQATGETITEDDI 133
Cdd:cd16225 171 KEILHDLDQDGDEKLTLDEFVSLPPGTVEEQQAEDDDEWKKERKKEFeeviDLNHDGKVTKEELEEYMDPRNERHALNEA 250
                        90       100
                ....*....|....*....|..
gi 4507615  134 EELMKDGDKNNDGRIDYDEFLE 155
Cdd:cd16225 251 KQLIAVADENKDGKLSLEEILK 272
EFh_PI-PLCeta cd16205
EF-hand motif found in phosphoinositide phospholipase C eta (PI-PLC-eta); PI-PLC-eta isozymes ...
97-158 4.79e-03

EF-hand motif found in phosphoinositide phospholipase C eta (PI-PLC-eta); PI-PLC-eta isozymes represent a class of neuron-specific metazoan PI-PLCs that are most abundant in the brain, particularly in the hippocampus, habenula, olfactory bulb, cerebellum, and throughout the cerebral cortex. They are phosphatidylinositol 4,5-bisphosphate-hydrolyzing enzymes that are more sensitive to Ca2+ than other PI-PLC isozymes. They function as calcium sensors activated by small increases in intracellular calcium concentrations. They are also activated through G-protein-coupled receptor (GPCR) stimulation, and further mediate GPCR signalling pathways. PI-PLC-eta isozymes contain an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core domain, a C2 domain, and a unique C-terminal tail that terminates with a PDZ-binding motif, a potential interaction site for other signaling proteins. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. The C-terminal tail harbors a number of proline-rich motifs which may interact with SH3 (Src homology 3) domain-containing proteins, as well as many serine/threonine residues, suggesting possible regulation of interactions by protein kinases/phosphatases. There are two PI-PLC-eta isozymes (1-2). Aside from the PI-PLC-eta isozymes identified in mammals, their eukaryotic homologs are also present in this family.


Pssm-ID: 320035 [Multi-domain]  Cd Length: 141  Bit Score: 35.43  E-value: 4.79e-03
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 4507615   97 LSDLFRMFDKNADGYIDLDELKIMLQATGETITEDDIEELMKDGDK-NNDGRIDYDEFLEFMK 158
Cdd:cd16205   2 LKQTFEEADKNGDGLLSIGEILQLMHKLNVNLPRRKVRQMFKEADTdDNQGTLDFEEFCAFYK 64
EFh_MICU cd15900
EF-hand, calcium binding motif, found in mitochondrial calcium uptake proteins MICU1, MICU2, ...
20-158 5.05e-03

EF-hand, calcium binding motif, found in mitochondrial calcium uptake proteins MICU1, MICU2, MICU3, and similar proteins; This family includes mitochondrial calcium uptake protein MICU1 and its two additional paralogs, MICU2 and MICU3. MICU1 localizes to the inner mitochondrial membrane (IMM). It functions as a gatekeeper of the mitochondrial calcium uniporter (MCU) and regulates MCU-mediated mitochondrial Ca2+ uptake, which is essential for maintaining mitochondrial homoeostasis. MICU1 and MICU2 are physically associated within the uniporter complex and are co-expressed across all tissues. They may play non-redundant roles in the regulation of the mitochondrial calcium uniporter. At present, the precise molecular function of MICU2 and MICU3 remain unclear. MICU2 may play possible roles in Ca2+ sensing and regulation of MCU, calcium buffering with a secondary impact on transport or assembly and stabilization of MCU. MICU3 likely has a role in mitochondrial calcium handling. All members in this family contains an N-terminal mitochondrial targeting sequence (MTS) as well as two evolutionarily conserved canonical Ca2+-binding EF-hands separated by a long stretch of residues predicted to form alpha-helices.


Pssm-ID: 320080 [Multi-domain]  Cd Length: 152  Bit Score: 35.67  E-value: 5.05e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4507615   20 FKAAFDIFVLGAeDGCISTKELGKVMR------MLGQNPTPEELQEMIDEVD----------EDGSGTVDFDEFLVMMVR 83
Cdd:cd15900   2 FEIAFKMFDLDG-DGELDKEEFNKVQSiirsqtSVGQRHRDHTNGESTKLGMnstlaryffgKDGKQKLSIEKFLEFQEN 80
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 4507615   84 CMKDdskgksEEELSDLFRMFdKNADGYIDLDELK-IMLQATGETITEDDIEELMKDGDKNNDGRIDYDEFLEFMK 158
Cdd:cd15900  81 LQEE------IDDVDTALTFY-HLAGASIDRKTFKrAAKVVAGVELSDHVVDVVFTIFDEDGDGILSHKEFISVMK 149
EFh_CREC_RCN1 cd16229
EF-hand, calcium binding motif, found in reticulocalbin-1 (RCN-1); RCN-1 is an endoplasmic ...
92-153 5.09e-03

EF-hand, calcium binding motif, found in reticulocalbin-1 (RCN-1); RCN-1 is an endoplasmic reticulum resident low-affinity Ca2+-binding protein with six EF-hand motifs and a carboxyl-terminal His-Asp-Glu-Leu (HDEL) tetrapeptide signal. It is expressed at the cell surface. RCN-1 acts as a potential negative regulator of B-RAF activation and can negatively modulate cardiomyocyte hypertrophy by inhibition of the mitogen-activated protein kinase signaling cascade. It also plays a key role in the development of doxorubicin-associated resistance.


Pssm-ID: 320027 [Multi-domain]  Cd Length: 267  Bit Score: 36.01  E-value: 5.09e-03
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 4507615   92 KSEEELSDLFRMFDKNADGYIDLDELKIMLQATGETITEDDIEELMKDGDKNNDGRIDYDEF 153
Cdd:cd16229  32 ESKERLGKIVDRIDDDKDGFVTTEELKAWIKRVQKRYIYENVAKVWKDYDLNKDNKISWEEY 93
EF-hand_1 pfam00036
EF hand; The EF-hands can be divided into two classes: signalling proteins and buffering ...
96-124 6.19e-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: 32.76  E-value: 6.19e-03
                          10        20
                  ....*....|....*....|....*....
gi 4507615     96 ELSDLFRMFDKNADGYIDLDELKIMLQAT 124
Cdd:pfam00036   1 ELKEIFRLFDKDGDGKIDFEEFKELLKKL 29
EFh_PEF_ALG-2 cd16183
EF-hand, calcium binding motif, found in apoptosis-linked gene 2 protein (ALG-2) and similar ...
34-114 7.22e-03

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: 35.31  E-value: 7.22e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4507615   34 GCISTKELGKVMRMLGQNPTPEELQEMIDEVDEDGSGTVDFDEFL---VMMVRcmkddskgkseeeLSDLFRMFDKNADG 110
Cdd:cd16183  82 GNIDKNELKQALTSFGYRLSDQFYDILVRKFDRQGRGTIAFDDFIqccVVLQT-------------LTDSFRRYDTDQDG 148

                ....
gi 4507615  111 YIDL 114
Cdd:cd16183 149 WIQI 152
PRK08332 PRK08332
vitamin B12-dependent ribonucleotide reductase;
55-138 7.96e-03

vitamin B12-dependent ribonucleotide reductase;


Pssm-ID: 181392 [Multi-domain]  Cd Length: 1740  Bit Score: 35.90  E-value: 7.96e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4507615     55 EELQEMIDEVDEDGSGTVDFDEFLVMMVRCMKDdskgKSEEELSDLFRM-----FDKNADGYIDLDELKIMLQATGETIT 129
Cdd:PRK08332  203 ERMVNLYRELAEKGKMKVSIDEFLKMLERGEFD----KYEKEIEEYFRLmtnqiFMPNTPALINSGRPLGMLSACFVVPI 278

                  ....*....
gi 4507615    130 EDDIEELMK 138
Cdd:PRK08332  279 EDDMESIMK 287
EFh_CREC cd15899
EF-hand, calcium binding motif, found in CREC-EF hand family; The CREC (Cab45/reticulocalbin ...
67-153 8.06e-03

EF-hand, calcium binding motif, found in CREC-EF hand family; The CREC (Cab45/reticulocalbin/ERC45/calumenin)-EF hand family contains a group of six EF-hand, low-affinity Ca2+-binding proteins, including reticulocalbin (RCN-1), ER Ca2+-binding protein of 55 kDa (ERC-55, also known as TCBP-49 or E6BP), reticulocalbin-3 (RCN-3), Ca2+-binding protein of 45 kDa (Cab45 and its splice variant Cab45b), and calumenin ( also known as crocalbin or CBP-50). The proteins are not only localized in various parts of the secretory pathway, but also found in the cytosolic compartment and at the cell surface. They interact with different ligands or proteins and have been implicated in the secretory process, chaperone activity, signal transduction as well as in a large variety of disease processes.


Pssm-ID: 320021 [Multi-domain]  Cd Length: 267  Bit Score: 35.50  E-value: 8.06e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4507615   67 DGSGTVDFDEFLVMMVRCMKDDSKGKSEEELSDLFRMFDK---NADGYIDLDELKIMLQATGETITEDDIEELMKDGDKN 143
Cdd:cd15899   4 DGHLNSDYDHEAFLGKEEAEEFDQLTPEESKRRLGVIVSKmdvDKDGFISAKELHSWILESFKRHAMEESKEQFRAVDPD 83
                        90
                ....*....|
gi 4507615  144 NDGRIDYDEF 153
Cdd:cd15899  84 EDGHVSWDEY 93
 
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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