Homeobox protein TGIF1

<p>Provides any useful information about the protein, mostly biological knowledge.</p><p><a href='../manual/function_section' target='_top'>More...</a></p>Functionⁱ

Regions

Feature key	Position(s)	Length	Description	Graphical view	Feature identifier	Actions
<p>Specifies the position and type of each <span class="caps">DNA</span>-binding domain present within the protein.</p><p><a href='../manual/dna_bind' target='_top'>More...</a></p>DNA bindingi	164 – 226	63	Homeobox; TALE-typePROSITE-ProRule annotation <p>Manual validated information which has been generated by the UniProtKB automatic annotation system.</p> <p><a href="/manual/evidences#ECO:0000255">More…</a></p> Manual assertion according to rulesi PROSITE-ProRule:PRU00108			Add BLAST

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:</p><p><a href='../manual/gene_ontology' target='_top'>More...</a></p>GO - Molecular functionⁱ

• RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: NTNU_SB

  <p>Inferred from Direct Assay</p> <p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#ida">GO evidence code guide</a></p> Inferred from direct assayⁱ

  • 10764806

• transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding Source: NTNU_SB

  <p>Inferred from Direct Assay</p> <p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#ida">GO evidence code guide</a></p> Inferred from direct assayⁱ

  • 10764806

• transcription corepressor activity Source: ProtInc

  <p>Traceable Author Statement</p> <p>Used for information from review articles where the original experiments are traceable through that article and also for information from text books or dictionaries.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#tas">GO evidence code guide</a></p> Traceable author statementⁱ

  • 10764806

• transcription factor activity, sequence-specific DNA binding Source: ProtInc

  <p>Traceable Author Statement</p> <p>Used for information from review articles where the original experiments are traceable through that article and also for information from text books or dictionaries.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#tas">GO evidence code guide</a></p> Traceable author statementⁱ

  • 8537382

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:</p><p><a href='../manual/gene_ontology' target='_top'>More...</a></p>GO - Biological processⁱ

• cellular response to growth factor stimulus Source: Ensembl
• multicellular organism development Source: ProtInc

  <p>Traceable Author Statement</p> <p>Used for information from review articles where the original experiments are traceable through that article and also for information from text books or dictionaries.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#tas">GO evidence code guide</a></p> Traceable author statementⁱ

  • 8537382

• negative regulation of transcription from RNA polymerase II promoter Source: NTNU_SB

  <p>Inferred from Direct Assay</p> <p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#ida">GO evidence code guide</a></p> Inferred from direct assayⁱ

  • 10764806

• response to drug Source: Ensembl
• transcription, DNA-templated Source: UniProtKB-KW

<p>UniProtKB Keywords constitute a <a target="_top" href="/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywords - Molecular functionⁱ

<p>UniProtKB Keywords constitute a <a target="_top" href="/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywords - Biological processⁱ

<p>UniProtKB Keywords constitute a <a target="_top" href="/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywords - Ligandⁱ

Enzyme and pathway databases

<p>Provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.</p><p><a href='../manual/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyⁱ

Organism-specific databases

<p>Provides information on the location and the topology of the mature protein in the cell.</p><p><a href='../manual/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationⁱ

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:</p><p><a href='../manual/gene_ontology' target='_top'>More...</a></p>GO - Cellular componentⁱ

• nucleoplasm Source: Reactome

<p>UniProtKB Keywords constitute a <a target="_top" href="/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywords - Cellular componentⁱ

<p>Provides information on the disease(s) and phenotype(s) associated with a protein.</p><p><a href='../manual/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechⁱ

<p>Provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim"><span class="caps">OMIM</span></a> database are represented with a <a href="/diseases">controlled vocabulary</a> in the following way:</p><p><a href='../manual/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseaseⁱ

Holoprosencephaly 4 (HPE4)2 Publications

<p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment inⁱ

• Ref.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.
• Ref.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.

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA 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.

See also OMIM:142946

Feature key	Position(s)	Length	Description	Graphical view	Feature identifier	Actions
<p>Describes natural variant(s) of the protein sequence.</p><p><a href='../manual/variant' target='_top'>More...</a></p>Natural varianti	157 – 157	1	S → C in HPE4. 1 Publication <p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment ini Ref.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. Corresponds to variant rs121909066 [ dbSNP | Ensembl ].		VAR_009961
<p>Describes natural variant(s) of the protein sequence.</p><p><a href='../manual/variant' target='_top'>More...</a></p>Natural varianti	192 – 192	1	P → R in HPE4. 1 Publication <p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment ini Ref.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. Corresponds to variant rs121909067 [ dbSNP | Ensembl ].		VAR_009962
<p>Describes natural variant(s) of the protein sequence.</p><p><a href='../manual/variant' target='_top'>More...</a></p>Natural varianti	236 – 236	1	Q → L in HPE4. 1 Publication <p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment ini Ref.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. Corresponds to variant rs28939693 [ dbSNP | Ensembl ].		VAR_023803
<p>Describes natural variant(s) of the protein sequence.</p><p><a href='../manual/variant' target='_top'>More...</a></p>Natural varianti	280 – 280	1	T → A in HPE4. 1 Publication <p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment ini Ref.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. Corresponds to variant rs121909068 [ dbSNP | Ensembl ].		VAR_009963
<p>Describes natural variant(s) of the protein sequence.</p><p><a href='../manual/variant' target='_top'>More...</a></p>Natural varianti	291 – 291	1	S → F in HPE4. 1 Publication <p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment ini Ref.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. Corresponds to variant rs121909069 [ dbSNP | Ensembl ].		VAR_009964

<p>UniProtKB Keywords constitute a <a target="_top" href="/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywords - Diseaseⁱ

Organism-specific databases

Polymorphism and mutation databases

<p>Describes post-translational modifications (PTMs) and/or processing events.</p><p><a href='../manual/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	Length	Description	Graphical view	Feature identifier	Actions
<p>Describes the extent of a polypeptide chain in the mature protein following processing.</p><p><a href='../manual/chain' target='_top'>More...</a></p>Chaini	1 – 401	401	Homeobox protein TGIF1		PRO_0000049318	Add BLAST

Proteomic databases

PTM databases

<p>Provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.</p><p><a href='../manual/expression_section' target='_top'>More...</a></p>Expressionⁱ

Gene expression databases

<p>Provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.</p><p><a href='../manual/interaction_section' target='_top'>More...</a></p>Interactionⁱ

<p>Provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="/help/function_section">‘Function’</a> section).</p><p><a href='../manual/subunit_structure' target='_top'>More...</a></p>Subunit structureⁱ

<p>Provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.</p><p><a href='../manual/binary_interactions' target='_top'>More...</a></p>Binary interactionsⁱ

Protein-protein interaction databases

<p>Provides information on the tertiary and secondary structure of a protein.</p><p><a href='../manual/structure_section' target='_top'>More...</a></p>Structureⁱ

Secondary structure

Feature key	Position(s)	Length	Description	Graphical view	Feature identifier	Actions
<p>Is used to indicate the positions of experimentally determined helical regions within the protein sequence.</p><p><a href='../manual/helix' target='_top'>More...</a></p>Helixi	173 – 185	13	Combined sources <p>Manually validated information inferred from a combination of experimental and computational evidence.</p> <p><a href="/manual/evidences#ECO:0000244">More…</a></p> Manual assertion inferred from combination of experimental and computational evidencei PDB:2LK2
<p>Is used to indicate the positions of experimentally determined helical regions within the protein sequence.</p><p><a href='../manual/helix' target='_top'>More...</a></p>Helixi	188 – 190	3	Combined sources <p>Manually validated information inferred from a combination of experimental and computational evidence.</p> <p><a href="/manual/evidences#ECO:0000244">More…</a></p> Manual assertion inferred from combination of experimental and computational evidencei PDB:2LK2
<p>Is used to indicate the positions of experimentally determined helical regions within the protein sequence.</p><p><a href='../manual/helix' target='_top'>More...</a></p>Helixi	194 – 203	10	Combined sources <p>Manually validated information inferred from a combination of experimental and computational evidence.</p> <p><a href="/manual/evidences#ECO:0000244">More…</a></p> Manual assertion inferred from combination of experimental and computational evidencei PDB:2LK2
<p>Is used to indicate the positions of experimentally determined beta strands within the protein sequence.</p><p><a href='../manual/strand' target='_top'>More...</a></p>Beta strandi	204 – 206	3	Combined sources <p>Manually validated information inferred from a combination of experimental and computational evidence.</p> <p><a href="/manual/evidences#ECO:0000244">More…</a></p> Manual assertion inferred from combination of experimental and computational evidencei PDB:2LK2
<p>Is used to indicate the positions of experimentally determined helical regions within the protein sequence.</p><p><a href='../manual/helix' target='_top'>More...</a></p>Helixi	208 – 230	23	Combined sources <p>Manually validated information inferred from a combination of experimental and computational evidence.</p> <p><a href="/manual/evidences#ECO:0000244">More…</a></p> Manual assertion inferred from combination of experimental and computational evidencei PDB:2LK2

3D structure databases

Miscellaneous databases

<p>Provides information on sequence similarities with other proteins and the domain(s) present in a protein.</p><p><a href='../manual/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsⁱ

Motif

Feature key	Position(s)	Length	Description	Graphical view	Feature identifier	Actions
<p>Describes a short (usually not more than 20 amino acids) conserved sequence motif of biological significance.</p><p><a href='../manual/motif' target='_top'>More...</a></p>Motifi	153 – 157	5	CTBP-binding motif

Compositional bias

Feature key	Position(s)	Length	Description	Graphical view	Feature identifier	Actions
<p>Describes the position of regions of compositional bias within the protein and the particular amino acids that are over-represented within those regions.</p><p><a href='../manual/compbias' target='_top'>More...</a></p>Compositional biasi	165 – 168	4	Poly-Arg

<p>Provides information about the sequence similarity with other proteins.</p><p><a href='../manual/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesⁱ

<p>UniProtKB Keywords constitute a <a target="_top" href="/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywords - Domainⁱ

Phylogenomic databases

Family and domain databases

<p>Displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including length and molecular weight.</p><p><a href='../manual/sequences_section' target='_top'>More...</a></p>Sequences (4)ⁱ

<p>Indicates if the <a href="/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.</p><p><a href='../manual/sequence_status' target='_top'>More...</a></p>Sequence statusⁱ: Complete.

This entry describes 4<p>Lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.</p><p><a href='../manual/alternative_products' target='_top'>More...</a></p> isoformsⁱ produced by alternative splicing. AlignAdd to basketAdded to basket

        10         20         30         40         50
MVLAQSRVSA GVGSPHCSGS GGGGSDSFPW PASHPGNPQC SFSTAFLASP 
        60         70         80         90        100
RLSRGTLAYL PPAPWSSLAT PSALLGSSCA PPPPPARCPQ PRALSPELGT 
       110        120        130        140        150
KAGPRRPHRW ELPRSPSQGA QGPAPRRRLL ETMKGIVAAS GSETEDEDSM 
       160        170        180        190        200
DIPLDLSSSA GSGKRRRRGN LPKESVQILR DWLYEHRYNA YPSEQEKALL 
       210        220        230        240        250
SQQTHLSTLQ VCNWFINARR RLLPDMLRKD GKDPNQFTIS RRGAKISETS 
       260        270        280        290        300
SVESVMGIKN FMPALEETPF HSCTAGPNPT LGRPLSPKPS SPGSVLARPS 
       310        320        330        340        350
VICHTTVTAL KDVPFSLCQS VGVGQNTDIQ QIAAKNFTDT SLMYPEDTCK 
       360        370        380        390        400
SGPSTNTQSG LFNTPPPTPP DLNQDFSGFQ LLVDVALKRA AEMELQAKLT 

A                                             

        10         20         30         40         50
MKGKKGIVAA SGSETEDEDS MDIPLDLSSS AGSGKRRRRG NLPKESVQIL 
        60         70         80         90        100
RDWLYEHRYN AYPSEQEKAL LSQQTHLSTL QVCNWFINAR RRLLPDMLRK 
       110        120        130        140        150
DGKDPNQFTI SRRGAKISET SSVESVMGIK NFMPALEETP FHSCTAGPNP 
       160        170        180        190        200
TLGRPLSPKP SSPGSVLARP SVICHTTVTA LKDVPFSLCQ SVGVGQNTDI 
       210        220        230        240        250
QQIAAKNFTD TSLMYPEDTC KSGPSTNTQS GLFNTPPPTP PDLNQDFSGF 
       260        270 
QLLVDVALKR AAEMELQAKL TA                       

        10         20         30         40         50
MTCSGKSCAL ARSSLTSSQG IVAASGSETE DEDSMDIPLD LSSSAGSGKR 
        60         70         80         90        100
RRRGNLPKES VQILRDWLYE HRYNAYPSEQ EKALLSQQTH LSTLQVCNWF 
       110        120        130        140        150
INARRRLLPD MLRKDGKDPN QFTISRRGAK ISETSSVESV MGIKNFMPAL 
       160        170        180        190        200
EETPFHSCTA GPNPTLGRPL SPKPSSPGSV LARPSVICHT TVTALKDVPF 
       210        220        230        240        250
SLCQSVGVGQ NTDIQQIAAK NFTDTSLMYP EDTCKSGPST NTQSGLFNTP 
       260        270        280 
PPTPPDLNQD FSGFQLLVDV ALKRAAEMEL QAKLTA            

        10         20         30         40         50
MDIPLDLSSS AGSGKRRRRG NLPKESVQIL RDWLYEHRYN AYPSEQEKAL 
        60         70         80         90        100
LSQQTHLSTL QVCNWFINAR RRLLPDMLRK DGKDPNQFTI SRRGAKISET 
       110        120        130        140        150
SSVESVMGIK NFMPALEETP FHSCTAGPNP TLGRPLSPKP SSPGSVLARP 
       160        170        180        190        200
SVICHTTVTA LKDVPFSLCQ SVGVGQNTDI QQIAAKNFTD TSLMYPEDTC 
       210        220        230        240        250
KSGPSTNTQS GLFNTPPPTP PDLNQDFSGF QLLVDVALKR AAEMELQAKL 

TA                                             

Experimental Info

Feature key	Position(s)	Length	Description	Graphical view	Feature identifier	Actions
<p>Reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.</p><p><a href='../manual/conflict' target='_top'>More...</a></p>Sequence conflicti	96 – 96	1	P → Q in AAH31268 (PubMed:15489334).Curated

Natural variant

Feature key	Position(s)	Length	Description	Graphical view	Feature identifier	Actions
<p>Describes natural variant(s) of the protein sequence.</p><p><a href='../manual/variant' target='_top'>More...</a></p>Natural varianti	157 – 157	1	S → C in HPE4. 1 Publication <p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment ini Ref.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. Corresponds to variant rs121909066 [ dbSNP | Ensembl ].		VAR_009961
<p>Describes natural variant(s) of the protein sequence.</p><p><a href='../manual/variant' target='_top'>More...</a></p>Natural varianti	192 – 192	1	P → R in HPE4. 1 Publication <p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment ini Ref.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. Corresponds to variant rs121909067 [ dbSNP | Ensembl ].		VAR_009962
<p>Describes natural variant(s) of the protein sequence.</p><p><a href='../manual/variant' target='_top'>More...</a></p>Natural varianti	236 – 236	1	Q → L in HPE4. 1 Publication <p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment ini Ref.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. Corresponds to variant rs28939693 [ dbSNP | Ensembl ].		VAR_023803
<p>Describes natural variant(s) of the protein sequence.</p><p><a href='../manual/variant' target='_top'>More...</a></p>Natural varianti	280 – 280	1	T → A in HPE4. 1 Publication <p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment ini Ref.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. Corresponds to variant rs121909068 [ dbSNP | Ensembl ].		VAR_009963
<p>Describes natural variant(s) of the protein sequence.</p><p><a href='../manual/variant' target='_top'>More...</a></p>Natural varianti	289 – 289	1	P → S. Corresponds to variant rs11571512 [ dbSNP | Ensembl ].		VAR_047363
<p>Describes natural variant(s) of the protein sequence.</p><p><a href='../manual/variant' target='_top'>More...</a></p>Natural varianti	291 – 291	1	S → F in HPE4. 1 Publication <p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment ini Ref.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. Corresponds to variant rs121909069 [ dbSNP | Ensembl ].		VAR_009964
<p>Describes natural variant(s) of the protein sequence.</p><p><a href='../manual/variant' target='_top'>More...</a></p>Natural varianti	292 – 292	1	P → L. Corresponds to variant rs2229333 [ dbSNP | Ensembl ].		VAR_020151
<p>Describes natural variant(s) of the protein sequence.</p><p><a href='../manual/variant' target='_top'>More...</a></p>Natural varianti	292 – 292	1	P → S.2 Publications <p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment ini Ref.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. Ref.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. Corresponds to variant rs4468717 [ dbSNP | Ensembl ].		VAR_061268

Alternative sequence

Feature key	Position(s)	Length	Description	Graphical view	Feature identifier	Actions
<p>Describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting. The information stored in this subsection is used to automatically construct alternative protein sequence(s) for display.</p><p><a href='../manual/var_seq' target='_top'>More...</a></p>Alternative sequencei	1 – 149	149	Missing in isoform 4. 1 Publication <p>Manually curated information that is based on statements in scientific articles for which there is no experimental support.</p> <p><a href="/manual/evidences#ECO:0000303">More…</a></p> Manual assertion based on opinion ini Ref.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).		VSP_046848	Add BLAST
<p>Describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting. The information stored in this subsection is used to automatically construct alternative protein sequence(s) for display.</p><p><a href='../manual/var_seq' target='_top'>More...</a></p>Alternative sequencei	1 – 129	129	Missing in isoform 2. 4 Publications <p>Manually curated information that is based on statements in scientific articles for which there is no experimental support.</p> <p><a href="/manual/evidences#ECO:0000303">More…</a></p> Manual assertion based on opinion ini Ref.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). Ref.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. Ref.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. Ref.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).		VSP_013020	Add BLAST
<p>Describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting. The information stored in this subsection is used to automatically construct alternative protein sequence(s) for display.</p><p><a href='../manual/var_seq' target='_top'>More...</a></p>Alternative sequencei	1 – 115	115	Missing in isoform 3. 1 Publication <p>Manually curated information that is based on statements in scientific articles for which there is no experimental support.</p> <p><a href="/manual/evidences#ECO:0000303">More…</a></p> Manual assertion based on opinion ini Ref.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. , 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).		VSP_043108	Add BLAST
<p>Describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting. The information stored in this subsection is used to automatically construct alternative protein sequence(s) for display.</p><p><a href='../manual/var_seq' target='_top'>More...</a></p>Alternative sequencei	116 – 134	19	PSQGA…LETMK → MTCSGKSCALARSSLTSSQ in isoform 3. 1 Publication <p>Manually curated information that is based on statements in scientific articles for which there is no experimental support.</p> <p><a href="/manual/evidences#ECO:0000303">More…</a></p> Manual assertion based on opinion ini Ref.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. , 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).		VSP_043109	Add BLAST
<p>Describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting. The information stored in this subsection is used to automatically construct alternative protein sequence(s) for display.</p><p><a href='../manual/var_seq' target='_top'>More...</a></p>Alternative sequencei	130 – 133	4	LETM → MKGK in isoform 2. 4 Publications <p>Manually curated information that is based on statements in scientific articles for which there is no experimental support.</p> <p><a href="/manual/evidences#ECO:0000303">More…</a></p> Manual assertion based on opinion ini Ref.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). Ref.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. Ref.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. Ref.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).		VSP_013021

Sequence databases

Genome annotation databases

<p>UniProtKB Keywords constitute a <a target="_top" href="/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywords - Coding sequence diversityⁱ

<p>Is used to point to information related to entries and found in data collections other than UniProtKB.</p><p><a href='../manual/cross_references_section' target='_top'>More...</a></p>Cross-referencesⁱ

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Polymorphism and mutation databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Miscellaneous databases

Gene expression databases

Family and domain databases

<p>Provides general information on the entry.</p><p><a href='../manual/entry_information_section' target='_top'>More...</a></p>Entry informationⁱ

<p>Contains any relevant information that doesn’t fit in any other defined sections</p><p><a href='../manual/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousⁱ

<p>UniProtKB Keywords constitute a <a target="_top" href="/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywords - Technical termⁱ

Documents

1. Human chromosome 18
   Human chromosome 18: 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. PDB cross-references
   Index of Protein Data Bank (PDB) cross-references
6. SIMILARITY comments
   Index of protein domains and families

<p>Provides links to the UniProt Reference Clusters (<a href="/help/uniref">UniRef</a>). UniRef consists of clusters for UniProtKB sequences (including isoforms) and selected UniParc sequences, in order to obtain complete coverage of the sequence space at resolutions of 100%, 90% and 50% identity.</p><p><a href='../manual/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsⁱ