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 27-MAR-2024, entry version 181. 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 DELINS RP GLY-CYS-PHE-ASP-SER-SER-HIS-SER-CYS-THR-VAL-PRO-VAL-THR-GLN-GLU-CYS-LEU-PHE, RP 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 --------------------------------------------------------------------------- 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; 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 CCDS; CCDS94196.1; -. [Q9Y5L0-1] 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; 254. DR IntAct; Q9Y5L0; 82. 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; 9606-ENSP00000265388; -. DR PeptideAtlas; Q9Y5L0; -. DR ProteomicsDB; 7822; -. DR ProteomicsDB; 86436; -. [Q9Y5L0-2] DR ProteomicsDB; 86437; -. [Q9Y5L0-1] DR ProteomicsDB; 86438; -. [Q9Y5L0-3] DR Pumba; Q9Y5L0; -. DR Antibodypedia; 17836; 176 antibodies from 31 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 AGR; HGNC:17103; -. 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; LECITSW; -. DR OrthoDB; 5343383at2759; -. DR PhylomeDB; Q9Y5L0; -. DR TreeFam; TF314539; -. DR PathwayCommons; Q9Y5L0; -. DR SignaLink; Q9Y5L0; -. DR BioGRID-ORCS; 23534; 791 hits in 1168 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 222 other cell types or tissues. DR ExpressionAtlas; Q9Y5L0; baseline and differential. 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; Leucine-rich Repeat Variant; 1. DR IDEAL; IID00632; -. DR InterPro; IPR011989; ARM-like. DR InterPro; IPR016024; ARM-type_fold. DR InterPro; IPR013598; Exportin-1/Importin-b-like. DR PANTHER; PTHR12363; TRANSPORTIN 3 AND IMPORTIN 13; 1. DR PANTHER; PTHR12363:SF33; TRANSPORTIN-3; 1. DR Pfam; PF08389; Xpo1; 1. DR SUPFAM; SSF48371; ARM repeat; 1. DR Genevisible; Q9Y5L0; HS. 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, FT A-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, FT A-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 FT A-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, FT A-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 FT A-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 FT A-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 FT A-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, FT A-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 FT A-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 //