LOCUS       NM_182810               1419 bp    mRNA    linear   PRI 12-NOV-2024
DEFINITION  Homo sapiens activating transcription factor 4 (ATF4), transcript
            variant 2, mRNA.
ACCESSION   NM_182810
VERSION     NM_182810.3
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 1419)
  AUTHORS   Zheng,T., Zhang,D., Fu,Q., Wang,M., Cheng,Z., Cao,Y., Wang,L.,
            Liu,J. and Zhao,Y.
  TITLE     DNA methylation-driven gene FAM3D promotes colorectal cancer growth
            via the ATF4-SESN2-mTORC1 pathway
  JOURNAL   Aging (Albany NY) 16 (19), 12866-12892 (2024)
   PUBMED   39388305
  REMARK    GeneRIF: DNA methylation-driven gene FAM3D promotes colorectal
            cancer growth via the ATF4-SESN2-mTORC1 pathway.
REFERENCE   2  (bases 1 to 1419)
  AUTHORS   Xue,T., Wang,X., Pan,X., Liu,M. and Xu,F.
  TITLE     PTX promotes breast cancer migration and invasion by recruiting
            ATF4 to upregulate FGF19
  JOURNAL   Cell Signal 122, 111309 (2024)
   PUBMED   39053672
  REMARK    GeneRIF: PTX promotes breast cancer migration and invasion by
            recruiting ATF4 to upregulate FGF19.
REFERENCE   3  (bases 1 to 1419)
  AUTHORS   Zhang,B., Wu,Y., Zhou,C., Xie,J., Zhang,Y., Yang,X., Xiao,J.,
            Wang,D.W., Shan,C., Zhou,X., Xiang,Y. and Yang,B.
  TITLE     Hyperactivation of ATF4/TGF-beta1 signaling contributes to the
            progressive cardiac fibrosis in Arrhythmogenic cardiomyopathy
            caused by DSG2 Variant
  JOURNAL   BMC Med 22 (1), 361 (2024)
   PUBMED   39227800
  REMARK    GeneRIF: Hyperactivation of ATF4/TGF-beta1 signaling contributes to
            the progressive cardiac fibrosis in Arrhythmogenic cardiomyopathy
            caused by DSG2 Variant.
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 1419)
  AUTHORS   Chen,J., Huang,X., Zhang,S. and Zhu,X.
  TITLE     ATF4 inhibits tumor development and mediates p-GCN2/ASNS
            upregulation in colon cancer
  JOURNAL   Sci Rep 14 (1), 13042 (2024)
   PUBMED   38844625
  REMARK    GeneRIF: ATF4 inhibits tumor development and mediates p-GCN2/ASNS
            upregulation in colon cancer.
            Publication Status: Online-Only
REFERENCE   5  (bases 1 to 1419)
  AUTHORS   Andreev,D.E., O'Connor,P.B., Fahey,C., Kenny,E.M., Terenin,I.M.,
            Dmitriev,S.E., Cormican,P., Morris,D.W., Shatsky,I.N. and
            Baranov,P.V.
  TITLE     Translation of 5' leaders is pervasive in genes resistant to eIF2
            repression
  JOURNAL   Elife 4, e03971 (2015)
   PUBMED   25621764
  REMARK    Publication Status: Online-Only
REFERENCE   6  (bases 1 to 1419)
  AUTHORS   Chan,C.P., Kok,K.H., Tang,H.M., Wong,C.M. and Jin,D.Y.
  TITLE     Internal ribosome entry site-mediated translational regulation of
            ATF4 splice variant in mammalian unfolded protein response
  JOURNAL   Biochim Biophys Acta 1833 (10), 2165-2175 (2013)
   PUBMED   23665047
REFERENCE   7  (bases 1 to 1419)
  AUTHORS   Vattem,K.M. and Wek,R.C.
  TITLE     Reinitiation involving upstream ORFs regulates ATF4 mRNA
            translation in mammalian cells
  JOURNAL   Proc Natl Acad Sci U S A 101 (31), 11269-11274 (2004)
   PUBMED   15277680
REFERENCE   8  (bases 1 to 1419)
  AUTHORS   Karpinski,B.A., Morle,G.D., Huggenvik,J., Uhler,M.D. and
            Leiden,J.M.
  TITLE     Molecular cloning of human CREB-2: an ATF/CREB transcription factor
            that can negatively regulate transcription from the cAMP response
            element
  JOURNAL   Proc Natl Acad Sci U S A 89 (11), 4820-4824 (1992)
   PUBMED   1534408
REFERENCE   9  (bases 1 to 1419)
  AUTHORS   Nishizawa,M. and Nagata,S.
  TITLE     cDNA clones encoding leucine-zipper proteins which interact with
            G-CSF gene promoter element 1-binding protein
  JOURNAL   FEBS Lett 299 (1), 36-38 (1992)
   PUBMED   1371974
REFERENCE   10 (bases 1 to 1419)
  AUTHORS   Hai,T. and Curran,T.
  TITLE     Cross-family dimerization of transcription factors Fos/Jun and
            ATF/CREB alters DNA binding specificity
  JOURNAL   Proc Natl Acad Sci U S A 88 (9), 3720-3724 (1991)
   PUBMED   1827203
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AL022312.7.
            
            On Oct 29, 2020 this sequence version replaced NM_182810.2.
            
            Summary: This gene encodes a transcription factor that was
            originally identified as a widely expressed mammalian DNA binding
            protein that could bind a tax-responsive enhancer element in the
            LTR of HTLV-1. The encoded protein was also isolated and
            characterized as the cAMP-response element binding protein 2
            (CREB-2). The protein encoded by this gene belongs to a family of
            DNA-binding proteins that includes the AP-1 family of transcription
            factors, cAMP-response element binding proteins (CREBs) and
            CREB-like proteins. These transcription factors share a leucine
            zipper region that is involved in protein-protein interactions,
            located C-terminal to a stretch of basic amino acids that functions
            as a DNA binding domain. Two alternative transcripts encoding the
            same protein have been described. Two pseudogenes are located on
            the X chromosome at q28 in a region containing a large inverted
            duplication. [provided by RefSeq, Sep 2011].
            
            Transcript Variant: This variant (2) lacks an internal segment in
            the 5' UTR, compared to variant 1. The protein translation of this
            variant is regulated by two upstream open reading frames (PMID:
            15277680). Both variants 1 and 2 encode the same protein.
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: BC022088.2, AK057751.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000674920.3/ ENSP00000501863.1
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            regulatory uORF        :: PMID: 15277680
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-190               AL022312.7         61251-61440
            191-508             AL022312.7         62043-62360
            509-1419            AL022312.7         62462-63372
FEATURES             Location/Qualifiers
     source          1..1419
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="22"
                     /map="22q13.1"
     gene            1..1419
                     /gene="ATF4"
                     /gene_synonym="CREB-2; CREB2; TAXREB67; TXREB"
                     /note="activating transcription factor 4"
                     /db_xref="GeneID:468"
                     /db_xref="HGNC:HGNC:786"
                     /db_xref="MIM:604064"
     exon            1..190
                     /gene="ATF4"
                     /gene_synonym="CREB-2; CREB2; TAXREB67; TXREB"
                     /inference="alignment:Splign:2.1.0"
     regulatory      87..98
                     /regulatory_class="uORF"
                     /gene="ATF4"
                     /gene_synonym="CREB-2; CREB2; TAXREB67; TXREB"
                     /experiment="DESCRIPTION:regulatory uORF[PMID:15277680]"
                     /note="this uORF is predicted to encode a 3 aa peptide
                     (PMID:15277680)"
     regulatory      186..365
                     /regulatory_class="uORF"
                     /gene="ATF4"
                     /gene_synonym="CREB-2; CREB2; TAXREB67; TXREB"
                     /experiment="DESCRIPTION:regulatory uORF[PMID:15277680]"
                     /note="this uORF is predicted to encode a 59 aa peptide
                     (PMID:15277680)"
     exon            191..508
                     /gene="ATF4"
                     /gene_synonym="CREB-2; CREB2; TAXREB67; TXREB"
                     /inference="alignment:Splign:2.1.0"
     CDS             283..1338
                     /gene="ATF4"
                     /gene_synonym="CREB-2; CREB2; TAXREB67; TXREB"
                     /note="cAMP response element-binding protein 2;
                     DNA-binding protein TAXREB67; cAMP-dependent transcription
                     factor ATF-4; cAMP-responsive element-binding protein 2;
                     cyclic AMP-responsive element-binding protein 2;
                     tax-responsive enhancer element-binding protein 67;
                     tax-responsive enhancer element B67"
                     /codon_start=1
                     /product="cyclic AMP-dependent transcription factor ATF-4"
                     /protein_id="NP_877962.1"
                     /db_xref="CCDS:CCDS13996.1"
                     /db_xref="GeneID:468"
                     /db_xref="HGNC:HGNC:786"
                     /db_xref="MIM:604064"
                     /translation="MTEMSFLSSEVLVGDLMSPFDQSGLGAEESLGLLDDYLEVAKHF
                     KPHGFSSDKAKAGSSEWLAVDGLVSPSNNSKEDAFSGTDWMLEKMDLKEFDLDALLGI
                     DDLETMPDDLLTTLDDTCDLFAPLVQETNKQPPQTVNPIGHLPESLTKPDQVAPFTFL
                     QPLPLSPGVLSSTPDHSFSLELGSEVDITEGDRKPDYTAYVAMIPQCIKEEDTPSDND
                     SGICMSPESYLGSPQHSPSTRGSPNRSLPSPGVLCGSARPKPYDPPGEKMVAAKVKGE
                     KLDKKLKKMEQNKTAATRYRQKKRAEQEALTGECKELEKKNEALKERADSLAKEIQYL
                     KDLIEEVRKARGKKRVP"
     exon            509..1419
                     /gene="ATF4"
                     /gene_synonym="CREB-2; CREB2; TAXREB67; TXREB"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1398..1403
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ATF4"
                     /gene_synonym="CREB-2; CREB2; TAXREB67; TXREB"
                     /note="hexamer: AATAAA"
     polyA_site      1419
                     /gene="ATF4"
                     /gene_synonym="CREB-2; CREB2; TAXREB67; TXREB"
                     /note="major polyA site"
ORIGIN      
        1 catttctact ttgcccgccc acagatgtag ttttctctgc gcgtgtgcgt tttccctcct
       61 ccccgccctc agggtccacg gccaccatgg cgtattaggg gcagcagtgc ctgcggcagc
      121 attggccttt gcagcggcgg cagcagcacc aggctctgca gcggcaaccc ccagcggctt
      181 aagccatggc gcttctcacg gcattcagca gcagcgttgc tgtaaccgac aaagacacct
      241 tcgaattaag cacattcctc gattccagca aagcaccgca acatgaccga aatgagcttc
      301 ctgagcagcg aggtgttggt gggggacttg atgtccccct tcgaccagtc gggtttgggg
      361 gctgaagaaa gcctaggtct cttagatgat tacctggagg tggccaagca cttcaaacct
      421 catgggttct ccagcgacaa ggctaaggcg ggctcctccg aatggctggc tgtggatggg
      481 ttggtcagtc cctccaacaa cagcaaggag gatgccttct ccgggacaga ttggatgttg
      541 gagaaaatgg atttgaagga gttcgacttg gatgccctgt tgggtataga tgacctggaa
      601 accatgccag atgaccttct gaccacgttg gatgacactt gtgatctctt tgccccccta
      661 gtccaggaga ctaataagca gcccccccag acggtgaacc caattggcca tctcccagaa
      721 agtttaacaa aacccgacca ggttgccccc ttcaccttct tacaacctct tcccctttcc
      781 ccaggggtcc tgtcctccac tccagatcat tcctttagtt tagagctggg cagtgaagtg
      841 gatatcactg aaggagatag gaagccagac tacactgctt acgttgccat gatccctcag
      901 tgcataaagg aggaagacac cccttcagat aatgatagtg gcatctgtat gagcccagag
      961 tcctatctgg ggtctcctca gcacagcccc tctaccaggg gctctccaaa taggagcctc
     1021 ccatctccag gtgttctctg tgggtctgcc cgtcccaaac cttacgatcc tcctggagag
     1081 aagatggtag cagcaaaagt aaagggtgag aaactggata agaagctgaa aaaaatggag
     1141 caaaacaaga cagcagccac taggtaccgc cagaagaaga gggcggagca ggaggctctt
     1201 actggtgagt gcaaagagct ggaaaagaag aacgaggctc taaaagagag ggcggattcc
     1261 ctggccaagg agatccagta cctgaaagat ttgatagaag aggtccgcaa ggcaaggggg
     1321 aagaaaaggg tcccctagtt gaggatagtc aggagcgtca atgtgcttgt acatagagtg
     1381 ctgtagctgt gtgttccaat aaattatttt gtagggaaa
//
