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Conserved domains on  [gi|1907121837|ref|XP_036016150|]
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guanylyl cyclase-activating protein 2 isoform X1 [Mus musculus]

Protein Classification

EF-hand domain-containing protein( domain architecture ID 13418767)

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

Gene Ontology:  GO:0005509

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
EFh cd00051
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...
 57-118 4.58e-13

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: 61.79  E-value: 4.58e-13
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907121837  57 YVESMFRAFDKNGDNTIDFLEYVAALNLVLRGSLEHKLKWTFKIYDKDRNGCIDRLELLDIV 118
Cdd:cd00051     1 ELREAFRLFDKDGDGTISADELKAALKSLGEGLSEEEIDEMIREVDKDGDGKIDFEEFLELM 62
FRQ1 super family cl34916
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
34-161 5.77e-09

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


The actual alignment was detected with superfamily member COG5126:

Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 52.87  E-value: 5.77e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907121837  34 SGTLFMHEFKRFFkvtgneeaSQYVESMFRAFDKNGDNTIDFLEYVAALNLVLRGSLEHKLKWTFKIYDKDRNGCIDRLE 113
Cdd:COG5126    19 DGVLERDDFEALF--------RRLWATLFSEADTDGDGRISREEFVAGMESLFEATVEPFARAAFDLLDTDGDGKISADE 90

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1907121837 114 LLDIVEAIYklkkacraeldlehqgqllTPEEVVDRIFLLVDENGDGK 161
Cdd:COG5126    91 FRRLLTALG-------------------VSEEEADELFARLDTDGDGK 119
 
Name Accession Description Interval E-value
EFh cd00051
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...
 57-118 4.58e-13

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: 61.79  E-value: 4.58e-13
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907121837  57 YVESMFRAFDKNGDNTIDFLEYVAALNLVLRGSLEHKLKWTFKIYDKDRNGCIDRLELLDIV 118
Cdd:cd00051     1 ELREAFRLFDKDGDGTISADELKAALKSLGEGLSEEEIDEMIREVDKDGDGKIDFEEFLELM 62
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
34-161 5.77e-09

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


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 52.87  E-value: 5.77e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907121837  34 SGTLFMHEFKRFFkvtgneeaSQYVESMFRAFDKNGDNTIDFLEYVAALNLVLRGSLEHKLKWTFKIYDKDRNGCIDRLE 113
Cdd:COG5126    19 DGVLERDDFEALF--------RRLWATLFSEADTDGDGRISREEFVAGMESLFEATVEPFARAAFDLLDTDGDGKISADE 90

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1907121837 114 LLDIVEAIYklkkacraeldlehqgqllTPEEVVDRIFLLVDENGDGK 161
Cdd:COG5126    91 FRRLLTALG-------------------VSEEEADELFARLDTDGDGK 119
EFh cd00051
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...
 93-161 7.95e-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: 7.95e-09
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907121837  93 KLKWTFKIYDKDRNGCIDRLELLDIVEAIYklkkacraeldlehqgqLLTPEEVVDRIFLLVDENGDGK 161
Cdd:cd00051     1 ELREAFRLFDKDGDGTISADELKAALKSLG-----------------EGLSEEEIDEMIREVDKDGDGK 52
PTZ00184 PTZ00184
calmodulin; Provisional
 10-161 5.49e-07

calmodulin; Provisional


Pssm-ID: 185504 [Multi-domain]  Cd Length: 149  Bit Score: 47.83  E-value: 5.49e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907121837  10 AEAAGEMDVAELQEWYKKFVVEcPSGTLFMHEFKRFFKVTGNEEASQYVESMFRAFDKNGDNTIDFLEYVAALNLVLRGS 89
Cdd:PTZ00184    2 ADQLTEEQIAEFKEAFSLFDKD-GDGTITTKELGTVMRSLGQNPTEAELQDMINEVDADGNGTIDFPEFLTLMARKMKDT 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907121837  90 -LEHKLKWTFKIYDKDRNGCIDRLELLDIveaiyklkkacraeldLEHQGQLLTPEEvVDRIFLLVDENGDGK 161
Cdd:PTZ00184   81 dSEEEIKEAFKVFDRDGNGFISAAELRHV----------------MTNLGEKLTDEE-VDEMIREADVDGDGQ 136
EF-hand_8 pfam13833
EF-hand domain pair;
33-82 8.27e-05

EF-hand domain pair;


Pssm-ID: 404678 [Multi-domain]  Cd Length: 54  Bit Score: 39.22  E-value: 8.27e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1907121837  33 PSGTLFMHEFKRFFKVTGNEEASQY-VESMFRAFDKNGDNTIDFLEYVAAL 82
Cdd:pfam13833   1 EKGVITREELKRALALLGLKDLSEDeVDILFREFDTDGDGYISFDEFCVLL 51
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
41-82 5.02e-04

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


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 39.00  E-value: 5.02e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 1907121837  41 EFKRFFKVTGNEEASqyVESMFRAFDKNGDNTIDFLEYVAAL 82
Cdd:COG5126    90 EFRRLLTALGVSEEE--ADELFARLDTDGDGKISFEEFVAAV 129
PTZ00183 PTZ00183
centrin; Provisional
 51-161 6.23e-04

centrin; Provisional


Pssm-ID: 185503 [Multi-domain]  Cd Length: 158  Bit Score: 38.90  E-value: 6.23e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907121837  51 NEEASQYVESMFRAFDKNGDNTIDFLEYVAALNLVLRGSLEHKLKWTFKIYDKDRNGCIDRLELLDIVEAiyKLkkacrA 130
Cdd:PTZ00183   12 TEDQKKEIREAFDLFDTDGSGTIDPKELKVAMRSLGFEPKKEEIKQMIADVDKDGSGKIDFEEFLDIMTK--KL-----G 84

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1907121837 131 ELDlehqgqlltPEEVVDRIFLLVDENGDGK 161
Cdd:PTZ00183   85 ERD---------PREEILKAFRLFDDDKTGK 106
EFh smart00054
EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in ...
 93-121 1.19e-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: 35.43  E-value: 1.19e-03
                           10        20
                   ....*....|....*....|....*....
gi 1907121837   93 KLKWTFKIYDKDRNGCIDRLELLDIVEAI 121
Cdd:smart00054   1 ELKEAFRLFDKDGDGKIDFEEFKDLLKAL 29
 
Name Accession Description Interval E-value
EFh cd00051
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...
 57-118 4.58e-13

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: 61.79  E-value: 4.58e-13
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907121837  57 YVESMFRAFDKNGDNTIDFLEYVAALNLVLRGSLEHKLKWTFKIYDKDRNGCIDRLELLDIV 118
Cdd:cd00051     1 ELREAFRLFDKDGDGTISADELKAALKSLGEGLSEEEIDEMIREVDKDGDGKIDFEEFLELM 62
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
34-161 5.77e-09

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


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 52.87  E-value: 5.77e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907121837  34 SGTLFMHEFKRFFkvtgneeaSQYVESMFRAFDKNGDNTIDFLEYVAALNLVLRGSLEHKLKWTFKIYDKDRNGCIDRLE 113
Cdd:COG5126    19 DGVLERDDFEALF--------RRLWATLFSEADTDGDGRISREEFVAGMESLFEATVEPFARAAFDLLDTDGDGKISADE 90

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1907121837 114 LLDIVEAIYklkkacraeldlehqgqllTPEEVVDRIFLLVDENGDGK 161
Cdd:COG5126    91 FRRLLTALG-------------------VSEEEADELFARLDTDGDGK 119
EFh cd00051
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...
 93-161 7.95e-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: 7.95e-09
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907121837  93 KLKWTFKIYDKDRNGCIDRLELLDIVEAIYklkkacraeldlehqgqLLTPEEVVDRIFLLVDENGDGK 161
Cdd:cd00051     1 ELREAFRLFDKDGDGTISADELKAALKSLG-----------------EGLSEEEIDEMIREVDKDGDGK 52
EFh_HEF cd15902
EF-hand, calcium binding motif, found in the hexa-EF hand proteins family; The hexa-EF hand ...
 34-161 9.17e-08

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: 51.20  E-value: 9.17e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907121837  34 SGTLFMHEFKRFFK--VTGNEEAS------QYVESMFRAFDKNGDNTIDFLEYVAAL----NLVLRGSLEHKLKWT---- 97
Cdd:cd15902   104 SGFIEAKELKGFLKdlLLKNKKHVsppkldEYTKLILKEFDANKDGKLELDEMAKLLpvqeNFLLKFQILGAMDLTkedf 183

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907121837  98 ---FKIYDKDRNGCIDRLELLDIVEAIYKLKKACRAELDLEHQgqlltpeevVDRIFLLVDENGDGK 161
Cdd:cd15902   184 ekvFEHYDKDNNGVIEGNELDALLKDLLEKNKADIDKPDLENF---------RDAILRACDKNKDGK 241
PTZ00184 PTZ00184
calmodulin; Provisional
 10-161 5.49e-07

calmodulin; Provisional


Pssm-ID: 185504 [Multi-domain]  Cd Length: 149  Bit Score: 47.83  E-value: 5.49e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907121837  10 AEAAGEMDVAELQEWYKKFVVEcPSGTLFMHEFKRFFKVTGNEEASQYVESMFRAFDKNGDNTIDFLEYVAALNLVLRGS 89
Cdd:PTZ00184    2 ADQLTEEQIAEFKEAFSLFDKD-GDGTITTKELGTVMRSLGQNPTEAELQDMINEVDADGNGTIDFPEFLTLMARKMKDT 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907121837  90 -LEHKLKWTFKIYDKDRNGCIDRLELLDIveaiyklkkacraeldLEHQGQLLTPEEvVDRIFLLVDENGDGK 161
Cdd:PTZ00184   81 dSEEEIKEAFKVFDRDGNGFISAAELRHV----------------MTNLGEKLTDEE-VDEMIREADVDGDGQ 136
EFh cd00051
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...
 34-82 2.16e-06

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: 43.69  E-value: 2.16e-06
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1907121837  34 SGTLFMHEFKRFFKVTGNEEASQYVESMFRAFDKNGDNTIDFLEYVAAL 82
Cdd:cd00051    14 DGTISADELKAALKSLGEGLSEEEIDEMIREVDKDGDGKIDFEEFLELM 62
EFh_PEF_Group_I cd16180
Penta-EF hand, calcium binding motifs, found in Group I PEF proteins; The family corresponds ...
 20-114 5.03e-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: 42.13  E-value: 5.03e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907121837  20 ELQEWYKKFVVECpSGTLFMHEFKR--------FFKvtgneeaSQYVESMFRAFDKNGDNTIDFLEYVAALNLVLRgsle 91
Cdd:cd16180     1 ELRRIFQAVDRDR-SGRISAKELQRalsngdwtPFS-------IETVRLMINMFDRDRSGTINFDEFVGLWKYIQD---- 68

                          90       100
                  ....*....|....*....|....*
gi 1907121837  92 hklkWT--FKIYDKDRNGCIDRLEL 114
Cdd:cd16180    69 ----WRrlFRRFDRDRSGSIDFNEL 89
EF-hand_8 pfam13833
EF-hand domain pair;
33-82 8.27e-05

EF-hand domain pair;


Pssm-ID: 404678 [Multi-domain]  Cd Length: 54  Bit Score: 39.22  E-value: 8.27e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1907121837  33 PSGTLFMHEFKRFFKVTGNEEASQY-VESMFRAFDKNGDNTIDFLEYVAAL 82
Cdd:pfam13833   1 EKGVITREELKRALALLGLKDLSEDeVDILFREFDTDGDGYISFDEFCVLL 51
EFh_PEF_Group_I cd16180
Penta-EF hand, calcium binding motifs, found in Group I PEF proteins; The family corresponds ...
 34-109 1.09e-04

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: 41.36  E-value: 1.09e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907121837  34 SGTLFMHEFKRFFKvtgneeasqYVESM---FRAFDKNGDNTIDFLEYVAALNlvlrgSLEHKL-----KWTFKIYDKDR 105
Cdd:cd16180    51 SGTINFDEFVGLWK---------YIQDWrrlFRRFDRDRSGSIDFNELQNALS-----SFGYRLspqfvQLLVRKFDRRR 116


                  ....
gi 1907121837 106 NGCI 109
Cdd:cd16180   117 RGSI 120
EF-hand_7 pfam13499
EF-hand domain pair;
61-118 1.12e-04

EF-hand domain pair;


Pssm-ID: 463900 [Multi-domain]  Cd Length: 67  Bit Score: 39.16  E-value: 1.12e-04
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907121837  61 MFRAFDKNGDNTIDFLEYVAALNLVLRGS--LEHKLKWTFKIYDKDRNGCIDRLELLDIV 118
Cdd:pfam13499   7 AFKLLDSDGDGYLDVEELKKLLRKLEEGEplSDEEVEELFKEFDLDKDGRISFEEFLELY 66
PTZ00183 PTZ00183
centrin; Provisional
 34-160 1.68e-04

centrin; Provisional


Pssm-ID: 185503 [Multi-domain]  Cd Length: 158  Bit Score: 40.83  E-value: 1.68e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907121837  34 SGTLFMHEFKRFFKVTGNEEASQYVESMFRAFDKNGDNTIDFLEY--VAALNLVLRGSLEHKLKwTFKIYDKDRNGCIdr 111
Cdd:PTZ00183   31 SGTIDPKELKVAMRSLGFEPKKEEIKQMIADVDKDGSGKIDFEEFldIMTKKLGERDPREEILK-AFRLFDDDKTGKI-- 107

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1907121837 112 lelldiveAIYKLKKACRaELdlehqGQLLTPEEVVDRIFlLVDENGDG 160
Cdd:PTZ00183  108 --------SLKNLKRVAK-EL-----GETITDEELQEMID-EADRNGDG 141
EFh_PEF_ALG-2_like cd16185
EF-hand, calcium binding motif, found in homologs of mammalian apoptosis-linked gene 2 protein ...
 58-140 3.28e-04

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: 39.89  E-value: 3.28e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907121837  58 VESMFRAFDKNGDNTIDFLEYvAALNLVLRgslehKLKWTFKIYDKDRNGcidRLELLDIVEAI----YKL-----KKAC 128
Cdd:cd16185    38 AEKLIRMFDRDGNGTIDFEEF-AALHQFLS-----NMQNGFEQRDTSRSG---RLDANEVHEALaasgFQLdppafQALF 108

                          90
                  ....*....|..
gi 1907121837 129 RAeLDLEHQGQL 140
Cdd:cd16185   109 RK-FDPDRGGSL 119
EF-hand_7 pfam13499
EF-hand domain pair;
34-82 4.88e-04

EF-hand domain pair;


Pssm-ID: 463900 [Multi-domain]  Cd Length: 67  Bit Score: 37.62  E-value: 4.88e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1907121837  34 SGTLFMHEFKRFFKV--TGNEEASQYVESMFRAFDKNGDNTIDFLEYVAAL 82
Cdd:pfam13499  16 DGYLDVEELKKLLRKleEGEPLSDEEVEELFKEFDLDKDGRISFEEFLELY 66
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
41-82 5.02e-04

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


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 39.00  E-value: 5.02e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 1907121837  41 EFKRFFKVTGNEEASqyVESMFRAFDKNGDNTIDFLEYVAAL 82
Cdd:COG5126    90 EFRRLLTALGVSEEE--ADELFARLDTDGDGKISFEEFVAAV 129
EFh_PEF_ALG-2 cd16183
EF-hand, calcium binding motif, found in apoptosis-linked gene 2 protein (ALG-2) and similar ...
 58-114 5.30e-04

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: 39.16  E-value: 5.30e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1907121837  58 VESMFRAFDKNGDNTIDFLEYVAALNLVlrgsleHKLKWTFKIYDKDRNGCIDRLEL 114
Cdd:cd16183    39 VRLMIGMFDRDNSGTINFQEFAALWKYI------TDWQNCFRSFDRDNSGNIDKNEL 89
EFh_PI-PLC cd15898
EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4. ...
 57-168 5.56e-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: 38.80  E-value: 5.56e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907121837  57 YVESMFRAFDKNGDNTIDFLEYVAALNLVLRGSLEHKLKWTFKIYDKDRNGCIDRLELldiVEAIYKLKKacRAELDL-- 134
Cdd:cd15898     1 WLRRQWIKADKDGDGKLSLKEIKKLLKRLNIRVSEKELKKLFKEVDTNGDGTLTFDEF---EELYKSLTE--RPELEPif 75

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1907121837 135 ----EHQGQLLTPEEVVDriFlLVDENGDGKRDAVCRE 168
Cdd:cd15898    76 kkyaGTNRDYMTLEEFIR--F-LREEQGENVSEEECEE 110
PTZ00183 PTZ00183
centrin; Provisional
 51-161 6.23e-04

centrin; Provisional


Pssm-ID: 185503 [Multi-domain]  Cd Length: 158  Bit Score: 38.90  E-value: 6.23e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907121837  51 NEEASQYVESMFRAFDKNGDNTIDFLEYVAALNLVLRGSLEHKLKWTFKIYDKDRNGCIDRLELLDIVEAiyKLkkacrA 130
Cdd:PTZ00183   12 TEDQKKEIREAFDLFDTDGSGTIDPKELKVAMRSLGFEPKKEEIKQMIADVDKDGSGKIDFEEFLDIMTK--KL-----G 84

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1907121837 131 ELDlehqgqlltPEEVVDRIFLLVDENGDGK 161
Cdd:PTZ00183   85 ERD---------PREEILKAFRLFDDDKTGK 106
EFh smart00054
EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in ...
 93-121 1.19e-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: 35.43  E-value: 1.19e-03
                           10        20
                   ....*....|....*....|....*....
gi 1907121837   93 KLKWTFKIYDKDRNGCIDRLELLDIVEAI 121
Cdd:smart00054   1 ELKEAFRLFDKDGDGKIDFEEFKDLLKAL 29
EF-hand_6 pfam13405
EF-hand domain;
93-121 1.38e-03

EF-hand domain;


Pssm-ID: 463869 [Multi-domain]  Cd Length: 30  Bit Score: 35.23  E-value: 1.38e-03
                          10        20
                  ....*....|....*....|....*....
gi 1907121837  93 KLKWTFKIYDKDRNGCIDRLELLDIVEAI 121
Cdd:pfam13405   1 ELREAFKLFDKDGDGKISLEELRKALRSL 29
EF-hand_1 pfam00036
EF hand; The EF-hands can be divided into two classes: signalling proteins and buffering ...
 58-82 2.05e-03

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


Pssm-ID: 425435 [Multi-domain]  Cd Length: 29  Bit Score: 34.68  E-value: 2.05e-03
                          10        20
                  ....*....|....*....|....*
gi 1907121837  58 VESMFRAFDKNGDNTIDFLEYVAAL 82
Cdd:pfam00036   2 LKEIFRLFDKDGDGKIDFEEFKELL 26
EFh_PEF_peflin cd16184
EF-hand, calcium binding motif, found in peflin and similar proteins; Peflin, also termed ...
 34-114 2.23e-03

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: 37.63  E-value: 2.23e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907121837  34 SGTLFMHEFKRFFKVTG----NEEASQYVESMFrafDKNGDNTIDFLEYVAALNLVlrgsleHKLKWTFKIYDKDRNGCI 109
Cdd:cd16184    14 SGKISAKELQQALVNGNwshfNDETCRLMIGMF---DKDKSGTIDIYEFQALWNYI------QQWKQVFQQFDRDRSGSI 84


                  ....*
gi 1907121837 110 DRLEL 114
Cdd:cd16184    85 DENEL 89
S-100 cd00213
S-100: S-100 domain, which represents the largest family within the superfamily of proteins ...
 37-79 2.25e-03

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: 35.93  E-value: 2.25e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1907121837  37 LFMHEFKRFFKVTGNEEasqYVESMFRAFDKNGDNTIDFLEYV 79
Cdd:cd00213    35 LLETELPNFLKNQKDPE---AVDKIMKDLDVNKDGKVDFQEFL 74
EFh smart00054
EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in ...
 58-82 2.39e-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: 34.66  E-value: 2.39e-03
                           10        20
                   ....*....|....*....|....*
gi 1907121837   58 VESMFRAFDKNGDNTIDFLEYVAAL 82
Cdd:smart00054   2 LKEAFRLFDKDGDGKIDFEEFKDLL 26
EFh_HEF_CBN cd16179
EF-hand, calcium binding motif, found in Drosophila melanogaster calbindin-32 (CBN) and ...
 56-161 3.02e-03

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: 37.77  E-value: 3.02e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907121837  56 QYVESMFRAFDKNGDNTIDFLEYVAAL----NLVLRGSLEHKLKWT-------FKIYDKDRNGCIDRLELLDIVEAIYKL 124
Cdd:cd16179   141 EYTDTILQLFDRNKDGKLQLSEMARLLpvkeNFLCRPIFKGAGKLTredidrvFALYDRDNNGTIENEELTGFLKDLLEL 220

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1907121837 125 KKACRAELDLehqgqlltpEEVVDRIFLLVDENGDGK 161
Cdd:cd16179   221 VQEDYDEQDL---------EEFKEIILRGWDFNNDGK 248
EFh_HEF_CBN cd16179
EF-hand, calcium binding motif, found in Drosophila melanogaster calbindin-32 (CBN) and ...
 55-161 5.44e-03

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: 37.00  E-value: 5.44e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907121837  55 SQYVESMFRAFDKNGDNTIDFLEYVAAL----NLVLRGSLEHKLKWT------FKIYDKDRNGCIDRLELLDIVEaiyKL 124
Cdd:cd16179    48 EELKEEFMEAYDENQDGRIDIRELAQLLpteeNFLLLFRRDNPLDSSvefmkvWREYDKDNSGYIEADELKNFLK---HL 124

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1907121837 125 KKACRAELDLEhQGQLLtpeEVVDRIFLLVDENGDGK 161
Cdd:cd16179   125 LKEAKRDNDVS-EDKLI---EYTDTILQLFDRNKDGK 157
 
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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