ID   ATF1_HUMAN              Reviewed;         271 AA.
AC   P18846; P25168; Q9H4A8;
DT   01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1995, sequence version 2.
DT   25-JAN-2012, entry version 123.
DE   RecName: Full=Cyclic AMP-dependent transcription factor ATF-1;
DE            Short=cAMP-dependent transcription factor ATF-1;
DE   AltName: Full=Activating transcription factor 1;
DE   AltName: Full=Protein TREB36;
GN   Name=ATF1;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   MEDLINE=90316112; PubMed=2196176;
RA   Yoshimura T., Fujisawa J., Yoshida M.;
RT   "Multiple cDNA clones encoding nuclear proteins that bind to the tax-
RT   dependent enhancer of HTLV-1: all contain a leucine zipper structure
RT   and basic amino acid domain.";
RL   EMBO J. 9:2537-2542(1990).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   MEDLINE=92011588; PubMed=1655749;
RA   Rehfuss R.P., Walton K.M., Loriaux M.M., Goodman R.H.;
RT   "The cAMP-regulated enhancer-binding protein ATF-1 activates
RT   transcription in response to cAMP-dependent protein kinase A.";
RL   J. Biol. Chem. 266:18431-18434(1991).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Bone marrow;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 39-271.
RX   MEDLINE=90185187; PubMed=2516827;
RA   Hai T., Liu F., Coukos W.J., Green M.R.;
RT   "Transcription factor ATF cDNA clones: an extensive family of leucine
RT   zipper proteins able to selectively form DNA-binding heterodimers.";
RL   Genes Dev. 3:2083-2090(1989).
RN   [5]
RP   ERRATUM.
RA   Hai T., Liu F., Coukos W.J., Green M.R.;
RL   Genes Dev. 4:682-682(1990).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 22-246, CHROMOSOMAL TRANSLOCATION WITH
RP   FUS, AND ASSOCIATION WITH ANGIOMATOID FIBROUS HISTIOCYTOMA.
RX   PubMed=11063792; DOI=10.1016/S0165-4608(00)00237-5;
RA   Waters B.L., Panagopoulos I., Allen E.F.;
RT   "Genetic characterization of angiomatoid fibrous histiocytoma
RT   identifies fusion of the FUS and ATF-1 genes induced by a chromosomal
RT   translocation involving bands 12q13 and 16p11.";
RL   Cancer Genet. Cytogenet. 121:109-116(2000).
RN   [7]
RP   PHOSPHORYLATION AT SER-63, AND PHOSPHORYLATION BY CAMK1.
RX   MEDLINE=96216380; PubMed=8621702; DOI=10.1074/jbc.271.16.9503;
RA   Sun P., Lou L., Maurer R.A.;
RT   "Regulation of activating transcription factor-1 and the cAMP response
RT   element-binding protein by Ca2+/calmodulin-dependent protein kinases
RT   type I, II, and IV.";
RL   J. Biol. Chem. 271:3066-3073(1996).
RN   [8]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-198, AND MASS
RP   SPECTROMETRY.
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA   Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA   Elledge S.J., Gygi S.P.;
RT   "A quantitative atlas of mitotic phosphorylation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN   [9]
RP   CHROMOSOMAL TRANSLOCATION WITH EWSR1, AND ASSOCIATION WITH ANGIOMATOID
RP   FIBROUS HISTIOCYTOMA.
RX   PubMed=15884099; DOI=10.1002/gcc.20201;
RA   Hallor K.H., Mertens F., Jin Y., Meis-Kindblom J.M., Kindblom L.-G.,
RA   Behrendtz M., Kalen A., Mandahl N., Panagopoulos I.;
RT   "Fusion of the EWSR1 and ATF1 genes without expression of the MITF-M
RT   transcript in angiomatoid fibrous histiocytoma.";
RL   Genes Chromosomes Cancer 44:97-102(2005).
RN   [10]
RP   FUNCTION, PHOSPHORYLATION AT SER-63 BY CDK3, INTERACTION WITH CDK3,
RP   AND MUTAGENESIS OF SER-63.
RX   PubMed=18794154; DOI=10.1158/0008-5472.CAN-08-1137;
RA   Zheng D., Cho Y.-Y., Lau A.T.Y., Zhang J., Ma W.-Y., Bode A.M.,
RA   Dong Z.;
RT   "Cyclin-dependent kinase 3-mediated activating transcription factor 1
RT   phosphorylation enhances cell transformation.";
RL   Cancer Res. 68:7650-7660(2008).
RN   [11]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-198, AND MASS
RP   SPECTROMETRY.
RC   TISSUE=Leukemic T-cell;
RX   PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA   Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA   Rodionov V., Han D.K.;
RT   "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT   reveals system-wide modulation of protein-protein interactions.";
RL   Sci. Signal. 2:RA46-RA46(2009).
RN   [12]
RP   FUNCTION AS REPRESSOR, PHOSPHORYLATION AT SER-198 BY HIPK2, AND
RP   INTERACTION WITH HIPK2.
RX   PubMed=20980392; DOI=10.1242/jcs.073627;
RA   Hailemariam K., Iwasaki K., Huang B.W., Sakamoto K., Tsuji Y.;
RT   "Transcriptional regulation of ferritin and antioxidant genes by HIPK2
RT   under genotoxic stress.";
RL   J. Cell Sci. 123:3863-3871(2010).
CC   -!- FUNCTION: This protein binds the cAMP response element (CRE)
CC       (consensus: 5'-GTGACGT[AC][AG]-3'), a sequence present in many
CC       viral and cellular promoters. Binds to the Tax-responsive element
CC       (TRE) of HTLV-I. Mediates PKA-induced stimulation of CRE-reporter
CC       genes. Represses the expression of FTH1 and other antioxidant
CC       detoxification genes. Triggers cell proliferation and
CC       transformation.
CC   -!- SUBUNIT: Binds DNA as a dimer. Interacts with HIPK2 and CDK3.
CC   -!- SUBCELLULAR LOCATION: Nucleus.
CC   -!- PTM: Phosphorylated at Ser-198 by HIPK2 in response to genotoxic
CC       stress. This phosphorylation promotes transcription repression of
CC       FTH1 and other antioxidant detoxification genes. The CDK3-mediated
CC       phosphorylation at Ser-63 promotes its transactivation and
CC       transcriptional activities. Phosphorylated at Ser-63 by RPS6KA4
CC       and RPS6KA5 in response to mitogenic or stress stimuli.
CC   -!- DISEASE: Defects in ATF1 may be a cause of angiomatoid fibrous
CC       histiocytoma (AFH) [MIM:612160]. A distinct variant of malignant
CC       fibrous histiocytoma that typically occurs in children and
CC       adolescents and is manifest by nodular subcutaneous growth.
CC       Characteristic microscopic features include lobulated sheets of
CC       histiocyte-like cells intimately associated with areas of
CC       hemorrhage and cystic pseudovascular spaces, as well as a striking
CC       cuffing of inflammatory cells, mimicking a lymph node metastasis.
CC       Note=Chromosomal aberrations involving ATF1 are found in patients
CC       with angiomatoid fibrous histiocytoma. Translocation
CC       t(12;16)(q13;p11.2) with FUS generates a chimeric ATF1/FUS
CC       protein. Translocation t(12;22)(q13;q12) with EWSR1 generates a
CC       chimeric ATF1/EWSR1 protein.
CC   -!- SIMILARITY: Belongs to the bZIP family. ATF subfamily.
CC   -!- SIMILARITY: Contains 1 bZIP domain.
CC   -!- SIMILARITY: Contains 1 KID (kinase-inducible) domain.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=CAC15058.1; Type=Erroneous initiation;
CC   -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC       and Haematology;
CC       URL="http://atlasgeneticsoncology.org/Genes/ATF1ID81.html";
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DR   EMBL; X55544; CAA39150.1; -; Genomic_DNA.
DR   EMBL; BC029619; AAH29619.1; -; mRNA.
DR   EMBL; AJ295163; CAC15058.1; ALT_INIT; mRNA.
DR   IPI; IPI00002501; -.
DR   PIR; S12560; S12560.
DR   RefSeq; NP_005162.1; NM_005171.4.
DR   UniGene; Hs.648565; -.
DR   ProteinModelPortal; P18846; -.
DR   SMR; P18846; 49-76, 215-269.
DR   DIP; DIP-652N; -.
DR   IntAct; P18846; 2.
DR   MINT; MINT-142718; -.
DR   STRING; P18846; -.
DR   PhosphoSite; P18846; -.
DR   DMDM; 1168542; -.
DR   PRIDE; P18846; -.
DR   Ensembl; ENST00000262053; ENSP00000262053; ENSG00000123268.
DR   GeneID; 466; -.
DR   KEGG; hsa:466; -.
DR   UCSC; uc001rww.2; human.
DR   CTD; 466; -.
DR   GeneCards; GC12P051189; -.
DR   H-InvDB; HIX0010631; -.
DR   HGNC; HGNC:783; ATF1.
DR   HPA; CAB016222; -.
DR   MIM; 123803; gene.
DR   MIM; 612160; phenotype.
DR   neXtProt; NX_P18846; -.
DR   Orphanet; 97338; Melanoma of soft part.
DR   PharmGKB; PA25083; -.
DR   eggNOG; prNOG14008; -.
DR   GeneTree; ENSGT00390000008655; -.
DR   HOGENOM; HBG446032; -.
DR   HOVERGEN; HBG011077; -.
DR   InParanoid; P18846; -.
DR   OMA; DSHKSTT; -.
DR   OrthoDB; EOG4TB4C8; -.
DR   PhylomeDB; P18846; -.
DR   Pathway_Interaction_DB; p38alphabetadownstreampathway; Signaling mediated by p38-alpha and p38-beta.
DR   Reactome; REACT_111102; Signal Transduction.
DR   Reactome; REACT_6900; Immune System.
DR   NextBio; 1921; -.
DR   ArrayExpress; P18846; -.
DR   Bgee; P18846; -.
DR   CleanEx; HS_ATF1; -.
DR   Genevestigator; P18846; -.
DR   GermOnline; ENSG00000123268; Homo sapiens.
DR   GO; GO:0045087; P:innate immune response; TAS:Reactome.
DR   GO; GO:0002755; P:MyD88-dependent toll-like receptor signaling pathway; TAS:Reactome.
DR   GO; GO:0002756; P:MyD88-independent toll-like receptor signaling pathway; TAS:Reactome.
DR   GO; GO:0048011; P:nerve growth factor receptor signaling pathway; TAS:Reactome.
DR   GO; GO:0051403; P:stress-activated MAPK cascade; TAS:Reactome.
DR   GO; GO:0008063; P:Toll signaling pathway; TAS:Reactome.
DR   GO; GO:0034130; P:toll-like receptor 1 signaling pathway; TAS:Reactome.
DR   GO; GO:0034134; P:toll-like receptor 2 signaling pathway; TAS:Reactome.
DR   GO; GO:0034138; P:toll-like receptor 3 signaling pathway; TAS:Reactome.
DR   GO; GO:0034142; P:toll-like receptor 4 signaling pathway; TAS:Reactome.
DR   InterPro; IPR004827; bZIP.
DR   InterPro; IPR011616; bZIP_1.
DR   InterPro; IPR003102; Coactivator_CBP_pKID.
DR   InterPro; IPR001630; Leuzip_CREB.
DR   KO; K09053; -.
DR   Pfam; PF00170; bZIP_1; 1.
DR   Pfam; PF02173; pKID; 1.
DR   PRINTS; PR00041; LEUZIPPRCREB.
DR   SMART; SM00338; BRLZ; 1.
DR   PROSITE; PS50217; BZIP; 1.
DR   PROSITE; PS00036; BZIP_BASIC; 1.
DR   PROSITE; PS50953; KID; 1.
PE   1: Evidence at protein level;
KW   Activator; Chromosomal rearrangement; Complete proteome; DNA-binding;
KW   Nucleus; Phosphoprotein; Polymorphism; Reference proteome;
KW   Transcription; Transcription regulation.
FT   CHAIN         1    271       Cyclic AMP-dependent transcription factor
FT                                ATF-1.
FT                                /FTId=PRO_0000076575.
FT   DOMAIN       31     90       KID.
FT   DOMAIN      241    262       Leucine-zipper.
FT   DNA_BIND    215    235       Basic motif.
FT   SITE        110    110       Breakpoint for translocation to form
FT                                chimeric EWSR1/ATF1 protein.
FT   SITE        112    112       Breakpoint for translocation to form
FT                                chimeric FUS/ATF1 protein.
FT   MOD_RES      63     63       Phosphoserine; by CaMK1, CDK3, RPS6KA4
FT                                and RPS6KA5 (Probable).
FT   MOD_RES     198    198       Phosphoserine; by HIPK2.
FT   VARIANT     191    191       P -> A (in dbSNP:rs2230674).
FT                                /FTId=VAR_024382.
FT   MUTAGEN      63     63       S->A: Impaired CDK3-mediated
FT                                phosphorylation and altered
FT                                transactivation and transcriptional
FT                                activities.
FT   CONFLICT     55     55       H -> A (in Ref. 4; no nucleotide entry).
FT   CONFLICT    227    227       Missing (in Ref. 4; no nucleotide entry).
SQ   SEQUENCE   271 AA;  29233 MW;  BAFECBFFB244FCED CRC64;
     MEDSHKSTTS ETAPQPGSAV QGAHISHIAQ QVSSLSESEE SQDSSDSIGS SQKAHGILAR
     RPSYRKILKD LSSEDTRGRK GDGENSGVSA AVTSMSVPTP IYQTSSGQYI AIAPNGALQL
     ASPGTDGVQG LQTLTMTNSG STQQGTTILQ YAQTSDGQQI LVPSNQVVVQ TASGDMQTYQ
     IRTTPSATSL PQTVVMTSPV TLTSQTTKTD DPQLKREIRL MKNREAAREC RRKKKEYVKC
     LENRVAVLEN QNKTLIEELK TLKDLYSNKS V
//