NCBI Conserved Domain Search

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

Pssm-ID: 444056 [Multi-domain] Cd Length: 137 Bit Score: 74.83 E-value: 2.35e-17

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4406346   58 DQVYNTFDTNKDGFIDFLEFIAAVNLIMQEKMEQKLKWYFKLYDADGNGSIDKNELldmFMAVQALNGqqtlsPEEFINL 137
Cdd:COG5126  36 ATLFSEADTDGDGRISREEFVAGMESLFEATVEPFARAAFDLLDTDGDGKISADEF---RRLLTALGV-----SEEEADE 107

                        90       100
                ....*....|....*....|....
gi 4406346  138 VFHKIDINNDGELTLEEFINGMAK 161
Cdd:COG5126 108 LFARLDTDGDGKISFEEFVAAVRD 131

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: 62.18 E-value: 2.61e-13

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 4406346   92 KLKWYFKLYDADGNGSIDKNELldmFMAVQALNGQQTlspEEFINLVFHKIDINNDGELTLEEFINGMA 160
Cdd:cd00051   1 ELREAFRLFDKDGDGTISADEL---KAALKSLGEGLS---EEEIDEMIREVDKDGDGKIDFEEFLELMA 63

EF-hand domain pair;

Pssm-ID: 463900 [Multi-domain] Cd Length: 67 Bit Score: 60.34 E-value: 1.33e-12

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4406346     90 EQKLKWYFKLYDADGNGSIDKNELLDMFmavQALNGQQTLSPEEfINLVFHKIDINNDGELTLEEFINGM 159
Cdd:pfam13499   1 EEKLKEAFKLLDSDGDGYLDVEELKKLL---RKLEEGEPLSDEE-VEELFKEFDLDKDGRISFEEFLELY 66

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

Pssm-ID: 238008 [Multi-domain] Cd Length: 63 Bit Score: 58.71 E-value: 5.68e-12

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 4406346   56 HIDQVYNTFDTNKDGFIDFLEFIAAVNLIMQEKMEQKLKWYFKLYDADGNGSIDKNELLDMFM 118
Cdd:cd00051   1 ELREAFRLFDKDGDGTISADELKAALKSLGEGLSEEEIDEMIREVDKDGDGKIDFEEFLELMA 63

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

Pssm-ID: 444056 [Multi-domain] Cd Length: 137 Bit Score: 56.34 E-value: 2.62e-10

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4406346   87 EKMEQKLKWYFKLYDADGNGSIDKNELLDMFMAVQAL-------NGQQTLSPEEFINLV---------------FHKIDI 144
Cdd:COG5126   1 DLQRRKLDRRFDLLDADGDGVLERDDFEALFRRLWATlfseadtDGDGRISREEFVAGMeslfeatvepfaraaFDLLDT 80

                        90       100       110
                ....*....|....*....|....*....|...
gi 4406346  145 NNDGELTLEEF---INGMAKDQDLLEIVYKSFD 174
Cdd:COG5126  81 DGDGKISADEFrrlLTALGVSEEEADELFARLD 113

calmodulin; Provisional

Pssm-ID: 185504 [Multi-domain] Cd Length: 149 Bit Score: 52.46 E-value: 7.43e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4406346    62 NTFDTNKDGFIDFLEFIAavnlIMQEKM-----EQKLKWYFKLYDADGNGSIDKNELLDMFMavqalNGQQTLSPEEFIN 136
Cdd:PTZ00184  54 NEVDADGNGTIDFPEFLT----LMARKMkdtdsEEEIKEAFKVFDRDGNGFISAAELRHVMT-----NLGEKLTDEEVDE 124

                         90       100
                 ....*....|....*....|...
gi 4406346   137 LVfHKIDINNDGELTLEEFINGM 159
Cdd:PTZ00184 125 MI-READVDGDGQINYEEFVKMM 146

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: 50.73 E-value: 4.73e-08

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4406346   62 NTFDTNKDGFIDFLEFIAAVNLImqekmeQKLKWYFKLYDADGNGSIDKNELldmfmaVQALN--GQQtLSPeEFINLVF 139
Cdd:cd16184  44 GMFDKDKSGTIDIYEFQALWNYI------QQWKQVFQQFDRDRSGSIDENEL------HQALSqmGYR-LSP-QFVQFLV 109

                        90
                ....*....|....*...
gi 4406346  140 HKIDINNDGELTLEEFIN 157
Cdd:cd16184 110 SKYDPRARRSLTLDQFIQ 127

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: 50.33 E-value: 5.76e-08

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4406346   64 FDTNKDGFIDFLEFIAAVNLImqekmeQKLKWYFKLYDADGNGSIDKNELldmfmaVQALNG-QQTLSPeEFINLVFHKI 142
Cdd:cd16183  46 FDRDNSGTINFQEFAALWKYI------TDWQNCFRSFDRDNSGNIDKNEL------KQALTSfGYRLSD-QFYDILVRKF 112

                        90
                ....*....|....
gi 4406346  143 DINNDGELTLEEFI 156
Cdd:cd16183 113 DRQGRGTIAFDDFI 126

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

Pssm-ID: 320025 [Multi-domain] Cd Length: 263 Bit Score: 49.62 E-value: 2.80e-07

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4406346   57 IDQVYNTFDTNKDGFIDFLEFIAavnlimQEKMEQKLKWYF-------KLYDADGNGSIDKNELLDMfmavqALNGQQTL 129
Cdd:cd16227 161 IEQTLRDKDKDNDGFISFQEFLG------DRAGHEDKEWLLvekdrfdEDYDKDGDGKLDGEEILSW-----LVPDNEEI 229

                        90       100
                ....*....|....*....|....*...
gi 4406346  130 SPEEFINLvFHKIDINNDGELTLEEFIN 157
Cdd:cd16227 230 AEEEVDHL-FASADDDHDDRLSFDEILD 256

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: 48.29 E-value: 2.86e-07

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4406346   62 NTFDTNKDGFIDFLEFIAAVNLIMQekmeqklkW--YFKLYDADGNGSIDKNELldmfmaVQALNG-QQTLSPeEFINLV 138
Cdd:cd16180  44 NMFDRDRSGTINFDEFVGLWKYIQD--------WrrLFRRFDRDRSGSIDFNEL------QNALSSfGYRLSP-QFVQLL 108

                        90
                ....*....|....*...
gi 4406346  139 FHKIDINNDGELTLEEFI 156
Cdd:cd16180 109 VRKFDRRRRGSISFDDFV 126

centrin; Provisional

Pssm-ID: 185503 [Multi-domain] Cd Length: 158 Bit Score: 48.15 E-value: 3.09e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4406346    48 GLNQKANKHIDQVYNTFDTNKDGFIDFLEFIAAVNLIMQEKMEQKLKWYFKLYDADGNGSIDKNELLD------------ 115
Cdd:PTZ00183  10 GLTEDQKKEIREAFDLFDTDGSGTIDPKELKVAMRSLGFEPKKEEIKQMIADVDKDGSGKIDFEEFLDimtkklgerdpr 89

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 4406346   116 -----MF----------MAVQALNG-----QQTLSPEEfINLVFHKIDINNDGELTLEEFINGMAKD 162
Cdd:PTZ00183  90 eeilkAFrlfdddktgkISLKNLKRvakelGETITDEE-LQEMIDEADRNGDGEISEEEFYRIMKKT 155

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: 45.28 E-value: 3.62e-06

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4406346   64 FDTNKDGFIDFLEFiAAVN---LIMQEKmeqklkwyFKLYDADGNGSIDKNElldMFMAVQAlNGQQtLSPEEFiNLVFH 140
Cdd:cd16185  45 FDRDGNGTIDFEEF-AALHqflSNMQNG--------FEQRDTSRSGRLDANE---VHEALAA-SGFQ-LDPPAF-QALFR 109

                        90
                ....*....|....*..
gi 4406346  141 KIDINNDGELTLEEFIN 157
Cdd:cd16185 110 KFDPDRGGSLGFDDYIE 126

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

Pssm-ID: 320029 [Multi-domain] Cd Length: 137 Bit Score: 44.58 E-value: 4.39e-06

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4406346   32 SGLQTLHEFKTLLglQGLN-QKANKHIDQVYNTFDTNKDGFIDFLEFIAAVNLIMQEKmeqKLKWYFKLYDADGNGSIDK 110
Cdd:cd15898  14 DGKLSLKEIKKLL--KRLNiRVSEKELKKLFKEVDTNGDGTLTFDEFEELYKSLTERP---ELEPIFKKYAGTNRDYMTL 88

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|
gi 4406346  111 NELLDMFMAVQalngQQTLSPEE---FINLVFHKidiNNDGELTLEEFIN 157
Cdd:cd15898  89 EEFIRFLREEQ----GENVSEEEceeLIEKYEPE---RENRQLSFEGFTN 131

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

Pssm-ID: 320025 [Multi-domain] Cd Length: 263 Bit Score: 46.16 E-value: 4.52e-06

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4406346   65 DTNKDGFIDFLEFIAAVNLIMQEKMEQ----------KL----KWYFKLYDADGNGSIDKNElldmFMAVQalngqqtlS 130
Cdd:cd16227  82 DEDGDGKVTWEEYLADSFGYDDEDNEEmikdsteddlKLleddKEMFEAADLNKDGKLDKTE----FSAFQ--------H 149

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 4406346  131 PEEF-------INLVFHKIDINNDGELTLEEFINGMAKDQD 164
Cdd:cd16227 150 PEEYphmhpvlIEQTLRDKDKDNDGFISFQEFLGDRAGHED 190

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

Pssm-ID: 320024 [Multi-domain] Cd Length: 264 Bit Score: 45.65 E-value: 6.40e-06

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4406346   65 DTNKDGFIDFLEFIAavNLIMQEKMEQKLKW------YFKLY-DADGNGSIDKNELLDMFMAVQALNGQqtlspEEFINL 137
Cdd:cd16226 166 DKNKDGFISLEEYIG--DMYRDDDEEEDPDWvksereQFKEFrDKNKDGKMDREEVKDWILPEDYDHAE-----AEAKHL 238

                        90       100
                ....*....|....*....|
gi 4406346  138 VFHKiDINNDGELTLEEFIN 157
Cdd:cd16226 239 IYEA-DDDKDGKLTKEEILD 257

Eps15 homology domain; Pair of EF hand motifs that recognise proteins containing Asn-Pro-Phe (NPF) sequences.

Pssm-ID: 197477 [Multi-domain] Cd Length: 96 Bit Score: 40.72 E-value: 4.43e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4406346      58 DQVYNTFDTNKDGFIDFLEfiaAVNLIMQEKMEQKL---KWyfKLYDADGNGSIDKNEL-LDMFMAVQALNGQQ---TLS 130
Cdd:smart00027  13 EQIFRSLDKNQDGTVTGAQ---AKPILLKSGLPQTLlakIW--NLADIDNDGELDKDEFaLAMHLIYRKLNGYPipaSLP 87


                   ..
gi 4406346     131 PE 132
Cdd:smart00027  88 PS 89

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

Pssm-ID: 320075 [Multi-domain] Cd Length: 254 Bit Score: 42.73 E-value: 5.31e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4406346   64 FDTNKDGFIDFLE----------FIAAVNLIMQEKMEQKLKWYFKLYDADGNGSIDKNELLDMFMAVQALNGQQTLSP-- 131
Cdd:cd15902  53 YDENEDGKIEIRElanilpteenFLLLFRREQPLISSVEFMKIWRKYDTDGSGFIEAKELKGFLKDLLLKNKKHVSPPkl 132

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....
gi 4406346  132 EEFINLVFHKIDINNDGELTLEEFI-------NGMAKDQDLLEIVYKSFDFSNV 178
Cdd:cd15902 133 DEYTKLILKEFDANKDGKLELDEMAkllpvqeNFLLKFQILGAMDLTKEDFEKV 186

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

Pssm-ID: 320022 [Multi-domain] Cd Length: 268 Bit Score: 42.80 E-value: 6.28e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4406346   57 IDQVYNTFDTNKDGFIDFLEFIA------AVNLIMQEKMEQKLKwYFKLYDADGNGSIDKNELLDMFMAvqalnGQQTLS 130
Cdd:cd16224 163 IQEALEEHDKDGDGFISLEEFLGdyrkdpTANEDPEWIIVEKDR-FVNDYDKDNDGKLDPQELLPWVVP-----NNYGIA 236

                        90       100
                ....*....|....*....|....*....
gi 4406346  131 PEEFINLVfHKIDINNDGELTLEEFINGM 159
Cdd:cd16224 237 QEEALHLI-DEMDLNGDGRLSEEEILENQ 264

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

Pssm-ID: 444056 [Multi-domain] Cd Length: 137 Bit Score: 40.93 E-value: 9.28e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4406346   32 SGLQTLHEFKTLLGLQGLNQKANKhIDQVYNTFDTNKDGFID---FLEFIAAVNLIMQEkmeqkLKWYFKLYDADGNGSI 108
Cdd:COG5126  47 DGRISREEFVAGMESLFEATVEPF-ARAAFDLLDTDGDGKISadeFRRLLTALGVSEEE-----ADELFARLDTDGDGKI 120

                        90
                ....*....|
gi 4406346  109 DKNELLDMFM 118
Cdd:COG5126 121 SFEEFVAAVR 130

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

Pssm-ID: 320024 [Multi-domain] Cd Length: 264 Bit Score: 42.19 E-value: 9.84e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4406346   53 ANKHI----DQVYNTFDTNKDGFIDFLEFIAAV-------------NLIMQEKMEQKLKwYFKLYDADGNGSIDKNElld 115
Cdd:cd16226  65 QKKYIredvDRQWKEYDPNKDGKLSWEEYKKATygflddeeedddlHESYKKMIRRDER-RWKAADQDGDGKLTKEE--- 140

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 4406346  116 mFMAVqalngqqtLSPEEFINL-------VFHKIDINNDGELTLEEFINGMAKDQDLLE 167
Cdd:cd16226 141 -FTAF--------LHPEEFPHMrdivvqeTLEDIDKNKDGFISLEEYIGDMYRDDDEEE 190

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: 40.73 E-value: 9.87e-05

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 4406346   92 KLKWYFKLYDADGNGSIDKNELLDMfmaVQALNGQqtlSPEEFINLVFHKIDINNDGELTLEEFIN 157
Cdd:cd15898   1 WLRRQWIKADKDGDGKLSLKEIKKL---LKRLNIR---VSEKELKKLFKEVDTNGDGTLTFDEFEE 60

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

Pssm-ID: 320021 [Multi-domain] Cd Length: 267 Bit Score: 41.27 E-value: 1.54e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4406346   65 DTNKDGFIDFLEFIAavNLIMQEKMEQKLKW-------YFKLYDADGNGSIDKNELLDMfmaVQALNGQQtlsPEEFINL 137
Cdd:cd15899 170 DKNGDGFISLEEFIS--DPYSADENEEEPEWvkvekerFVELRDKDKDGKLDGEELLSW---VDPSNQEI---ALEEAKH 241

                        90       100
                ....*....|....*....|
gi 4406346  138 VFHKIDINNDGELTLEEFIN 157
Cdd:cd15899 242 LIAESDENKDGKLSPEEILD 261

EF-hand domain pair;

Pssm-ID: 463900 [Multi-domain] Cd Length: 67 Bit Score: 38.39 E-value: 2.25e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 4406346     59 QVYNTFDTNKDGFIDFLEFIAAV-NLIMQEKM-EQKLKWYFKLYDADGNGSIDKNELLDMFM 118
Cdd:pfam13499   6 EAFKLLDSDGDGYLDVEELKKLLrKLEEGEPLsDEEVEELFKEFDLDKDGRISFEEFLELYS 67

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: 37.91 E-value: 2.35e-04

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 4406346   32 SGLQTLHEFKTLLGLQGLNQKaNKHIDQVYNTFDTNKDGFIDFLEFIAAV 81
Cdd:cd00051  14 DGTISADELKAALKSLGEGLS-EEEIDEMIREVDKDGDGKIDFEEFLELM 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.

Pssm-ID: 320029 [Multi-domain] Cd Length: 137 Bit Score: 39.57 E-value: 2.75e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4406346   57 IDQVYNTFDTNKDGFIDFLEFIAAVNLIMQEKMEQKLKWYFKLYDADGNGSIDKNELLDMFMAVqalngqqTLSPEefIN 136
Cdd:cd15898   2 LRRQWIKADKDGDGKLSLKEIKKLLKRLNIRVSEKELKKLFKEVDTNGDGTLTFDEFEELYKSL-------TERPE--LE 72

                        90       100
                ....*....|....*....|.
gi 4406346  137 LVFHKIDINNDGELTLEEFIN 157
Cdd:cd15898  73 PIFKKYAGTNRDYMTLEEFIR 93

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

Pssm-ID: 320057 [Multi-domain] Cd Length: 167 Bit Score: 39.51 E-value: 3.70e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4406346   59 QVYNTFDTNKDGFIDFLEFiaavnlimqEKMEQKLKWY---FKLYDADGNGSIDKNELLDMFMA---------VQAL--- 123
Cdd:cd16182  46 SLIALMDTNGSGRLDLEEF---------KTLWSDLKKWqaiFKKFDTDRSGTLSSYELRKALESagfhlsnkvLQALvlr 116

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 4406346  124 --NGQQTLSPEEFINLV---------FHKIDINNDG--ELTLEEFI 156
Cdd:cd16182 117 yaDSTGRITFEDFVSCLvrlktafetFSALDKKNEGviPLTLEEWL 162

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

Pssm-ID: 320024 [Multi-domain] Cd Length: 264 Bit Score: 40.26 E-value: 3.83e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4406346   65 DTNKDGFIDFLEFIAAVNLIMQEKMEQKLKWYFKLYDADGNGSIDKNELLDMFMAVQALNGQQTLSPEEFINLV------ 138
Cdd:cd16226  45 DKNGDGFVTEEELKDWIKYVQKKYIREDVDRQWKEYDPNKDGKLSWEEYKKATYGFLDDEEEDDDLHESYKKMIrrderr 124

                        90
                ....*....|....*..
gi 4406346  139 FHKIDINNDGELTLEEF 155
Cdd:cd16226 125 WKAADQDGDGKLTKEEF 141

XopAW family type III secretion system calcium-binding effector;

Pssm-ID: 469301 [Multi-domain] Cd Length: 227 Bit Score: 40.05 E-value: 4.40e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 4406346    86 QEKMEQKLkwyFKLYDADGNGSIDKNELldmfmaVQALNGQQTLSPEEFINLVFHKIDINNDGELTLEEFINGMA 160
Cdd:NF041410  25 SQQFQKQL---FAKLDSDGDGSVSQDEL------SSALSSKSDDGSLIDLSELFSDLDSDGDGSLSSDELAAAAP 90

EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in pairs. Links between disease states and genes encoding EF-hands, particularly the S100 subclass, are emerging. Each motif consists of a 12 residue loop flanked on either side by a 12 residue alpha-helix. EF-hands undergo a conformational change unpon binding calcium ions.

Pssm-ID: 197492 [Multi-domain] Cd Length: 29 Bit Score: 35.82 E-value: 7.94e-04

                           10        20
                   ....*....|....*....|....*....
gi 4406346      92 KLKWYFKLYDADGNGSIDKNELLDMFMAV 120
Cdd:smart00054   1 ELKEAFRLFDKDGDGKIDFEEFKDLLKAL 29

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

Pssm-ID: 320023 [Multi-domain] Cd Length: 278 Bit Score: 38.82 E-value: 1.03e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4406346   59 QVYNTFDTNKDGFIDFLEFIAAVnLIMQEKMEQKLKWYFKLYDADGNGSIDKNELLDM-FMAVQALNGQ-QTLSPEEFI- 135
Cdd:cd16225  77 QIFKAVDTDKDGNVSWEEYRVHF-LLSKGYSEEEAEEKIKNNEELKLDEDDKEVLDRYkDRWSQADEPEdGLLDVEEFLs 155

                        90       100       110
                ....*....|....*....|....*....|....*...
gi 4406346  136 ------------NLVF---HKIDINNDGELTLEEFING 158
Cdd:cd16225 156 frhpehsrgmlkNMVKeilHDLDQDGDEKLTLDEFVSL 193

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: 38.28 E-value: 1.05e-03

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 4406346   97 FKLYDADGNGSIDKNELldmfmaVQAL-NGQQTLSPEEFINLVFHKIDINNDGELTLEEFIN 157
Cdd:cd16180   6 FQAVDRDRSGRISAKEL------QRALsNGDWTPFSIETVRLMINMFDRDRSGTINFDEFVG 61

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

Pssm-ID: 320021 [Multi-domain] Cd Length: 267 Bit Score: 38.96 E-value: 1.09e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4406346   53 ANKHIDQVYNTFDTNKDGFIDFLEFIA-------------AVNLIMQE---KMEQKLKWYFKLYDADGNGSIDKNELLdM 116
Cdd:cd15899  69 AMEESKEQFRAVDPDEDGHVSWDEYKNdtygsvgddeenvADNIKEDEeykKLLLKDKKRFEAADQDGDLILTLEEFL-A 147

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....
gi 4406346  117 FmavqalngqqtLSPEEF-------INLVFHKIDINNDGELTLEEFINGMAKDQ 163
Cdd:cd15899 148 F-----------LHPEESpymldfvIKETLEDLDKNGDGFISLEEFISDPYSAD 190

calmodulin; Provisional

Pssm-ID: 185504 [Multi-domain] Cd Length: 149 Bit Score: 37.82 E-value: 1.34e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4406346    59 QVYNTFDTNKDGFIDFLEFIAAVNLIMQEKMEQKLKWYFKLYDADGNGSIDKNElldmFMAVQALNGQQTLSPEEFINlV 138
Cdd:PTZ00184  15 EAFSLFDKDGDGTITTKELGTVMRSLGQNPTEAELQDMINEVDADGNGTIDFPE----FLTLMARKMKDTDSEEEIKE-A 89

                         90
                 ....*....|....*.
gi 4406346   139 FHKIDINNDGELTLEE 154
Cdd:PTZ00184  90 FKVFDRDGNGFISAAE 105

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: 38.49 E-value: 1.66e-03

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 4406346   97 FKLYDADGNGSIDKNELLDMFMA-VQALNGQQTLSPE--EFINLVFHKIDINNDGELTLEEFINGMAKDQDLL 166
Cdd:cd15902   5 WMHFDADGNGYIEGKELDSFLRElLKALNGKDKTDDEvaEKKKEFMEKYDENEDGKIEIRELANILPTEENFL 77

EF-hand, calcium binding motif, found in calbindin (CB); CB, also termed calbindin D28, or D-28K, or avian-type vitamin D-dependent calcium-binding protein, is a unique intracellular calcium binding protein that functions as both a calcium sensor and buffer in eukaryotic cells, which undergoes a conformational change upon calcium binding and protects cells against insults of high intracellular calcium concentration. CB is highly expressed in brain and sensory neurons. It plays essential roles in neural functioning, altering synaptic interactions in the hippocampus, modulating calcium channel activity, calcium transients, and intrinsic neuronal firing activity. It prevents a neuronal death, as well as maintains and controls calcium homeostasis. CB also modulates the activity of proteins participating in the development of neurodegenerative disorders such as Alzheimer's disease, Huntington's disease, and bipolar disorder. Moreover, CB interacts with Ran-binding protein M, a protein known to involve in microtubule function. It also interacts with alkaline phosphatase and myo-inositol monophosphatase, as well as caspase 3, an enzyme that plays an important role in the regulation of apoptosis. CB contains six EF-hand motifs in a single globular domain, where EF-hands 1, 3, 4, 5 bind four calcium ions with high affinity.

Pssm-ID: 320076 [Multi-domain] Cd Length: 243 Bit Score: 38.28 E-value: 1.91e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4406346   32 SGLQTLHEFKTLLglQGLNQKANKHIDQV---------YNTFDTNKDGFIDFLEFiaAVNLIMQE---------KMEQK- 92
Cdd:cd16176  99 SGFIEADELKSFL--KDLLKKANKPFDESkleeythtmLKMFDSNNDGKLGLTEM--ARLLPVQEnfllkfqgvKMCGKe 174

                        90       100
                ....*....|....*....|.
gi 4406346   93 LKWYFKLYDADGNGSIDKNEL 113
Cdd:cd16176 175 FNKIFELYDQDGNGYIDENEL 195

EF-hand domain;

Pssm-ID: 463869 [Multi-domain] Cd Length: 30 Bit Score: 34.46 E-value: 2.48e-03

                          10        20
                  ....*....|....*....|....*....
gi 4406346     92 KLKWYFKLYDADGNGSIDKNELLDMFMAV 120
Cdd:pfam13405   1 ELREAFKLFDKDGDGKISLEELRKALRSL 29

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.

Pssm-ID: 238009 [Multi-domain] Cd Length: 67 Bit Score: 35.27 E-value: 2.70e-03

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 4406346   96 YFKLYDADGNGSIDKNELLDMFMavqalngQQTLSPEEfINLVFHKIDINNDGELTLEEFINGMAKDQDLLE 167
Cdd:cd00052   4 IFRSLDPDGDGLISGDEARPFLG-------KSGLPRSV-LAQIWDLADTDKDGKLDKEEFAIAMHLIALALN 67

EF-hand motif found in phosphoinositide phospholipase C delta (PI-PLC-delta); PI-PLC-delta isozymes represent a class of metazoan PI-PLCs that are some of the most sensitive to calcium among all PLCs. Their activation is modulated by intracellular calcium ion concentration, phospholipids, polyamines, and other proteins, such as RhoAGAP. Like other PI-PLC isozymes, PI-PLC-delta isozymes contain a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C-terminal C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are three PI-PLC-delta isozymes (1, 3 and 4). PI-PLC-delta1 is relatively well characterized. It is activated by high calcium levels generated by other PI-PLC family members, and therefore functions as a calcium amplifier within the cell. Different PI-PLC-delta isozymes have different tissue distribution and different subcellular locations. PI-PLC-delta1 is mostly a cytoplasmic protein, PI-PLC-delta3 is located in the membrane, and PI-PLC-delta4 is predominantly detected in the cell nucleus. PI-PLC-delta isozymes is evolutionarily conserved even in non-mammalian species, such as yeast, slime molds and plants.

Pssm-ID: 320032 [Multi-domain] Cd Length: 140 Bit Score: 36.82 E-value: 2.83e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4406346   57 IDQVYNTFDTNKDGFIDFLE---FIAAVNLIMQEKMEQKLkwyFKLYDADGNGSIDKNELLDMFMAVqalngqqTLSPEe 133
Cdd:cd16202   2 LKDQFRKADKNGDGKLSFKEckkLLKKLNVKVDKDYAKKL---FQEADTSGEDVLDEEEFVQFYNRL-------TKRPE- 70

                        90       100       110
                ....*....|....*....|....*....|....*
gi 4406346  134 fINLVFHKIDiNNDGELTLEEFINGMAKDQDLLEI 168
Cdd:cd16202  71 -IEELFKKYS-GDDEALTVEELRRFLQEEQKVKDV 103

EF-hand-like motif found in the dystrophin/dystrobrevin/dystrotelin family; The dystrophin/dystrobrevin/dystrotelin family has been characterized by a compact cluster of domains comprising four EF-hand-like motifs and a ZZ-domain, followed by a looser region with two coiled-coils. Dystrophin is the founder member of this family. It is a sub-membrane cytoskeletal protein associated with the inner surface membrane. Dystrophin and its close paralog utrophin have a large N-terminal extension of actin-binding CH domains, up to 24 spectrin repeats, and a WW domain. Its further paralog, dystrophin-related protein 2 (DRP-2), retains only two of the spectrin repeats. Dystrophin, utrophin or DRP2 can form the core of a membrane-bound complex consisting of dystroglycan, sarcoglycans and syntrophins, known as the dystrophin-glycoprotein complex (DGC) that plays an important role in brain development and disease, as well as in the prevention of muscle damage. Dystrobrevins, including alpha- and beta-dystrobrevin, lack the large N-terminal extension found in dystrophin, but alpha-dystrobrevin has a characteristic C-terminal extension. Dystrobrevins are part of the DGC. They physically associate with members of the dystrophin family and with the syntrophins through their homologous C-terminal coiled coil motifs. In contrast, dystrotelins lack both the large N-terminal extension found in dystrophin and the obvious syntrophin-binding sites (SBSs). Dystrotelins are not critical for mammalian development. They may be involved in other forms of cytokinesis. Moreover, dystrotelin is unable to heterodimerize with members of the dystrophin or dystrobrevin families, or to homodimerize.

Pssm-ID: 319999 Cd Length: 163 Bit Score: 36.87 E-value: 3.56e-03

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 4406346   62 NTFDTNKDGFIDFLEFIAAVNLIMQEKMEQKLKWYFKLYdADGNGSIDKnELLDMFMA 119
Cdd:cd15901  61 NLYDRNRTGCIRLLSVKIALITLCAASLLDKYRYLFGQL-ADSSGFISR-ERLTQFLQ 116

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

Pssm-ID: 320025 [Multi-domain] Cd Length: 263 Bit Score: 37.30 E-value: 3.93e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4406346   65 DTNKDGFIDFLEFIAAVNLIMQEKMEQKLKWYFKLYDADGNGSIDKNELL-DMF-MAVQALNGQQTLSPEEFINLV---- 138
Cdd:cd16227  46 DLNDDGFIDRKELKAWILRSFKMLDEEEANERFEEADEDGDGKVTWEEYLaDSFgYDDEDNEEMIKDSTEDDLKLLeddk 125

                        90       100
                ....*....|....*....|
gi 4406346  139 --FHKIDINNDGELTLEEFI 156
Cdd:cd16227 126 emFEAADLNKDGKLDKTEFS 145

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

Pssm-ID: 320023 [Multi-domain] Cd Length: 278 Bit Score: 37.28 E-value: 4.36e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4406346   65 DTNKDGFIDFLEFIAAVNLIMQEKMEQKL---KWYFKLYDADGNGSIDKNELLDMFMAVQALN---------GQQTLS-- 130
Cdd:cd16225  44 DVNTDGFLSAEELEDWIMEKTQEHFQEAVeenEQIFKAVDTDKDGNVSWEEYRVHFLLSKGYSeeeaeekikNNEELKld 123

                        90       100       110
                ....*....|....*....|....*....|..
gi 4406346  131 ---PEEFINLVFH--KIDINNDGELTLEEFIN 157
Cdd:cd16225 124 eddKEVLDRYKDRwsQADEPEDGLLDVEEFLS 155

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

Pssm-ID: 320080 [Multi-domain] Cd Length: 152 Bit Score: 36.44 E-value: 4.47e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4406346   97 FKLYDADGNGSIDKNELLDMFMAVQALNGQQTLSPEEFI----------NLVFHKIDINNDGELTLEEFINGMAKDQDLL 166
Cdd:cd15900   6 FKMFDLDGDGELDKEEFNKVQSIIRSQTSVGQRHRDHTNgestklgmnsTLARYFFGKDGKQKLSIEKFLEFQENLQEEI 85


                ....*....
gi 4406346  167 EIVYKSFDF 175
Cdd:cd15900  86 DDVDTALTF 94

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

Pssm-ID: 320054 [Multi-domain] Cd Length: 165 Bit Score: 36.25 E-value: 5.22e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4406346   47 QGLNQKANKHIDQVYN---------TFDTNKDGFIDFLEFIAAVNLI--MQEKmeqklkwyFKLYDADGNGSIDKNELLd 115
Cdd:cd15897  23 QALSNVGWTHFDLGFSletcrsmiaMMDRDHSGKLNFSEFKGLWNYIkaWQEI--------FRTYDTDGSGTIDSNELR- 93

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 4406346  116 mfmavQALNGQQTLSPEEFINLVFHKIDINNdGELTLEEFINGMAKDQDLLEIvYKSFD 174
Cdd:cd15897  94 -----QALSGAGYRLSEQTYDIIIRRYDRGR-GNIDFDDFIQCCVRLQRLTDA-FRRYD 145

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

Pssm-ID: 425435 [Multi-domain] Cd Length: 29 Bit Score: 33.53 E-value: 5.26e-03

                          10        20
                  ....*....|....*....|....*....
gi 4406346     92 KLKWYFKLYDADGNGSIDKNELLDMFMAV 120
Cdd:pfam00036   1 ELKEIFRLFDKDGDGKIDFEEFKELLKKL 29

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

Pssm-ID: 320024 [Multi-domain] Cd Length: 264 Bit Score: 36.79 E-value: 5.49e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4406346   87 EKMEQKLKWYFKLYDADGNGSIDKNELLDMfmavqaLNGQQTLSPEEFINLVFHKIDINNDGELTLEEFINGM-AKDQDL 165
Cdd:cd16226  31 EESKERLGIIVDKIDKNGDGFVTEEELKDW------IKYVQKKYIREDVDRQWKEYDPNKDGKLSWEEYKKATyGFLDDE 104

                        90
                ....*....|....*
gi 4406346  166 LEIVYKSFDFSNVLR 180
Cdd:cd16226 105 EEDDDLHESYKKMIR 119

serine/threonine protein phosphatase 2A regulatory subunit B"; Heterotrimeric serine/threonine protein phosphatase 2A (PP2A) consists of scaffolding (A), catalytic (C), and variable (B, B', and B") subunits. The variable subunits dictate subcellular localization and substrate specificity of the PP2A holoenzyme. This family includes PP2A regulatory B'' subunits alpha, beta and gamma, encoded by PPP2R3A, PPP2R3B and PPP2R3C, respectively. It also includes subunit delta encoded by PPP2R3D in mouse. These B-family regulatory subunits play various roles including regulation of cytoskeletal assembly, neuronal differentiation, mitogen-activated protein kinase signaling, and apoptosis. Subunits alpha and beta contain two-domain elongated structure with two calcium EF-hands which mediate Ca2+-dependent changes in phosphatase activity.

Pssm-ID: 410336 Cd Length: 259 Bit Score: 36.40 E-value: 6.91e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4406346   53 ANKHIDQVYNTFDT-----NKDGFIDFLEFIAAVNLIMQEKMEQKLKWYFKLYDADGNGSIDKNELLDMFMAVQAL---N 124
Cdd:cd21339 136 SNVFIDRIFSGAVTrgktiQKEGEMSYADFVWFLISEEDKKEPTSIEYWFRCLDIDGDGYLSVFELEYFYEEQCERmkiH 215

                        90       100       110
                ....*....|....*....|....*....|...
gi 4406346  125 GQQTLSPEEFINLVFHKIDINNDGELTLEEFIN 157
Cdd:cd21339 216 GIEPLPFQDVLCQILDLVKPKDPGKITLQDLKR 248

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: 35.65 E-value: 8.07e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4406346   65 DTNKDGFIDFLEF---IAAVNLIMQEKMEQKLkwyFKLYDADGNGSIDKNElldmFMAVQalngqqtlspeEFINLV--- 138
Cdd:cd16185  10 DRDRSGSIDVNELqkaLAGGGLLFSLATAEKL---IRMFDRDGNGTIDFEE----FAALH-----------QFLSNMqng 71

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 4406346  139 FHKIDINNDGELTLEEFINGMAK-----DQDLLEIVYKSFDFSN 177
Cdd:cd16185  72 FEQRDTSRSGRLDANEVHEALAAsgfqlDPPAFQALFRKFDPDR 115