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

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 22122571  57 YVESMFRAFDKNGDNTIDFLEYVAALNLVLRGSLEHKLKWTFKIYDKDRNGCIDRLELLDIV 118
Cdd:cd00051   1 ELREAFRLFDKDGDGTISADELKAALKSLGEGLSEEEIDEMIREVDKDGDGKIDFEEFLELM 62

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

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 22122571  57 YVESMFRAFDKNGDNTIDFLEYVAALNLVLRGSLEHKLKWTFKIYDKDRNGCIDRLELLDIV 118
Cdd:cd00051   1 ELREAFRLFDKDGDGTISADELKAALKSLGEGLSEEEIDEMIREVDKDGDGKIDFEEFLELM 62

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22122571  93 KLKWTFKIYDKDRNGCIDRLELLDIVEAIYklkkacraeldlehqgqLLTPEEVVDRIFLLVDENGDGQLSLTEFIEGAR 172
Cdd:cd00051   1 ELREAFRLFDKDGDGTISADELKAALKSLG-----------------EGLSEEEIDEMIREVDKDGDGKIDFEEFLELMA 63

EF-hand domain pair;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22122571    93 KLKWTFKIYDKDRNGCIDRLELLDIVEAIyklkkacraeldleHQGQLLTPEEVvDRIFLLVDENGDGQLSLTEFIEGAR 172
Cdd:pfam13499   3 KLKEAFKLLDSDGDGYLDVEELKKLLRKL--------------EEGEPLSDEEV-EELFKEFDLDKDGRISFEEFLELYS 67

centrin; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22122571   51 NEEASQYVESMFRAFDKNGDNTIDFLEYVAALNLVLRGSLEHKLKWTFKIYDKDRNGCIDRLELLDIVEAiyKLkkacrA 130
Cdd:PTZ00183  12 TEDQKKEIREAFDLFDTDGSGTIDPKELKVAMRSLGFEPKKEEIKQMIADVDKDGSGKIDFEEFLDIMTK--KL-----G 84

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 22122571  131 ELDlehqgqlltPEEVVDRIFLLVDENGDGQLSLT 165
Cdd:PTZ00183  85 ERD---------PREEILKAFRLFDDDKTGKISLK 110

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

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 22122571  57 YVESMFRAFDKNGDNTIDFLEYVAALNLVLRGSLEHKLKWTFKIYDKDRNGCIDRLELLDIV 118
Cdd:cd00051   1 ELREAFRLFDKDGDGTISADELKAALKSLGEGLSEEEIDEMIREVDKDGDGKIDFEEFLELM 62

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22122571  93 KLKWTFKIYDKDRNGCIDRLELLDIVEAIYklkkacraeldlehqgqLLTPEEVVDRIFLLVDENGDGQLSLTEFIEGAR 172
Cdd:cd00051   1 ELREAFRLFDKDGDGTISADELKAALKSLG-----------------EGLSEEEIDEMIREVDKDGDGKIDFEEFLELMA 63

EF-hand domain pair;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22122571    93 KLKWTFKIYDKDRNGCIDRLELLDIVEAIyklkkacraeldleHQGQLLTPEEVvDRIFLLVDENGDGQLSLTEFIEGAR 172
Cdd:pfam13499   3 KLKEAFKLLDSDGDGYLDVEELKKLLRKL--------------EEGEPLSDEEV-EELFKEFDLDKDGRISFEEFLELYS 67

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).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22122571  58 VESMFRAFDKNGDNTIDFLEYvAALNLVLRgslehKLKWTFKIYDKDRNGcidRLELLDIVEAiyklkkacraeldLEHQ 137
Cdd:cd16185  38 AEKLIRMFDRDGNGTIDFEEF-AALHQFLS-----NMQNGFEQRDTSRSG---RLDANEVHEA-------------LAAS 95

                        90       100       110
                ....*....|....*....|....*....|...
gi 22122571 138 G-QLltPEEVVDRIFLLVDENGDGQLSLTEFIE 169
Cdd:cd16185  96 GfQL--DPPAFQALFRKFDPDRGGSLGFDDYIE 126

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

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*....
gi 22122571  34 SGTLFMHEFKRFFKVTGNEEASQYVESMFRAFDKNGDNTIDFLEYVAAL 82
Cdd:cd00051  14 DGTISADELKAALKSLGEGLSEEEIDEMIREVDKDGDGKIDFEEFLELM 62

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22122571  57 YVESMFRAFDKNGDNTIDFLEYVAALNLVLRGSLEHKLKWTFKIYDKDRNGCIDRLELL----------DIVEAIYKLKK 126
Cdd:cd15898   1 WLRRQWIKADKDGDGKLSLKEIKKLLKRLNIRVSEKELKKLFKEVDTNGDGTLTFDEFEelykslterpELEPIFKKYAG 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|
gi 22122571 127 ACRAELDLEH--------QGQLLTPEEVVDRIFLLVDENGDGQLSLTEFI 168
Cdd:cd15898  81 TNRDYMTLEEfirflreeQGENVSEEECEELIEKYEPERENRQLSFEGFT 130

centrin; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22122571   51 NEEASQYVESMFRAFDKNGDNTIDFLEYVAALNLVLRGSLEHKLKWTFKIYDKDRNGCIDRLELLDIVEAiyKLkkacrA 130
Cdd:PTZ00183  12 TEDQKKEIREAFDLFDTDGSGTIDPKELKVAMRSLGFEPKKEEIKQMIADVDKDGSGKIDFEEFLDIMTK--KL-----G 84

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 22122571  131 ELDlehqgqlltPEEVVDRIFLLVDENGDGQLSLT 165
Cdd:PTZ00183  85 ERD---------PREEILKAFRLFDDDKTGKISLK 110

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+.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22122571  34 SGTLFMHEFKRFFKvtgneeasqYVESM---FRAFDKNGDNTIDFLEYVAALNlvlrgSLEHKL-----KWTFKIYDKDR 105
Cdd:cd16180  51 SGTINFDEFVGLWK---------YIQDWrrlFRRFDRDRSGSIDFNELQNALS-----SFGYRLspqfvQLLVRKFDRRR 116

                ....
gi 22122571 106 NGCI 109
Cdd:cd16180 117 RGSI 120

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22122571  55 SQYVESMFRAFDKNGDNTIDFLEYVAAL----NLVLRGSLEHKLKWT------FKIYDKDRNGCIDRLELLDIVEaiyKL 124
Cdd:cd16179  48 EELKEEFMEAYDENQDGRIDIRELAQLLpteeNFLLLFRRDNPLDSSvefmkvWREYDKDNSGYIEADELKNFLK---HL 124

                        90       100       110       120
                ....*....|....*....|....*....|....*....|..
gi 22122571 125 KKACRAELDLEhQGQLLtpeEVVDRIFLLVDENGDGQLSLTE 166
Cdd:cd16179 125 LKEAKRDNDVS-EDKLI---EYTDTILQLFDRNKDGKLQLSE 162

Eps15 homology domain; found in proteins implicated in endocytosis, vesicle transport, and signal transduction. The alignment contains a pair of EF-hand motifs, typically one of them is canonical and binds to Ca2+, while the other may not bind to Ca2+. A hydrophobic binding pocket is formed by residues from both EF-hand motifs. The EH domain binds to proteins containing NPF (class I), [WF]W or SWG (class II), or H[TS]F (class III) sequence motifs.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 22122571  98 FKIYDKDRNGCIDRLELLDIVEAIyKLkkacraeldlehqgqlltPEEVVDRIFLLVDENGDGQLSLTEFI 168
Cdd:cd00052   5 FRSLDPDGDGLISGDEARPFLGKS-GL------------------PRSVLAQIWDLADTDKDGKLDKEEFA 56

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22122571  40 HEFKRFFKVT-----GNEEASQYVESMFRAF----DKNGDNTIDFLEYVAAL-----NLVLRGSLEHKLKW-----TFKI 100
Cdd:cd15902  19 KELDSFLRELlkalnGKDKTDDEVAEKKKEFmekyDENEDGKIEIRELANILpteenFLLLFRREQPLISSvefmkIWRK 98

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 22122571 101 YDKDRNGCIDRLELldiveaiyklkKACRAELDLEHQGQLLTP--EEVVDRIFLLVDENGDGQLSLTEF 167
Cdd:cd15902  99 YDTDGSGFIEAKEL-----------KGFLKDLLLKNKKHVSPPklDEYTKLILKEFDANKDGKLELDEM 156

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22122571  56 QYVESMFRAFDKNGDNTIDFLEYVAAL----NLVLRGSLEHKLKWT-------FKIYDKDRNGCIDRLELLDIVEAIYKL 124
Cdd:cd16179 141 EYTDTILQLFDRNKDGKLQLSEMARLLpvkeNFLCRPIFKGAGKLTredidrvFALYDRDNNGTIENEELTGFLKDLLEL 220

                        90       100       110       120
                ....*....|....*....|....*....|....*....|..
gi 22122571 125 KKACRAELDLehqgqlltpEEVVDRIFLLVDENGDGQLSLTE 166
Cdd:cd16179 221 VQEDYDEQDL---------EEFKEIILRGWDFNNDGKISRKE 253

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.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 22122571  37 LFMHEFKRFFKVTGNEEasqYVESMFRAFDKNGDNTIDFLEYV 79
Cdd:cd00213  35 LLETELPNFLKNQKDPE---AVDKIMKDLDVNKDGKVDFQEFL 74

EF-hand, extracellular calcium-binding (EC) motif, found in secreted protein acidic and rich in cysteine (SPARC)-like proteins; The SPARC protein family represents a diverse group of proteins that share a follistatin-like (FS) domain and an extracellular calcium-binding (EC) domain with two EF-hand motifs. It includes SPARC (for secreted protein acidic and rich in cysteine, also termed osteonectin/ON, or basement-membrane protein 40/BM-40), SPARC-like protein 1 (for secreted protein, acidic and rich in cysteines-like 1/ SPARCL1, also termed high endothelial venule protein/Hevi, or MAST 9, or SC-1, or RAGS-1, or QR1, or ECM 2), testicans 1, 2, and 3 (also termed SPARC/osteonectin, CWCV, and Kazal-like domains proteoglycans, or SPOCK), secreted modular calcium-binding protein SMOC-1 (also termed SPARC-related modular calcium-binding protein 1) and SMOC-2 (also termed SPARC-related modular calcium-binding protein 2, or smooth muscle-associated protein 2/SMAP-2), follistatin-related protein 1 (FRP-1, also termed follistatin-like protein 1/fstl-1, TSC-36/Flik, TGF-beta inducible protein). The SPARC proteins have been implicated in modulating cell interaction with the extracellular milieu, including regulation of extracellular matrix assembly and deposition, counter-adhesion, effects on extracellular protease activity, and modulation of growth factor/cytokine signaling pathways, as well as in development and disease.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 22122571  94 LKWTFKIYDKDRNGCIDRLELLDIVEaiyklkkacraeldlehqgQLLTPEEVVDRIFLLVDENGDGQLSLTEFIE 169
Cdd:cd00252  47 AQWEFDNLDNNKDGKLDKRELAPFRA-------------------PLMPLEHCARGFFESCDLNKDKKISLQEWLG 103

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22122571  34 SGTLFMHEFKRFFKVTG----NEEASQYVESMFrafDKNGDNTIDFLEYVAALNLVlrgsleHKLKWTFKIYDKDRNGCI 109
Cdd:cd16184  14 SGKISAKELQQALVNGNwshfNDETCRLMIGMF---DKDKSGTIDIYEFQALWNYI------QQWKQVFQQFDRDRSGSI 84

                ....*
gi 22122571 110 DRLEL 114
Cdd:cd16184  85 DENEL 89