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Database: UniProt
Entry: Q06507
LinkDB: Q06507
Original site: Q06507 
ID   ATF4_MOUSE              Reviewed;         349 AA.
AC   Q06507; Q5U4B2; Q61906;
DT   01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT   27-JUL-2011, sequence version 2.
DT   27-MAR-2024, entry version 176.
DE   RecName: Full=Cyclic AMP-dependent transcription factor ATF-4 {ECO:0000305};
DE            Short=cAMP-dependent transcription factor ATF-4 {ECO:0000305};
DE   AltName: Full=Activating transcription factor 4 {ECO:0000303|PubMed:11018027};
DE   AltName: Full=C/EBP-related ATF {ECO:0000303|PubMed:8506317};
DE            Short=C/ATF {ECO:0000303|PubMed:8506317};
DE   AltName: Full=Cyclic AMP-responsive element-binding protein 2 {ECO:0000303|PubMed:10885750};
DE            Short=CREB-2 {ECO:0000303|PubMed:10885750};
DE            Short=cAMP-responsive element-binding protein 2 {ECO:0000303|PubMed:10885750};
GN   Name=Atf4 {ECO:0000303|PubMed:10096021, ECO:0000312|MGI:MGI:88096};
GN   Synonyms=Creb2 {ECO:0000303|PubMed:10885750};
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBUNIT, AND SUBCELLULAR LOCATION.
RC   TISSUE=Adipocyte;
RX   PubMed=8506317; DOI=10.1073/pnas.90.10.4679;
RA   Vallejo M., Ron D., Miller C.P., Habener J.F.;
RT   "C/ATF, a member of the activating transcription factor family of DNA-
RT   binding proteins, dimerizes with CAAT/enhancer-binding proteins and directs
RT   their binding to cAMP response elements.";
RL   Proc. Natl. Acad. Sci. U.S.A. 90:4679-4683(1993).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=CD-1; TISSUE=Embryo;
RX   PubMed=1631061; DOI=10.1073/pnas.89.13.5789;
RA   Chevray P.M., Nathans D.;
RT   "Protein interaction cloning in yeast: identification of mammalian proteins
RT   that react with the leucine zipper of Jun.";
RL   Proc. Natl. Acad. Sci. U.S.A. 89:5789-5793(1992).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=BALB/cJ, C57BL/6J, and NOD; TISSUE=Lung, Spinal cord, and Spleen;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Eye;
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 project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [6]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=10096021; DOI=10.1046/j.1365-2443.1998.00230.x;
RA   Tanaka T., Tsujimura T., Takeda K., Sugihara A., Maekawa A., Terada N.,
RA   Yoshida N., Akira S.;
RT   "Targeted disruption of ATF4 discloses its essential role in the formation
RT   of eye lens fibres.";
RL   Genes Cells 3:801-810(1998).
RN   [7]
RP   FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND DISRUPTION
RP   PHENOTYPE.
RX   PubMed=10885750; DOI=10.1006/dbio.2000.9699;
RA   Hettmann T., Barton K., Leiden J.M.;
RT   "Microphthalmia due to p53-mediated apoptosis of anterior lens epithelial
RT   cells in mice lacking the CREB-2 transcription factor.";
RL   Dev. Biol. 222:110-123(2000).
RN   [8]
RP   FUNCTION, AND INDUCTION.
RX   PubMed=11106749; DOI=10.1016/s1097-2765(00)00108-8;
RA   Harding H.P., Novoa I., Zhang Y., Zeng H., Wek R., Schapira M., Ron D.;
RT   "Regulated translation initiation controls stress-induced gene expression
RT   in mammalian cells.";
RL   Mol. Cell 6:1099-1108(2000).
RN   [9]
RP   INTERACTION WITH CEBPB, AND DNA-BINDING.
RX   PubMed=11018027; DOI=10.1074/jbc.m005594200;
RA   Podust L.M., Krezel A.M., Kim Y.;
RT   "Crystal structure of the CCAAT box/enhancer-binding protein beta
RT   activating transcription factor-4 basic leucine zipper heterodimer in the
RT   absence of DNA.";
RL   J. Biol. Chem. 276:505-513(2001).
RN   [10]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=11806972; DOI=10.1182/blood.v99.3.736;
RA   Masuoka H.C., Townes T.M.;
RT   "Targeted disruption of the activating transcription factor 4 gene results
RT   in severe fetal anemia in mice.";
RL   Blood 99:736-745(2002).
RN   [11]
RP   FUNCTION, AND INDUCTION.
RX   PubMed=12667446; DOI=10.1016/s1097-2765(03)00105-9;
RA   Harding H.P., Zhang Y., Zeng H., Novoa I., Lu P.D., Calfon M., Sadri N.,
RA   Yun C., Popko B., Paules R., Stojdl D.F., Bell J.C., Hettmann T.,
RA   Leiden J.M., Ron D.;
RT   "An integrated stress response regulates amino acid metabolism and
RT   resistance to oxidative stress.";
RL   Mol. Cell 11:619-633(2003).
RN   [12]
RP   FUNCTION.
RX   PubMed=12925279; DOI=10.1016/s0896-6273(03)00501-4;
RA   Chen A., Muzzio I.A., Malleret G., Bartsch D., Verbitsky M., Pavlidis P.,
RA   Yonan A.L., Vronskaya S., Grody M.B., Cepeda I., Gilliam T.C., Kandel E.R.;
RT   "Inducible enhancement of memory storage and synaptic plasticity in
RT   transgenic mice expressing an inhibitor of ATF4 (CREB-2) and C/EBP
RT   proteins.";
RL   Neuron 39:655-669(2003).
RN   [13]
RP   FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, PHOSPHORYLATION AT
RP   SER-251, AND MUTAGENESIS OF SER-247; SER-251 AND SER-254.
RX   PubMed=15109498; DOI=10.1016/s0092-8674(04)00344-7;
RA   Yang X., Matsuda K., Bialek P., Jacquot S., Masuoka H.C., Schinke T.,
RA   Li L., Brancorsini S., Sassone-Corsi P., Townes T.M., Hanauer A.,
RA   Karsenty G.;
RT   "ATF4 is a substrate of RSK2 and an essential regulator of osteoblast
RT   biology; implication for Coffin-Lowry Syndrome.";
RL   Cell 117:387-398(2004).
RN   [14]
RP   INDUCTION.
RX   PubMed=15277680; DOI=10.1073/pnas.0400541101;
RA   Vattem K.M., Wek R.C.;
RT   "Reinitiation involving upstream ORFs regulates ATF4 mRNA translation in
RT   mammalian cells.";
RL   Proc. Natl. Acad. Sci. U.S.A. 101:11269-11274(2004).
RN   [15]
RP   FUNCTION.
RX   PubMed=15775988; DOI=10.1038/sj.emboj.7600596;
RA   Ohoka N., Yoshii S., Hattori T., Onozaki K., Hayashi H.;
RT   "TRB3, a novel ER stress-inducible gene, is induced via ATF4-CHOP pathway
RT   and is involved in cell death.";
RL   EMBO J. 24:1243-1255(2005).
RN   [16]
RP   INTERACTION WITH TXLNG.
RX   PubMed=15911876; DOI=10.1083/jcb.200412139;
RA   Yu V.W., Ambartsoumian G., Verlinden L., Moir J.M., Prud'homme J.,
RA   Gauthier C., Roughley P.J., St-Arnaud R.;
RT   "FIAT represses ATF4-mediated transcription to regulate bone mass in
RT   transgenic mice.";
RL   J. Cell Biol. 169:591-601(2005).
RN   [17]
RP   INTERACTION WITH SATB2.
RX   PubMed=16751105; DOI=10.1016/j.cell.2006.05.012;
RA   Dobreva G., Chahrour M., Dautzenberg M., Chirivella L., Kanzler B.,
RA   Farinas I., Karsenty G., Grosschedl R.;
RT   "SATB2 is a multifunctional determinant of craniofacial patterning and
RT   osteoblast differentiation.";
RL   Cell 125:971-986(2006).
RN   [18]
RP   FUNCTION, AND INTERACTION WITH TRIB3.
RX   PubMed=17369260; DOI=10.1074/jbc.m611723200;
RA   Jousse C., Deval C., Maurin A.C., Parry L., Cherasse Y., Chaveroux C.,
RA   Lefloch R., Lenormand P., Bruhat A., Fafournoux P.;
RT   "TRB3 inhibits the transcriptional activation of stress-regulated genes by
RT   a negative feedback on the ATF4 pathway.";
RL   J. Biol. Chem. 282:15851-15861(2007).
RN   [19]
RP   DEVELOPMENTAL STAGE, AND SUBCELLULAR LOCATION.
RX   PubMed=19232401; DOI=10.1016/j.gep.2009.02.002;
RA   Yu V.W., Akhouayri O., St-Arnaud R.;
RT   "FIAT is co-expressed with its dimerization target ATF4 in early
RT   osteoblasts, but not in osteocytes.";
RL   Gene Expr. Patterns 9:335-340(2009).
RN   [20]
RP   FUNCTION, AND INDUCTION.
RX   PubMed=21159964; DOI=10.1523/jneurosci.1598-10.2010;
RA   Galehdar Z., Swan P., Fuerth B., Callaghan S.M., Park D.S., Cregan S.P.;
RT   "Neuronal apoptosis induced by endoplasmic reticulum stress is regulated by
RT   ATF4-CHOP-mediated induction of the Bcl-2 homology 3-only member PUMA.";
RL   J. Neurosci. 30:16938-16948(2010).
RN   [21]
RP   FUNCTION, AND INDUCTION.
RX   PubMed=21768648; DOI=10.1074/jbc.m111.258970;
RA   Koyanagi S., Hamdan A.M., Horiguchi M., Kusunose N., Okamoto A.,
RA   Matsunaga N., Ohdo S.;
RT   "cAMP-response element (CRE)-mediated transcription by activating
RT   transcription factor-4 (ATF4) is essential for circadian expression of the
RT   Period2 gene.";
RL   J. Biol. Chem. 286:32416-32423(2011).
RN   [22]
RP   INTERACTION WITH ABRAXAS2, AND SUBCELLULAR LOCATION.
RX   PubMed=22974638; DOI=10.1016/j.bbamcr.2012.08.020;
RA   Ambivero C.T., Cilenti L., Zervos A.S.;
RT   "ATF4 interacts with Abro1/KIAA0157 scaffold protein and participates in a
RT   cytoprotective pathway.";
RL   Biochim. Biophys. Acta 1823:2149-2156(2012).
RN   [23]
RP   DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, INTERACTION WITH FOXO1, AND
RP   FUNCTION.
RX   PubMed=22298775; DOI=10.1074/jbc.m111.282897;
RA   Kode A., Mosialou I., Silva B.C., Joshi S., Ferron M., Rached M.T.,
RA   Kousteni S.;
RT   "FoxO1 protein cooperates with ATF4 protein in osteoblasts to control
RT   glucose homeostasis.";
RL   J. Biol. Chem. 287:8757-8768(2012).
RN   [24]
RP   FUNCTION, AND INDUCTION.
RX   PubMed=22572884; DOI=10.1124/mol.112.079079;
RA   Ushijima K., Koyanagi S., Sato Y., Ogata T., Matsunaga N., Fujimura A.,
RA   Ohdo S.;
RT   "Role of activating transcription factor-4 in 24-hour rhythm of serotonin
RT   transporter expression in the mouse midbrain.";
RL   Mol. Pharmacol. 82:264-270(2012).
RN   [25]
RP   FUNCTION, UBIQUITINATION, PHOSPHORYLATION AT THR-212; SER-218; SER-223;
RP   SER-230; SER-234 AND SER-247, AND MUTAGENESIS OF THR-212; SER-218; SER-223;
RP   SER-230; SER-234 AND SER-247.
RX   PubMed=23663782; DOI=10.1016/j.cell.2013.04.023;
RA   Csibi A., Fendt S.M., Li C., Poulogiannis G., Choo A.Y., Chapski D.J.,
RA   Jeong S.M., Dempsey J.M., Parkhitko A., Morrison T., Henske E.P.,
RA   Haigis M.C., Cantley L.C., Stephanopoulos G., Yu J., Blenis J.;
RT   "The mTORC1 pathway stimulates glutamine metabolism and cell proliferation
RT   by repressing SIRT4.";
RL   Cell 153:840-854(2013).
RN   [26]
RP   FUNCTION, DNA-BINDING, AND INTERACTION WITH DDIT3.
RX   PubMed=23624402; DOI=10.1038/ncb2738;
RA   Han J., Back S.H., Hur J., Lin Y.H., Gildersleeve R., Shan J., Yuan C.L.,
RA   Krokowski D., Wang S., Hatzoglou M., Kilberg M.S., Sartor M.A.,
RA   Kaufman R.J.;
RT   "ER-stress-induced transcriptional regulation increases protein synthesis
RT   leading to cell death.";
RL   Nat. Cell Biol. 15:481-490(2013).
RN   [27]
RP   HYDROXYLATION AT PRO-60 AND PRO-235.
RX   PubMed=24809345; DOI=10.1371/journal.pgen.1004348;
RA   Scortegagna M., Kim H., Li J.L., Yao H., Brill L.M., Han J., Lau E.,
RA   Bowtell D., Haddad G., Kaufman R.J., Ronai Z.A.;
RT   "Fine tuning of the UPR by the ubiquitin ligases Siah1/2.";
RL   PLoS Genet. 10:e1004348-e1004348(2014).
RN   [28] {ECO:0007744|PDB:6IRR}
RP   STRUCTURE BY NMR OF 314-349 IN COMPLEX WITH DISC1, INTERACTION WITH DISC1,
RP   AND FUNCTION.
RX   PubMed=31444471; DOI=10.1038/s41380-019-0485-2;
RA   Wang X., Ye F., Wen Z., Guo Z., Yu C., Huang W.K., Rojas Ringeling F.,
RA   Su Y., Zheng W., Zhou G., Christian K.M., Song H., Zhang M., Ming G.L.;
RT   "Structural interaction between DISC1 and ATF4 underlying transcriptional
RT   and synaptic dysregulation in an iPSC model of mental disorders.";
RL   Mol. Psychiatry 26:1346-1360(2021).
CC   -!- FUNCTION: Transcription factor that binds the cAMP response element
CC       (CRE) (consensus: 5'-GTGACGT[AC][AG]-3') and displays two biological
CC       functions, as regulator of metabolic and redox processes under normal
CC       cellular conditions, and as master transcription factor during
CC       integrated stress response (ISR) (PubMed:8506317, PubMed:11106749,
CC       PubMed:12667446, PubMed:23624402). Binds to asymmetric CRE's as a
CC       heterodimer and to palindromic CRE's as a homodimer (PubMed:8506317,
CC       PubMed:23624402). Core effector of the ISR, which is required for
CC       adaptation to various stress such as endoplasmic reticulum (ER) stress,
CC       amino acid starvation, mitochondrial stress or oxidative stress
CC       (PubMed:11106749, PubMed:12667446). During ISR, ATF4 translation is
CC       induced via an alternative ribosome translation re-initiation mechanism
CC       in response to EIF2S1/eIF-2-alpha phosphorylation, and stress-induced
CC       ATF4 acts as a master transcription factor of stress-responsive genes
CC       in order to promote cell recovery (PubMed:11106749, PubMed:12667446).
CC       Promotes the transcription of genes linked to amino acid sufficiency
CC       and resistance to oxidative stress to protect cells against metabolic
CC       consequences of ER oxidation (PubMed:12667446). Activates the
CC       transcription of NLRP1, possibly in concert with other factors in
CC       response to ER stress (By similarity). Activates the transcription of
CC       asparagine synthetase (ASNS) in response to amino acid deprivation or
CC       ER stress (PubMed:15775988, PubMed:21159964). However, when associated
CC       with DDIT3/CHOP, the transcriptional activation of the ASNS gene is
CC       inhibited in response to amino acid deprivation (By similarity).
CC       Together with DDIT3/CHOP, mediates programmed cell death by promoting
CC       the expression of genes involved in cellular amino acid metabolic
CC       processes, mRNA translation and the terminal unfolded protein response
CC       (terminal UPR), a cellular response that elicits programmed cell death
CC       when ER stress is prolonged and unresolved (PubMed:23624402). Together
CC       with DDIT3/CHOP, activates the transcription of the IRS-regulator TRIB3
CC       and promotes ER stress-induced neuronal cell death by regulating the
CC       expression of BBC3/PUMA in response to ER stress (PubMed:15775988,
CC       PubMed:17369260, PubMed:21159964). May cooperate with the UPR
CC       transcriptional regulator QRICH1 to regulate ER protein homeostasis
CC       which is critical for cell viability in response to ER stress (By
CC       similarity). In the absence of stress, ATF4 translation is at low
CC       levels and it is required for normal metabolic processes such as
CC       embryonic lens formation, fetal liver hematopoiesis, bone development
CC       and synaptic plasticity (PubMed:10096021, PubMed:10885750,
CC       PubMed:11806972, PubMed:12925279, PubMed:15109498, PubMed:22298775).
CC       Acts as a regulator of osteoblast differentiation in response to
CC       phosphorylation by RPS6KA3/RSK2: phosphorylation in osteoblasts
CC       enhances transactivation activity and promotes expression of
CC       osteoblast-specific genes and post-transcriptionally regulates the
CC       synthesis of Type I collagen, the main constituent of the bone matrix
CC       (PubMed:15109498). Cooperates with FOXO1 in osteoblasts to regulate
CC       glucose homeostasis through suppression of beta-cell production and
CC       decrease in insulin production (PubMed:22298775). Activates
CC       transcription of SIRT4 (PubMed:23663782). Regulates the circadian
CC       expression of the core clock component PER2 and the serotonin
CC       transporter SLC6A4 (PubMed:21768648, PubMed:22572884). Binds in a
CC       circadian time-dependent manner to the cAMP response elements (CRE) in
CC       the SLC6A4 and PER2 promoters and periodically activates the
CC       transcription of these genes (PubMed:21768648, PubMed:22572884). Mainly
CC       acts as a transcriptional activator in cellular stress adaptation, but
CC       it can also act as a transcriptional repressor: acts as a regulator of
CC       synaptic plasticity by repressing transcription, thereby inhibiting
CC       induction and maintenance of long-term memory (PubMed:12925279).
CC       Regulates synaptic functions via interaction with DISC1 in neurons,
CC       which inhibits ATF4 transcription factor activity by disrupting ATF4
CC       dimerization and DNA-binding (PubMed:31444471).
CC       {ECO:0000250|UniProtKB:P18848, ECO:0000269|PubMed:10096021,
CC       ECO:0000269|PubMed:10885750, ECO:0000269|PubMed:11106749,
CC       ECO:0000269|PubMed:11806972, ECO:0000269|PubMed:12667446,
CC       ECO:0000269|PubMed:12925279, ECO:0000269|PubMed:15109498,
CC       ECO:0000269|PubMed:15775988, ECO:0000269|PubMed:17369260,
CC       ECO:0000269|PubMed:21159964, ECO:0000269|PubMed:21768648,
CC       ECO:0000269|PubMed:22298775, ECO:0000269|PubMed:22572884,
CC       ECO:0000269|PubMed:23624402, ECO:0000269|PubMed:23663782,
CC       ECO:0000269|PubMed:31444471, ECO:0000269|PubMed:8506317}.
CC   -!- SUBUNIT: Binds DNA as a homodimer and as a heterodimer
CC       (PubMed:23624402). Heterodimer; heterodimerizes with CEBPB
CC       (PubMed:11018027). Heterodimer; heterodimerizes with DDIT3/CHOP
CC       (PubMed:23624402). Interacts with CEP290 (via an N-terminal region) (By
CC       similarity). Interacts with NEK6, DAPK2 (isoform 2) and ZIPK/DAPK3 (By
CC       similarity). Interacts (via its leucine zipper domain) with GABBR1 and
CC       GABBR2 (via their C-termini) (By similarity). Forms a heterodimer with
CC       TXLNG in osteoblasts (PubMed:15911876). Interacts (via its DNA binding
CC       domain) with FOXO1 (C-terminal half); the interaction occurs in
CC       osteoblasts and regulates glucose homeostasis through suppression of
CC       beta-cell proliferation and a decrease in insulin production
CC       (PubMed:22298775). Interacts with SATB2; the interaction results in
CC       enhanced DNA binding and transactivation by these transcription factors
CC       (PubMed:16751105). Interacts with ABRAXAS2 (PubMed:22974638). Interacts
CC       with TRIB3, inhibiting the transactivation activity of ATF4
CC       (PubMed:17369260). Interacts with DISC1; which inhibits ATF4
CC       transcription factor activity by disrupting ATF4 dimerization and DNA-
CC       binding (PubMed:31444471). Interacts with EP300/p300; EP300/p300
CC       stabilizes ATF4 and increases its transcriptional activity
CC       independently of its catalytic activity by preventing its
CC       ubiquitination (By similarity). {ECO:0000250|UniProtKB:P18848,
CC       ECO:0000250|UniProtKB:Q9ES19, ECO:0000269|PubMed:11018027,
CC       ECO:0000269|PubMed:15911876, ECO:0000269|PubMed:16751105,
CC       ECO:0000269|PubMed:17369260, ECO:0000269|PubMed:22298775,
CC       ECO:0000269|PubMed:22974638, ECO:0000269|PubMed:23624402,
CC       ECO:0000269|PubMed:31444471}.
CC   -!- INTERACTION:
CC       Q06507; O54784: Dapk3; NbExp=3; IntAct=EBI-77383, EBI-77359;
CC       Q06507; P35639: Ddit3; NbExp=3; IntAct=EBI-77383, EBI-10636142;
CC       Q06507; Q8K4K2: Trib3; NbExp=3; IntAct=EBI-77383, EBI-448962;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:15109498,
CC       ECO:0000269|PubMed:19232401, ECO:0000269|PubMed:22974638}. Nucleus
CC       speckle {ECO:0000250|UniProtKB:P18848}. Cytoplasm
CC       {ECO:0000269|PubMed:19232401}. Cell membrane
CC       {ECO:0000250|UniProtKB:Q9ES19}. Cytoplasm, cytoskeleton, microtubule
CC       organizing center, centrosome {ECO:0000250|UniProtKB:P18848}.
CC       Note=Colocalizes with GABBR1 in hippocampal neuron dendritic membranes.
CC       Colocalizes with NEK6 in the centrosome (By similarity). Recruited to
CC       nuclear speckles following interaction with EP300/p300 (By similarity).
CC       {ECO:0000250|UniProtKB:P18848, ECO:0000250|UniProtKB:Q9ES19}.
CC   -!- TISSUE SPECIFICITY: Ubiquitously expressed in adults.
CC       {ECO:0000305|PubMed:10885750}.
CC   -!- DEVELOPMENTAL STAGE: During embryonic development, expressed at high
CC       levels in anterior epithelial lens cells at 14.5 dpc (PubMed:10885750).
CC       At 16.5 dpc, expressed in osteoblasts surrounding newly formed
CC       trabecular bone (PubMed:19232401). At postnatal day 2, detected in most
CC       osteoblasts and lining cells (PubMed:19232401). By postnatal week 4, is
CC       detected in fewer osteoblasts, but remains present in lining cells (at
CC       protein level) (PubMed:19232401). {ECO:0000269|PubMed:10885750,
CC       ECO:0000269|PubMed:19232401}.
CC   -!- INDUCTION: Regulated at the translational level in response to various
CC       stress such as endoplasmic reticulum stress, amino acid starvation or
CC       oxidative stress (PubMed:11106749, PubMed:12667446, PubMed:15277680,
CC       PubMed:21159964). In the absence of stress, ribosomes re-initiate
CC       translation at an inhibitory open reading frame (uORF) upstream of the
CC       ATF4 transcript, which precludes AFT4 translation (PubMed:11106749,
CC       PubMed:15277680). In response to stress and subsequent EIF2S1/eIF-2-
CC       alpha phosphorylation, ribosomes bypass the inhibitory uORF and re-
CC       initiate translation at the AFT4 coding sequence (PubMed:15277680).
CC       Expressed in a circadian manner in the midbrain with an increased
CC       expression seen during the dark phase (at protein level)
CC       (PubMed:21768648, PubMed:22572884). Expressed in a circadian manner
CC       also in the suprachiasmatic nucleus (SCN) of the brain, cerebral
CC       cortex, kidney and small intestine (PubMed:21768648, PubMed:22572884).
CC       {ECO:0000269|PubMed:11106749, ECO:0000269|PubMed:12667446,
CC       ECO:0000269|PubMed:15277680, ECO:0000269|PubMed:21159964,
CC       ECO:0000269|PubMed:21768648, ECO:0000269|PubMed:22572884}.
CC   -!- DOMAIN: The BetaTrCP degron motif promotes binding to BTRC when
CC       phosphorylated. {ECO:0000269|PubMed:23663782}.
CC   -!- PTM: Ubiquitinated by SCF(BTRC) in response to mTORC1 signal, followed
CC       by proteasomal degradation and leading to down-regulate expression of
CC       SIRT4 (PubMed:23663782). Interaction with EP300/p300 inhibits
CC       ubiquitination by SCF(BTRC) (By similarity).
CC       {ECO:0000250|UniProtKB:P18848, ECO:0000269|PubMed:23663782}.
CC   -!- PTM: Phosphorylation at Ser-251 by RPS6KA3/RSK2 in osteoblasts enhances
CC       transactivation activity and promotes osteoblast differentiation
CC       (PubMed:15109498). Phosphorylated on the betaTrCP degron motif at Ser-
CC       218, followed by phosphorylation at Thr-212, Ser-223, Ser-230, Ser-234
CC       and Ser-247, promoting interaction with BTRC and ubiquitination
CC       (PubMed:23663782). Phosphorylation is promoted by mTORC1
CC       (PubMed:23663782). Phosphorylation at Ser-214 by CK2 decreases its
CC       stability (By similarity). Phosphorylated by NEK6 (By similarity).
CC       {ECO:0000250|UniProtKB:P18848, ECO:0000269|PubMed:15109498,
CC       ECO:0000269|PubMed:23663782}.
CC   -!- PTM: Hydroxylated by PHD3, leading to decreased protein stability.
CC       {ECO:0000269|PubMed:24809345}.
CC   -!- DISRUPTION PHENOTYPE: Mice were born at a much lower rate than
CC       predicted by the Mendelian ratio (PubMed:10096021, PubMed:10885750).
CC       Homozygous pups generally die during the first hour after birth,
CC       although excess mortality occurrs throughout the first 3 weeks of life
CC       (PubMed:10096021, PubMed:11806972). Embryos are severely anemic during
CC       fetal development, due to an impairment in definitive hematopoiesis
CC       (PubMed:11806972). Surviving mice display defects in embryonic lens
CC       formation leading to severe microphthalmia in adults (PubMed:10096021,
CC       PubMed:10885750). Embryos show delayed bone formation and surviving
CC       mice display low bone mass throughout postnatal life (PubMed:15109498).
CC       Surviving null mice exhibit an increase in serum insulin levels and low
CC       blood glucose levels (PubMed:22298775). There is a decrease in total
CC       fat content, gonadal fat, lean mass and body weight (PubMed:22298775).
CC       Serum levels of osteocalcin/BGLAP are decreased (PubMed:22298775).
CC       PBK/AKT1-mediated phosphorylation of FOXO1 at 'Ser-258' is increased
CC       with a subsequent decrease of FOXO1-mediated transcriptional activity
CC       (PubMed:22298775). {ECO:0000269|PubMed:10096021,
CC       ECO:0000269|PubMed:10885750, ECO:0000269|PubMed:11806972,
CC       ECO:0000269|PubMed:15109498, ECO:0000269|PubMed:22298775}.
CC   -!- SIMILARITY: Belongs to the bZIP family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAA53043.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR   EMBL; L13791; AAA40476.1; -; mRNA.
DR   EMBL; M94087; AAA53043.1; ALT_INIT; mRNA.
DR   EMBL; AK138657; BAE23736.1; -; mRNA.
DR   EMBL; AK144777; BAE26060.1; -; mRNA.
DR   EMBL; AK146193; BAE26967.1; -; mRNA.
DR   EMBL; AK156298; BAE33662.1; -; mRNA.
DR   EMBL; CH466550; EDL04604.1; -; Genomic_DNA.
DR   EMBL; CH466550; EDL04605.1; -; Genomic_DNA.
DR   EMBL; BC085169; AAH85169.1; -; mRNA.
DR   CCDS; CCDS37145.1; -.
DR   RefSeq; NP_001274109.1; NM_001287180.1.
DR   RefSeq; NP_033846.2; NM_009716.3.
DR   PDB; 6IRR; NMR; -; A=314-349.
DR   PDBsum; 6IRR; -.
DR   AlphaFoldDB; Q06507; -.
DR   SMR; Q06507; -.
DR   BioGRID; 198235; 12.
DR   ComplexPortal; CPX-6; bZIP transcription factor complex, Atf4-Creb1.
DR   ComplexPortal; CPX-7; bZIP transcription factor complex, Atf1-Atf4.
DR   CORUM; Q06507; -.
DR   DIP; DIP-30969N; -.
DR   IntAct; Q06507; 10.
DR   STRING; 10090.ENSMUSP00000105234; -.
DR   iPTMnet; Q06507; -.
DR   PhosphoSitePlus; Q06507; -.
DR   PaxDb; 10090-ENSMUSP00000105234; -.
DR   ProteomicsDB; 265159; -.
DR   Antibodypedia; 12687; 1290 antibodies from 47 providers.
DR   DNASU; 11911; -.
DR   Ensembl; ENSMUST00000109605.5; ENSMUSP00000105234.4; ENSMUSG00000042406.9.
DR   GeneID; 11911; -.
DR   KEGG; mmu:11911; -.
DR   UCSC; uc007wvl.2; mouse.
DR   AGR; MGI:88096; -.
DR   CTD; 468; -.
DR   MGI; MGI:88096; Atf4.
DR   VEuPathDB; HostDB:ENSMUSG00000042406; -.
DR   eggNOG; KOG4571; Eukaryota.
DR   GeneTree; ENSGT00530000063801; -.
DR   HOGENOM; CLU_055748_1_0_1; -.
DR   InParanoid; Q06507; -.
DR   OMA; WMTEKID; -.
DR   OrthoDB; 4843682at2759; -.
DR   TreeFam; TF316136; -.
DR   BioGRID-ORCS; 11911; 20 hits in 85 CRISPR screens.
DR   ChiTaRS; Atf4; mouse.
DR   PRO; PR:Q06507; -.
DR   Proteomes; UP000000589; Chromosome 15.
DR   RNAct; Q06507; Protein.
DR   Bgee; ENSMUSG00000042406; Expressed in ankle joint and 288 other cell types or tissues.
DR   ExpressionAtlas; Q06507; baseline and differential.
DR   Genevisible; Q06507; MM.
DR   GO; GO:1990590; C:ATF1-ATF4 transcription factor complex; IDA:ParkinsonsUK-UCL.
DR   GO; GO:1990589; C:ATF4-CREB1 transcription factor complex; IDA:ParkinsonsUK-UCL.
DR   GO; GO:0005813; C:centrosome; IEA:UniProtKB-SubCell.
DR   GO; GO:1990617; C:CHOP-ATF4 complex; ISO:MGI.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0032590; C:dendrite membrane; ISO:MGI.
DR   GO; GO:1990037; C:Lewy body core; ISO:MGI.
DR   GO; GO:0043005; C:neuron projection; ISO:MGI.
DR   GO; GO:0034399; C:nuclear periphery; ISO:MGI.
DR   GO; GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell.
DR   GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR   GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR   GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR   GO; GO:0090575; C:RNA polymerase II transcription regulator complex; IDA:MGI.
DR   GO; GO:0005667; C:transcription regulator complex; IDA:MGI.
DR   GO; GO:0008140; F:cAMP response element binding protein binding; IDA:UniProtKB.
DR   GO; GO:0003677; F:DNA binding; IGI:MGI.
DR   GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IMP:NTNU_SB.
DR   GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:UniProtKB.
DR   GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISO:MGI.
DR   GO; GO:0140297; F:DNA-binding transcription factor binding; ISO:MGI.
DR   GO; GO:0140296; F:general transcription initiation factor binding; ISO:MGI.
DR   GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR   GO; GO:0043522; F:leucine zipper domain binding; ISO:MGI.
DR   GO; GO:1990841; F:promoter-specific chromatin binding; IDA:MGI.
DR   GO; GO:0046982; F:protein heterodimerization activity; IDA:UniProtKB.
DR   GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR   GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:UniProtKB.
DR   GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR   GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISO:MGI.
DR   GO; GO:0043565; F:sequence-specific DNA binding; ISO:MGI.
DR   GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR   GO; GO:0000976; F:transcription cis-regulatory region binding; ISO:MGI.
DR   GO; GO:0030282; P:bone mineralization; IMP:UniProtKB.
DR   GO; GO:0034198; P:cellular response to amino acid starvation; IDA:UniProtKB.
DR   GO; GO:0042149; P:cellular response to glucose starvation; ISO:MGI.
DR   GO; GO:0071456; P:cellular response to hypoxia; IEA:Ensembl.
DR   GO; GO:1990253; P:cellular response to leucine starvation; IDA:MGI.
DR   GO; GO:0034599; P:cellular response to oxidative stress; IMP:UniProtKB.
DR   GO; GO:0032922; P:circadian regulation of gene expression; IMP:UniProtKB.
DR   GO; GO:0007623; P:circadian rhythm; IEP:UniProtKB.
DR   GO; GO:0035162; P:embryonic hemopoiesis; IMP:UniProtKB.
DR   GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; IDA:UniProtKB.
DR   GO; GO:0007214; P:gamma-aminobutyric acid signaling pathway; ISO:MGI.
DR   GO; GO:0006094; P:gluconeogenesis; IDA:MGI.
DR   GO; GO:0140468; P:HRI-mediated signaling; ISS:UniProtKB.
DR   GO; GO:0140467; P:integrated stress response signaling; IMP:UniProtKB.
DR   GO; GO:0006874; P:intracellular calcium ion homeostasis; IMP:MGI.
DR   GO; GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; IDA:UniProtKB.
DR   GO; GO:0070982; P:L-asparagine metabolic process; ISO:MGI.
DR   GO; GO:0070309; P:lens fiber cell morphogenesis; IMP:UniProtKB.
DR   GO; GO:0042789; P:mRNA transcription by RNA polymerase II; IDA:UniProtKB.
DR   GO; GO:0120163; P:negative regulation of cold-induced thermogenesis; IMP:YuBioLab.
DR   GO; GO:1903377; P:negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway; ISO:MGI.
DR   GO; GO:0043267; P:negative regulation of potassium ion transport; ISO:MGI.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR   GO; GO:0030182; P:neuron differentiation; IEA:Ensembl.
DR   GO; GO:0036499; P:PERK-mediated unfolded protein response; IDA:UniProtKB.
DR   GO; GO:0070169; P:positive regulation of biomineral tissue development; IMP:MGI.
DR   GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB.
DR   GO; GO:0010628; P:positive regulation of gene expression; IMP:ParkinsonsUK-UCL.
DR   GO; GO:0043525; P:positive regulation of neuron apoptotic process; IMP:UniProtKB.
DR   GO; GO:2000120; P:positive regulation of sodium-dependent phosphate transport; IMP:MGI.
DR   GO; GO:0045943; P:positive regulation of transcription by RNA polymerase I; ISO:MGI.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR   GO; GO:1905461; P:positive regulation of vascular associated smooth muscle cell apoptotic process; IMP:MGI.
DR   GO; GO:0010575; P:positive regulation of vascular endothelial growth factor production; ISO:MGI.
DR   GO; GO:0006355; P:regulation of DNA-templated transcription; IDA:MGI.
DR   GO; GO:0045667; P:regulation of osteoblast differentiation; IMP:UniProtKB.
DR   GO; GO:0048167; P:regulation of synaptic plasticity; IMP:UniProtKB.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:MGI.
DR   GO; GO:0034976; P:response to endoplasmic reticulum stress; IDA:UniProtKB.
DR   GO; GO:1990737; P:response to manganese-induced endoplasmic reticulum stress; IEA:Ensembl.
DR   GO; GO:0031667; P:response to nutrient levels; ISO:MGI.
DR   GO; GO:0009636; P:response to toxic substance; IEA:Ensembl.
DR   GO; GO:0006366; P:transcription by RNA polymerase II; IGI:MGI.
DR   CDD; cd14692; bZIP_ATF4; 1.
DR   Gene3D; 1.20.5.170; -; 1.
DR   InterPro; IPR004827; bZIP.
DR   InterPro; IPR046347; bZIP_sf.
DR   PANTHER; PTHR13044; ACTIVATING TRANSCRIPTION FACTOR ATF 4/5; 1.
DR   PANTHER; PTHR13044:SF2; CYCLIC AMP-DEPENDENT TRANSCRIPTION FACTOR ATF-4; 1.
DR   Pfam; PF00170; bZIP_1; 1.
DR   SMART; SM00338; BRLZ; 1.
DR   SUPFAM; SSF57959; Leucine zipper domain; 1.
DR   PROSITE; PS50217; BZIP; 1.
DR   PROSITE; PS00036; BZIP_BASIC; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Acetylation; Activator; Biological rhythms; Cell membrane;
KW   Cytoplasm; Cytoskeleton; DNA-binding; Hydroxylation; Isopeptide bond;
KW   Membrane; Nucleus; Phosphoprotein; Reference proteome; Repressor;
KW   Transcription; Transcription regulation; Ubl conjugation.
FT   CHAIN           1..349
FT                   /note="Cyclic AMP-dependent transcription factor ATF-4"
FT                   /id="PRO_0000076585"
FT   DOMAIN          276..339
FT                   /note="bZIP"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT   REGION          49..75
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          204..271
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          278..298
FT                   /note="Basic motif"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT   REGION          279..298
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          303..339
FT                   /note="Interaction with GABBR1"
FT                   /evidence="ECO:0000250"
FT   REGION          304..332
FT                   /note="Leucine-zipper"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT   MOTIF           214..223
FT                   /note="BetaTrCP degron motif"
FT                   /evidence="ECO:0000269|PubMed:23663782"
FT   COMPBIAS        216..244
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         60
FT                   /note="4-hydroxyproline"
FT                   /evidence="ECO:0000269|PubMed:24809345"
FT   MOD_RES         212
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000269|PubMed:23663782"
FT   MOD_RES         214
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P18848"
FT   MOD_RES         218
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:23663782"
FT   MOD_RES         223
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:23663782"
FT   MOD_RES         230
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:23663782"
FT   MOD_RES         234
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:23663782"
FT   MOD_RES         235
FT                   /note="4-hydroxyproline"
FT                   /evidence="ECO:0000269|PubMed:24809345"
FT   MOD_RES         247
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:23663782"
FT   MOD_RES         251
FT                   /note="Phosphoserine; by RPS6KA3"
FT                   /evidence="ECO:0000269|PubMed:15109498"
FT   MOD_RES         309
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P18848"
FT   CROSSLNK        258
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0000250|UniProtKB:P18848"
FT   CROSSLNK        270
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0000250|UniProtKB:P18848"
FT   MUTAGEN         212
FT                   /note="T->A: Promotes stabilization due to impaired
FT                   ubiquitination; when associated with A-223; A-230; A-234
FT                   and A-247."
FT                   /evidence="ECO:0000269|PubMed:23663782"
FT   MUTAGEN         218
FT                   /note="S->A: Promotes stabilization due to impaired
FT                   ubiquitination."
FT                   /evidence="ECO:0000269|PubMed:23663782"
FT   MUTAGEN         223
FT                   /note="S->A: Promotes stabilization due to impaired
FT                   ubiquitination; when associated with A-212; A-230; A-234
FT                   and A-247."
FT                   /evidence="ECO:0000269|PubMed:23663782"
FT   MUTAGEN         230
FT                   /note="S->A: Promotes stabilization due to impaired
FT                   ubiquitination; when associated with A-212; A-223; A-234
FT                   and A-247."
FT                   /evidence="ECO:0000269|PubMed:23663782"
FT   MUTAGEN         234
FT                   /note="S->A: Promotes stabilization due to impaired
FT                   ubiquitination; when associated with A-212; A-223; A-230
FT                   and A-247."
FT                   /evidence="ECO:0000269|PubMed:23663782"
FT   MUTAGEN         247
FT                   /note="S->A: Promotes stabilization due to impaired
FT                   ubiquitination; when associated with A-212; A-223; A-230
FT                   and A-234. Does not affect phosphorylation by
FT                   RPS6KA3/RSK2."
FT                   /evidence="ECO:0000269|PubMed:15109498,
FT                   ECO:0000269|PubMed:23663782"
FT   MUTAGEN         251
FT                   /note="S->A,R,D: Abolished phosphorylation by
FT                   RPS6KA3/RSK2."
FT                   /evidence="ECO:0000269|PubMed:15109498"
FT   MUTAGEN         254
FT                   /note="S->A: Does not affect phosphorylation by
FT                   RPS6KA3/RSK2."
FT                   /evidence="ECO:0000269|PubMed:15109498"
FT   CONFLICT        345
FT                   /note="K -> Q (in Ref. 1; AAA40476)"
FT                   /evidence="ECO:0000305"
FT   HELIX           317..342
FT                   /evidence="ECO:0007829|PDB:6IRR"
SQ   SEQUENCE   349 AA;  38355 MW;  0C3F895755B1C7B9 CRC64;
     MTEMSFLNSE VLAGDLMSPF DQSGLGAEES LGLLDDYLEV AKHLKPHGFS SDKAGSSEWP
     AMDDGLASAS DTGKEDAFSG TDWMLEKMDL KEFDFDALFR MDDLETMPDE LLTTLDDTCD
     LFAPLVQETN KEPPQTVNPI GHLPESLIKV DQVAPFTFLQ PFPCSPGVLS STPEHSFSLE
     LGSEVDISEG DRKPDSAAYI TLIPPCVKEE DTPSDNDSGI CMSPESYLGS PQHSPSTSRA
     PPDNLPSPGG SRGSPRPKPY DPPGVSLTAK VKTEKLDKKL KKMEQNKTAA TRYRQKKRAE
     QEALTGECKE LEKKNEALKE KADSLAKEIQ YLKDLIEEVR KARGKKRVP
//
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