TGFI1_MOUSE
ID TGFI1_MOUSE Reviewed; 461 AA.
AC Q62219; Q3YBY7; Q3YBY8; Q3YBZ0; Q3YBZ1; Q3YBZ3; Q3YBZ4; Q3YBZ5; Q3YBZ6;
DT 26-JUN-2007, integrated into UniProtKB/Swiss-Prot.
DT 26-JUN-2007, sequence version 2.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=Transforming growth factor beta-1-induced transcript 1 protein;
DE AltName: Full=Androgen receptor-associated protein of 55 kDa;
DE AltName: Full=Hydrogen peroxide-inducible clone 5 protein;
DE Short=Hic-5;
DE AltName: Full=TGF beta-stimulated clone 5;
DE Short=TSC-5;
GN Name=Tgfb1i1; Synonyms=Ara55;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, INDUCTION BY TGFB1 AND
RP HYDROGEN PEROXIDE, AND TISSUE SPECIFICITY.
RC TISSUE=Calvaria;
RX PubMed=7929412; DOI=10.1016/s0021-9258(18)47085-8;
RA Shibanuma M., Mashimo J.I., Kuroki T., Nose K.;
RT "Characterization of the TGF beta 1-inducible hic-5 gene that encodes a
RT putative novel zinc finger protein and its possible involvement in cellular
RT senescence.";
RL J. Biol. Chem. 269:26767-26774(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10831843; DOI=10.1016/s0378-1119(00)00163-3;
RA Mashimo J.I., Shibanuma M., Satoh H., Chida K., Nose K.;
RT "Genomic structure and chromosomal mapping of the mouse hic-5 gene that
RT encodes a focal adhesion protein.";
RL Gene 249:99-103(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3; 4; 5; 6; 7; 8; 9 AND 10), AND
RP TISSUE SPECIFICITY.
RC STRAIN=BALB/cJ;
RX PubMed=16219310; DOI=10.1016/j.febslet.2005.08.086;
RA Gao Z., Schwartz L.M.;
RT "Identification and analysis of Hic-5/ARA55 isoforms: implications for
RT integrin signaling and steroid hormone action.";
RL FEBS Lett. 579:5651-5657(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 6).
RC STRAIN=NOD; TISSUE=Inner ear, and Spleen;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Brain, and Mammary tumor;
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 INTERACTION WITH PTK2 AND PTK2B.
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 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 [8]
RP FUNCTION.
RX PubMed=9722648; DOI=10.1093/nar/26.18.4267;
RA Nishiya N., Sabe H., Nose K., Shibanuma M.;
RT "The LIM domains of hic-5 protein recognize specific DNA fragments in a
RT zinc-dependent manner in vitro.";
RL Nucleic Acids Res. 26:4267-4273(1998).
RN [9]
RP INTERACTION WITH PTPN12, AND MUTAGENESIS OF HIS-366 AND CYS-369.
RX PubMed=10092676; DOI=10.1074/jbc.274.14.9847;
RA Nishiya N., Iwabuchi Y., Shibanuma M., Cote J.-F., Tremblay M.L., Nose K.;
RT "Hic-5, a paxillin homologue, binds to the protein-tyrosine phosphatase
RT PEST (PTP-PEST) through its LIM 3 domain.";
RL J. Biol. Chem. 274:9847-9853(1999).
RN [10]
RP INTERACTION WITH ARHGEF7; GIT2; NCK2; PTK2 AND PAK.
RX PubMed=10330411; DOI=10.1083/jcb.145.4.851;
RA Turner C.E., Brown M.C., Perrotta J.A., Riedy M.C., Nikolopoulos S.N.,
RA McDonald A.R., Bagrodia S., Thomas S.M., Leventhal P.S.;
RT "Paxillin LD4 motif binds PAK and PIX through a novel 95-kD ankyrin repeat,
RT ARF-GAP protein: a role in cytoskeletal remodeling.";
RL J. Cell Biol. 145:851-863(1999).
RN [11]
RP INTERACTION WITH CSK; PTK2 AND VCL, AND SUBCELLULAR LOCATION.
RX PubMed=9858471; DOI=10.1242/jcs.112.2.181;
RA Thomas S.M., Hagel M., Turner C.E.;
RT "Characterization of a focal adhesion protein, Hic-5, that shares extensive
RT homology with paxillin.";
RL J. Cell Sci. 112:181-190(1999).
RN [12]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH PTK2.
RX PubMed=10649439;
RX DOI=10.1002/(sici)1097-4644(20000301)76:3<411::aid-jcb9>3.0.co;2-j;
RA Ishino K., Kim Kaneyama J.-R., Shibanuma M., Nose K.;
RT "Specific decrease in the level of Hic-5, a focal adhesion protein, during
RT immortalization of mouse embryonic fibroblasts, and its association with
RT focal adhesion kinase.";
RL J. Cell. Biochem. 76:411-419(2000).
RN [13]
RP INTERACTION WITH PARVA.
RX PubMed=11134073; DOI=10.1083/jcb.151.7.1435;
RA Nikolopoulos S.N., Turner C.E.;
RT "Actopaxin, a new focal adhesion protein that binds paxillin LD motifs and
RT actin and regulates cell adhesion.";
RL J. Cell Biol. 151:1435-1448(2000).
RN [14]
RP FUNCTION, INTERACTION WITH NR3C1, AND SUBCELLULAR LOCATION.
RX PubMed=10848625; DOI=10.1091/mbc.11.6.2007;
RA Yang L., Guerrero J., Hong H., DeFranco D.B., Stallcup M.R.;
RT "Interaction of the tau2 transcriptional activation domain of
RT glucocorticoid receptor with a novel steroid receptor coactivator, Hic-5,
RT which localizes to both focal adhesions and the nuclear matrix.";
RL Mol. Biol. Cell 11:2007-2018(2000).
RN [15]
RP DEVELOPMENTAL STAGE.
RX PubMed=11437454; DOI=10.1006/dbio.2001.0313;
RA Brunskill E.W., Witte D.P., Yutzey K.E., Potter S.S.;
RT "Novel cell lines promote the discovery of genes involved in early heart
RT development.";
RL Dev. Biol. 235:507-520(2001).
RN [16]
RP FUNCTION, AND INTERACTION WITH HSPB1.
RX PubMed=11546764; DOI=10.1074/jbc.m103510200;
RA Jia Y., Ransom R.F., Shibanuma M., Liu C., Welsh M.J., Smoyer W.E.;
RT "Identification and characterization of hic-5/ARA55 as an hsp27 binding
RT protein.";
RL J. Biol. Chem. 276:39911-39918(2001).
RN [17]
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 [18]
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=11937715; DOI=10.1247/csf.27.21;
RA Shibanuma M., Iwabuchi Y., Nose K.;
RT "Possible involvement of hic-5, a focal adhesion protein, in the
RT differentiation of C2C12 myoblasts.";
RL Cell Struct. Funct. 27:21-27(2002).
RN [19]
RP FUNCTION, AND INTERACTION WITH GIT1 AND ARHGEF7.
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 [20]
RP INTERACTION WITH AR.
RX PubMed=11779876; DOI=10.1074/jbc.m111975200;
RA He B., Minges J.T., Lee L.W., Wilson E.M.;
RT "The FXXLF motif mediates androgen receptor-specific interactions with
RT coregulators.";
RL J. Biol. Chem. 277:10226-10235(2002).
RN [21]
RP INTERACTION WITH NUDT16L1.
RX PubMed=11805099; DOI=10.1074/jbc.m110291200;
RA Denhez F., Wilcox-Adelman S.A., Baciu P.C., Saoncella S., Lee S.,
RA French B., Neveu W., Goetinck P.F.;
RT "Syndesmos, a syndecan-4 cytoplasmic domain interactor, binds to the focal
RT adhesion adaptor proteins paxillin and Hic-5.";
RL J. Biol. Chem. 277:12270-12274(2002).
RN [22]
RP INTERACTION WITH SLC6A3, AND TISSUE SPECIFICITY.
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 [23]
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF CYS-64; CYS-91 AND LEU-161.
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 SMAD3.
RX PubMed=14755691; DOI=10.1002/jcb.10754;
RA Shibanuma M., Kim-Kaneyama J.-R., Sato S., Nose K.;
RT "A LIM protein, Hic-5, functions as a potential coactivator for Sp1.";
RL J. Cell. Biochem. 91:633-645(2004).
RN [25]
RP FUNCTION, MUTAGENESIS OF TYR-38; TYR-60; CYS-369 AND CYS-372, SUBCELLULAR
RP LOCATION, AND PHOSPHORYLATION AT TYR-38 AND TYR-60.
RX PubMed=16183059; DOI=10.1016/j.yexcr.2005.08.011;
RA Hetey S.E., Lalonde D.P., Turner C.E.;
RT "Tyrosine-phosphorylated Hic-5 inhibits epidermal growth factor-induced
RT lamellipodia formation.";
RL Exp. Cell Res. 311:147-156(2005).
RN [26]
RP FUNCTION, INTERACTION WITH PPARG, AND DEVELOPMENTAL STAGE.
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 [27]
RP FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND INTERACTION WITH
RP CRIP2.
RX PubMed=15713747; DOI=10.1242/jcs.01683;
RA Kim-Kaneyama J.-R., Suzuki W., Ichikawa K., Ohki T., Kohno Y., Sata M.,
RA Nose K., Shibanuma M.;
RT "Uni-axial stretching regulates intracellular localization of Hic-5
RT expressed in smooth-muscle cells in vivo.";
RL J. Cell Sci. 118:937-949(2005).
RN [28]
RP INDUCTION, AND TISSUE SPECIFICITY.
RX PubMed=16219691; DOI=10.1242/jcs.02615;
RA Tumbarello D.A., Brown M.C., Hetey S.E., Turner C.E.;
RT "Regulation of paxillin family members during epithelial-mesenchymal
RT transformation: a putative role for paxillin delta.";
RL J. Cell Sci. 118:4849-4863(2005).
RN [29]
RP FUNCTION, AND INTERACTION WITH TCF3 AND TCF7L2.
RX PubMed=16291758; DOI=10.1074/jbc.m505869200;
RA Ghogomu S.M., van Venrooy S., Ritthaler M., Wedlich D., Gradl D.;
RT "HIC-5 is a novel repressor of lymphoid enhancer factor/T-cell factor-
RT driven transcription.";
RL J. Biol. Chem. 281:1755-1764(2006).
RN [30]
RP INTERACTION WITH MAPK15.
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 [31]
RP FUNCTION, HOMOOLIGOMERIZATION, SUBCELLULAR LOCATION, AND INTERACTION WITH
RP ILK; LIMS1 AND LIMS2.
RX PubMed=16737959; DOI=10.1074/jbc.m513111200;
RA Mori K., Asakawa M., Hayashi M., Imura M., Ohki T., Hirao E.,
RA Kim-Kaneyama J.-R., Nose K., Shibanuma M.;
RT "Oligomerizing potential of a focal adhesion LIM protein Hic-5 organizing a
RT nuclear-cytoplasmic shuttling complex.";
RL J. Biol. Chem. 281:22048-22061(2006).
RN [32]
RP FUNCTION, TISSUE SPECIFICITY, PHOSPHORYLATION, AND INTERACTION WITH CSK.
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 [33]
RP FUNCTION.
RX PubMed=17299801; DOI=10.1002/jcp.20991;
RA Tumbarello D.A., Turner C.E.;
RT "Hic-5 contributes to epithelial-mesenchymal transformation through a
RT RhoA/ROCK-dependent pathway.";
RL J. Cell. Physiol. 211:736-747(2007).
RN [34]
RP FUNCTION.
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 [35]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-68; SER-186; THR-188; SER-194
RP AND SER-403, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Spleen, and
RC Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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:10649439,
CC ECO:0000269|PubMed:10848625, ECO:0000269|PubMed:11463817,
CC ECO:0000269|PubMed:11546764, ECO:0000269|PubMed:11937715,
CC ECO:0000269|PubMed:12153727, ECO:0000269|PubMed:14755691,
CC ECO:0000269|PubMed:15687259, ECO:0000269|PubMed:15713747,
CC ECO:0000269|PubMed:16183059, ECO:0000269|PubMed:16291758,
CC ECO:0000269|PubMed:16737959, ECO:0000269|PubMed:17166536,
CC ECO:0000269|PubMed:17233630, ECO:0000269|PubMed:17299801,
CC ECO:0000269|PubMed:7929412, ECO:0000269|PubMed:9722648}.
CC -!- SUBUNIT: Homooligomer (PubMed:16737959). Interacts with PPARG
CC (PubMed:15687259). Interacts with TRAF4 (By similarity). Interacts with
CC CRIP2 (PubMed:15713747). Interacts with HSPB1 (PubMed:11546764).
CC Interacts with ILK (PubMed:16737959). Interacts with LIMS1 and LIMS2
CC (PubMed:16737959). Interacts with NCK2 (PubMed:10330411). Interacts
CC with NUDT16L1 (PubMed:11805099). Interacts with PAK (PubMed:10330411).
CC Interacts with PTPN12 (PubMed:10092676). Interacts with TCF3
CC (PubMed:16291758). Interacts with TCF7L2 (PubMed:16291758). Interacts
CC with VCL (PubMed:9858471). Interacts (via LD motif 3) with GIT1
CC (PubMed:12153727). Also interacts with GIT2 (PubMed:10330411). Forms a
CC complex with ARHGEF7 (PubMed:10330411, PubMed:12153727). Interacts with
CC AR/androgen receptor in a ligand-dependent manner (PubMed:11779876).
CC Interacts with CSK (PubMed:9858471, PubMed:17233630). Interacts with
CC PTK2/FAK1 and PTK2B/PYK2 (PubMed:9422762, PubMed:9756887,
CC PubMed:10330411, PubMed:9858471, PubMed:10649439). Interacts with
CC SLC6A3 (PubMed:12177201). Interacts with SLC6A4 (By similarity).
CC Interacts with NR3C1 (PubMed:10848625). Interacts with SMAD3
CC (PubMed:14755691). Interacts with MAPK15 (PubMed:16624805). Interacts
CC with SRC (By similarity). Interacts with LYN (By similarity). Interacts
CC with talin (By similarity). Interacts (via LIM zinc-binding domain 2)
CC with CBLC (via RING-type zinc finger); the interaction is direct and
CC enhances CBLC E3 ubiquitin-protein ligase activity (By similarity).
CC Interacts with PARVA (PubMed:11134073). Interacts with PXN (By
CC similarity). {ECO:0000250|UniProtKB:O43294,
CC ECO:0000250|UniProtKB:Q99PD6, ECO:0000269|PubMed:10092676,
CC ECO:0000269|PubMed:10330411, ECO:0000269|PubMed:10649439,
CC ECO:0000269|PubMed:10848625, ECO:0000269|PubMed:11134073,
CC ECO:0000269|PubMed:11546764, ECO:0000269|PubMed:11779876,
CC ECO:0000269|PubMed:11805099, ECO:0000269|PubMed:12153727,
CC ECO:0000269|PubMed:12177201, ECO:0000269|PubMed:14755691,
CC ECO:0000269|PubMed:15687259, ECO:0000269|PubMed:15713747,
CC ECO:0000269|PubMed:16291758, ECO:0000269|PubMed:16624805,
CC ECO:0000269|PubMed:16737959, ECO:0000269|PubMed:17233630,
CC ECO:0000269|PubMed:9422762, ECO:0000269|PubMed:9756887,
CC ECO:0000269|PubMed:9858471}.
CC -!- INTERACTION:
CC Q62219; Q8C115: Plekhh2; NbExp=3; IntAct=EBI-642844, EBI-6512409;
CC Q62219; Q05397: PTK2; Xeno; NbExp=3; IntAct=EBI-642844, EBI-702142;
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=10;
CC Name=1; Synonyms=Alpha;
CC IsoId=Q62219-1; Sequence=Displayed;
CC Name=2; Synonyms=Beta;
CC IsoId=Q62219-2; Sequence=VSP_026191;
CC Name=3; Synonyms=Alpha-B;
CC IsoId=Q62219-3; Sequence=VSP_026190;
CC Name=4; Synonyms=Alpha-E;
CC IsoId=Q62219-4; Sequence=VSP_026193;
CC Name=5; Synonyms=Beta-G;
CC IsoId=Q62219-5; Sequence=VSP_026189, VSP_026192;
CC Name=6; Synonyms=Alpha-C;
CC IsoId=Q62219-6; Sequence=VSP_039813, VSP_039814;
CC Name=7; Synonyms=Beta-B, Beta-D;
CC IsoId=Q62219-7; Sequence=VSP_026184;
CC Name=8; Synonyms=Beta-C;
CC IsoId=Q62219-8; Sequence=VSP_026191, VSP_039813, VSP_039814;
CC Name=9; Synonyms=Beta-E, Beta-F;
CC IsoId=Q62219-9; Sequence=VSP_026188, VSP_026194;
CC Name=10; Synonyms=Alpha-D;
CC IsoId=Q62219-10; Sequence=VSP_026185, VSP_026197;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed. Higher expression is
CC detected in lung and spleen. Expression decreases during pregnancy in
CC mammary glands. Expressed in all brain areas, with higher levels in
CC cerebellum, prefrontal cortex and hypothalamus. Expressed in smooth
CC muscle, myoepithelial cells and platelets (at protein level).
CC Preferentially expressed in mesenchymal versus epithelial cells (at
CC protein level). {ECO:0000269|PubMed:12177201,
CC ECO:0000269|PubMed:15713747, ECO:0000269|PubMed:16219310,
CC ECO:0000269|PubMed:16219691, ECO:0000269|PubMed:17233630,
CC ECO:0000269|PubMed:7929412}.
CC -!- DEVELOPMENTAL STAGE: First detected in the developing heart tube at 8.0
CC dpc and then in cardiac, skeletal and smooth muscle during early stages
CC of development. Highly expressed in differentiating gut epithelial
CC cells. {ECO:0000269|PubMed:11437454, ECO:0000269|PubMed:11937715,
CC ECO:0000269|PubMed:15687259}.
CC -!- INDUCTION: Up-regulated during epithelial to mesenchymal
CC transformation. Up-regulated by TGFB1 and hydrogen peroxide.
CC {ECO:0000269|PubMed:16219691, ECO:0000269|PubMed:7929412}.
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:0000250}.
CC -!- MISCELLANEOUS: [Isoform 1]: Transcripts of the alpha group are more
CC abundantly expressed.
CC -!- MISCELLANEOUS: [Isoform 3]: Transcripts of the alpha group are more
CC abundantly expressed. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 4]: Transcripts of the alpha group are more
CC abundantly expressed. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 6]: Transcripts of the alpha group are more
CC abundantly expressed. May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 8]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 10]: Transcripts of the alpha group are more
CC abundantly expressed. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the paxillin family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH02049.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAZ82195.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAZ82200.1; Type=Erroneous translation; Note=Wrong choice of CDS.; Evidence={ECO:0000305};
CC Sequence=BAE33707.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAE34493.1; Type=Erroneous translation; Note=Wrong choice of CDS.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
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DR EMBL; L22482; AAA62226.1; -; mRNA.
DR EMBL; AF083064; AAD51090.1; -; Genomic_DNA.
DR EMBL; DQ143891; AAZ82195.1; ALT_FRAME; mRNA.
DR EMBL; DQ143892; AAZ82196.1; -; mRNA.
DR EMBL; DQ143893; AAZ82197.1; -; mRNA.
DR EMBL; DQ143894; AAZ82198.1; -; mRNA.
DR EMBL; DQ143895; AAZ82199.1; -; mRNA.
DR EMBL; DQ143896; AAZ82200.1; ALT_SEQ; mRNA.
DR EMBL; DQ143897; AAZ82201.1; -; mRNA.
DR EMBL; DQ143898; AAZ82202.1; -; mRNA.
DR EMBL; DQ143899; AAZ82203.1; -; mRNA.
DR EMBL; DQ143900; AAZ82204.1; -; mRNA.
DR EMBL; AK156423; BAE33707.1; ALT_INIT; mRNA.
DR EMBL; AK158409; BAE34493.1; ALT_SEQ; mRNA.
DR EMBL; BC002049; AAH02049.1; ALT_INIT; mRNA.
DR EMBL; BC056362; AAH56362.1; -; mRNA.
DR CCDS; CCDS21893.2; -. [Q62219-1]
DR CCDS; CCDS80812.1; -. [Q62219-7]
DR PIR; A55071; A55071.
DR RefSeq; NP_001276479.1; NM_001289550.1. [Q62219-1]
DR RefSeq; NP_001276481.1; NM_001289552.1.
DR RefSeq; NP_001276482.1; NM_001289553.1. [Q62219-7]
DR RefSeq; XP_006507630.1; XM_006507567.2.
DR AlphaFoldDB; Q62219; -.
DR SMR; Q62219; -.
DR BioGRID; 204158; 7.
DR IntAct; Q62219; 5.
DR STRING; 10090.ENSMUSP00000068529; -.
DR iPTMnet; Q62219; -.
DR PhosphoSitePlus; Q62219; -.
DR jPOST; Q62219; -.
DR MaxQB; Q62219; -.
DR PaxDb; Q62219; -.
DR PeptideAtlas; Q62219; -.
DR PRIDE; Q62219; -.
DR ProteomicsDB; 263042; -. [Q62219-1]
DR ProteomicsDB; 263043; -. [Q62219-2]
DR ProteomicsDB; 263044; -. [Q62219-3]
DR ProteomicsDB; 263045; -. [Q62219-4]
DR ProteomicsDB; 263046; -. [Q62219-5]
DR ProteomicsDB; 263047; -. [Q62219-6]
DR ProteomicsDB; 263048; -. [Q62219-7]
DR ProteomicsDB; 263050; -. [Q62219-9]
DR ProteomicsDB; 263051; -. [Q62219-10]
DR Antibodypedia; 1738; 255 antibodies from 29 providers.
DR DNASU; 21804; -.
DR Ensembl; ENSMUST00000070656; ENSMUSP00000068529; ENSMUSG00000030782. [Q62219-2]
DR Ensembl; ENSMUST00000164710; ENSMUSP00000130964; ENSMUSG00000030782. [Q62219-3]
DR Ensembl; ENSMUST00000167965; ENSMUSP00000132100; ENSMUSG00000030782. [Q62219-1]
DR Ensembl; ENSMUST00000169919; ENSMUSP00000131705; ENSMUSG00000030782. [Q62219-6]
DR GeneID; 21804; -.
DR KEGG; mmu:21804; -.
DR UCSC; uc009jyl.3; mouse. [Q62219-1]
DR UCSC; uc009jyo.2; mouse. [Q62219-4]
DR CTD; 7041; -.
DR MGI; MGI:102784; Tgfb1i1.
DR VEuPathDB; HostDB:ENSMUSG00000030782; -.
DR eggNOG; KOG1703; Eukaryota.
DR GeneTree; ENSGT00940000160447; -.
DR HOGENOM; CLU_2922022_0_0_1; -.
DR InParanoid; Q62219; -.
DR OMA; CREPFGD; -.
DR OrthoDB; 1593918at2759; -.
DR PhylomeDB; Q62219; -.
DR TreeFam; TF314113; -.
DR BioGRID-ORCS; 21804; 2 hits in 75 CRISPR screens.
DR PRO; PR:Q62219; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q62219; protein.
DR Bgee; ENSMUSG00000030782; Expressed in ascending aorta and 242 other tissues.
DR ExpressionAtlas; Q62219; baseline and differential.
DR Genevisible; Q62219; MM.
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; IDA:MGI.
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; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0050681; F:nuclear androgen receptor binding; ISO:MGI.
DR GO; GO:0048495; F:Roundabout binding; ISO:MGI.
DR GO; GO:0003713; F:transcription coactivator activity; ISS:UniProtKB.
DR GO; GO:0003712; F:transcription coregulator activity; IBA:GO_Central.
DR GO; GO:0045165; P:cell fate commitment; IGI:MGI.
DR GO; GO:0030855; P:epithelial cell differentiation; IGI:MGI.
DR GO; GO:0045444; P:fat cell differentiation; IGI:MGI.
DR GO; GO:0016331; P:morphogenesis of embryonic epithelium; IMP:MGI.
DR GO; GO:0045599; P:negative regulation of fat cell differentiation; IGI:MGI.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; ISO:MGI.
DR GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; ISO:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:0030511; P:positive regulation of transforming growth factor beta receptor signaling pathway; ISO:MGI.
DR GO; GO:0009408; P:response to heat; ISO:MGI.
DR GO; GO:0030579; P:ubiquitin-dependent SMAD protein catabolic process; ISO:MGI.
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_0000291583"
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 /evidence="ECO:0000250"
FT REGION 1..200
FT /note="Transcription activation"
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 REGION 116..154
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 171..204
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 42..57
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 176..190
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:O43294"
FT MOD_RES 33
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O43294"
FT MOD_RES 38
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:16183059"
FT MOD_RES 60
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:16183059"
FT MOD_RES 68
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 141
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O43294"
FT MOD_RES 164
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O43294"
FT MOD_RES 186
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 188
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 194
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 403
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 407
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O43294"
FT VAR_SEQ 1..111
FT /note="Missing (in isoform 7)"
FT /evidence="ECO:0000303|PubMed:16219310"
FT /id="VSP_026184"
FT VAR_SEQ 1..110
FT /note="Missing (in isoform 10)"
FT /evidence="ECO:0000303|PubMed:16219310"
FT /id="VSP_026185"
FT VAR_SEQ 1..62
FT /note="Missing (in isoform 9)"
FT /evidence="ECO:0000303|PubMed:16219310"
FT /id="VSP_026188"
FT VAR_SEQ 1..59
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:16219310"
FT /id="VSP_026189"
FT VAR_SEQ 1..43
FT /note="MEDLDALLSDLETTTSHMSRLGAPKERPPETLTPPPPYGHQPQ -> MSPCS
FT PFIAPPPPTVSQRVPASIHGHGPASNSLTSPPSPSSAPTGHGPRPTLPKLSASAPPWRT
FT W (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16219310"
FT /id="VSP_026190"
FT VAR_SEQ 1..17
FT /note="Missing (in isoform 2 and isoform 8)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16219310, ECO:0000303|PubMed:7929412"
FT /id="VSP_026191"
FT VAR_SEQ 60..82
FT /note="YSTVCKPRSPKPVAPVAPPFSSS -> MATSHRQGLENLQEPLGTRIIYT
FT (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:16219310"
FT /id="VSP_026192"
FT VAR_SEQ 61
FT /note="S -> R (in isoform 6 and isoform 8)"
FT /evidence="ECO:0000303|PubMed:16141072,
FT ECO:0000303|PubMed:16219310"
FT /id="VSP_039813"
FT VAR_SEQ 62..461
FT /note="Missing (in isoform 6 and isoform 8)"
FT /evidence="ECO:0000303|PubMed:16141072,
FT ECO:0000303|PubMed:16219310"
FT /id="VSP_039814"
FT VAR_SEQ 62..107
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:16219310"
FT /id="VSP_026193"
FT VAR_SEQ 63..138
FT /note="VCKPRSPKPVAPVAPPFSSSSGVLGNGLCELDRLLQELNATQFNITDEIMSQ
FT FPSSKMAEGEEKEDQSEDKSSPTV -> MPPSSTLQMKSCLSSHLVKWLKGKRRRTNLK
FT TRAHPLCEFGRVGRAGKRMMGPACLTYQRGVRLAGSEVIHGVLHN (in isoform
FT 9)"
FT /evidence="ECO:0000303|PubMed:16219310"
FT /id="VSP_026194"
FT VAR_SEQ 111..148
FT /note="IMSQFPSSKMAEGEEKEDQSEDKSSPTVPPSPFPAPSK -> MPPSSTLQMK
FT SCLSSHLVKWLKGKRRRTNLKTRAHPLS (in isoform 10)"
FT /evidence="ECO:0000303|PubMed:16219310"
FT /id="VSP_026197"
FT MUTAGEN 38
FT /note="Y->F: Reduced phosphorylation. Loss of
FT phosphorylation; when associated with F-60."
FT /evidence="ECO:0000269|PubMed:16183059"
FT MUTAGEN 60
FT /note="Y->F: Reduced phosphorylation. Loss of
FT phosphorylation; when associated with F-38."
FT /evidence="ECO:0000269|PubMed:16183059"
FT MUTAGEN 64
FT /note="C->N: Increase in nuclear localization."
FT /evidence="ECO:0000269|PubMed:12631731"
FT MUTAGEN 91
FT /note="C->S: Increase in nuclear localization."
FT /evidence="ECO:0000269|PubMed:12631731"
FT MUTAGEN 161
FT /note="L->A: Increase in nuclear localization."
FT /evidence="ECO:0000269|PubMed:12631731"
FT MUTAGEN 366
FT /note="H->G: Loss of interaction with PTPN12; when
FT associated with G-369."
FT /evidence="ECO:0000269|PubMed:10092676"
FT MUTAGEN 369
FT /note="C->A: Loss of localization to focal adhesion; when
FT associated with A-372."
FT /evidence="ECO:0000269|PubMed:10092676,
FT ECO:0000269|PubMed:16183059"
FT MUTAGEN 369
FT /note="C->G: Loss of interaction with PTPN12; when
FT associated with G-366."
FT /evidence="ECO:0000269|PubMed:10092676,
FT ECO:0000269|PubMed:16183059"
FT MUTAGEN 372
FT /note="C->A: Loss of localization to focal adhesion; when
FT associated with A-369."
FT /evidence="ECO:0000269|PubMed:16183059"
SQ SEQUENCE 461 AA; 50101 MW; 6AB15FFF466FEE73 CRC64;
MEDLDALLSD LETTTSHMSR LGAPKERPPE TLTPPPPYGH QPQTGSGESS GTTGDKDHLY
STVCKPRSPK PVAPVAPPFS SSSGVLGNGL CELDRLLQEL NATQFNITDE IMSQFPSSKM
AEGEEKEDQS EDKSSPTVPP SPFPAPSKPS ATSATQELDR LMASLSDFRV QNHLPASGPP
QPPAASPTRE GCPSPPGQTS KGSLDTMLGL LQSDLSRRGV PTQAKGLCGS CNKPIAGQVV
TALGRAWHPE HFLCSGCSTT LGGSSFFEKD GAPFCPECYF ERFSPRCGFC NQPIRHKMVT
ALGTHWHPEH FCCVSCGEPF GEEGFHEREG RPYCRRDFLQ LFAPRCQGCQ GPILDNYISA
LSALWHPDCF VCRECLAPFS GGSFFEHEGR PLCENHFHAQ RGSLCATCGL PVTGRCVSAL
GRRFHPDHFT CTFCLRPLTK GSFQERASKP YCQPCFLKLF G
