Reviewed, UniProtKB/Swiss-Prot Q15583 (TGIF1_HUMAN)

Names and origin

Protein names

Recommended name:
    Homeobox protein TGIF1
Alternative name(s):
    5'-TG-3'-interacting factor 1

Gene names

Name:	TGIF1
Synonyms:	TGIF

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	Nucleus.
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.2 Traceable 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.2 Traceable author statement. Source: ProtInc transcription factor activity Ref.1 Traceable 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

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 25, 2008. Version 3. Checksum: 4D9C76AFB37A29F0	FASTA	401	43,013
	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
	Isoform 2 [UniParc]. Checksum: 948D1F689996E84E		272	29,737
	10 20 30 40 50 60 MKGKKGIVAA SGSETEDEDS MDIPLDLSSS AGSGKRRRRG NLPKESVQIL RDWLYEHRYN 70 80 90 100 110 120 AYPSEQEKAL LSQQTHLSTL QVCNWFINAR RRLLPDMLRK DGKDPNQFTI SRRGAKISET 130 140 150 160 170 180 SSVESVMGIK NFMPALEETP FHSCTAGPNP TLGRPLSPKP SSPGSVLARP SVICHTTVTA 190 200 210 220 230 240 LKDVPFSLCQ SVGVGQNTDI QQIAAKNFTD TSLMYPEDTC KSGPSTNTQS GLFNTPPPTP 250 260 270 PDLNQDFSGF QLLVDVALKR AAEMELQAKL TA

References

	« Hide 'large scale' referencesShow '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. , 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: 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.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBLGenBankDDBJ	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

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 25, 2008
Last modified:	November 25, 2008
This is version 96 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)