2ZN9,1HQV,2ZN8,2ZNE,2ZRS,3AAJ,3AAK


Conserved Protein Domain Family
EFh_PEF_ALG-2

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cd16183: EFh_PEF_ALG-2 
Click on image for an interactive view with Cn3D
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.
Statistics
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PSSM-Id: 320058
View PSSM: cd16183
Aligned: 33 rows
Threshold Bit Score: 299.17
Threshold Setting Gi: 514484647
Created: 18-Nov-2014
Updated: 18-Aug-2016
Structure
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Program:
Drawing:
Aligned Rows:
  next features
Conserved site includes 11 residues -Click on image for an interactive view with Cn3D
Feature 1:Ca binding site [ion binding site]
Evidence:
  • Structure:2ZN9; Homo sapiens ALG-2 binds three Ca2+ ions through its EF1, EF3 and EF5 hands.
    View structure with Cn3D

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                 # # #      #                                                       # # 
2ZN9_A         8 FLWNVFQRVDKDRSGVISDTELQQALSNGTwtpfnpvTVRSIISMFDRENKAGVNFSEFTGVWKYITDWQNVFRTYDRDN 87
gi 351050110   7 NLQQIFSSVDKDRSGQISSDELQTALSNGTwnpfnpeTCRLMIGMFDSNGDGAINFQEFQALWRYINDWTNCFRGFDTDG 86
gi 675389898  34 FLWNIFQGVDKDRSGFITATELQAALSNGTwrpfnpeTVRLMIGMFDQDGNGTVNFDEFCALWKYVTDWLNCFKSFDKDG 113
gi 514484647  76 TLWAWFMAVDTDRSGQIDANELKQALVNGNwspfndtTCRMMIGLFDTDRSGTINFLEFSGLWKYIQDWKACFDRFDRDR 155
gi 198421619  40 TVFYWFQAVDQDRSGKINAAELRKALMNNKmkqfnpeTCRLMIGMFDKNKDGTIDLREFSALWNYIQQWRQCFDSFDTDK 119
gi 449679573 155 TLWGWFLAVDRDNSGAITSDELQQALLNNNwshfngeTCRLMIGMFDKDRSGTINVYEFAALWKYIQEWKQCFDSFDRDR 234
gi 291226734 122 SLWSMFQVVDQDKNGRITSDELRLALLNGNwspfnpeTCRLMIGMFDKNKDGTIDIHEFAALWKYIQQWKECFDKFDLDR 201
gi 524881407 162 ELWTWFQSVDADRSGQITAIELQQALMNGNwspfnpeTCRLMIGMFDKDRNGTINAHEFAALWKYIQDWKACFDRFDTDR 241
gi 340367991 123 TVYEWFRTVDADGSGQISAVELRQALVNSNwshfndeTCRLLIGMFDKDKNGTIDVHEFGSLWKYVQEWKGCFDRFDKDR 202
gi 390352016 131 TLWSWFKAVDADSSGGITAEELQHALLNGNmtpfnheTCRLMIGMFDLDRNGTINFNEFASLWKYIQDWRGCFDRFDRDR 210
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1        #      #                                                       # # #            
2ZN9_A        88 SGMIDKNELKQALSGFGYrlsdqFHDILIRKFDR-QGRGQIAFDDFIQGCIVLQRLTDIFRRYDTDQDGWIQVSYEQYLS 166
gi 351050110  87 SGNIDKSELTNALTQFGYrlspqFYNILMHKFDR-SHSNRINFDDFIQLCVVLQTLTAAFRDVDTDRDGVITVGYEQFLT 165
gi 675389898 114 SGTIDKNELKTAFSSFGFrlsdvFYDLLIKKFDR-NNTNSITFDDYIQACVMLQSLTAAFRARDTQQTGIIQISYEDFLI 192
gi 514484647 156 SGTIEASELQTALQTFGYhlspqFSQLVVRKFDR-TSGSGIRFDDFIQTCVLIKGLSESFAQADTERNGFARFGFEQFLA 234
gi 198421619 120 SGNIDCGELHRAFHTFGYrlsmeFCKMIVRVFDK-TSANTIDFDDFIQVCVMLHTLTDKFRQNDKNQSGYIQVHYEQFLE 198
gi 449679573 235 SGTIDQNELNQAFTSFGYrlspyFCQLCVRTFDR-TGSNTMKFDDFIQCCVMLKTLTDAFRKHDVQQRGVVNVTYEQFLE 313
gi 291226734 202 SGNIDANELNNAFRTFGYtlsmdFCRLIVTKFDR-ASSSTINFDDFIQCCVMLKSLTEAFRVKDTQQSGWITVTYEQFLE 280
gi 524881407 242 SGNIDANELGNAFQTFGYrlspqFSQTVVRVFDRrRGGRSINFDDFIQACVMLKSLTDKFRVKDSQQNGSINISYEEFLE 321
gi 340367991 203 SGNIDSGELQEALGAFGYrlsrdFCQLCTRVFDR-KDVNSMKFDDFIQCCVMLRSLTETFQRVDTDRDGVIDISYEQFLE 281
gi 390352016 211 SGNIDANELNTAFQTFGYrlspqFCNLIVRRFDR-NHAGTIKFDDFIQVCVMLKSLTEAFRKRDKSMNGVINVHYEDFLE 289

                 ....*.
Feature 1              
2ZN9_A       167 MVFSIV 172
gi 351050110 166 MVFSLK 171
gi 675389898 193 MVVRTM 198
gi 514484647 235 IVFSRA 240
gi 198421619 199 MVLDNT 204
gi 449679573 314 MVLNNT 319
gi 291226734 281 MILENT 286
gi 524881407 322 MVLDTT 327
gi 340367991 282 MAIDNT 287
gi 390352016 290 MVLENA 295

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