Abstract
ALG-2 (a gene product of PDCD6) is a 22-kD protein containing five serially repetitive EF-hand structures and belongs to the penta-EF-hand (PEF) family, including the subunits of typical calpains. ALG-2 is the most conserved protein among the PEF family members and its homologs are widely found in eukaryotes. X-ray crystal structures of various PEF proteins including ALG-2 have common features: presence of eight α-helices and dimer formation via paired EF5s that are positioned in anti-parallel orientation. ALG-2 forms a homodimer and a heterodimer with its closest paralog peflin. Like calmodulin, a well-known four-EF-hand protein, ALG-2 interacts with various proteins in a Ca2+-dependent fashion, but the binding motifs are completely different. With some exceptions, ALG-2-interacting proteins commonly contain Pro-rich regions, and ALG-2 recognizes at least two distinct Pro-containing motifs: PPYP(X)nYP (X, variable; n=4 in ALIX and PLSCR3) and PXPGF (represented by Sec31A). A shorter alternatively spliced isoform, lacking two residues and designated ALG-2ΔGF122, does not bind ALIX but maintains binding capacity to Sec31A. X-ray crystal structural analyses have revealed that binding of calcium ions induces the configuration of the side chain of R125 so that it opens Pocket 1, which accepts PPYP, but Pocket 1 remains closed in the case of ALG-2ΔGF122. ALG-2 dimer has two ligand-binding sites, each in a monomer molecule, and appears to function as a Ca2+-dependent adaptor protein to either stabilize a preformed complex or to bridge two proteins on scaffolds in systems of the endosomal sorting complex required for transport (ESCRT) and ER-to-Golgi transport.
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Ohno S, Emori Y, Imajoh S, et al. Evolutionary origin of a calcium-dependent protease by fusion of genes for a thiol protease and a calcium-binding protein? Nature, 1984, 312: 566–570 6095110, 10.1038/312566a0, 1:CAS:528:DyaL2MXhtVOgsrc%3D
Sakihama T, Kakidani H, Zenita K, et al. A putative Ca2+-binding protein: structure of the light subunit of porcine calpain elucidated by molecular cloning and protein sequence analysis. Proc Natl Acad Sci USA, 1985, 82: 6075–6079 2994060, 10.1073/pnas.82.18.6075, 1:CAS:528:DyaL2MXmtVOrtbs%3D
Blanchard H, Grochulski P, Li Y, et al. Structure of a calpain Ca2+-binding domain reveals a novel EF-hand and Ca2+-induced conformational changes. Nat Struct Biol, 1997, 4: 532–538 9228945, 10.1038/nsb0797-532, 1:CAS:528:DyaK2sXksVelu74%3D
Lin G D, Chattopadhyay D, Maki M, et al. Crystal structure of calcium bound domain VI of calpain at 1.9 Å resolution and its role in enzyme assembly, regulation, and inhibitor binding. Nat Struct Biol, 1997, 4: 539–547 9228946, 10.1038/nsb0797-539, 1:CAS:528:DyaK2sXksVelu7Y%3D
Kretsinger R H. EF-hands embrace. Nat Struct Biol, 1997, 4: 514–516 9228939, 10.1038/nsb0797-514, 1:CAS:528:DyaK2sXksVeltbY%3D
Kawasaki H, Nakayama S, Kretsinger R H. Classification and evolution of EF-hand proteins. Biometals, 1998, 11: 277–295 10191494, 10.1023/A:1009282307967, 1:CAS:528:DyaK1MXit1Omsb8%3D
Grabarek Z. Structural basis for diversity of the EF-hand calcium-binding proteins. J Mol Biol, 2006, 359: 509–525 16678204, 10.1016/j.jmb.2006.03.066, 1:CAS:528:DC%2BD28XltFGjtLs%3D
Hosfield C M, Elce J S, Davies P L, et al. Crystal structure of calpain reveals the structural basis for Ca2+-dependent protease activity and a novel mode of enzyme activation. EMBO J, 1999, 18: 6880–6889 10601010, 10.1093/emboj/18.24.6880, 1:CAS:528:DC%2BD3cXhtFensA%3D%3D
Strobl S, Fernandez-Catalan C, Braun M, et al. The crystal structure of calcium-free human m-calpain suggests an electrostatic switch mechanism for activation by calcium. Proc Natl Acad Sci USA, 2000, 97: 588–592 10639123, 10.1073/pnas.97.2.588, 1:CAS:528:DC%2BD3cXot1ajug%3D%3D
Maki M, Narayana S V, Hitomi K. A growing family of the Ca2+-binding proteins with five EF-hand motifs. Biochem J, 1997, 328: 718–720 9441591, 1:CAS:528:DyaK2sXotVGgur4%3D
Vito P, Lacanà E, D’Adamio L. Interfering with apoptosis: Ca2+-binding protein ALG-2 and Alzheimer’s disease gene ALG-3. Science, 1996, 271: 521–525 8560270, 10.1126/science.271.5248.521, 1:CAS:528:DyaK28XmvFyqsg%3D%3D
Lacanà E, Ganjei J K, Vito P, et al. Dissociation of apoptosis and activation of IL-1β-converting enzyme/Ced-3 proteases by ALG-2 and the truncated Alzheimer’s gene ALG-3. J Immunol, 1997, 158: 5129–5135 9164928
Kageyama H, Shimizu M, Tokunaga K, et al. A partial cDNA for a novel protein which has a typical EF-hand structure. Biochim Biophys Acta, 1989, 1008: 255–257 2736249, 1:CAS:528:DyaL1MXksFWmtb0%3D
Van der Bliek A M, Meyers M B, Biedler J L, et al. A 22-kD protein (sorcin/V19) encoded by an amplified gene in multidrug-resistant cells, is homologous to the calcium-binding light chain of calpain. EMBO J, 1986, 5: 3201–3208 3028774
Hamada H, Okochi E, Oh-hara T, et al. Purification of the Mr 22000 calcium-binding protein (sorcin) associated with multidrug resistance and its detection with monoclonal antibodies. Cancer Res, 1988, 48: 3173–3178 3365700, 1:CAS:528:DyaL1cXksVOqsLg%3D
Boyhan A, Casimir C M, French J K, et al. Molecular cloning and characterization of grancalcin, a novel EF-hand calcium-binding protein abundant in neutrophils and monocytes. J Biol Chem, 1992, 267: 2928–2933 1737748, 1:CAS:528:DyaK3sXhs1enu7s%3D
Kitaura Y, Watanabe M, Satoh H, et al. Peflin, a novel member of the five-EF-hand-protein family, is similar to the apoptosis-linked gene 2 (ALG-2) protein but possesses nonapeptide repeats in the N-terminal hydrophobic region. Biochem Biophys Res Commun, 1999, 263: 68–75 10486255, 10.1006/bbrc.1999.1189, 1:CAS:528:DyaK1MXlvVWqtLo%3D
Kitaura Y, Matsumoto S, Satoh H, et al. Peflin and ALG-2, members of the penta-EF-hand protein family, form a heterodimer that dissociates in a Ca2+-dependent manner. J Biol Chem, 2001, 276: 14053–14058 11278427, 1:CAS:528:DC%2BD3MXjt12rs7Y%3D
Maki M, Kitaura Y, Satoh H, et al. Structures, functions and molecular evolution of the penta-EF-hand Ca2+-binding proteins. Biochim Biophys Acta, 2002, 1600: 51–60 12445459, 1:CAS:528:DC%2BD38XoslChurg%3D
Maki M, Yamaguchi K, Kitaura Y, et al. Calcium-induced exposure of a hydrophobic surface of mouse ALG-2, which is a member of the penta-EF-hand protein family. J Biochem, 1998, 124: 1170–1177 9832622, 1:CAS:528:DyaK1MXnsVSitw%3D%3D
Lo K W, Zhang Q, Li M, et al. Apoptosis-linked gene product ALG-2 is a new member of the calpain small subunit subfamily of Ca2+-binding proteins. Biochemistry, 1999, 38: 7498–7508 10360947, 10.1021/bi990034n, 1:CAS:528:DyaK1MXjtVCntrw%3D
Subramanian L, Crabb J W, Cox J, et al. Ca2+ binding to EF hands 1 and 3 is essential for the interaction of apoptosis-linked gene-2 with Alix/AIP1 in ocular melanoma. Biochemistry, 2004, 43: 11175–11186 15366927, 10.1021/bi048848d, 1:CAS:528:DC%2BD2cXmsVKiu7Y%3D
Tarabykina S, Møller A L, Durussel I, et al. Two forms of the apoptosis-linked protein ALG-2 with different Ca2+ affinities and target recognition. J Biol Chem, 2000, 275: 10514–10518 10744743, 10.1074/jbc.275.14.10514, 1:CAS:528:DC%2BD3cXisFWjtLk%3D
LaPorte D C, Wierman B M, Storm D R. Calcium-induced exposure of a hydrophobic surface on calmodulin. Biochemistry, 1980, 19: 3814–3819 6250577, 10.1021/bi00557a025, 1:CAS:528:DyaL3cXlt1OgtL4%3D
Tanaka T, Hidaka H. Hydrophobic regions function in calmodulin-enzyme(s) interactions. J Biol Chem, 1980, 255: 11078–11080 6254958, 1:CAS:528:DyaL3cXmtlektbg%3D
Jia J, Tarabykina S, Hansen C, et al. Structure of apoptosis-linked protein ALG-2: insights into Ca2+-induced changes in penta-EF-hand proteins. Structure, 2001b, 9: 267–275 11525164, 10.1016/S0969-2126(01)00585-8, 1:CAS:528:DC%2BD3MXjsValsr4%3D
Wu F, Zhang M, Gong W. Crystallization and preliminary crystallographic studies of an apoptosis-linked calcium-binding protein ALG-2. Acta Crystallogr D Biol Crystallogr, 2001, 57: 1162–1163 11468406, 10.1107/S090744490100926X, 1:STN:280:DC%2BD3MvitVWqsg%3D%3D
Suzuki H, Kawasaki M, Inuzuka T, et al. Structural basis for Ca2+-dependent formation of ALG-2/Alix peptide complex: Ca2+/ EF3-driven arginine switch mechanism. Structure, 2008, 16: 1562–1573 18940611, 10.1016/j.str.2008.07.012, 1:CAS:528:DC%2BD1cXht1Siu7%2FF
Suzuki H, Kawasaki M, Kakiuchi T, et al. Crystallization and X-ray diffraction analysis of N-terminally truncated human ALG-2. Acta Crystallogr Sect F Struct Biol Cryst Commun, 2008, 64: 974–977 18997320, 10.1107/S1744309108030297
Kitaura Y, Satoh H, Takahashi H, et al. Both ALG-2 and peflin, penta-EF-hand (PEF) proteins, are stabilized by dimerization through their fifth EF-hand regions. Arch Biochem Biophys, 2002, 399: 12–18 11883899, 10.1006/abbi.2001.2736, 1:CAS:528:DC%2BD38Xhs1yktrs%3D
Missotten M, Nichols A, Rieger K, et al. Alix, a novel mouse protein undergoing calcium-dependent interaction with the apoptosis-linked-gene 2 (ALG-2) protein. Cell Death Differ, 1999, 6: 124–129 10200558, 10.1038/sj.cdd.4400456, 1:CAS:528:DyaK1MXhs1Cnsrw%3D
Vito P, Pellegrini L, Guiet C, et al. Cloning of AIP1, a novel protein that associates with the apoptosis-linked gene ALG-2 in a Ca2+-dependent reaction. J Biol Chem, 1999, 274: 1533–1540 9880530, 10.1074/jbc.274.3.1533, 1:CAS:528:DyaK1MXpsFOhsA%3D%3D
Satoh H, Shibata H, Nakano Y, et al. ALG-2 interacts with the amino-terminal domain of annexin XI in a Ca2+-dependent manner. Biochem Biophys Res Commun, 2002, 291: 1166–1172 11883939, 10.1006/bbrc.2002.6600, 1:CAS:528:DC%2BD38XhslWnsLo%3D
Satoh H, Nakano Y, Shibata H, et al. The penta-EF-hand domain of ALG-2 interacts with amino-terminal domains of both annexin VII and annexin XI in a Ca2+-dependent manner. Biochim Biophys Acta, 2002, 1600: 61–67 12445460, 1:CAS:528:DC%2BD38XoslChurk%3D
Jung Y S, Kim K S, Kim K D, et al.. Apoptosis-linked gene 2 binds to the death domain of Fas and dissociates from Fas during Fas-mediated apoptosis in Jurkat cells. Biochem Biophys Res Commun, 2001, 288: 420–426 11606059, 10.1006/bbrc.2001.5769, 1:CAS:528:DC%2BD3MXnsF2qtrg%3D
Mollerup J, Krogh T N, Nielsen P F, et al. Properties of the co-chaperone protein p23 erroneously attributed to ALG-2 (apoptosis-linked gene 2). FEBS Lett, 2003, 555: 478–482 14675759, 10.1016/S0014-5793(03)01310-3, 1:CAS:528:DC%2BD3sXpvVent78%3D
la Cour J M, Mollerup J, Winding P, et al. Up-regulation of ALG-2 in hepatomas and lung cancer tissue. Am J Pathol, 2003, 163: 81–89 12819013, 10.1016/S0002-9440(10)63632-2
Hwang I S, Jung Y S, Kim E. Interaction of ALG-2 with ASK1 influences ASK1 localization and subsequent JNK activation. FEBS Lett, 2002, 529: 183–187 12372597, 10.1016/S0014-5793(02)03329-X, 1:CAS:528:DC%2BD38Xns1agurc%3D
Chen C, Sytkowski A J. Apoptosis-linked gene-2 connects the Raf-1 and ASK1 signalings. Biochem Biophys Res Commun, 2005, 333: 51–57 15925322, 10.1016/j.bbrc.2005.05.074, 1:CAS:528:DC%2BD2MXlt1Sktrw%3D
Vergarajauregui S, Martina J A, Puertollano R. Identification of the penta-EF-hand protein ALG-2 as a Ca2+-dependent interactor of mucolipin-1. J Biol Chem, 2009, 284: 36357–36366 19864416, 10.1074/jbc.M109.047241, 1:CAS:528:DC%2BD1MXhsFyiurvE
Shibata H, Yamada K, Mizuno T, et al. The penta-EF-hand protein ALG-2 interacts with a region containing PxY repeats in Alix/AIP1, which is required for the subcellular punctate distribution of the amino-terminal truncation form of Alix/AIP1. J Biochem, 2004, 135: 117–128 14999017, 10.1093/jb/mvh014, 1:CAS:528:DC%2BD2cXjt1Slsr4%3D
Shibata H, Suzuki H, Kakiuchi T, et al. Identification of Alix-type and Non-Alix-type ALG-2-binding sites in human phospholipid scramblase 3: differential binding to an alternatively spliced isoform and amino acid-substituted mutants. J Biol Chem, 2008, 283: 9623–9632 18256029, 10.1074/jbc.M800717200, 1:CAS:528:DC%2BD1cXkt1aks7c%3D
Shibata H, Inuzuka T, Yoshida H, et al. The ALG-2 binding site in Sec31A influences the retention kinetics of Sec31A at the endoplasmic reticulum exit sites as revealed by live-cell time-lapse imaging. Biosci Biotechnol Biochem, 2010a, 74: 1819–1826 20834162, 10.1271/bbb.100215, 1:CAS:528:DC%2BC3cXht12qs77J
Shibata H, Suzuki H, Yoshida H, et al. ALG-2 directly binds Sec31A and localizes at endoplasmic reticulum exit sites in a Ca2+-dependent manner. Biochem Biophys Res Commun, 2007, 353: 756–763 17196169, 10.1016/j.bbrc.2006.12.101, 1:CAS:528:DC%2BD2sXmtVagtA%3D%3D
Katoh K, Suzuki H, Terasawa Y, et al. The penta-EF-hand protein ALG-2 interacts directly with the ESCRT-I component TSG101, and Ca2+-dependently co-localizes to aberrant endosomes with dominant-negative AAA ATPase SKD1/Vps4B. Biochem J, 2005, 391: 677–685 16004603, 10.1042/BJ20050398, 1:CAS:528:DC%2BD2MXhtFCqs7%2FJ
Draeby I, Woods Y L, la Cour J M, et al. The calcium binding protein ALG-2 binds and stabilizes Scotin, a p53-inducible gene product localized at the endoplasmic reticulum membrane. Arch Biochem Biophys, 2007, 467: 87–94 17889823, 10.1016/j.abb.2007.07.028, 1:CAS:528:DC%2BD2sXht1ams7%2FK
Montaville P, Dai Y, Cheung C Y, et al. Nuclear translocation of the calcium-binding protein ALG-2 induced by the RNA-binding protein RBM22. Biochim Biophys Acta, 2006, 1763: 1335–1343 17045351, 10.1016/j.bbamcr.2006.09.003, 1:CAS:528:DC%2BD28Xht1CnsLfM
Inuzuka T, Suzuki H, Kawasaki M, et al. Molecular basis for defect in Alix-binding by alternatively spliced isoform of ALG-2 (ALG-2DeltaGF122) and structural roles of F122 in target recognition. BMC Struct Biol, 2010, 10: 25 20691033
Suzuki H, Kawasaki M, Inuzuka T, et al. The mechanism of Ca2+-dependent recognition of Alix by ALG-2: insights from X-ray crystal structures. Biochem Soc Trans, 2009, 37: 190–194 19143629, 10.1042/BST0370190, 1:CAS:528:DC%2BD1MXotVWmtg%3D%3D
Kay B K, Williamson M P, Sudol M. The importance of being proline: the interaction of proline-rich motifs in signaling proteins with their cognate domains. FASEB J, 2000, 14: 231–241 10657980, 1:CAS:528:DC%2BD3cXisFKlurY%3D
Raiborg C, Stenmark H. The ESCRT machinery in endosomal sorting of ubiquitylated membrane proteins. Nature, 2009, 458: 445–452 19325624, 10.1038/nature07961, 1:CAS:528:DC%2BD1MXjs1Klurs%3D
Hurley J H, Hanson P I. Membrane budding and scission by the ESCRT machinery: it’s all in the neck. Nat Rev Mol Cell Biol, 2010, 11: 556–566 20588296, 10.1038/nrm2937, 1:CAS:528:DC%2BC3cXotFeltL0%3D
Morita E, Sundquist W I. Retrovirus budding. Annu Rev Cell Dev Biol, 2004, 20: 395–425 15473846, 10.1146/annurev.cellbio.20.010403.102350, 1:CAS:528:DC%2BD2cXhtVaqu7fM
Morita E, Sandrin V, Chung H Y, et al. Human ESCRT and ALIX proteins interact with proteins of the midbody and function in cytokinesis. EMBO J, 2007, 26: 4215–4227 17853893, 10.1038/sj.emboj.7601850, 1:CAS:528:DC%2BD2sXhtFWiu73I
Katoh K, Shibata H, Suzuki H, et al. The ALG-2-interacting protein Alix associates with CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting. J Biol Chem, 2003, 278: 39104–39113 12860994, 10.1074/jbc.M301604200, 1:CAS:528:DC%2BD3sXnslWjtLo%3D
Garrus J E, von Schwedler U K, Pornillos O W, et al. Tsg101 and the vacuolar protein sorting pathway are essential for HIV-1 budding. Cell, 2001, 107: 55–65 11595185, 10.1016/S0092-8674(01)00506-2, 1:CAS:528:DC%2BD3MXnsFOntLo%3D
von Schwedler U K, Stuchell M, Müller B, et al. The protein network of HIV budding. Cell, 2003, 114: 701–713 10.1016/S0092-8674(03)00714-1
Ichioka F, Takaya E, Suzuki H, et al. HD-PTP and Alix share some membrane-traffic related proteins that interact with their Bro1 domains or proline-rich regions. Arch Biochem Biophys, 2007, 457: 142–149 17174262, 10.1016/j.abb.2006.11.008, 1:CAS:528:DC%2BD2sXmtVGhsg%3D%3D
Okumura M, Ichioka F, Kobayashi R, et al. Penta-EF-hand protein ALG-2 functions as a Ca2+-dependent adaptor that bridges Alix and TSG101. Biochem Biophys Res Commun, 2009, 386: 237–241 19520058, 10.1016/j.bbrc.2009.06.015, 1:CAS:528:DC%2BD1MXnvVagu7g%3D
Yamasaki A, Tani K, Yamamoto A, et al. The Ca2+-binding protein ALG-2 is recruited to endoplasmic reticulum exit sites by Sec31A and stabilizes the localization of Sec31A. Mol Biol Cell, 2006, 17: 4876–4887 16957052, 10.1091/mbc.E06-05-0444, 1:CAS:528:DC%2BD28XhtFygtrzF
la Cour J M, Mollerup J, Berchtold M W. ALG-2 oscillates in subcellular localization, unitemporally with calcium oscillations. Biochem Biophys Res Commun, 2007, 353: 1063–1067 17214967, 10.1016/j.bbrc.2006.12.143
Bentley M, Nycz D C, Joglekar A, et al. Vesicular calcium regulates coat retention, fusogenicity, and size of pre-Golgi intermediates. Mol Biol Cell, 2010, 21: 1033–1046 20089833, 10.1091/mbc.E09-10-0914, 1:CAS:528:DC%2BC3cXjs1eqsLk%3D
Shibata H, Sugiura H, Yokoyama T, et al. Recruitment of annexin A11 to endoplasmic reticulum exit sites is mediated by the adaptor function of the penta-EF-hand protein ALG-2. Acta Biochim Pol, 2010b, 57: 27
Jang I K, Hu R, Lacaná E, et al. Apoptosis-linked gene 2-deficient mice exhibit normal T-cell development and function. Mol Cell Biol, 2002, 22: 4094–4100 12024023, 10.1128/MCB.22.12.4094-4100.2002, 1:CAS:528:DC%2BD38XktlSmuro%3D
Rao R V, Poksay K S, Castro-Obregon S, et al. Molecular components of a cell death pathway activated by endoplasmic reticulum stress. J Biol Chem, 2004, 279: 177–187 14561754, 10.1074/jbc.M304490200, 1:CAS:528:DC%2BD3sXhtVSqtrrN
Mahul-Mellier A L, Hemming F J, Blot B, et al. Alix, making a link between apoptosis-linked gene-2, the endosomal sorting complexes required for transport, and neuronal death in vivo. J Neurosci, 2006, 26: 542–549 16407552, 10.1523/JNEUROSCI.3069-05.2006, 1:CAS:528:DC%2BD28XosFWrtQ%3D%3D
Mahul-Mellier A L, Strappazzon F, Petiot A, et al. Alix and ALG-2 are involved in tumor necrosis factor receptor 1-induced cell death. J Biol Chem, 2008, 283: 34954–34965 18936101, 10.1074/jbc.M803140200, 1:CAS:528:DC%2BD1cXhsVGqt77K
Høj B R, la Cour J M, Mollerup J, et al. ALG-2 knockdown in HeLa cells results in G2/M cell cycle phase accumulation and cell death. Biochem Biophys Res Commun, 2009, 378: 145–148 19013425
la Cour J M, Høj B R, Mollerup J, et al. The apoptosis linked gene ALG-2 is dysregulated in tumors of various origin and contributes to cancer cell viability. Mol Oncol, 2008, 1: 431–439 19383317, 10.1016/j.molonc.2007.08.002
Aviel-Ronen S, Coe B P, Lau S K, et al. Genomic markers for malignant progression in pulmonary adenocarcinoma with bronchioloalveolar features. Proc Natl Acad Sci USA, 2008, 105: 10155–10160 18632575, 10.1073/pnas.0709618105, 1:CAS:528:DC%2BD1cXptF2rsb0%3D
Yamada Y, Arao T, Gotoda T, et al. Identification of prognostic biomarkers in gastric cancer using endoscopic biopsy samples. Cancer Sci, 2008, 99: 2193–2199 18957060, 10.1111/j.1349-7006.2008.00935.x, 1:CAS:528:DC%2BD1cXhsVKgtLvO
Yap K L, Ames J B, Swindells M B, et al. Diversity of conformational states and changes within the EF-hand protein superfamily. Proteins, 1999, 37: 499–507 10591109, 10.1002/(SICI)1097-0134(19991115)37:3<499::AID-PROT17>3.0.CO;2-Y, 1:CAS:528:DyaK1MXntFOjtro%3D
Crivici A, Ikura M. Molecular and structural basis of target recognition by calmodulin. Ann Rev Biophys Biomol Struct, 1995, 24: 85–116 10.1146/annurev.bb.24.060195.000505, 1:CAS:528:DyaK2MXmt1ams7g%3D
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Maki, M., Suzuki, H. & Shibata, H. Structure and function of ALG-2, a penta-EF-hand calcium-dependent adaptor protein. Sci. China Life Sci. 54, 770–779 (2011). https://doi.org/10.1007/s11427-011-4204-8
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DOI: https://doi.org/10.1007/s11427-011-4204-8