P18846 (ATF1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names 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

Name:

ATF1

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	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.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

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Chromosomal rearrangement Polymorphism
Ligand	DNA-binding
Molecular function	Activator
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	MyD88-dependent toll-like receptor signaling pathway Traceable author statement. Source: Reactome MyD88-independent toll-like receptor signaling pathway Traceable author statement. Source: Reactome Toll signaling pathway Traceable author statement. Source: Reactome innate immune response Traceable author statement. Source: Reactome nerve growth factor receptor signaling pathway Traceable author statement. Source: Reactome stress-activated MAPK cascade Traceable author statement. Source: Reactome toll-like receptor 1 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
Complete GO annotation...

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

	Sequence		Length	Mass (Da)
	P18846 [UniParc]. Last modified November 1, 1995. Version 2. Checksum: BAFECBFFB244FCED	FASTA	271	29,233
	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

References

	« Hide 'large scale' referencesShow '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.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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

Integrated into UniProtKB/Swiss-Prot:	November 1, 1990
Last sequence update:	November 1, 1995
Last modified:	January 25, 2012
This is version 123 of the entry and version 2 of the sequence. [Complete history]

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.