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P18846 (ATF1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 145. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
Name:ATF1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length271 AA.
Sequence statusComplete.
Protein existenceEvidence 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.9 Ref.12

Subunit structure

Binds DNA as a dimer. Interacts with HIPK2 and CDK3. Ref.9 Ref.12

Subcellular location

Nucleus.

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.9 Ref.12

Involvement in disease

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: The gene represented in this entry may be involved in disease pathogenesis. 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 (basic-leucine zipper) domain.

Contains 1 KID (kinase-inducible) domain.

Sequence caution

The sequence CAC15058.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityChromosomal rearrangement
Polymorphism
   LigandDNA-binding
   Molecular functionActivator
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processMyD88-dependent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

MyD88-independent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

TRIF-dependent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

cellular protein complex assembly

Inferred from electronic annotation. Source: Ensembl

innate immune response

Traceable author statement. Source: Reactome

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

positive regulation of DNA replication

Inferred from electronic annotation. Source: Ensembl

positive regulation of neuron projection development

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

response to cobalt ion

Inferred from electronic annotation. Source: Ensembl

response to organic cyclic compound

Inferred from electronic annotation. Source: Ensembl

stress-activated MAPK cascade

Traceable author statement. Source: Reactome

toll-like receptor 10 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 3 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 4 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 5 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 9 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor TLR1:TLR2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor TLR6:TLR2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

   Cellular_componentnucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay. Source: HPA

transcription factor complex

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionRNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity

Inferred from electronic annotation. Source: Ensembl

sequence-specific DNA binding

Inferred from electronic annotation. Source: Ensembl

sequence-specific DNA binding transcription factor activity

Traceable author statement Ref.1PubMed 8401579. Source: ProtInc

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

P03259-22EBI-852794,EBI-7225021From a different organism.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 271271Cyclic AMP-dependent transcription factor ATF-1
PRO_0000076575

Regions

Domain31 – 9060KID
Domain213 – 27159bZIP
Region215 – 23925Basic motif By similarity
Region241 – 26222Leucine-zipper By similarity

Sites

Site1101Breakpoint for translocation to form chimeric EWSR1/ATF1 protein
Site1121Breakpoint for translocation to form chimeric FUS/ATF1 protein

Amino acid modifications

Modified residue631Phosphoserine; by CaMK1, CDK3, RPS6KA4 and RPS6KA5 Probable
Modified residue1981Phosphoserine; by HIPK2 Ref.10 Ref.11 Ref.12

Natural variations

Natural variant1911P → A.
Corresponds to variant rs2230674 [ dbSNP | Ensembl ].
VAR_024382

Experimental info

Mutagenesis631S → A: Impaired CDK3-mediated phosphorylation and altered transactivation and transcriptional activities. Ref.9
Sequence conflict551H → A no nucleotide entry Ref.4
Sequence conflict2271Missing no nucleotide entry Ref.4

Sequences

Sequence LengthMass (Da)Tools
P18846 [UniParc].

Last modified November 1, 1995. Version 2.
Checksum: BAFECBFFB244FCED

FASTA27129,233
        10         20         30         40         50         60 
MEDSHKSTTS ETAPQPGSAV QGAHISHIAQ QVSSLSESEE SQDSSDSIGS SQKAHGILAR 

        70         80         90        100        110        120 
RPSYRKILKD LSSEDTRGRK GDGENSGVSA AVTSMSVPTP IYQTSSGQYI AIAPNGALQL 

       130        140        150        160        170        180 
ASPGTDGVQG LQTLTMTNSG STQQGTTILQ YAQTSDGQQI LVPSNQVVVQ TASGDMQTYQ 

       190        200        210        220        230        240 
IRTTPSATSL PQTVVMTSPV TLTSQTTKTD DPQLKREIRL MKNREAAREC RRKKKEYVKC 

       250        260        270 
LENRVAVLEN QNKTLIEELK TLKDLYSNKS V 

« Hide

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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-63, PHOSPHORYLATION BY CAMK1.
[8]"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] [Europe PMC] [Abstract]
Cited for: CHROMOSOMAL TRANSLOCATION WITH EWSR1, ASSOCIATION WITH ANGIOMATOID FIBROUS HISTIOCYTOMA.
[9]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION, PHOSPHORYLATION AT SER-63 BY CDK3, INTERACTION WITH CDK3, MUTAGENESIS OF SER-63.
[10]"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] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-198, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[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] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-198, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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] [Europe PMC] [Abstract]
Cited for: FUNCTION AS REPRESSOR, PHOSPHORYLATION AT SER-198 BY HIPK2, INTERACTION WITH HIPK2.
[13]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
+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.
PIRS12560.
RefSeqNP_005162.1. NM_005171.4.
UniGeneHs.648565.

3D structure databases

ProteinModelPortalP18846.
SMRP18846. Positions 49-76, 215-269.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106956. 12 interactions.
DIPDIP-652N.
IntActP18846. 3 interactions.
MINTMINT-142718.
STRING9606.ENSP00000262053.

Chemistry

BindingDBP18846.
ChEMBLCHEMBL3255.

PTM databases

PhosphoSiteP18846.

Polymorphism databases

DMDM1168542.

Proteomic databases

PaxDbP18846.
PRIDEP18846.

Protocols and materials databases

DNASU466.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000262053; ENSP00000262053; ENSG00000123268.
GeneID466.
KEGGhsa:466.
UCSCuc001rww.4. human.

Organism-specific databases

CTD466.
GeneCardsGC12P051189.
HGNCHGNC:783. ATF1.
HPACAB016222.
HPA055069.
HPA055406.
MIM123803. gene.
612160. phenotype.
neXtProtNX_P18846.
Orphanet97338. Melanoma of soft part.
PharmGKBPA25083.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG255464.
HOGENOMHOG000007365.
HOVERGENHBG011077.
InParanoidP18846.
KOK09053.
OMAHIAQQMS.
PhylomeDBP18846.
TreeFamTF106464.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_6782. TRAF6 Mediated Induction of proinflammatory cytokines.
REACT_6900. Immune System.
SignaLinkP18846.

Gene expression databases

ArrayExpressP18846.
BgeeP18846.
CleanExHS_ATF1.
GenevestigatorP18846.

Family and domain databases

InterProIPR004827. bZIP.
IPR003102. Coactivator_CBP_pKID.
IPR001630. Leuzip_CREB.
[Graphical view]
PfamPF00170. bZIP_1. 1 hit.
PF02173. pKID. 1 hit.
[Graphical view]
PRINTSPR00041. LEUZIPPRCREB.
SMARTSM00338. BRLZ. 1 hit.
[Graphical view]
PROSITEPS50217. BZIP. 1 hit.
PS00036. BZIP_BASIC. 1 hit.
PS50953. KID. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSATF1. human.
GeneWikiATF1.
GenomeRNAi466.
NextBio1921.
PROP18846.
SOURCESearch...

Entry information

Entry nameATF1_HUMAN
AccessionPrimary (citable) accession number: P18846
Secondary accession number(s): P25168, Q9H4A8
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1990
Last sequence update: November 1, 1995
Last modified: April 16, 2014
This is version 145 of the entry and version 2 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

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 12

Human chromosome 12: entries, gene names and cross-references to MIM