PDCD6_HUMAN
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 03-AUG-2022, entry version 201.
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 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="http://atlasgeneticsoncology.org/Genes/PDCD6ID43402ch5p15.html";
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; 183.
DR CORUM; O75340; -.
DR DIP; DIP-33217N; -.
DR ELM; O75340; -.
DR IntAct; O75340; 84.
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 iPTMnet; O75340; -.
DR MetOSite; O75340; -.
DR PhosphoSitePlus; O75340; -.
DR BioMuta; PDCD6; -.
DR EPD; O75340; -.
DR jPOST; O75340; -.
DR MassIVE; O75340; -.
DR MaxQB; O75340; -.
DR PaxDb; O75340; -.
DR PeptideAtlas; O75340; -.
DR PRIDE; O75340; -.
DR ProteomicsDB; 18039; -.
DR ProteomicsDB; 49909; -. [O75340-1]
DR ProteomicsDB; 61550; -.
DR TopDownProteomics; O75340-1; -. [O75340-1]
DR Antibodypedia; 36748; 327 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 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; SREFLWD; -.
DR PhylomeDB; O75340; -.
DR TreeFam; TF314682; -.
DR PathwayCommons; O75340; -.
DR SignaLink; O75340; -.
DR BioGRID-ORCS; 10016; 274 hits in 1076 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 94 other tissues.
DR ExpressionAtlas; O75340; baseline and differential.
DR Genevisible; O75340; HS.
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:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IEA:Ensembl.
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 protein kinase B signaling; 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 InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR Pfam; PF13202; EF-hand_5; 1.
DR Pfam; PF13499; EF-hand_7; 1.
DR SMART; SM00054; EFh; 5.
DR SUPFAM; SSF47473; SSF47473; 1.
DR PROSITE; PS00018; EF_HAND_1; 2.
DR PROSITE; PS50222; EF_HAND_2; 3.
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 stauroporine-
FT 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
