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Protein

Transforming growth factor beta-1-induced transcript 1 protein

Gene

TGFB1I1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Functions as a molecular adapter coordinating multiple protein-protein interactions at the focal adhesion complex and in the nucleus. Links various intracellular signaling modules to plasma membrane receptors and regulates the Wnt and TGFB signaling pathways. May also regulate SLC6A3 and SLC6A4 targeting to the plasma membrane hence regulating their activity. In the nucleus, functions as a nuclear receptor coactivator regulating glucocorticoid, androgen, mineralocorticoid and progesterone receptor transcriptional activity. May play a role in the processes of cell growth, proliferation, migration, differentiation and senescence. May have a zinc-dependent DNA-binding activity.15 Publications

GO - Molecular functioni

  • androgen receptor binding Source: UniProtKB
  • I-SMAD binding Source: BHF-UCL
  • Roundabout binding Source: UniProtKB
  • transcription coactivator activity Source: UniProtKB
  • zinc ion binding Source: InterPro

GO - Biological processi

  • androgen receptor signaling pathway Source: UniProtKB
  • cell adhesion Source: ProtInc
  • cell differentiation Source: UniProtKB-KW
  • negative regulation of cell proliferation Source: ProtInc
  • negative regulation of transforming growth factor beta receptor signaling pathway Source: BHF-UCL
  • positive regulation of epithelial to mesenchymal transition Source: BHF-UCL
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transforming growth factor beta receptor signaling pathway Source: BHF-UCL
  • response to heat Source: Ensembl
  • transcription from RNA polymerase II promoter Source: ProtInc
  • ubiquitin-dependent SMAD protein catabolic process Source: BHF-UCL
  • Wnt signaling pathway Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Differentiation, Wnt signaling pathway

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

SignaLinkiO43294.

Names & Taxonomyi

Protein namesi
Recommended name:
Transforming growth factor beta-1-induced transcript 1 protein
Alternative name(s):
Androgen receptor coactivator 55 kDa protein
Androgen receptor-associated protein of 55 kDa
Hydrogen peroxide-inducible clone 5 protein
Short name:
Hic-5
Gene namesi
Name:TGFB1I1
Synonyms:ARA55
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

HGNCiHGNC:11767. TGFB1I1.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB-KW
  • cytoskeleton Source: UniProtKB-SubCell
  • focal adhesion Source: UniProtKB
  • intracellular Source: UniProtKB
  • nuclear matrix Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cytoplasm, Cytoskeleton, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi60Y → F: Prevents phosphorylation by FAK2 and FYN. Prevents interaction with CSK. 1 Publication1
Mutagenesisi287C → A: Abolishes interaction with CBLC and enhancement of CBLC E3 ubiquitin-protein ligase activity. 1 Publication1
Mutagenesisi313C → A: No effect on interaction with CBLC. 1 Publication1
Mutagenesisi338 – 342FLQLF → ALQAA: Loss of interaction with AR; when associated with 456-A--A-460. 1 Publication5
Mutagenesisi369C → S: Loss of AR coactivation; when associated with S-372. 1 Publication1
Mutagenesisi372C → S: Loss of AR coactivation; when associated with S-369. 1 Publication1
Mutagenesisi428H → S: Loss of AR coactivation; when associated with S-431. 1 Publication1
Mutagenesisi431C → S: Loss of AR coactivation; when associated with S-428. 1 Publication1
Mutagenesisi456 – 460FLKLF → ALKAA: Loss of interaction with AR; when associated with 338-A--A-342. 1 Publication5

Organism-specific databases

DisGeNETi7041.
OpenTargetsiENSG00000140682.
PharmGKBiPA36481.

Polymorphism and mutation databases

BioMutaiTGFB1I1.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002915821 – 461Transforming growth factor beta-1-induced transcript 1 proteinAdd BLAST461

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei33PhosphothreonineCombined sources1
Modified residuei38PhosphotyrosineBy similarity1
Modified residuei60Phosphotyrosine; by FAK2 and FYN2 Publications1
Modified residuei68PhosphoserineCombined sources1
Modified residuei137PhosphoserineCombined sources1
Modified residuei140PhosphoserineCombined sources1
Modified residuei141PhosphoserineCombined sources1
Modified residuei143PhosphoserineCombined sources1
Modified residuei164PhosphoserineCombined sources1
Modified residuei186PhosphoserineBy similarity1
Modified residuei188PhosphothreonineBy similarity1
Modified residuei192PhosphoserineCombined sources1
Modified residuei194PhosphoserineCombined sources1
Modified residuei403PhosphoserineCombined sources1
Modified residuei407PhosphothreonineCombined sources1

Post-translational modificationi

Phosphorylated by gonadotropin-releasing hormone-activated SRC.5 Publications

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiO43294.
MaxQBiO43294.
PaxDbiO43294.
PeptideAtlasiO43294.
PRIDEiO43294.

PTM databases

iPTMnetiO43294.
PhosphoSitePlusiO43294.

Expressioni

Tissue specificityi

Expressed in platelets, smooth muscle and prostate stromal cells (at protein level).9 Publications

Inductioni

Up-regulated by TNF and hydrogen peroxide.2 Publications

Gene expression databases

BgeeiENSG00000140682.
CleanExiHS_TGFB1I1.
ExpressionAtlasiO43294. baseline and differential.
GenevisibleiO43294. HS.

Organism-specific databases

HPAiCAB020844.
HPA006376.

Interactioni

Subunit structurei

Homooligomer. Interacts with CRIP2, HSPB1, ILK, LIMS1, LIMS2, NCK2, NUDT16L1, PAK, PPARG, PTPN12, TCF3, TCF7L2 and VCL. Forms a complex with GIT1 and ARHGEF7. Interacts with AR/androgen receptor in a ligand-dependent manner. Interacts with CSK, LYN, MAPK15, NR3C1, PPARG, PTK2/FAK1, PTK2B/PYK2, SLC6A3, SLC6A4, SMAD3, SRC and talin. Interacts (via LIM zinc-binding domain 2) with CBLC (via RING-type zinc finger); the interaction is direct and enhances CBLC E3 ubiquitin-protein ligase activity.20 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ITGA4P136122EBI-1051449,EBI-703044
PTK2Q053972EBI-1051449,EBI-702142

GO - Molecular functioni

  • androgen receptor binding Source: UniProtKB
  • I-SMAD binding Source: BHF-UCL
  • Roundabout binding Source: UniProtKB

Protein-protein interaction databases

BioGridi112899. 31 interactors.
DIPiDIP-5931N.
IntActiO43294. 22 interactors.
MINTiMINT-243624.
STRINGi9606.ENSP00000378332.

Structurei

3D structure databases

ProteinModelPortaliO43294.
SMRiO43294.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini226 – 285LIM zinc-binding 1PROSITE-ProRule annotationAdd BLAST60
Domaini286 – 343LIM zinc-binding 2PROSITE-ProRule annotationAdd BLAST58
Domaini344 – 403LIM zinc-binding 3PROSITE-ProRule annotationAdd BLAST60
Domaini404 – 461LIM zinc-binding 4PROSITE-ProRule annotationAdd BLAST58

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 240Interaction with PTK2B/PYK2Add BLAST240
Regioni1 – 200Transcription activationBy similarityAdd BLAST200
Regioni83 – 136Interaction with PTK2/FAK1By similarityAdd BLAST54

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi3 – 15LD motif 1Add BLAST13
Motifi92 – 104LD motif 2Add BLAST13
Motifi157 – 168LD motif 3Add BLAST12
Motifi203 – 215LD motif 4Add BLAST13

Domaini

The LIM zinc-binding domains mediate glucocorticoid receptor coactivation and interaction with AR, CRIP2, ILK, LIMS1, NR3C1, PPARG, TCF3, TCF7L2, SLC6A3 and SMAD3. The LIM zinc-binding 2 and LIM zinc-binding 3 domains mediate targeting to focal adhesions and actin stress fibers. The LIM zinc-binding 3 and LIM zinc-binding 4 domains mediate interaction with TRAF4 and MAPK15. The LIM zinc-binding 4 domain mediates interaction with HSPB1, homooligomerization and targeting to the nuclear matrix. The LIM zinc-binding 3 domain mediates interaction with PTPN12.
The LD (leucine and aspartate-rich) motif 3 mediates interaction with GIT1 and functions as a nuclear export signal.

Sequence similaritiesi

Belongs to the paxillin family.Curated
Contains 4 LIM zinc-binding domains.PROSITE-ProRule annotation

Keywords - Domaini

LIM domain, Repeat

Phylogenomic databases

eggNOGiKOG1703. Eukaryota.
ENOG410XRD4. LUCA.
GeneTreeiENSGT00760000118910.
HOGENOMiHOG000018764.
HOVERGENiHBG001512.
InParanoidiO43294.
OMAiCGEPFGE.
OrthoDBiEOG091G05AW.
PhylomeDBiO43294.
TreeFamiTF314113.

Family and domain databases

Gene3Di2.10.110.10. 4 hits.
InterProiIPR017305. Tgfb1i1/Leupaxin.
IPR001781. Znf_LIM.
[Graphical view]
PfamiPF00412. LIM. 4 hits.
[Graphical view]
PIRSFiPIRSF037881. Leupaxin. 1 hit.
SMARTiSM00132. LIM. 4 hits.
[Graphical view]
PROSITEiPS00478. LIM_DOMAIN_1. 4 hits.
PS50023. LIM_DOMAIN_2. 4 hits.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O43294-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MEDLDALLSD LETTTSHMPR SGAPKERPAE PLTPPPSYGH QPQTGSGESS
60 70 80 90 100
GASGDKDHLY STVCKPRSPK PAAPAAPPFS SSSGVLGTGL CELDRLLQEL
110 120 130 140 150
NATQFNITDE IMSQFPSSKV ASGEQKEDQS EDKKRPSLPS SPSPGLPKAS
160 170 180 190 200
ATSATLELDR LMASLSDFRV QNHLPASGPT QPPVVSSTNE GSPSPPEPTG
210 220 230 240 250
KGSLDTMLGL LQSDLSRRGV PTQAKGLCGS CNKPIAGQVV TALGRAWHPE
260 270 280 290 300
HFVCGGCSTA LGGSSFFEKD GAPFCPECYF ERFSPRCGFC NQPIRHKMVT
310 320 330 340 350
ALGTHWHPEH FCCVSCGEPF GDEGFHEREG RPYCRRDFLQ LFAPRCQGCQ
360 370 380 390 400
GPILDNYISA LSALWHPDCF VCRECFAPFS GGSFFEHEGR PLCENHFHAR
410 420 430 440 450
RGSLCATCGL PVTGRCVSAL GRRFHPDHFT CTFCLRPLTK GSFQERAGKP
460
YCQPCFLKLF G
Length:461
Mass (Da):49,814
Last modified:June 26, 2007 - v2
Checksum:iD2C7C32C3FD2C496
GO
Isoform 2 (identifier: O43294-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-17: Missing.

Show »
Length:444
Mass (Da):47,941
Checksum:iEC9E92DADE7156B4
GO

Sequence cautioni

The sequence AAH32545 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti166S → P in AAD22552 (PubMed:10075738).Curated1
Sequence conflicti200G → A in AAD22552 (PubMed:10075738).Curated1
Sequence conflicti363A → L in AAD22552 (PubMed:10075738).Curated1
Sequence conflicti405 – 406CA → WP in AAD22552 (PubMed:10075738).Curated2
Sequence conflicti430T → A in AAD22552 (PubMed:10075738).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_032831129Q → H.1 PublicationCorresponds to variant rs45475699dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0261831 – 17Missing in isoform 2. 3 PublicationsAdd BLAST17

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF116343 mRNA. Translation: AAD22552.1.
DQ309025 Genomic DNA. Translation: ABB96286.1.
AK313327 mRNA. Translation: BAG36132.1.
CH471192 Genomic DNA. Translation: EAW52126.1.
BC001507 mRNA. Translation: AAH01507.2.
BC001830 mRNA. Translation: AAH01830.1.
BC017288 mRNA. Translation: AAH17288.1.
BC032545 mRNA. Translation: AAH32545.1. Different initiation.
AB007836 mRNA. Translation: BAA24799.1.
CCDSiCCDS10713.1. [O43294-2]
CCDS42156.1. [O43294-1]
RefSeqiNP_001035919.1. NM_001042454.2. [O43294-1]
NP_001158191.1. NM_001164719.1. [O43294-2]
NP_057011.2. NM_015927.4. [O43294-2]
UniGeneiHs.513530.

Genome annotation databases

EnsembliENST00000361773; ENSP00000355117; ENSG00000140682. [O43294-2]
ENST00000394858; ENSP00000378327; ENSG00000140682. [O43294-2]
ENST00000394863; ENSP00000378332; ENSG00000140682. [O43294-1]
ENST00000567607; ENSP00000457586; ENSG00000140682. [O43294-2]
GeneIDi7041.
KEGGihsa:7041.
UCSCiuc002ecd.3. human. [O43294-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF116343 mRNA. Translation: AAD22552.1.
DQ309025 Genomic DNA. Translation: ABB96286.1.
AK313327 mRNA. Translation: BAG36132.1.
CH471192 Genomic DNA. Translation: EAW52126.1.
BC001507 mRNA. Translation: AAH01507.2.
BC001830 mRNA. Translation: AAH01830.1.
BC017288 mRNA. Translation: AAH17288.1.
BC032545 mRNA. Translation: AAH32545.1. Different initiation.
AB007836 mRNA. Translation: BAA24799.1.
CCDSiCCDS10713.1. [O43294-2]
CCDS42156.1. [O43294-1]
RefSeqiNP_001035919.1. NM_001042454.2. [O43294-1]
NP_001158191.1. NM_001164719.1. [O43294-2]
NP_057011.2. NM_015927.4. [O43294-2]
UniGeneiHs.513530.

3D structure databases

ProteinModelPortaliO43294.
SMRiO43294.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112899. 31 interactors.
DIPiDIP-5931N.
IntActiO43294. 22 interactors.
MINTiMINT-243624.
STRINGi9606.ENSP00000378332.

PTM databases

iPTMnetiO43294.
PhosphoSitePlusiO43294.

Polymorphism and mutation databases

BioMutaiTGFB1I1.

Proteomic databases

EPDiO43294.
MaxQBiO43294.
PaxDbiO43294.
PeptideAtlasiO43294.
PRIDEiO43294.

Protocols and materials databases

DNASUi7041.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000361773; ENSP00000355117; ENSG00000140682. [O43294-2]
ENST00000394858; ENSP00000378327; ENSG00000140682. [O43294-2]
ENST00000394863; ENSP00000378332; ENSG00000140682. [O43294-1]
ENST00000567607; ENSP00000457586; ENSG00000140682. [O43294-2]
GeneIDi7041.
KEGGihsa:7041.
UCSCiuc002ecd.3. human. [O43294-1]

Organism-specific databases

CTDi7041.
DisGeNETi7041.
GeneCardsiTGFB1I1.
HGNCiHGNC:11767. TGFB1I1.
HPAiCAB020844.
HPA006376.
MIMi602353. gene.
neXtProtiNX_O43294.
OpenTargetsiENSG00000140682.
PharmGKBiPA36481.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1703. Eukaryota.
ENOG410XRD4. LUCA.
GeneTreeiENSGT00760000118910.
HOGENOMiHOG000018764.
HOVERGENiHBG001512.
InParanoidiO43294.
OMAiCGEPFGE.
OrthoDBiEOG091G05AW.
PhylomeDBiO43294.
TreeFamiTF314113.

Enzyme and pathway databases

SignaLinkiO43294.

Miscellaneous databases

GeneWikiiTGFB1I1.
GenomeRNAii7041.
PROiO43294.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000140682.
CleanExiHS_TGFB1I1.
ExpressionAtlasiO43294. baseline and differential.
GenevisibleiO43294. HS.

Family and domain databases

Gene3Di2.10.110.10. 4 hits.
InterProiIPR017305. Tgfb1i1/Leupaxin.
IPR001781. Znf_LIM.
[Graphical view]
PfamiPF00412. LIM. 4 hits.
[Graphical view]
PIRSFiPIRSF037881. Leupaxin. 1 hit.
SMARTiSM00132. LIM. 4 hits.
[Graphical view]
PROSITEiPS00478. LIM_DOMAIN_1. 4 hits.
PS50023. LIM_DOMAIN_2. 4 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTGFI1_HUMAN
AccessioniPrimary (citable) accession number: O43294
Secondary accession number(s): B2R8D5, Q9BPW3, Q9Y2V5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 26, 2007
Last sequence update: June 26, 2007
Last modified: November 2, 2016
This is version 130 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.