ID TLN1_HUMAN Reviewed; 2541 AA. AC Q9Y490; A0A1S5UZ07; A6NMY0; Q86YD0; Q9NZQ2; Q9UHH8; Q9UPX3; DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot. DT 08-NOV-2005, sequence version 3. DT 27-MAR-2024, entry version 226. DE RecName: Full=Talin-1; GN Name=TLN1; Synonyms=KIAA1027, TLN; 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), AND VARIANT LEU-1227. RA Mao L., Fan Y.H.; RT "Complete cDNA sequence of human talin."; RL Submitted (JUL-1998) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]. RX PubMed=10610730; DOI=10.1006/geno.1999.6019; RA Ben-Yosef T., Francomano C.A.; RT "Characterization of the human talin (TLN) gene: genomic structure, RT chromosomal localization, and expression pattern."; RL Genomics 62:316-319(1999). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; RX PubMed=10470851; DOI=10.1093/dnares/6.3.197; RA Kikuno R., Nagase T., Ishikawa K., Hirosawa M., Miyajima N., Tanaka A., RA Kotani H., Nomura N., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XIV. The RT complete sequences of 100 new cDNA clones from brain which code for large RT proteins in vitro."; RL DNA Res. 6:197-205(1999). RN [4] 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 [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RC TISSUE=Placenta; RX PubMed=28251419; DOI=10.1007/s10142-017-0555-y; RA Majewska M., Lipka A., Paukszto L., Jastrzebski J.P., Myszczynski K., RA Gowkielewicz M., Jozwik M., Majewski M.K.; RT "Transcriptome profile of the human placenta."; RL Funct. Integr. Genomics 17:551-563(2017). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164053; DOI=10.1038/nature02465; RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., RA Dunham I.; RT "DNA sequence and analysis of human chromosome 9."; RL Nature 429:369-374(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT TRP-1919. RC TISSUE=Embryonic carcinoma; 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 PROTEIN SEQUENCE OF 8-15; 34-82; 99-106; 119-131; 138-146; 148-156; RP 165-178; 182-194; 197-234; 257-268; 307-316; 344-358; 428-438; 442-454; RP 593-634; 674-685; 722-741; 766-824; 828-854; 862-869; 876-910; 923-943; RP 958-999; 1026-1035; 1076-1086; 1097-1122; 1130-1184; 1191-1198; 1208-1214; RP 1223-1269; 1274-1306; 1321-1340; 1362-1368; 1402-1431; 1531-1541; RP 1560-1646; 1674-1780; 1863-1917; 1961-1973; 2007-2016; 2025-2057; RP 2064-2085; 2090-2099; 2105-2115; 2120-2130; 2134-2141; 2145-2154; RP 2169-2177; 2198-2209; 2221-2233; 2267-2274; 2276-2321; 2322-2329; RP 2334-2361; 2369-2398; 2430-2443; 2456-2472; 2477-2491; 2494-2510 AND RP 2512-2519, AND IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Platelet; RA Bienvenut W.V., Claeys D.; RL Submitted (NOV-2005) to UniProtKB. RN [10] RP INTERACTION WITH NRAP. RX PubMed=10320340; DOI=10.1021/bi982395t; RA Luo G., Herrera A.H., Horowits R.; RT "Molecular interactions of N-RAP, a nebulin-related protein of striated RT muscle myotendon junctions and intercalated disks."; RL Biochemistry 38:6135-6143(1999). RN [11] RP INTERACTION WITH PIP5K1C. RX PubMed=12422220; DOI=10.1038/nature01082; RA Ling K., Doughman R.L., Firestone A.J., Bunce M.W., Anderson R.A.; RT "Type I gamma phosphatidylinositol phosphate kinase targets and regulates RT focal adhesions."; RL Nature 420:89-93(2002). RN [12] RP INTERACTION WITH ITGB1. RX PubMed=12473654; DOI=10.1074/jbc.m211258200; RA Bouvard D., Vignoud L., Dupe-Manet S., Abed N., Fournier H.N., RA Vincent-Monegat C., Retta S.F., Fassler R., Block M.R.; RT "Disruption of focal adhesions by integrin cytoplasmic domain-associated RT protein-1 alpha."; RL J. Biol. Chem. 278:6567-6574(2003). RN [13] 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 [14] RP INTERACTION WITH SYNM. RX PubMed=18342854; DOI=10.1016/j.yexcr.2008.01.034; RA Sun N., Critchley D.R., Paulin D., Li Z., Robson R.M.; RT "Identification of a repeated domain within mammalian alpha-synemin that RT interacts directly with talin."; RL Exp. Cell Res. 314:1839-1849(2008). RN [15] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Platelet; RX PubMed=18088087; DOI=10.1021/pr0704130; RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., RA Schuetz C., Walter U., Gambaryan S., Sickmann A.; RT "Phosphoproteome of resting human platelets."; RL J. Proteome Res. 7:526-534(2008). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-425, AND IDENTIFICATION BY RP 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 [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-425, 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 [18] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-2031 AND LYS-2115, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-425, AND IDENTIFICATION BY RP 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 [20] 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 [21] RP INTERACTION WITH ITGB1. RX PubMed=21768292; DOI=10.1083/jcb.201007108; RA Brunner M., Millon-Fremillon A., Chevalier G., Nakchbandi I.A., Mosher D., RA Block M.R., Albiges-Rizo C., Bouvard D.; RT "Osteoblast mineralization requires beta1 integrin/ICAP-1-dependent RT fibronectin deposition."; RL J. Cell Biol. 194:307-322(2011). RN [22] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2040, AND IDENTIFICATION BY RP 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 [23] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-167 AND SER-425, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE 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 [24] RP INTERACTION WITH HUMAN CYTOMEGALOVIRUS PROTEIN UL135. RX PubMed=25121749; DOI=10.1016/j.chom.2014.07.005; RA Stanton R.J., Prod'homme V., Purbhoo M.A., Moore M., Aicheler R.J., RA Heinzmann M., Bailer S.M., Haas J., Antrobus R., Weekes M.P., Lehner P.J., RA Vojtesek B., Miners K.L., Man S., Wilkie G.S., Davison A.J., Wang E.C., RA Tomasec P., Wilkinson G.W.; RT "HCMV pUL135 remodels the actin cytoskeleton to impair immune recognition RT of infected cells."; RL Cell Host Microbe 16:201-214(2014). RN [25] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-405; SER-1021; THR-1142; RP SER-1201; SER-1225; THR-1263; SER-1323; SER-1849; THR-1855 AND SER-2040, RP AND 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 [26] 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 [27] RP INTERACTION WITH THSD1. RX PubMed=27895300; DOI=10.1161/strokeaha.116.014161; RA Santiago-Sim T., Fang X., Hennessy M.L., Nalbach S.V., DePalma S.R., RA Lee M.S., Greenway S.C., McDonough B., Hergenroeder G.W., Patek K.J., RA Colosimo S.M., Qualmann K.J., Hagan J.P., Milewicz D.M., MacRae C.A., RA Dymecki S.M., Seidman C.E., Seidman J.G., Kim D.H.; RT "THSD1 (thrombospondin type 1 domain containing protein 1) mutation in the RT pathogenesis of intracranial aneurysm and subarachnoid emorrhage."; RL Stroke 47:3005-3013(2016). RN [28] RP ERRATUM OF PUBMED:27895300. RA Santiago-Sim T., Fang X., Hennessy M.L., Nalbach S.V., DePalma S.R., RA Lee M.S., Greenway S.C., McDonough B., Hergenroeder G.W., Patek K.J., RA Colosimo S.M., Qualmann K.J., Hagan J.P., Milewicz D.M., MacRae C.A., RA Dymecki S.M., Seidman C.E., Seidman J.G., Kim D.H.; RT "THSD1 (thrombospondin type 1 domain containing protein 1) mutation in the RT pathogenesis of intracranial aneurysm and subarachnoid emorrhage."; RL Stroke 48:e240-e240(2016). RN [29] RP INTERACTION WITH THSD1. RX PubMed=29069646; DOI=10.1159/000484298; RA Rui Y.N., Xu Z., Fang X., Menezes M.R., Balzeau J., Niu A., Hagan J.P., RA Kim D.H.; RT "The Intracranial Aneurysm Gene THSD1 Connects Endosome Dynamics to Nascent RT Focal Adhesion Assembly."; RL Cell. Physiol. Biochem. 43:2200-2211(2017). RN [30] RP ALTERNATIVE SPLICING, INTERACTION WITH VCL AND APBB1IP (ISOFORMS 1 AND 2), RP INDUCTION (ISOFORM 1), AND TISSUE SPECIFICITY (ISOFORM 2). RX PubMed=36880935; DOI=10.1083/jcb.202209010; RA Gallego-Paez L.M., Edwards W.J.S., Chanduri M., Guo Y., Koorman T., RA Lee C.Y., Grexa N., Derksen P., Yan J., Schwartz M.A., Mauer J., RA Goult B.T.; RT "TLN1 contains a cancer-associated cassette exon that alters talin-1 RT mechanosensitivity."; RL J. Cell Biol. 222:0-0(2023). RN [31] RP X-RAY CRYSTALLOGRAPHY (2.42 ANGSTROMS) OF 607-631 IN COMPLEX WITH VCL. RX PubMed=15070891; DOI=10.1074/jbc.m403076200; RA Izard T., Vonrhein C.; RT "Structural basis for amplifying vinculin activation by talin."; RL J. Biol. Chem. 279:27667-27678(2004). CC -!- FUNCTION: High molecular weight cytoskeletal protein concentrated at CC regions of cell-substratum contact and, in lymphocytes, at cell-cell CC contacts (By similarity). Involved in connections of major cytoskeletal CC structures to the plasma membrane (By similarity). {ECO:0000250}. CC -!- SUBUNIT: Part of a complex composed of THSD1, PTK2/FAK1, TLN1 and VCL CC (PubMed:29069646). Interacts with THSD1 (PubMed:27895300, CC PubMed:29069646); this promotes interaction with PTK2/FAK1 and VCL. CC Binds with high affinity to VCL and with low affinity to integrins CC (PubMed:15070891). Interacts with APBB1IP; this inhibits VCL binding. CC Interacts with PTK2/FAK1 (By similarity). Interacts with PIP5K1C and CC NRAP (PubMed:10320340, PubMed:12422220). Interacts with LAYN (By CC similarity). Interacts with SYNM (PubMed:18342854). Interacts with CC ITGB1; the interaction is prevented by competitive binding of ITGB1BP1 CC (PubMed:21768292, PubMed:12473654). Interacts with SVEP1 (By CC similarity). {ECO:0000250|UniProtKB:P26039, CC ECO:0000250|UniProtKB:P54939, ECO:0000269|PubMed:10320340, CC ECO:0000269|PubMed:12422220, ECO:0000269|PubMed:12473654, CC ECO:0000269|PubMed:15070891, ECO:0000269|PubMed:18342854, CC ECO:0000269|PubMed:21768292, ECO:0000269|PubMed:25121749, CC ECO:0000269|PubMed:27895300, ECO:0000269|PubMed:29069646}. CC -!- SUBUNIT: [Isoform 1]: Interacts with VCL; shows reduced VCL binding CC compared to isoform 2 (PubMed:36880935). Interacts with APBB1IP; shows CC similar level of binding compared to isoform 2 (PubMed:36880935). CC {ECO:0000269|PubMed:36880935}. CC -!- SUBUNIT: [Isoform 2]: Interacts with VCL; shows enhanced VCL binding CC compared to isoform 1 (PubMed:36880935). Interacts with APBB1IP; shows CC similar level of binding compared to isoform 1 (PubMed:36880935). CC {ECO:0000269|PubMed:36880935}. CC -!- SUBUNIT: (Microbial infection) Interacts with human cytomegalovirus CC protein UL135. {ECO:0000269|PubMed:25121749}. CC -!- INTERACTION: CC Q9Y490; Q2M1Z3: ARHGAP31; NbExp=2; IntAct=EBI-2462036, EBI-2803146; CC Q9Y490; P00533: EGFR; NbExp=2; IntAct=EBI-2462036, EBI-297353; CC Q9Y490; P04626: ERBB2; NbExp=3; IntAct=EBI-2462036, EBI-641062; CC Q9Y490; P05556: ITGB1; NbExp=2; IntAct=EBI-2462036, EBI-703066; CC Q9Y490; P05106: ITGB3; NbExp=5; IntAct=EBI-2462036, EBI-702847; CC Q9Y490; O60331: PIP5K1C; NbExp=8; IntAct=EBI-2462036, EBI-8869029; CC -!- SUBCELLULAR LOCATION: Cell projection, ruffle membrane {ECO:0000250}; CC Peripheral membrane protein {ECO:0000250}; Cytoplasmic side CC {ECO:0000250}. Cytoplasm, cytoskeleton {ECO:0000250}. Cell surface CC {ECO:0000250|UniProtKB:P26039}. Cell junction, focal adhesion CC {ECO:0000250|UniProtKB:P26039}. Note=Colocalizes with LAYN at the CC membrane ruffles. Localized preferentially in focal adhesions than CC fibrillar adhesions (By similarity). {ECO:0000250}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9Y490-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9Y490-2; Sequence=VSP_061952; CC -!- TISSUE SPECIFICITY: [Isoform 2]: Expressed at low to non-detectable CC levels in many tissues but highly expressed in skin and pancreas with CC other tissues including kidney cortex, endocervix, testis, pituitary, CC liver, and spleen also showing robust expression. CC {ECO:0000269|PubMed:28251419}. CC -!- INDUCTION: [Isoform 1]: By a combination of TGFB and EGF. CC {ECO:0000269|PubMed:36880935}. CC -!- DOMAIN: Consists of an N-terminal FERM domain linked via a short CC unstructured region to a large flexible C-terminal rod which contains CC 13 amphipathic helical bundles (R1-R13). The rod begins with a five- CC helix bundle (R1) followed by three four-helix bundles (R2-R4). These CC are followed by a series of eight five-helix bundles (R5-R7 and R9-R13) CC in which the N- and C-termini are positioned at opposite ends of the CC bundle, creating a linear chain. The four-helix bundle R8 does not CC disrupt the chain because it is inserted into a loop in the R7 five- CC helix bundle. The uneven distribution of four- and five-helix bundles CC creates two distinctly different zones: a compact N-terminal region CC sensitive to stretch and a linear C-terminal region that is optimal for CC force transmission. {ECO:0000250|UniProtKB:P26039}. CC -!- MISCELLANEOUS: [Isoform 2]: Shows reduced mechanical stability compared CC to isoform 1 (PubMed:36880935). Shows altered focal adhesion formation CC compared to isoform 1 with cells having a greater number of small CC adhesions compared to those expressing isoform 1 (PubMed:36880935). CC {ECO:0000269|PubMed:36880935}. CC -!- MISCELLANEOUS: [Isoform 2]: Expression in cancer cells is associated CC with altered drug responses. Cells show increased sensitivity to EGFR CC inhibitors but are resistant to drugs targeting PI3K signaling and CC cytoskeleton regulation. {ECO:0000269|PubMed:28251419}. CC -!- SEQUENCE CAUTION: CC Sequence=BAA82979.2; Type=Erroneous initiation; Note=Extended N-terminus.; 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; AF078828; AAD13152.1; -; mRNA. DR EMBL; AF177198; AAF23322.1; -; mRNA. DR EMBL; AF178534; AAF27330.1; -; Genomic_DNA. DR EMBL; AF178081; AAF27330.1; JOINED; Genomic_DNA. DR EMBL; AB028950; BAA82979.2; ALT_INIT; mRNA. DR EMBL; KX533478; AQN67632.1; -; mRNA. DR EMBL; AL133410; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471071; EAW58352.1; -; Genomic_DNA. DR EMBL; BC042923; AAH42923.1; -; mRNA. DR CCDS; CCDS35009.1; -. [Q9Y490-1] DR RefSeq; NP_006280.3; NM_006289.3. [Q9Y490-1] DR PDB; 1SYQ; X-ray; 2.42 A; B=607-631. DR PDB; 2MWN; NMR; -; B=308-400. DR PDB; 4DJ9; X-ray; 2.25 A; B=2075-2103. DR PDB; 6R9T; EM; 6.20 A; A=1-2541. DR PDBsum; 1SYQ; -. DR PDBsum; 2MWN; -. DR PDBsum; 4DJ9; -. DR PDBsum; 6R9T; -. DR AlphaFoldDB; Q9Y490; -. DR BMRB; Q9Y490; -. DR EMDB; EMD-4772; -. DR SASBDB; Q9Y490; -. DR SMR; Q9Y490; -. DR BioGRID; 112949; 237. DR ComplexPortal; CPX-791; Talin-1-Vinculin focal adhesion activation complex. DR CORUM; Q9Y490; -. DR ELM; Q9Y490; -. DR IntAct; Q9Y490; 61. DR MINT; Q9Y490; -. DR STRING; 9606.ENSP00000316029; -. DR TCDB; 8.A.25.1.6; the ezrin/radixin/moesin (ezrin) family. DR CarbonylDB; Q9Y490; -. DR GlyCosmos; Q9Y490; 2 sites, 1 glycan. DR GlyGen; Q9Y490; 3 sites, 1 O-linked glycan (3 sites). DR iPTMnet; Q9Y490; -. DR MetOSite; Q9Y490; -. DR PhosphoSitePlus; Q9Y490; -. DR SwissPalm; Q9Y490; -. DR BioMuta; TLN1; -. DR DMDM; 81175200; -. DR OGP; Q9Y490; -. DR CPTAC; CPTAC-282; -. DR CPTAC; CPTAC-283; -. DR EPD; Q9Y490; -. DR jPOST; Q9Y490; -. DR MassIVE; Q9Y490; -. DR MaxQB; Q9Y490; -. DR PaxDb; 9606-ENSP00000316029; -. DR PeptideAtlas; Q9Y490; -. DR PRIDE; Q9Y490; -. DR ProteomicsDB; 86131; -. DR Pumba; Q9Y490; -. DR Antibodypedia; 1497; 755 antibodies from 42 providers. DR DNASU; 7094; -. DR Ensembl; ENST00000314888.10; ENSP00000316029.9; ENSG00000137076.22. [Q9Y490-1] DR Ensembl; ENST00000706939.1; ENSP00000516659.1; ENSG00000137076.22. [Q9Y490-2] DR GeneID; 7094; -. DR KEGG; hsa:7094; -. DR MANE-Select; ENST00000314888.10; ENSP00000316029.9; NM_006289.4; NP_006280.3. DR UCSC; uc003zxt.3; human. [Q9Y490-1] DR AGR; HGNC:11845; -. DR CTD; 7094; -. DR DisGeNET; 7094; -. DR GeneCards; TLN1; -. DR HGNC; HGNC:11845; TLN1. DR HPA; ENSG00000137076; Low tissue specificity. DR MIM; 186745; gene. DR neXtProt; NX_Q9Y490; -. DR OpenTargets; ENSG00000137076; -. DR PharmGKB; PA36547; -. DR VEuPathDB; HostDB:ENSG00000137076; -. DR eggNOG; KOG4261; Eukaryota. DR GeneTree; ENSGT00940000157006; -. DR HOGENOM; CLU_000364_1_1_1; -. DR InParanoid; Q9Y490; -. DR OMA; VDMTQHY; -. DR OrthoDB; 25353at2759; -. DR PhylomeDB; Q9Y490; -. DR TreeFam; TF314677; -. DR PathwayCommons; Q9Y490; -. DR Reactome; R-HSA-114608; Platelet degranulation. DR Reactome; R-HSA-354192; Integrin signaling. DR Reactome; R-HSA-354194; GRB2:SOS provides linkage to MAPK signaling for Integrins. DR Reactome; R-HSA-372708; p130Cas linkage to MAPK signaling for integrins. DR Reactome; R-HSA-381038; XBP1(S) activates chaperone genes. DR Reactome; R-HSA-399955; SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion. DR Reactome; R-HSA-445355; Smooth Muscle Contraction. DR Reactome; R-HSA-5674135; MAP2K and MAPK activation. DR Reactome; R-HSA-6802946; Signaling by moderate kinase activity BRAF mutants. DR Reactome; R-HSA-6802948; Signaling by high-kinase activity BRAF mutants. DR Reactome; R-HSA-6802952; Signaling by BRAF and RAF1 fusions. DR Reactome; R-HSA-6802955; Paradoxical activation of RAF signaling by kinase inactive BRAF. DR Reactome; R-HSA-9649948; Signaling downstream of RAS mutants. DR Reactome; R-HSA-9656223; Signaling by RAF1 mutants. DR SignaLink; Q9Y490; -. DR SIGNOR; Q9Y490; -. DR BioGRID-ORCS; 7094; 447 hits in 1170 CRISPR screens. DR ChiTaRS; TLN1; human. DR EvolutionaryTrace; Q9Y490; -. DR GeneWiki; TLN1; -. DR GenomeRNAi; 7094; -. DR Pharos; Q9Y490; Tbio. DR PRO; PR:Q9Y490; -. DR Proteomes; UP000005640; Chromosome 9. DR RNAct; Q9Y490; Protein. DR Bgee; ENSG00000137076; Expressed in popliteal artery and 180 other cell types or tissues. DR GO; GO:0005912; C:adherens junction; IMP:ARUK-UCL. DR GO; GO:0009986; C:cell surface; IEA:UniProtKB-SubCell. DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005925; C:focal adhesion; IDA:ComplexPortal. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0001726; C:ruffle; ISS:HGNC-UCL. DR GO; GO:0032587; C:ruffle membrane; IEA:UniProtKB-SubCell. DR GO; GO:0051015; F:actin filament binding; IEA:InterPro. DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL. DR GO; GO:0005178; F:integrin binding; IPI:UniProtKB. DR GO; GO:0030274; F:LIM domain binding; IPI:UniProtKB. DR GO; GO:0035091; F:phosphatidylinositol binding; IEA:Ensembl. DR GO; GO:0001786; F:phosphatidylserine binding; IEA:Ensembl. DR GO; GO:0005200; F:structural constituent of cytoskeleton; IEA:InterPro. DR GO; GO:0017166; F:vinculin binding; IPI:UniProtKB. DR GO; GO:0098609; P:cell-cell adhesion; IBA:GO_Central. DR GO; GO:0007043; P:cell-cell junction assembly; TAS:UniProtKB. DR GO; GO:0007044; P:cell-substrate junction assembly; IEA:Ensembl. DR GO; GO:0030866; P:cortical actin cytoskeleton organization; IEA:Ensembl. DR GO; GO:0033622; P:integrin activation; IEA:Ensembl. DR GO; GO:0007229; P:integrin-mediated signaling pathway; IEA:Ensembl. DR GO; GO:0070527; P:platelet aggregation; HMP:UniProtKB. DR GO; GO:0051893; P:regulation of focal adhesion assembly; NAS:ComplexPortal. DR CDD; cd14473; FERM_B-lobe; 1. DR CDD; cd10569; FERM_C_Talin; 1. DR CDD; cd17171; FERM_F0_TLN1; 1. DR CDD; cd17173; FERM_F1_TLN1; 1. DR CDD; cd12150; talin-RS; 1. DR Gene3D; 1.20.80.10; -; 1. DR Gene3D; 1.20.120.230; Alpha-catenin/vinculin-like; 5. DR Gene3D; 1.20.1410.10; I/LWEQ domain; 1. DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1. DR Gene3D; 1.20.1420.10; Talin, central domain; 7. DR InterPro; IPR036723; Alpha-catenin/vinculin-like_sf. DR InterPro; IPR019749; Band_41_domain. DR InterPro; IPR014352; FERM/acyl-CoA-bd_prot_sf. DR InterPro; IPR035963; FERM_2. DR InterPro; IPR019748; FERM_central. DR InterPro; IPR019747; FERM_CS. DR InterPro; IPR000299; FERM_domain. DR InterPro; IPR032425; FERM_f0. DR InterPro; IPR035964; I/LWEQ_dom_sf. DR InterPro; IPR002558; ILWEQ_dom. DR InterPro; IPR011993; PH-like_dom_sf. DR InterPro; IPR037438; Talin1/2-RS. DR InterPro; IPR015224; Talin_cent. DR InterPro; IPR036476; Talin_cent_sf. DR InterPro; IPR049108; Talin_R4. DR InterPro; IPR029071; Ubiquitin-like_domsf. DR InterPro; IPR015009; Vinculin-bd_dom. DR PANTHER; PTHR19981; TALIN; 1. DR PANTHER; PTHR19981:SF7; TALIN-1; 1. DR Pfam; PF16511; FERM_f0; 1. DR Pfam; PF00373; FERM_M; 1. DR Pfam; PF01608; I_LWEQ; 1. DR Pfam; PF09141; Talin_middle; 1. DR Pfam; PF21692; Talin_R4; 2. DR Pfam; PF08913; VBS; 1. DR SMART; SM00295; B41; 1. DR SMART; SM00307; ILWEQ; 1. DR SMART; SM01244; IRS; 1. DR SUPFAM; SSF109880; A middle domain of Talin 1; 1. DR SUPFAM; SSF47220; alpha-catenin/vinculin-like; 5. DR SUPFAM; SSF109885; I/LWEQ domain; 4. DR SUPFAM; SSF50729; PH domain-like; 1. DR SUPFAM; SSF47031; Second domain of FERM; 1. DR SUPFAM; SSF54236; Ubiquitin-like; 1. DR PROSITE; PS00660; FERM_1; 1. DR PROSITE; PS00661; FERM_2; 1. DR PROSITE; PS50057; FERM_3; 1. DR PROSITE; PS50945; I_LWEQ; 1. DR Genevisible; Q9Y490; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Cell junction; KW Cell membrane; Cell projection; Cytoplasm; Cytoskeleton; KW Direct protein sequencing; Host-virus interaction; Membrane; KW Phosphoprotein; Reference proteome. FT CHAIN 1..2541 FT /note="Talin-1" FT /id="PRO_0000219428" FT DOMAIN 86..403 FT /note="FERM" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00084" FT DOMAIN 2293..2533 FT /note="I/LWEQ" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00292" FT REGION 280..435 FT /note="Interaction with LAYN" FT /evidence="ECO:0000250|UniProtKB:P54939" FT REGION 482..655 FT /note="Helical bundle R1" FT /evidence="ECO:0000250|UniProtKB:P26039" FT REGION 656..786 FT /note="Helical bundle R2" FT /evidence="ECO:0000250|UniProtKB:P26039" FT REGION 787..911 FT /note="Helical bundle R3" FT /evidence="ECO:0000250|UniProtKB:P26039" FT REGION 913..1044 FT /note="Helical bundle R4" FT /evidence="ECO:0000250|UniProtKB:P26039" FT REGION 1046..1206 FT /note="Helical bundle R5" FT /evidence="ECO:0000250|UniProtKB:P26039" FT REGION 1207..1357 FT /note="Helical bundle R6" FT /evidence="ECO:0000250|UniProtKB:P26039" FT REGION 1327..1948 FT /note="Interaction with SYNM" FT /evidence="ECO:0000269|PubMed:18342854" FT REGION 1358..1453 FT /note="Helical bundle R7A" FT /evidence="ECO:0000250|UniProtKB:P26039" FT REGION 1359..1659 FT /note="Interaction with VCL and F-actin" FT /evidence="ECO:0000250|UniProtKB:P26039" FT REGION 1461..1580 FT /note="Helical bundle R8" FT /evidence="ECO:0000250|UniProtKB:P26039" FT REGION 1581..1653 FT /note="Helical bundle R7B" FT /evidence="ECO:0000250|UniProtKB:P26039" FT REGION 1655..1822 FT /note="Helical bundle R9" FT /evidence="ECO:0000250|UniProtKB:P26039" FT REGION 1823..1973 FT /note="Helical bundle R10" FT /evidence="ECO:0000250|UniProtKB:P26039" FT REGION 1974..2140 FT /note="Helical bundle R11" FT /evidence="ECO:0000250|UniProtKB:P26039" FT REGION 2141..2294 FT /note="Helical bundle R12" FT /evidence="ECO:0000250|UniProtKB:P26039" FT REGION 2300..2482 FT /note="Helical bundle R13" FT /evidence="ECO:0000250|UniProtKB:P26039" FT MOD_RES 167 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 405 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 425 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT MOD_RES 446 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P26039" FT MOD_RES 620 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P26039" FT MOD_RES 729 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P26039" FT MOD_RES 1021 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 1116 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P26039" FT MOD_RES 1142 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 1201 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 1225 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 1263 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 1323 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 1544 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P26039" FT MOD_RES 1849 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 1855 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 1878 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P26039" FT MOD_RES 2031 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 2040 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:24275569" FT MOD_RES 2115 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT VAR_SEQ 665 FT /note="Q -> QICASRGAGVRSPPDSPT (in isoform 2)" FT /id="VSP_061952" FT VARIANT 1227 FT /note="S -> L (in dbSNP:rs2295795)" FT /evidence="ECO:0000269|Ref.1" FT /id="VAR_023751" FT VARIANT 1919 FT /note="R -> W (in dbSNP:rs17854239)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_023752" FT VARIANT 1984 FT /note="A -> T (in dbSNP:rs35642290)" FT /id="VAR_055538" FT CONFLICT 824 FT /note="R -> G (in Ref. 1; AAD13152 and 2; AAF23322)" FT /evidence="ECO:0000305" FT CONFLICT 1549 FT /note="A -> P (in Ref. 1; AAD13152 and 2; AAF23322)" FT /evidence="ECO:0000305" FT CONFLICT 1604 FT /note="K -> Q (in Ref. 1; AAD13152 and 2; AAF23322)" FT /evidence="ECO:0000305" FT CONFLICT 1701 FT /note="Q -> E (in Ref. 1; AAD13152 and 2; AAF23322)" FT /evidence="ECO:0000305" FT CONFLICT 1718 FT /note="N -> H (in Ref. 1; AAD13152 and 2; AAF23322)" FT /evidence="ECO:0000305" FT CONFLICT 1966 FT /note="A -> R (in Ref. 1; AAD13152)" FT /evidence="ECO:0000305" FT CONFLICT 2256 FT /note="Missing (in Ref. 2; AAF27330)" FT /evidence="ECO:0000305" FT STRAND 311..313 FT /evidence="ECO:0007829|PDB:2MWN" FT STRAND 316..318 FT /evidence="ECO:0007829|PDB:2MWN" FT STRAND 320..327 FT /evidence="ECO:0007829|PDB:2MWN" FT STRAND 329..333 FT /evidence="ECO:0007829|PDB:2MWN" FT STRAND 336..340 FT /evidence="ECO:0007829|PDB:2MWN" FT TURN 342..344 FT /evidence="ECO:0007829|PDB:2MWN" FT STRAND 363..369 FT /evidence="ECO:0007829|PDB:2MWN" FT STRAND 377..381 FT /evidence="ECO:0007829|PDB:2MWN" FT HELIX 385..399 FT /evidence="ECO:0007829|PDB:2MWN" FT HELIX 608..625 FT /evidence="ECO:0007829|PDB:1SYQ" FT HELIX 2079..2098 FT /evidence="ECO:0007829|PDB:4DJ9" SQ SEQUENCE 2541 AA; 269767 MW; E21575E9199BBC5C CRC64; MVALSLKISI GNVVKTMQFE PSTMVYDACR IIRERIPEAP AGPPSDFGLF LSDDDPKKGI WLEAGKALDY YMLRNGDTME YRKKQRPLKI RMLDGTVKTI MVDDSKTVTD MLMTICARIG ITNHDEYSLV RELMEEKKEE ITGTLRKDKT LLRDEKKMEK LKQKLHTDDE LNWLDHGRTL REQGVEEHET LLLRRKFFYS DQNVDSRDPV QLNLLYVQAR DDILNGSHPV SFDKACEFAG FQCQIQFGPH NEQKHKAGFL DLKDFLPKEY VKQKGERKIF QAHKNCGQMS EIEAKVRYVK LARSLKTYGV SFFLVKEKMK GKNKLVPRLL GITKECVMRV DEKTKEVIQE WNLTNIKRWA ASPKSFTLDF GDYQDGYYSV QTTEGEQIAQ LIAGYIDIIL KKKKSKDHFG LEGDEESTML EDSVSPKKST VLQQQYNRVG KVEHGSVALP AIMRSGASGP ENFQVGSMPP AQQQITSGQM HRGHMPPLTS AQQALTGTIN SSMQAVQAAQ ATLDDFDTLP PLGQDAASKA WRKNKMDESK HEIHSQVDAI TAGTASVVNL TAGDPAETDY TAVGCAVTTI SSNLTEMSRG VKLLAALLED EGGSGRPLLQ AAKGLAGAVS ELLRSAQPAS AEPRQNLLQA AGNVGQASGE LLQQIGESDT DPHFQDALMQ LAKAVASAAA ALVLKAKSVA QRTEDSGLQT QVIAAATQCA LSTSQLVACT KVVAPTISSP VCQEQLVEAG RLVAKAVEGC VSASQAATED GQLLRGVGAA ATAVTQALNE LLQHVKAHAT GAGPAGRYDQ ATDTILTVTE NIFSSMGDAG EMVRQARILA QATSDLVNAI KADAEGESDL ENSRKLLSAA KILADATAKM VEAAKGAAAH PDSEEQQQRL REAAEGLRMA TNAAAQNAIK KKLVQRLEHA AKQAAASATQ TIAAAQHAAS TPKASAGPQP LLVQSCKAVA EQIPLLVQGV RGSQAQPDSP SAQLALIAAS QSFLQPGGKM VAAAKASVPT IQDQASAMQL SQCAKNLGTA LAELRTAAQK AQEACGPLEM DSALSVVQNL EKDLQEVKAA ARDGKLKPLP GETMEKCTQD LGNSTKAVSS AIAQLLGEVA QGNENYAGIA ARDVAGGLRS LAQAARGVAA LTSDPAVQAI VLDTASDVLD KASSLIEEAK KAAGHPGDPE SQQRLAQVAK AVTQALNRCV SCLPGQRDVD NALRAVGDAS KRLLSDSLPP STGTFQEAQS RLNEAAAGLN QAATELVQAS RGTPQDLARA SGRFGQDFST FLEAGVEMAG QAPSQEDRAQ VVSNLKGISM SSSKLLLAAK ALSTDPAAPN LKSQLAAAAR AVTDSINQLI TMCTQQAPGQ KECDNALREL ETVRELLENP VQPINDMSYF GCLDSVMENS KVLGEAMTGI SQNAKNGNLP EFGDAISTAS KALCGFTEAA AQAAYLVGVS DPNSQAGQQG LVEPTQFARA NQAIQMACQS LGEPGCTQAQ VLSAATIVAK HTSALCNSCR LASARTTNPT AKRQFVQSAK EVANSTANLV KTIKALDGAF TEENRAQCRA ATAPLLEAVD NLSAFASNPE FSSIPAQISP EGRAAMEPIV ISAKTMLESA GGLIQTARAL AVNPRDPPSW SVLAGHSRTV SDSIKKLITS MRDKAPGQLE CETAIAALNS CLRDLDQASL AAVSQQLAPR EGISQEALHT QMLTAVQEIS HLIEPLANAA RAEASQLGHK VSQMAQYFEP LTLAAVGAAS KTLSHPQQMA LLDQTKTLAE SALQLLYTAK EAGGNPKQAA HTQEALEEAV QMMTEAVEDL TTTLNEAASA AGVVGGMVDS ITQAINQLDE GPMGEPEGSF VDYQTTMVRT AKAIAVTVQE MVTKSNTSPE ELGPLANQLT SDYGRLASEA KPAAVAAENE EIGSHIKHRV QELGHGCAAL VTKAGALQCS PSDAYTKKEL IECARRVSEK VSHVLAALQA GNRGTQACIT AASAVSGIIA DLDTTIMFAT AGTLNREGTE TFADHREGIL KTAKVLVEDT KVLVQNAAGS QEKLAQAAQS SVATITRLAD VVKLGAASLG AEDPETQVVL INAVKDVAKA LGDLISATKA AAGKVGDDPA VWQLKNSAKV MVTNVTSLLK TVKAVEDEAT KGTRALEATT EHIRQELAVF CSPEPPAKTS TPEDFIRMTK GITMATAKAV AAGNSCRQED VIATANLSRR AIADMLRACK EAAYHPEVAP DVRLRALHYG RECANGYLEL LDHVLLTLQK PSPELKQQLT GHSKRVAGSV TELIQAAEAM KGTEWVDPED PTVIAENELL GAAAAIEAAA KKLEQLKPRA KPKEADESLN FEEQILEAAK SIAAATSALV KAASAAQREL VAQGKVGAIP ANALDDGQWS QGLISAARMV AAATNNLCEA ANAAVQGHAS QEKLISSAKQ VAASTAQLLV ACKVKADQDS EAMKRLQAAG NAVKRASDNL VKAAQKAAAF EEQENETVVV KEKMVGGIAQ IIAAQEEMLR KERELEEARK KLAQIRQQQY KFLPSELRDE H //