ID PDCD6_HUMAN Reviewed; 191 AA. AC O75340; B2RD16; E7ESR3; Q2YDC2; Q5TZS0; DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1998, sequence version 1. DT 27-MAR-2024, entry version 210. DE RecName: Full=Programmed cell death protein 6; DE AltName: Full=Apoptosis-linked gene 2 protein homolog {ECO:0000250|UniProtKB:P12815}; DE Short=ALG-2 {ECO:0000250|UniProtKB:P12815}; GN Name=PDCD6; Synonyms=ALG2 {ECO:0000250|UniProtKB:P12815}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RA Ganjei J.K., D'Adamio L.; RL Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Liver; RA Urcelay E., Ibarreta D., Parrilla R., Ayuso M.S.; RL Submitted (MAY-1996) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Cerebellum; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15372022; DOI=10.1038/nature02919; RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S., RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.; RT "The DNA sequence and comparative analysis of human chromosome 5."; RL Nature 431:268-274(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3). RC TISSUE=Colon, Ovary, and Placenta; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP INTERACTION WITH PEF1. RX PubMed=11278427; DOI=10.1074/jbc.m008649200; RA Kitaura Y., Matsumoto S., Satoh H., Hitomi K., Maki M.; RT "Peflin and ALG-2, members of the penta-EF-hand protein family, form a RT heterodimer that dissociates in a Ca2+-dependent manner."; RL J. Biol. Chem. 276:14053-14058(2001). RN [9] RP INTERACTION WITH PEF1. RX PubMed=11883899; DOI=10.1006/abbi.2001.2736; RA Kitaura Y., Satoh H., Takahashi H., Shibata H., Maki M.; RT "Both ALG-2 and peflin, penta-EF-hand (PEF) proteins, are stabilized by RT dimerization through their fifth EF-hand regions."; RL Arch. Biochem. Biophys. 399:12-18(2002). RN [10] RP INTERACTION WITH ANXA11. RX PubMed=11883939; DOI=10.1006/bbrc.2002.6600; RA Satoh H., Shibata H., Nakano Y., Kitaura Y., Maki M.; RT "ALG-2 interacts with the amino-terminal domain of annexin XI in a Ca(2+)- RT dependent manner."; RL Biochem. Biophys. Res. Commun. 291:1166-1172(2002). RN [11] RP FUNCTION, AND INTERACTION WITH DAPK1. RX PubMed=16132846; DOI=10.1007/s10529-005-7869-x; RA Lee J.H., Rho S.B., Chun T.; RT "Programmed cell death 6 (PDCD6) protein interacts with death-associated RT protein kinase 1 (DAPk1): additive effect on apoptosis via caspase-3 RT dependent pathway."; RL Biotechnol. Lett. 27:1011-1015(2005). RN [12] RP SUBCELLULAR LOCATION, AND INTERACTION WITH RBM22. RX PubMed=17045351; DOI=10.1016/j.bbamcr.2006.09.003; RA Montaville P., Dai Y., Cheung C.Y., Giller K., Becker S., Michalak M., RA Webb S.E., Miller A.L., Krebs J.; RT "Nuclear translocation of the calcium-binding protein ALG-2 induced by the RT RNA-binding protein RBM22."; RL Biochim. Biophys. Acta 1763:1335-1343(2006). RN [13] RP INTERACTION WITH SEC31A AND PDCD6IP, MUTAGENESIS OF GLU-47 AND GLU-114, AND RP SUBCELLULAR LOCATION. RX PubMed=16957052; DOI=10.1091/mbc.e06-05-0444; RA Yamasaki A., Tani K., Yamamoto A., Kitamura N., Komada M.; RT "The Ca2+-binding protein ALG-2 is recruited to endoplasmic reticulum exit RT sites by Sec31A and stabilizes the localization of Sec31A."; RL Mol. Biol. Cell 17:4876-4887(2006). RN [14] RP INTERACTION WITH SHISA5. RX PubMed=17889823; DOI=10.1016/j.abb.2007.07.028; RA Draeby I., Woods Y.L., la Cour J.M., Mollerup J., Bourdon J.C., RA Berchtold M.W.; RT "The calcium binding protein ALG-2 binds and stabilizes Scotin, a p53- RT inducible gene product localized at the endoplasmic reticulum membrane."; RL Arch. Biochem. Biophys. 467:87-94(2007). RN [15] RP INTERACTION WITH PLSCR3; PLSCR4; PDCD6IP; ANXA7; ANXA11; SEC31A AND TSG101, RP AND MUTAGENESIS OF GLU-47; TRP-57; PHE-60; TYR-91; TRP-95; GLU-114 AND RP TYR-180. RX PubMed=18256029; DOI=10.1074/jbc.m800717200; RA Shibata H., Suzuki H., Kakiuchi T., Inuzuka T., Yoshida H., Mizuno T., RA Maki M.; RT "Identification of Alix-type and non-Alix-type ALG-2-binding sites in human RT phospholipid scramblase 3: differential binding to an alternatively spliced RT isoform and amino acid-substituted mutants."; RL J. Biol. Chem. 283:9623-9632(2008). RN [16] RP FUNCTION. RX PubMed=19520058; DOI=10.1016/j.bbrc.2009.06.015; RA Okumura M., Ichioka F., Kobayashi R., Suzuki H., Yoshida H., Shibata H., RA Maki M.; RT "Penta-EF-hand protein ALG-2 functions as a Ca2+-dependent adaptor that RT bridges Alix and TSG101."; RL Biochem. Biophys. Res. Commun. 386:237-241(2009). RN [17] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH MCOLN1. RX PubMed=19864416; DOI=10.1074/jbc.m109.047241; RA Vergarajauregui S., Martina J.A., Puertollano R.; RT "Identification of the penta-EF-hand protein ALG-2 as a Ca2+-dependent RT interactor of mucolipin-1."; RL J. Biol. Chem. 284:36357-36366(2009). RN [18] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [19] RP SUBCELLULAR LOCATION. RX PubMed=21122810; DOI=10.1016/j.bbamcr.2010.11.010; RA Janowicz A., Michalak M., Krebs J.; RT "Stress induced subcellular distribution of ALG-2, RBM22 and hSlu7."; RL Biochim. Biophys. Acta 1813:1045-1049(2011). RN [20] RP FUNCTION, AND INTERACTION WITH KDR. RX PubMed=21893193; DOI=10.1016/j.cellsig.2011.08.013; RA Rho S.B., Song Y.J., Lim M.C., Lee S.H., Kim B.R., Park S.Y.; RT "Programmed cell death 6 (PDCD6) inhibits angiogenesis through RT PI3K/mTOR/p70S6K pathway by interacting of VEGFR-2."; RL Cell. Signal. 24:131-139(2012). RN [21] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.m111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., RA Giglione C.; RT "Comparative large-scale characterisation of plant vs. mammal proteins RT reveals similar and idiosyncratic N-alpha acetylation features."; RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012). RN [22] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [23] RP FUNCTION, INTERACTION WITH PEF1, SUBCELLULAR LOCATION, AND MUTAGENESIS OF RP GLU-47 AND PHE-60. RX PubMed=27716508; DOI=10.1016/j.cell.2016.09.026; RA McGourty C.A., Akopian D., Walsh C., Gorur A., Werner A., Schekman R., RA Bautista D., Rape M.; RT "Regulation of the CUL3 ubiquitin ligase by a calcium-dependent co- RT adaptor."; RL Cell 167:525-538(2016). RN [24] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH TFG. RX PubMed=27813252; DOI=10.1111/febs.13949; RA Kanadome T., Shibata H., Kuwata K., Takahara T., Maki M.; RT "The calcium-binding protein ALG-2 promotes endoplasmic reticulum exit site RT localization and polymerization of Trk-fused gene (TFG) protein."; RL FEBS J. 284:56-76(2017). RN [25] RP X-RAY CRYSTALLOGRAPHY (3.10 ANGSTROMS) OF 24-191 IN COMPLEX WITH CALCIUM RP AND ZINC. RX PubMed=18997320; DOI=10.1107/s1744309108030297; RA Suzuki H., Kawasaki M., Kakiuchi T., Shibata H., Wakatsuki S., Maki M.; RT "Crystallization and X-ray diffraction analysis of N-terminally truncated RT human ALG-2."; RL Acta Crystallogr. F 64:974-977(2008). RN [26] RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 24-191 IN COMPLEXES WITH CALCIUM; RP ZINC AND PDCD6IP, SUBUNIT, AND INTERACTION WITH PDCD6IP. RX PubMed=18940611; DOI=10.1016/j.str.2008.07.012; RA Suzuki H., Kawasaki M., Inuzuka T., Okumura M., Kakiuchi T., Shibata H., RA Wakatsuki S., Maki M.; RT "Structural basis for Ca2+ -dependent formation of ALG-2/Alix peptide RT complex: Ca2+/EF3-driven arginine switch mechanism."; RL Structure 16:1562-1573(2008). RN [27] RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 24-191 IN COMPLEX WITH CALCIUM, RP INTERACTION WITH PDCD6IP; TSG101; ANXA7 AND ANXA11, CALCIUM-BINDING, RP DOMAIN, AND MUTAGENESIS OF PHE-122. RX PubMed=20691033; DOI=10.1186/1472-6807-10-25; RA Inuzuka T., Suzuki H., Kawasaki M., Shibata H., Wakatsuki S., Maki M.; RT "Molecular basis for defect in Alix-binding by alternatively spliced RT isoform of ALG-2 (ALG-2DeltaGF122) and structural roles of F122 in target RT recognition."; RL BMC Struct. Biol. 10:25-25(2010). RN [28] RP X-RAY CRYSTALLOGRAPHY (2.36 ANGSTROMS) OF 20-191 IN COMPLEX WITH ZINC AND RP SEC31A, INTERACTION WITH SEC31A AND PDCD6IP, CALCIUM-BINDING, DOMAIN, AND RP MUTAGENESIS OF LEU-52; SER-53; TRP-57; PHE-85; TRP-89; ILE-92 AND PHE-148. RX PubMed=25667979; DOI=10.3390/ijms16023677; RA Takahashi T., Kojima K., Zhang W., Sasaki K., Ito M., Suzuki H., RA Kawasaki M., Wakatsuki S., Takahara T., Shibata H., Maki M.; RT "Structural analysis of the complex between penta-EF-hand ALG-2 protein and RT Sec31A peptide reveals a novel target recognition mechanism of ALG-2."; RL Int. J. Mol. Sci. 16:3677-3699(2015). RN [29] RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 24-191 IN COMPLEX WITH HEBP2, RP FUNCTION, INTERACTION WITH HEBP2, SUBCELLULAR LOCATION, AND MUTAGENESIS OF RP TRP-57. RX PubMed=27784779; DOI=10.1074/jbc.m116.752444; RA Ma J., Zhang X., Feng Y., Zhang H., Wang X., Zheng Y., Qiao W., Liu X.; RT "Structural and functional study of apoptosis-linked gene-2.Heme-binding RT protein 2 interactions in HIV-1 production."; RL J. Biol. Chem. 291:26670-26685(2016). RN [30] RP VARIANT [LARGE SCALE ANALYSIS] CYS-123. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). CC -!- FUNCTION: Calcium sensor that plays a key role in processes such as CC endoplasmic reticulum (ER)-Golgi vesicular transport, endosomal CC biogenesis or membrane repair. Acts as an adapter that bridges CC unrelated proteins or stabilizes weak protein-protein complexes in CC response to calcium: calcium-binding triggers exposure of apolar CC surface, promoting interaction with different sets of proteins thanks CC to 3 different hydrophobic pockets, leading to translocation to CC membranes (PubMed:20691033, PubMed:25667979). Involved in ER-Golgi CC transport by promoting the association between PDCD6IP and TSG101, CC thereby bridging together the ESCRT-III and ESCRT-I complexes CC (PubMed:19520058). Together with PEF1, acts as a calcium-dependent CC adapter for the BCR(KLHL12) complex, a complex involved in ER-Golgi CC transport by regulating the size of COPII coats (PubMed:27716508). In CC response to cytosolic calcium increase, the heterodimer formed with CC PEF1 interacts with, and bridges together the BCR(KLHL12) complex and CC SEC31 (SEC31A or SEC31B), promoting monoubiquitination of SEC31 and CC subsequent collagen export, which is required for neural crest CC specification (PubMed:27716508). Involved in the regulation of the CC distribution and function of MCOLN1 in the endosomal pathway CC (PubMed:19864416). Promotes localization and polymerization of TFG at CC endoplasmic reticulum exit site (PubMed:27813252). Required for T-cell CC receptor-, Fas-, and glucocorticoid-induced apoptosis (By similarity). CC May mediate Ca(2+)-regulated signals along the death pathway: CC interaction with DAPK1 can accelerate apoptotic cell death by CC increasing caspase-3 activity (PubMed:16132846). Its role in apoptosis CC may however be indirect, as suggested by knockout experiments (By CC similarity). May inhibit KDR/VEGFR2-dependent angiogenesis; the CC function involves inhibition of VEGF-induced phosphorylation of the Akt CC signaling pathway (PubMed:21893193). In case of infection by HIV-1 CC virus, indirectly inhibits HIV-1 production by affecting viral Gag CC expression and distribution (PubMed:27784779). CC {ECO:0000250|UniProtKB:P12815, ECO:0000269|PubMed:16132846, CC ECO:0000269|PubMed:19520058, ECO:0000269|PubMed:19864416, CC ECO:0000269|PubMed:20691033, ECO:0000269|PubMed:21893193, CC ECO:0000269|PubMed:25667979, ECO:0000269|PubMed:27716508, CC ECO:0000269|PubMed:27784779, ECO:0000269|PubMed:27813252}. CC -!- FUNCTION: [Isoform 2]: Has a lower Ca(2+) affinity than isoform 1 (By CC similarity). {ECO:0000250|UniProtKB:P12815}. CC -!- SUBUNIT: Homodimer and heterodimer; heterodimerizes (via the EF-hand 5) CC with PEF1 (PubMed:11278427, PubMed:11883899, PubMed:27784779). Isoform CC 1 and isoform 2 self-associate; probably forming homodimers. Interacts CC with CPNE4 (via VWFA domain) (By similarity). Interacts with PDCD6IP; CC the interaction is calcium-dependent (PubMed:16957052, PubMed:18256029, CC PubMed:18940611, PubMed:20691033, PubMed:25667979). Interacts with CC RBM22 (PubMed:17045351). Interacts with PLSCR4 (PubMed:18256029). CC Interacts with ANXA7 and TSG101 (PubMed:18256029, PubMed:20691033). CC Interacts with DAPK1 (PubMed:16132846). Interacts with SEC31A; the CC interaction is calcium-dependent and promotes monoubiquitination of CC SEC31A (PubMed:16957052, PubMed:18256029, PubMed:27716508, CC PubMed:25667979). Interacts with ANXA11 (via N-terminus); the CC interaction is calcium-dependent (PubMed:11883939, PubMed:18256029, CC PubMed:18940611). Interacts with PLSCR3 (via N-terminus); the CC interaction is calcium-dependent (PubMed:18256029). Interacts with CC MCOLN1; the interaction is calcium-dependent (PubMed:19864416). CC Interacts with KDR; the interaction is calcium-dependent CC (PubMed:21893193). Interacts with HEBP2; the interaction is calcium- CC dependent (PubMed:27784779). Interacts with TFG (PubMed:27813252). CC Isoform 1: Interacts with SHISA5, leading to stabilize it CC (PubMed:17889823). Isoform 2: Does not interact with SHISA5 CC (PubMed:17889823). Isoform 2: Does not interact with PDCD6IP, TSG101, CC ANXA7 and ANXA11 (PubMed:18256029, PubMed:20691033). CC {ECO:0000250|UniProtKB:P12815, ECO:0000269|PubMed:11278427, CC ECO:0000269|PubMed:11883899, ECO:0000269|PubMed:11883939, CC ECO:0000269|PubMed:16132846, ECO:0000269|PubMed:16957052, CC ECO:0000269|PubMed:17045351, ECO:0000269|PubMed:17889823, CC ECO:0000269|PubMed:18256029, ECO:0000269|PubMed:18940611, CC ECO:0000269|PubMed:19864416, ECO:0000269|PubMed:20691033, CC ECO:0000269|PubMed:21893193, ECO:0000269|PubMed:25667979, CC ECO:0000269|PubMed:27716508, ECO:0000269|PubMed:27784779, CC ECO:0000269|PubMed:27813252}. CC -!- INTERACTION: CC O75340; P50995: ANXA11; NbExp=5; IntAct=EBI-352915, EBI-715243; CC O75340; Q5T0G8: ANXA11; NbExp=3; IntAct=EBI-352915, EBI-10245225; CC O75340; O95429: BAG4; NbExp=3; IntAct=EBI-352915, EBI-2949658; CC O75340; P53355: DAPK1; NbExp=3; IntAct=EBI-352915, EBI-358616; CC O75340; Q13561: DCTN2; NbExp=4; IntAct=EBI-352915, EBI-715074; CC O75340; Q9Y5Z4: HEBP2; NbExp=8; IntAct=EBI-352915, EBI-741593; CC O75340; P35968: KDR; NbExp=4; IntAct=EBI-352915, EBI-1005487; CC O75340; O75340: PDCD6; NbExp=4; IntAct=EBI-352915, EBI-352915; CC O75340; Q8WUM4: PDCD6IP; NbExp=12; IntAct=EBI-352915, EBI-310624; CC O75340; Q9UBV8: PEF1; NbExp=10; IntAct=EBI-352915, EBI-724639; CC O75340; Q9NRY6: PLSCR3; NbExp=9; IntAct=EBI-352915, EBI-750734; CC O75340; A6NJB7-2: PRR19; NbExp=3; IntAct=EBI-352915, EBI-11998870; CC O75340; Q9H3S7: PTPN23; NbExp=3; IntAct=EBI-352915, EBI-724478; CC O75340; O94979: SEC31A; NbExp=6; IntAct=EBI-352915, EBI-1767898; CC O75340; A5D8V6: VPS37C; NbExp=6; IntAct=EBI-352915, EBI-2559305; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000269|PubMed:16957052, ECO:0000269|PubMed:27813252}; Peripheral CC membrane protein {ECO:0000269|PubMed:16957052}. Cytoplasmic vesicle, CC COPII-coated vesicle membrane {ECO:0000269|PubMed:27716508}. Cytoplasm CC {ECO:0000269|PubMed:27716508, ECO:0000269|PubMed:27784779}. Nucleus CC {ECO:0000269|PubMed:17045351, ECO:0000269|PubMed:21122810, CC ECO:0000269|PubMed:27784779}. Endosome {ECO:0000269|PubMed:19864416}. CC Note=Interaction with RBM22 induces relocalization from the cytoplasm CC to the nucleus (PubMed:17045351). Translocated from the cytoplasm to CC the nucleus after heat shock cell treatment. Accumulates in cytoplasmic CC vesicle-like organelles after heat shock treatment, which may represent CC stress granules (PubMed:21122810). In response to calcium increase, CC relocates from cytoplasm to COPII vesicle coat (PubMed:27716508). CC Localizes to endoplasmic reticulum exit site (ERES) (PubMed:27813252). CC {ECO:0000269|PubMed:17045351, ECO:0000269|PubMed:21122810, CC ECO:0000269|PubMed:27716508, ECO:0000269|PubMed:27813252}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=O75340-1; Sequence=Displayed; CC Name=2; Synonyms=ALG-2(delta)GF122; CC IsoId=O75340-2; Sequence=VSP_045113; CC Name=3; CC IsoId=O75340-3; Sequence=VSP_045542; CC -!- DOMAIN: Interacts with different set of proteins thanks to 3 different CC hydrophobic pockets (PubMed:20691033, PubMed:25667979). Hydrophobic CC pockets 1 and 2, which mediate interaction with PDCD6IP, are largely CC formed by residues from EF-hand 3 (EF3) to 5 (EF5), as well as by Tyr- CC 180 (EF5) of a dimerizing molecule (Pocket 1) and from EF-hand (EF2) to CC 4 (EF4) (Pocket 2) (PubMed:20691033). Hydrophobic pocket 3, which CC mediates interaction with SEC31A, is mainly formed by residues from EF- CC hand 1 (EF1) to 3 (EF3) (PubMed:25667979). CC {ECO:0000269|PubMed:20691033, ECO:0000269|PubMed:25667979}. CC -!- DOMAIN: EF-hand 1 (EF1) and 3 (EF3) are the high-affinity calcium- CC binding sites, while EF-hand 5 (EF5) binds calcium with low-affinity CC (PubMed:18940611, PubMed:20691033). A one-residue insertion in the EF5- CC binding loop prevents the glutamyl residue at the C-terminal end of the CC loop from serving as the canonical bidentate calcium ligand CC (PubMed:18940611, PubMed:20691033). EF5 acts as a high-affinity CC magnesium-binding domain instead (By similarity). Magnesium, may affect CC dimerization (By similarity). EF5 may bind either calcium or magnesium CC depending on the context (By similarity). CC {ECO:0000250|UniProtKB:P12815, ECO:0000269|PubMed:18940611, CC ECO:0000269|PubMed:20691033}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/43402/PDCD6"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF035606; AAC27697.1; -; mRNA. DR EMBL; U58773; AAF14336.1; -; mRNA. DR EMBL; AK315370; BAG37763.1; -; mRNA. DR EMBL; BT020072; AAV38875.1; -; mRNA. DR EMBL; AC010442; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC021087; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC118458; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471235; EAW50991.1; -; Genomic_DNA. DR EMBL; BC012384; AAH12384.1; -; mRNA. DR EMBL; BC106706; AAI06707.1; -; mRNA. DR EMBL; BC110291; AAI10292.1; -; mRNA. DR EMBL; CB991882; -; NOT_ANNOTATED_CDS; mRNA. DR CCDS; CCDS3854.1; -. [O75340-1] DR CCDS; CCDS58940.1; -. [O75340-2] DR CCDS; CCDS58941.1; -. [O75340-3] DR RefSeq; NP_001254485.1; NM_001267556.1. [O75340-2] DR RefSeq; NP_001254486.1; NM_001267557.1. DR RefSeq; NP_001254487.1; NM_001267558.1. DR RefSeq; NP_001254488.1; NM_001267559.1. [O75340-3] DR RefSeq; NP_037364.1; NM_013232.3. [O75340-1] DR PDB; 2ZN8; X-ray; 2.70 A; A=2-191. DR PDB; 2ZN9; X-ray; 2.40 A; A/B=20-191. DR PDB; 2ZND; X-ray; 1.70 A; A=20-191. DR PDB; 2ZNE; X-ray; 2.20 A; A/B=24-191. DR PDB; 2ZRS; X-ray; 3.10 A; A/B/C/D/E/F/G/H=24-191. DR PDB; 2ZRT; X-ray; 3.30 A; A/B/C/D/E/F/G/H=24-191. DR PDB; 3AAJ; X-ray; 2.40 A; A/B=24-191. DR PDB; 3AAK; X-ray; 2.70 A; A=20-191. DR PDB; 3WXA; X-ray; 2.36 A; A/B=20-191. DR PDB; 5GQQ; X-ray; 2.20 A; C/D=24-191. DR PDBsum; 2ZN8; -. DR PDBsum; 2ZN9; -. DR PDBsum; 2ZND; -. DR PDBsum; 2ZNE; -. DR PDBsum; 2ZRS; -. DR PDBsum; 2ZRT; -. DR PDBsum; 3AAJ; -. DR PDBsum; 3AAK; -. DR PDBsum; 3WXA; -. DR PDBsum; 5GQQ; -. DR AlphaFoldDB; O75340; -. DR SMR; O75340; -. DR BioGRID; 115333; 201. DR CORUM; O75340; -. DR DIP; DIP-33217N; -. DR ELM; O75340; -. DR IntAct; O75340; 87. DR MINT; O75340; -. DR STRING; 9606.ENSP00000264933; -. DR ChEMBL; CHEMBL4105994; -. DR DrugBank; DB01373; Calcium. DR DrugBank; DB11093; Calcium citrate. DR DrugBank; DB11348; Calcium Phosphate. DR DrugBank; DB14481; Calcium phosphate dihydrate. DR DrugBank; DB01593; Zinc. DR DrugBank; DB14487; Zinc acetate. DR TCDB; 3.A.5.9.1; the general secretory pathway (sec) family. DR GlyGen; O75340; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; O75340; -. DR MetOSite; O75340; -. DR PhosphoSitePlus; O75340; -. DR SwissPalm; O75340; -. DR BioMuta; PDCD6; -. DR EPD; O75340; -. DR jPOST; O75340; -. DR MassIVE; O75340; -. DR MaxQB; O75340; -. DR PaxDb; 9606-ENSP00000264933; -. DR PeptideAtlas; O75340; -. DR ProteomicsDB; 18039; -. DR ProteomicsDB; 49909; -. [O75340-1] DR ProteomicsDB; 61550; -. DR Pumba; O75340; -. DR TopDownProteomics; O75340-1; -. [O75340-1] DR Antibodypedia; 36748; 352 antibodies from 34 providers. DR DNASU; 10016; -. DR Ensembl; ENST00000264933.9; ENSP00000264933.4; ENSG00000249915.9. [O75340-1] DR Ensembl; ENST00000505221.5; ENSP00000422085.1; ENSG00000249915.9. [O75340-3] DR Ensembl; ENST00000507528.5; ENSP00000423815.1; ENSG00000249915.9. [O75340-2] DR GeneID; 10016; -. DR KEGG; hsa:10016; -. DR MANE-Select; ENST00000264933.9; ENSP00000264933.4; NM_013232.4; NP_037364.1. DR UCSC; uc003jat.1; human. [O75340-1] DR AGR; HGNC:8765; -. DR CTD; 10016; -. DR DisGeNET; 10016; -. DR GeneCards; PDCD6; -. DR HGNC; HGNC:8765; PDCD6. DR HPA; ENSG00000249915; Low tissue specificity. DR MIM; 601057; gene. DR neXtProt; NX_O75340; -. DR OpenTargets; ENSG00000249915; -. DR PharmGKB; PA33115; -. DR VEuPathDB; HostDB:ENSG00000249915; -. DR eggNOG; KOG0037; Eukaryota. DR GeneTree; ENSGT00940000160982; -. DR HOGENOM; CLU_051357_1_1_1; -. DR InParanoid; O75340; -. DR OMA; EFLWDVF; -. DR OrthoDB; 318691at2759; -. DR PhylomeDB; O75340; -. DR TreeFam; TF314682; -. DR PathwayCommons; O75340; -. DR SignaLink; O75340; -. DR BioGRID-ORCS; 10016; 280 hits in 1155 CRISPR screens. DR EvolutionaryTrace; O75340; -. DR GeneWiki; PDCD6; -. DR GenomeRNAi; 10016; -. DR Pharos; O75340; Tbio. DR PRO; PR:O75340; -. DR Proteomes; UP000005640; Chromosome 5. DR RNAct; O75340; Protein. DR Bgee; ENSG00000249915; Expressed in lower esophagus mucosa and 96 other cell types or tissues. DR ExpressionAtlas; O75340; baseline and differential. DR GO; GO:0030127; C:COPII vesicle coat; IDA:UniProtKB. DR GO; GO:0031463; C:Cul3-RING ubiquitin ligase complex; IDA:GO_Central. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB. DR GO; GO:0070971; C:endoplasmic reticulum exit site; IDA:UniProtKB. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005768; C:endosome; IEA:UniProtKB-SubCell. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB. DR GO; GO:0048306; F:calcium-dependent protein binding; IPI:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB. DR GO; GO:0046983; F:protein dimerization activity; IPI:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB. DR GO; GO:0030674; F:protein-macromolecule adaptor activity; IMP:UniProtKB. DR GO; GO:0043495; F:protein-membrane adaptor activity; IMP:UniProtKB. DR GO; GO:1990756; F:ubiquitin ligase-substrate adaptor activity; IMP:GO_Central. DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW. DR GO; GO:0097190; P:apoptotic signaling pathway; TAS:ProtInc. DR GO; GO:0034605; P:cellular response to heat; IDA:UniProtKB. DR GO; GO:0048208; P:COPII vesicle coating; IMP:UniProtKB. DR GO; GO:0006888; P:endoplasmic reticulum to Golgi vesicle-mediated transport; IMP:UniProtKB. DR GO; GO:0006886; P:intracellular protein transport; IDA:UniProtKB. DR GO; GO:0051898; P:negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IDA:UniProtKB. DR GO; GO:0032007; P:negative regulation of TOR signaling; IDA:UniProtKB. DR GO; GO:0030948; P:negative regulation of vascular endothelial growth factor receptor signaling pathway; IDA:UniProtKB. DR GO; GO:0014032; P:neural crest cell development; IMP:UniProtKB. DR GO; GO:0014029; P:neural crest formation; IMP:UniProtKB. DR GO; GO:0045766; P:positive regulation of angiogenesis; IDA:UniProtKB. DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:UniProtKB. DR GO; GO:0010595; P:positive regulation of endothelial cell migration; IDA:UniProtKB. DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; IDA:UniProtKB. DR GO; GO:1902527; P:positive regulation of protein monoubiquitination; IMP:UniProtKB. DR GO; GO:0051592; P:response to calcium ion; ISS:UniProtKB. DR GO; GO:0036324; P:vascular endothelial growth factor receptor-2 signaling pathway; IDA:UniProtKB. DR CDD; cd16183; EFh_PEF_ALG-2; 1. DR Gene3D; 1.10.238.10; EF-hand; 1. DR InterPro; IPR011992; EF-hand-dom_pair. DR InterPro; IPR018247; EF_Hand_1_Ca_BS. DR InterPro; IPR002048; EF_hand_dom. DR PANTHER; PTHR46212; PEFLIN; 1. DR PANTHER; PTHR46212:SF9; PROGRAMMED CELL DEATH PROTEIN 6; 1. DR Pfam; PF13499; EF-hand_7; 2. DR SMART; SM00054; EFh; 5. DR SUPFAM; SSF47473; EF-hand; 1. DR PROSITE; PS00018; EF_HAND_1; 2. DR PROSITE; PS50222; EF_HAND_2; 3. DR Genevisible; O75340; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Angiogenesis; Apoptosis; KW Calcium; Cytoplasm; Cytoplasmic vesicle; Endoplasmic reticulum; Endosome; KW Magnesium; Membrane; Metal-binding; Nucleus; Reference proteome; Repeat. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:22223895" FT CHAIN 2..191 FT /note="Programmed cell death protein 6" FT /id="PRO_0000073729" FT DOMAIN 23..58 FT /note="EF-hand 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT DOMAIN 59..89 FT /note="EF-hand 2" FT /evidence="ECO:0000305" FT DOMAIN 90..125 FT /note="EF-hand 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT DOMAIN 126..161 FT /note="EF-hand 4" FT /evidence="ECO:0000305" FT DOMAIN 162..191 FT /note="EF-hand 5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 36 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448, FT ECO:0000269|PubMed:18940611, ECO:0000269|PubMed:18997320, FT ECO:0000269|PubMed:20691033, ECO:0000269|PubMed:25667979" FT BINDING 38 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448, FT ECO:0000269|PubMed:18940611, ECO:0000269|PubMed:18997320, FT ECO:0000269|PubMed:20691033, ECO:0000269|PubMed:25667979" FT BINDING 40 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448, FT ECO:0000269|PubMed:18940611, ECO:0000269|PubMed:18997320, FT ECO:0000269|PubMed:20691033, ECO:0000269|PubMed:25667979" FT BINDING 42 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:18940611, FT ECO:0000269|PubMed:18997320, ECO:0000269|PubMed:20691033, FT ECO:0000269|PubMed:25667979" FT BINDING 47 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448, FT ECO:0000269|PubMed:18940611, ECO:0000269|PubMed:18997320, FT ECO:0000269|PubMed:20691033, ECO:0000269|PubMed:25667979" FT BINDING 103 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448, FT ECO:0000269|PubMed:18940611, ECO:0000269|PubMed:18997320, FT ECO:0000269|PubMed:20691033, ECO:0000269|PubMed:25667979" FT BINDING 105 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448, FT ECO:0000269|PubMed:18940611, ECO:0000269|PubMed:18997320, FT ECO:0000269|PubMed:20691033, ECO:0000269|PubMed:25667979" FT BINDING 107 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448, FT ECO:0000269|PubMed:18940611, ECO:0000269|PubMed:18997320, FT ECO:0000269|PubMed:20691033, ECO:0000269|PubMed:25667979" FT BINDING 109 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448, FT ECO:0000269|PubMed:18940611, ECO:0000269|PubMed:18997320, FT ECO:0000269|PubMed:20691033, ECO:0000269|PubMed:25667979" FT BINDING 114 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448, FT ECO:0000269|PubMed:18940611, ECO:0000269|PubMed:18997320, FT ECO:0000269|PubMed:20691033, ECO:0000269|PubMed:25667979" FT BINDING 169 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:P12815" FT BINDING 171 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:P12815" FT BINDING 173 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:P12815" FT BINDING 175 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:P12815" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0007744|PubMed:22223895" FT VAR_SEQ 70..191 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_045542" FT VAR_SEQ 121..122 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_045113" FT VARIANT 123 FT /note="G -> C (in a breast cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_035459" FT MUTAGEN 47 FT /note="E->A: Loss of interaction with SEC31A and PLSCR3, FT and loss of localization to the endoplasmic reticulum; when FT associated with A-114." FT /evidence="ECO:0000269|PubMed:16957052, FT ECO:0000269|PubMed:18256029, ECO:0000269|PubMed:27716508" FT MUTAGEN 52 FT /note="L->A: Strongly impaired interaction with SEC31A. FT Slightly reduced interaction with PDCD6IP." FT /evidence="ECO:0000269|PubMed:25667979" FT MUTAGEN 53 FT /note="S->G: Slightly reduced interaction with SEC31A. Does FT not affect interaction with PDCD6IP." FT /evidence="ECO:0000269|PubMed:25667979" FT MUTAGEN 57 FT /note="W->A: Does not affect interaction with SEC31A. FT Reduces the interaction with HEBP2, PDCD6IP and ANXA7." FT /evidence="ECO:0000269|PubMed:18256029, FT ECO:0000269|PubMed:25667979, ECO:0000269|PubMed:27784779" FT MUTAGEN 60 FT /note="F->A: Abolishes the interaction with SEC31A, FT PDCD6IP, ANXA7 and ANXA11." FT /evidence="ECO:0000269|PubMed:18256029, FT ECO:0000269|PubMed:27716508" FT MUTAGEN 85 FT /note="F->A: Strongly impaired interaction with SEC31A and FT TFG. Does not affect interaction with PDCD6IP." FT /evidence="ECO:0000269|PubMed:25667979, FT ECO:0000269|PubMed:27813252" FT MUTAGEN 89 FT /note="W->A: Does not affect interaction with SEC31A. Does FT not affect interaction with PDCD6IP." FT /evidence="ECO:0000269|PubMed:25667979" FT MUTAGEN 91 FT /note="Y->A: Abolishes the interaction with PDCD6IP, ANXA7 FT and ANXA11." FT /evidence="ECO:0000269|PubMed:18256029" FT MUTAGEN 92 FT /note="I->A: Does not affect interaction with SEC31A. Does FT not affect interaction with PDCD6IP." FT /evidence="ECO:0000269|PubMed:25667979" FT MUTAGEN 95 FT /note="W->A: Abolishes the interaction with PDCD6IP, ANXA7 FT and ANXA11." FT /evidence="ECO:0000269|PubMed:18256029" FT MUTAGEN 114 FT /note="E->A: Loss of interaction with SEC31A and PLSCR3, FT and loss of localization to the endoplasmic reticulum; when FT associated with A-47." FT /evidence="ECO:0000269|PubMed:16957052, FT ECO:0000269|PubMed:18256029" FT MUTAGEN 122 FT /note="F->A: Increases interaction with PDCD6IP and ANXA7. FT Impairs interaction with ANXA11. Augments FT stauroporine-induced cell death." FT /evidence="ECO:0000269|PubMed:20691033" FT MUTAGEN 122 FT /note="F->G: Increases interaction with PDCD6IP. Impairs FT interaction with ANXA11." FT /evidence="ECO:0000269|PubMed:20691033" FT MUTAGEN 122 FT /note="F->S: Increases interaction with PDCD6IP. Impairs FT interaction with ANAX7 and ANXA11." FT /evidence="ECO:0000269|PubMed:20691033" FT MUTAGEN 122 FT /note="F->W: Impairs interaction with ANXA11." FT /evidence="ECO:0000269|PubMed:20691033" FT MUTAGEN 148 FT /note="F->S: Slightly reduced interaction with SEC31A. Does FT not affect interaction with PDCD6IP." FT /evidence="ECO:0000269|PubMed:25667979" FT MUTAGEN 180 FT /note="Y->A: Abolishes the interaction with PDCD6IP, FT TSG101, ANXA7 and ANXA11. Does not affect interaction with FT TFG and SEC31A." FT /evidence="ECO:0000269|PubMed:18256029, FT ECO:0000269|PubMed:27813252" FT HELIX 26..35 FT /evidence="ECO:0007829|PDB:2ZND" FT STRAND 36..40 FT /evidence="ECO:0007829|PDB:2ZRT" FT STRAND 41..43 FT /evidence="ECO:0007829|PDB:2ZNE" FT HELIX 45..51 FT /evidence="ECO:0007829|PDB:2ZND" FT STRAND 55..58 FT /evidence="ECO:0007829|PDB:2ZND" FT HELIX 62..72 FT /evidence="ECO:0007829|PDB:2ZND" FT STRAND 74..80 FT /evidence="ECO:0007829|PDB:2ZND" FT HELIX 82..102 FT /evidence="ECO:0007829|PDB:2ZND" FT STRAND 107..110 FT /evidence="ECO:0007829|PDB:2ZND" FT HELIX 112..121 FT /evidence="ECO:0007829|PDB:2ZND" FT HELIX 128..138 FT /evidence="ECO:0007829|PDB:2ZND" FT STRAND 143..147 FT /evidence="ECO:0007829|PDB:2ZND" FT HELIX 148..168 FT /evidence="ECO:0007829|PDB:2ZND" FT STRAND 172..174 FT /evidence="ECO:0007829|PDB:2ZND" FT HELIX 180..188 FT /evidence="ECO:0007829|PDB:2ZND" SQ SEQUENCE 191 AA; 21868 MW; D0B5944CF3C696AD CRC64; MAAYSYRPGP GAGPGPAAGA ALPDQSFLWN VFQRVDKDRS GVISDTELQQ ALSNGTWTPF NPVTVRSIIS MFDRENKAGV NFSEFTGVWK YITDWQNVFR TYDRDNSGMI DKNELKQALS GFGYRLSDQF HDILIRKFDR QGRGQIAFDD FIQGCIVLQR LTDIFRRYDT DQDGWIQVSY EQYLSMVFSI V //