Full text data of TLN1
TLN1
(KIAA1027, TLN)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Talin-1
Talin-1
UniProt
Q9Y490
ID TLN1_HUMAN Reviewed; 2541 AA.
AC Q9Y490; A6NMY0; Q86YD0; Q9NZQ2; Q9UHH8; Q9UPX3;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
read moreDT 08-NOV-2005, sequence version 3.
DT 22-JAN-2014, entry version 142.
DE RecName: Full=Talin-1;
GN Name=TLN1; Synonyms=KIAA1027, TLN;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], 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].
RC TISSUE=Brain;
RX PubMed=10470851; DOI=10.1093/dnares/6.3.197;
RA Kikuno R., Nagase T., Ishikawa K., Hirosawa M., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIV.
RT The complete sequences of 100 new cDNA clones from brain which code
RT for large 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 [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.,
RA Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S.,
RA Babbage A.K., Babbage S., Bagguley C.L., Bailey J., Banerjee R.,
RA Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W.,
RA Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G.,
RA Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M.,
RA Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W.,
RA Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A.,
RA Frankland J.A., French L., Fricker D.G., Garner P., Garnett J.,
RA 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.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M.,
RA Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S.,
RA McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J.,
RA Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R.,
RA Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M.,
RA Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M.,
RA Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A.,
RA Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W.,
RA 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.,
RA Rogers J., Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], 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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
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;
RP 442-454; 593-634; 674-685; 722-741; 766-824; 828-854; 862-869;
RP 876-910; 923-943; 958-999; 1026-1035; 1076-1086; 1097-1122; 1130-1184;
RP 1191-1198; 1208-1214; 1223-1269; 1274-1306; 1321-1340; 1362-1368;
RP 1402-1431; 1531-1541; 1560-1646; 1674-1780; 1863-1917; 1961-1973;
RP 2007-2016; 2025-2057; 2064-2085; 2090-2099; 2105-2115; 2120-2130;
RP 2134-2141; 2145-2154; 2169-2177; 2198-2209; 2221-2233; 2267-2274;
RP 2276-2321; 2322-2329; 2334-2361; 2369-2398; 2430-2443; 2456-2472;
RP 2477-2491; 2494-2510 AND 2512-2519, AND MASS SPECTROMETRY.
RC TISSUE=Platelet;
RA Bienvenut W.V., Claeys D.;
RL Submitted (NOV-2005) to UniProtKB.
RN [9]
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
RT striated muscle myotendon junctions and intercalated disks.";
RL Biochemistry 38:6135-6143(1999).
RN [10]
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
RT regulates focal adhesions.";
RL Nature 420:89-93(2002).
RN [11]
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-
RT associated protein-1 alpha.";
RL J. Biol. Chem. 278:6567-6574(2003).
RN [12]
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.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [13]
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
RT that interacts directly with talin.";
RL Exp. Cell Res. 314:1839-1849(2008).
RN [14]
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 [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-425, AND MASS
RP SPECTROMETRY.
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 [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-425, AND MASS
RP SPECTROMETRY.
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 [17]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-2031 AND LYS-2115, AND MASS
RP SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., 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 [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-425, AND MASS
RP SPECTROMETRY.
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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [19]
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.,
RA Buerckstuemmer T., 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 [20]
RP INTERACTION WITH ITGB1.
RX PubMed=21768292; DOI=10.1083/jcb.201007108;
RA Brunner M., Millon-Fremillon A., Chevalier G., Nakchbandi I.A.,
RA Mosher D., 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 [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2040, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [22]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [23]
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: Probably involved in connections of major cytoskeletal
CC structures to the plasma membrane. High molecular weight
CC cytoskeletal protein concentrated at regions of cell-substratum
CC contact and, in lymphocytes, at cell-cell contacts (By
CC similarity).
CC -!- SUBUNIT: Binds with high affinity to VCL and with low affinity to
CC integrins. Interacts with APBB1IP; this inhibits VCL binding.
CC Interacts with PTK2/FAK1 (By similarity). Interacts with PIP5K1C
CC and NRAP. Interacts with LAYN. Interacts with SYNM. Interacts with
CC ITGB1; the interaction is prevented by competitive binding of
CC ITGB1BP1.
CC -!- INTERACTION:
CC P00533:EGFR; NbExp=2; IntAct=EBI-2462036, EBI-297353;
CC P04626:ERBB2; NbExp=3; IntAct=EBI-2462036, EBI-641062;
CC P05556:ITGB1; NbExp=2; IntAct=EBI-2462036, EBI-703066;
CC P05106:ITGB3; NbExp=4; IntAct=EBI-2462036, EBI-702847;
CC -!- SUBCELLULAR LOCATION: Cell projection, ruffle membrane; Peripheral
CC membrane protein; Cytoplasmic side (By similarity). Cytoplasm,
CC cytoskeleton (By similarity). Cell surface (By similarity). Cell
CC junction, focal adhesion (By similarity). Note=Colocalizes with
CC LAYN at the membrane ruffles. Localized preferentially in focal
CC adhesions than fibrillar adhesions (By similarity).
CC -!- SIMILARITY: Contains 1 FERM domain.
CC -!- SIMILARITY: Contains 1 I/LWEQ domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA82979.2; Type=Erroneous initiation;
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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; AL133410; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471071; EAW58352.1; -; Genomic_DNA.
DR EMBL; BC042923; AAH42923.1; -; mRNA.
DR RefSeq; NP_006280.3; NM_006289.3.
DR UniGene; Hs.471014; -.
DR PDB; 1SYQ; X-ray; 2.42 A; B=607-631.
DR PDB; 4DJ9; X-ray; 2.25 A; B=2075-2103.
DR PDBsum; 1SYQ; -.
DR PDBsum; 4DJ9; -.
DR ProteinModelPortal; Q9Y490; -.
DR SMR; Q9Y490; 1-400, 485-911, 913-1044, 1046-1357, 1359-1973, 1975-2291, 2296-2482, 2496-2529.
DR IntAct; Q9Y490; 10.
DR MINT; MINT-5002070; -.
DR STRING; 9606.ENSP00000316029; -.
DR PhosphoSite; Q9Y490; -.
DR DMDM; 81175200; -.
DR OGP; Q9Y490; -.
DR PaxDb; Q9Y490; -.
DR PRIDE; Q9Y490; -.
DR Ensembl; ENST00000314888; ENSP00000316029; ENSG00000137076.
DR GeneID; 7094; -.
DR KEGG; hsa:7094; -.
DR UCSC; uc003zxt.2; human.
DR CTD; 7094; -.
DR GeneCards; GC09M035687; -.
DR HGNC; HGNC:11845; TLN1.
DR HPA; CAB002006; -.
DR HPA; HPA004748; -.
DR MIM; 186745; gene.
DR neXtProt; NX_Q9Y490; -.
DR PharmGKB; PA36547; -.
DR eggNOG; NOG324465; -.
DR HOGENOM; HOG000006734; -.
DR HOVERGEN; HBG023870; -.
DR InParanoid; Q9Y490; -.
DR KO; K06271; -.
DR OMA; ITNHEEY; -.
DR OrthoDB; EOG7TBC1J; -.
DR Reactome; REACT_111045; Developmental Biology.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_17015; Metabolism of proteins.
DR Reactome; REACT_17044; Muscle contraction.
DR Reactome; REACT_604; Hemostasis.
DR ChiTaRS; TLN1; human.
DR EvolutionaryTrace; Q9Y490; -.
DR GeneWiki; TLN1; -.
DR GenomeRNAi; 7094; -.
DR NextBio; 27751; -.
DR PRO; PR:Q9Y490; -.
DR ArrayExpress; Q9Y490; -.
DR Bgee; Q9Y490; -.
DR CleanEx; HS_TLN1; -.
DR Genevestigator; Q9Y490; -.
DR GO; GO:0015629; C:actin cytoskeleton; IEA:InterPro.
DR GO; GO:0009986; C:cell surface; IEA:UniProtKB-SubCell.
DR GO; GO:0005911; C:cell-cell junction; IC:UniProtKB.
DR GO; GO:0005813; C:centrosome; IDA:HPA.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular vesicular exosome; IDA:UniProtKB.
DR GO; GO:0005925; C:focal adhesion; NAS:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0001726; C:ruffle; ISS:HGNC.
DR GO; GO:0032587; C:ruffle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005200; F:structural constituent of cytoskeleton; NAS:UniProtKB.
DR GO; GO:0006987; P:activation of signaling protein activity involved in unfolded protein response; TAS:Reactome.
DR GO; GO:0007411; P:axon guidance; TAS:Reactome.
DR GO; GO:0007155; P:cell adhesion; IEA:InterPro.
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:0044267; P:cellular protein metabolic process; TAS:Reactome.
DR GO; GO:0030866; P:cortical actin cytoskeleton organization; IEA:Ensembl.
DR GO; GO:0007016; P:cytoskeletal anchoring at plasma membrane; NAS:UniProtKB.
DR GO; GO:0006936; P:muscle contraction; TAS:Reactome.
DR GO; GO:0030168; P:platelet activation; TAS:Reactome.
DR GO; GO:0002576; P:platelet degranulation; TAS:Reactome.
DR Gene3D; 1.20.1420.10; -; 1.
DR Gene3D; 1.20.80.10; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR019749; Band_41_domain.
DR InterPro; IPR014352; FERM/acyl-CoA-bd_prot_3-hlx.
DR InterPro; IPR019748; FERM_central.
DR InterPro; IPR019747; FERM_CS.
DR InterPro; IPR000299; FERM_domain.
DR InterPro; IPR018979; FERM_N.
DR InterPro; IPR002558; ILWEQ_dom.
DR InterPro; IPR002404; Insln_rcpt_S1.
DR InterPro; IPR011993; PH_like_dom.
DR InterPro; IPR015710; Talin-1.
DR InterPro; IPR015224; Talin_cent.
DR InterPro; IPR015009; Vinculin-bd_dom.
DR InterPro; IPR006077; Vinculin/catenin.
DR PANTHER; PTHR19981:SF7; PTHR19981:SF7; 1.
DR Pfam; PF00373; FERM_M; 1.
DR Pfam; PF09379; FERM_N; 1.
DR Pfam; PF01608; I_LWEQ; 1.
DR Pfam; PF02174; IRS; 1.
DR Pfam; PF09141; Talin_middle; 1.
DR Pfam; PF08913; VBS; 2.
DR ProDom; PD011820; ILWEQ; 1.
DR SMART; SM00295; B41; 1.
DR SMART; SM00307; ILWEQ; 1.
DR SUPFAM; SSF109880; SSF109880; 1.
DR SUPFAM; SSF47031; SSF47031; 1.
DR SUPFAM; SSF47220; SSF47220; 5.
DR PROSITE; PS00660; FERM_1; 1.
DR PROSITE; PS00661; FERM_2; 1.
DR PROSITE; PS50057; FERM_3; 1.
DR PROSITE; PS50945; I_LWEQ; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cell junction; Cell membrane;
KW Cell projection; Complete proteome; Cytoplasm; Cytoskeleton;
KW Direct protein sequencing; Membrane; Phosphoprotein; Polymorphism;
KW Reference proteome.
FT CHAIN 1 2541 Talin-1.
FT /FTId=PRO_0000219428.
FT DOMAIN 86 403 FERM.
FT DOMAIN 2293 2533 I/LWEQ.
FT REGION 280 435 Interaction with LAYN (By similarity).
FT REGION 1327 1948 Interaction with SYNM.
FT MOD_RES 425 425 Phosphoserine.
FT MOD_RES 1116 1116 Phosphotyrosine (By similarity).
FT MOD_RES 2031 2031 N6-acetyllysine.
FT MOD_RES 2040 2040 Phosphoserine.
FT MOD_RES 2115 2115 N6-acetyllysine.
FT VARIANT 1227 1227 S -> L (in dbSNP:rs2295795).
FT /FTId=VAR_023751.
FT VARIANT 1919 1919 R -> W (in dbSNP:rs17854239).
FT /FTId=VAR_023752.
FT VARIANT 1984 1984 A -> T (in dbSNP:rs35642290).
FT /FTId=VAR_055538.
FT CONFLICT 824 824 R -> G (in Ref. 1; AAD13152 and 2;
FT AAF23322).
FT CONFLICT 1549 1549 A -> P (in Ref. 1; AAD13152 and 2;
FT AAF23322).
FT CONFLICT 1604 1604 K -> Q (in Ref. 1; AAD13152 and 2;
FT AAF23322).
FT CONFLICT 1701 1701 Q -> E (in Ref. 1; AAD13152 and 2;
FT AAF23322).
FT CONFLICT 1718 1718 N -> H (in Ref. 1; AAD13152 and 2;
FT AAF23322).
FT CONFLICT 1966 1966 A -> R (in Ref. 1; AAD13152).
FT CONFLICT 2256 2256 Missing (in Ref. 2; AAF27330).
FT HELIX 608 625
FT HELIX 2079 2098
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
//
ID TLN1_HUMAN Reviewed; 2541 AA.
AC Q9Y490; A6NMY0; Q86YD0; Q9NZQ2; Q9UHH8; Q9UPX3;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
read moreDT 08-NOV-2005, sequence version 3.
DT 22-JAN-2014, entry version 142.
DE RecName: Full=Talin-1;
GN Name=TLN1; Synonyms=KIAA1027, TLN;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], 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].
RC TISSUE=Brain;
RX PubMed=10470851; DOI=10.1093/dnares/6.3.197;
RA Kikuno R., Nagase T., Ishikawa K., Hirosawa M., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIV.
RT The complete sequences of 100 new cDNA clones from brain which code
RT for large 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 [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.,
RA Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S.,
RA Babbage A.K., Babbage S., Bagguley C.L., Bailey J., Banerjee R.,
RA Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W.,
RA Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G.,
RA Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M.,
RA Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W.,
RA Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A.,
RA Frankland J.A., French L., Fricker D.G., Garner P., Garnett J.,
RA 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.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M.,
RA Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S.,
RA McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J.,
RA Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R.,
RA Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M.,
RA Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M.,
RA Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A.,
RA Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W.,
RA 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.,
RA Rogers J., Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], 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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
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;
RP 442-454; 593-634; 674-685; 722-741; 766-824; 828-854; 862-869;
RP 876-910; 923-943; 958-999; 1026-1035; 1076-1086; 1097-1122; 1130-1184;
RP 1191-1198; 1208-1214; 1223-1269; 1274-1306; 1321-1340; 1362-1368;
RP 1402-1431; 1531-1541; 1560-1646; 1674-1780; 1863-1917; 1961-1973;
RP 2007-2016; 2025-2057; 2064-2085; 2090-2099; 2105-2115; 2120-2130;
RP 2134-2141; 2145-2154; 2169-2177; 2198-2209; 2221-2233; 2267-2274;
RP 2276-2321; 2322-2329; 2334-2361; 2369-2398; 2430-2443; 2456-2472;
RP 2477-2491; 2494-2510 AND 2512-2519, AND MASS SPECTROMETRY.
RC TISSUE=Platelet;
RA Bienvenut W.V., Claeys D.;
RL Submitted (NOV-2005) to UniProtKB.
RN [9]
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
RT striated muscle myotendon junctions and intercalated disks.";
RL Biochemistry 38:6135-6143(1999).
RN [10]
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
RT regulates focal adhesions.";
RL Nature 420:89-93(2002).
RN [11]
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-
RT associated protein-1 alpha.";
RL J. Biol. Chem. 278:6567-6574(2003).
RN [12]
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.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [13]
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
RT that interacts directly with talin.";
RL Exp. Cell Res. 314:1839-1849(2008).
RN [14]
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 [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-425, AND MASS
RP SPECTROMETRY.
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 [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-425, AND MASS
RP SPECTROMETRY.
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 [17]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-2031 AND LYS-2115, AND MASS
RP SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., 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 [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-425, AND MASS
RP SPECTROMETRY.
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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [19]
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.,
RA Buerckstuemmer T., 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 [20]
RP INTERACTION WITH ITGB1.
RX PubMed=21768292; DOI=10.1083/jcb.201007108;
RA Brunner M., Millon-Fremillon A., Chevalier G., Nakchbandi I.A.,
RA Mosher D., 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 [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2040, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [22]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [23]
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: Probably involved in connections of major cytoskeletal
CC structures to the plasma membrane. High molecular weight
CC cytoskeletal protein concentrated at regions of cell-substratum
CC contact and, in lymphocytes, at cell-cell contacts (By
CC similarity).
CC -!- SUBUNIT: Binds with high affinity to VCL and with low affinity to
CC integrins. Interacts with APBB1IP; this inhibits VCL binding.
CC Interacts with PTK2/FAK1 (By similarity). Interacts with PIP5K1C
CC and NRAP. Interacts with LAYN. Interacts with SYNM. Interacts with
CC ITGB1; the interaction is prevented by competitive binding of
CC ITGB1BP1.
CC -!- INTERACTION:
CC P00533:EGFR; NbExp=2; IntAct=EBI-2462036, EBI-297353;
CC P04626:ERBB2; NbExp=3; IntAct=EBI-2462036, EBI-641062;
CC P05556:ITGB1; NbExp=2; IntAct=EBI-2462036, EBI-703066;
CC P05106:ITGB3; NbExp=4; IntAct=EBI-2462036, EBI-702847;
CC -!- SUBCELLULAR LOCATION: Cell projection, ruffle membrane; Peripheral
CC membrane protein; Cytoplasmic side (By similarity). Cytoplasm,
CC cytoskeleton (By similarity). Cell surface (By similarity). Cell
CC junction, focal adhesion (By similarity). Note=Colocalizes with
CC LAYN at the membrane ruffles. Localized preferentially in focal
CC adhesions than fibrillar adhesions (By similarity).
CC -!- SIMILARITY: Contains 1 FERM domain.
CC -!- SIMILARITY: Contains 1 I/LWEQ domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA82979.2; Type=Erroneous initiation;
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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; AL133410; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471071; EAW58352.1; -; Genomic_DNA.
DR EMBL; BC042923; AAH42923.1; -; mRNA.
DR RefSeq; NP_006280.3; NM_006289.3.
DR UniGene; Hs.471014; -.
DR PDB; 1SYQ; X-ray; 2.42 A; B=607-631.
DR PDB; 4DJ9; X-ray; 2.25 A; B=2075-2103.
DR PDBsum; 1SYQ; -.
DR PDBsum; 4DJ9; -.
DR ProteinModelPortal; Q9Y490; -.
DR SMR; Q9Y490; 1-400, 485-911, 913-1044, 1046-1357, 1359-1973, 1975-2291, 2296-2482, 2496-2529.
DR IntAct; Q9Y490; 10.
DR MINT; MINT-5002070; -.
DR STRING; 9606.ENSP00000316029; -.
DR PhosphoSite; Q9Y490; -.
DR DMDM; 81175200; -.
DR OGP; Q9Y490; -.
DR PaxDb; Q9Y490; -.
DR PRIDE; Q9Y490; -.
DR Ensembl; ENST00000314888; ENSP00000316029; ENSG00000137076.
DR GeneID; 7094; -.
DR KEGG; hsa:7094; -.
DR UCSC; uc003zxt.2; human.
DR CTD; 7094; -.
DR GeneCards; GC09M035687; -.
DR HGNC; HGNC:11845; TLN1.
DR HPA; CAB002006; -.
DR HPA; HPA004748; -.
DR MIM; 186745; gene.
DR neXtProt; NX_Q9Y490; -.
DR PharmGKB; PA36547; -.
DR eggNOG; NOG324465; -.
DR HOGENOM; HOG000006734; -.
DR HOVERGEN; HBG023870; -.
DR InParanoid; Q9Y490; -.
DR KO; K06271; -.
DR OMA; ITNHEEY; -.
DR OrthoDB; EOG7TBC1J; -.
DR Reactome; REACT_111045; Developmental Biology.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_17015; Metabolism of proteins.
DR Reactome; REACT_17044; Muscle contraction.
DR Reactome; REACT_604; Hemostasis.
DR ChiTaRS; TLN1; human.
DR EvolutionaryTrace; Q9Y490; -.
DR GeneWiki; TLN1; -.
DR GenomeRNAi; 7094; -.
DR NextBio; 27751; -.
DR PRO; PR:Q9Y490; -.
DR ArrayExpress; Q9Y490; -.
DR Bgee; Q9Y490; -.
DR CleanEx; HS_TLN1; -.
DR Genevestigator; Q9Y490; -.
DR GO; GO:0015629; C:actin cytoskeleton; IEA:InterPro.
DR GO; GO:0009986; C:cell surface; IEA:UniProtKB-SubCell.
DR GO; GO:0005911; C:cell-cell junction; IC:UniProtKB.
DR GO; GO:0005813; C:centrosome; IDA:HPA.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular vesicular exosome; IDA:UniProtKB.
DR GO; GO:0005925; C:focal adhesion; NAS:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0001726; C:ruffle; ISS:HGNC.
DR GO; GO:0032587; C:ruffle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005200; F:structural constituent of cytoskeleton; NAS:UniProtKB.
DR GO; GO:0006987; P:activation of signaling protein activity involved in unfolded protein response; TAS:Reactome.
DR GO; GO:0007411; P:axon guidance; TAS:Reactome.
DR GO; GO:0007155; P:cell adhesion; IEA:InterPro.
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:0044267; P:cellular protein metabolic process; TAS:Reactome.
DR GO; GO:0030866; P:cortical actin cytoskeleton organization; IEA:Ensembl.
DR GO; GO:0007016; P:cytoskeletal anchoring at plasma membrane; NAS:UniProtKB.
DR GO; GO:0006936; P:muscle contraction; TAS:Reactome.
DR GO; GO:0030168; P:platelet activation; TAS:Reactome.
DR GO; GO:0002576; P:platelet degranulation; TAS:Reactome.
DR Gene3D; 1.20.1420.10; -; 1.
DR Gene3D; 1.20.80.10; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR019749; Band_41_domain.
DR InterPro; IPR014352; FERM/acyl-CoA-bd_prot_3-hlx.
DR InterPro; IPR019748; FERM_central.
DR InterPro; IPR019747; FERM_CS.
DR InterPro; IPR000299; FERM_domain.
DR InterPro; IPR018979; FERM_N.
DR InterPro; IPR002558; ILWEQ_dom.
DR InterPro; IPR002404; Insln_rcpt_S1.
DR InterPro; IPR011993; PH_like_dom.
DR InterPro; IPR015710; Talin-1.
DR InterPro; IPR015224; Talin_cent.
DR InterPro; IPR015009; Vinculin-bd_dom.
DR InterPro; IPR006077; Vinculin/catenin.
DR PANTHER; PTHR19981:SF7; PTHR19981:SF7; 1.
DR Pfam; PF00373; FERM_M; 1.
DR Pfam; PF09379; FERM_N; 1.
DR Pfam; PF01608; I_LWEQ; 1.
DR Pfam; PF02174; IRS; 1.
DR Pfam; PF09141; Talin_middle; 1.
DR Pfam; PF08913; VBS; 2.
DR ProDom; PD011820; ILWEQ; 1.
DR SMART; SM00295; B41; 1.
DR SMART; SM00307; ILWEQ; 1.
DR SUPFAM; SSF109880; SSF109880; 1.
DR SUPFAM; SSF47031; SSF47031; 1.
DR SUPFAM; SSF47220; SSF47220; 5.
DR PROSITE; PS00660; FERM_1; 1.
DR PROSITE; PS00661; FERM_2; 1.
DR PROSITE; PS50057; FERM_3; 1.
DR PROSITE; PS50945; I_LWEQ; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cell junction; Cell membrane;
KW Cell projection; Complete proteome; Cytoplasm; Cytoskeleton;
KW Direct protein sequencing; Membrane; Phosphoprotein; Polymorphism;
KW Reference proteome.
FT CHAIN 1 2541 Talin-1.
FT /FTId=PRO_0000219428.
FT DOMAIN 86 403 FERM.
FT DOMAIN 2293 2533 I/LWEQ.
FT REGION 280 435 Interaction with LAYN (By similarity).
FT REGION 1327 1948 Interaction with SYNM.
FT MOD_RES 425 425 Phosphoserine.
FT MOD_RES 1116 1116 Phosphotyrosine (By similarity).
FT MOD_RES 2031 2031 N6-acetyllysine.
FT MOD_RES 2040 2040 Phosphoserine.
FT MOD_RES 2115 2115 N6-acetyllysine.
FT VARIANT 1227 1227 S -> L (in dbSNP:rs2295795).
FT /FTId=VAR_023751.
FT VARIANT 1919 1919 R -> W (in dbSNP:rs17854239).
FT /FTId=VAR_023752.
FT VARIANT 1984 1984 A -> T (in dbSNP:rs35642290).
FT /FTId=VAR_055538.
FT CONFLICT 824 824 R -> G (in Ref. 1; AAD13152 and 2;
FT AAF23322).
FT CONFLICT 1549 1549 A -> P (in Ref. 1; AAD13152 and 2;
FT AAF23322).
FT CONFLICT 1604 1604 K -> Q (in Ref. 1; AAD13152 and 2;
FT AAF23322).
FT CONFLICT 1701 1701 Q -> E (in Ref. 1; AAD13152 and 2;
FT AAF23322).
FT CONFLICT 1718 1718 N -> H (in Ref. 1; AAD13152 and 2;
FT AAF23322).
FT CONFLICT 1966 1966 A -> R (in Ref. 1; AAD13152).
FT CONFLICT 2256 2256 Missing (in Ref. 2; AAF27330).
FT HELIX 608 625
FT HELIX 2079 2098
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
//
MIM
186745
*RECORD*
*FIELD* NO
186745
*FIELD* TI
*186745 TALIN 1; TLN1
;;TALIN; TLN
*FIELD* TX
DESCRIPTION
Talin links vinculin (193065) to the integrins, and, thus, the
read morecytoskeleton to extracellular matrix (ECM) receptors. It has a mass of
270 kD and shares 23% N-terminal identity with ezrin (123900), which has
similar functions (Rees et al., 1990).
GENE FUNCTION
DiPaolo et al. (2002) and Ling et al. (2002) presented evidence that
talin, through its FERM domain, interacts with the C-terminal tail of
the 90-kD PIP5K1C (606102) isoform. The authors showed that this
interaction induces clustering of PIP5D1C and talin at focal adhesions
and increases the local production of
phosphatidylinositol-4,5-bisphosphate.
Mechanical forces on matrix-integrin-cytoskeleton linkages are crucial
for cell viability, morphology, and organ function. The production of
force depends on the molecular connections from ECM-integrin complexes
to the cytoskeleton. The minimal matrix complex causing
integrin-cytoskeleton connections is a trimer of fibronectin's (135600)
integrin-binding domain FNIII7-10. Jiang et al. (2003) reported a
specific molecular slip bond that was repeatedly broken by a force of 2
pN at the cellular loading rate of 60 nm/second; this occurred with
single trimer beads but not with the monomer. Talin-1, which binds to
integrins and actin filaments in vitro, is required for the 2-pN slip
bond and rapid cytoskeleton binding. Furthermore, Jiang et al. (2003)
showed that inhibition of fibronectin binding to alpha-v-beta-3 integrin
(193210 and 173470) and deletion of beta-3 markedly decreased the 2-pN
force peak. They suggested that talin-1 initially forms a molecular slip
bond between closely packed fibronectin-integrin complexes and the actin
cytoskeleton, which can apply a low level of force to fibronectin until
many bonds form or a signal is received to activate a force response.
Tadokoro et al. (2003) reported that specific binding of the
cytoskeletal protein talin to integrin beta subunit (135630) cytoplasmic
tails leads to the conformational rearrangements of integrin
extracellular domains that increase their affinity. They found that
regulated binding of talin to integrin beta tails is a final common
element of cellular signaling cascades that control integrin activation.
Hu et al. (2007) developed correlational fluorescent speckle microscopy
to measure the coupling of focal adhesion proteins to actin filaments
(see 102610). Different classes of focal adhesion structural and
regulatory molecules exhibited varying degrees of correlated motions
with actin filaments, indicating hierarchical transmission of actin
motion through focal adhesions. Interactions between vinculin (193065),
talin, and actin filaments appear to constitute a slippage interface
between the cytoskeleton and integrins, generating a molecular clutch
that is regulated during the morphodynamic transitions of cell
migration.
Kanchanawong et al. (2010) used 3-dimensional super-resolution
fluorescence microscopy to map nanoscale protein organization in focal
adhesions. Their results revealed that integrins and actin are
vertically separated by an approximately 40-nm focal adhesion core
region consisting of multiple protein-specific strata: a
membrane-apposed integrin signaling layer containing integrin
cytoplasmic tails (see 193210), focal adhesion kinase (600758), and
paxillin (602505); an intermediate force-transduction layer containing
talin and vinculin; and an uppermost actin-regulatory layer containing
zyxin (602002), vasodilator-stimulated phosphoprotein (601703), and
alpha-actinin (102575). By localizing amino- and carboxy-terminally
tagged talins, Kanchanawong et al. (2010) revealed talin's polarized
orientation, indicative of a role in organizing the focal adhesion
strata. Kanchanawong et al. (2010) concluded that their composite
multilaminar protein architecture provided a molecular blueprint for
understanding focal adhesion functions.
Shen et al. (2013) demonstrated that G-alpha-13 (604406) and talin bind
to mutually exclusive but distinct sites within the integrin beta-3
cytoplasmic domain in opposing waves. The first talin-binding wave
mediates inside-out signaling and also ligand-induced integrin
activation, but is not required for outside-in signaling. Integrin
ligation induces transient talin dissociation and G-alpha-13 binding to
an EXE motif (in which X denotes any residue), which selectively
mediates outside-in signaling and platelet spreading. The second
talin-binding wave is associated with clot retraction. An
EXE-motif-based inhibitor of G-alpha-13-integrin interaction selectively
abolishes outside-in signaling without affecting integrin ligation, and
suppresses occlusive arterial thrombosis without affecting bleeding
time. Shen et al. (2013) concluded that they discovered a mechanism for
the directional switch of integrin signaling and, on the basis of this
mechanism, designed a potent antithrombotic drug that does not cause
bleeding.
BIOCHEMICAL FEATURES
Using magnetic tweezers, total internal reflection fluorescence, and
atomic force microscopy, del Rio et al. (2009) investigated the effect
of force on the interaction between talin, a protein that links liganded
membrane integrins to the cytoskeleton, and vinculin, a focal adhesion
protein that is activated by talin binding, leading to reorganization of
the cytoskeleton. Application of physiologically relevant forces caused
stretching of single talin rods that exposed cryptic binding sites for
vinculin. Thus in the talin-vinculin system, molecular
mechanotransduction can occur by protein binding after exposure of
buried binding sites in the talin-vinculin system.
MAPPING
Using PCR amplification and DNA from a panel of human/rodent somatic
cell hybrids, Gilmore et al. (1995) assigned the TLN gene to 9p.
Deletions in 9p have been implicated in a variety of cancers. That a
cytoskeletal protein associated with the cell adhesion apparatus, such
as talin, might behave as a tumor suppressor gene has been proposed. For
example, the APC tumor suppressor gene (APC; 611731) encodes a protein
that associates with beta-catenin (CTNNB1; 116806), a component of a
complex of proteins linked to the cytoplasmic face of the cadherin
family of cell-cell adhesion molecules. Similarly, talin is a component
of a complex of proteins linked to the cytoplasmic face of integrins in
cell-ECM junctions (Luna and Hitt, 1992).
*FIELD* RF
1. del Rio, A.; Perez-Jimenez, R.; Liu, R.; Roca-Cusachs, P.; Fernandez,
J. M.; Sheetz, M. P.: Stretching single talin rod molecules activates
vinculin binding. Science 323: 638-641, 2009.
2. Di Paolo, G.; Pellegrini, L.; Letinic, K.; Cestra, G.; Zoncu, R.;
Voronov, S.; Chang, S.; Guo, J.; Wenk, M. R.; De Camill, P.: Recruitment
and regulation of phosphatidylinositol phosphate kinase type I-gamma
by the FERM domain of talin. Nature 420: 85-89, 2002.
3. Gilmore, A. P.; Ohanian, V.; Spurr, N. K.; Critchley, D. R.: Localisation
of the human gene encoding the cytoskeletal protein talin to chromosome
9p. Hum. Genet. 96: 221-224, 1995.
4. Hu, K.; Ji, L.; Applegate, K. T.; Danuser, G.; Waterman-Storer,
C. M.: Differential transmission of actin motion within focal adhesions. Science 315:
111-115, 2007.
5. Jiang, G.; Giannone, G.; Critchley, D. R.; Fukumoto, E.; Sheetz,
M. P.: Two-piconewton slip bond between fibronectin and the cytoskeleton
depends on talin. Nature 424: 334-337, 2003.
6. Kanchanawong, P.; Shtengel, G.; Pasapera, A. M.; Ramko, E. B.;
Davidson, M. W.; Hess, H. F.; Waterman, C. M.: Nanoscale architecture
of integrin-based cell adhesions. Nature 468: 580-584, 2010.
7. Ling, K.; Doughman, R. L.; Firestone, A. J.; Bunce, M. W.; Anderson,
R. A.: Type I-gamma phosphatidylinositol phosphate kinase targets
and regulates focal adhesions. Nature 420: 89-93, 2002.
8. Luna, E. J.; Hitt, A. L.: Cytoskeleton-plasma membrane interactions. Science 258:
955-964, 1992.
9. Rees, D. J. G.; Ades, S. E.; Singer, S. J.; Hynes, R. O.: Sequence
and domain structure of talin. Nature 347: 685-689, 1990.
10. Shen, B.; Zhao, X.; O'Brien, K. A.; Stojanovic-Terpo, A.; Delaney,
M. K.; Kim, K.; Cho, J.; Lam, S. C.-T.; Du, X.: A directional switch
of integrin signalling and a new anti-thrombotic strategy. Nature 503:
131-135, 2013.
11. Tadokoro, S.; Shattil, S. J.; Eto, K.; Tai, V.; Liddington, R.
C.; de Pereda, J. M.; Ginsberg, M. H.; Calderwood, D. A.: Talin binding
to integrin beta tails: a final common step in integrin activation. Science 302:
103-106, 2003.
*FIELD* CN
Ada Hamosh - updated: 11/21/2013
Ada Hamosh - updated: 2/2/2011
Ada Hamosh - updated: 3/10/2009
Ada Hamosh - updated: 2/20/2007
Ada Hamosh - updated: 10/29/2003
Ada Hamosh - updated: 7/24/2003
Patricia A. Hartz - updated: 11/7/2002
*FIELD* CD
Victor A. McKusick: 1/10/1992
*FIELD* ED
alopez: 11/21/2013
alopez: 2/7/2011
terry: 2/2/2011
alopez: 3/12/2009
terry: 3/10/2009
ckniffin: 2/5/2008
alopez: 2/21/2007
terry: 2/20/2007
alopez: 10/29/2003
terry: 10/29/2003
tkritzer: 7/25/2003
terry: 7/24/2003
mgross: 11/14/2002
mgross: 11/7/2002
mark: 8/22/1995
carol: 4/27/1994
supermim: 3/16/1992
carol: 1/10/1992
*RECORD*
*FIELD* NO
186745
*FIELD* TI
*186745 TALIN 1; TLN1
;;TALIN; TLN
*FIELD* TX
DESCRIPTION
Talin links vinculin (193065) to the integrins, and, thus, the
read morecytoskeleton to extracellular matrix (ECM) receptors. It has a mass of
270 kD and shares 23% N-terminal identity with ezrin (123900), which has
similar functions (Rees et al., 1990).
GENE FUNCTION
DiPaolo et al. (2002) and Ling et al. (2002) presented evidence that
talin, through its FERM domain, interacts with the C-terminal tail of
the 90-kD PIP5K1C (606102) isoform. The authors showed that this
interaction induces clustering of PIP5D1C and talin at focal adhesions
and increases the local production of
phosphatidylinositol-4,5-bisphosphate.
Mechanical forces on matrix-integrin-cytoskeleton linkages are crucial
for cell viability, morphology, and organ function. The production of
force depends on the molecular connections from ECM-integrin complexes
to the cytoskeleton. The minimal matrix complex causing
integrin-cytoskeleton connections is a trimer of fibronectin's (135600)
integrin-binding domain FNIII7-10. Jiang et al. (2003) reported a
specific molecular slip bond that was repeatedly broken by a force of 2
pN at the cellular loading rate of 60 nm/second; this occurred with
single trimer beads but not with the monomer. Talin-1, which binds to
integrins and actin filaments in vitro, is required for the 2-pN slip
bond and rapid cytoskeleton binding. Furthermore, Jiang et al. (2003)
showed that inhibition of fibronectin binding to alpha-v-beta-3 integrin
(193210 and 173470) and deletion of beta-3 markedly decreased the 2-pN
force peak. They suggested that talin-1 initially forms a molecular slip
bond between closely packed fibronectin-integrin complexes and the actin
cytoskeleton, which can apply a low level of force to fibronectin until
many bonds form or a signal is received to activate a force response.
Tadokoro et al. (2003) reported that specific binding of the
cytoskeletal protein talin to integrin beta subunit (135630) cytoplasmic
tails leads to the conformational rearrangements of integrin
extracellular domains that increase their affinity. They found that
regulated binding of talin to integrin beta tails is a final common
element of cellular signaling cascades that control integrin activation.
Hu et al. (2007) developed correlational fluorescent speckle microscopy
to measure the coupling of focal adhesion proteins to actin filaments
(see 102610). Different classes of focal adhesion structural and
regulatory molecules exhibited varying degrees of correlated motions
with actin filaments, indicating hierarchical transmission of actin
motion through focal adhesions. Interactions between vinculin (193065),
talin, and actin filaments appear to constitute a slippage interface
between the cytoskeleton and integrins, generating a molecular clutch
that is regulated during the morphodynamic transitions of cell
migration.
Kanchanawong et al. (2010) used 3-dimensional super-resolution
fluorescence microscopy to map nanoscale protein organization in focal
adhesions. Their results revealed that integrins and actin are
vertically separated by an approximately 40-nm focal adhesion core
region consisting of multiple protein-specific strata: a
membrane-apposed integrin signaling layer containing integrin
cytoplasmic tails (see 193210), focal adhesion kinase (600758), and
paxillin (602505); an intermediate force-transduction layer containing
talin and vinculin; and an uppermost actin-regulatory layer containing
zyxin (602002), vasodilator-stimulated phosphoprotein (601703), and
alpha-actinin (102575). By localizing amino- and carboxy-terminally
tagged talins, Kanchanawong et al. (2010) revealed talin's polarized
orientation, indicative of a role in organizing the focal adhesion
strata. Kanchanawong et al. (2010) concluded that their composite
multilaminar protein architecture provided a molecular blueprint for
understanding focal adhesion functions.
Shen et al. (2013) demonstrated that G-alpha-13 (604406) and talin bind
to mutually exclusive but distinct sites within the integrin beta-3
cytoplasmic domain in opposing waves. The first talin-binding wave
mediates inside-out signaling and also ligand-induced integrin
activation, but is not required for outside-in signaling. Integrin
ligation induces transient talin dissociation and G-alpha-13 binding to
an EXE motif (in which X denotes any residue), which selectively
mediates outside-in signaling and platelet spreading. The second
talin-binding wave is associated with clot retraction. An
EXE-motif-based inhibitor of G-alpha-13-integrin interaction selectively
abolishes outside-in signaling without affecting integrin ligation, and
suppresses occlusive arterial thrombosis without affecting bleeding
time. Shen et al. (2013) concluded that they discovered a mechanism for
the directional switch of integrin signaling and, on the basis of this
mechanism, designed a potent antithrombotic drug that does not cause
bleeding.
BIOCHEMICAL FEATURES
Using magnetic tweezers, total internal reflection fluorescence, and
atomic force microscopy, del Rio et al. (2009) investigated the effect
of force on the interaction between talin, a protein that links liganded
membrane integrins to the cytoskeleton, and vinculin, a focal adhesion
protein that is activated by talin binding, leading to reorganization of
the cytoskeleton. Application of physiologically relevant forces caused
stretching of single talin rods that exposed cryptic binding sites for
vinculin. Thus in the talin-vinculin system, molecular
mechanotransduction can occur by protein binding after exposure of
buried binding sites in the talin-vinculin system.
MAPPING
Using PCR amplification and DNA from a panel of human/rodent somatic
cell hybrids, Gilmore et al. (1995) assigned the TLN gene to 9p.
Deletions in 9p have been implicated in a variety of cancers. That a
cytoskeletal protein associated with the cell adhesion apparatus, such
as talin, might behave as a tumor suppressor gene has been proposed. For
example, the APC tumor suppressor gene (APC; 611731) encodes a protein
that associates with beta-catenin (CTNNB1; 116806), a component of a
complex of proteins linked to the cytoplasmic face of the cadherin
family of cell-cell adhesion molecules. Similarly, talin is a component
of a complex of proteins linked to the cytoplasmic face of integrins in
cell-ECM junctions (Luna and Hitt, 1992).
*FIELD* RF
1. del Rio, A.; Perez-Jimenez, R.; Liu, R.; Roca-Cusachs, P.; Fernandez,
J. M.; Sheetz, M. P.: Stretching single talin rod molecules activates
vinculin binding. Science 323: 638-641, 2009.
2. Di Paolo, G.; Pellegrini, L.; Letinic, K.; Cestra, G.; Zoncu, R.;
Voronov, S.; Chang, S.; Guo, J.; Wenk, M. R.; De Camill, P.: Recruitment
and regulation of phosphatidylinositol phosphate kinase type I-gamma
by the FERM domain of talin. Nature 420: 85-89, 2002.
3. Gilmore, A. P.; Ohanian, V.; Spurr, N. K.; Critchley, D. R.: Localisation
of the human gene encoding the cytoskeletal protein talin to chromosome
9p. Hum. Genet. 96: 221-224, 1995.
4. Hu, K.; Ji, L.; Applegate, K. T.; Danuser, G.; Waterman-Storer,
C. M.: Differential transmission of actin motion within focal adhesions. Science 315:
111-115, 2007.
5. Jiang, G.; Giannone, G.; Critchley, D. R.; Fukumoto, E.; Sheetz,
M. P.: Two-piconewton slip bond between fibronectin and the cytoskeleton
depends on talin. Nature 424: 334-337, 2003.
6. Kanchanawong, P.; Shtengel, G.; Pasapera, A. M.; Ramko, E. B.;
Davidson, M. W.; Hess, H. F.; Waterman, C. M.: Nanoscale architecture
of integrin-based cell adhesions. Nature 468: 580-584, 2010.
7. Ling, K.; Doughman, R. L.; Firestone, A. J.; Bunce, M. W.; Anderson,
R. A.: Type I-gamma phosphatidylinositol phosphate kinase targets
and regulates focal adhesions. Nature 420: 89-93, 2002.
8. Luna, E. J.; Hitt, A. L.: Cytoskeleton-plasma membrane interactions. Science 258:
955-964, 1992.
9. Rees, D. J. G.; Ades, S. E.; Singer, S. J.; Hynes, R. O.: Sequence
and domain structure of talin. Nature 347: 685-689, 1990.
10. Shen, B.; Zhao, X.; O'Brien, K. A.; Stojanovic-Terpo, A.; Delaney,
M. K.; Kim, K.; Cho, J.; Lam, S. C.-T.; Du, X.: A directional switch
of integrin signalling and a new anti-thrombotic strategy. Nature 503:
131-135, 2013.
11. Tadokoro, S.; Shattil, S. J.; Eto, K.; Tai, V.; Liddington, R.
C.; de Pereda, J. M.; Ginsberg, M. H.; Calderwood, D. A.: Talin binding
to integrin beta tails: a final common step in integrin activation. Science 302:
103-106, 2003.
*FIELD* CN
Ada Hamosh - updated: 11/21/2013
Ada Hamosh - updated: 2/2/2011
Ada Hamosh - updated: 3/10/2009
Ada Hamosh - updated: 2/20/2007
Ada Hamosh - updated: 10/29/2003
Ada Hamosh - updated: 7/24/2003
Patricia A. Hartz - updated: 11/7/2002
*FIELD* CD
Victor A. McKusick: 1/10/1992
*FIELD* ED
alopez: 11/21/2013
alopez: 2/7/2011
terry: 2/2/2011
alopez: 3/12/2009
terry: 3/10/2009
ckniffin: 2/5/2008
alopez: 2/21/2007
terry: 2/20/2007
alopez: 10/29/2003
terry: 10/29/2003
tkritzer: 7/25/2003
terry: 7/24/2003
mgross: 11/14/2002
mgross: 11/7/2002
mark: 8/22/1995
carol: 4/27/1994
supermim: 3/16/1992
carol: 1/10/1992