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Conserved domains on  [gi|38570107|ref|NP_073622|]
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EF-hand calcium-binding domain-containing protein 6 isoform a [Homo sapiens]

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
EF-hand_11 pfam08976
EF-hand domain; This domain is found predominantly in DJ binding proteins.
 1160-1260 3.45e-63

EF-hand domain; This domain is found predominantly in DJ binding proteins.


:

Pssm-ID: 401068  Cd Length: 105  Bit Score: 209.96  E-value: 3.45e-63
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38570107   1160 ATADRDILARLHKAVTSHYHAITQEFENFDTMKTNTISREEFRAICNRRVQILTDEQFDRLWNEMPVNAKGRLKYPDFLS 1239
Cdd:pfam08976    1 ATADRDILARLHKAVASHYHAITQEFENFDTLKSNTISRDEFRAICNRHIQILTDEQFDRLWNELPVNAKGRLKYPDFLS 80

                           90       100
                   ....*....|....*....|....*
gi 38570107   1240 RFSSE-TAATPMATGD---SAVAQR 1260
Cdd:pfam08976   81 KFSIErTAAPPMAAGDsgeSAMAQR 105
EF-hand_7 pfam13499
EF-hand domain pair;
1439-1500 1.72e-08

EF-hand domain pair;


:

Pssm-ID: 463900 [Multi-domain]  Cd Length: 67  Bit Score: 52.26  E-value: 1.72e-08
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 38570107   1439 MRRTFKSYDEAGTGLLSVADFRTVLRQ--YSINLSEEEFFHILEYYDKTLSSKISYNDFLRAFL 1500
Cdd:pfam13499    4 LKEAFKLLDSDGDGYLDVEELKKLLRKleEGEPLSDEEVEELFKEFDLDKDGRISFEEFLELYS 67
EF-hand_11 super family cl25355
EF-hand domain; This domain is found predominantly in DJ binding proteins.
 59-135 3.42e-06

EF-hand domain; This domain is found predominantly in DJ binding proteins.


The actual alignment was detected with superfamily member pfam08976:

Pssm-ID: 401068  Cd Length: 105  Bit Score: 47.40  E-value: 3.42e-06
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 38570107     59 DVKRILFQKITDRGDELQKAFQLLDTGQNLTVSKSELRRIITDFLMPLTREQFQDVLAQIPLSTSGTVPYLAFLSRF 135
Cdd:pfam08976    6 DILARLHKAVASHYHAITQEFENFDTLKSNTISRDEFRAICNRHIQILTDEQFDRLWNELPVNAKGRLKYPDFLSKF 82
PTZ00184 super family cl33172
calmodulin; Provisional
 74-235 2.16e-05

calmodulin; Provisional


The actual alignment was detected with superfamily member PTZ00184:

Pssm-ID: 185504 [Multi-domain]  Cd Length: 149  Bit Score: 45.91  E-value: 2.16e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38570107    74 ELQKAFQLLDTGQNLTVSKSELRRIITDFLMPLTREQFQDVLAQIPLSTSGTVPYLAFLSRFGgidlyingikrgggNEM 153
Cdd:PTZ00184   12 EFKEAFSLFDKDGDGTITTKELGTVMRSLGQNPTEAELQDMINEVDADGNGTIDFPEFLTLMA--------------RKM 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38570107   154 NCCRTLRELeiqvgekvfkniktvMKAFELIDVNKTGLVRPQELRRVLETFCMKLRDEEYEKFSKHYNIHKDTAVDYNVF 233
Cdd:PTZ00184   78 KDTDSEEEI---------------KEAFKVFDRDGNGFISAAELRHVMTNLGEKLTDEEVDEMIREADVDGDGQINYEEF 142


                  ..
gi 38570107   234 LK 235
Cdd:PTZ00184  143 VK 144
EF-hand_7 pfam13499
EF-hand domain pair;
856-910 3.65e-04

EF-hand domain pair;


:

Pssm-ID: 463900 [Multi-domain]  Cd Length: 67  Bit Score: 40.31  E-value: 3.65e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 38570107    856 FLETDNEGNGILRRRDIKNALYGF--DIPLTPREFEKLWARYDTEGKGHITYQEFLQ 910
Cdd:pfam13499    8 FKLLDSDGDGYLDVEELKKLLRKLeeGEPLSDEEVEELFKEFDLDKDGRISFEEFLE 64
 
Name Accession Description Interval E-value
EF-hand_11 pfam08976
EF-hand domain; This domain is found predominantly in DJ binding proteins.
 1160-1260 3.45e-63

EF-hand domain; This domain is found predominantly in DJ binding proteins.


Pssm-ID: 401068  Cd Length: 105  Bit Score: 209.96  E-value: 3.45e-63
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38570107   1160 ATADRDILARLHKAVTSHYHAITQEFENFDTMKTNTISREEFRAICNRRVQILTDEQFDRLWNEMPVNAKGRLKYPDFLS 1239
Cdd:pfam08976    1 ATADRDILARLHKAVASHYHAITQEFENFDTLKSNTISRDEFRAICNRHIQILTDEQFDRLWNELPVNAKGRLKYPDFLS 80

                           90       100
                   ....*....|....*....|....*
gi 38570107   1240 RFSSE-TAATPMATGD---SAVAQR 1260
Cdd:pfam08976   81 KFSIErTAAPPMAAGDsgeSAMAQR 105
EF-hand_7 pfam13499
EF-hand domain pair;
1439-1500 1.72e-08

EF-hand domain pair;


Pssm-ID: 463900 [Multi-domain]  Cd Length: 67  Bit Score: 52.26  E-value: 1.72e-08
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 38570107   1439 MRRTFKSYDEAGTGLLSVADFRTVLRQ--YSINLSEEEFFHILEYYDKTLSSKISYNDFLRAFL 1500
Cdd:pfam13499    4 LKEAFKLLDSDGDGYLDVEELKKLLRKleEGEPLSDEEVEELFKEFDLDKDGRISFEEFLELYS 67
EF-hand_11 pfam08976
EF-hand domain; This domain is found predominantly in DJ binding proteins.
 59-135 3.42e-06

EF-hand domain; This domain is found predominantly in DJ binding proteins.


Pssm-ID: 401068  Cd Length: 105  Bit Score: 47.40  E-value: 3.42e-06
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 38570107     59 DVKRILFQKITDRGDELQKAFQLLDTGQNLTVSKSELRRIITDFLMPLTREQFQDVLAQIPLSTSGTVPYLAFLSRF 135
Cdd:pfam08976    6 DILARLHKAVASHYHAITQEFENFDTLKSNTISRDEFRAICNRHIQILTDEQFDRLWNELPVNAKGRLKYPDFLSKF 82
PTZ00184 PTZ00184
calmodulin; Provisional
 74-235 2.16e-05

calmodulin; Provisional


Pssm-ID: 185504 [Multi-domain]  Cd Length: 149  Bit Score: 45.91  E-value: 2.16e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38570107    74 ELQKAFQLLDTGQNLTVSKSELRRIITDFLMPLTREQFQDVLAQIPLSTSGTVPYLAFLSRFGgidlyingikrgggNEM 153
Cdd:PTZ00184   12 EFKEAFSLFDKDGDGTITTKELGTVMRSLGQNPTEAELQDMINEVDADGNGTIDFPEFLTLMA--------------RKM 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38570107   154 NCCRTLRELeiqvgekvfkniktvMKAFELIDVNKTGLVRPQELRRVLETFCMKLRDEEYEKFSKHYNIHKDTAVDYNVF 233
Cdd:PTZ00184   78 KDTDSEEEI---------------KEAFKVFDRDGNGFISAAELRHVMTNLGEKLTDEEVDEMIREADVDGDGQINYEEF 142


                  ..
gi 38570107   234 LK 235
Cdd:PTZ00184  143 VK 144
EFh cd00051
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...
 1440-1499 9.76e-05

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: 41.76  E-value: 9.76e-05
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 38570107 1440 RRTFKSYDEAGTGLLSVADFRTVLRQYSINLSEEEFFHILEYYDKTLSSKISYNDFLRAF 1499
Cdd:cd00051    3 REAFRLFDKDGDGTISADELKAALKSLGEGLSEEEIDEMIREVDKDGDGKIDFEEFLELM 62
EF-hand_7 pfam13499
EF-hand domain pair;
178-235 2.00e-04

EF-hand domain pair;


Pssm-ID: 463900 [Multi-domain]  Cd Length: 67  Bit Score: 41.08  E-value: 2.00e-04
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 38570107    178 MKAFELIDVNKTGLVRPQELRRVLETFCM--KLRDEEYEKFSKHYNIHKDTAVDYNVFLK 235
Cdd:pfam13499    5 KEAFKLLDSDGDGYLDVEELKKLLRKLEEgePLSDEEVEELFKEFDLDKDGRISFEEFLE 64
EF-hand_7 pfam13499
EF-hand domain pair;
856-910 3.65e-04

EF-hand domain pair;


Pssm-ID: 463900 [Multi-domain]  Cd Length: 67  Bit Score: 40.31  E-value: 3.65e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 38570107    856 FLETDNEGNGILRRRDIKNALYGF--DIPLTPREFEKLWARYDTEGKGHITYQEFLQ 910
Cdd:pfam13499    8 FKLLDSDGDGYLDVEELKKLLRKLeeGEPLSDEEVEELFKEFDLDKDGRISFEEFLE 64
EFh_PI-PLC cd15898
EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4. ...
 852-930 7.39e-04

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: 41.11  E-value: 7.39e-04
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 38570107  852 LSKNFLETDNEGNGILRRRDIKNALYGFDIPLTPREFEKLWARYDTEGKGHITYQEFlQKLginYSPAVHRPCAEDYFN 930
Cdd:cd15898    2 LRRQWIKADKDGDGKLSLKEIKKLLKRLNIRVSEKELKKLFKEVDTNGDGTLTFDEF-EEL---YKSLTERPELEPIFK 76
EFh cd00051
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...
 177-235 3.17e-03

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: 37.53  E-value: 3.17e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 38570107  177 VMKAFELIDVNKTGLVRPQELRRVLETFCMKLRDEEYEKFSKHYNIHKDTAVDYNVFLK 235
Cdd:cd00051    2 LREAFRLFDKDGDGTISADELKAALKSLGEGLSEEEIDEMIREVDKDGDGKIDFEEFLE 60
EFh cd00051
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...
 74-126 3.23e-03

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: 37.53  E-value: 3.23e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 38570107   74 ELQKAFQLLDTGQNLTVSKSELRRIITDFLMPLTREQFQDVLAQIPLSTSGTV 126
Cdd:cd00051    1 ELREAFRLFDKDGDGTISADELKAALKSLGEGLSEEEIDEMIREVDKDGDGKI 53
EFh cd00051
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...
 1185-1238 9.19e-03

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: 35.99  E-value: 9.19e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 38570107 1185 FENFDTMKTNTISREEFRAICNRRVQILTDEQFDRLWNEMPVNAKGRLKYPDFL 1238
Cdd:cd00051    6 FRLFDKDGDGTISADELKAALKSLGEGLSEEEIDEMIREVDKDGDGKIDFEEFL 59
 
Name Accession Description Interval E-value
EF-hand_11 pfam08976
EF-hand domain; This domain is found predominantly in DJ binding proteins.
 1160-1260 3.45e-63

EF-hand domain; This domain is found predominantly in DJ binding proteins.


Pssm-ID: 401068  Cd Length: 105  Bit Score: 209.96  E-value: 3.45e-63
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38570107   1160 ATADRDILARLHKAVTSHYHAITQEFENFDTMKTNTISREEFRAICNRRVQILTDEQFDRLWNEMPVNAKGRLKYPDFLS 1239
Cdd:pfam08976    1 ATADRDILARLHKAVASHYHAITQEFENFDTLKSNTISRDEFRAICNRHIQILTDEQFDRLWNELPVNAKGRLKYPDFLS 80

                           90       100
                   ....*....|....*....|....*
gi 38570107   1240 RFSSE-TAATPMATGD---SAVAQR 1260
Cdd:pfam08976   81 KFSIErTAAPPMAAGDsgeSAMAQR 105
EF-hand_7 pfam13499
EF-hand domain pair;
1439-1500 1.72e-08

EF-hand domain pair;


Pssm-ID: 463900 [Multi-domain]  Cd Length: 67  Bit Score: 52.26  E-value: 1.72e-08
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 38570107   1439 MRRTFKSYDEAGTGLLSVADFRTVLRQ--YSINLSEEEFFHILEYYDKTLSSKISYNDFLRAFL 1500
Cdd:pfam13499    4 LKEAFKLLDSDGDGYLDVEELKKLLRKleEGEPLSDEEVEELFKEFDLDKDGRISFEEFLELYS 67
EF-hand_11 pfam08976
EF-hand domain; This domain is found predominantly in DJ binding proteins.
 59-135 3.42e-06

EF-hand domain; This domain is found predominantly in DJ binding proteins.


Pssm-ID: 401068  Cd Length: 105  Bit Score: 47.40  E-value: 3.42e-06
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 38570107     59 DVKRILFQKITDRGDELQKAFQLLDTGQNLTVSKSELRRIITDFLMPLTREQFQDVLAQIPLSTSGTVPYLAFLSRF 135
Cdd:pfam08976    6 DILARLHKAVASHYHAITQEFENFDTLKSNTISRDEFRAICNRHIQILTDEQFDRLWNELPVNAKGRLKYPDFLSKF 82
PTZ00184 PTZ00184
calmodulin; Provisional
 74-235 2.16e-05

calmodulin; Provisional


Pssm-ID: 185504 [Multi-domain]  Cd Length: 149  Bit Score: 45.91  E-value: 2.16e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38570107    74 ELQKAFQLLDTGQNLTVSKSELRRIITDFLMPLTREQFQDVLAQIPLSTSGTVPYLAFLSRFGgidlyingikrgggNEM 153
Cdd:PTZ00184   12 EFKEAFSLFDKDGDGTITTKELGTVMRSLGQNPTEAELQDMINEVDADGNGTIDFPEFLTLMA--------------RKM 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38570107   154 NCCRTLRELeiqvgekvfkniktvMKAFELIDVNKTGLVRPQELRRVLETFCMKLRDEEYEKFSKHYNIHKDTAVDYNVF 233
Cdd:PTZ00184   78 KDTDSEEEI---------------KEAFKVFDRDGNGFISAAELRHVMTNLGEKLTDEEVDEMIREADVDGDGQINYEEF 142


                  ..
gi 38570107   234 LK 235
Cdd:PTZ00184  143 VK 144
EFh cd00051
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...
 1440-1499 9.76e-05

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: 41.76  E-value: 9.76e-05
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 38570107 1440 RRTFKSYDEAGTGLLSVADFRTVLRQYSINLSEEEFFHILEYYDKTLSSKISYNDFLRAF 1499
Cdd:cd00051    3 REAFRLFDKDGDGTISADELKAALKSLGEGLSEEEIDEMIREVDKDGDGKIDFEEFLELM 62
EF-hand_7 pfam13499
EF-hand domain pair;
178-235 2.00e-04

EF-hand domain pair;


Pssm-ID: 463900 [Multi-domain]  Cd Length: 67  Bit Score: 41.08  E-value: 2.00e-04
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 38570107    178 MKAFELIDVNKTGLVRPQELRRVLETFCM--KLRDEEYEKFSKHYNIHKDTAVDYNVFLK 235
Cdd:pfam13499    5 KEAFKLLDSDGDGYLDVEELKKLLRKLEEgePLSDEEVEELFKEFDLDKDGRISFEEFLE 64
EF-hand_7 pfam13499
EF-hand domain pair;
856-910 3.65e-04

EF-hand domain pair;


Pssm-ID: 463900 [Multi-domain]  Cd Length: 67  Bit Score: 40.31  E-value: 3.65e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 38570107    856 FLETDNEGNGILRRRDIKNALYGF--DIPLTPREFEKLWARYDTEGKGHITYQEFLQ 910
Cdd:pfam13499    8 FKLLDSDGDGYLDVEELKKLLRKLeeGEPLSDEEVEELFKEFDLDKDGRISFEEFLE 64
EFh_PI-PLC cd15898
EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4. ...
 852-930 7.39e-04

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: 41.11  E-value: 7.39e-04
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 38570107  852 LSKNFLETDNEGNGILRRRDIKNALYGFDIPLTPREFEKLWARYDTEGKGHITYQEFlQKLginYSPAVHRPCAEDYFN 930
Cdd:cd15898    2 LRRQWIKADKDGDGKLSLKEIKKLLKRLNIRVSEKELKKLFKEVDTNGDGTLTFDEF-EEL---YKSLTERPELEPIFK 76
EF-hand_7 pfam13499
EF-hand domain pair;
73-135 1.71e-03

EF-hand domain pair;


Pssm-ID: 463900 [Multi-domain]  Cd Length: 67  Bit Score: 38.39  E-value: 1.71e-03
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 38570107     73 DELQKAFQLLDTGQNLTVSKSELRRIITDFLM--PLTREQFQDVLAQIPLSTSGTVPYLAFLSRF 135
Cdd:pfam13499    2 EKLKEAFKLLDSDGDGYLDVEELKKLLRKLEEgePLSDEEVEELFKEFDLDKDGRISFEEFLELY 66
EFh cd00051
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...
 177-235 3.17e-03

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: 37.53  E-value: 3.17e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 38570107  177 VMKAFELIDVNKTGLVRPQELRRVLETFCMKLRDEEYEKFSKHYNIHKDTAVDYNVFLK 235
Cdd:cd00051    2 LREAFRLFDKDGDGTISADELKAALKSLGEGLSEEEIDEMIREVDKDGDGKIDFEEFLE 60
EFh cd00051
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...
 74-126 3.23e-03

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: 37.53  E-value: 3.23e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 38570107   74 ELQKAFQLLDTGQNLTVSKSELRRIITDFLMPLTREQFQDVLAQIPLSTSGTV 126
Cdd:cd00051    1 ELREAFRLFDKDGDGTISADELKAALKSLGEGLSEEEIDEMIREVDKDGDGKI 53
EF-hand_7 pfam13499
EF-hand domain pair;
1180-1242 5.34e-03

EF-hand domain pair;


Pssm-ID: 463900 [Multi-domain]  Cd Length: 67  Bit Score: 36.85  E-value: 5.34e-03
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 38570107   1180 AITQEFENFDTMKTNTISREEFRAICNR--RVQILTDEQFDRLWNEMPVNAKGRLKYPDFLSRFS 1242
Cdd:pfam13499    3 KLKEAFKLLDSDGDGYLDVEELKKLLRKleEGEPLSDEEVEELFKEFDLDKDGRISFEEFLELYS 67
EFh_PEF_Group_I cd16180
Penta-EF hand, calcium binding motifs, found in Group I PEF proteins; The family corresponds ...
 1439-1498 5.92e-03

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


Pssm-ID: 320055 [Multi-domain]  Cd Length: 164  Bit Score: 39.05  E-value: 5.92e-03
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 38570107 1439 MRRTFKSYDEAGTGLLSVADFRTVLRQYSINLSEEEFFHILEYYDKTLSSKISYNDFLRA 1498
Cdd:cd16180   69 WRRLFRRFDRDRSGSIDFNELQNALSSFGYRLSPQFVQLLVRKFDRRRRGSISFDDFVEA 128
EFh cd00051
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...
 1185-1238 9.19e-03

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: 35.99  E-value: 9.19e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 38570107 1185 FENFDTMKTNTISREEFRAICNRRVQILTDEQFDRLWNEMPVNAKGRLKYPDFL 1238
Cdd:cd00051    6 FRLFDKDGDGTISADELKAALKSLGEGLSEEEIDEMIREVDKDGDGKIDFEEFL 59
 
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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