TNPO3_HUMAN
ID TNPO3_HUMAN Reviewed; 923 AA.
AC Q9Y5L0; A4D1K9; C9IZM0; Q6NUM1; Q96G71; Q96GU9; Q9Y3R2;
DT 16-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 15-JAN-2008, sequence version 3.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=Transportin-3 {ECO:0000303|PubMed:23667635};
DE AltName: Full=Importin-12;
DE Short=Imp12;
DE AltName: Full=Transportin-SR {ECO:0000303|PubMed:10366588, ECO:0000303|PubMed:18722123};
DE Short=TRN-SR {ECO:0000303|PubMed:10366588};
GN Name=TNPO3 {ECO:0000303|PubMed:23667635, ECO:0000312|HGNC:HGNC:17103};
GN Synonyms=IPO12;
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, AND INTERACTION WITH
RP SFRS1 AND SFRS2.
RX PubMed=10366588; DOI=10.1083/jcb.145.6.1145;
RA Kataoka N., Bachorik J.L., Dreyfuss G.;
RT "Transportin-SR, a nuclear import receptor for SR proteins.";
RL J. Cell Biol. 145:1145-1152(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA Kutay U., Izaurralde E., Hartmann E., Goerlich D.;
RT "A human homologue of yeast Mtr10p and its role in nuclear protein
RT import.";
RL Submitted (APR-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC TISSUE=Colon;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.;
RL Submitted (JUL-2006) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [5]
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 586-923 (ISOFORM 3).
RC TISSUE=Ovary;
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 [7]
RP FUNCTION, INTERACTION WITH SFRS1, AND SUBCELLULAR LOCATION.
RX PubMed=10713112; DOI=10.1074/jbc.275.11.7950;
RA Lai M.-C., Lin R.-I., Huang S.-Y., Tsai C.-W., Tarn W.-Y.;
RT "A human importin-beta family protein, transportin-SR2, interacts with the
RT phosphorylated RS domain of SR proteins.";
RL J. Biol. Chem. 275:7950-7957(2000).
RN [8]
RP FUNCTION, AND INTERACTION WITH SFRS1 AND NUP62.
RX PubMed=11517331; DOI=10.1073/pnas.181354098;
RA Lai M.-C., Lin R.-I., Tarn W.-Y.;
RT "Transportin-SR2 mediates nuclear import of phosphorylated SR proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:10154-10159(2001).
RN [9]
RP FUNCTION, AND INTERACTION WITH RBM4.
RX PubMed=12628928; DOI=10.1093/emboj/cdg126;
RA Lai M.-C., Kuo H.-W., Chang W.-C., Tarn W.-Y.;
RT "A novel splicing regulator shares a nuclear import pathway with SR
RT proteins.";
RL EMBO J. 22:1359-1369(2003).
RN [10]
RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH THE HIV-1
RP PRE-INTEGRATION COMPLEX (MICROBIAL INFECTION).
RX PubMed=18722123; DOI=10.1016/j.cub.2008.07.079;
RA Christ F., Thys W., De Rijck J., Gijsbers R., Albanese A., Arosio D.,
RA Emiliani S., Rain J.C., Benarous R., Cereseto A., Debyser Z.;
RT "Transportin-SR2 imports HIV into the nucleus.";
RL Curr. Biol. 18:1192-1202(2008).
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-896, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [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 [13]
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 [14]
RP FUNCTION (MICROBIAL INFECTION).
RX PubMed=21901095; DOI=10.1371/journal.ppat.1002194;
RA Zhou L., Sokolskaja E., Jolly C., James W., Cowley S.A., Fassati A.;
RT "Transportin 3 promotes a nuclear maturation step required for efficient
RT HIV-1 integration.";
RL PLoS Pathog. 7:E1002194-E1002194(2011).
RN [15]
RP FUNCTION (MICROBIAL INFECTION).
RX PubMed=22398280; DOI=10.1128/jvi.00451-12;
RA Valle-Casuso J.C., Di Nunzio F., Yang Y., Reszka N., Lienlaf M., Arhel N.,
RA Perez P., Brass A.L., Diaz-Griffero F.;
RT "TNPO3 is required for HIV-1 replication after nuclear import but prior to
RT integration and binds the HIV-1 core.";
RL J. Virol. 86:5931-5936(2012).
RN [16]
RP FUNCTION, INTERACTION WITH RAN, AND MUTAGENESIS OF 145-GLU--GLU-153.
RX PubMed=23878195; DOI=10.1074/jbc.m113.484345;
RA Taltynov O., Demeulemeester J., Christ F., De Houwer S., Tsirkone V.G.,
RA Gerard M., Weeks S.D., Strelkov S.V., Debyser Z.;
RT "Interaction of transportin-SR2 with Ras-related nuclear protein (Ran)
RT GTPase.";
RL J. Biol. Chem. 288:25603-25613(2013).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-74, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=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 [18]
RP INVOLVEMENT IN LGMDD2, TISSUE SPECIFICITY, AND VARIANTS LGMDD2 PRO-818 AND
RP CYS-SER-HIS-SER-CYS-THR-VAL-PRO-VAL-THR-GLN-GLU-CYS-LEU-PHE-923 EXT.
RX PubMed=23667635; DOI=10.1371/journal.pone.0063536;
RA Torella A., Fanin M., Mutarelli M., Peterle E., Del Vecchio Blanco F.,
RA Rispoli R., Savarese M., Garofalo A., Piluso G., Morandi L., Ricci G.,
RA Siciliano G., Angelini C., Nigro V.;
RT "Next-generation sequencing identifies transportin 3 as the causative gene
RT for LGMD1F.";
RL PLoS ONE 8:E63536-E63536(2013).
RN [19]
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 [20]
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 [21]
RP INTERACTION WITH HIV-1 INTEGRASE (MICROBIAL INFECTION).
RX PubMed=28356354; DOI=10.1074/jbc.m117.777029;
RA Tsirkone V.G., Blokken J., De Wit F., Breemans J., De Houwer S.,
RA Debyser Z., Christ F., Strelkov S.V.;
RT "N-terminal half of transportin SR2 interacts with HIV integrase.";
RL J. Biol. Chem. 292:9699-9710(2017).
RN [22]
RP FUNCTION (MICROBIAL INFECTION).
RX PubMed=29329553; DOI=10.1186/s12977-018-0389-2;
RA Demeulemeester J., Blokken J., De Houwer S., Dirix L., Klaassen H.,
RA Marchand A., Chaltin P., Christ F., Debyser Z.;
RT "Inhibitors of the integrase-transportin-SR2 interaction block HIV nuclear
RT import.";
RL Retrovirology 15:5-5(2018).
RN [23]
RP FUNCTION, POLYMORPHISM, VARIANT LGMDD2
RP CYS-SER-HIS-SER-CYS-THR-VAL-PRO-VAL-THR-GLN-GLU-CYS-LEU-PHE-923 EXT, AND
RP CHARACTERIZATION OF VARIANT LGMDD2
RP CYS-SER-HIS-SER-CYS-THR-VAL-PRO-VAL-THR-GLN-GLU-CYS-LEU-PHE-923 EXT.
RX PubMed=31465518; DOI=10.1371/journal.ppat.1007958;
RA Rodriguez-Mora S., De Wit F., Garcia-Perez J., Bermejo M.,
RA Lopez-Huertas M.R., Mateos E., Marti P., Rocha S., Vigon L., Christ F.,
RA Debyser Z., Vilchez J.J., Coiras M., Alcami J.;
RT "The mutation of Transportin 3 gene that causes limb girdle muscular
RT dystrophy 1F induces protection against HIV-1 infection.";
RL PLoS Pathog. 15:E1007958-E1007958(2019).
RN [24] {ECO:0007744|PDB:4OL0}
RP X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 3-923 IN COMPLEX WITH RAN.
RX PubMed=24915079; DOI=10.1107/s2053230x14009492;
RA Tsirkone V.G., Beutels K.G., Demeulemeester J., Debyser Z., Christ F.,
RA Strelkov S.V.;
RT "Structure of transportin SR2, a karyopherin involved in human disease, in
RT complex with Ran.";
RL Acta Crystallogr. F 70:723-729(2014).
RN [25] {ECO:0007744|PDB:4C0O, ECO:0007744|PDB:4C0P, ECO:0007744|PDB:4C0Q}
RP X-RAY CRYSTALLOGRAPHY (2.56 ANGSTROMS) IN COMPLEX WITH RAN AND SFRS1,
RP FUNCTION, INTERACTION WITH CPSF6; RAN AND SFRS1, AND MUTAGENESIS OF
RP ARG-620; GLU-660; ARG-664; ARG-667; ARG-671; TYR-702; ASP-750; ASP-751;
RP ARG-754 AND ARG-758.
RX PubMed=24449914; DOI=10.1073/pnas.1320755111;
RA Maertens G.N., Cook N.J., Wang W., Hare S., Gupta S.S., Oztop I., Lee K.,
RA Pye V.E., Cosnefroy O., Snijders A.P., KewalRamani V.N., Fassati A.,
RA Engelman A., Cherepanov P.;
RT "Structural basis for nuclear import of splicing factors by human
RT Transportin 3.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:2728-2733(2014).
RN [26] {ECO:0007744|PDB:6GX9}
RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) IN COMPLEX WITH CPSF6, AND FUNCTION.
RX PubMed=30916345; DOI=10.1093/nar/gkz206;
RA Jang S., Cook N.J., Pye V.E., Bedwell G.J., Dudek A.M., Singh P.K.,
RA Cherepanov P., Engelman A.N.;
RT "Differential role for phosphorylation in alternative polyadenylation
RT function versus nuclear import of SR-like protein CPSF6.";
RL Nucleic Acids Res. 47:4663-4683(2019).
RN [27]
RP VARIANT LGMDD2
RP CYS-SER-HIS-SER-CYS-THR-VAL-PRO-VAL-THR-GLN-GLU-CYS-LEU-PHE-923 EXT,
RP CHARACTERIZATION OF VARIANT LGMDD2
RP CYS-SER-HIS-SER-CYS-THR-VAL-PRO-VAL-THR-GLN-GLU-CYS-LEU-PHE-923 EXT, AND
RP SUBCELLULAR LOCATION.
RX PubMed=23543484; DOI=10.1093/brain/awt074;
RA Melia M.J., Kubota A., Ortolano S., Vilchez J.J., Gamez J., Tanji K.,
RA Bonilla E., Palenzuela L., Fernandez-Cadenas I., Pristoupilova A.,
RA Garcia-Arumi E., Andreu A.L., Navarro C., Hirano M., Marti R.;
RT "Limb-girdle muscular dystrophy 1F is caused by a microdeletion in the
RT transportin 3 gene.";
RL Brain 136:1508-1517(2013).
RN [28]
RP VARIANT LGMDD2 ARG-923 DELINS
RP ASP-SER-SER-HIS-SER-CYS-THR-VAL-PRO-VAL-THR-GLN-GLU-CYS-LEU-PHE.
RX PubMed=31071488; DOI=10.1016/j.ejmg.2019.05.001;
RA Pal E., Zima J., Hadzsiev K., Ito Y.A., Hartley T., Boycott K.M.,
RA Melegh B.;
RT "A novel pathogenic variant in TNPO3 in a Hungarian family with limb-girdle
RT muscular dystrophy 1F.";
RL Eur. J. Med. Genet. 62:103662-103662(2019).
RN [29]
RP VARIANT LGMDD2 920-ARG--ARG-923
RP DELINS GLY-CYS-PHE-ASP-SER-SER-HIS-SER-CYS-THR-VAL-PRO-VAL-THR-GLN-GLU-CYS-
RP LEU-PHE, AND SUBCELLULAR LOCATION.
RX PubMed=31192305; DOI=10.1212/nxg.0000000000000337;
RA Vihola A., Palmio J., Danielsson O., Penttilae S., Louiselle D.,
RA Pittman S., Weihl C., Udd B.;
RT "Novel mutation in TNPO3 causes congenital limb-girdle myopathy with slow
RT progression.";
RL Neurol. Genet. 5:E337-E337(2019).
CC -!- FUNCTION: Importin, which transports target proteins into the nucleus
CC (PubMed:10366588, PubMed:10713112, PubMed:11517331, PubMed:12628928,
CC PubMed:24449914). Specifically mediates the nuclear import of splicing
CC factor serine/arginine (SR) proteins, such as RBM4, SFRS1 and SFRS2, by
CC recognizing phosphorylated SR domains (PubMed:10366588,
CC PubMed:10713112, PubMed:11517331, PubMed:12628928, PubMed:24449914).
CC Also mediates the nuclear import of serine/arginine (SR) protein CPSF6,
CC independently of CPSF6 phosphorylation (PubMed:30916345,
CC PubMed:31465518). The nuclear import process is regulated by the small
CC GTPase Ran that partitions between cytoplasm and nucleus in the
CC predominantly GDP- and GTP-bound form, respectively (PubMed:23878195,
CC PubMed:24449914). Importin associates with target cargo proteins in the
CC cytoplasm, and the competitive binding of GTP-bound Ran induces the
CC release of cargos in the nucleus (PubMed:23878195, PubMed:24449914).
CC {ECO:0000269|PubMed:10366588, ECO:0000269|PubMed:10713112,
CC ECO:0000269|PubMed:11517331, ECO:0000269|PubMed:12628928,
CC ECO:0000269|PubMed:23878195, ECO:0000269|PubMed:24449914,
CC ECO:0000269|PubMed:30916345, ECO:0000269|PubMed:31465518}.
CC -!- FUNCTION: (Microbial infection) Involved in immunodeficiency virus
CC (HIV-1) infection by importing the pre-integration complex (PIC) into
CC the nucleus (PubMed:18722123, PubMed:21901095, PubMed:22398280,
CC PubMed:29329553). Required for a nuclear maturation step of HIV-1 prior
CC to integration (PubMed:21901095, PubMed:22398280).
CC {ECO:0000269|PubMed:18722123, ECO:0000269|PubMed:21901095,
CC ECO:0000269|PubMed:22398280, ECO:0000269|PubMed:29329553}.
CC -!- SUBUNIT: Interacts with (GTP-bound) Ran (PubMed:23878195,
CC PubMed:24915079, PubMed:24449914). Interacts with (phosphorylated)
CC SFRS1 and SFRS2; leading to their nuclear import (PubMed:10366588,
CC PubMed:10713112, PubMed:11517331). Interacts with NUP62
CC (PubMed:11517331, PubMed:24449914). Interacts with RBM4
CC (PubMed:12628928). Interacts with CPSF6, promoting its nuclear import
CC (PubMed:24449914). {ECO:0000269|PubMed:10366588,
CC ECO:0000269|PubMed:10713112, ECO:0000269|PubMed:11517331,
CC ECO:0000269|PubMed:12628928, ECO:0000269|PubMed:23878195,
CC ECO:0000269|PubMed:24449914, ECO:0000269|PubMed:24915079}.
CC -!- SUBUNIT: (Microbial infection) Interacts with the HIV-1 pre-integration
CC complex (PIC), which is composed of viral genome, matrix protein, Vpr
CC and integrase (PubMed:18722123, PubMed:29329553). Interacts with HIV-1
CC integrase protein; the interaction is direct (PubMed:29329553).
CC {ECO:0000269|PubMed:18722123, ECO:0000269|PubMed:29329553}.
CC -!- INTERACTION:
CC Q9Y5L0; Q13867: BLMH; NbExp=3; IntAct=EBI-1042571, EBI-718504;
CC Q9Y5L0; Q13554-3: CAMK2B; NbExp=3; IntAct=EBI-1042571, EBI-11523526;
CC Q9Y5L0; Q13557-8: CAMK2D; NbExp=3; IntAct=EBI-1042571, EBI-11534483;
CC Q9Y5L0; Q13555-5: CAMK2G; NbExp=3; IntAct=EBI-1042571, EBI-12020154;
CC Q9Y5L0; Q16740: CLPP; NbExp=3; IntAct=EBI-1042571, EBI-1056029;
CC Q9Y5L0; O75521: ECI2; NbExp=3; IntAct=EBI-1042571, EBI-2512024;
CC Q9Y5L0; P30793: GCH1; NbExp=3; IntAct=EBI-1042571, EBI-958183;
CC Q9Y5L0; Q8NDH6-2: ICA1L; NbExp=3; IntAct=EBI-1042571, EBI-12141931;
CC Q9Y5L0; O95678: KRT75; NbExp=3; IntAct=EBI-1042571, EBI-2949715;
CC Q9Y5L0; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-1042571, EBI-10171774;
CC Q9Y5L0; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-1042571, EBI-16439278;
CC Q9Y5L0; P15531: NME1; NbExp=3; IntAct=EBI-1042571, EBI-741141;
CC Q9Y5L0; Q8WVI7: PPP1R1C; NbExp=3; IntAct=EBI-1042571, EBI-23791378;
CC Q9Y5L0; Q16385-2: SSX2B; NbExp=3; IntAct=EBI-1042571, EBI-17564583;
CC Q9Y5L0; Q9Y5L0: TNPO3; NbExp=3; IntAct=EBI-1042571, EBI-1042571;
CC Q9Y5L0; PRO_0000042447 [P04585]: gag-pol; Xeno; NbExp=6; IntAct=EBI-1042571, EBI-9872653;
CC -!- SUBCELLULAR LOCATION: Nucleus envelope {ECO:0000269|PubMed:31192305,
CC ECO:0000305|PubMed:10713112, ECO:0000305|PubMed:23543484}. Cytoplasm
CC {ECO:0000269|PubMed:10713112}. Note=Localizes to the nuclear envelope
CC and annulate lamellae, which consists in stacks of endoplasmic
CC reticulum membranes containing a high density of nuclear pores.
CC {ECO:0000269|PubMed:31192305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=2; Synonyms=Transportin-SR2 {ECO:0000303|PubMed:10713112,
CC ECO:0000303|PubMed:11517331, ECO:0000303|PubMed:18722123}, TRN-SR2
CC {ECO:0000303|PubMed:10713112, ECO:0000303|PubMed:11517331,
CC ECO:0000303|PubMed:18722123};
CC IsoId=Q9Y5L0-2; Sequence=Displayed;
CC Name=1;
CC IsoId=Q9Y5L0-1; Sequence=VSP_030174;
CC Name=3;
CC IsoId=Q9Y5L0-3; Sequence=VSP_011178;
CC Name=4;
CC IsoId=Q9Y5L0-5; Sequence=VSP_045494;
CC -!- TISSUE SPECIFICITY: Expressed in skeletal muscle.
CC {ECO:0000269|PubMed:23667635}.
CC -!- POLYMORPHISM: Variations in TNPO3 are associated with resistance or
CC susceptibility to immunodeficiency virus type 1 (resistance or
CC susceptibility to HIV-1) [MIM:609423] (PubMed:31465518). A variation
CC that causes LGMDD2 muscular dystrophy induces protection against HIV-1
CC infection (PubMed:31465518). {ECO:0000269|PubMed:31465518}.
CC -!- DISEASE: Muscular dystrophy, limb-girdle, autosomal dominant 2 (LGMDD2)
CC [MIM:608423]: An autosomal dominant myopathy characterized by proximal
CC muscle weakness primarily affecting the lower limbs, but also affecting
CC the upper limbs in most patients. Affected individuals also have distal
CC muscle weakness of the hands and lower leg muscles. The disease has
CC generally a benign clinical course but some individuals with childhood
CC or juvenile onset manifest severe widespread myopathy, leading to
CC wheelchair dependency and respiratory insufficiency. Muscle biopsy
CC shows dystrophic changes with abnormal nuclei, rimmed vacuoles, and
CC filamentous inclusions. {ECO:0000269|PubMed:23543484,
CC ECO:0000269|PubMed:23667635, ECO:0000269|PubMed:31071488,
CC ECO:0000269|PubMed:31192305, ECO:0000269|PubMed:31465518}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD38537.1; Type=Frameshift; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
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DR EMBL; AF145029; AAD38537.1; ALT_FRAME; mRNA.
DR EMBL; AJ133769; CAB42643.1; -; mRNA.
DR EMBL; AK225999; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AC018639; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC025594; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH236950; EAL24106.1; -; Genomic_DNA.
DR EMBL; BC009221; AAH09221.2; -; mRNA.
DR CCDS; CCDS55162.1; -. [Q9Y5L0-5]
DR CCDS; CCDS5809.1; -. [Q9Y5L0-2]
DR RefSeq; NP_001177957.2; NM_001191028.2. [Q9Y5L0-5]
DR RefSeq; NP_036602.1; NM_012470.3. [Q9Y5L0-2]
DR PDB; 4C0O; X-ray; 2.56 A; A/B=1-923.
DR PDB; 4C0P; X-ray; 2.95 A; A/B/C/D=1-923.
DR PDB; 4C0Q; X-ray; 3.42 A; A/B=1-923.
DR PDB; 4OL0; X-ray; 2.90 A; B=3-923.
DR PDB; 6GX9; X-ray; 2.70 A; A/B=1-923.
DR PDBsum; 4C0O; -.
DR PDBsum; 4C0P; -.
DR PDBsum; 4C0Q; -.
DR PDBsum; 4OL0; -.
DR PDBsum; 6GX9; -.
DR AlphaFoldDB; Q9Y5L0; -.
DR SMR; Q9Y5L0; -.
DR BioGRID; 117080; 204.
DR IntAct; Q9Y5L0; 76.
DR MINT; Q9Y5L0; -.
DR STRING; 9606.ENSP00000265388; -.
DR GlyGen; Q9Y5L0; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9Y5L0; -.
DR PhosphoSitePlus; Q9Y5L0; -.
DR SwissPalm; Q9Y5L0; -.
DR BioMuta; TNPO3; -.
DR DMDM; 166215035; -.
DR EPD; Q9Y5L0; -.
DR jPOST; Q9Y5L0; -.
DR MassIVE; Q9Y5L0; -.
DR MaxQB; Q9Y5L0; -.
DR PaxDb; Q9Y5L0; -.
DR PeptideAtlas; Q9Y5L0; -.
DR PRIDE; Q9Y5L0; -.
DR ProteomicsDB; 7822; -.
DR ProteomicsDB; 86436; -. [Q9Y5L0-2]
DR ProteomicsDB; 86437; -. [Q9Y5L0-1]
DR ProteomicsDB; 86438; -. [Q9Y5L0-3]
DR Antibodypedia; 17836; 152 antibodies from 30 providers.
DR DNASU; 23534; -.
DR Ensembl; ENST00000265388.10; ENSP00000265388.5; ENSG00000064419.14. [Q9Y5L0-2]
DR Ensembl; ENST00000471234.5; ENSP00000418646.1; ENSG00000064419.14. [Q9Y5L0-5]
DR GeneID; 23534; -.
DR KEGG; hsa:23534; -.
DR MANE-Select; ENST00000265388.10; ENSP00000265388.5; NM_012470.4; NP_036602.1.
DR UCSC; uc003vol.3; human. [Q9Y5L0-2]
DR CTD; 23534; -.
DR DisGeNET; 23534; -.
DR GeneCards; TNPO3; -.
DR HGNC; HGNC:17103; TNPO3.
DR HPA; ENSG00000064419; Low tissue specificity.
DR MalaCards; TNPO3; -.
DR MIM; 608423; phenotype.
DR MIM; 609423; phenotype.
DR MIM; 610032; gene.
DR neXtProt; NX_Q9Y5L0; -.
DR OpenTargets; ENSG00000064419; -.
DR Orphanet; 186; Primary biliary cholangitis.
DR Orphanet; 55595; TNP03-related limb-girdle muscular dystrophy D2.
DR PharmGKB; PA134888159; -.
DR VEuPathDB; HostDB:ENSG00000064419; -.
DR eggNOG; KOG2081; Eukaryota.
DR GeneTree; ENSGT00530000063347; -.
DR HOGENOM; CLU_005996_0_2_1; -.
DR InParanoid; Q9Y5L0; -.
DR OMA; KTINYCR; -.
DR PhylomeDB; Q9Y5L0; -.
DR TreeFam; TF314539; -.
DR PathwayCommons; Q9Y5L0; -.
DR SignaLink; Q9Y5L0; -.
DR BioGRID-ORCS; 23534; 764 hits in 1090 CRISPR screens.
DR ChiTaRS; TNPO3; human.
DR GeneWiki; Transportin-3; -.
DR GenomeRNAi; 23534; -.
DR Pharos; Q9Y5L0; Tbio.
DR PRO; PR:Q9Y5L0; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q9Y5L0; protein.
DR Bgee; ENSG00000064419; Expressed in secondary oocyte and 220 other tissues.
DR ExpressionAtlas; Q9Y5L0; baseline and differential.
DR Genevisible; Q9Y5L0; HS.
DR GO; GO:0005642; C:annulate lamellae; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005635; C:nuclear envelope; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0061608; F:nuclear import signal receptor activity; TAS:GO_Central.
DR GO; GO:0031267; F:small GTPase binding; IDA:UniProtKB.
DR GO; GO:0006606; P:protein import into nucleus; IDA:UniProtKB.
DR Gene3D; 1.25.10.10; -; 1.
DR IDEAL; IID00632; -.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR013598; Exportin-1/Importin-b-like.
DR Pfam; PF08389; Xpo1; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cytoplasm;
KW Disease variant; Limb-girdle muscular dystrophy; Nucleus; Phosphoprotein;
KW Protein transport; Reference proteome; Transport.
FT CHAIN 1..923
FT /note="Transportin-3"
FT /id="PRO_0000120781"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:19413330"
FT MOD_RES 74
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 896
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT VAR_SEQ 453
FT /note="P -> PKKPFSNAACHHSLLFGQNITSEISNCEYLPPVLR (in isoform
FT 1)"
FT /evidence="ECO:0000303|PubMed:10366588"
FT /id="VSP_030174"
FT VAR_SEQ 500..563
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_045494"
FT VAR_SEQ 904..923
FT /note="SAEECKQVCWALRDFTRLFR -> RNVFFN (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_011178"
FT VARIANT 818
FT /note="R -> P (in LGMDD2; dbSNP:rs587777431)"
FT /evidence="ECO:0000269|PubMed:23667635"
FT /id="VAR_071822"
FT VARIANT 920..923
FT /note="RLFR -> GCFDSSHSCTVPVTQECLF (in LGMDD2)"
FT /evidence="ECO:0000269|PubMed:31192305"
FT /id="VAR_082591"
FT VARIANT 923
FT /note="R -> DSSHSCTVPVTQECLF (in LGMDD2)"
FT /evidence="ECO:0000269|PubMed:31071488"
FT /id="VAR_082592"
FT VARIANT 923
FT /note="R -> RCSHSCTVPVTQECLF (in LGMDD2; induces
FT relocalization to nuclear periphery; impaired ability to
FT transport target proteins into the nucleus; induces
FT resistance to HIV-1 infection; dbSNP:rs587777431)"
FT /evidence="ECO:0000269|PubMed:23543484,
FT ECO:0000269|PubMed:23667635, ECO:0000269|PubMed:31465518"
FT /id="VAR_082593"
FT MUTAGEN 145..153
FT /note="EILTVLPEE->QILTALPQQ: Decreased interaction with
FT GTP-bound Ran."
FT /evidence="ECO:0000269|PubMed:23878195"
FT MUTAGEN 620
FT /note="R->A: In 9Ala; abolished interaction with SRSF1 and
FT CPSF6 without affecting interaction with GTP-bound Ran;
FT when associated with A-660, A-664, A-667, A-671, A-702, A-
FT 750, A-751 and A-758."
FT /evidence="ECO:0000269|PubMed:24449914"
FT MUTAGEN 660
FT /note="E->A: In 9Ala; abolished interaction with SRSF1 and
FT CPSF6 without affecting interaction with GTP-bound Ran;
FT when associated with A-620, A-664, A-667, A-671, A-702, A-
FT 750, A-751 and A-758."
FT /evidence="ECO:0000269|PubMed:24449914"
FT MUTAGEN 664
FT /note="R->A: Abolished interaction with SRSF1. In 9Ala;
FT abolished interaction with SRSF1 and CPSF6 without
FT affecting interaction with GTP-bound Ran; when associated
FT with A-620, A-660, A-667, A-671, A-702, A-750, A-751 and A-
FT 758."
FT /evidence="ECO:0000269|PubMed:24449914"
FT MUTAGEN 667
FT /note="R->A: In 9Ala; abolished interaction with SRSF1 and
FT CPSF6 without affecting interaction with GTP-bound Ran;
FT when associated with A-620, A-660, A-664, A-671, A-702, A-
FT 750, A-751 and A-758."
FT /evidence="ECO:0000269|PubMed:24449914"
FT MUTAGEN 671
FT /note="R->A: Abolished interaction with SRSF1. In 9Ala;
FT abolished interaction with SRSF1 and CPSF6 without
FT affecting interaction with GTP-bound Ran; when associated
FT with A-620, A-660, A-664, A-667, A-702, A-750, A-751 and A-
FT 758."
FT /evidence="ECO:0000269|PubMed:24449914"
FT MUTAGEN 702
FT /note="Y->A: Abolished interaction with SRSF1. In 9Ala;
FT abolished interaction with SRSF1 and CPSF6 without
FT affecting interaction with GTP-bound Ran; when associated
FT with A-620, A-660, A-664, A-667, A-671, A-750, A-751 and A-
FT 758."
FT /evidence="ECO:0000269|PubMed:24449914"
FT MUTAGEN 750
FT /note="D->A: Abolished interaction with SRSF1. In 9Ala;
FT abolished interaction with SRSF1 and CPSF6 without
FT affecting interaction with GTP-bound Ran; when associated
FT with A-620, A-660, A-664, A-667, A-671, A-702, A-751 and A-
FT 758."
FT /evidence="ECO:0000269|PubMed:24449914"
FT MUTAGEN 751
FT /note="D->A: In 9Ala; abolished interaction with SRSF1 and
FT CPSF6 without affecting interaction with GTP-bound Ran;
FT when associated with A-620, A-660, A-664, A-667, A-671, A-
FT 702, A-750 and A-758."
FT /evidence="ECO:0000269|PubMed:24449914"
FT MUTAGEN 754
FT /note="R->A: Abolished interaction with SRSF1."
FT /evidence="ECO:0000269|PubMed:24449914"
FT MUTAGEN 758
FT /note="R->A: Abolished interaction with SRSF1. In 9Ala;
FT abolished interaction with SRSF1 and CPSF6 without
FT affecting interaction with GTP-bound Ran; when associated
FT with A-620, A-660, A-664, A-667, A-671, A-702, A-750 and A-
FT 751."
FT /evidence="ECO:0000269|PubMed:24449914"
FT CONFLICT 87
FT /note="R -> W (in Ref. 1; AAD38537)"
FT /evidence="ECO:0000305"
FT CONFLICT 265
FT /note="L -> S (in Ref. 3; AK225999)"
FT /evidence="ECO:0000305"
FT CONFLICT 358
FT /note="D -> G (in Ref. 3; AK225999)"
FT /evidence="ECO:0000305"
FT CONFLICT 480
FT /note="T -> A (in Ref. 3; AK225999)"
FT /evidence="ECO:0000305"
FT CONFLICT 624
FT /note="P -> L (in Ref. 3; AK225999)"
FT /evidence="ECO:0000305"
FT HELIX 8..20
FT /evidence="ECO:0007829|PDB:4C0O"
FT HELIX 24..39
FT /evidence="ECO:0007829|PDB:4C0O"
FT STRAND 40..42
FT /evidence="ECO:0007829|PDB:4OL0"
FT HELIX 43..53
FT /evidence="ECO:0007829|PDB:4C0O"
FT HELIX 57..73
FT /evidence="ECO:0007829|PDB:4C0O"
FT HELIX 75..77
FT /evidence="ECO:0007829|PDB:4C0O"
FT HELIX 82..96
FT /evidence="ECO:0007829|PDB:4C0O"
FT TURN 97..100
FT /evidence="ECO:0007829|PDB:4C0O"
FT HELIX 102..117
FT /evidence="ECO:0007829|PDB:4C0O"
FT STRAND 121..123
FT /evidence="ECO:0007829|PDB:4OL0"
FT HELIX 125..133
FT /evidence="ECO:0007829|PDB:4C0O"
FT STRAND 134..136
FT /evidence="ECO:0007829|PDB:4C0O"
FT TURN 137..139
FT /evidence="ECO:0007829|PDB:4C0O"
FT HELIX 140..152
FT /evidence="ECO:0007829|PDB:4C0O"
FT HELIX 153..155
FT /evidence="ECO:0007829|PDB:4C0O"
FT TURN 157..159
FT /evidence="ECO:0007829|PDB:4C0O"
FT HELIX 163..188
FT /evidence="ECO:0007829|PDB:4C0O"
FT TURN 190..193
FT /evidence="ECO:0007829|PDB:6GX9"
FT HELIX 195..211
FT /evidence="ECO:0007829|PDB:4C0O"
FT HELIX 216..220
FT /evidence="ECO:0007829|PDB:4C0O"
FT HELIX 223..233
FT /evidence="ECO:0007829|PDB:4C0O"
FT HELIX 239..254
FT /evidence="ECO:0007829|PDB:4C0O"
FT TURN 259..262
FT /evidence="ECO:0007829|PDB:4C0O"
FT HELIX 263..274
FT /evidence="ECO:0007829|PDB:4C0O"
FT HELIX 277..285
FT /evidence="ECO:0007829|PDB:4C0O"
FT HELIX 289..305
FT /evidence="ECO:0007829|PDB:4C0O"
FT HELIX 307..312
FT /evidence="ECO:0007829|PDB:4C0O"
FT HELIX 317..319
FT /evidence="ECO:0007829|PDB:4C0O"
FT HELIX 322..331
FT /evidence="ECO:0007829|PDB:4C0O"
FT HELIX 336..339
FT /evidence="ECO:0007829|PDB:4C0O"
FT HELIX 340..342
FT /evidence="ECO:0007829|PDB:4C0O"
FT HELIX 343..355
FT /evidence="ECO:0007829|PDB:4C0O"
FT HELIX 362..364
FT /evidence="ECO:0007829|PDB:4C0O"
FT HELIX 366..379
FT /evidence="ECO:0007829|PDB:4C0O"
FT STRAND 392..394
FT /evidence="ECO:0007829|PDB:4C0O"
FT HELIX 395..410
FT /evidence="ECO:0007829|PDB:4C0O"
FT HELIX 411..413
FT /evidence="ECO:0007829|PDB:4C0O"
FT HELIX 416..425
FT /evidence="ECO:0007829|PDB:4C0O"
FT TURN 426..430
FT /evidence="ECO:0007829|PDB:4C0O"
FT HELIX 434..447
FT /evidence="ECO:0007829|PDB:4C0O"
FT TURN 448..450
FT /evidence="ECO:0007829|PDB:4C0O"
FT HELIX 453..455
FT /evidence="ECO:0007829|PDB:4OL0"
FT HELIX 456..467
FT /evidence="ECO:0007829|PDB:4C0O"
FT HELIX 475..487
FT /evidence="ECO:0007829|PDB:4C0O"
FT HELIX 490..494
FT /evidence="ECO:0007829|PDB:4C0O"
FT HELIX 496..498
FT /evidence="ECO:0007829|PDB:4C0O"
FT HELIX 499..510
FT /evidence="ECO:0007829|PDB:4C0O"
FT HELIX 513..515
FT /evidence="ECO:0007829|PDB:4C0O"
FT HELIX 516..529
FT /evidence="ECO:0007829|PDB:4C0O"
FT HELIX 532..534
FT /evidence="ECO:0007829|PDB:6GX9"
FT TURN 535..537
FT /evidence="ECO:0007829|PDB:4C0O"
FT HELIX 538..546
FT /evidence="ECO:0007829|PDB:4C0O"
FT HELIX 547..550
FT /evidence="ECO:0007829|PDB:4C0O"
FT HELIX 555..569
FT /evidence="ECO:0007829|PDB:4C0O"
FT HELIX 574..595
FT /evidence="ECO:0007829|PDB:4C0O"
FT HELIX 609..621
FT /evidence="ECO:0007829|PDB:4C0O"
FT HELIX 635..651
FT /evidence="ECO:0007829|PDB:4C0O"
FT TURN 652..654
FT /evidence="ECO:0007829|PDB:4C0O"
FT HELIX 656..673
FT /evidence="ECO:0007829|PDB:4C0O"
FT HELIX 678..680
FT /evidence="ECO:0007829|PDB:6GX9"
FT HELIX 681..694
FT /evidence="ECO:0007829|PDB:4C0O"
FT HELIX 698..711
FT /evidence="ECO:0007829|PDB:4C0O"
FT STRAND 712..714
FT /evidence="ECO:0007829|PDB:4C0P"
FT TURN 715..717
FT /evidence="ECO:0007829|PDB:4C0O"
FT HELIX 718..737
FT /evidence="ECO:0007829|PDB:4C0O"
FT HELIX 741..744
FT /evidence="ECO:0007829|PDB:4C0O"
FT HELIX 746..762
FT /evidence="ECO:0007829|PDB:4C0O"
FT HELIX 764..768
FT /evidence="ECO:0007829|PDB:4C0O"
FT STRAND 769..771
FT /evidence="ECO:0007829|PDB:4C0O"
FT HELIX 773..783
FT /evidence="ECO:0007829|PDB:4C0O"
FT HELIX 789..803
FT /evidence="ECO:0007829|PDB:4C0O"
FT HELIX 804..806
FT /evidence="ECO:0007829|PDB:4C0O"
FT HELIX 815..842
FT /evidence="ECO:0007829|PDB:4C0O"
FT HELIX 847..849
FT /evidence="ECO:0007829|PDB:4C0O"
FT HELIX 850..877
FT /evidence="ECO:0007829|PDB:4C0O"
FT HELIX 892..903
FT /evidence="ECO:0007829|PDB:4C0O"
FT HELIX 908..919
FT /evidence="ECO:0007829|PDB:4C0O"
SQ SEQUENCE 923 AA; 104203 MW; CF7CDC14CDBA56AB CRC64;
MEGAKPTLQL VYQAVQALYH DPDPSGKERA SFWLGELQRS VHAWEISDQL LQIRQDVESC
YFAAQTMKMK IQTSFYELPT DSHASLRDSL LTHIQNLKDL SPVIVTQLAL AIADLALQMP
SWKGCVQTLV EKYSNDVTSL PFLLEILTVL PEEVHSRSLR IGANRRTEII EDLAFYSSTV
VSLLMTCVEK AGTDEKMLMK VFRCLGSWFN LGVLDSNFMA NNKLLALLFE VLQQDKTSSN
LHEAASDCVC SALYAIENVE TNLPLAMQLF QGVLTLETAY HMAVAREDLD KVLNYCRIFT
ELCETFLEKI VCTPGQGLGD LRTLELLLIC AGHPQYEVVE ISFNFWYRLG EHLYKTNDEV
IHGIFKAYIQ RLLHALARHC QLEPDHEGVP EETDDFGEFR MRVSDLVKDL IFLIGSMECF
AQLYSTLKEG NPPWEVTEAV LFIMAAIAKS VDPENNPTLV EVLEGVVRLP ETVHTAVRYT
SIELVGEMSE VVDRNPQFLD PVLGYLMKGL CEKPLASAAA KAIHNICSVC RDHMAQHFNG
LLEIARSLDS FLLSPEAAVG LLKGTALVLA RLPLDKITEC LSELCSVQVM ALKKLLSQEP
SNGISSDPTV FLDRLAVIFR HTNPIVENGQ THPCQKVIQE IWPVLSETLN KHRADNRIVE
RCCRCLRFAV RCVGKGSAAL LQPLVTQMVN VYHVHQHSCF LYLGSILVDE YGMEEGCRQG
LLDMLQALCI PTFQLLEQQN GLQNHPDTVD DLFRLATRFI QRSPVTLLRS QVVIPILQWA
IASTTLDHRD ANCSVMRFLR DLIHTGVAND HEEDFELRKE LIGQVMNQLG QQLVSQLLHT
CCFCLPPYTL PDVAEVLWEI MQVDRPTFCR WLENSLKGLP KETTVGAVTV THKQLTDFHK
QVTSAEECKQ VCWALRDFTR LFR
