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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1BU3_A       23 DSFNYKAFFAKVGLTAKSADDIKKAFFVIDQDKSGFIEEDELKLFLQVFSAGARALTDAETKAFLKAGDSDGDGAIGVDE 102
Cdd:cd16255  15 DSFNFKKFFATSGLSKKSADDVKKVFEIIDQDKSGFIEEEELKLFLQNFSSGARELTDAETKAFLKAGDSDGDGKIGVEE 94

                ....*..
1BU3_A      103 WAALVKA 109
Cdd:cd16255  95 FQALVKA 101

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1BU3_A       23 DSFNYKAFFAKVGLTAKSADDIKKAFFVIDQDKSGFIEEDELKLFLQVFSAGARALTDAETKAFLKAGDSDGDGAIGVDE 102
Cdd:cd16255  15 DSFNFKKFFATSGLSKKSADDVKKVFEIIDQDKSGFIEEEELKLFLQNFSSGARELTDAETKAFLKAGDSDGDGKIGVEE 94

                ....*..
1BU3_A      103 WAALVKA 109
Cdd:cd16255  95 FQALVKA 101

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

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
1BU3_A       35 GLTAKSADDIKKAFFVIDQDKSGFIEEDELKLFLQVFSagaraLTDAETKAFLKAGDSDGDGAIGVDEWAALVK 108
Cdd:COG5126  62 LFEATVEPFARAAFDLLDTDGDGKISADEFRRLLTALG-----VSEEEADELFARLDTDGDGKISFEEFVAAVR 130

XopAW family type III secretion system calcium-binding effector;

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
1BU3_A        36 LTAKSAD----DIKKAFFVIDQDKSGFIEEDELKLFLQV---FSAGARALTDAEtkAFLKAGDSDGDGAIGVDEWAALV 107
Cdd:NF041410  53 LSSKSDDgsliDLSELFSDLDSDGDGSLSSDELAAAAPPpppPPDQAPSTELAD--DLLSALDTDGDGSISSDELSAGL 129

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1BU3_A       23 DSFNYKAFFAKVGLTAKSADDIKKAFFVIDQDKSGFIEEDELKLFLQVFSAGARALTDAETKAFLKAGDSDGDGAIGVDE 102
Cdd:cd16255  15 DSFNFKKFFATSGLSKKSADDVKKVFEIIDQDKSGFIEEEELKLFLQNFSSGARELTDAETKAFLKAGDSDGDGKIGVEE 94

                ....*..
1BU3_A      103 WAALVKA 109
Cdd:cd16255  95 FQALVKA 101

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1BU3_A       23 DSFNYKAFFAKVGLTAKSADDIKKAFFVIDQDKSGFIEEDELKLFLQVFSAGARALTDAETKAFLKAGDSDGDGAIGVDE 102
Cdd:cd16251  15 GSFNYKKFFEHVGLKQKSEDQIKKVFQILDKDKSGFIEEEELKYILKGFSIAGRDLTDEETKALLAAGDTDGDGKIGVEE 94

                ....*..
1BU3_A      103 WAALVKA 109
Cdd:cd16251  95 FATLVAG 101

EF-hand, calcium binding motif, found in uncharacterized calglandulin-like proteins; The family corresponds to a group of uncharacterized calglandulin-like proteins. Although their biological function remain unclear, they show high sequence similarity with human calglandulin-like protein GAGLP, which is an ortholog of calglandulin from the venom glands of Bothrops insularis snake. Both GAGLP and calglandulin are putative Ca2+-binding proteins with four EF-hand motifs. However, members in this family contain only three EF-hand motifs. In this point, they may belong to the parvalbumin-like EF-hand family, which is characterized by the presence of three consecutive EF-hand motifs (helix-loop-helix).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1BU3_A       24 SFNYKAFFA---KVGLTAKSADDIKKAFFVIDQDKSGFIEEDELKLFLQVF--SAGARALTDAETKAFLKAGDSDGDGAI 98
Cdd:cd16252  16 SFNYSKFFEymqKFQTSEQQEEAIRKAFQMLDKDKSGFIEWNEIKYILSTVpsSMPVAPLSDEEAEAMIQAADTDGDGRI 95

                        90
                ....*....|
1BU3_A       99 GVDEWAALVK 108
Cdd:cd16252  96 DFQEFSDMVK 105

EF-hand domain pair;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
1BU3_A         42 DDIKKAFFVIDQDKSGFIEEDELKLFLQVFSaGARALTDAETKAFLKAGDSDGDGAIGVDEWAALVK 108
Cdd:pfam13499   2 EKLKEAFKLLDSDGDGYLDVEELKKLLRKLE-EGEPLSDEEVEELFKEFDLDKDGRISFEEFLELYS 67

calmodulin; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
1BU3_A        40 SADDIKKAFFVIDQDKSGFIEEDELKlflQVFSAGARALTDAETKAFLKAGDSDGDGAIGVDEWAALV 107
Cdd:PTZ00184  82 SEEEIKEAFKVFDRDGNGFISAAELR---HVMTNLGEKLTDEEVDEMIREADVDGDGQINYEEFVKMM 146

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.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
1BU3_A       39 KSADDIKKAFFVIDQDKSGFIEEDELKLFLQVFSAGARALTDAE-----TKAFLKAGDSDGDGAIGVDEWAALV 107
Cdd:cd16176  82 KSSEEFMQTWRKYDADHSGFIEADELKSFLKDLLKKANKPFDESkleeyTHTMLKMFDSNNDGKLGLTEMARLL 155

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
1BU3_A       40 SADDIKKAFFVIDQDKSGFIEEDELKLFLQ-VFSAGARALTDAETKAF----LKAGDSDGDGAIGVDE 102
Cdd:cd16179 186 TREDIDRVFALYDRDNNGTIENEELTGFLKdLLELVQEDYDEQDLEEFkeiiLRGWDFNNDGKISRKE 253

XopAW family type III secretion system calcium-binding effector;

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
1BU3_A        36 LTAKSAD----DIKKAFFVIDQDKSGFIEEDELKLFLQV---FSAGARALTDAEtkAFLKAGDSDGDGAIGVDEWAALV 107
Cdd:NF041410  53 LSSKSDDgsliDLSELFSDLDSDGDGSLSSDELAAAAPPpppPPDQAPSTELAD--DLLSALDTDGDGSISSDELSAGL 129

EF-hand, calcium binding motif, found in calretinin (CR); CR, also termed 29 kDa calbindin, 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 possibly functions as a calcium buffer, calcium sensor, and apoptosis regulator, which may be implicated in many biological processes, including cell proliferation, differentiation, and cell death. CR contains six EF-hand motifs within two independent domains, CR I-II and CR III-VI. CR I-II consists of EF-hand motifs 1 and 2, and CR III-VI consists of EF-hand motifs 3-6. The first 5 EF-hand motifs are capable of binding calcium ions, while the EF-hand 6 is inactive. Thus, CR has two pairs of cooperative binding sites (I-II and III-IV), which display high affinity calcium-binding sites, and one independent calcium ion-binding site (V), which displays lower affinity binding.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
1BU3_A       40 SADDIKKAFFVIDQDKSGFIEEDELKLFL-QVFSAGARALTDAE----TKAFLKAGDSDGDGAIGVDEWAALV 107
Cdd:cd16177  88 SSSEFMEAWRKYDTDRSGYIEANELKGFLsDLLKKANRPYDEKKlqeyTQTILRMFDLNGDGKLGLSEMARLL 160

XopAW family type III secretion system calcium-binding effector;

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
1BU3_A        38 AKSADDIkkaFFVIDQDKSGFIEEDELKlflqvfSAGARALTDAETKAFLKAGDSDGDGAIGVDEWAA 105
Cdd:NF041410 102 TELADDL---LSALDTDGDGSISSDELS------AGLTSAGSSADSSQLFSALDSDGDGSVSSDELAA 160

EF-hand, calcium binding motif, found in secretagogin (SCGN); 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 calcium sensor/coincidence detector modulating vesicular exocytosis of neurotransmitters, neuropeptides or hormones. It also serves as a calcium buffer in neurons. Thus, SCGN may be linked to the pathogenesis of neurological diseases such as Alzheimer's, and also acts as a serum marker of neuronal damage, or as a tumor biomarker. SCGN consists of the three globular domains each of which contains a pair of EF-hand motifs. All six EF hand motifs of SCGN in some eukaryotes, including D. rerio, X. laevis, M. domestica, G. gallus, O. anatinus, could potentially bind six calcium ions. In contrast, SCGNs from higher eukaryotes have at least one non-functional EF-hand motif due to the mutation(s) or deletions. For instance, the EF1 loop does not coordinate calcium ion due to the key residue asparagine replaced by lysine in SCGNs of many mammalian species. Moreover, the EF2 loop seems to be competent for calcium-binding in most mammalian SCGNs except for human and chimpanzee orthologs.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
1BU3_A       52 DQDKSGFIEEDELKLFLQ-VFSAGARALTDAE----TKAFLKAGDSDGDGAIGVDEWAALV 107
Cdd:cd16178 102 DADSSGYISAAELKNFLRdLFLQHKKVITEDKldeyTDTMMKIFDKNKDGRLDLNDMARIL 162