Reviewed,
UniProtKB/Swiss-Prot Q15583 (TGIF1_HUMAN)
Last modified
November 25, 2008.
Version 96.
History...
Clusters with 100%,
90%,
50% identity |
Documents (6) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Homeobox protein TGIF1 Alternative name(s): 5'-TG-3'-interacting factor 1 | ||||
| Gene names |
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| Organism | Homo sapiens (Human) | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 401 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence 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 | |
| Involvement in disease | Defects in TGIF1 are the cause of holoprosencephaly type 4 (HPE4) [MIM:142946]. Holoprosencephaly (HPE) [MIM:236100] is the most common 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. |
| Sequence similarities | Belongs to the TALE/TGIF homeobox family. Contains 1 homeobox DNA-binding domain. |
Ontologies
Keywords | |
|---|---|
| Biological process | Transcription Transcription regulation |
| Cellular component | Nucleus |
| Coding sequence diversity | Alternative splicing Polymorphism |
| Disease | Disease mutation Holoprosencephaly |
| Domain | Homeobox |
| Ligand | DNA-binding |
| Molecular function | Repressor |
Gene Ontology (GO) | |
| Biological process | multicellular organismal development Ref.1 Traceable author statement. Source: ProtInc negative regulation of transcription from RNA polymerase II promoter Ref.2Traceable author statement. Source: ProtInc |
| Cellular component | nucleus Inferred from electronic annotation. Source: InterPro |
| Molecular function | sequence-specific DNA binding Inferred from electronic annotation. Source: InterPro transcription corepressor activity Ref.2Traceable author statement. Source: ProtInc transcription factor activity Ref.1Traceable author statement. Source: ProtInc |
| Complete GO annotation... | |
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| MKKS | Q9HB66 | 1 | EBI-714215,EBI-1054754 | |
| SDAD1 | Q9NVU7 | 1 | EBI-714215,EBI-1043768 | |
| STK16 | O75716 | 1 | EBI-714215,EBI-1046308 |
Alternative products
| This entry describes 2 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 |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 401 | 401 | Homeobox protein TGIF1 | PRO_0000049318 | |||||
Regions | |||||||||
| DNA binding | 164 – 226 | 63 | Homeobox; TALE-type | ||||||
| Motif | 153 – 157 | 5 | CTBP-binding motif | ||||||
| Compositional bias | 165 – 168 | 4 | Poly-Arg | ||||||
Natural variations | |||||||||
| Alternative sequence | 1 – 129 | 129 | Missing in isoform 2. | VSP_013020 | |||||
| Alternative sequence | 130 – 133 | 4 | LETM → MKGK in isoform 2. | VSP_013021 | |||||
| Natural variant | 157 | 1 | S → C in HPE4. | VAR_009961 | |||||
| Natural variant | 192 | 1 | P → R in HPE4. | VAR_009962 | |||||
| Natural variant | 236 | 1 | Q → L in HPE4. | VAR_023803 | |||||
| Natural variant | 280 | 1 | T → A in HPE4. | VAR_009963 | |||||
| Natural variant | 289 | 1 | P → S: dbSNP rs11571512. | VAR_047363 | |||||
| Natural variant | 291 | 1 | S → F in HPE4. | VAR_009964 | |||||
| Natural variant | 292 | 1 | P → L: dbSNP rs2229333. | VAR_020151 | |||||
Experimental info | |||||||||
| Sequence conflict | 96 | 1 | P → Q in AAH31268. Ref.5 | ||||||
| Sequence conflict | 292 | 1 | P → S in AAF81643. Ref.2 | ||||||
| Sequence conflict | 292 | 1 | P → S in CAG29329. Ref.3 | ||||||
Sequences
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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: 8537382] [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: 10764806] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). 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). |
| [4] | "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. Lander E.S.Nature 437:551-555(2005) [PubMed: 16177791] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [5] | "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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Brain and Placenta. |
| [6] | "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: 10835638] [Abstract] Cited for: VARIANTS HPE4 CYS-157; ARG-192; ALA-280 AND PHE-291. |
| [7] | "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: 15221788] [Abstract] Cited for: VARIANT HPE4 LEU-236. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| X89750 mRNA. Translation: CAA61897.1. AF179900 mRNA. Translation: AAF81643.1. CR450333 mRNA. Translation: CAG29329.1. AP001025 Genomic DNA. No translation available. BC000814 mRNA. Translation: AAH00814.1. BC031268 mRNA. Translation: AAH31268.1. | |
| RefSeq | NP_003235.1. NP_733796.2. NP_775299.1. NP_775300.1. NP_775301.1. NP_775302.1. NP_775303.1. NP_777480.1. |
| UniGene | Hs.373550 |
3D structure databases | |
| HSSP | HSSP built from PDB template 1LFU based on UniProtKB P41778. |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | Q15583. |
Genome annotation databases | |
| Ensembl | ENSG00000177426. Homo sapiens. [Contig view] |
| GeneID | 7050. |
| KEGG | hsa:7050. |
Organism-specific databases | |
| H-InvDB | HIX0014308. |
| HGNC | HGNC:11776. TGIF1. |
| HPA | CAB004596. |
| MIM | 142946. phenotype. 602630. gene. |
| Orphanet | 2162. Holoprosencephaly. |
| GenAtlas | Search... |
| GeneCards | Search... |
Phylogenomic databases | |
| HOVERGEN | Q15583. |
Gene expression databases | |
| ArrayExpress | Q15583. |
| CleanEx | HS_TGIF1. |
| GermOnline | ENSG00000177426. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR001356. Homeobox. IPR012287. Homeodomain-rel. [Graphical view] |
| Gene3D | G3DSA:1.10.10.60. Homeodomain-rel. 1 hit. |
| Pfam | PF00046. Homeobox. 1 hit. [Graphical view] |
| ProDom | PD000010. Homeobox. 1 hit. [Graphical view] [Entries sharing at least one domain] |
| SMART | SM00389. HOX. 1 hit. [Graphical view] |
| PROSITE | PS00027. HOMEOBOX_1. False negative. PS50071. HOMEOBOX_2. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| LinkHub | Q15583. |
| NextBio | 27551. |
| SOURCE | Search... |
Entry information
| Entry name | TGIF1_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q15583 Secondary accession number(s): Q6ICR0, Q8N5X9, Q9NRS0 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| Human chromosome 18 Human chromosome 18: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| UniProtKB secondary accession numbers Index of UniProtKB secondary accession numbers |
| SIMILARITY comments Index of protein domains and families |

Clusters with


