Cyclic AMP-dependent transcription factor ATF-4

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

<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><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functionⁱ

• cAMP response element binding protein binding Source: UniProtKB
• DNA binding Source: UniProtKB <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%2Dgo%2Devidence%2Dcodes#ida">GO evidence code guide</a></p> Inferred from direct assayⁱ
  • "The oxidative stressor arsenite activates vascular endothelial growth factor mRNA transcription by an ATF4-dependent mechanism."
    Roybal C.N., Hunsaker L.A., Barbash O., Vander Jagt D.L., Abcouwer S.F.
    J Biol Chem 280:20331-20339(2005) [PubMed] [Europe PMC] [Abstract]
  • Ref.14

    "FIAT represses ATF4-mediated transcription to regulate bone mass in transgenic mice."
    Yu V.W., Ambartsoumian G., Verlinden L., Moir J.M., Prud'homme J., Gauthier C., Roughley P.J., St-Arnaud R.
    J. Cell Biol. 169:591-601(2005) [PubMed] [Europe PMC] [Abstract]

    Cited for: INTERACTION WITH TXLNG.
  • Ref.17

    "C/EBP homology protein (CHOP) interacts with activating transcription factor 4 (ATF4) and negatively regulates the stress-dependent induction of the asparagine synthetase gene."
    Su N., Kilberg M.S.
    J. Biol. Chem. 283:35106-35117(2008) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, INTERACTION WITH DDIT3.
• DNA-binding transcription activator activity, RNA polymerase II-specific Source: GO_Central <p>Inferred from Biological aspect of Ancestor</p> <p>A type of phylogenetic evidence whereby an aspect of a descendent is inferred through the characterization of an aspect of a ancestral gene.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#iba">GO evidence code guide</a></p> Inferred from biological aspect of ancestorⁱ
  • "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
    Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
    Brief Bioinform 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
• DNA-binding transcription factor activity Source: UniProtKBInferred from direct assayⁱ
  • Ref.10

    "ATF4 is a mediator of the nutrient-sensing response pathway that activates the human asparagine synthetase gene."
    Siu F., Bain P.J., LeBlanc-Chaffin R., Chen H., Kilberg M.S.
    J. Biol. Chem. 277:24120-24127(2002) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION.
  • Ref.11

    "ATF4 is a substrate of RSK2 and an essential regulator of osteoblast biology; implication for Coffin-Lowry Syndrome."
    Yang X., Matsuda K., Bialek P., Jacquot S., Masuoka H.C., Schinke T., Li L., Brancorsini S., Sassone-Corsi P., Townes T.M., Hanauer A., Karsenty G.
    Cell 117:387-398(2004) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, PHOSPHORYLATION AT SER-245, MUTAGENESIS OF SER-245.
  • Ref.22

    "Functional interaction of protein kinase CK2 and activating transcription factor 4 (ATF4), a key player in the cellular stress response."
    Ampofo E., Sokolowsky T., Goetz C., Montenarh M.
    Biochim. Biophys. Acta 1833:439-451(2013) [PubMed] [Europe PMC] [Abstract]

    Cited for: PHOSPHORYLATION AT SER-215, SUBCELLULAR LOCATION, MUTAGENESIS OF THR-213 AND SER-215.
  • Ref.29

    "Mitochondrial stress is relayed to the cytosol by an OMA1-DELE1-HRI pathway."
    Guo X., Aviles G., Liu Y., Tian R., Unger B.A., Lin Y.T., Wiita A.P., Xu K., Correia M.A., Kampmann M.
    Nature 0:0-0(2020) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION.
• DNA-binding transcription factor activity, RNA polymerase II-specific Source: ParkinsonsUK-UCLInferred from direct assayⁱ
  • "The cAMP response element binding protein-2 (CREB-2) can interact with the C/EBP-homologous protein (CHOP)."
    Gachon F., Gaudray G., Thebault S., Basbous J., Koffi J.A., Devaux C., Mesnard J.
    FEBS Lett 502:57-62(2001) [PubMed] [Europe PMC] [Abstract]
  • "Induction of Grp78/BiP by translational block: activation of the Grp78 promoter by ATF4 through and upstream ATF/CRE site independent of the endoplasmic reticulum stress elements."
    Luo S., Baumeister P., Yang S., Abcouwer S.F., Lee A.S.
    J Biol Chem 278:37375-37385(2003) [PubMed] [Europe PMC] [Abstract]
• leucine zipper domain binding Source: ParkinsonsUK-UCLInferred from direct assayⁱ
  • "The cAMP response element binding protein-2 (CREB-2) can interact with the C/EBP-homologous protein (CHOP)."
    Gachon F., Gaudray G., Thebault S., Basbous J., Koffi J.A., Devaux C., Mesnard J.
    FEBS Lett 502:57-62(2001) [PubMed] [Europe PMC] [Abstract]
• protein C-terminus binding Source: Ensembl
• protein heterodimerization activity Source: UniProtKB
• protein kinase binding Source: UniProtKB <p>Inferred from Physical Interaction</p> <p>Covers physical interactions between the gene product of interest and another molecule (or ion, or complex).</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#ipi">GO evidence code guide</a></p> Inferred from physical interactionⁱ
  • Ref.18

    "Characterization of hNek6 interactome reveals an important role for its short N-terminal domain and colocalization with proteins at the centrosome."
    Vaz Meirelles G., Ferreira Lanza D.C., da Silva J.C., Santana Bernachi J., Paes Leme A.F., Kobarg J.
    J. Proteome Res. 9:6298-6316(2010) [PubMed] [Europe PMC] [Abstract]

    Cited for: SUBCELLULAR LOCATION, INTERACTION WITH NEK6, PHOSPHORYLATION.
• RNA polymerase II cis-regulatory region sequence-specific DNA binding Source: UniProtKB
• RNA polymerase II transcription factor binding Source: ParkinsonsUK-UCLInferred from physical interactionⁱ
  • "The cAMP response element binding protein-2 (CREB-2) can interact with the C/EBP-homologous protein (CHOP)."
    Gachon F., Gaudray G., Thebault S., Basbous J., Koffi J.A., Devaux C., Mesnard J.
    FEBS Lett 502:57-62(2001) [PubMed] [Europe PMC] [Abstract]
• RNA polymerase II transcription regulatory region sequence-specific DNA binding Source: GO_CentralInferred from biological aspect of ancestorⁱ
  • "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
    Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
    Brief Bioinform 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
• sequence-specific DNA binding Source: ParkinsonsUK-UCLInferred from direct assayⁱ
  • "The unfolded protein response induces the angiogenic switch in human tumor cells through the PERK/ATF4 pathway."
    Wang Y., Alam G.N., Ning Y., Visioli F., Dong Z., Nor J.E., Polverini P.J.
    Cancer Res 72:5396-5406(2012) [PubMed] [Europe PMC] [Abstract]
• sequence-specific double-stranded DNA binding Source: ARUK-UCLInferred from direct assayⁱ
  • "Impact of cytosine methylation on DNA binding specificities of human transcription factors."
    Yin Y., Morgunova E., Jolma A., Kaasinen E., Sahu B., Khund-Sayeed S., Das P.K., Kivioja T., Dave K., Zhong F., Nitta K.R., Taipale M., Popov A., Ginno P.A., Domcke S., Yan J., Schubeler D., Vinson C., Taipale J.
    Science 356:0-0(2017) [PubMed] [Europe PMC] [Abstract]
• transcription regulatory region sequence-specific DNA binding Source: ParkinsonsUK-UCLInferred from direct assayⁱ
  • "Parkin is transcriptionally regulated by ATF4: evidence for an interconnection between mitochondrial stress and ER stress."
    Bouman L., Schlierf A., Lutz A.K., Shan J., Deinlein A., Kast J., Galehdar Z., Palmisano V., Patenge N., Berg D., Gasser T., Augustin R., Trumbach D., Irrcher I., Park D.S., Wurst W., Kilberg M.S., Tatzelt J., Winklhofer K.F.
    Cell Death Differ 18:769-782(2011) [PubMed] [Europe PMC] [Abstract]

GO - Biological processⁱ

• bone mineralization Source: UniProtKB
• cellular calcium ion homeostasis Source: Ensembl
• cellular response to amino acid starvation Source: UniProtKB
• cellular response to dopamine Source: CAFA <p>Inferred from Mutant Phenotype</p> <p>Describes annotations that are concluded from looking at variations or changes in a gene product such as mutations or abnormal levels and includes techniques such as knockouts, overexpression, anti-sense experiments and use of specific protein inhibitors.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#imp">GO evidence code guide</a></p> Inferred from mutant phenotypeⁱ
  • "Cytosolic sulfotransferase 1A3 is induced by dopamine and protects neuronal cells from dopamine toxicity: role of D1 receptor-N-methyl-D-aspartate receptor coupling."
    Sidharthan N.P., Minchin R.F., Butcher N.J.
    J Biol Chem 288:34364-34374(2013) [PubMed] [Europe PMC] [Abstract]
• cellular response to glucose starvation Source: ParkinsonsUK-UCLInferred from mutant phenotypeⁱ
  • "The unfolded protein response induces the angiogenic switch in human tumor cells through the PERK/ATF4 pathway."
    Wang Y., Alam G.N., Ning Y., Visioli F., Dong Z., Nor J.E., Polverini P.J.
    Cancer Res 72:5396-5406(2012) [PubMed] [Europe PMC] [Abstract]
• cellular response to oxidative stress Source: UniProtKB
• cellular response to oxygen-glucose deprivation Source: Ensembl
• cellular response to UV Source: UniProtKB
• circadian regulation of gene expression Source: UniProtKB
• embryonic hemopoiesis Source: UniProtKB
• endoplasmic reticulum unfolded protein response Source: UniProtKB
• gamma-aminobutyric acid signaling pathway Source: Ensembl
• gluconeogenesis Source: UniProtKB
• HRI-mediated signaling Source: UniProtKBInferred from direct assayⁱ
  • Ref.29

    "Mitochondrial stress is relayed to the cytosol by an OMA1-DELE1-HRI pathway."
    Guo X., Aviles G., Liu Y., Tian R., Unger B.A., Lin Y.T., Wiita A.P., Xu K., Correia M.A., Kampmann M.
    Nature 0:0-0(2020) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION.
• integrated stress response signaling Source: UniProtKBInferred from direct assayⁱ
  • Ref.29

    "Mitochondrial stress is relayed to the cytosol by an OMA1-DELE1-HRI pathway."
    Guo X., Aviles G., Liu Y., Tian R., Unger B.A., Lin Y.T., Wiita A.P., Xu K., Correia M.A., Kampmann M.
    Nature 0:0-0(2020) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION.
• intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress Source: UniProtKB
• L-asparagine metabolic process Source: UniProtKBInferred from direct assayⁱ
  • Ref.10

    "ATF4 is a mediator of the nutrient-sensing response pathway that activates the human asparagine synthetase gene."
    Siu F., Bain P.J., LeBlanc-Chaffin R., Chen H., Kilberg M.S.
    J. Biol. Chem. 277:24120-24127(2002) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION.
• lens fiber cell morphogenesis Source: UniProtKB
• mRNA transcription by RNA polymerase II Source: UniProtKB
• negative regulation of cold-induced thermogenesis Source: YuBioLab <p>Inferred from Sequence or Structural Similarity<br />Used for any analysis based on sequence alignment, structure comparison, or evaluation of sequence features such as composition.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#iss">GO evidence code guide</a></p> Inferred from sequence or structural similarityⁱ
  • "Effects of ATF4 on PGC1alpha expression in brown adipose tissue and metabolic responses to cold stress."
    Wang C., Xia T., Du Y., Meng Q., Li H., Liu B., Chen S., Guo F.
    Metabolism 62:282-289(2013) [PubMed] [Europe PMC] [Abstract]
• negative regulation of oxidative stress-induced neuron death Source: ParkinsonsUK-UCL <p>Inferred from Genetic Interaction</p> <p>Used to describe "traditional" genetic interactions such as suppressors and synthetic lethals as well as other techniques such as functional complementation, rescue experiments, or inferences about a gene drawn from the phenotype of a mutation in a different gene.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#igi">GO evidence code guide</a></p> Inferred from genetic interactionⁱ
  • "ATF4 protects against neuronal death in cellular Parkinson's disease models by maintaining levels of parkin."
    Sun X., Liu J., Crary J.F., Malagelada C., Sulzer D., Greene L.A., Levy O.A.
    J Neurosci 33:2398-2407(2013) [PubMed] [Europe PMC] [Abstract]
• negative regulation of potassium ion transport Source: Ensembl
• negative regulation of transcription by RNA polymerase II Source: UniProtKB
• negative regulation of translational initiation in response to stress Source: UniProtKB
• neuron differentiation Source: Ensembl
• PERK-mediated unfolded protein response Source: UniProtKB
• positive regulation of apoptotic process Source: ParkinsonsUK-UCL <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%2Dgo%2Devidence%2Dcodes#tas">GO evidence code guide</a></p> Traceable author statementⁱ
  • "ATF4 protects against neuronal death in cellular Parkinson's disease models by maintaining levels of parkin."
    Sun X., Liu J., Crary J.F., Malagelada C., Sulzer D., Greene L.A., Levy O.A.
    J Neurosci 33:2398-2407(2013) [PubMed] [Europe PMC] [Abstract]
• positive regulation of biomineral tissue development Source: Ensembl
• positive regulation of gene expression Source: ARUK-UCLInferred from mutant phenotypeⁱ
  • "Characterization of the amino acid response element within the human sodium-coupled neutral amino acid transporter 2 (SNAT2) System A transporter gene."
    Palii S.S., Thiaville M.M., Pan Y.X., Zhong C., Kilberg M.S.
    Biochem J 395:517-527(2006) [PubMed] [Europe PMC] [Abstract]
• positive regulation of neuron apoptotic process Source: UniProtKB
• positive regulation of sodium-dependent phosphate transport Source: Ensembl
• positive regulation of transcription, DNA-templated Source: UniProtKBInferred from direct assayⁱ
  • Ref.12

    "TRB3, a novel ER stress-inducible gene, is induced via ATF4-CHOP pathway and is involved in cell death."
    Ohoka N., Yoshii S., Hattori T., Onozaki K., Hayashi H.
    EMBO J. 24:1243-1255(2005) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION.
  • Ref.17

    "C/EBP homology protein (CHOP) interacts with activating transcription factor 4 (ATF4) and negatively regulates the stress-dependent induction of the asparagine synthetase gene."
    Su N., Kilberg M.S.
    J. Biol. Chem. 283:35106-35117(2008) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, INTERACTION WITH DDIT3.
• positive regulation of transcription by RNA polymerase I Source: ParkinsonsUK-UCLInferred from mutant phenotypeⁱ
  • "The unfolded protein response induces the angiogenic switch in human tumor cells through the PERK/ATF4 pathway."
    Wang Y., Alam G.N., Ning Y., Visioli F., Dong Z., Nor J.E., Polverini P.J.
    Cancer Res 72:5396-5406(2012) [PubMed] [Europe PMC] [Abstract]
• positive regulation of transcription by RNA polymerase II Source: UniProtKBInferred from direct assayⁱ
  • Ref.10

    "ATF4 is a mediator of the nutrient-sensing response pathway that activates the human asparagine synthetase gene."
    Siu F., Bain P.J., LeBlanc-Chaffin R., Chen H., Kilberg M.S.
    J. Biol. Chem. 277:24120-24127(2002) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION.
  • Ref.11

    "ATF4 is a substrate of RSK2 and an essential regulator of osteoblast biology; implication for Coffin-Lowry Syndrome."
    Yang X., Matsuda K., Bialek P., Jacquot S., Masuoka H.C., Schinke T., Li L., Brancorsini S., Sassone-Corsi P., Townes T.M., Hanauer A., Karsenty G.
    Cell 117:387-398(2004) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, PHOSPHORYLATION AT SER-245, MUTAGENESIS OF SER-245.
  • Ref.22

    "Functional interaction of protein kinase CK2 and activating transcription factor 4 (ATF4), a key player in the cellular stress response."
    Ampofo E., Sokolowsky T., Goetz C., Montenarh M.
    Biochim. Biophys. Acta 1833:439-451(2013) [PubMed] [Europe PMC] [Abstract]

    Cited for: PHOSPHORYLATION AT SER-215, SUBCELLULAR LOCATION, MUTAGENESIS OF THR-213 AND SER-215.
• positive regulation of transcription from RNA polymerase II promoter in response to arsenic-containing substance Source: ParkinsonsUK-UCLTraceable author statementⁱ
  • "Roles of CHOP/GADD153 in endoplasmic reticulum stress."
    Oyadomari S., Mori M.
    Cell Death Differ. 11:381-389(2004) [PubMed] [Europe PMC] [Abstract]
• positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress Source: ParkinsonsUK-UCLInferred from direct assayⁱ
  • "Induction of Grp78/BiP by translational block: activation of the Grp78 promoter by ATF4 through and upstream ATF/CRE site independent of the endoplasmic reticulum stress elements."
    Luo S., Baumeister P., Yang S., Abcouwer S.F., Lee A.S.
    J Biol Chem 278:37375-37385(2003) [PubMed] [Europe PMC] [Abstract]
• positive regulation of transcription from RNA polymerase II promoter in response to oxidative stress Source: ParkinsonsUK-UCLInferred from mutant phenotypeⁱ
  • "Parkin is transcriptionally regulated by ATF4: evidence for an interconnection between mitochondrial stress and ER stress."
    Bouman L., Schlierf A., Lutz A.K., Shan J., Deinlein A., Kast J., Galehdar Z., Palmisano V., Patenge N., Berg D., Gasser T., Augustin R., Trumbach D., Irrcher I., Park D.S., Wurst W., Kilberg M.S., Tatzelt J., Winklhofer K.F.
    Cell Death Differ 18:769-782(2011) [PubMed] [Europe PMC] [Abstract]
• positive regulation of transcription from RNA polymerase II promoter in response to stress Source: ParkinsonsUK-UCL <p>Inferred by Curator</p> <p>Used for cases where an annotation is not supported by any evidence but can be reasonably inferred by a curator from other GO annotations for which evidence<br />is available.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#ic">GO evidence code guide</a></p> Inferred by curatorⁱ
  • "Loss of lysosome-associated membrane protein 3 (LAMP3) enhances cellular vulnerability against proteasomal inhibition."
    Dominguez-Bautista J.A., Klinkenberg M., Brehm N., Subramaniam M., Kern B., Roeper J., Auburger G., Jendrach M.
    Eur J Cell Biol 94:148-161(2015) [PubMed] [Europe PMC] [Abstract]
• positive regulation of vascular associated smooth muscle cell apoptotic process Source: Ensembl
• positive regulation of vascular endothelial growth factor production Source: ParkinsonsUK-UCLInferred from mutant phenotypeⁱ
  • "The unfolded protein response induces the angiogenic switch in human tumor cells through the PERK/ATF4 pathway."
    Wang Y., Alam G.N., Ning Y., Visioli F., Dong Z., Nor J.E., Polverini P.J.
    Cancer Res 72:5396-5406(2012) [PubMed] [Europe PMC] [Abstract]
• regulation of eIF2 alpha phosphorylation by heme Source: Reactome
• regulation of osteoblast differentiation Source: UniProtKBInferred from direct assayⁱ
  • Ref.11

    "ATF4 is a substrate of RSK2 and an essential regulator of osteoblast biology; implication for Coffin-Lowry Syndrome."
    Yang X., Matsuda K., Bialek P., Jacquot S., Masuoka H.C., Schinke T., Li L., Brancorsini S., Sassone-Corsi P., Townes T.M., Hanauer A., Karsenty G.
    Cell 117:387-398(2004) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, PHOSPHORYLATION AT SER-245, MUTAGENESIS OF SER-245.
• regulation of synaptic plasticity Source: UniProtKB
• regulation of transcription, DNA-templated Source: UniProtKB
• regulation of transcription by RNA polymerase II Source: GO_CentralInferred from biological aspect of ancestorⁱ
  • "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
    Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
    Brief Bioinform 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
• response to endoplasmic reticulum stress Source: BHF-UCLInferred from direct assayⁱ
  • "Role of SERCA1 truncated isoform in the proapoptotic calcium transfer from ER to mitochondria during ER stress."
    Chami M., Oules B., Szabadkai G., Tacine R., Rizzuto R., Paterlini-Brechot P.
    Mol Cell 32:641-651(2008) [PubMed] [Europe PMC] [Abstract]
• response to manganese-induced endoplasmic reticulum stress Source: Ensembl
• response to nutrient levels Source: UniProtKBInferred from direct assayⁱ
  • Ref.10

    "ATF4 is a mediator of the nutrient-sensing response pathway that activates the human asparagine synthetase gene."
    Siu F., Bain P.J., LeBlanc-Chaffin R., Chen H., Kilberg M.S.
    J. Biol. Chem. 277:24120-24127(2002) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION.
• response to toxic substance Source: Ensembl
• transcription by RNA polymerase II Source: UniProtKB

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/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>Keywordsⁱ

Enzyme and pathway databases

<p>This section 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><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyⁱ

Organism-specific databases

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

• UniProt annotation
• GO - Cellular component

Keywords - Cellular componentⁱ

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

Mutagenesis

Organism-specific databases

Miscellaneous databases

Chemistry databases

Genetic variation databases

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

Molecule processing

Amino acid modifications

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationⁱ

Keywords - PTMⁱ

Proteomic databases

PTM databases

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

<p>This subsection of the 'Expression' section reports the experimentally proven effects of inducers and repressors (usually chemical compounds or environmental factors) on the level of protein (or mRNA) expression (up-regulation, down-regulation, constitutive expression).<p><a href='/help/induction' target='_top'>More...</a></p>Inductionⁱ

Gene expression databases

Organism-specific databases

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

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section 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="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structureⁱ

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection">Interaction</a>' section 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="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsⁱ

GO - Molecular functionⁱ

• cAMP response element binding protein binding Source: UniProtKB
• leucine zipper domain binding Source: ParkinsonsUK-UCLInferred from direct assayⁱ
  • "The cAMP response element binding protein-2 (CREB-2) can interact with the C/EBP-homologous protein (CHOP)."
    Gachon F., Gaudray G., Thebault S., Basbous J., Koffi J.A., Devaux C., Mesnard J.
    FEBS Lett 502:57-62(2001) [PubMed] [Europe PMC] [Abstract]
• protein C-terminus binding Source: Ensembl
• protein heterodimerization activity Source: UniProtKB
• protein kinase binding Source: UniProtKBInferred from physical interactionⁱ
  • Ref.18

    "Characterization of hNek6 interactome reveals an important role for its short N-terminal domain and colocalization with proteins at the centrosome."
    Vaz Meirelles G., Ferreira Lanza D.C., da Silva J.C., Santana Bernachi J., Paes Leme A.F., Kobarg J.
    J. Proteome Res. 9:6298-6316(2010) [PubMed] [Europe PMC] [Abstract]

    Cited for: SUBCELLULAR LOCATION, INTERACTION WITH NEK6, PHOSPHORYLATION.
• RNA polymerase II transcription factor binding Source: ParkinsonsUK-UCLInferred from physical interactionⁱ
  • "The cAMP response element binding protein-2 (CREB-2) can interact with the C/EBP-homologous protein (CHOP)."
    Gachon F., Gaudray G., Thebault S., Basbous J., Koffi J.A., Devaux C., Mesnard J.
    FEBS Lett 502:57-62(2001) [PubMed] [Europe PMC] [Abstract]

Protein-protein interaction databases

Miscellaneous databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structureⁱ

Secondary structure

3D structure databases

Miscellaneous databases

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

Domains and Repeats

Region

Coiled coil

Motif

<p>This subsection of the 'Family and domains' section provides general information on the biological role of a domain. The term 'domain' is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domainⁱ

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesⁱ

Keywords - Domainⁱ

Phylogenomic databases

Family and domain databases

<p>This section 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 <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequence (1+)ⁱ

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusⁱ: Complete.

This entry has 1 described isoform and 5 potential isoforms that are computationally mapped.Show allAlign All

        10         20         30         40         50
MTEMSFLSSE VLVGDLMSPF DQSGLGAEES LGLLDDYLEV AKHFKPHGFS 
        60         70         80         90        100
SDKAKAGSSE WLAVDGLVSP SNNSKEDAFS GTDWMLEKMD LKEFDLDALL 
       110        120        130        140        150
GIDDLETMPD DLLTTLDDTC DLFAPLVQET NKQPPQTVNP IGHLPESLTK 
       160        170        180        190        200
PDQVAPFTFL QPLPLSPGVL SSTPDHSFSL ELGSEVDITE GDRKPDYTAY 
       210        220        230        240        250
VAMIPQCIKE EDTPSDNDSG ICMSPESYLG SPQHSPSTRG SPNRSLPSPG 
       260        270        280        290        300
VLCGSARPKP YDPPGEKMVA AKVKGEKLDK KLKKMEQNKT AATRYRQKKR 
       310        320        330        340        350
AEQEALTGEC KELEKKNEAL KERADSLAKE IQYLKDLIEE VRKARGKKRV 

P                                                      

Experimental Info

Natural variant

Sequence databases

Genome annotation databases

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsⁱ

• 100% Identity
• 90% Identity
• 50% Identity

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

<p>This subsection of the <a href="http://www.uniprot.org/manual/cross%5Freferences%5Fsection">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>Web resourcesⁱ

Sequence databases

3D structure databases

Protein-protein interaction databases

Chemistry databases

PTM databases

Genetic variation 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>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationⁱ

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousⁱ

Keywords - Technical termⁱ

Documents

1. Human chromosome 22
   Human chromosome 22: entries, gene names and cross-references to MIM
2. Human entries with genetic variants
   List of human entries with genetic variants
3. Human variants curated from literature reports
   Index of human variants curated from literature reports
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