Reviewed,
UniProtKB/Swiss-Prot P15336 (ATF2_HUMAN)
Last modified
June 16, 2009.
Version 107.
History...
Clusters with 100%,
90%,
50% identity |
Documents (6) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Cyclic AMP-dependent transcription factor ATF-2 Short name=cAMP-dependent transcription factor ATF-2 Alternative name(s): Activating transcription factor 2 cAMP response element-binding protein CRE-BP1 HB16 Cyclic AMP-responsive element-binding protein 2 Short name=cAMP-responsive element-binding protein 2 Short name=CREB-2 | ||||
| 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 | 505 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Transcriptional activator, probably constitutive, which binds to the cAMP-responsive element (CRE) (consensus: 5'-GTGACGT[AC][AG]-3'), a sequence present in many viral and cellular promoters. Interaction with JUN redirects JUN to bind to CRES preferentially over the 12-O-tetradecanoylphorbol-13-acetate response elements (TRES) as part of an ATF2-c-Jun complex. |
| Subunit structure | Binds DNA as a dimer and can form a homodimer in the absence of DNA. Can form a heterodimer with JUN. Interacts with SMAD3 and SMAD4. Binds through its N-terminal region to UTF1 which acts as a coactivator of ATF2 transcriptional activity. Ref.5 |
| Subcellular location | |
| Tissue specificity | Abundant expression seen in the brain. |
| Post-translational modification | Phosphorylation of Thr-69 and Thr-71 by MAPK14 causes increased transcriptional activity. Also phosphorylated and activated by JNK. Ref.6 Ref.7 Ref.8 Ref.9 |
| Sequence similarities | Belongs to the bZIP family. ATF subfamily. Contains 1 bZIP domain. Contains 1 C2H2-type zinc finger. |
| Caution | It is uncertain whether Met-1 or Met-19 is the initiator. |
Ontologies
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| MAPK11 | Q15759 | 1 | EBI-1170906,EBI-298304 | |
| MAPK13 | O15264 | 1 | EBI-1170906,EBI-2116951 | |
| MAPK8 | P45983-1 | 1 | EBI-1170906,EBI-288687 | |
| MAPK9 | P45984-1 | 1 | EBI-1170906,EBI-713586 | |
| pmk-1 | Q17446 | 1 | EBI-1170906,EBI-312987 | From a different organism. |
| VRK1 | Q99986 | 1 | EBI-1170906,EBI-1769146 |
Alternative products
| This entry describes 2 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: P15336-1) 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 2 (identifier: P15336-2) The sequence of this isoform differs from the canonical sequence as follows: 1-176: Missing. 177-185: TSSDSSVII → MSTAYFQMM |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||||||||||
Molecule processing | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 505 | 505 | Cyclic AMP-dependent transcription factor ATF-2 | PRO_0000076577 | |||||||||||||
Regions | |||||||||||||||||
| Domain | 380 – 408 | 29 | Leucine-zipper | ||||||||||||||
| Zinc finger | 25 – 49 | 25 | C2H2-type | ||||||||||||||
| DNA binding | 351 – 374 | 24 | Basic motif | ||||||||||||||
Amino acid modifications | |||||||||||||||||
| Modified residue | 69 | 1 | Phosphothreonine; by MAPK14 Ref.7 Ref.9 | ||||||||||||||
| Modified residue | 71 | 1 | Phosphothreonine; by MAPK14 Ref.7 Ref.9 | ||||||||||||||
| Modified residue | 112 | 1 | Phosphoserine Ref.6 Ref.7 Ref.9 | ||||||||||||||
| Modified residue | 328 | 1 | Phosphoserine Ref.8 | ||||||||||||||
Natural variations | |||||||||||||||||
| Alternative sequence | 1 – 176 | 176 | Missing in isoform 2. | VSP_000587 | |||||||||||||
| Alternative sequence | 177 – 185 | 9 | TSSDSSVII → MSTAYFQMM in isoform 2. | VSP_000588 | |||||||||||||
| Natural variant | 352 | 1 | D → H in a breast cancer sample; somatic mutation. Ref.11 | VAR_035999 | |||||||||||||
Experimental info | |||||||||||||||||
| Sequence conflict | 209 | 1 | V → L in AAB64017. Ref.2 | ||||||||||||||
| Sequence conflict | 223 | 1 | N → S in CAA33886. Ref.1 | ||||||||||||||
| Sequence conflict | 311 | 1 | R → L in AAB64017. Ref.2 | ||||||||||||||
Secondary structure | |||||||||||||||||
Helix Strand Turn | |||||||||||||||||
| Turn | 30 – 32 | 3 | |||||||||||||||
| Beta strand | 35 – 38 | 4 | |||||||||||||||
| Helix | 39 – 50 | 12 | |||||||||||||||
| Turn | 51 – 55 | 5 | |||||||||||||||
| Helix | 355 – 412 | 58 | |||||||||||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Leucine zipper structure of the protein CRE-BP1 binding to the cyclic AMP response element in brain." Maekawa T., Sakura H., Kanei-Ishii C., Sudo T., Yoshimura T., Fujisawa J., Yoshida M., Ishii S. EMBO J. 8:2023-2028(1989) [PubMed: 2529117] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Fetal brain. |
| [2] | "Identification of a novel, spliced variant of CREB that is preferentially expressed in the thymus." Yang L., Lanier E.R., Kraig E. J. Immunol. 158:2522-2525(1997) [PubMed: 9058782] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Thymus. |
| [3] | "Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. Wilson R.K.Nature 434:724-731(2005) [PubMed: 15815621] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [4] | "A cDNA for a human cyclic AMP response element-binding protein which is distinct from CREB and expressed preferentially in brain." Kara C.J., Liou H.-C., Ivashkiv L.B., Glimcher L.H. Mol. Cell. Biol. 10:1347-1357(1990) [PubMed: 2320002] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 211-505 (ISOFORMS 1/2). |
| [5] | "Characterization of functional domains of an embryonic stem cell coactivator UTF1 which are conserved and essential for potentiation of ATF-2 activity." Fukushima A., Okuda A., Nishimoto M., Seki N., Hori T.A., Muramatsu M. J. Biol. Chem. 273:25840-25849(1998) [PubMed: 9748258] [Abstract] Cited for: INTERACTION WITH UTF1. |
| [6] | "Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-112, MASS SPECTROMETRY. Tissue: Epithelium. |
| [7] | "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-69; THR-71 AND SER-112, MASS SPECTROMETRY. Tissue: Epithelium. |
| [8] | "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed: 18220336] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-328, MASS SPECTROMETRY. |
| [9] | "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 THR-69; THR-71 AND SER-112, MASS SPECTROMETRY. |
| [10] | "Solution structure of the transactivation domain of ATF-2 comprising a zinc finger-like subdomain and a flexible subdomain." Nagadoi A., Nakazawa K., Uda H., Okuno K., Maekawa T., Ishii S., Nishimura Y. J. Mol. Biol. 287:593-607(1999) [PubMed: 10092462] [Abstract] Cited for: STRUCTURE BY NMR OF 19-56. |
| [11] | "The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. Velculescu V.E.Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] HIS-352. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| X15875 mRNA. Translation: CAA33886.1. U16028 mRNA. Translation: AAB64017.1. AC131958 Genomic DNA. Translation: AAX88876.1. AC074291 Genomic DNA. Translation: AAY15004.1. AC007435 Genomic DNA. No translation available. AC096649 Genomic DNA. No translation available. M31630 mRNA. Translation: AAA35951.1. | |||||||||||||||||||
| IPI | IPI00234446. IPI00748604. | ||||||||||||||||||
| PIR | S05380. | ||||||||||||||||||
| RefSeq | NP_001871.2. | ||||||||||||||||||
| UniGene | Hs.592510 | ||||||||||||||||||
3D structure databases | |||||||||||||||||||
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| ModBase | Search... | ||||||||||||||||||
Protein-protein interaction databases | |||||||||||||||||||
| DIP | DIP:632N. | ||||||||||||||||||
| IntAct | P15336. 12 interactions. | ||||||||||||||||||
PTM databases | |||||||||||||||||||
| PhosphoSite | P15336. | ||||||||||||||||||
Proteomic databases | |||||||||||||||||||
| PRIDE | P15336. | ||||||||||||||||||
Genome annotation databases | |||||||||||||||||||
| Ensembl | ENSG00000115966. Homo sapiens. [Contig view] | ||||||||||||||||||
| GeneID | 1386. | ||||||||||||||||||
| KEGG | hsa:1386. | ||||||||||||||||||
Organism-specific databases | |||||||||||||||||||
| GeneCards | GC02M175645. | ||||||||||||||||||
| HGNC | HGNC:784. ATF2. | ||||||||||||||||||
| MIM | 123811. gene. | ||||||||||||||||||
| PharmGKB | PA25084. | ||||||||||||||||||
| GenAtlas | Search... | ||||||||||||||||||
Phylogenomic databases | |||||||||||||||||||
| HOGENOM | P15336. | ||||||||||||||||||
| HOVERGEN | P15336. | ||||||||||||||||||
| OMA | P15336. QNEVTLL. | ||||||||||||||||||
Enzyme and pathway databases | |||||||||||||||||||
| Pathway_Interaction_DB | il12_2pathway. IL12-mediated signaling events. smad2_3nuclearpathway. Regulation of nuclear SMAD2/3 signaling. p38alphabetadownstreampathway. Signaling mediated by p38-alpha and p38-beta. | ||||||||||||||||||
| Reactome | REACT_6900. Signaling in Immune system. | ||||||||||||||||||
Gene expression databases | |||||||||||||||||||
| ArrayExpress | P15336. | ||||||||||||||||||
| Bgee | P15336. | ||||||||||||||||||
| CleanEx | HS_ATF2. | ||||||||||||||||||
| GermOnline | ENSG00000115966. Homo sapiens. | ||||||||||||||||||
Family and domain databases | |||||||||||||||||||
| InterPro | IPR011616. bZIP_1. IPR004827. TF_bZIP. IPR016378. TF_cAMP-dep. IPR007087. Znf_C2H2. IPR015880. Znf_C2H2-like. [Graphical view] | ||||||||||||||||||
| Pfam | PF00170. bZIP_1. 1 hit. PF00096. zf-C2H2. 1 hit. [Graphical view] | ||||||||||||||||||
| PIRSF | PIRSF003153. ATF2_CRE-BP1. 1 hit. | ||||||||||||||||||
| SMART | SM00338. BRLZ. 1 hit. SM00355. ZnF_C2H2. 1 hit. [Graphical view] | ||||||||||||||||||
| PROSITE | PS50217. BZIP. 1 hit. PS00036. BZIP_BASIC. 1 hit. PS00028. ZINC_FINGER_C2H2_1. 1 hit. PS50157. ZINC_FINGER_C2H2_2. 1 hit. [Graphical view] | ||||||||||||||||||
| ProtoNet | Search... | ||||||||||||||||||
Other Resources | |||||||||||||||||||
| NextBio | 5631. | ||||||||||||||||||
| SOURCE | Search... | ||||||||||||||||||
Entry information
| Entry name | ATF2_HUMAN | ||||||||
| Accession | Primary (citable) accession number: P15336 Secondary accession number(s): Q13000, Q4ZFU9, Q53RY2 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| Human chromosome 2 Human chromosome 2: 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 |
| PDB cross-references Index of Protein Data Bank (PDB) cross-references |
| SIMILARITY comments Index of protein domains and families |

Clusters with


