EF-hand, calcium binding motif, found in peflin and similar proteins; Peflin, also termed penta-EF hand (PEF) protein with a long N-terminal hydrophobic domain, or penta-EF hand domain-containing protein 1, is a ubiquitously expressed 30-kD PEF protein containing five EF-hand motifs in its C-terminal domain and a longer N-terminal hydrophobic domain (NHB domain) than any other member of the PEF family. The NHB domain harbors nine repeats of a nonapeptide (A/PPGGPYGGP). Peflin may modulate the function of ALG-2 in Ca2+ signaling. It exists only as a heterodimer with ALG-2, and binds two Ca2+ ions through its EF1 and EF3 hands. Its additional EF5 hand is unpaired and does not bind Ca2+ ion but mediates the heterodimerization with ALG-2. The dissociation of heterodimer occurs in the presence of Ca2+. In lower vertebrates, peflin may interact with transient receptor potential N (TRPN1), suggesting a potential role of peflin in fast transducer channel adaptation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307174834  20 NINQWFSMVDKDGSGQITAKELQSALANGQGGTFSDIACKLMIGMFDKEKNGTINVSEFQALYNYINAWLGVFRGFDHDN 99
Cdd:cd16184    1 EVQQWFQAVDRDRSGKISAKELQQALVNGNWSHFNDETCRLMIGMFDKDKSGTIDIYEFQALWNYIQQWKQVFQQFDRDR 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307174834 100 SGSIQESELNAALTQMGYRLSSEFIEFLIKKSDLRGHQSITVDQFIVLCVQIQRFTEAFRTRDTDQTGTISINFEDFLGV 179
Cdd:cd16184   81 SGSIDENELHQALSQMGYRLSPQFVQFLVSKYDPRARRSLTLDQFIQVCVQLQSLTDAFRQRDTQMTGTITISYEDFLTM 160

                 ....*
gi 307174834 180 ALSCS 184
Cdd:cd16184  161 ALLNK 165

EF-hand, calcium binding motif, found in peflin and similar proteins; Peflin, also termed penta-EF hand (PEF) protein with a long N-terminal hydrophobic domain, or penta-EF hand domain-containing protein 1, is a ubiquitously expressed 30-kD PEF protein containing five EF-hand motifs in its C-terminal domain and a longer N-terminal hydrophobic domain (NHB domain) than any other member of the PEF family. The NHB domain harbors nine repeats of a nonapeptide (A/PPGGPYGGP). Peflin may modulate the function of ALG-2 in Ca2+ signaling. It exists only as a heterodimer with ALG-2, and binds two Ca2+ ions through its EF1 and EF3 hands. Its additional EF5 hand is unpaired and does not bind Ca2+ ion but mediates the heterodimerization with ALG-2. The dissociation of heterodimer occurs in the presence of Ca2+. In lower vertebrates, peflin may interact with transient receptor potential N (TRPN1), suggesting a potential role of peflin in fast transducer channel adaptation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307174834  20 NINQWFSMVDKDGSGQITAKELQSALANGQGGTFSDIACKLMIGMFDKEKNGTINVSEFQALYNYINAWLGVFRGFDHDN 99
Cdd:cd16184    1 EVQQWFQAVDRDRSGKISAKELQQALVNGNWSHFNDETCRLMIGMFDKDKSGTIDIYEFQALWNYIQQWKQVFQQFDRDR 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307174834 100 SGSIQESELNAALTQMGYRLSSEFIEFLIKKSDLRGHQSITVDQFIVLCVQIQRFTEAFRTRDTDQTGTISINFEDFLGV 179
Cdd:cd16184   81 SGSIDENELHQALSQMGYRLSPQFVQFLVSKYDPRARRSLTLDQFIQVCVQLQSLTDAFRQRDTQMTGTITISYEDFLTM 160

                 ....*
gi 307174834 180 ALSCS 184
Cdd:cd16184  161 ALLNK 165

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307174834  20 NINQWFSMVDKDGSGQITAKELQSALANGQGGTFSDiacklmigmFDKEKNGTINVSEFQALYNYINAWLG------VFR 93
Cdd:COG5126    6 KLDRRFDLLDADGDGVLERDDFEALFRRLWATLFSE---------ADTDGDGRISREEFVAGMESLFEATVepfaraAFD 76

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 307174834  94 GFDHDNSGSIQESELNAALTQMGyrLSSEFIEFLIKKSDLRGHQSITVDQF 144
Cdd:COG5126   77 LLDTDGDGKISADEFRRLLTALG--VSEEEADELFARLDTDGDGKISFEEF 125

XopAW family type III secretion system calcium-binding effector;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307174834   2 AYPNTMYGSTNSQSGINPNiNQWFSMVDKDGSGQITAKELQSALANGQGGTFSDIACKLMiGMFDKEKNGTINVSEFQAL 81
Cdd:NF041410  11 SYTSTSSSSTSSARSQQFQ-KQLFAKLDSDGDGSVSQDELSSALSSKSDDGSLIDLSELF-SDLDSDGDGSLSSDELAAA 88

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 307174834  82 Y--------NYINAWLG--VFRGFDHDNSGSIQESELNAALTQMGYRLSSE 122
Cdd:NF041410  89 ApppppppdQAPSTELAddLLSALDTDGDGSISSDELSAGLTSAGSSADSS 139

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.

                           10        20
                   ....*....|....*....|....*..
gi 307174834    21 INQWFSMVDKDGSGQITAKELQSALAN 47
Cdd:smart00054   2 LKEAFRLFDKDGDGKIDFEEFKDLLKA 28

EF-hand, calcium binding motif, found in peflin and similar proteins; Peflin, also termed penta-EF hand (PEF) protein with a long N-terminal hydrophobic domain, or penta-EF hand domain-containing protein 1, is a ubiquitously expressed 30-kD PEF protein containing five EF-hand motifs in its C-terminal domain and a longer N-terminal hydrophobic domain (NHB domain) than any other member of the PEF family. The NHB domain harbors nine repeats of a nonapeptide (A/PPGGPYGGP). Peflin may modulate the function of ALG-2 in Ca2+ signaling. It exists only as a heterodimer with ALG-2, and binds two Ca2+ ions through its EF1 and EF3 hands. Its additional EF5 hand is unpaired and does not bind Ca2+ ion but mediates the heterodimerization with ALG-2. The dissociation of heterodimer occurs in the presence of Ca2+. In lower vertebrates, peflin may interact with transient receptor potential N (TRPN1), suggesting a potential role of peflin in fast transducer channel adaptation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307174834  20 NINQWFSMVDKDGSGQITAKELQSALANGQGGTFSDIACKLMIGMFDKEKNGTINVSEFQALYNYINAWLGVFRGFDHDN 99
Cdd:cd16184    1 EVQQWFQAVDRDRSGKISAKELQQALVNGNWSHFNDETCRLMIGMFDKDKSGTIDIYEFQALWNYIQQWKQVFQQFDRDR 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307174834 100 SGSIQESELNAALTQMGYRLSSEFIEFLIKKSDLRGHQSITVDQFIVLCVQIQRFTEAFRTRDTDQTGTISINFEDFLGV 179
Cdd:cd16184   81 SGSIDENELHQALSQMGYRLSPQFVQFLVSKYDPRARRSLTLDQFIQVCVQLQSLTDAFRQRDTQMTGTITISYEDFLTM 160

                 ....*
gi 307174834 180 ALSCS 184
Cdd:cd16184  161 ALLNK 165

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307174834  23 QWFSMVDKDGSGQITAKELQSALANGQGGTFSDIACKLMIGMFDKEKNGTINVSEFQALYNYINAWLGVFRGFDHDNSGS 102
Cdd:cd16180    4 RIFQAVDRDRSGRISAKELQRALSNGDWTPFSIETVRLMINMFDRDRSGTINFDEFVGLWKYIQDWRRLFRRFDRDRSGS 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307174834 103 IQESELNAALTQMGYRLSSEFIEFLIKKSDLRGHQSITVDQFIVLCVQIQRFTEAFRTRDTDQTGTISINFEDFLGVALS 182
Cdd:cd16180   84 IDFNELQNALSSFGYRLSPQFVQLLVRKFDRRRRGSISFDDFVEACVTLKRLTDAFRKYDTNRTGYATISYEDFLTMVLS 163

                 .
gi 307174834 183 C 183
Cdd:cd16180  164 I 164

Penta-EF hand, calcium binding motifs, found in sorcin, grancalcin, and similar proteins; The family corresponds to the second group of penta-EF hand (PEF) proteins that includes sorcin, grancalcin, and similar proteins. Sorcin, also termed 22 kDa Ca2+-binding protein, CP-22, or V19, is a soluble resistance-related calcium-binding protein that is expressed in normal mammalian tissues, such as the liver, lungs and heart. It contains a flexible glycine and proline-rich N-terminal extension and five EF-hand motifs that associate with membranes in a calcium-dependent manner. It may harbor three potential Ca2+ binding sites through its EF1, EF2 and EF3 hands. However, binding of only two Ca2+/monomer suffices to trigger the conformational change that exposes hydrophobic regions and leads to interaction with the respective targets. Sorcin forms homodimers through the association of the unpaired EF5 hand. Among the PEF proteins, sorcin is unique in that it contains potential phosphorylation sites by cAMP-dependent protein kinase (PKA), and it can form a tetramer at slightly acid pH values although remaining a stable dimer at neutral pH. Grancalcin (GCA) is a cytosolic Ca2+-binding protein specifically expressed in neutrophils and monocytes/macrophages. It can strongly interact with sorcin to form a heterodimer and further modulate the function of sorcin. GCA exists as homodimers in solution. It contains five EF-hand motifs attached to an N-terminal region of an approximately 50 residue-long segment rich in glycines and prolines. In contrast with sorcin, GCA binds two Ca2+ ions through its EF1 and EF3 hands.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307174834  23 QWFSMV-DKDGsgQITAKELQSALAN-GQGGT---FSDIACKLMIGMFDKEKNGTINVSEFQALYNYINAWLGVFRGFDH 97
Cdd:cd16181    4 GYFSAVaGQDG--QIDADELQRCLTQsGISGNyqpFSLETCRLMIAMLDRDHSGKMGFNEFKELWAALNQWKTTFMQYDR 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307174834  98 DNSGSIQESELNAALTQMGYRLSSEFIEFLIKKSDLRGHqsITVDQFIVLCVQIQRFTEAFRTRDTDQTGTISINFEDFL 177
Cdd:cd16181   82 DRSGTVEPQELQQAIRSFGYNLSPQALNVIVKRYSKNGR--ITFDDFVACAVRLRALTDRFRRRDTQQNGTATFQYDDFI 159

                 ....*.
gi 307174834 178 GVALSC 183
Cdd:cd16181  160 QVTMSI 165

Penta-EF hand, calcium binding motifs, found in sorcin; Sorcin, also termed 22 kDa Ca2+-binding protein, CP-22, or V19, is a soluble resistance-related calcium-binding protein that is expressed in normal mammalian tissues, such as the liver, lungs and heart. The up-regulation of sorcin is correlated with a number of cancer types, including colorectal, gastric and breast cancer. It may represent a therapeutic target for reversing tumor multidrug resistance (MDR). Sorcin participates in the regulation of calcium homeostasis in cells and is necessary for the activation of mitosis and cytokinesis. It enhances metastasis and promotes epithelial-to-mesenchymal transition of colorectal cancer. Moreover, sorcin has been implicated in the regulation of intracellular Ca2+ cycling and cardiac excitation-contraction coupling. It displays the anti-apoptotic properties via the modulation of mitochondrial Ca2+ handling in cardiac myocytes. It can target and activate the sarcolemmal Na+/Ca2+ exchanger (NCX1) in cardiac muscle. Meanwhile, sorcin modulates cardiac L-type Ca2+ current by functional interaction with the alpha1C subunit. It also associates with calcium/calmodulin-dependent protein kinase IIdeltaC (CaMKIIdelta(C)) and further modulates ryanodine receptor (RyR) function in cardiac myocytes. Furthermore, sorcin may act as a Ca2+ sensor for glucose-induced nuclear translocation and the activation of carbohydrate-responsive element-binding protein (ChREBP)-dependent genes. As a mitochondrial chaperone TRAP1 interactor, sorcin involves in mitochondrial metabolism through the TRAP1 pathway. In addition, sorcin may regulate the inhibition of type I interferon response in cells through interacting with foot-and-mouth disease virus (FMDV) VP1. Sorcin contains a flexible glycine and proline-rich N-terminal extension and five EF-hand motifs that associate with membranes in a calcium-dependent manner. It may harbor three potential Ca2+ binding sites through its EF1, EF2 and EF3 hands. However, binding of only two Ca2+/monomer suffices to trigger the conformational change that exposes hydrophobic regions and leads to interaction with the respective targets. Sorcin forms homodimers through the association of the unpaired EF5 hand. Among the PEF proteins, sorcin is unique in that it contains potential phosphorylation sites by cAMP-dependent protein kinase (PKA), and it can form a tetramer at slightly acid pH values although remaining a stable dimer at neutral pH.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307174834  34 GQITAKELQSALAN----GQGGTFSDIACKLMIGMFDKEKNGTINVSEFQALYNYINAWLGVFRGFDHDNSGSIQESELN 109
Cdd:cd16187   14 GQIDADELQRCLTQsgiaGGYKPFNLETCRLMISMLDRDMSGTMGFNEFKELWAVLNGWRQHFISFDSDRSGTVDPQELQ 93

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 307174834 110 AALTQMGYRLSSEFIEFLIKKSDLRGhqSITVDQFIVLCVQIQRFTEAFRTRDTDQTGTISINFEDFLGVALS 182
Cdd:cd16187   94 KALTTMGFRLSPQAVNSIAKRYSTNG--KITFDDYIACCVKLRALTDSFRRRDTSQQGVVNFPYDDFIQCVMS 164

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307174834  21 INQWFSMVdKDGSGQITAKELQ----SALANGQGGT--FSDIACKLMIGMFDKEKNGTINVSEFQALYNYINAWLGVFRG 94
Cdd:cd16182    2 VRELFEKL-AGEDEEIDAVELQkllnASLLKDMPKFdgFSLETCRSLIALMDTNGSGRLDLEEFKTLWSDLKKWQAIFKK 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307174834  95 FDHDNSGSIQESELNAALTQMGYRLSSEFIEFLIKK-SDLRGHqsITVDQFIVLCVQIQRFTEAFRTRDTDQTGTISINF 173
Cdd:cd16182   81 FDTDRSGTLSSYELRKALESAGFHLSNKVLQALVLRyADSTGR--ITFEDFVSCLVRLKTAFETFSALDKKNEGVIPLTL 158

                 ....
gi 307174834 174 EDFL 177
Cdd:cd16182  159 EEWL 162

Penta-EF hand, calcium binding motifs, found in mu-type calpain (CAPN1); CAPN1, also termed calpain-1 80-kDa catalytic subunit, or calpain-1 large subunit, or micromolar-calpain (muCANP), or calcium-activated neutral proteinase 1 (CANP 1), or cell proliferation-inducing gene 30 protein, is a ubiquitously expressed 80-kDa Ca2+-dependent intracellular cysteine protease that contains 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 catalytic subunit CAPN1 in complex with a regulatory subunit encoded by CAPNS1 forms a mu-calpain heterodimer. CAPN1 plays a central role in postmortem proteolysis and meat tenderization processes, as well as in regulation of proliferation and survival of skeletal satellite cells. It also acts as a novel regulator in IgE-mediated mast cell activation and could serve as a potential therapeutic target for the management of allergic inflammation. Moreover, CAPN1 is involved in neutrophil motility and functions as a potential target for intervention in inflammatory disease. It also facilitates age-associated aortic wall calcification and fibrosis through the regulation of matrix metalloproteinase 2 activity in vascular smooth muscle cells, and thus plays a role in hypertension and atherosclerosis. The proteolytic cleavage of beta-amyloid precursor protein and tau protein by CAPN1 may be involved in plaque formation. Furthermore, CAPN1 is activated in the brains of individuals with Alzheimer's disease. It is involved in the maintenance of a proliferative neural stem cell pool. The activation and macrophage inflammation of CAPN1 in hypercholesterolemic nephropathy is promoted by nicotinic acetylcholine receptor alpha1 (nAChRalpha1). In addition, CAPN1 displays a functional role in hemostasis, as well as in sickle cell disease.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307174834  35 QITAKELQSAL-------ANGQGGTFSDIACKLMIGMFDKEKNGTINVSEFQALYNYINAWLGVFRGFDHDNSGSIQESE 107
Cdd:cd16198   15 EISVFELKTILnriiskhKDLRTDGFSLESCRSMVNLMDKDGNGKLGLVEFNILWNKIRNYLTIFRKFDLDKSGSMSAYE 94

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 307174834 108 LNAALTQMGYRLSSEFIEFLIKK-SDlrGHQSITVDQFIVLCVQIQRFTEAFRTRDTDQTGTISINFEDFL 177
Cdd:cd16198   95 MRLALESAGFKLNNRLHQVIVARyAD--PNLAIDFDNFVCCLVRLETMFRFFKQLDTEETGTIEMDLFEWL 163

Calcium-activated neutral; CAPN3, also termed calcium-activated neutral proteinase 3 (CANP 3), or calpain L3, or calpain p94, or muscle-specific calcium-activated neutral protease 3, or new calpain 1 (nCL-1), is a calpain large subunit that is mainly expressed in skeletal muscle, or lens. The skeletal muscle-specific CAPN3 are pathologically associated with limb girdle muscular dystrophy type 2A (LGMD2A). Its autolytic activity can be positively regulated by calmodulin (CaM), a known transducer of the calcium signal. CAPN3 is also involved in human melanoma tumorigenesis and progression. It impairs cell proliferation and stimulates oxidative stress-mediated cell death in melanoma cells. Moreover, it plays an important role in sarcomere remodeling and mitochondrial protein turnover. Furthermore, the phosphorylated skeletal muscle-specific CAPN3 acts as a myofibril structural component and may participate in myofibril-based signaling pathways. In the eye, the lens-specific CAPN3, together with CAPN2, is responsible for proteolytic cleavages of alpha and beta-crystallin. Overactivated alpha and beta-crystallin can lead to cataract formation. CAPN3 exists as a homodimer, rather than a heterodimer with the calpain small subunit. It may also form heterodimers with other calpain large subunits. CAPN3 contains a long N-terminal region, 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. Ca2+ binding at EF5 of the CAPN3 PEF domain is a distinct feature not observed in other calpain isoforms.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307174834  35 QITAKELQSALANG-------QGGTFSDIACKLMIGMFDKEKNGTINVSEFQALYNYINAWLGVFRGFDHDNSGSIQESE 107
Cdd:cd16190   15 EISADELRSVLNRVvkkhkdlKTEGFTLESCRSMIALMDTDGSGKLNLQEFRHLWNKIKQWQKIFKRYDTDKSGTINSYE 94

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307174834 108 LNAALTQMGYRLSSEFIEfLIKKSDLRGHQSITVDQFIVLCVQIQRFTEAFRTRDTDQTGTISINFEDFL 177
Cdd:cd16190   95 MRNAVNDAGFRLNNQLYD-IITMRYADKHMNIDFDSFICCFVRLEGMFRAFHAFDKDGDGIIKLNVLEWL 163

Penta-EF hand, calcium binding motifs, found in calpain-9 (CAPN9); CAPN9, also termed digestive tract-specific calpain, or new calpain 4 (nCL-4), or protein CG36, is a calpain large subunit predominantly expressed in gastrointestinal tract. It plays a physiological role in the suppression of tumorigenesis. It acts as an important biomolecule link for the regression of colorectal cancer via intracellular calcium homeostasis. CAPN9 may also play a critical role in lumen formation. Moreover, CAPN9, together with CAPN8, forms an active protease complex, G-calpain, in which both proteins are essential for stability and activity. The G-Calpain has been implicated in gastric mucosal defense. Furthermore, down-regulation of calpain 9 has been linked to hypertensive heart and kidney disease in salt-sensitive Dahl rats. CAPN9 contains 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307174834  35 QITAKELQSALANGQGGT-------FSDIACKLMIGMFDKEKNGTINVSEFQALYNYINAWLGVFRGFDHDNSGSIQESE 107
Cdd:cd16192   15 EISAEELQYVLNAVLARTkeikfkkLSLLSCKNIISLMDTSGNGKLGFSEFKVFWDKLKKWIGLFLKYDADRSGTMSSYE 94

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 307174834 108 LNAALTQMGYRLSSEFIEFLIkksdLR---GHQSITVDQFIVLCVQIQRFTEAFRTRDTDQTGTISINFEDFL 177
Cdd:cd16192   95 LRSALKAAGFQLNNQLLQLIV----LRyadDYLQIDFDDFLNCLVRLENSFRVFQALDTKNTGEISLNMLEFI 163

Penta-EF hand, calcium binding motifs, found in calpain-12 (CAPN12); CAPN12, also termed calcium-activated neutral proteinase 12 (CANP 12), is a calpain large subunit mainly expressed in the cortex of the hair follicle. It may affect apoptosis regulation. CAPN12 contains 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307174834  58 CKLMIGMFDKEKNGTINVSEFQALYNYINAWLGVFRGFDHDNSGSIQESELNAALTQMGYRLSSEFIEFLIKKSDLRGHQ 137
Cdd:cd16194   45 CRQLIQCFDHGQNGKLALEEFQQLWGYLLEWQAIFTKFDEDTSGTMDSYELRLALNAAGFHLNNQLTETLTSRYRDSRLR 124

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 307174834 138 sITVDQFiVLCVqiQRFTEAFR---TRDTDQTGTISINFEDFLGVA 180
Cdd:cd16194  125 -VDFESF-LSCL--AHLTCIFCqcsQHDDGGEGVICLTHRQWLELA 166

Penta-EF hand, calcium binding motifs, found in m-type calpain (CAPN2); CAPN2, also termed millimolar-calpain (m-calpain), or calpain-2 catalytic subunit, or calcium-activated neutral proteinase 2 (CANP 2), or calpain large polypeptide L2, or calpain-2 large subunit, is a ubiquitously expressed 80-kDa Ca2+-dependent intracellular cysteine protease that contains 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 catalytic subunit CAPN2 in complex with a regulatory subunit encoded by CAPNS1 forms an m-calpain heterodimer. CAPN2 acts as the key protease responsible for N-methyl-d-aspartic acid (NMDA)-induced cytoplasmic polyadenylation element-binding protein 3 (CPEB3) degradation in neurons. It cleaves several components of the focal adhesion complex, such as FAK and talin, triggering disassembly of the complex at the rear of the cell. The stimulation of CAPN2 activity is required for Golgi antiapoptotic proteins (GAAPs) to promote cleavage of FA kinase (FAK), cell spreading, and enhanced migration. calpain 2 is also involved in the onset of glial differentiation. It regulates proliferation, survival, migration, and tumorigenesis of breast cancer cells through a PP2A-Akt-FoxO-p27(Kip1) signaling cascade. Its expression is associated with response to platinum based chemotherapy, progression-free and overall survival in ovarian cancer. Moreover, CAPN2 may play a role in fundamental mitotic functions, such as the maintenance of sister chromatid cohesion. The activation of CAPN2 plays an essential role in hippocampal synaptic plasticity and in learning and memory. In the eye, CAPN2, together with a lens-specific variant of CAPN3, is responsible for proteolytic cleavages of alpha and beta-crystallin. Overactivated alpha and beta-crystallin can lead to cataract formation. Sometimes, CAPN2 compensates for loss of CAPN1, and both calpain isoforms are involved in AngII-induced aortic aneurysm formation. The main phosphorylation sites in m-calpain are Ser50 and Ser369/Thr370.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307174834  35 QITAKELQSAL-------ANGQGGTFSDIACKLMIGMFDKEKNGTINVSEFQALYNYINAWLGVFRGFDHDNSGSIQESE 107
Cdd:cd16199   15 EISAFELQTILrrvlakrEDIKSDGFSIETCKIMVDMLDSDGSGKLGLKEFYILWTKIQKYQKIYREIDVDRSGTMNSYE 94

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 307174834 108 LNAALTQMGYRLSSEFIEFLIKK-SDlrGHQSITVDQFIVLCVQIQRFTEAFRTRDTDQTGTISINFEDFL 177
Cdd:cd16199   95 MRKALEEAGFKLPCQLHQVIVARfAD--DDLIIDFDNFVRCLVRLETLFKIFKQLDPENTGTIELDLISWL 163

Penta-EF hand, calcium binding motifs, found in calpain-8 (CAPN8); CAPN8, also termed new calpain 2 (nCL-2), or stomach-specific M-type calpain, is a calpain large subunit predominantly expressed in the stomach. It appears to be involved in membrane trafficking in the gastric surface mucus cells (pit cells), via its location at the Golgi and interaction with the beta-subunit of coatomer complex (beta-COP) of vesicles derived from the Golgi. Moreover, CAPN8, together with CAPN9, forms an active protease complex, G-calpain, in which both proteins are essential for stability and activity. The G-Calpain has been implicated in gastric mucosal defense. CAPN8 exists as both a monomer and homo-oligomer, but not as a heterodimer with the conventional calpain regulatory subunit (30K). The monomer and homodimer forms predominate. CAPN8 contains 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307174834  35 QITAKELQSAL-------ANGQGGTFSDIACKLMIGMFDKEKNGTINVSEFQALYNYINAWLGVFRGFDHDNSGSIQESE 107
Cdd:cd16191   15 EVTANELQTILnrvlskrKDIKSDGFTINTCREMISLLDTDGTGTLGLVEFRILWMKIQKYLAIYKKVDSDRSGTIDAHE 94

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 307174834 108 LNAALTQMGYRLSSEFIEFLIKK---SDLrghqSITVDQFIVLCVQIQRFTEAFRTRDTDQTGTISINFEDFLGVAL 181
Cdd:cd16191   95 MRNALQEAGFTLNNKIQQSIVQRyasNKL----TINFDGFIACMIRLETLFKMFQLLDKDKSGVVQLSLAEWLCCTL 167

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307174834  20 NINQWFSMVDKDGSGQITAKELQSALANGQGGTFSDiacklmigmFDKEKNGTINVSEFQALYNYINAWLG------VFR 93
Cdd:COG5126    6 KLDRRFDLLDADGDGVLERDDFEALFRRLWATLFSE---------ADTDGDGRISREEFVAGMESLFEATVepfaraAFD 76

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 307174834  94 GFDHDNSGSIQESELNAALTQMGyrLSSEFIEFLIKKSDLRGHQSITVDQF 144
Cdd:COG5126   77 LLDTDGDGKISADEFRRLLTALG--VSEEEADELFARLDTDGDGKISFEEF 125

EF-hand domain pair;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 307174834   25 FSMVDKDGSGQITAKELQSALAN-GQGGTFSDIACKLMIGMFDKEKNGTINVSEFQALY 82
Cdd:pfam13499   8 FKLLDSDGDGYLDVEELKKLLRKlEEGEPLSDEEVEELFKEFDLDKDGRISFEEFLELY 66

Penta-EF hand, calcium binding motifs, found in Drosophila melanogaster calpain-C (CalpC) and similar proteins; CalpC, also termed calcium-activated neutral proteinase homolog C (CANP C), is a catalytically inactive homolog of CalpA and CalpB found in Drosophila. It is strongly expressed in the salivary glands. In contrast with CalpA and CalpB, both of which are closely related to that of vertebrate calpains, and they share similar domain architecture, which consists of four domains: the N-terminal domain I, the catalytic domain II carrying the three active site residues, Cys, His and Asn, the Ca2+-regulated phospholipid-binding domain III, and penta-EF-hand Ca2+-binding domain IV. CalpC is a truncated calpain form missing domain I and about 20 residues from domain II. Moreover, due to all three mutated active site residues (Cys to Arg, His to Val and Asn to Ser), it may not have proteolytic activity.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307174834  58 CKLMIGMFDKEKNGTINVSEFQALYNYINAWLGVFRGFDHDNSGSIQESELNAALTQMGYRLSSEFIEFLIKKSdLRGHQ 137
Cdd:cd16197   43 CRQVVLLMDNSGLGRLKFQDFKDFMCSLKWWQGVFKMHTKEKTGILRAERLRDALEDVGFQLNTDVLSILILRY-MRKDG 121

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 307174834 138 SITVDQFIVLCVQIQRFTEAFRTRDTDQTGTISINFEDFLGVALS 182
Cdd:cd16197  122 TLRFGDFVSAVLHLTAAFGSFEKKDPLQNGFIKLSLTEWLKSCLM 166

XopAW family type III secretion system calcium-binding effector;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307174834  10 STNSQSGINPNINQWFSMVDKDGSGQITAKELQSALA-------NGQGGTFSDIacklMIGMFDKEKNGTINVSEFQALY 82
Cdd:NF041410  54 SSKSDDGSLIDLSELFSDLDSDGDGSLSSDELAAAAPppppppdQAPSTELADD----LLSALDTDGDGSISSDELSAGL 129

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 307174834  83 NyiNAWLG-----VFRGFDHDNSGSIQESELNAALTQMG 116
Cdd:NF041410 130 T--SAGSSadssqLFSALDSDGDGSVSSDELAAALQPPP 166

EF-hand, calcium binding motif, found in alpha-parvalbumin; Alpha-parvalbumin is cytosolic Ca2+/Mg2+-binding protein expressed mainly in fast-twitch skeletal myofibrils, where it may act as a soluble relaxing factor facilitating the Ca2+-mediated relaxation phase. It is also expressed in rapidly firing neurons, particularly GABA-ergic neurons, and thus may confer protection against Ca2+ toxicity. The major role of alpha-parvalbumin is metal buffering and transport of Ca2+. It binds different metal cations, and exhibits very high affinity for Ca2+ and physiologically significant affinity for Mg2+. Alpha-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+. Both metal ion-binding sites in alpha-parvalbumin are high-affinity sites. Additionally, in contrast to beta-parvalbumin, alpha-parvalbumin is less acidic and has an additional residue in the C-terminal helix.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 307174834  20 NINQWFSMVDKDGSGQITAKELQSALA--NGQGGTFSDIACKLMIGMFDKEKNGTINVSEFQALYN 83
Cdd:cd16254   35 DVKKVFHILDKDKSGFIEEDELKFVLKgfSPDGRDLSDKETKALLAAGDKDGDGKIGIDEFATLVA 100

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307174834  29 DKDGSGQITAKELQSALAN---GQGGTFS----DIACKLMIGMFDKEKNGTINVSEFQALYNYINAWLGVFRG------- 94
Cdd:cd15902  100 DTDGSGFIEAKELKGFLKDlllKNKKHVSppklDEYTKLILKEFDANKDGKLELDEMAKLLPVQENFLLKFQIlgamdlt 179

                         90       100
                 ....*....|....*....|....*...
gi 307174834  95 ----------FDHDNSGSIQESELNAAL 112
Cdd:cd15902  180 kedfekvfehYDKDNNGVIEGNELDALL 207

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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 307174834  21 INQWFSMVDKDGSGQITAKELqSALANGQGGTFSDIACKLMIGMFDKEKNGTINVSEFQALYNYIN 86
Cdd:cd15898    2 LRRQWIKADKDGDGKLSLKEI-KKLLKRLNIRVSEKELKKLFKEVDTNGDGTLTFDEFEELYKSLT 66

EF-hand, calcium binding motif, found in parvalbumins; 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 307174834  20 NINQWFSMVDKDGSGQITAKELQSALANGQGGT--FSDIACKLMIGMFDKEKNGTINVSEFQAL 81
Cdd:cd16253   35 DIKKVFNILDQDKSGFIEEEELKLFLKNFSDGArvLSDKETKNFLAAGDSDGDGKIGVDEFKSM 98

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.

                           10        20
                   ....*....|....*....|....*..
gi 307174834    21 INQWFSMVDKDGSGQITAKELQSALAN 47
Cdd:smart00054   2 LKEAFRLFDKDGDGKIDFEEFKDLLKA 28

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.

                          10        20
                  ....*....|....*....|....*.
gi 307174834   21 INQWFSMVDKDGSGQITAKELQSALA 46
Cdd:pfam00036   2 LKEIFRLFDKDGDGKIDFEEFKELLK 27

calmodulin; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307174834  92 FRGFDHDNSGSIQESELNAALTQMGYRLSSEFIEFLIKKSDLRGHQSITVDQFIVLCVQIQRFT-------EAFRTRDTD 164
Cdd:PTZ00184  17 FSLFDKDGDGTITTKELGTVMRSLGQNPTEAELQDMINEVDADGNGTIDFPEFLTLMARKMKDTdseeeikEAFKVFDRD 96