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Q15583 (TGIF1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 153. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Homeobox protein TGIF1
Alternative name(s):
5'-TG-3'-interacting factor 1
Gene names
Name:TGIF1
Synonyms:TGIF
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length401 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Binds to a retinoid X receptor (RXR) responsive element from the cellular retinol-binding protein II promoter (CRBPII-RXRE). Inhibits the 9-cis-retinoic acid-dependent RXR alpha transcription activation of the retinoic acid responsive element. Active transcriptional corepressor of SMAD2. Links the nodal signaling pathway to the bifurcation of the forebrain and the establishment of ventral midline structures. May participate in the transmission of nuclear signals during development and in the adult, as illustrated by the down-modulation of the RXR alpha activities.

Subunit structure

Interacts with CTBP, SMAD2, SMAD3 and HDAC1.

Subcellular location

Nucleus.

Involvement in disease

Holoprosencephaly 4 (HPE4) [MIM:142946]: A structural anomaly of the brain, in which the developing forebrain fails to correctly separate into right and left hemispheres. Holoprosencephaly is genetically heterogeneous and associated with several distinct facies and phenotypic variability.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9 Ref.10

Sequence similarities

Belongs to the TALE/TGIF homeobox family.

Contains 1 homeobox DNA-binding domain.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
Holoprosencephaly
   DomainHomeobox
   LigandDNA-binding
   Molecular functionRepressor
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processdetermination of left/right symmetry

Inferred from electronic annotation. Source: Ensembl

dorsal/ventral pattern formation

Inferred from electronic annotation. Source: Ensembl

gene expression

Traceable author statement. Source: Reactome

multicellular organismal development

Traceable author statement Ref.1. Source: ProtInc

negative regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

negative regulation of retinoic acid receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription from RNA polymerase II promoter

Traceable author statement. Source: Reactome

neural tube closure

Inferred from electronic annotation. Source: Ensembl

nodal signaling pathway

Inferred from electronic annotation. Source: Ensembl

positive regulation of fibroblast proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of neuron differentiation

Inferred from electronic annotation. Source: Ensembl

regulation of gastrulation

Inferred from electronic annotation. Source: Ensembl

response to drug

Inferred from electronic annotation. Source: Ensembl

retina development in camera-type eye

Inferred from electronic annotation. Source: Ensembl

transcription initiation from RNA polymerase II promoter

Traceable author statement. Source: Reactome

transcription, DNA-templated

Traceable author statement. Source: Reactome

transforming growth factor beta receptor signaling pathway

Traceable author statement. Source: Reactome

   Cellular_componentnucleoplasm

Traceable author statement. Source: Reactome

   Molecular_functionchromatin binding

Inferred from electronic annotation. Source: Ensembl

sequence-specific DNA binding

Inferred from electronic annotation. Source: InterPro

sequence-specific DNA binding transcription factor activity

Traceable author statement Ref.1. Source: ProtInc

transcription corepressor activity

Traceable author statement Ref.2. Source: ProtInc

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

LGALS8O0021410EBI-714215,EBI-740058
PMLP295903EBI-714215,EBI-295890

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q15583-1)

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.
Isoform 2 (identifier: Q15583-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-129: Missing.
     130-133: LETM → MKGK
Isoform 3 (identifier: Q15583-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-115: Missing.
     116-134: PSQGAQGPAPRRRLLETMK → MTCSGKSCALARSSLTSSQ
Isoform 4 (identifier: Q15583-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-149: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 401401Homeobox protein TGIF1
PRO_0000049318

Regions

DNA binding164 – 22663Homeobox; TALE-type
Motif153 – 1575CTBP-binding motif
Compositional bias165 – 1684Poly-Arg

Natural variations

Alternative sequence1 – 149149Missing in isoform 4.
VSP_046848
Alternative sequence1 – 129129Missing in isoform 2.
VSP_013020
Alternative sequence1 – 115115Missing in isoform 3.
VSP_043108
Alternative sequence116 – 13419PSQGA…LETMK → MTCSGKSCALARSSLTSSQ in isoform 3.
VSP_043109
Alternative sequence130 – 1334LETM → MKGK in isoform 2.
VSP_013021
Natural variant1571S → C in HPE4. Ref.9
VAR_009961
Natural variant1921P → R in HPE4. Ref.9
VAR_009962
Natural variant2361Q → L in HPE4. Ref.10
VAR_023803
Natural variant2801T → A in HPE4. Ref.9
VAR_009963
Natural variant2891P → S.
Corresponds to variant rs11571512 [ dbSNP | Ensembl ].
VAR_047363
Natural variant2911S → F in HPE4. Ref.9
VAR_009964
Natural variant2921P → L.
Corresponds to variant rs2229333 [ dbSNP | Ensembl ].
VAR_020151
Natural variant2921P → S. Ref.2 Ref.3
Corresponds to variant rs4468717 [ dbSNP | Ensembl ].
VAR_061268

Experimental info

Sequence conflict961P → Q in AAH31268. Ref.7

Secondary structure

.......... 401
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 25, 2008. Version 3.
Checksum: 4D9C76AFB37A29F0

FASTA40143,013
        10         20         30         40         50         60 
MVLAQSRVSA GVGSPHCSGS GGGGSDSFPW PASHPGNPQC SFSTAFLASP RLSRGTLAYL 

        70         80         90        100        110        120 
PPAPWSSLAT PSALLGSSCA PPPPPARCPQ PRALSPELGT KAGPRRPHRW ELPRSPSQGA 

       130        140        150        160        170        180 
QGPAPRRRLL ETMKGIVAAS GSETEDEDSM DIPLDLSSSA GSGKRRRRGN LPKESVQILR 

       190        200        210        220        230        240 
DWLYEHRYNA YPSEQEKALL SQQTHLSTLQ VCNWFINARR RLLPDMLRKD GKDPNQFTIS 

       250        260        270        280        290        300 
RRGAKISETS SVESVMGIKN FMPALEETPF HSCTAGPNPT LGRPLSPKPS SPGSVLARPS 

       310        320        330        340        350        360 
VICHTTVTAL KDVPFSLCQS VGVGQNTDIQ QIAAKNFTDT SLMYPEDTCK SGPSTNTQSG 

       370        380        390        400 
LFNTPPPTPP DLNQDFSGFQ LLVDVALKRA AEMELQAKLT A 

« Hide

Isoform 2 [UniParc].

Checksum: 948D1F689996E84E
Show »

FASTA27229,737
Isoform 3 [UniParc].

Checksum: 39EA173EECBFD391
Show »

FASTA28631,064
Isoform 4 [UniParc].

Checksum: A3426BEBB9753C87
Show »

FASTA25227,715

References

« Hide 'large scale' references
[1]"A novel homeobox protein which recognizes a TGT core and functionally interferes with a retinoid-responsive motif."
Bertolino E., Reimund B., Wildt-Perinic D., Clerc R.G.
J. Biol. Chem. 270:31178-31188(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
Tissue: Liver.
[2]"Three-amino acid extension loop homeodomain proteins Meis2 and TGIF differentially regulate transcription."
Yang Y., Hwang C.K., D'Souza U.M., Lee S.-H., Junn E., Mouradian M.M.
J. Biol. Chem. 275:20734-20741(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANT SER-292.
Tissue: Brain.
[3]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT SER-292.
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
[5]"DNA sequence and analysis of human chromosome 18."
Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J. expand/collapse author list , Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L., Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A., Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C., Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K., Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R., Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.
Nature 437:551-555(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-137 (ISOFORM 4).
Tissue: Brain, Placenta and Rhabdomyosarcoma.
[8]"Solution NMR structure of homeobox domain (171-248) of human homeobox protein TGIF1, northeast structural genomics consortium target hr4411b."
Northeast structural genomics consortium (NESG)
Submitted (OCT-2011) to the PDB data bank
Cited for: STRUCTURE BY NMR OF 171-248.
[9]"Mutations in TGIF cause holoprosencephaly and link NODAL signalling to human neural axis determination."
Gripp K.W., Wotton D., Edwards M.C., Roessler E., Ades L., Meinecke P., Richieri-Costa A., Zackai E.H., Massague J., Muenke M., Elledge S.J.
Nat. Genet. 25:205-208(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HPE4 CYS-157; ARG-192; ALA-280 AND PHE-291.
[10]"Molecular screening of SHH, ZIC2, SIX3, and TGIF genes in patients with features of holoprosencephaly spectrum: mutation review and genotype-phenotype correlations."
Dubourg C., Lazaro L., Pasquier L., Bendavid C., Blayau M., Le Duff F., Durou M.-R., Odent S., David V.
Hum. Mutat. 24:43-51(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HPE4 LEU-236.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X89750 mRNA. Translation: CAA61897.1.
AF179900 mRNA. Translation: AAF81643.1.
CR450333 mRNA. Translation: CAG29329.1.
AK291112 mRNA. Translation: BAF83801.1.
AP001025 Genomic DNA. No translation available.
CH471113 Genomic DNA. Translation: EAX01672.1.
BC000814 mRNA. Translation: AAH00814.1.
BC031268 mRNA. Translation: AAH31268.1.
BE296707 mRNA. No translation available.
RefSeqNP_001265611.1. NM_001278682.1.
NP_001265613.1. NM_001278684.1.
NP_001265615.1. NM_001278686.1.
NP_003235.1. NM_003244.3.
NP_733796.2. NM_170695.3.
NP_775299.1. NM_173207.2.
NP_775300.1. NM_173208.2.
NP_775301.1. NM_173209.2.
NP_775302.1. NM_173210.2.
NP_775303.1. NM_173211.1.
NP_777480.1. NM_174886.2.
XP_005258192.1. XM_005258135.1.
UniGeneHs.373550.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2LK2NMR-A171-248[»]
ProteinModelPortalQ15583.
SMRQ15583. Positions 171-248.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112908. 21 interactions.
IntActQ15583. 8 interactions.
MINTMINT-145985.
STRING9606.ENSP00000327959.

PTM databases

PhosphoSiteQ15583.

Polymorphism databases

DMDM215274200.

Proteomic databases

PaxDbQ15583.
PRIDEQ15583.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000330513; ENSP00000327959; ENSG00000177426. [Q15583-1]
ENST00000343820; ENSP00000339631; ENSG00000177426. [Q15583-2]
ENST00000345133; ENSP00000343969; ENSG00000177426. [Q15583-4]
ENST00000400167; ENSP00000383031; ENSG00000177426. [Q15583-4]
ENST00000401449; ENSP00000385206; ENSG00000177426. [Q15583-4]
ENST00000405385; ENSP00000384970; ENSG00000177426. [Q15583-4]
ENST00000407501; ENSP00000384133; ENSG00000177426. [Q15583-2]
ENST00000472042; ENSP00000449501; ENSG00000177426. [Q15583-4]
ENST00000548489; ENSP00000447747; ENSG00000177426. [Q15583-3]
ENST00000551541; ENSP00000450025; ENSG00000177426. [Q15583-4]
GeneID7050.
KEGGhsa:7050.
UCSCuc002klu.3. human. [Q15583-1]
uc002klv.3. human. [Q15583-3]
uc002klw.3. human. [Q15583-2]

Organism-specific databases

CTD7050.
GeneCardsGC18P003412.
H-InvDBHIX0174209.
HGNCHGNC:11776. TGIF1.
HPACAB004596.
MIM142946. phenotype.
602630. gene.
neXtProtNX_Q15583.
Orphanet93925. Alobar holoprosencephaly.
93924. Lobar holoprosencephaly.
280200. Microform holoprosencephaly.
93926. Midline interhemispheric variant of holoprosencephaly.
220386. Semilobar holoprosencephaly.
280195. Septopreoptic holoprosencephaly.
PharmGKBPA36489.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG308174.
HOGENOMHOG000232039.
HOVERGENHBG001143.
InParanoidQ15583.
OMAIAANNFT.
PhylomeDBQ15583.
TreeFamTF318093.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_71. Gene Expression.
SignaLinkQ15583.

Gene expression databases

ArrayExpressQ15583.
BgeeQ15583.
CleanExHS_TGIF1.
GenevestigatorQ15583.

Family and domain databases

Gene3D1.10.10.60. 1 hit.
InterProIPR001356. Homeobox_dom.
IPR008422. Homeobox_KN_domain.
IPR009057. Homeodomain-like.
[Graphical view]
PfamPF05920. Homeobox_KN. 1 hit.
[Graphical view]
SMARTSM00389. HOX. 1 hit.
[Graphical view]
SUPFAMSSF46689. SSF46689. 1 hit.
PROSITEPS50071. HOMEOBOX_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ15583.
GeneWikiHomeobox_protein_TGIF1.
GenomeRNAi7050.
NextBio27551.
PROQ15583.
SOURCESearch...

Entry information

Entry nameTGIF1_HUMAN
AccessionPrimary (citable) accession number: Q15583
Secondary accession number(s): A6NE42 expand/collapse secondary AC list , A6NLU7, F8VZB6, Q6ICR0, Q8N5X9, Q9NRS0
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 25, 2008
Last modified: April 16, 2014
This is version 153 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 18

Human chromosome 18: entries, gene names and cross-references to MIM