P18846 (ATF1_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
January 25, 2012.
Version 123.
History...
Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended name: Cyclic AMP-dependent transcription factor ATF-1 Short name=cAMP-dependent transcription factor ATF-1 Alternative name(s): Activating transcription factor 1 Protein TREB36 | ||
| Gene names |
| ||
| Organism | Homo sapiens (Human) | ||
| Taxonomic identifier | 9606 [NCBI] | ||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 271 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence at protein level |
General annotation (Comments)
| Function | This protein binds the cAMP response element (CRE) (consensus: 5'-GTGACGT[AC][AG]-3'), a sequence present in many viral and cellular promoters. Binds to the Tax-responsive element (TRE) of HTLV-I. Mediates PKA-induced stimulation of CRE-reporter genes. Represses the expression of FTH1 and other antioxidant detoxification genes. Triggers cell proliferation and transformation. Ref.10 Ref.12 |
| Subunit structure | Binds DNA as a dimer. Interacts with HIPK2 and CDK3. Ref.10 Ref.12 |
| Subcellular location | |
| Post-translational modification | Phosphorylated at Ser-198 by HIPK2 in response to genotoxic stress. This phosphorylation promotes transcription repression of FTH1 and other antioxidant detoxification genes. The CDK3-mediated phosphorylation at Ser-63 promotes its transactivation and transcriptional activities. Phosphorylated at Ser-63 by RPS6KA4 and RPS6KA5 in response to mitogenic or stress stimuli. Ref.7 Ref.8 Ref.10 Ref.11 Ref.12 |
| Involvement in disease | Defects in ATF1 may be a cause of angiomatoid fibrous histiocytoma (AFH) [MIM:612160]. A distinct variant of malignant fibrous histiocytoma that typically occurs in children and adolescents and is manifest by nodular subcutaneous growth. Characteristic microscopic features include lobulated sheets of histiocyte-like cells intimately associated with areas of hemorrhage and cystic pseudovascular spaces, as well as a striking cuffing of inflammatory cells, mimicking a lymph node metastasis. Note=Chromosomal aberrations involving ATF1 are found in patients with angiomatoid fibrous histiocytoma. Translocation t(12;16)(q13;p11.2) with FUS generates a chimeric ATF1/FUS protein. Translocation t(12;22)(q13;q12) with EWSR1 generates a chimeric ATF1/EWSR1 protein. |
| Sequence similarities | Belongs to the bZIP family. ATF subfamily. Contains 1 bZIP domain. Contains 1 KID (kinase-inducible) domain. |
| Sequence caution | The sequence CAC15058.1 differs from that shown. Reason: Erroneous initiation. |
Ontologies
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 271 | 271 | Cyclic AMP-dependent transcription factor ATF-1 | PRO_0000076575 | |||||
Regions | |||||||||
| Domain | 31 – 90 | 60 | KID | ||||||
| Domain | 241 – 262 | 22 | Leucine-zipper | ||||||
| DNA binding | 215 – 235 | 21 | Basic motif | ||||||
Sites | |||||||||
| Site | 110 | 1 | Breakpoint for translocation to form chimeric EWSR1/ATF1 protein | ||||||
| Site | 112 | 1 | Breakpoint for translocation to form chimeric FUS/ATF1 protein | ||||||
Amino acid modifications | |||||||||
| Modified residue | 63 | 1 | Phosphoserine; by CaMK1, CDK3, RPS6KA4 and RPS6KA5 Probable | ||||||
| Modified residue | 198 | 1 | Phosphoserine; by HIPK2 Ref.8 Ref.11 Ref.12 | ||||||
Natural variations | |||||||||
| Natural variant | 191 | 1 | P → A. Corresponds to variant rs2230674 [ dbSNP | Ensembl ]. | VAR_024382 | |||||
Experimental info | |||||||||
| Mutagenesis | 63 | 1 | S → A: Impaired CDK3-mediated phosphorylation and altered transactivation and transcriptional activities. Ref.10 | ||||||
| Sequence conflict | 55 | 1 | H → A no nucleotide entry Ref.4 | ||||||
| Sequence conflict | 227 | 1 | Missing no nucleotide entry Ref.4 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Multiple cDNA clones encoding nuclear proteins that bind to the tax-dependent enhancer of HTLV-1: all contain a leucine zipper structure and basic amino acid domain." Yoshimura T., Fujisawa J., Yoshida M. EMBO J. 9:2537-2542(1990) [PubMed: 2196176] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. |
| [2] | "The cAMP-regulated enhancer-binding protein ATF-1 activates transcription in response to cAMP-dependent protein kinase A." Rehfuss R.P., Walton K.M., Loriaux M.M., Goodman R.H. J. Biol. Chem. 266:18431-18434(1991) [PubMed: 1655749] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. |
| [3] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Bone marrow. |
| [4] | "Transcription factor ATF cDNA clones: an extensive family of leucine zipper proteins able to selectively form DNA-binding heterodimers." Hai T., Liu F., Coukos W.J., Green M.R. Genes Dev. 3:2083-2090(1989) [PubMed: 2516827] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 39-271. |
| [5] | Erratum Hai T., Liu F., Coukos W.J., Green M.R. Genes Dev. 4:682-682(1990) |
| [6] | "Genetic characterization of angiomatoid fibrous histiocytoma identifies fusion of the FUS and ATF-1 genes induced by a chromosomal translocation involving bands 12q13 and 16p11." Waters B.L., Panagopoulos I., Allen E.F. Cancer Genet. Cytogenet. 121:109-116(2000) [PubMed: 11063792] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 22-246, CHROMOSOMAL TRANSLOCATION WITH FUS, ASSOCIATION WITH ANGIOMATOID FIBROUS HISTIOCYTOMA. |
| [7] | "Regulation of activating transcription factor-1 and the cAMP response element-binding protein by Ca2+/calmodulin-dependent protein kinases type I, II, and IV." Sun P., Lou L., Maurer R.A. J. Biol. Chem. 271:3066-3073(1996) [PubMed: 8621702] [Abstract] Cited for: PHOSPHORYLATION AT SER-63, PHOSPHORYLATION BY CAMK1. |
| [8] | "A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-198, MASS SPECTROMETRY. Tissue: Cervix carcinoma. |
| [9] | "Fusion of the EWSR1 and ATF1 genes without expression of the MITF-M transcript in angiomatoid fibrous histiocytoma." Hallor K.H., Mertens F., Jin Y., Meis-Kindblom J.M., Kindblom L.-G., Behrendtz M., Kalen A., Mandahl N., Panagopoulos I. Genes Chromosomes Cancer 44:97-102(2005) [PubMed: 15884099] [Abstract] Cited for: CHROMOSOMAL TRANSLOCATION WITH EWSR1, ASSOCIATION WITH ANGIOMATOID FIBROUS HISTIOCYTOMA. |
| [10] | "Cyclin-dependent kinase 3-mediated activating transcription factor 1 phosphorylation enhances cell transformation." Zheng D., Cho Y.-Y., Lau A.T.Y., Zhang J., Ma W.-Y., Bode A.M., Dong Z. Cancer Res. 68:7650-7660(2008) [PubMed: 18794154] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION AT SER-63 BY CDK3, INTERACTION WITH CDK3, MUTAGENESIS OF SER-63. |
| [11] | "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-198, MASS SPECTROMETRY. Tissue: Leukemic T-cell. |
| [12] | "Transcriptional regulation of ferritin and antioxidant genes by HIPK2 under genotoxic stress." Hailemariam K., Iwasaki K., Huang B.W., Sakamoto K., Tsuji Y. J. Cell Sci. 123:3863-3871(2010) [PubMed: 20980392] [Abstract] Cited for: FUNCTION AS REPRESSOR, PHOSPHORYLATION AT SER-198 BY HIPK2, INTERACTION WITH HIPK2. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | X55544 Genomic DNA. Translation: CAA39150.1. BC029619 mRNA. Translation: AAH29619.1. AJ295163 mRNA. Translation: CAC15058.1. Different initiation. |
| IPI | IPI00002501. |
| PIR | S12560. |
| RefSeq | NP_005162.1. NM_005171.4. |
| UniGene | Hs.648565. |
3D structure databases | |
| ProteinModelPortal | P18846. |
| SMR | P18846. Positions 49-76, 215-269. |
| ModBase | Search... |
Protein-protein interaction databases | |
| DIP | DIP-652N. |
| IntAct | P18846. 2 interactions. |
| MINT | MINT-142718. |
| STRING | P18846. |
PTM databases | |
| PhosphoSite | P18846. |
Polymorphism databases | |
| DMDM | 1168542. |
Proteomic databases | |
| PRIDE | P18846. |
Protocols and materials databases | |
| StructuralBiologyKnowledgebase | Search... |
Genome annotation databases | |
| Ensembl | ENST00000262053; ENSP00000262053; ENSG00000123268. |
| GeneID | 466. |
| KEGG | hsa:466. |
| UCSC | uc001rww.2. human. |
Organism-specific databases | |
| CTD | 466. |
| GeneCards | GC12P051189. |
| H-InvDB | HIX0010631. |
| HGNC | HGNC:783. ATF1. |
| HPA | CAB016222. |
| MIM | 123803. gene. 612160. phenotype. |
| neXtProt | NX_P18846. |
| Orphanet | 97338. Melanoma of soft part. |
| PharmGKB | PA25083. |
| GenAtlas | Search... |
Phylogenomic databases | |
| eggNOG | prNOG14008. |
| GeneTree | ENSGT00390000008655. |
| HOGENOM | HBG446032. |
| HOVERGEN | HBG011077. |
| InParanoid | P18846. |
| OMA | DSHKSTT. |
| OrthoDB | EOG4TB4C8. |
| PhylomeDB | P18846. |
Enzyme and pathway databases | |
| Pathway_Interaction_DB | p38alphabetadownstreampathway. Signaling mediated by p38-alpha and p38-beta. |
| Reactome | REACT_111102. Signal Transduction. REACT_6900. Immune System. |
Gene expression databases | |
| ArrayExpress | P18846. |
| Bgee | P18846. |
| CleanEx | HS_ATF1. |
| Genevestigator | P18846. |
| GermOnline | ENSG00000123268. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR004827. bZIP. IPR011616. bZIP_1. IPR003102. Coactivator_CBP_pKID. IPR001630. Leuzip_CREB. [Graphical view] |
| KO | K09053. |
| Pfam | PF00170. bZIP_1. 1 hit. PF02173. pKID. 1 hit. [Graphical view] |
| PRINTS | PR00041. LEUZIPPRCREB. |
| SMART | SM00338. BRLZ. 1 hit. [Graphical view] |
| PROSITE | PS50217. BZIP. 1 hit. PS00036. BZIP_BASIC. 1 hit. PS50953. KID. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other | |
| NextBio | 1921. |
| SOURCE | Search... |
Entry information
| Entry name | ATF1_HUMAN | ||||||||
| Accession | Primary (citable) accession number: P18846 Secondary accession number(s): P25168, Q9H4A8 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation program | Chordata Protein Annotation Program | ||||||||
| Disclaimer | Any 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
| Human chromosome 12 Human chromosome 12: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

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