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Q15561

- TEAD4_HUMAN

UniProt

Q15561 - TEAD4_HUMAN

Protein

Transcriptional enhancer factor TEF-3

Gene

TEAD4

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 125 (01 Oct 2014)
      Sequence version 3 (25 Nov 2008)
      Previous versions | rss
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    Functioni

    Transcription factor which plays a key role in the Hippo signaling pathway, a pathway involved in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein MST1/MST2, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Acts by mediating gene expression of YAP1 and WWTR1/TAZ, thereby regulating cell proliferation, migration and epithelial mesenchymal transition (EMT) induction. Binds specifically and non-cooperatively to the Sph and GT-IIC 'enhansons' (5'-GTGGAATGT-3') and activates transcription. Binds to the M-CAT motif.2 Publications

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    DNA bindingi38 – 10568TEAPROSITE-ProRule annotationAdd
    BLAST

    GO - Molecular functioni

    1. DNA binding Source: UniProtKB-KW
    2. protein binding Source: UniProtKB
    3. sequence-specific DNA binding transcription factor activity Source: UniProtKB

    GO - Biological processi

    1. gene expression Source: Reactome
    2. hippo signaling Source: UniProtKB
    3. muscle organ development Source: ProtInc
    4. regulation of transcription from RNA polymerase II promoter Source: ProtInc
    5. skeletal system development Source: ProtInc
    6. transcription initiation from RNA polymerase II promoter Source: Reactome

    Keywords - Molecular functioni

    Activator

    Keywords - Biological processi

    Transcription, Transcription regulation

    Keywords - Ligandi

    DNA-binding

    Enzyme and pathway databases

    ReactomeiREACT_116145. PPARA activates gene expression.
    REACT_118713. YAP1- and WWTR1 (TAZ)-stimulated gene expression.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Transcriptional enhancer factor TEF-3
    Alternative name(s):
    TEA domain family member 4
    Short name:
    TEAD-4
    Transcription factor 13-like 1
    Transcription factor RTEF-1
    Gene namesi
    Name:TEAD4
    Synonyms:RTEF1, TCF13L1, TEF3
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 12

    Organism-specific databases

    HGNCiHGNC:11717. TEAD4.

    Subcellular locationi

    GO - Cellular componenti

    1. nucleoplasm Source: Reactome

    Keywords - Cellular componenti

    Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi266 – 2661D → A: Reduced transforming ability. 1 Publication
    Mutagenesisi297 – 2971K → A: Important loss of interaction with YAP1 and complete loss of transforming ability. 1 Publication
    Mutagenesisi299 – 2991W → A: Important loss of interaction with YAP1 and complete loss of transforming ability. 1 Publication
    Mutagenesisi337 – 3371F → A: Reduced interaction with YAP1. 1 Publication
    Mutagenesisi373 – 3731F → A: Reduced transforming ability. 1 Publication
    Mutagenesisi380 – 3801L → A: Reduced transforming ability. 1 Publication
    Mutagenesisi391 – 3911E → A: Reduced transforming ability. 1 Publication
    Mutagenesisi393 – 3931F → A: Reduced transforming ability. 1 Publication
    Mutagenesisi427 – 4271H → A: Reduced transforming ability. 1 Publication
    Mutagenesisi429 – 4291Y → A or H: Loss of interaction with YAP1 and also activation by YAP1. 2 Publications
    Mutagenesisi429 – 4291Y → A: Important loss of interaction with YAP1 and complete loss of transforming ability. 2 Publications

    Organism-specific databases

    PharmGKBiPA36435.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 434434Transcriptional enhancer factor TEF-3PRO_0000205937Add
    BLAST

    Proteomic databases

    MaxQBiQ15561.
    PaxDbiQ15561.
    PRIDEiQ15561.

    PTM databases

    PhosphoSiteiQ15561.

    Expressioni

    Tissue specificityi

    Preferentially expressed in skeletal muscle. Lower levels in pancreas, placenta, and heart.

    Gene expression databases

    ArrayExpressiQ15561.
    BgeeiQ15561.
    CleanExiHS_TEAD4.
    GenevestigatoriQ15561.

    Organism-specific databases

    HPAiHPA056896.

    Interactioni

    Subunit structurei

    Interacts with YAP1 and WWTR1/TAZ.3 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    WWTR1Q9GZV52EBI-747736,EBI-747743

    Protein-protein interaction databases

    BioGridi112863. 5 interactions.
    IntActiQ15561. 3 interactions.
    MINTiMINT-1460562.
    STRINGi9606.ENSP00000352926.

    Structurei

    3D structure databases

    ProteinModelPortaliQ15561.
    SMRiQ15561. Positions 35-113, 217-433.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Contains 1 TEA DNA-binding domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiNOG246992.
    HOGENOMiHOG000253933.
    HOVERGENiHBG056905.
    InParanoidiQ15561.
    KOiK09448.
    PhylomeDBiQ15561.

    Family and domain databases

    InterProiIPR000818. TEA/ATTS.
    IPR016361. TEF.
    IPR027255. TEF-3.
    [Graphical view]
    PANTHERiPTHR11834. PTHR11834. 1 hit.
    PfamiPF01285. TEA. 1 hit.
    [Graphical view]
    PIRSFiPIRSF002603. TEF. 1 hit.
    PIRSF500722. TEF-3. 1 hit.
    PRINTSiPR00065. TEADOMAIN.
    SMARTiSM00426. TEA. 1 hit.
    [Graphical view]
    PROSITEiPS00554. TEA_1. 1 hit.
    PS51088. TEA_2. 1 hit.
    [Graphical view]

    Sequences (3)i

    Sequence statusi: Complete.

    This entry describes 3 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q15561-1) [UniParc]FASTAAdd to Basket

    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.

    « Hide

    MEGTAGTITS NEWSSPTSPE GSTASGGSQA LDKPIDNDAE GVWSPDIEQS    50
    FQEALAIYPP CGRRKIILSD EGKMYGRNEL IARYIKLRTG KTRTRKQVSS 100
    HIQVLARRKA REIQAKLKDQ AAKDKALQSM AAMSSAQIIS ATAFHSSMAL 150
    ARGPGRPAVS GFWQGALPGQ AGTSHDVKPF SQQTYAVQPP LPLPGFESPA 200
    GPAPSPSAPP APPWQGRSVA SSKLWMLEFS AFLEQQQDPD TYNKHLFVHI 250
    GQSSPSYSDP YLEAVDIRQI YDKFPEKKGG LKDLFERGPS NAFFLVKFWA 300
    DLNTNIEDEG SSFYGVSSQY ESPENMIITC STKVCSFGKQ VVEKVETEYA 350
    RYENGHYSYR IHRSPLCEYM INFIHKLKHL PEKYMMNSVL ENFTILQVVT 400
    NRDTQETLLC IAYVFEVSAS EHGAQHHIYR LVKE 434
    Length:434
    Mass (Da):48,329
    Last modified:November 25, 2008 - v3
    Checksum:i544DDFD86E88D9A8
    GO
    Isoform 2 (identifier: Q15561-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-129: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:305
    Mass (Da):34,158
    Checksum:i6A3BDF596BCE7797
    GO
    Isoform 3 (identifier: Q15561-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         119-161: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:391
    Mass (Da):44,058
    Checksum:i68B36C4E607ADB1E
    GO

    Sequence cautioni

    The sequence CAA64212.2 differs from that shown. Reason: Unusual initiator. The initiator methionine is coded by a non-canonical ATA isoleucine codon.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti39 – 391A → G in AAC50763. (PubMed:8921372)Curated
    Sequence conflicti149 – 1491A → R in AAC50763. (PubMed:8921372)Curated
    Sequence conflicti172 – 1721G → E in AAC50763. (PubMed:8921372)Curated
    Sequence conflicti218 – 2203SVA → RRG in AAC50763. (PubMed:8921372)Curated
    Sequence conflicti258 – 2592SD → LR in AAC50763. (PubMed:8921372)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti323 – 3231P → S.
    Corresponds to variant rs11550887 [ dbSNP | Ensembl ].
    VAR_052279

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 129129Missing in isoform 2. 1 PublicationVSP_043099Add
    BLAST
    Alternative sequencei119 – 16143Missing in isoform 3. 1 PublicationVSP_045657Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U63824 mRNA. Translation: AAC50763.1.
    BX640921 mRNA. Translation: CAE45959.1.
    AC005911 Genomic DNA. No translation available.
    AC125807 Genomic DNA. No translation available.
    AC131234 Genomic DNA. No translation available.
    CH471116 Genomic DNA. Translation: EAW88872.1.
    BC015497 mRNA. Translation: AAH15497.2.
    X94438 mRNA. Translation: CAA64212.2. Sequence problems.
    AY101179 mRNA. Translation: AAM89497.1.
    CCDSiCCDS31729.1. [Q15561-1]
    CCDS31730.1. [Q15561-3]
    CCDS41737.1. [Q15561-2]
    RefSeqiNP_003204.2. NM_003213.3. [Q15561-1]
    NP_958849.1. NM_201441.2. [Q15561-3]
    NP_958851.1. NM_201443.2. [Q15561-2]
    UniGeneiHs.94865.

    Genome annotation databases

    EnsembliENST00000397122; ENSP00000380311; ENSG00000197905. [Q15561-2]
    GeneIDi7004.
    KEGGihsa:7004.
    UCSCiuc001qln.3. human. [Q15561-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U63824 mRNA. Translation: AAC50763.1 .
    BX640921 mRNA. Translation: CAE45959.1 .
    AC005911 Genomic DNA. No translation available.
    AC125807 Genomic DNA. No translation available.
    AC131234 Genomic DNA. No translation available.
    CH471116 Genomic DNA. Translation: EAW88872.1 .
    BC015497 mRNA. Translation: AAH15497.2 .
    X94438 mRNA. Translation: CAA64212.2 . Sequence problems.
    AY101179 mRNA. Translation: AAM89497.1 .
    CCDSi CCDS31729.1. [Q15561-1 ]
    CCDS31730.1. [Q15561-3 ]
    CCDS41737.1. [Q15561-2 ]
    RefSeqi NP_003204.2. NM_003213.3. [Q15561-1 ]
    NP_958849.1. NM_201441.2. [Q15561-3 ]
    NP_958851.1. NM_201443.2. [Q15561-2 ]
    UniGenei Hs.94865.

    3D structure databases

    ProteinModelPortali Q15561.
    SMRi Q15561. Positions 35-113, 217-433.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 112863. 5 interactions.
    IntActi Q15561. 3 interactions.
    MINTi MINT-1460562.
    STRINGi 9606.ENSP00000352926.

    PTM databases

    PhosphoSitei Q15561.

    Proteomic databases

    MaxQBi Q15561.
    PaxDbi Q15561.
    PRIDEi Q15561.

    Protocols and materials databases

    DNASUi 7004.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000397122 ; ENSP00000380311 ; ENSG00000197905 . [Q15561-2 ]
    GeneIDi 7004.
    KEGGi hsa:7004.
    UCSCi uc001qln.3. human. [Q15561-1 ]

    Organism-specific databases

    CTDi 7004.
    GeneCardsi GC12P003068.
    HGNCi HGNC:11717. TEAD4.
    HPAi HPA056896.
    MIMi 601714. gene.
    neXtProti NX_Q15561.
    PharmGKBi PA36435.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG246992.
    HOGENOMi HOG000253933.
    HOVERGENi HBG056905.
    InParanoidi Q15561.
    KOi K09448.
    PhylomeDBi Q15561.

    Enzyme and pathway databases

    Reactomei REACT_116145. PPARA activates gene expression.
    REACT_118713. YAP1- and WWTR1 (TAZ)-stimulated gene expression.

    Miscellaneous databases

    GeneWikii TEAD4.
    GenomeRNAii 7004.
    NextBioi 27354.
    PROi Q15561.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q15561.
    Bgeei Q15561.
    CleanExi HS_TEAD4.
    Genevestigatori Q15561.

    Family and domain databases

    InterProi IPR000818. TEA/ATTS.
    IPR016361. TEF.
    IPR027255. TEF-3.
    [Graphical view ]
    PANTHERi PTHR11834. PTHR11834. 1 hit.
    Pfami PF01285. TEA. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF002603. TEF. 1 hit.
    PIRSF500722. TEF-3. 1 hit.
    PRINTSi PR00065. TEADOMAIN.
    SMARTi SM00426. TEA. 1 hit.
    [Graphical view ]
    PROSITEi PS00554. TEA_1. 1 hit.
    PS51088. TEA_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Cloning of human RTEF-1, a transcriptional enhancer factor-1-related gene preferentially expressed in skeletal muscle: evidence for an ancient multigene family."
      Stewart A.F.R., Richard C.W. III, Suzow J., Stephan D., Weremowicz S., Morton C.C., Adra C.N.
      Genomics 37:68-76(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
      Tissue: Heart.
    2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
      Tissue: Uterine endothelium.
    3. "The finished DNA sequence of human chromosome 12."
      Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.
      , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A.
      Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    4. 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] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
      Tissue: Uterus.
    6. "A novel family of developmentally regulated mammalian transcription factors containing the TEA/ATTS DNA binding domain."
      Jacquemin P., Hwang J.-J., Martial J.A., Dolle P., Davidson I.
      J. Biol. Chem. 271:21775-21785(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 8-434 (ISOFORM 1).
    7. "Role of MCAT binding factors during muscle hypertrophy."
      Tsika R.W., Karasseva N.G., Tsika G.L.
      Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 8-391 (ISOFORM 3).
    8. "TEAD mediates YAP-dependent gene induction and growth control."
      Zhao B., Ye X., Yu J., Li L., Li W., Li S., Yu J., Lin J.D., Wang C.Y., Chinnaiyan A.M., Lai Z.C., Guan K.L.
      Genes Dev. 22:1962-1971(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH YAP1, MUTAGENESIS OF TYR-429.
    9. "TEAD transcription factors mediate the function of TAZ in cell growth and epithelial-mesenchymal transition."
      Zhang H., Liu C.Y., Zha Z.Y., Zhao B., Yao J., Zhao S., Xiong Y., Lei Q.Y., Guan K.L.
      J. Biol. Chem. 284:13355-13362(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, INTERACTION WITH WWTR1.
    10. "Structural basis of YAP recognition by TEAD4 in the hippo pathway."
      Chen L., Chan S.W., Zhang X., Walsh M., Lim C.J., Hong W., Song H.
      Genes Dev. 24:290-300(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH YAP1, MUTAGENESIS OF ASP-266; LYS-297; TRP-299; PHE-337; PHE-373; LEU-380; GLU-391; PHE-393; HIS-427 AND TYR-429.

    Entry informationi

    Entry nameiTEAD4_HUMAN
    AccessioniPrimary (citable) accession number: Q15561
    Secondary accession number(s): H0Y308
    , Q6MZR9, Q8NEV5, Q92883, Q96BK2
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1997
    Last sequence update: November 25, 2008
    Last modified: October 1, 2014
    This is version 125 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (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.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 12
      Human chromosome 12: 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. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3