ESYT2_HUMAN
ID ESYT2_HUMAN Reviewed; 921 AA.
AC A0FGR8; A4D229; Q69YJ2; Q6UKI4; Q6ZTU0; Q6ZVU1; Q9BQS0; Q9NW47; Q9ULJ2;
DT 20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 28-NOV-2006, sequence version 1.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=Extended synaptotagmin-2 {ECO:0000305};
DE Short=E-Syt2 {ECO:0000303|PubMed:29469807};
DE AltName: Full=Chr2Syt;
GN Name=ESYT2 {ECO:0000312|HGNC:HGNC:22211}; Synonyms=FAM62B, KIAA1228;
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), FUNCTION, SUBCELLULAR LOCATION,
RP CALCIUM-DEPENDENT LIPID-BINDING, AND TISSUE SPECIFICITY.
RX PubMed=17360437; DOI=10.1073/pnas.0611725104;
RA Min S.-W., Chang W.-P., Suedhof T.C.;
RT "E-Syts, a family of membranous Ca2+-sensor proteins with multiple C2
RT domains.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:3823-3828(2007).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RA Shan Y.X., Yu L.;
RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 4 AND 5), NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 511-921 (ISOFORMS 1/2), AND VARIANT GLY-638.
RC TISSUE=Esophageal carcinoma, and Thymus;
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 GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 79-921 (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=10574462; DOI=10.1093/dnares/6.5.337;
RA Nagase T., Ishikawa K., Kikuno R., Hirosawa M., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XV. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 6:337-345(1999).
RN [6]
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 141-921.
RC TISSUE=Melanoma;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 454-921 (ISOFORM 6).
RC TISSUE=Colon;
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 [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 747-904.
RC TISSUE=Brain;
RX PubMed=11543631; DOI=10.1006/geno.2001.6619;
RA Craxton M.A.;
RT "Genomic analysis of synaptotagmin genes.";
RL Genomics 77:43-49(2001).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-743, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17924679; DOI=10.1021/pr070152u;
RA Yu L.R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D.;
RT "Improved titanium dioxide enrichment of phosphopeptides from HeLa cells
RT and high confident phosphopeptide identification by cross-validation of
RT MS/MS and MS/MS/MS spectra.";
RL J. Proteome Res. 6:4150-4162(2007).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-743; SER-758 AND SER-761, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-743; SER-755; SER-758 AND
RP SER-761, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-691; SER-739; SER-748;
RP SER-755; SER-758 AND SER-761, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [15]
RP INTERACTION WITH FGFR1 AND AP2B1, SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=20833364; DOI=10.1016/j.devcel.2010.08.007;
RA Jean S., Mikryukov A., Tremblay M.G., Baril J., Guillou F., Bellenfant S.,
RA Moss T.;
RT "Extended-synaptotagmin-2 mediates FGF receptor endocytosis and ERK
RT activation in vivo.";
RL Dev. Cell 19:426-439(2010).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-743; SER-758 AND SER-761, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [17]
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 [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-758 AND SER-761, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [19]
RP FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY, LIPID-BINDING, DOMAIN,
RP MUTAGENESIS OF 833-LYS--LYS-840, AND INTERACTION WITH ESYT1 AND ESYT3.
RX PubMed=23791178; DOI=10.1016/j.cell.2013.05.026;
RA Giordano F., Saheki Y., Idevall-Hagren O., Colombo S.F., Pirruccello M.,
RA Milosevic I., Gracheva E.O., Bagriantsev S.N., Borgese N., De Camilli P.;
RT "PI(4,5)P(2)-dependent and Ca(2+)-regulated ER-PM interactions mediated by
RT the extended synaptotagmins.";
RL Cell 153:1494-1509(2013).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-691; SER-736; SER-739;
RP SER-743 AND SER-761, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-693; THR-705 AND SER-761, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
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 SUBCELLULAR LOCATION.
RX PubMed=30220461; DOI=10.1016/j.cell.2018.08.033;
RA Sandhu J., Li S., Fairall L., Pfisterer S.G., Gurnett J.E., Xiao X.,
RA Weston T.A., Vashi D., Ferrari A., Orozco J.L., Hartman C.L.,
RA Strugatsky D., Lee S.D., He C., Hong C., Jiang H., Bentolila L.A.,
RA Gatta A.T., Levine T.P., Ferng A., Lee R., Ford D.A., Young S.G.,
RA Ikonen E., Schwabe J.W.R., Tontonoz P.;
RT "Aster proteins facilitate nonvesicular plasma membrane to ER cholesterol
RT transport in mammalian cells.";
RL Cell 175:514-529(2018).
RN [24]
RP SUBCELLULAR LOCATION.
RX PubMed=29469807; DOI=10.7554/elife.31019;
RA Besprozvannaya M., Dickson E., Li H., Ginburg K.S., Bers D.M., Auwerx J.,
RA Nunnari J.;
RT "GRAM domain proteins specialize functionally distinct ER-PM contact sites
RT in human cells.";
RL Elife 7:0-0(2018).
RN [25]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=27044890; DOI=10.1083/jcb.201508106;
RA Dickson E.J., Jensen J.B., Vivas O., Kruse M., Traynor-Kaplan A.E.,
RA Hille B.;
RT "Dynamic formation of ER-PM junctions presents a lipid phosphatase to
RT regulate phosphoinositides.";
RL J. Cell Biol. 213:33-48(2016).
RN [26]
RP STRUCTURE BY NMR OF 222-350.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the third C2 domain of KIAA1228 protein.";
RL Submitted (OCT-2006) to the PDB data bank.
RN [27]
RP X-RAY CRYSTALLOGRAPHY (2.44 ANGSTROMS) OF 191-662 IN COMPLEX WITH
RP PHOSPHATIDYLETHANOLAMINE, LIPID-BINDING, FUNCTION, DOMAIN, AND SUBUNIT.
RX PubMed=24847877; DOI=10.1038/nature13269;
RA Schauder C.M., Wu X., Saheki Y., Narayanaswamy P., Torta F., Wenk M.R.,
RA De Camilli P., Reinisch K.M.;
RT "Structure of a lipid-bound extended synaptotagmin indicates a role in
RT lipid transfer.";
RL Nature 510:552-555(2014).
RN [28]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 363-660 IN COMPLEX WITH CALCIUM,
RP DOMAIN, CALCIUM-BINDING, AND MUTAGENESIS OF ASP-401; ASP-413 AND ASP-466.
RX PubMed=24373768; DOI=10.1016/j.str.2013.11.011;
RA Xu J., Bacaj T., Zhou A., Tomchick D.R., Sudhof T.C., Rizo J.;
RT "Structure and Ca(2+)-binding properties of the tandem C(2) domains of E-
RT Syt2.";
RL Structure 22:269-280(2014).
CC -!- FUNCTION: Tethers the endoplasmic reticulum to the cell membrane and
CC promotes the formation of appositions between the endoplasmic reticulum
CC and the cell membrane. Binds glycerophospholipids in a barrel-like
CC domain and may play a role in cellular lipid transport. Plays a role in
CC FGF signaling via its role in the rapid internalization of FGFR1 that
CC has been activated by FGF1 binding; this occurs most likely via the AP-
CC 2 complex. Promotes the localization of SACM1L at endoplasmic
CC reticulum-plasma membrane contact sites (EPCS) (PubMed:27044890).
CC {ECO:0000269|PubMed:17360437, ECO:0000269|PubMed:20833364,
CC ECO:0000269|PubMed:23791178, ECO:0000269|PubMed:24847877,
CC ECO:0000269|PubMed:27044890}.
CC -!- SUBUNIT: Homodimer. Interacts with ESYT1 and ESYT3. Interacts with
CC FGFR1 that has been activated by FGF1 binding. Interacts with the AP-2
CC complex; identified in a complex with the AP-2 complex and FGFR1.
CC {ECO:0000269|PubMed:20833364, ECO:0000269|PubMed:23791178,
CC ECO:0000269|PubMed:24373768, ECO:0000269|PubMed:24847877}.
CC -!- INTERACTION:
CC A0FGR8; Q9BSJ8: ESYT1; NbExp=6; IntAct=EBI-3184170, EBI-355956;
CC A0FGR8; A0FGR8: ESYT2; NbExp=3; IntAct=EBI-3184170, EBI-3184170;
CC A0FGR8; A0FGR9: ESYT3; NbExp=4; IntAct=EBI-3184170, EBI-8771391;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:17360437,
CC ECO:0000269|PubMed:20833364, ECO:0000269|PubMed:23791178,
CC ECO:0000269|PubMed:29469807}; Peripheral membrane protein
CC {ECO:0000269|PubMed:17360437}. Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:23791178, ECO:0000269|PubMed:29469807}; Multi-pass
CC membrane protein {ECO:0000255}. Note=Localizes to endoplasmic
CC reticulum-plasma membrane contact sites (EPCS) (PubMed:29469807,
CC PubMed:23791178, PubMed:30220461, PubMed:27044890). Recruited to the
CC cell membrane via the third C2 domain (PubMed:17360437).
CC {ECO:0000269|PubMed:17360437, ECO:0000269|PubMed:23791178,
CC ECO:0000269|PubMed:29469807, ECO:0000269|PubMed:30220461}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=A0FGR8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=A0FGR8-2; Sequence=VSP_023239;
CC Name=4;
CC IsoId=A0FGR8-4; Sequence=VSP_023238, VSP_023241, VSP_023242;
CC Name=5;
CC IsoId=A0FGR8-5; Sequence=VSP_023236, VSP_023240;
CC Name=6;
CC IsoId=A0FGR8-6; Sequence=VSP_038324;
CC -!- TISSUE SPECIFICITY: Widely expressed with high level in cerebellum.
CC {ECO:0000269|PubMed:17360437}.
CC -!- DOMAIN: Anchored to the endoplasmic reticulum membrane by a
CC transmembrane hairpin structure; both N-terminus and C-terminus are
CC cytoplasmic. {ECO:0000269|PubMed:23791178}.
CC -!- DOMAIN: The C2 domains mediate lipid and calcium binding. The N-
CC terminal C2 domain binds calcium ions and is important for calcium-
CC dependent lipid binding and interaction with membranes. Two calcium
CC ions are bound at a high-affinity site and a third calcium ion is bound
CC with lower affinity. May bind up to four calcium ions. In contrast, the
CC second C2 domain apparently does not bind calcium (PubMed:24373768).
CC The third C2 domain mediates interaction with membranes enriched in
CC phosphatidylinositol 4,5-bisphosphate and is required for location at
CC the cell membrane (PubMed:23791178). {ECO:0000269|PubMed:23791178,
CC ECO:0000269|PubMed:24373768}.
CC -!- DOMAIN: The SMP-LTD domain is a barrel-like domain that binds
CC glycerophospholipids in its interior; can bind two lipid molecules
CC simultaneously. Binds a variety of lipids, including
CC phosphatidylethanolamine, phosphatidylcholine and phosphatidylinositol
CC (PubMed:24847877). {ECO:0000269|PubMed:24847877}.
CC -!- SIMILARITY: Belongs to the extended synaptotagmin family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA91539.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAC85769.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; DQ993201; ABJ97706.1; -; mRNA.
DR EMBL; AY368150; AAR89381.1; -; mRNA.
DR EMBL; AK001181; BAA91539.1; ALT_INIT; mRNA.
DR EMBL; AK124091; BAC85769.1; ALT_FRAME; mRNA.
DR EMBL; AK126214; BAC86489.1; -; mRNA.
DR EMBL; CH236954; EAL23931.1; -; Genomic_DNA.
DR EMBL; AB033054; BAA86542.2; -; mRNA.
DR EMBL; AL833233; CAH10642.1; -; mRNA.
DR EMBL; BC013957; AAH13957.2; -; mRNA.
DR EMBL; AJ303365; CAC33887.1; -; mRNA.
DR RefSeq; NP_065779.1; NM_020728.2.
DR PDB; 2DMG; NMR; -; A=785-913.
DR PDB; 4NPJ; X-ray; 2.10 A; A/B=363-660.
DR PDB; 4NPK; X-ray; 2.55 A; A=363-660.
DR PDB; 4P42; X-ray; 2.44 A; A/B=191-662.
DR PDBsum; 2DMG; -.
DR PDBsum; 4NPJ; -.
DR PDBsum; 4NPK; -.
DR PDBsum; 4P42; -.
DR AlphaFoldDB; A0FGR8; -.
DR SMR; A0FGR8; -.
DR BioGRID; 121556; 199.
DR CORUM; A0FGR8; -.
DR DIP; DIP-61039N; -.
DR IntAct; A0FGR8; 56.
DR MINT; A0FGR8; -.
DR STRING; 9606.ENSP00000251527; -.
DR TCDB; 9.A.57.1.2; the extended-synaptotagmin (e-syt) family.
DR GlyGen; A0FGR8; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; A0FGR8; -.
DR PhosphoSitePlus; A0FGR8; -.
DR SwissPalm; A0FGR8; -.
DR BioMuta; ESYT2; -.
DR EPD; A0FGR8; -.
DR jPOST; A0FGR8; -.
DR MassIVE; A0FGR8; -.
DR MaxQB; A0FGR8; -.
DR PaxDb; A0FGR8; -.
DR PeptideAtlas; A0FGR8; -.
DR PRIDE; A0FGR8; -.
DR ProteomicsDB; 30; -. [A0FGR8-1]
DR ProteomicsDB; 31; -. [A0FGR8-2]
DR ProteomicsDB; 32; -. [A0FGR8-4]
DR ProteomicsDB; 33; -. [A0FGR8-5]
DR ProteomicsDB; 34; -. [A0FGR8-6]
DR Antibodypedia; 950; 109 antibodies from 21 providers.
DR DNASU; 57488; -.
DR Ensembl; ENST00000652148.1; ENSP00000499020.1; ENSG00000117868.18. [A0FGR8-2]
DR GeneID; 57488; -.
DR KEGG; hsa:57488; -.
DR UCSC; uc003wob.2; human. [A0FGR8-1]
DR CTD; 57488; -.
DR DisGeNET; 57488; -.
DR GeneCards; ESYT2; -.
DR HGNC; HGNC:22211; ESYT2.
DR HPA; ENSG00000117868; Low tissue specificity.
DR neXtProt; NX_A0FGR8; -.
DR OpenTargets; ENSG00000117868; -.
DR PharmGKB; PA165617947; -.
DR VEuPathDB; HostDB:ENSG00000117868; -.
DR eggNOG; KOG1012; Eukaryota.
DR GeneTree; ENSGT00940000156086; -.
DR InParanoid; A0FGR8; -.
DR OrthoDB; 52746at2759; -.
DR PhylomeDB; A0FGR8; -.
DR TreeFam; TF324255; -.
DR PathwayCommons; A0FGR8; -.
DR Reactome; R-HSA-1660662; Glycosphingolipid metabolism.
DR SignaLink; A0FGR8; -.
DR BioGRID-ORCS; 57488; 12 hits in 1078 CRISPR screens.
DR ChiTaRS; ESYT2; human.
DR EvolutionaryTrace; A0FGR8; -.
DR GeneWiki; FAM62B; -.
DR GenomeRNAi; 57488; -.
DR Pharos; A0FGR8; Tbio.
DR PRO; PR:A0FGR8; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; A0FGR8; protein.
DR Bgee; ENSG00000117868; Expressed in layer of synovial tissue and 189 other tissues.
DR ExpressionAtlas; A0FGR8; baseline and differential.
DR Genevisible; A0FGR8; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0140268; C:endoplasmic reticulum-plasma membrane contact site; IDA:UniProtKB.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IMP:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:FlyBase.
DR GO; GO:0031227; C:intrinsic component of endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0044232; C:organelle membrane contact site; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0005544; F:calcium-dependent phospholipid binding; IDA:FlyBase.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0031210; F:phosphatidylcholine binding; IDA:UniProtKB.
DR GO; GO:0008429; F:phosphatidylethanolamine binding; IDA:UniProtKB.
DR GO; GO:0035091; F:phosphatidylinositol binding; IDA:UniProtKB.
DR GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
DR GO; GO:0061817; P:endoplasmic reticulum-plasma membrane tethering; IEA:InterPro.
DR GO; GO:0006869; P:lipid transport; IEA:UniProtKB-KW.
DR CDD; cd08391; C2A_C2C_Synaptotagmin_like; 1.
DR CDD; cd04050; C2B_Synaptotagmin-like; 1.
DR CDD; cd04030; C2C_KIAA1228; 1.
DR Gene3D; 2.60.40.150; -; 3.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR037752; C2C_KIAA1228.
DR InterPro; IPR037733; Ext_Synaptotagmin_C2A.
DR InterPro; IPR037749; Ext_Synaptotagmin_C2B.
DR InterPro; IPR031468; SMP_LBD.
DR InterPro; IPR039010; Synaptotagmin_SMP.
DR Pfam; PF00168; C2; 3.
DR Pfam; PF17047; SMP_LBD; 1.
DR SMART; SM00239; C2; 3.
DR SUPFAM; SSF49562; SSF49562; 3.
DR PROSITE; PS50004; C2; 3.
DR PROSITE; PS51847; SMP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Calcium; Cell membrane; Endocytosis;
KW Endoplasmic reticulum; Lipid transport; Lipid-binding; Membrane;
KW Metal-binding; Phosphoprotein; Reference proteome; Repeat; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..921
FT /note="Extended synaptotagmin-2"
FT /id="PRO_0000278258"
FT TOPO_DOM 1..103
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 104..124
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 125..127
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 128..148
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 149..921
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 191..370
FT /note="SMP-LTD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01194,
FT ECO:0000269|PubMed:24847877"
FT DOMAIN 369..489
FT /note="C2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 514..639
FT /note="C2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 786..908
FT /note="C2 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT REGION 1..103
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 660..754
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 833..840
FT /note="Required for phosphatidylinositol 4,5-bisphosphate-
FT dependent location at the cell membrane"
FT COMPBIAS 22..36
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 56..71
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 660..686
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 687..707
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 400
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:24373768"
FT BINDING 401
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:24373768"
FT BINDING 401
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:24373768"
FT BINDING 413
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:24373768"
FT BINDING 460
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:24373768"
FT BINDING 460
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:24373768"
FT BINDING 461
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:24373768"
FT BINDING 462
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:24373768"
FT BINDING 462
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:24373768"
FT BINDING 462
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:24373768"
FT BINDING 464
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:24373768"
FT BINDING 466
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:24373768"
FT BINDING 467
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:24373768"
FT MOD_RES 691
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 693
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 705
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 736
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 738
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3TZZ7"
FT MOD_RES 739
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 743
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17924679,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 748
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 755
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332"
FT MOD_RES 758
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692"
FT MOD_RES 761
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT VAR_SEQ 1..593
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_023236"
FT VAR_SEQ 1..204
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_023238"
FT VAR_SEQ 1..97
FT /note="MTANRDAALSSHRHPGCAQRPRTPTFASSSQRRSAFGFDDGNFPGLGERSHA
FT PGSRLGARRRAKTARGLRGHRQRGAGAGLSRPGSARAPSPPRPGG -> MTPPSRAEAG
FT VRRSRVPSEGRWRGAEPPGISASTQPASAGRAARHCGAMSGARGEGPEAGAGGAGGRAA
FT (in isoform 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_023239"
FT VAR_SEQ 550
FT /note="S -> SNPLEFNPDVLKKTAVQRALKS (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_038324"
FT VAR_SEQ 594..603
FT /note="NPKRQDLEVE -> MPVLPPCVLQ (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_023240"
FT VAR_SEQ 706..731
FT /note="PVIGGSDKPGMEEKAQPPEAGPQGLH -> SQSRSRPPASPRTSRCPSPPRS
FT CGKG (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_023241"
FT VAR_SEQ 732..921
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_023242"
FT VARIANT 210
FT /note="C -> S (in dbSNP:rs13233513)"
FT /id="VAR_030725"
FT VARIANT 638
FT /note="S -> G (in dbSNP:rs2305473)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_030726"
FT MUTAGEN 401
FT /note="D->A: Abolishes calcium binding; when associated
FT with A-413."
FT /evidence="ECO:0000269|PubMed:24373768"
FT MUTAGEN 413
FT /note="D->A: Abolishes calcium binding; when associated
FT with A-401."
FT /evidence="ECO:0000269|PubMed:24373768"
FT MUTAGEN 413
FT /note="D->N: Strongly reduces calcium binding."
FT /evidence="ECO:0000269|PubMed:24373768"
FT MUTAGEN 466
FT /note="D->A: Impairs binding of the third calcium ion, but
FT has no effect on the binding of the other two calcium
FT ions."
FT /evidence="ECO:0000269|PubMed:24373768"
FT MUTAGEN 833..840
FT /note="KRRSGRRK->AAASGAAA: Abolishes location at the cell
FT membrane."
FT /evidence="ECO:0000269|PubMed:23791178"
FT CONFLICT 141
FT /note="L -> V (in Ref. 7; CAH10642)"
FT /evidence="ECO:0000305"
FT CONFLICT 612
FT /note="S -> P (in Ref. 3; BAC85769)"
FT /evidence="ECO:0000305"
FT CONFLICT 615
FT /note="N -> S (in Ref. 3; BAC86489)"
FT /evidence="ECO:0000305"
FT CONFLICT 795
FT /note="R -> Q (in Ref. 3; BAC85769)"
FT /evidence="ECO:0000305"
FT HELIX 196..219
FT /evidence="ECO:0007829|PDB:4P42"
FT HELIX 221..226
FT /evidence="ECO:0007829|PDB:4P42"
FT HELIX 230..232
FT /evidence="ECO:0007829|PDB:4P42"
FT STRAND 235..241
FT /evidence="ECO:0007829|PDB:4P42"
FT STRAND 248..255
FT /evidence="ECO:0007829|PDB:4P42"
FT STRAND 264..282
FT /evidence="ECO:0007829|PDB:4P42"
FT TURN 283..286
FT /evidence="ECO:0007829|PDB:4P42"
FT STRAND 287..304
FT /evidence="ECO:0007829|PDB:4P42"
FT STRAND 316..323
FT /evidence="ECO:0007829|PDB:4P42"
FT STRAND 326..333
FT /evidence="ECO:0007829|PDB:4P42"
FT HELIX 334..337
FT /evidence="ECO:0007829|PDB:4P42"
FT TURN 341..345
FT /evidence="ECO:0007829|PDB:4P42"
FT HELIX 348..358
FT /evidence="ECO:0007829|PDB:4P42"
FT STRAND 365..370
FT /evidence="ECO:0007829|PDB:4P42"
FT HELIX 372..379
FT /evidence="ECO:0007829|PDB:4P42"
FT STRAND 384..396
FT /evidence="ECO:0007829|PDB:4NPJ"
FT TURN 405..407
FT /evidence="ECO:0007829|PDB:4P42"
FT STRAND 414..420
FT /evidence="ECO:0007829|PDB:4NPJ"
FT STRAND 423..426
FT /evidence="ECO:0007829|PDB:4NPJ"
FT STRAND 437..446
FT /evidence="ECO:0007829|PDB:4NPJ"
FT STRAND 453..460
FT /evidence="ECO:0007829|PDB:4NPJ"
FT STRAND 463..465
FT /evidence="ECO:0007829|PDB:4NPJ"
FT STRAND 467..475
FT /evidence="ECO:0007829|PDB:4NPJ"
FT HELIX 476..482
FT /evidence="ECO:0007829|PDB:4NPJ"
FT STRAND 483..490
FT /evidence="ECO:0007829|PDB:4NPJ"
FT STRAND 494..496
FT /evidence="ECO:0007829|PDB:4NPJ"
FT STRAND 498..512
FT /evidence="ECO:0007829|PDB:4NPJ"
FT HELIX 515..524
FT /evidence="ECO:0007829|PDB:4NPJ"
FT STRAND 535..547
FT /evidence="ECO:0007829|PDB:4NPJ"
FT STRAND 552..554
FT /evidence="ECO:0007829|PDB:4P42"
FT STRAND 560..566
FT /evidence="ECO:0007829|PDB:4NPJ"
FT STRAND 569..572
FT /evidence="ECO:0007829|PDB:4NPJ"
FT STRAND 583..593
FT /evidence="ECO:0007829|PDB:4NPJ"
FT TURN 595..597
FT /evidence="ECO:0007829|PDB:4NPJ"
FT STRAND 599..606
FT /evidence="ECO:0007829|PDB:4NPJ"
FT TURN 607..609
FT /evidence="ECO:0007829|PDB:4NPJ"
FT STRAND 612..619
FT /evidence="ECO:0007829|PDB:4NPJ"
FT HELIX 621..624
FT /evidence="ECO:0007829|PDB:4NPJ"
FT HELIX 627..629
FT /evidence="ECO:0007829|PDB:4NPJ"
FT STRAND 630..636
FT /evidence="ECO:0007829|PDB:4NPJ"
FT STRAND 638..640
FT /evidence="ECO:0007829|PDB:4NPJ"
FT STRAND 645..656
FT /evidence="ECO:0007829|PDB:4NPJ"
FT STRAND 789..797
FT /evidence="ECO:0007829|PDB:2DMG"
FT TURN 798..801
FT /evidence="ECO:0007829|PDB:2DMG"
FT STRAND 802..811
FT /evidence="ECO:0007829|PDB:2DMG"
FT STRAND 823..831
FT /evidence="ECO:0007829|PDB:2DMG"
FT STRAND 835..837
FT /evidence="ECO:0007829|PDB:2DMG"
FT STRAND 851..858
FT /evidence="ECO:0007829|PDB:2DMG"
FT HELIX 862..867
FT /evidence="ECO:0007829|PDB:2DMG"
FT STRAND 869..876
FT /evidence="ECO:0007829|PDB:2DMG"
FT STRAND 889..894
FT /evidence="ECO:0007829|PDB:2DMG"
FT TURN 899..902
FT /evidence="ECO:0007829|PDB:2DMG"
SQ SEQUENCE 921 AA; 102357 MW; D57F1BD9BB0A0C8A CRC64;
MTANRDAALS SHRHPGCAQR PRTPTFASSS QRRSAFGFDD GNFPGLGERS HAPGSRLGAR
RRAKTARGLR GHRQRGAGAG LSRPGSARAP SPPRPGGPEN PGGVLSVELP GLLAQLARSF
ALLLPVYALG YLGLSFSWVL LALALLAWCR RSRGLKALRL CRALALLEDE ERVVRLGVRA
CDLPAWVHFP DTERAEWLNK TVKHMWPFIC QFIEKLFRET IEPAVRGANT HLSTFSFTKV
DVGQQPLRIN GVKVYTENVD KRQIILDLQI SFVGNCEIDL EIKRYFCRAG VKSIQIHGTM
RVILEPLIGD MPLVGALSIF FLRKPLLEIN WTGLTNLLDV PGLNGLSDTI ILDIISNYLV
LPNRITVPLV SEVQIAQLRF PVPKGVLRIH FIEAQDLQGK DTYLKGLVKG KSDPYGIIRV
GNQIFQSRVI KENLSPKWNE VYEALVYEHP GQELEIELFD EDPDKDDFLG SLMIDLIEVE
KERLLDEWFT LDEVPKGKLH LRLEWLTLMP NASNLDKVLT DIKADKDQAN DGLSSALLIL
YLDSARNLPS GKKISSNPNP VVQMSVGHKA QESKIRYKTN EPVWEENFTF FIHNPKRQDL
EVEVRDEQHQ CSLGNLKVPL SQLLTSEDMT VSQRFQLSNS GPNSTIKMKI ALRVLHLEKR
ERPPDHQHSA QVKRPSVSKE GRKTSIKSHM SGSPGPGGSN TAPSTPVIGG SDKPGMEEKA
QPPEAGPQGL HDLGRSSSSL LASPGHISVK EPTPSIASDI SLPIATQELR QRLRQLENGT
TLGQSPLGQI QLTIRHSSQR NKLIVVVHAC RNLIAFSEDG SDPYVRMYLL PDKRRSGRRK
THVSKKTLNP VFDQSFDFSV SLPEVQRRTL DVAVKNSGGF LSKDKGLLGK VLVALASEEL
AKGWTQWYDL TEDGTRPQAM T
