TGFI1_HUMAN
ID TGFI1_HUMAN Reviewed; 461 AA.
AC O43294; B2R8D5; Q9BPW3; Q9Y2V5;
DT 26-JUN-2007, integrated into UniProtKB/Swiss-Prot.
DT 26-JUN-2007, sequence version 2.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=Transforming growth factor beta-1-induced transcript 1 protein;
DE AltName: Full=Androgen receptor coactivator 55 kDa protein;
DE AltName: Full=Androgen receptor-associated protein of 55 kDa;
DE AltName: Full=Hydrogen peroxide-inducible clone 5 protein;
DE Short=Hic-5;
GN Name=TGFB1I1; Synonyms=ARA55;
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 2), FUNCTION, INTERACTION WITH AR, AND
RP TISSUE SPECIFICITY.
RC TISSUE=Cervix carcinoma;
RX PubMed=10075738; DOI=10.1074/jbc.274.12.8316;
RA Fujimoto N., Yeh S., Kang H.-Y., Inui S., Chang H.-C., Mizokami A.,
RA Chang C.;
RT "Cloning and characterization of androgen receptor coactivator, ARA55, in
RT human prostate.";
RL J. Biol. Chem. 274:8316-8321(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT HIS-129.
RG NIEHS SNPs program;
RL Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 3-461 (ISOFORM 1).
RC TISSUE=Muscle, Ovary, and Uterus;
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 [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 2-461 (ISOFORM 1), AND INTERACTION WITH PTK2
RP AND PTK2B.
RC TISSUE=Hippocampus;
RX PubMed=9422762; DOI=10.1074/jbc.273.2.1003;
RA Matsuya M., Sasaki H., Aoto H., Mitaka T., Nagura K., Ohba T., Ishino M.,
RA Takahashi S., Suzuki R., Sasaki T.;
RT "Cell adhesion kinase beta forms a complex with a new member, Hic-5, of
RT proteins localized at focal adhesions.";
RL J. Biol. Chem. 273:1003-1014(1998).
RN [7]
RP FUNCTION.
RX PubMed=9032249; DOI=10.1128/mcb.17.3.1224;
RA Shibanuma M., Mochizuki E., Maniwa R., Mashimo J.I., Nishiya N., Imai S.,
RA Takano T., Oshimura M., Nose K.;
RT "Induction of senescence-like phenotypes by forced expression of hic-5,
RT which encodes a novel LIM motif protein, in immortalized human
RT fibroblasts.";
RL Mol. Cell. Biol. 17:1224-1235(1997).
RN [8]
RP INTERACTION WITH PTK2.
RX PubMed=9756887; DOI=10.1074/jbc.273.41.26516;
RA Fujita H., Kamiguchi K., Cho D., Shibanuma M., Morimoto C., Tachibana K.;
RT "Interaction of Hic-5, A senescence-related protein, with focal adhesion
RT kinase.";
RL J. Biol. Chem. 273:26516-26521(1998).
RN [9]
RP INTERACTION WITH PTK2 AND TALIN, TISSUE SPECIFICITY, AND SUBCELLULAR
RP LOCATION.
RX PubMed=9664039; DOI=10.1242/jcs.111.15.2181;
RA Hagmann J., Grob M., Welman A., van Willigen G., Burger M.M.;
RT "Recruitment of the LIM protein hic-5 to focal contacts of human
RT platelets.";
RL J. Cell Sci. 111:2181-2188(1998).
RN [10]
RP MUTAGENESIS OF TYR-60, PHOSPHORYLATION AT TYR-60, AND INTERACTION WITH CSK
RP AND PTK2B.
RX PubMed=10838081; DOI=10.1016/s0014-5793(00)01597-0;
RA Ishino M., Aoto H., Sasaski H., Suzuki R., Sasaki T.;
RT "Phosphorylation of Hic-5 at tyrosine 60 by CAKbeta and Fyn.";
RL FEBS Lett. 474:179-183(2000).
RN [11]
RP TISSUE SPECIFICITY.
RX PubMed=10708479;
RX DOI=10.1002/(sici)1098-2744(200003)27:3<177::aid-mc4>3.0.co;2-s;
RA Zhang J., Zhang L.-X., Meltzer P.S., Barrett J.C., Trent J.M.;
RT "Molecular cloning of human Hic-5, a potential regulator involved in signal
RT transduction and cellular senescence.";
RL Mol. Carcinog. 27:177-183(2000).
RN [12]
RP TISSUE SPECIFICITY, PHOSPHORYLATION, INTERACTION WITH PTK2B, AND
RP SUBCELLULAR LOCATION.
RX PubMed=11311131; DOI=10.1042/bj3550691;
RA Osada M., Ohmori T., Yatomi Y., Satoh K., Hosogaya S., Ozaki Y.;
RT "Involvement of Hic-5 in platelet activation: integrin alphaIIbbeta3-
RT dependent tyrosine phosphorylation and association with proline-rich
RT tyrosine kinase 2.";
RL Biochem. J. 355:691-697(2001).
RN [13]
RP SUBCELLULAR LOCATION.
RX PubMed=11313252; DOI=10.1182/blood.v97.9.2633;
RA Oda A., Ochs H.D., Lasky L.A., Spencer S., Ozaki K., Fujihara M., Handa M.,
RA Ikebuchi K., Ikeda H.;
RT "CrkL is an adapter for Wiskott-Aldrich syndrome protein and Syk.";
RL Blood 97:2633-2639(2001).
RN [14]
RP INDUCTION BY HYDROGEN PEROXIDE.
RX PubMed=11532379; DOI=10.1016/s0923-1811(01)00129-3;
RA Inui S., Nakajima T., Fukuzato Y., Fujimoto N., Chang C., Yoshikawa K.,
RA Itami S.;
RT "Potential anti-androgenic activity of roxithromycin in skin.";
RL J. Dermatol. Sci. 27:147-151(2001).
RN [15]
RP FUNCTION.
RX PubMed=11463817; DOI=10.1128/mcb.21.16.5332-5345.2001;
RA Nishiya N., Tachibana K., Shibanuma M., Mashimo J.I., Nose K.;
RT "Hic-5-reduced cell spreading on fibronectin: competitive effects between
RT paxillin and Hic-5 through interaction with focal adhesion kinase.";
RL Mol. Cell. Biol. 21:5332-5345(2001).
RN [16]
RP INDUCTION BY TNF.
RX PubMed=11489729; DOI=10.1016/s0090-4295(01)01117-7;
RA Fujimoto N., Mizokami A., Harada S., Matsumoto T.;
RT "Different expression of androgen receptor coactivators in human
RT prostate.";
RL Urology 58:289-294(2001).
RN [17]
RP FUNCTION.
RX PubMed=12445807; DOI=10.1016/s0006-291x(02)02644-x;
RA Kim-Kaneyama J.-R., Shibanuma M., Nose K.;
RT "Transcriptional activation of the c-fos gene by a LIM protein, Hic-5.";
RL Biochem. Biophys. Res. Commun. 299:360-365(2002).
RN [18]
RP INTERACTION WITH GIT1.
RX PubMed=12153727; DOI=10.1093/oxfordjournals.jbchem.a003222;
RA Nishiya N., Shirai T., Suzuki W., Nose K.;
RT "Hic-5 interacts with GIT1 with a different binding mode from paxillin.";
RL J. Biochem. 132:279-289(2002).
RN [19]
RP FUNCTION, INTERACTION WITH PTK2B, AND PHOSPHORYLATION AT TYR-60 BY FAK2.
RX PubMed=11856738; DOI=10.1074/jbc.m111218200;
RA Wang X., Yang Y., Guo X., Sampson E.R., Hsu C.-L., Tsai M.-Y., Yeh S.,
RA Wu G., Guo Y., Chang C.;
RT "Suppression of androgen receptor transactivation by Pyk2 via interaction
RT and phosphorylation of the ARA55 coregulator.";
RL J. Biol. Chem. 277:15426-15431(2002).
RN [20]
RP FUNCTION, INTERACTION WITH SLC6A3, AND SUBCELLULAR LOCATION.
RX PubMed=12177201; DOI=10.1523/jneurosci.22-16-07045.2002;
RA Carneiro A.M.D., Ingram S.L., Beaulieu J.-M., Sweeney A., Amara S.G.,
RA Thomas S.M., Caron M.G., Torres G.E.;
RT "The multiple LIM domain-containing adaptor protein Hic-5 synaptically
RT colocalizes and interacts with the dopamine transporter.";
RL J. Neurosci. 22:7045-7054(2002).
RN [21]
RP INTERACTION WITH AR, AND MUTAGENESIS OF 338-PHE--PHE-342 AND
RP 456-PHE--PHE-460.
RX PubMed=12714604; DOI=10.1074/jbc.m211908200;
RA Hsu C.-L., Chen Y.-L., Yeh S., Ting H.-J., Hu Y.-C., Lin H., Wang X.,
RA Chang C.;
RT "The use of phage display technique for the isolation of androgen receptor
RT interacting peptides with (F/W)XXL(F/W) and FXXLY new signature motifs.";
RL J. Biol. Chem. 278:23691-23698(2003).
RN [22]
RP TISSUE SPECIFICITY.
RX PubMed=12642630; DOI=10.1177/002215540305100413;
RA Yuminamochi T., Yatomi Y., Osada M., Ohmori T., Ishii Y., Nakazawa K.,
RA Hosogaya S., Ozaki Y.;
RT "Expression of the LIM proteins paxillin and Hic-5 in human tissues.";
RL J. Histochem. Cytochem. 51:513-521(2003).
RN [23]
RP SUBCELLULAR LOCATION.
RX PubMed=12631731; DOI=10.1091/mbc.02-06-0099;
RA Shibanuma M., Kim-Kaneyama J.-R., Ishino K., Sakamoto N., Hishiki T.,
RA Yamaguchi K., Mori K., Mashimo J.I., Nose K.;
RT "Hic-5 communicates between focal adhesions and the nucleus through
RT oxidant-sensitive nuclear export signal.";
RL Mol. Biol. Cell 14:1158-1171(2003).
RN [24]
RP FUNCTION, AND INTERACTION WITH AR.
RX PubMed=12700349; DOI=10.1073/pnas.0530097100;
RA Rahman M.M., Miyamoto H., Lardy H., Chang C.;
RT "Inactivation of androgen receptor coregulator ARA55 inhibits androgen
RT receptor activity and agonist effect of antiandrogens in prostate cancer
RT cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:5124-5129(2003).
RN [25]
RP TISSUE SPECIFICITY.
RX PubMed=12772188; DOI=10.1002/pros.10229;
RA Mestayer C., Blanchere M., Jaubert F., Dufour B., Mowszowicz I.;
RT "Expression of androgen receptor coactivators in normal and cancer prostate
RT tissues and cultured cell lines.";
RL Prostate 56:192-200(2003).
RN [26]
RP FUNCTION, INTERACTION WITH NR3C1, AND SUBCELLULAR LOCATION.
RX PubMed=15211577; DOI=10.1002/jcb.20109;
RA Guerrero-Santoro J., Yang L., Stallcup M.R., DeFranco D.B.;
RT "Distinct LIM domains of Hic-5/ARA55 are required for nuclear matrix
RT targeting and glucocorticoid receptor binding and coactivation.";
RL J. Cell. Biochem. 92:810-819(2004).
RN [27]
RP INTERACTION WITH PPARG.
RX PubMed=15687259; DOI=10.1101/gad.1240705;
RA Drori S., Girnun G.D., Tou L., Szwaya J.D., Mueller E., Xia K.,
RA Shivdasani R.A., Spiegelman B.M.;
RT "Hic-5 regulates an epithelial program mediated by PPARgamma.";
RL Genes Dev. 19:362-375(2005).
RN [28]
RP FUNCTION, AND INTERACTION WITH SMAD3.
RX PubMed=15561701; DOI=10.1074/jbc.m411575200;
RA Wang H., Song K., Sponseller T.L., Danielpour D.;
RT "Novel function of androgen receptor-associated protein 55/Hic-5 as a
RT negative regulator of Smad3 signaling.";
RL J. Biol. Chem. 280:5154-5162(2005).
RN [29]
RP INTERACTION WITH TRAF4.
RX PubMed=16330715; DOI=10.1083/jcb.200507004;
RA Wu R.F., Xu Y.C., Ma Z., Nwariaku F.E., Sarosi G.A. Jr., Terada L.S.;
RT "Subcellular targeting of oxidants during endothelial cell migration.";
RL J. Cell Biol. 171:893-904(2005).
RN [30]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=16849583; DOI=10.1158/0008-5472.can-05-2379;
RA Heitzer M.D., DeFranco D.B.;
RT "Hic-5/ARA55, a LIM domain-containing nuclear receptor coactivator
RT expressed in prostate stromal cells.";
RL Cancer Res. 66:7326-7333(2006).
RN [31]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-68, AND IDENTIFICATION BY
RP 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 [32]
RP FUNCTION, INTERACTION WITH MAPK15, AND MUTAGENESIS OF CYS-369; CYS-372;
RP HIS-428 AND CYS-431.
RX PubMed=16624805; DOI=10.1074/jbc.m512418200;
RA Saelzler M.P., Spackman C.C., Liu Y., Martinez L.C., Harris J.P., Abe M.K.;
RT "ERK8 down-regulates transactivation of the glucocorticoid receptor through
RT Hic-5.";
RL J. Biol. Chem. 281:16821-16832(2006).
RN [33]
RP FUNCTION, AND INTERACTION WITH SLC6A4.
RX PubMed=16803896; DOI=10.1074/jbc.m603877200;
RA Carneiro A.M.D., Blakely R.D.;
RT "Serotonin-, protein kinase C-, and Hic-5-associated redistribution of the
RT platelet serotonin transporter.";
RL J. Biol. Chem. 281:24769-24780(2006).
RN [34]
RP FUNCTION.
RX PubMed=16141357; DOI=10.1210/me.2005-0065;
RA Heitzer M.D., DeFranco D.B.;
RT "Mechanism of action of Hic-5/androgen receptor activator 55, a LIM domain-
RT containing nuclear receptor coactivator.";
RL Mol. Endocrinol. 20:56-64(2006).
RN [35]
RP INTERACTION WITH AR; PTK2B AND SRC, AND PHOSPHORYLATION.
RX PubMed=17202804; DOI=10.1159/000098402;
RA Maudsley S., Davidson L., Pawson A.J., Freestone S.H.,
RA Lopez de Maturana R., Thomson A.A., Millar R.P.;
RT "Gonadotropin-releasing hormone functionally antagonizes testosterone
RT activation of the human androgen receptor in prostate cells through focal
RT adhesion complexes involving Hic-5.";
RL Neuroendocrinology 84:285-300(2006).
RN [36]
RP FUNCTION, TISSUE SPECIFICITY, PHOSPHORYLATION, AND INTERACTION WITH CSK AND
RP LYN.
RX PubMed=17233630; DOI=10.1042/bj20061618;
RA Rathore V.B., Okada M., Newman P.J., Newman D.K.;
RT "Paxillin family members function as Csk-binding proteins that regulate Lyn
RT activity in human and murine platelets.";
RL Biochem. J. 403:275-281(2007).
RN [37]
RP FUNCTION, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=17166536; DOI=10.1016/j.steroids.2006.11.010;
RA Heitzer M.D., DeFranco D.B.;
RT "Hic-5/ARA55 a prostate stroma-specific AR coactivator.";
RL Steroids 72:218-220(2007).
RN [38]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-33, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [39]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [40]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-137, 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 [41]
RP INTERACTION WITH CBLC, SUBCELLULAR LOCATION, AND MUTAGENESIS OF CYS-287 AND
RP CYS-313.
RX PubMed=23145173; DOI=10.1371/journal.pone.0049428;
RA Ryan P.E., Kales S.C., Yadavalli R., Nau M.M., Zhang H., Lipkowitz S.;
RT "Cbl-c ubiquitin ligase activity is increased via the interaction of its
RT RING finger domain with a LIM domain of the paxillin homolog, Hic 5.";
RL PLoS ONE 7:E49428-E49428(2012).
RN [42]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP 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., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [43]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-137; SER-141; SER-164;
RP SER-192 AND SER-194, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Cervix carcinoma;
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 [44]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-33; SER-68; SER-137; SER-140;
RP SER-143; SER-192; SER-403 AND THR-407, AND IDENTIFICATION BY MASS
RP 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).
CC -!- FUNCTION: Functions as a molecular adapter coordinating multiple
CC protein-protein interactions at the focal adhesion complex and in the
CC nucleus. Links various intracellular signaling modules to plasma
CC membrane receptors and regulates the Wnt and TGFB signaling pathways.
CC May also regulate SLC6A3 and SLC6A4 targeting to the plasma membrane
CC hence regulating their activity. In the nucleus, functions as a nuclear
CC receptor coactivator regulating glucocorticoid, androgen,
CC mineralocorticoid and progesterone receptor transcriptional activity.
CC May play a role in the processes of cell growth, proliferation,
CC migration, differentiation and senescence. May have a zinc-dependent
CC DNA-binding activity. {ECO:0000269|PubMed:10075738,
CC ECO:0000269|PubMed:11463817, ECO:0000269|PubMed:11856738,
CC ECO:0000269|PubMed:12177201, ECO:0000269|PubMed:12445807,
CC ECO:0000269|PubMed:12700349, ECO:0000269|PubMed:15211577,
CC ECO:0000269|PubMed:15561701, ECO:0000269|PubMed:16141357,
CC ECO:0000269|PubMed:16624805, ECO:0000269|PubMed:16803896,
CC ECO:0000269|PubMed:16849583, ECO:0000269|PubMed:17166536,
CC ECO:0000269|PubMed:17233630, ECO:0000269|PubMed:9032249}.
CC -!- SUBUNIT: Homooligomer (By similarity). Interacts with PPARG
CC (PubMed:15687259). Interacts with TRAF4 (PubMed:16330715). Interacts
CC with CRIP2 (By similarity). Interacts with HSPB1 (By similarity).
CC Interacts with ILK (By similarity). Interacts with LIMS1 and LIMS2 (By
CC similarity). Interacts with NCK2 (By similarity). Interacts with
CC NUDT16L1 (By similarity). Interacts with PAK (By similarity). Interacts
CC with PTPN12 (By similarity). Interacts with TCF3 (By similarity).
CC Interacts with TCF7L2 (By similarity). Interacts with VCL (By
CC similarity). Interacts (via LD motif 3) with GIT1 (PubMed:12153727).
CC Also interacts with GIT2 (By similarity). Forms a complex with ARHGEF7
CC (By similarity). Interacts with AR/androgen receptor in a ligand-
CC dependent manner (PubMed:10075738, PubMed:12714604, PubMed:12700349,
CC PubMed:17202804). Interacts with CSK (PubMed:10838081,
CC PubMed:17233630). Interacts with PTK2/FAK1 and PTK2B/PYK2
CC (PubMed:9422762, PubMed:9756887, PubMed:9664039, PubMed:10838081,
CC PubMed:11311131, PubMed:11856738, PubMed:17202804). Interacts with
CC SLC6A3 and SLC6A4 (PubMed:12177201, PubMed:16803896). Interacts with
CC NR3C1 (PubMed:15211577). Interacts with SMAD3 (PubMed:15561701).
CC Interacts with MAPK15 (PubMed:16624805). Interacts with SRC
CC (PubMed:17202804). Interacts with LYN (PubMed:17233630). Interacts with
CC talin (PubMed:9664039). Interacts (via LIM zinc-binding domain 2) with
CC CBLC (via RING-type zinc finger); the interaction is direct and
CC enhances CBLC E3 ubiquitin-protein ligase activity (PubMed:23145173).
CC Interacts with PARVA (By similarity). Interacts with PXN (By
CC similarity). {ECO:0000250|UniProtKB:Q62219,
CC ECO:0000250|UniProtKB:Q99PD6, ECO:0000269|PubMed:10075738,
CC ECO:0000269|PubMed:10838081, ECO:0000269|PubMed:11311131,
CC ECO:0000269|PubMed:11856738, ECO:0000269|PubMed:12153727,
CC ECO:0000269|PubMed:12177201, ECO:0000269|PubMed:12700349,
CC ECO:0000269|PubMed:12714604, ECO:0000269|PubMed:15211577,
CC ECO:0000269|PubMed:15561701, ECO:0000269|PubMed:15687259,
CC ECO:0000269|PubMed:16330715, ECO:0000269|PubMed:16624805,
CC ECO:0000269|PubMed:16803896, ECO:0000269|PubMed:17202804,
CC ECO:0000269|PubMed:17233630, ECO:0000269|PubMed:23145173,
CC ECO:0000269|PubMed:9422762, ECO:0000269|PubMed:9664039,
CC ECO:0000269|PubMed:9756887}.
CC -!- INTERACTION:
CC O43294; P13612: ITGA4; NbExp=2; IntAct=EBI-1051449, EBI-703044;
CC O43294; Q05397: PTK2; NbExp=4; IntAct=EBI-1051449, EBI-702142;
CC O43294; Q9BUZ4: TRAF4; NbExp=8; IntAct=EBI-1051449, EBI-3650647;
CC O43294; O68743: YPMT1.25Ac; Xeno; NbExp=2; IntAct=EBI-1051449, EBI-2849869;
CC -!- SUBCELLULAR LOCATION: Cell junction, focal adhesion. Nucleus matrix.
CC Cytoplasm, cytoskeleton. Note=Associated with the actin cytoskeleton;
CC colocalizes with stress fibers.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O43294-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O43294-2; Sequence=VSP_026183;
CC -!- TISSUE SPECIFICITY: Expressed in platelets, smooth muscle and prostate
CC stromal cells (at protein level). {ECO:0000269|PubMed:10075738,
CC ECO:0000269|PubMed:10708479, ECO:0000269|PubMed:11311131,
CC ECO:0000269|PubMed:12642630, ECO:0000269|PubMed:12772188,
CC ECO:0000269|PubMed:16849583, ECO:0000269|PubMed:17166536,
CC ECO:0000269|PubMed:17233630, ECO:0000269|PubMed:9664039}.
CC -!- INDUCTION: Up-regulated by TNF and hydrogen peroxide.
CC {ECO:0000269|PubMed:11489729, ECO:0000269|PubMed:11532379}.
CC -!- DOMAIN: The LIM zinc-binding domains mediate glucocorticoid receptor
CC coactivation and interaction with AR, CRIP2, ILK, LIMS1, NR3C1, PPARG,
CC TCF3, TCF7L2, SLC6A3 and SMAD3. The LIM zinc-binding 2 and LIM zinc-
CC binding 3 domains mediate targeting to focal adhesions and actin stress
CC fibers. The LIM zinc-binding 3 and LIM zinc-binding 4 domains mediate
CC interaction with TRAF4 and MAPK15. The LIM zinc-binding 4 domain
CC mediates interaction with HSPB1, homooligomerization and targeting to
CC the nuclear matrix. The LIM zinc-binding 3 domain mediates interaction
CC with PTPN12.
CC -!- DOMAIN: The LD (leucine and aspartate-rich) motif 3 mediates
CC interaction with GIT1 and functions as a nuclear export signal.
CC -!- PTM: Phosphorylated by gonadotropin-releasing hormone-activated SRC.
CC {ECO:0000269|PubMed:10838081, ECO:0000269|PubMed:11311131,
CC ECO:0000269|PubMed:11856738, ECO:0000269|PubMed:17202804,
CC ECO:0000269|PubMed:17233630}.
CC -!- SIMILARITY: Belongs to the paxillin family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH32545.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/tgfb1i1/";
CC ---------------------------------------------------------------------------
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DR EMBL; AF116343; AAD22552.1; -; mRNA.
DR EMBL; DQ309025; ABB96286.1; -; Genomic_DNA.
DR EMBL; AK313327; BAG36132.1; -; mRNA.
DR EMBL; CH471192; EAW52126.1; -; Genomic_DNA.
DR EMBL; BC001507; AAH01507.2; -; mRNA.
DR EMBL; BC001830; AAH01830.1; -; mRNA.
DR EMBL; BC017288; AAH17288.1; -; mRNA.
DR EMBL; BC032545; AAH32545.1; ALT_INIT; mRNA.
DR EMBL; AB007836; BAA24799.1; -; mRNA.
DR CCDS; CCDS10713.1; -. [O43294-2]
DR CCDS; CCDS42156.1; -. [O43294-1]
DR RefSeq; NP_001035919.1; NM_001042454.2. [O43294-1]
DR RefSeq; NP_001158191.1; NM_001164719.1. [O43294-2]
DR RefSeq; NP_057011.2; NM_015927.4. [O43294-2]
DR AlphaFoldDB; O43294; -.
DR SMR; O43294; -.
DR BioGRID; 112899; 38.
DR DIP; DIP-5931N; -.
DR ELM; O43294; -.
DR IntAct; O43294; 34.
DR MINT; O43294; -.
DR STRING; 9606.ENSP00000378332; -.
DR iPTMnet; O43294; -.
DR MetOSite; O43294; -.
DR PhosphoSitePlus; O43294; -.
DR BioMuta; TGFB1I1; -.
DR EPD; O43294; -.
DR jPOST; O43294; -.
DR MassIVE; O43294; -.
DR MaxQB; O43294; -.
DR PaxDb; O43294; -.
DR PeptideAtlas; O43294; -.
DR PRIDE; O43294; -.
DR ProteomicsDB; 48865; -. [O43294-1]
DR ProteomicsDB; 48866; -. [O43294-2]
DR Antibodypedia; 1738; 255 antibodies from 29 providers.
DR DNASU; 7041; -.
DR Ensembl; ENST00000361773.7; ENSP00000355117.3; ENSG00000140682.19. [O43294-2]
DR Ensembl; ENST00000394858.6; ENSP00000378327.2; ENSG00000140682.19. [O43294-2]
DR Ensembl; ENST00000394863.8; ENSP00000378332.3; ENSG00000140682.19. [O43294-1]
DR Ensembl; ENST00000567607.5; ENSP00000457586.1; ENSG00000140682.19. [O43294-2]
DR GeneID; 7041; -.
DR KEGG; hsa:7041; -.
DR MANE-Select; ENST00000394863.8; ENSP00000378332.3; NM_001042454.3; NP_001035919.1.
DR UCSC; uc002ecd.3; human. [O43294-1]
DR CTD; 7041; -.
DR DisGeNET; 7041; -.
DR GeneCards; TGFB1I1; -.
DR HGNC; HGNC:11767; TGFB1I1.
DR HPA; ENSG00000140682; Tissue enhanced (endometrium).
DR MIM; 602353; gene.
DR neXtProt; NX_O43294; -.
DR OpenTargets; ENSG00000140682; -.
DR PharmGKB; PA36481; -.
DR VEuPathDB; HostDB:ENSG00000140682; -.
DR eggNOG; KOG1703; Eukaryota.
DR GeneTree; ENSGT00940000160447; -.
DR HOGENOM; CLU_001357_1_2_1; -.
DR InParanoid; O43294; -.
DR OMA; CREPFGD; -.
DR OrthoDB; 1593918at2759; -.
DR PhylomeDB; O43294; -.
DR TreeFam; TF314113; -.
DR PathwayCommons; O43294; -.
DR SignaLink; O43294; -.
DR SIGNOR; O43294; -.
DR BioGRID-ORCS; 7041; 92 hits in 1076 CRISPR screens.
DR ChiTaRS; TGFB1I1; human.
DR GeneWiki; TGFB1I1; -.
DR GenomeRNAi; 7041; -.
DR Pharos; O43294; Tbio.
DR PRO; PR:O43294; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; O43294; protein.
DR Bgee; ENSG00000140682; Expressed in saphenous vein and 162 other tissues.
DR ExpressionAtlas; O43294; baseline and differential.
DR Genevisible; O43294; HS.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB.
DR GO; GO:0016363; C:nuclear matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0070411; F:I-SMAD binding; IPI:BHF-UCL.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0050681; F:nuclear androgen receptor binding; IPI:UniProtKB.
DR GO; GO:0048495; F:Roundabout binding; IPI:UniProtKB.
DR GO; GO:0003713; F:transcription coactivator activity; IDA:UniProtKB.
DR GO; GO:0003712; F:transcription coregulator activity; IBA:GO_Central.
DR GO; GO:0007155; P:cell adhesion; TAS:ProtInc.
DR GO; GO:0045165; P:cell fate commitment; IEA:Ensembl.
DR GO; GO:0030855; P:epithelial cell differentiation; IEA:Ensembl.
DR GO; GO:0045444; P:fat cell differentiation; IEA:Ensembl.
DR GO; GO:0016331; P:morphogenesis of embryonic epithelium; IEA:Ensembl.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; TAS:ProtInc.
DR GO; GO:0045599; P:negative regulation of fat cell differentiation; IEA:Ensembl.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; IDA:BHF-UCL.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0030511; P:positive regulation of transforming growth factor beta receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0030579; P:ubiquitin-dependent SMAD protein catabolic process; IDA:BHF-UCL.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR InterPro; IPR017305; Tgfb1i1/Leupaxin/TGFB1I1.
DR InterPro; IPR001781; Znf_LIM.
DR Pfam; PF00412; LIM; 4.
DR PIRSF; PIRSF037881; Leupaxin; 1.
DR SMART; SM00132; LIM; 4.
DR PROSITE; PS00478; LIM_DOMAIN_1; 4.
DR PROSITE; PS50023; LIM_DOMAIN_2; 4.
PE 1: Evidence at protein level;
KW Acetylation; Activator; Alternative splicing; Cell junction; Cytoplasm;
KW Cytoskeleton; Differentiation; LIM domain; Metal-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat; Wnt signaling pathway; Zinc.
FT CHAIN 1..461
FT /note="Transforming growth factor beta-1-induced transcript
FT 1 protein"
FT /id="PRO_0000291582"
FT DOMAIN 226..285
FT /note="LIM zinc-binding 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00125"
FT DOMAIN 286..343
FT /note="LIM zinc-binding 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00125"
FT DOMAIN 344..403
FT /note="LIM zinc-binding 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00125"
FT DOMAIN 404..461
FT /note="LIM zinc-binding 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00125"
FT REGION 1..240
FT /note="Interaction with PTK2B/PYK2"
FT REGION 1..200
FT /note="Transcription activation"
FT /evidence="ECO:0000250"
FT REGION 1..87
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 83..136
FT /note="Interaction with PTK2/FAK1"
FT /evidence="ECO:0000250"
FT REGION 116..152
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 172..205
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 3..15
FT /note="LD motif 1"
FT MOTIF 92..104
FT /note="LD motif 2"
FT MOTIF 157..168
FT /note="LD motif 3"
FT MOTIF 203..215
FT /note="LD motif 4"
FT COMPBIAS 172..196
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES 33
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 38
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q62219"
FT MOD_RES 60
FT /note="Phosphotyrosine; by FAK2 and FYN"
FT /evidence="ECO:0000269|PubMed:10838081,
FT ECO:0000269|PubMed:11856738"
FT MOD_RES 68
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 137
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 140
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 141
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 143
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 164
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 186
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q62219"
FT MOD_RES 188
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q62219"
FT MOD_RES 192
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 194
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 403
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 407
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT VAR_SEQ 1..17
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10075738,
FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334"
FT /id="VSP_026183"
FT VARIANT 129
FT /note="Q -> H (in dbSNP:rs45475699)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_032831"
FT MUTAGEN 60
FT /note="Y->F: Prevents phosphorylation by FAK2 and FYN.
FT Prevents interaction with CSK."
FT /evidence="ECO:0000269|PubMed:10838081"
FT MUTAGEN 287
FT /note="C->A: Abolishes interaction with CBLC and
FT enhancement of CBLC E3 ubiquitin-protein ligase activity."
FT /evidence="ECO:0000269|PubMed:23145173"
FT MUTAGEN 313
FT /note="C->A: No effect on interaction with CBLC."
FT /evidence="ECO:0000269|PubMed:23145173"
FT MUTAGEN 338..342
FT /note="FLQLF->ALQAA: Loss of interaction with AR; when
FT associated with 456-A--A-460."
FT /evidence="ECO:0000269|PubMed:12714604"
FT MUTAGEN 369
FT /note="C->S: Loss of AR coactivation; when associated with
FT S-372."
FT /evidence="ECO:0000269|PubMed:16624805"
FT MUTAGEN 372
FT /note="C->S: Loss of AR coactivation; when associated with
FT S-369."
FT /evidence="ECO:0000269|PubMed:16624805"
FT MUTAGEN 428
FT /note="H->S: Loss of AR coactivation; when associated with
FT S-431."
FT /evidence="ECO:0000269|PubMed:16624805"
FT MUTAGEN 431
FT /note="C->S: Loss of AR coactivation; when associated with
FT S-428."
FT /evidence="ECO:0000269|PubMed:16624805"
FT MUTAGEN 456..460
FT /note="FLKLF->ALKAA: Loss of interaction with AR; when
FT associated with 338-A--A-342."
FT /evidence="ECO:0000269|PubMed:12714604"
FT CONFLICT 166
FT /note="S -> P (in Ref. 1; AAD22552)"
FT /evidence="ECO:0000305"
FT CONFLICT 200
FT /note="G -> A (in Ref. 1; AAD22552)"
FT /evidence="ECO:0000305"
FT CONFLICT 363
FT /note="A -> L (in Ref. 1; AAD22552)"
FT /evidence="ECO:0000305"
FT CONFLICT 405..406
FT /note="CA -> WP (in Ref. 1; AAD22552)"
FT /evidence="ECO:0000305"
FT CONFLICT 430
FT /note="T -> A (in Ref. 1; AAD22552)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 461 AA; 49814 MW; D2C7C32C3FD2C496 CRC64;
MEDLDALLSD LETTTSHMPR SGAPKERPAE PLTPPPSYGH QPQTGSGESS GASGDKDHLY
STVCKPRSPK PAAPAAPPFS SSSGVLGTGL CELDRLLQEL NATQFNITDE IMSQFPSSKV
ASGEQKEDQS EDKKRPSLPS SPSPGLPKAS ATSATLELDR LMASLSDFRV QNHLPASGPT
QPPVVSSTNE GSPSPPEPTG KGSLDTMLGL LQSDLSRRGV PTQAKGLCGS CNKPIAGQVV
TALGRAWHPE HFVCGGCSTA LGGSSFFEKD GAPFCPECYF ERFSPRCGFC NQPIRHKMVT
ALGTHWHPEH FCCVSCGEPF GDEGFHEREG RPYCRRDFLQ LFAPRCQGCQ GPILDNYISA
LSALWHPDCF VCRECFAPFS GGSFFEHEGR PLCENHFHAR RGSLCATCGL PVTGRCVSAL
GRRFHPDHFT CTFCLRPLTK GSFQERAGKP YCQPCFLKLF G
