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P15884 (ITF2_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·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Transcription factor 4

Short name=TCF-4
Alternative name(s):
Class B basic helix-loop-helix protein 19
Short name=bHLHb19
Immunoglobulin transcription factor 2
Short name=ITF-2
SL3-3 enhancer factor 2
Short name=SEF-2
Gene names
Name:TCF4
Synonyms:BHLHB19, ITF2, SEF2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length667 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Transcription factor that binds to the immunoglobulin enchancer Mu-E5/KE5-motif. Involved in the initiation of neuronal differentiation. Activates transcription by binding to the E box (5'-CANNTG-3'). Binds to the E-box present in the somatostatin receptor 2 initiator element (SSTR2-INR) to activate transcription By similarity. Preferentially binds to either 5'-ACANNTGT-3' or 5'-CCANNTGG-3'.

Subunit structure

Efficient DNA binding requires dimerization with another bHLH protein. Forms homo- or heterooligomers with myogenin. Interacts with HIVEP2. Interacts with NEUROD2 By similarity. Interacts with AGBL1. Ref.14

Subcellular location

Nucleus Ref.13.

Tissue specificity

Expressed in adult heart, brain, placenta, skeletal muscle and to a lesser extent in the lung. In developing embryonic tissues, expression mostly occurs in the brain.

Domain

the 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors. Ref.11

Involvement in disease

Pitt-Hopkins syndrome (PTHS) [MIM:610954]: A syndrome characterized by mental retardation, wide mouth and distinctive facial features, and intermittent hyperventilation followed by apnea. Features include intellectual disability with severe speech impairment, normal growth parameters at birth, postnatal microcephaly, breathing anomalies, severe motor developmental delay, motor incoordination, ocular anomalies, constipation, seizures, typical behavior and subtle brain abnormalities.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.13 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20

Sequence similarities

Contains 1 bHLH (basic helix-loop-helix) domain.

Sequence caution

The sequence AAA60310.1 differs from that shown. Reason: Incomplete and probable erroneous sequence.

The sequence AAA60312.1 differs from that shown. Reason: Incomplete and probable erroneous sequence.

Ontologies

Keywords
   Biological processDifferentiation
Neurogenesis
Transcription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
Epilepsy
Mental retardation
Primary microcephaly
   LigandDNA-binding
   Molecular functionActivator
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA-templated transcription, initiation

Inferred from sequence or structural similarity PubMed 8978694. Source: BHF-UCL

positive regulation of neuron differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of transcription from RNA polymerase II promoter

Inferred from sequence or structural similarity PubMed 8978694. Source: BHF-UCL

positive regulation of transcription, DNA-templated

Inferred from direct assay Ref.10. Source: UniProtKB

protein-DNA complex assembly

Inferred from sequence or structural similarity PubMed 8978694. Source: BHF-UCL

transcription initiation from RNA polymerase II promoter

Inferred from sequence or structural similarity PubMed 8978694. Source: BHF-UCL

   Cellular_componentnucleus

Inferred from direct assay Ref.1. Source: UniProtKB

transcription factor complex

Inferred from sequence or structural similarity PubMed 8978694. Source: BHF-UCL

   Molecular_functionDNA binding

Inferred from direct assay Ref.1. Source: UniProtKB

E-box binding

Inferred from sequence or structural similarity. Source: UniProtKB

RNA polymerase II core promoter proximal region sequence-specific DNA binding

Inferred from sequence or structural similarity PubMed 8978694. Source: BHF-UCL

RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription

Inferred from sequence or structural similarity PubMed 8978694. Source: BHF-UCL

TFIIB-class binding transcription factor activity

Inferred from sequence or structural similarity PubMed 8978694. Source: BHF-UCL

TFIIB-class transcription factor binding

Inferred from sequence or structural similarity PubMed 8978694. Source: BHF-UCL

protein C-terminus binding

Inferred from physical interaction PubMed 10903890. Source: UniProtKB

protein heterodimerization activity

Inferred from sequence or structural similarity. Source: UniProtKB

sequence-specific DNA binding RNA polymerase recruiting transcription factor activity

Inferred from sequence or structural similarity PubMed 8978694. Source: BHF-UCL

sequence-specific DNA binding transcription factor activity

Inferred from direct assay Ref.10. Source: UniProtKB

Complete GO annotation...

Binary interactions

Alternative products

This entry describes 16 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.
Isoform SEF2-1B (identifier: P15884-1)

Also known as: B-;

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 SEF2-1A (identifier: P15884-2)

Also known as: A+;

The sequence of this isoform differs from the canonical sequence as follows:
     1-160: Missing.
     161-183: LHSSAMEVQTKKVRKVPPGLPSS → MYCAYTIPGMGGNSLMYYYNGKA
     545-545: T → TRSRS
Isoform SEF2-1D (identifier: P15884-3)

Also known as: B+;

The sequence of this isoform differs from the canonical sequence as follows:
     545-545: T → TRSRS
Isoform B+delta (identifier: P15884-4)

The sequence of this isoform differs from the canonical sequence as follows:
     124-183: Missing.
     545-545: T → TRSRS
Isoform B-delta (identifier: P15884-5)

The sequence of this isoform differs from the canonical sequence as follows:
     124-183: Missing.
Isoform A- (identifier: P15884-6)

The sequence of this isoform differs from the canonical sequence as follows:
     1-23: MHHQQRMAALGTDKELSDLLDFS → MYCAYTIPGMGGNSLMYYYNGKA
     24-123: Missing.
     124-183: Missing.
Isoform G- (identifier: P15884-7)

The sequence of this isoform differs from the canonical sequence as follows:
     1-32: MHHQQRMAALGTDKELSDLLDFSAMFSPPVSS → MKDIFFQFIIARVRKCYSLSCLHTLPVVPTLR
     33-102: Missing.
     123-123: Missing.
Isoform H- (identifier: P15884-8)

The sequence of this isoform differs from the canonical sequence as follows:
     1-23: MHHQQRMAALGTDKELSDLLDFS → MKFKQCRCSDTGLCCLDHEGKAE
     24-123: Missing.
Isoform D- (identifier: P15884-9)

The sequence of this isoform differs from the canonical sequence as follows:
     1-130: Missing.
Isoform F- (identifier: P15884-10)

The sequence of this isoform differs from the canonical sequence as follows:
     1-49: MHHQQRMAALGTDKELSDLLDFSAMFSPPVSSGKNGPTSLASGHFTGSN → MEEDSRD
Isoform 11 (identifier: P15884-11)

The sequence of this isoform differs from the canonical sequence as follows:
     1-102: MHHQQRMAAL...PPFVNSRIQS → MKDIFFQFIIARVRKCYSLSCLHTLPVVPTLR
     123-123: Missing.
     545-545: T → TRSRS
Isoform E- (identifier: P15884-12)

The sequence of this isoform differs from the canonical sequence as follows:
     1-24: MHHQQRMAALGTDKELSDLLDFSA → MQRAKTELFRLQIVTDDLRKNE
     357-357: Missing.
Isoform 13 (identifier: P15884-13)

The sequence of this isoform differs from the canonical sequence as follows:
     1-24: Missing.
     545-545: T → TRSRS
Isoform C- (identifier: P15884-14)

The sequence of this isoform differs from the canonical sequence as follows:
     1-24: Missing.
Isoform C-delta (identifier: P15884-15)

The sequence of this isoform differs from the canonical sequence as follows:
     1-24: Missing.
     124-183: Missing.
Isoform I- (identifier: P15884-16)

The sequence of this isoform differs from the canonical sequence as follows:
     1-216: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 667667Transcription factor 4
PRO_0000127256

Regions

Domain564 – 61754bHLH
Region1 – 8383Essential for MYOD1 inhibition By similarity
Region379 – 40022Leucine-zipper
Region619 – 64224Class A specific domain
Motif18 – 2699aaTAD
Compositional bias228 – 2314Poly-Ser

Amino acid modifications

Modified residue5151Phosphoserine Ref.12

Natural variations

Alternative sequence1 – 216216Missing in isoform I-.
VSP_054279
Alternative sequence1 – 160160Missing in isoform SEF2-1A.
VSP_030819
Alternative sequence1 – 130130Missing in isoform D-.
VSP_045149
Alternative sequence1 – 102102MHHQQ…SRIQS → MKDIFFQFIIARVRKCYSLS CLHTLPVVPTLR in isoform 11.
VSP_045150
Alternative sequence1 – 4949MHHQQ…FTGSN → MEEDSRD in isoform F-.
VSP_045151
Alternative sequence1 – 3232MHHQQ…PPVSS → MKDIFFQFIIARVRKCYSLS CLHTLPVVPTLR in isoform G-.
VSP_044334
Alternative sequence1 – 2424Missing in isoform 13, isoform C- and isoform C-delta.
VSP_047081
Alternative sequence1 – 2424MHHQQ…LDFSA → MQRAKTELFRLQIVTDDLRK NE in isoform E-.
VSP_047082
Alternative sequence1 – 2323MHHQQ…LLDFS → MYCAYTIPGMGGNSLMYYYN GKA in isoform A-.
VSP_044336
Alternative sequence1 – 2323MHHQQ…LLDFS → MKFKQCRCSDTGLCCLDHEG KAE in isoform H-.
VSP_044335
Alternative sequence24 – 123100Missing in isoform A- and isoform H-.
VSP_044337
Alternative sequence33 – 10270Missing in isoform G-.
VSP_044338
Alternative sequence1231Missing in isoform G- and isoform 11.
VSP_044339
Alternative sequence124 – 18360Missing in isoform A-, isoform B-delta, isoform B+delta and isoform C-delta.
VSP_044340
Alternative sequence161 – 18323LHSSA…GLPSS → MYCAYTIPGMGGNSLMYYYN GKA in isoform SEF2-1A.
VSP_002111
Alternative sequence3571Missing in isoform E-.
VSP_047083
Alternative sequence5451T → TRSRS in isoform B+delta, isoform SEF2-1A, isoform SEF2-1D, isoform 11 and isoform 13.
VSP_002112
Natural variant3581G → V in PTHS; also expressed in the nucleus with a pattern indistinguishable from the wild-type; does not have a major impact on homodimer formation; affects transcriptional activity in a context-dependent manner. Ref.13 Ref.17
VAR_066839
Natural variant4501M → I.
Corresponds to variant rs11660217 [ dbSNP | Ensembl ].
VAR_049545
Natural variant5351D → G in PTHS; loss of function; also expressed in the nucleus with a pattern indistinguishable from the wild-type; does not have a major impact on homodimer formation; affects transcriptional activity in a context-dependent manner. Ref.13 Ref.18
VAR_058632
Natural variant5651R → W in PTHS. Ref.20
VAR_066970
Natural variant5721R → G in PTHS; loss of function. Ref.18 Ref.20
VAR_058633
Natural variant5721R → Q in PTHS. Ref.20
VAR_066971
Natural variant5741R → H in PTHS. Ref.20
VAR_066972
Natural variant5741R → P in PTHS; mislocalized to small spherical punctae that are dispersed throughout the nucleus; can attenuate homo- and heterodimer formation; affects transcriptional activity in a context-dependent manner. Ref.13 Ref.17 Ref.20
VAR_066840
Natural variant5761R → Q in PTHS; loss of function. Ref.15 Ref.18 Ref.20
VAR_034704
Natural variant5761R → W in PTHS; mislocalized to small spherical punctae that are dispersed throughout the nucleus; can attenuate homo- and heterodimer formation; affects transcriptional activity in a context-dependent manner. Ref.13 Ref.15 Ref.16 Ref.20
VAR_034705
Natural variant5781R → H in PTHS. Ref.17
VAR_066841
Natural variant5781R → P in PTHS. Ref.19 Ref.20
VAR_066973
Natural variant5831A → P in PTHS. Ref.20
VAR_066974
Natural variant6101A → V in PTHS; loss of function; mislocalized to small spherical punctae that are dispersed throughout the nucleus; can attenuate homo- and heterodimer formation; affects transcriptional activity in a context-dependent manner. Ref.13 Ref.18 Ref.20
VAR_058634

Experimental info

Sequence conflict46 – 494TGSN → EFGG in CAA36298. Ref.9
Sequence conflict2051Missing in AV761952. Ref.7
Sequence conflict3341P → S in CAA36298. Ref.9

Secondary structure

... 667
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform SEF2-1B (B-) [UniParc].

Last modified December 15, 1998. Version 3.
Checksum: 53459FC7989D9487

FASTA66771,308
        10         20         30         40         50         60 
MHHQQRMAAL GTDKELSDLL DFSAMFSPPV SSGKNGPTSL ASGHFTGSNV EDRSSSGSWG 

        70         80         90        100        110        120 
NGGHPSPSRN YGDGTPYDHM TSRDLGSHDN LSPPFVNSRI QSKTERGSYS SYGRESNLQG 

       130        140        150        160        170        180 
CHQQSLLGGD MDMGNPGTLS PTKPGSQYYQ YSSNNPRRRP LHSSAMEVQT KKVRKVPPGL 

       190        200        210        220        230        240 
PSSVYAPSAS TADYNRDSPG YPSSKPATST FPSSFFMQDG HHSSDPWSSS SGMNQPGYAG 

       250        260        270        280        290        300 
MLGNSSHIPQ SSSYCSLHPH ERLSYPSHSS ADINSSLPPM STFHRSGTNH YSTSSCTPPA 

       310        320        330        340        350        360 
NGTDSIMANR GSGAAGSSQT GDALGKALAS IYSPDHTNNS FSSNPSTPVG SPPSLSAGTA 

       370        380        390        400        410        420 
VWSRNGGQAS SSPNYEGPLH SLQSRIEDRL ERLDDAIHVL RNHAVGPSTA MPGGHGDMHG 

       430        440        450        460        470        480 
IIGPSHNGAM GGLGSGYGTG LLSANRHSLM VGTHREDGVA LRGSHSLLPN QVPVPQLPVQ 

       490        500        510        520        530        540 
SATSPDLNPP QDPYRGMPPG LQGQSVSSGS SEIKSDDEGD ENLQDTKSSE DKKLDDDKKD 

       550        560        570        580        590        600 
IKSITSNNDD EDLTPEQKAE REKERRMANN ARERLRVRDI NEAFKELGRM VQLHLKSDKP 

       610        620        630        640        650        660 
QTKLLILHQA VAVILSLEQQ VRERNLNPKA ACLKRREEEK VSSEPPPLSL AGPHPGMGDA 


SNHMGQM 

« Hide

Isoform SEF2-1A (A+) [UniParc].

Checksum: 53BE8B2756C9C26B
Show »

FASTA51154,621
Isoform SEF2-1D (B+) [UniParc].

Checksum: 2A3AE4C1E87B81E4
Show »

FASTA67171,795
Isoform B+delta [UniParc].

Checksum: C9C6986AA5563828
Show »

FASTA61165,282
Isoform B-delta [UniParc].

Checksum: AE68260B30C1B9E6
Show »

FASTA60764,796
Isoform A- [UniParc].

Checksum: 2DF7DC48C2D3EE83
Show »

FASTA50754,135
Isoform G- [UniParc].

Checksum: 5912C40D16E30908
Show »

FASTA59664,116
Isoform H- [UniParc].

Checksum: D52C343573CF65BB
Show »

FASTA56760,681
Isoform D- [UniParc].

Checksum: 7F77B2E736AC27E4
Show »

FASTA53757,425
Isoform F- [UniParc].

Checksum: 36CF6C747000814D
Show »

FASTA62567,027
Isoform 11 [UniParc].

Checksum: FA530DE0722CDA2E
Show »

FASTA60064,602
Isoform E- [UniParc].

Checksum: 064EA9F64B55C741
Show »

FASTA66471,227
Isoform 13 [UniParc].

Checksum: 1ED8C14A73F678C1
Show »

FASTA64769,098
Isoform C- [UniParc].

Checksum: 68C866E2BBBAB621
Show »

FASTA64368,611
Isoform C-delta [UniParc].

Checksum: 6B694DB9DDCB93B6
Show »

FASTA58362,099
Isoform I- [UniParc].

Checksum: FD0EE9CD3312CFB4
Show »

FASTA45148,098

References

« Hide 'large scale' references
[1]"Helix-loop-helix transcriptional activators bind to a sequence in glucocorticoid response elements of retrovirus enhancers."
Corneliussen B., Thornell A., Hallberg B., Grundstroem T.
J. Virol. 65:6084-6093(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS SEF2-1A; SEF2-1B AND SEF2-1D), ALTERNATIVE SPLICING (ISOFORM SEF2-1C).
Tissue: Thymocyte and Thymus.
[2]"Functional diversity of human basic helix-loop-helix transcription factor TCF4 isoforms generated by alternative 5' exon usage and splicing."
Sepp M., Kannike K., Eesmaa A., Urb M., Timmusk T.
PLoS ONE 6:E22138-E22138(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A-; B-DELTA; B+DELTA; C-; C-DELTA; D-; E-; F-; G-; H-; I-; SEF2-1A; SEF2-1B AND SEF2-1D), ALTERNATIVE SPLICING.
[3]"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] (ISOFORMS SEF2-1A; C-; D-; F-; 11 AND 13).
Tissue: Brain, Hippocampus, Spleen and Teratocarcinoma.
[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. 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].
[5]Mural R.J., Istrail S., Sutton G.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 (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"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 SEF2-1B AND SEF2-1D).
[7]"MDSDCE06_MDS Homo sapiens cDNA clone MDSDCE06 5',mRNA sequence."
Gu J., Zhao M., Huang Q., Xu X., Li Y., Peng Y., Song H., Xiao H., Gu Y., Li N., Qian B., Liu F., Qu J., Gao X., Cheng Z., Xu Z., Zeng L., Xu S. expand/collapse author list , Gu W., Tu Y., Jia J., Fu G., Ren S., Zhong M., Lu G., Yang Y., Gao G., Zhang Q., Chen S., Han Z., Chen Z.
Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-278 (ISOFORM SEF2-1A).
[8]"A novel, heritable, expanding CTG repeat in an intron of the SEF2-1 gene on chromosome 18q21.1."
Breschel T.S., McInnis M.G., Margolis R.L., Sirugo G., Corneliussen B., Simpson S.G., McMahon F.J., Mackinnon D.F., Xu J.F., Pleasant N., Huo Y., Ashworth R.G., Grundstrom C., Grundstrom T., Kidd K.K., Depaulo J.R., Ross C.A.
Hum. Mol. Genet. 6:1855-1863(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 25-48.
Tissue: Skin fibroblast.
[9]"Sequence of the cDNA encoding ITF-2, a positive-acting transcription factor."
Henthorn P., McCarrick-Walmsley R., Kadesch T.
Nucleic Acids Res. 18:678-678(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 46-667 (ISOFORM SEF2-1B).
[10]"Two distinct transcription factors that bind the immunoglobulin enhancer microE5/kappa 2 motif."
Henthorn P., Kiledjian M., Kadesch T.
Science 247:467-470(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: DISCUSSION OF SEQUENCE.
[11]"Nine-amino-acid transactivation domain: establishment and prediction utilities."
Piskacek S., Gregor M., Nemethova M., Grabner M., Kovarik P., Piskacek M.
Genomics 89:756-768(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: DOMAIN.
[12]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-515, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]"Functional analysis of TCF4 missense mutations that cause Pitt-Hopkins syndrome."
Forrest M., Chapman R.M., Doyle A.M., Tinsley C.L., Waite A., Blake D.J.
Hum. Mutat. 33:1676-1686(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS PTHS VAL-358; GLY-535; PRO-574; TRP-576 AND VAL-610.
[14]"Mutations in AGBL1 cause dominant late-onset Fuchs corneal dystrophy and alter protein-protein interaction with TCF4."
Riazuddin S.A., Vasanth S., Katsanis N., Gottsch J.D.
Am. J. Hum. Genet. 93:758-764(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH AGBL1.
[15]"Mutations in TCF4, encoding a class I basic helix-loop-helix transcription factor, are responsible for Pitt-Hopkins syndrome, a severe epileptic encephalopathy associated with autonomic dysfunction."
Amiel J., Rio M., de Pontual L., Redon R., Malan V., Boddaert N., Plouin P., Carter N.P., Lyonnet S., Munnich A., Colleaux L.
Am. J. Hum. Genet. 80:988-993(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PTHS TRP-576 AND GLN-576.
[16]"Haploinsufficiency of TCF4 causes syndromal mental retardation with intermittent hyperventilation (Pitt-Hopkins syndrome)."
Zweier C., Peippo M.M., Hoyer J., Sousa S., Bottani A., Clayton-Smith J., Reardon W., Saraiva J., Cabral A., Goehring I., Devriendt K., de Ravel T., Bijlsma E.K., Hennekam R.C.M., Orrico A., Cohen M., Dreweke A., Reis A., Nuernberg P., Rauch A.
Am. J. Hum. Genet. 80:994-1001(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PTHS TRP-576.
[17]"Further delineation of Pitt-Hopkins syndrome: phenotypic and genotypic description of 16 novel patients."
Zweier C., Sticht H., Bijlsma E.K., Clayton-Smith J., Boonen S.E., Fryer A., Greally M.T., Hoffmann L., den Hollander N.S., Jongmans M., Kant S.G., King M.D., Lynch S.A., McKee S., Midro A.T., Park S.M., Ricotti V., Tarantino E. expand/collapse author list , Wessels M., Peippo M., Rauch A.
J. Med. Genet. 45:738-744(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PTHS VAL-358; PRO-574 AND HIS-578.
[18]"Mutational, functional, and expression studies of the TCF4 gene in Pitt-Hopkins syndrome."
de Pontual L., Mathieu Y., Golzio C., Rio M., Malan V., Boddaert N., Soufflet C., Picard C., Durandy A., Dobbie A., Heron D., Isidor B., Motte J., Newburry-Ecob R., Pasquier L., Tardieu M., Viot G., Jaubert F. expand/collapse author list , Munnich A., Colleaux L., Vekemans M., Etchevers H., Lyonnet S., Amiel J.
Hum. Mutat. 30:669-676(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PTHS GLY-535; GLY-572; GLN-576 AND VAL-610, CHARACTERIZATION OF VARIANTS PTHS GLY-535; GLY-572; GLN-576 AND VAL-610.
[19]"Two percent of patients suspected of having Angelman syndrome have TCF4 mutations."
Takano K., Lyons M., Moyes C., Jones J., Schwartz C.E.
Clin. Genet. 78:282-288(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PTHS PRO-578.
[20]"Novel comprehensive diagnostic strategy in Pitt-Hopkins syndrome: clinical score and further delineation of the TCF4 mutational spectrum."
Whalen S., Heron D., Gaillon T., Moldovan O., Rossi M., Devillard F., Giuliano F., Soares G., Mathieu-Dramard M., Afenjar A., Charles P., Mignot C., Burglen L., Van Maldergem L., Piard J., Aftimos S., Mancini G., Dias P. expand/collapse author list , Philip N., Goldenberg A., Le Merrer M., Rio M., Josifova D., Van Hagen J.M., Lacombe D., Edery P., Dupuis-Girod S., Putoux A., Sanlaville D., Fischer R., Drevillon L., Briand-Suleau A., Metay C., Goossens M., Amiel J., Jacquette A., Giurgea I.
Hum. Mutat. 33:64-72(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PTHS TRP-565; GLY-572; GLN-572; HIS-574; PRO-574; TRP-576; GLN-576; PRO-578; PRO-583 AND VAL-610.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M74718 mRNA. Translation: AAA60310.1. Sequence problems.
M74719 mRNA. Translation: AAA60311.1.
M74720 mRNA. Translation: AAA60312.1. Sequence problems.
FR748210 mRNA. Translation: CBY80189.1.
FR748211 mRNA. Translation: CBY80190.1.
FR748212 mRNA. Translation: CBY80191.1.
FR748213 mRNA. Translation: CBY80192.1.
FR748214 mRNA. Translation: CBY80193.1.
FR748215 mRNA. Translation: CBY80194.1.
FR748216 mRNA. Translation: CBY80195.1.
FR748217 mRNA. Translation: CBY80196.1.
FR748218 mRNA. Translation: CBY80197.1.
FR748219 mRNA. Translation: CBY80198.1.
FR748220 mRNA. Translation: CBY80199.1.
FR748221 mRNA. Translation: CBY80200.1.
FR748222 mRNA. Translation: CBY80201.1.
FR748223 mRNA. Translation: CBY80202.1.
AK095041 mRNA. Translation: BAG52974.1.
AK096862 mRNA. Translation: BAG53382.1.
AK299169 mRNA. Translation: BAH12962.1.
AK300636 mRNA. Translation: BAG62325.1.
AK300038 mRNA. Translation: BAG61849.1.
AK301144 mRNA. Translation: BAH13417.1.
AK300612 mRNA. Translation: BAH13314.1.
AK316165 mRNA. Translation: BAH14536.1.
AC013587 Genomic DNA. No translation available.
AC018994 Genomic DNA. No translation available.
AC090383 Genomic DNA. No translation available.
AC090684 Genomic DNA. No translation available.
AC091103 Genomic DNA. No translation available.
CH471096 Genomic DNA. Translation: EAW63017.1.
CH471096 Genomic DNA. Translation: EAW63018.1.
BC125084 mRNA. Translation: AAI25085.1.
BC125085 mRNA. Translation: AAI25086.1.
AV761952 mRNA. No translation available.
U75701 Genomic DNA. Translation: AAC51824.1.
X52079 mRNA. Translation: CAA36298.1.
PIRA41311.
RefSeqNP_001077431.1. NM_001083962.1.
NP_001230155.1. NM_001243226.1.
NP_001230156.1. NM_001243227.1.
NP_001230157.1. NM_001243228.1.
NP_001230159.1. NM_001243230.1.
NP_001230160.1. NM_001243231.1.
NP_001230161.1. NM_001243232.1.
NP_001230162.1. NM_001243233.1.
NP_001230163.1. NM_001243234.1.
NP_001230164.1. NM_001243235.1.
NP_001230165.1. NM_001243236.1.
NP_003190.1. NM_003199.2.
XP_005266800.1. XM_005266743.2.
XP_005266801.1. XM_005266744.2.
XP_005266803.1. XM_005266746.2.
XP_005266807.1. XM_005266750.2.
UniGeneHs.605153.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2KWFNMR-B11-27[»]
DisProtDP00224.
ProteinModelPortalP15884.
SMRP15884. Positions 565-624.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112787. 37 interactions.
DIPDIP-163N.
IntActP15884. 13 interactions.
MINTMINT-4508073.
STRING9606.ENSP00000346440.

PTM databases

PhosphoSiteP15884.

Proteomic databases

PaxDbP15884.
PRIDEP15884.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000354452; ENSP00000346440; ENSG00000196628. [P15884-3]
ENST00000356073; ENSP00000348374; ENSG00000196628. [P15884-1]
ENST00000457482; ENSP00000409447; ENSG00000196628. [P15884-2]
ENST00000537578; ENSP00000440731; ENSG00000196628. [P15884-13]
ENST00000537856; ENSP00000439827; ENSG00000196628. [P15884-9]
ENST00000540999; ENSP00000445202; ENSG00000196628. [P15884-14]
ENST00000543082; ENSP00000439656; ENSG00000196628. [P15884-10]
ENST00000544241; ENSP00000441562; ENSG00000196628. [P15884-11]
ENST00000561831; ENSP00000457765; ENSG00000196628.
ENST00000561992; ENSP00000455179; ENSG00000196628. [P15884-9]
ENST00000564228; ENSP00000455261; ENSG00000196628. [P15884-7]
ENST00000564999; ENSP00000457649; ENSG00000196628. [P15884-1]
ENST00000565018; ENSP00000455984; ENSG00000196628. [P15884-3]
ENST00000566279; ENSP00000456125; ENSG00000196628. [P15884-4]
ENST00000566286; ENSP00000455418; ENSG00000196628. [P15884-12]
ENST00000567880; ENSP00000454366; ENSG00000196628. [P15884-5]
ENST00000568673; ENSP00000455135; ENSG00000196628. [P15884-13]
ENST00000570177; ENSP00000454647; ENSG00000196628. [P15884-9]
ENST00000570287; ENSP00000455763; ENSG00000196628. [P15884-6]
GeneID6925.
KEGGhsa:6925.
UCSCuc002lfw.4. human. [P15884-2]
uc002lfx.2. human.
uc002lfy.2. human.
uc002lfz.2. human. [P15884-1]
uc010dph.1. human. [P15884-3]
uc021ukh.1. human. [P15884-6]
uc021uki.1. human. [P15884-7]
uc021ukj.1. human. [P15884-5]
uc021ukk.1. human. [P15884-4]

Organism-specific databases

CTD6925.
GeneCardsGC18M052889.
HGNCHGNC:11634. TCF4.
HPACAB020722.
HPA025958.
MIM602272. gene.
610954. phenotype.
neXtProtNX_P15884.
Orphanet178469. Autosomal dominant nonsyndromic intellectual deficit.
98974. Fuchs endothelial corneal dystrophy.
672. Pallister-Hall syndrome.
2896. Pitt-Hopkins syndrome.
171. Primary sclerosing cholangitis.
3140. Schizophrenia.
PharmGKBPA164742621.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG282899.
HOVERGENHBG003854.
KOK15603.
OrthoDBEOG72G16Q.
PhylomeDBP15884.
TreeFamTF321672.

Enzyme and pathway databases

ReactomeREACT_111045. Developmental Biology.
SignaLinkP15884.

Gene expression databases

ArrayExpressP15884.
BgeeP15884.
CleanExHS_TCF4.
GenevestigatorP15884.

Family and domain databases

Gene3D4.10.280.10. 1 hit.
InterProIPR011598. bHLH_dom.
[Graphical view]
PfamPF00010. HLH. 1 hit.
[Graphical view]
SMARTSM00353. HLH. 1 hit.
[Graphical view]
SUPFAMSSF47459. SSF47459. 1 hit.
PROSITEPS50888. BHLH. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSTCF4. human.
EvolutionaryTraceP15884.
GeneWikiTCF4.
GenomeRNAi6925.
NextBio27093.
PROP15884.
SOURCESearch...

Entry information

Entry nameITF2_HUMAN
AccessionPrimary (citable) accession number: P15884
Secondary accession number(s): B3KT62 expand/collapse secondary AC list , B3KUC0, B4DT37, B4DUG3, B7Z5M6, B7Z6Y1, G0LNT9, G0LNU0, G0LNU1, G0LNU2, G0LNU4, G0LNU5, G0LNU8, G0LNU9, G0LNV0, G0LNV1, G0LNV2, H3BPQ1, Q08AP2, Q08AP3, Q15439, Q15440, Q15441
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: December 15, 1998
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