TGFI1_RAT
ID TGFI1_RAT Reviewed; 461 AA.
AC Q99PD6;
DT 26-JUN-2007, integrated into UniProtKB/Swiss-Prot.
DT 26-JUN-2007, sequence version 2.
DT 03-AUG-2022, entry version 121.
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;
GN Name=Tgfb1i1; Synonyms=Ara55;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-224.
RC TISSUE=Thymus;
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 [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 132-461, INTERACTION WITH HSPB1, AND TISSUE
RP SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Renal glomerulus;
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 [3]
RP FUNCTION, AND INDUCTION BY RETINOIC ACID.
RX PubMed=9597752; DOI=10.1016/s1357-2725(97)00155-6;
RA Shibanuma M., Nose K.;
RT "Forced expression of hic-5, a senescence-related gene, potentiates a
RT differentiation process of RCT-1 cells induced by retinoic acid.";
RL Int. J. Biochem. Cell Biol. 30:39-45(1998).
RN [4]
RP SUBCELLULAR LOCATION, PHOSPHORYLATION, AND 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 [5]
RP SUBCELLULAR LOCATION.
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 [6]
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 [7]
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 [8]
RP 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 [9]
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 [10]
RP 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 [11]
RP SUBCELLULAR LOCATION, PHOSPHORYLATION, AND INTERACTION WITH PTK2B AND PXN.
RX PubMed=16546139; DOI=10.1016/j.bbrc.2006.02.162;
RA Guignandon A., Boutahar N., Rattner A., Vico L., Lafage-Proust M.-H.;
RT "Cyclic strain promotes shuttling of PYK2/Hic-5 complex from focal contacts
RT in osteoblast-like cells.";
RL Biochem. Biophys. Res. Commun. 343:407-414(2006).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-33, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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:9597752}.
CC -!- SUBUNIT: Homooligomer (By similarity). Interacts with PPARG (By
CC similarity). Interacts with TRAF4 (By similarity). Interacts with CRIP2
CC (By similarity). Interacts with HSPB1 (PubMed:11546764). Interacts with
CC ILK (By similarity). Interacts with LIMS1 and LIMS2 (By similarity).
CC Interacts with NCK2 (PubMed:10330411). Interacts with NUDT16L1 (By
CC similarity). Interacts with PAK (PubMed:10330411). Interacts with
CC PTPN12 (By similarity). Interacts with TCF3 (By similarity). Interacts
CC with TCF7L2 (By similarity). Interacts with VCL (By similarity).
CC Interacts (via LD motif 3) with GIT1 (PubMed:12153727). Also interacts
CC with GIT2 (PubMed:10330411). Forms a complex with ARHGEF7
CC (PubMed:10330411). Interacts with AR/androgen receptor in a ligand-
CC dependent manner (By similarity). Interacts with CSK (By similarity).
CC Interacts with PTK2/FAK1 and PTK2B/PYK2 (PubMed:9422762,
CC PubMed:10330411, PubMed:16546139). Interacts with SLC6A3 and SLC6A4 (By
CC similarity). Interacts with NR3C1 (By similarity). Interacts with SMAD3
CC (By similarity). Interacts with MAPK15 (By similarity). Interacts with
CC SRC (By similarity). Interacts with LYN (By similarity). Interacts with
CC talin (By similarity). 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 (By similarity).
CC Interacts with PARVA (PubMed:11134073). Interacts with PXN
CC (PubMed:16546139). {ECO:0000250|UniProtKB:O43294,
CC ECO:0000250|UniProtKB:Q62219, ECO:0000269|PubMed:10330411,
CC ECO:0000269|PubMed:11134073, ECO:0000269|PubMed:11546764,
CC ECO:0000269|PubMed:12153727, ECO:0000269|PubMed:16546139,
CC ECO:0000269|PubMed:9422762}.
CC -!- SUBCELLULAR LOCATION: Cell junction, focal adhesion. Nucleus matrix.
CC Cytoplasm, cytoskeleton. Note=Associated with the actin cytoskeleton,
CC colocalizes with stress fibers.
CC -!- TISSUE SPECIFICITY: Strongly expressed in large intestine, lung,
CC spleen, testis, uterus and to a lower extent in brain, kidney and liver
CC (at protein level). In brain, expressed by neuronal and non neuronal
CC cells (at protein level). {ECO:0000269|PubMed:11546764,
CC ECO:0000269|PubMed:12177201}.
CC -!- INDUCTION: Up-regulated by retinoic acid. {ECO:0000269|PubMed:9597752}.
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 (By similarity). {ECO:0000250}.
CC -!- DOMAIN: The LD (leucine and aspartate-rich) motif 3 mediates
CC interaction with GIT1 and functions as a nuclear export signal.
CC {ECO:0000250}.
CC -!- PTM: Phosphorylated by gonadotropin-releasing hormone-activated SRC.
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the paxillin family. {ECO:0000305}.
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DR EMBL; CV078574; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AF314960; AAK01175.1; -; mRNA.
DR RefSeq; NP_001178769.1; NM_001191840.1.
DR AlphaFoldDB; Q99PD6; -.
DR SMR; Q99PD6; -.
DR STRING; 10116.ENSRNOP00000051863; -.
DR iPTMnet; Q99PD6; -.
DR PhosphoSitePlus; Q99PD6; -.
DR PaxDb; Q99PD6; -.
DR PRIDE; Q99PD6; -.
DR GeneID; 84574; -.
DR KEGG; rno:84574; -.
DR UCSC; RGD:620173; rat.
DR CTD; 7041; -.
DR RGD; 620173; Tgfb1i1.
DR VEuPathDB; HostDB:ENSRNOG00000019965; -.
DR eggNOG; KOG1703; Eukaryota.
DR HOGENOM; CLU_001357_1_2_1; -.
DR InParanoid; Q99PD6; -.
DR OMA; CREPFGD; -.
DR OrthoDB; 1593918at2759; -.
DR PhylomeDB; Q99PD6; -.
DR PRO; PR:Q99PD6; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000019965; Expressed in colon and 20 other tissues.
DR Genevisible; Q99PD6; RN.
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; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0048495; F:Roundabout binding; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0030855; P:epithelial cell differentiation; ISO:RGD.
DR GO; GO:0016331; P:morphogenesis of embryonic epithelium; ISO:RGD.
DR GO; GO:0045599; P:negative regulation of fat cell differentiation; ISO:RGD.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; ISO:RGD.
DR GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; ISO:RGD.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0030511; P:positive regulation of transforming growth factor beta receptor signaling pathway; ISO:RGD.
DR GO; GO:0009408; P:response to heat; IDA:RGD.
DR GO; GO:0030579; P:ubiquitin-dependent SMAD protein catabolic process; ISO:RGD.
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; Cell junction; Cytoplasm; Cytoskeleton;
KW Differentiation; LIM domain; Metal-binding; Nucleus; Phosphoprotein;
KW 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_0000291584"
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 /evidence="ECO:0000250"
FT REGION 1..86
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..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 134..154
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:0007744|PubMed:22673903"
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:0000250|UniProtKB:O43294"
FT MOD_RES 68
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O43294"
FT MOD_RES 140
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O43294"
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:0000250|UniProtKB:Q62219"
FT MOD_RES 188
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q62219"
FT MOD_RES 194
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O43294"
FT MOD_RES 403
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O43294"
FT MOD_RES 407
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O43294"
SQ SEQUENCE 461 AA; 50123 MW; 61991D74ACF1681B CRC64;
MEDLDALLSD LETTTSHMSR LGAPKERPPE TLTPPPPYGH QPQTGSGESS GASGDKDHLY
STVCKPRSPK SVAPVAPPFS SSSGVLGNGL CELDRLLQEL NATQFNITDE IMSQFPSSKM
AEGEGKEDQS EDKSITTVPS STFPAPSKPS ATSATQELDR LMASLSDFRV QNHLPASGPP
QPPAVSPTRE GCPSPPGQTN KGSLDTMLGL LQSDLSRRGV PTQAKGLCGS CNKPIAGQVV
TALGRAWHPE HFLCRGCSTT LGGSSFFEKD GAPFCPECYF ERFSPRCGFC NQPIRHKMVT
ALGTHWHPEH FCCVSCGEPF GEEGFHEREG RPYCRRDFLQ LFAPRCQGCQ GPILDNYISA
LSALWHPDCF VCRECLAPFS GGSFFEHEGR PLCENHFHAQ RGSLCATCGL PVTGRCVSAL
GRRFHPDHFT CTFCLRPLTK GSFQERASKP YCQPCFLKLF G
