ATF5_HUMAN
ID ATF5_HUMAN Reviewed; 282 AA.
AC Q9Y2D1; B3KND3; Q9BSA1; Q9UNQ3;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 05-OCT-2010, sequence version 4.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=Cyclic AMP-dependent transcription factor ATF-5;
DE Short=cAMP-dependent transcription factor ATF-5;
DE AltName: Full=Activating transcription factor 5;
DE AltName: Full=Transcription factor ATFx;
GN Name=ATF5; Synonyms=ATFX;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=11087824; DOI=10.1073/pnas.240452197;
RA White J.H., McIllhinney R.A.J., Wise A., Ciruela F., Chan W.-Y.,
RA Emson P.C., Billinton A., Marshall F.H.;
RT "The GABAB receptor interacts directly with the related transcription
RT factors CREB2 and ATFx.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:13967-13972(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT LEU-121.
RC TISSUE=Hepatoblastoma;
RX PubMed=15221005; DOI=10.1038/sj.onc.1207782;
RA Yamada S., Ohira M., Horie H., Ando K., Takayasu H., Suzuki Y., Sugano S.,
RA Hirata T., Goto T., Matsunaga T., Hiyama E., Hayashi Y., Ando H., Suita S.,
RA Kaneko M., Sasaki F., Hashizume K., Ohnuma N., Nakagawara A.;
RT "Expression profiling and differential screening between hepatoblastomas
RT and the corresponding normal livers: identification of high expression of
RT the PLK1 oncogene as a poor-prognostic indicator of hepatoblastomas.";
RL Oncogene 23:5901-5911(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Kohroki J., Tanaka K.;
RT "cDNA clone encoding leucine-zipper protein.";
RL Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT LEU-121.
RC TISSUE=Placenta;
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 [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 161-282, FUNCTION, AND UBIQUITINATION.
RX PubMed=10373550; DOI=10.1128/mcb.19.7.5001;
RA Pati D., Meistrich M.L., Plon S.E.;
RT "Human Cdc34 and Rad6B ubiquitin-conjugating enzymes target repressors of
RT cyclic AMP-induced transcription for proteolysis.";
RL Mol. Cell. Biol. 19:5001-5013(1999).
RN [9]
RP INTERACTION WITH CCND3, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=15358120; DOI=10.1016/j.bbrc.2004.07.053;
RA Liu W., Sun M., Jiang J., Shen X., Sun Q., Liu W., Shen H., Gu J.;
RT "Cyclin D3 interacts with human activating transcription factor 5 and
RT potentiates its transcription activity.";
RL Biochem. Biophys. Res. Commun. 321:954-960(2004).
RN [10]
RP FUNCTION, AND DNA-BINDING.
RX PubMed=18701499; DOI=10.1158/0008-5472.can-07-6469;
RA Gho J.W., Ip W.K., Chan K.Y., Law P.T., Lai P.B., Wong N.;
RT "Re-expression of transcription factor ATF5 in hepatocellular carcinoma
RT induces G2-M arrest.";
RL Cancer Res. 68:6743-6751(2008).
RN [11]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=18332083; DOI=10.1124/dmd.107.019380;
RA Pascual M., Gomez-Lechon M.J., Castell J.V., Jover R.;
RT "ATF5 is a highly abundant liver-enriched transcription factor that
RT cooperates with constitutive androstane receptor in the transactivation of
RT CYP2B6: implications in hepatic stress responses.";
RL Drug Metab. Dispos. 36:1063-1072(2008).
RN [12]
RP UBIQUITINATION, AND INDUCTION BY CISPLATIN.
RX PubMed=18458088; DOI=10.1074/jbc.m707879200;
RA Wei Y., Jiang J., Liu D., Zhou J., Chen X., Zhang S., Zong H., Yun X.,
RA Gu J.;
RT "Cdc34-mediated degradation of ATF5 is blocked by cisplatin.";
RL J. Biol. Chem. 283:18773-18781(2008).
RN [13]
RP FUNCTION.
RX PubMed=20654631; DOI=10.1016/j.lfs.2010.07.006;
RA Yamazaki T., Ohmi A., Kurumaya H., Kato K., Abe T., Yamamoto H.,
RA Nakanishi N., Okuyama R., Umemura M., Kaise T., Watanabe R., Okawa Y.,
RA Takahashi S., Takahashi Y.;
RT "Regulation of the human CHOP gene promoter by the stress response
RT transcription factor ATF5 via the AARE1 site in human hepatoma HepG2
RT cells.";
RL Life Sci. 87:294-301(2010).
RN [14]
RP FUNCTION, AND INDUCTION BY PRO-APOPTOTIC STIMULI.
RX PubMed=21212266; DOI=10.1074/jbc.m110.207639;
RA Dluzen D., Li G., Tacelosky D., Moreau M., Liu D.X.;
RT "BCL-2 is a downstream target of ATF5 that mediates the prosurvival
RT function of ATF5 in a cell type-dependent manner.";
RL J. Biol. Chem. 286:7705-7713(2011).
RN [15]
RP FUNCTION.
RX PubMed=21791614; DOI=10.1128/mcb.05887-11;
RA Liu D.X., Qian D., Wang B., Yang J.M., Lu Z.;
RT "p300-Dependent ATF5 acetylation is essential for Egr-1 gene activation and
RT cell proliferation and survival.";
RL Mol. Cell. Biol. 31:3906-3916(2011).
RN [16]
RP FUNCTION, INTERACTION WITH HSPA1A; HSPA1B AND NPM1, SUBCELLULAR LOCATION,
RP POLYUBIQUITINATION, AND MUTAGENESIS OF ASP-157.
RX PubMed=22528486; DOI=10.1074/jbc.m112.363622;
RA Liu X., Liu D., Qian D., Dai J., An Y., Jiang S., Stanley B., Yang J.,
RA Wang B., Liu X., Liu D.X.;
RT "Nucleophosmin (NPM1/B23) interacts with activating transcription factor 5
RT (ATF5) protein and promotes proteasome- and caspase-dependent ATF5
RT degradation in hepatocellular carcinoma cells.";
RL J. Biol. Chem. 287:19599-19609(2012).
RN [17]
RP FUNCTION.
RX PubMed=22442021; DOI=10.1002/jcb.24150;
RA Leong D.T., Abraham M.C., Gupta A., Lim T.C., Chew F.T., Hutmacher D.W.;
RT "ATF5, a possible regulator of osteogenic differentiation in human adipose-
RT derived stem cells.";
RL J. Cell. Biochem. 113:2744-2753(2012).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-256, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [19]
RP FUNCTION, INDUCTION BY IL1B, INTERACTION WITH HSPA1A; HSPA1B AND NPM1, AND
RP MUTAGENESIS OF 3-LEU--VAL-25; 3-LEU-LEU-4; LEU-7; 9-LEU--LEU-11;
RP 15-LEU-LEU-16 AND 21-LEU--VAL-25.
RX PubMed=24379400; DOI=10.1074/jbc.m113.491217;
RA Abe T., Kojima M., Akanuma S., Iwashita H., Yamazaki T., Okuyama R.,
RA Ichikawa K., Umemura M., Nakano H., Takahashi S., Takahashi Y.;
RT "N-terminal hydrophobic amino acids of activating transcription factor 5
RT (ATF5) protein confer interleukin 1beta (IL-1beta)-induced stabilization.";
RL J. Biol. Chem. 289:3888-3900(2014).
RN [20]
RP FUNCTION.
RX PubMed=24216764; DOI=10.1128/mcb.00956-13;
RA Zhao Y., Zhang Y.D., Zhang Y.Y., Qian S.W., Zhang Z.C., Li S.F., Guo L.,
RA Liu Y., Wen B., Lei Q.Y., Tang Q.Q., Li X.;
RT "p300-dependent acetylation of activating transcription factor 5 enhances
RT C/EBPbeta transactivation of C/EBPalpha during 3T3-L1 differentiation.";
RL Mol. Cell. Biol. 34:315-324(2014).
RN [21]
RP FUNCTION, INTERACTION WITH ALPHA-TUBULIN; GAMMA-TUBULIN; PCNT; TUBGCP2 AND
RP TUBGCP4, AND SUBCELLULAR LOCATION.
RX PubMed=26213385; DOI=10.1016/j.cell.2015.06.055;
RA Madarampalli B., Yuan Y., Liu D., Lengel K., Xu Y., Li G., Yang J., Liu X.,
RA Lu Z., Liu D.X.;
RT "ATF5 Connects the Pericentriolar Materials to the Proximal End of the
RT Mother Centriole.";
RL Cell 162:580-592(2015).
RN [22]
RP FUNCTION, INTERACTION WITH NLK, PHOSPHORYLATION, UBIQUITINATION, AND
RP MUTAGENESIS OF 92-SER--THR-94; SER-126 AND SER-190.
RX PubMed=25512613; DOI=10.1128/mcb.01228-14;
RA Zhang Z.Y., Li S.Z., Zhang H.H., Wu Q.R., Gong J., Liang T., Gao L.,
RA Xing N.N., Liu W.B., Du R.L., Zhang X.D.;
RT "Stabilization of ATF5 by TAK1-Nemo-like kinase critically regulates the
RT interleukin-1beta-stimulated C/EBP signaling pathway.";
RL Mol. Cell. Biol. 35:778-788(2015).
CC -!- FUNCTION: Transcription factor that either stimulates or represses gene
CC transcription through binding of different DNA regulatory elements such
CC as cAMP response element (CRE) (consensus: 5'-GTGACGT[AC][AG]-3'),
CC ATF5-specific response element (ARE) (consensus: 5'-
CC C[CT]TCT[CT]CCTT[AT]-3') but also the amino acid response element
CC (AARE), present in many viral and cellular promoters. Critically
CC involved, often in a cell type-dependent manner, in cell survival,
CC proliferation, and differentiation (PubMed:10373550, PubMed:15358120,
CC PubMed:21212266, PubMed:20654631). Its transcriptional activity is
CC enhanced by CCND3 and slightly inhibited by CDK4 (PubMed:15358120).
CC Important regulator of the cerebral cortex formation, functions in
CC cerebral cortical neuroprogenitor cells to maintain proliferation and
CC to block differentiation into neurons. Must be down-regulated in order
CC for such cells to exit the cycle and differentiate (By similarity).
CC Participates in the pathways by which SHH promotes cerebellar granule
CC neuron progenitor cells proliferation (By similarity). Critical for
CC survival of mature olfactory sensory neurons (OSN), directs expression
CC of OSN-specific genes (By similarity). May be involved in osteogenic
CC differentiation (PubMed:22442021). Promotes cell proliferation and
CC survival by inducing the expression of EGR1 sinergistically with ELK1.
CC Once acetylated by EP300, binds to ARE sequences on target genes
CC promoters, such as BCL2 and EGR1 (PubMed:21791614). Plays an anti-
CC apoptotic role through the transcriptional regulation of BCL2, this
CC function seems to be cell type-dependent (By similarity). Cooperates
CC with NR1I3/CAR in the transcriptional activation of CYP2B6 in liver
CC (PubMed:18332083). In hepatic cells, represses CRE-dependent
CC transcription and inhibits proliferation by blocking at G2/M phase
CC (PubMed:22528486, PubMed:18701499). May act as a negative regulator of
CC IL1B transduction pathway in liver (PubMed:24379400). Upon IL1B
CC stimulus, cooperates with NLK to activate the transactivation activity
CC of C/EBP subfamily members (PubMed:25512613). Besides its function of
CC transcription factor, acts as a cofactor of CEBPB to activate CEBPA and
CC promote adipocyte differentiation (PubMed:24216764). Regulates
CC centrosome dynamics in a cell-cycle- and centriole-age-dependent
CC manner. Forms 9-foci symmetrical ring scaffold around the mother
CC centriole to control centrosome function and the interaction between
CC centrioles and pericentriolar material (PubMed:26213385).
CC {ECO:0000250|UniProtKB:O70191, ECO:0000250|UniProtKB:Q6P788,
CC ECO:0000269|PubMed:10373550, ECO:0000269|PubMed:15358120,
CC ECO:0000269|PubMed:18332083, ECO:0000269|PubMed:18701499,
CC ECO:0000269|PubMed:20654631, ECO:0000269|PubMed:21212266,
CC ECO:0000269|PubMed:21791614, ECO:0000269|PubMed:22442021,
CC ECO:0000269|PubMed:22528486, ECO:0000269|PubMed:24216764,
CC ECO:0000269|PubMed:24379400, ECO:0000269|PubMed:25512613,
CC ECO:0000269|PubMed:26213385}.
CC -!- SUBUNIT: Binds DNA as a dimer. Interacts with PTP4A1/PRL-1 (By
CC similarity). Interacts with CCND3, but not with CCND1 or CCND2
CC (PubMed:15358120). Interacts with HSPA1A or HSPA1B; the interaction
CC protects ATF5 from degradation via proteasome-dependent and caspase-
CC dependent processes. Interacts (via C-terminal region) with NPM1 (via
CC C-terminal region); the interaction leads to loss of association
CC between HSPA1A or HSPA1B and ATF5 and promotes ATF5 degradation via
CC proteasome-dependent and caspase-dependent processes (PubMed:22528486,
CC PubMed:24379400). Interacts with NLK; the interaction stabilizes ATF5
CC at the protein level in a kinase-independent manner (PubMed:25512613).
CC Interacts with alpha-tubulin, gamma-tubulin members TUBGCP2 and
CC TUBGCP4, PCNT; the ATF5:PCNT:polyglutamylated tubulin (PGT) tripartite
CC unites the mother centriole and the pericentriolar material (PCM) in
CC the centrosome (PubMed:26213385). Interacts with CEBPB and EP300; EP300
CC is required for ATF5 and CEBPB interaction and DNA binding (By
CC similarity). {ECO:0000250|UniProtKB:O70191,
CC ECO:0000269|PubMed:15358120, ECO:0000269|PubMed:22528486,
CC ECO:0000269|PubMed:24379400, ECO:0000269|PubMed:25512613,
CC ECO:0000269|PubMed:26213385}.
CC -!- INTERACTION:
CC Q9Y2D1; Q16204: CCDC6; NbExp=3; IntAct=EBI-492509, EBI-1045350;
CC Q9Y2D1; P49715: CEBPA; NbExp=2; IntAct=EBI-492509, EBI-1172054;
CC Q9Y2D1; P53567: CEBPG; NbExp=8; IntAct=EBI-492509, EBI-740209;
CC Q9Y2D1; Q9NRI5: DISC1; NbExp=8; IntAct=EBI-492509, EBI-529989;
CC Q9Y2D1; Q14232: EIF2B1; NbExp=5; IntAct=EBI-492509, EBI-491065;
CC Q9Y2D1; Q13227: GPS2; NbExp=3; IntAct=EBI-492509, EBI-713355;
CC Q9Y2D1; Q14145: KEAP1; NbExp=3; IntAct=EBI-492509, EBI-751001;
CC Q9Y2D1; P02766: TTR; NbExp=3; IntAct=EBI-492509, EBI-711909;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15358120}. Nucleus
CC {ECO:0000255|PROSITE-ProRule:PRU00978, ECO:0000269|PubMed:15358120,
CC ECO:0000269|PubMed:22528486}. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome {ECO:0000269|PubMed:26213385}.
CC Note=Actively transported to the centrosome and accumulated in the
CC pericentriolar material (PCM) during G1 to M phase via a microtubule-
CC dependent mechanism. During late telophase and cytokinesis,
CC translocates from the centrosome to the midbody.
CC {ECO:0000269|PubMed:26213385}.
CC -!- TISSUE SPECIFICITY: Widely expressed with higher expression levels in
CC liver. {ECO:0000269|PubMed:18332083}.
CC -!- INDUCTION: Down-regulated by pro-apoptotic stimuli (PubMed:21212266).
CC However, the pro-apoptotic cisplatin increases protein levels by
CC inhibiting polyubiquitination (PubMed:18458088). IL1B increases protein
CC levels through protein stabilization and increase of translation
CC efficiency (PubMed:24379400). {ECO:0000269|PubMed:18458088,
CC ECO:0000269|PubMed:21212266, ECO:0000269|PubMed:24379400}.
CC -!- PTM: Ubiquitinated by CDC34 and UBE2B in order to be degraded by the
CC proteasome. Cisplatin inhibits ubiquitination and proteasome-mediated
CC degradation by inhibiting the interaction with CDC34 (PubMed:18458088).
CC Ubiquitination and degradation by the proteasome are inhibited by NLK
CC in a kinase-independent manner (PubMed:25512613).
CC {ECO:0000269|PubMed:10373550, ECO:0000269|PubMed:18458088,
CC ECO:0000269|PubMed:22528486, ECO:0000269|PubMed:25512613}.
CC -!- PTM: Phosphorylated by NLK, probably at Ser-92, Thr-94, Ser-126 and
CC Ser-190. {ECO:0000269|PubMed:25512613}.
CC -!- PTM: Acetylated at Lys-29 by EP300, the acetylation enhances the
CC interaction with CEBPB, DNA-binding and transactivation activity.
CC {ECO:0000250|UniProtKB:O70191, ECO:0000250|UniProtKB:Q6P788}.
CC -!- SIMILARITY: Belongs to the bZIP family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/ATF5ID50361ch19q13.html";
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DR EMBL; AF305687; AAG22558.1; -; mRNA.
DR EMBL; AB073613; BAD38650.1; -; mRNA.
DR EMBL; AB021663; BAA78477.2; -; mRNA.
DR EMBL; AK024402; BAG51295.1; -; mRNA.
DR EMBL; AC011452; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471177; EAW52581.1; -; Genomic_DNA.
DR EMBL; BC005174; AAH05174.1; -; mRNA.
DR EMBL; AF101388; AAD28370.1; -; mRNA.
DR CCDS; CCDS12789.1; -.
DR RefSeq; NP_001180575.1; NM_001193646.1.
DR RefSeq; NP_001277675.1; NM_001290746.1.
DR RefSeq; NP_036200.2; NM_012068.5.
DR RefSeq; XP_011524931.1; XM_011526629.2.
DR AlphaFoldDB; Q9Y2D1; -.
DR SMR; Q9Y2D1; -.
DR BioGRID; 116487; 19.
DR ComplexPortal; CPX-6585; bZIP transcription factor complex, ATF5-BATF.
DR ComplexPortal; CPX-6586; bZIP transcription factor complex, ATF5-CEBPA.
DR ComplexPortal; CPX-6588; bZIP transcription factor complex, ATF5-CEBPG.
DR ComplexPortal; CPX-6589; bZIP transcription factor complex, ATF5-CEBPE.
DR IntAct; Q9Y2D1; 19.
DR STRING; 9606.ENSP00000396954; -.
DR DrugBank; DB00852; Pseudoephedrine.
DR iPTMnet; Q9Y2D1; -.
DR PhosphoSitePlus; Q9Y2D1; -.
DR BioMuta; ATF5; -.
DR DMDM; 308153647; -.
DR jPOST; Q9Y2D1; -.
DR MassIVE; Q9Y2D1; -.
DR PaxDb; Q9Y2D1; -.
DR PeptideAtlas; Q9Y2D1; -.
DR PRIDE; Q9Y2D1; -.
DR ProteomicsDB; 85733; -.
DR TopDownProteomics; Q9Y2D1; -.
DR Antibodypedia; 18799; 301 antibodies from 33 providers.
DR DNASU; 22809; -.
DR Ensembl; ENST00000423777.7; ENSP00000396954.1; ENSG00000169136.13.
DR Ensembl; ENST00000595125.5; ENSP00000470633.1; ENSG00000169136.13.
DR GeneID; 22809; -.
DR KEGG; hsa:22809; -.
DR MANE-Select; ENST00000423777.7; ENSP00000396954.1; NM_001193646.2; NP_001180575.1.
DR UCSC; uc002prd.4; human.
DR CTD; 22809; -.
DR DisGeNET; 22809; -.
DR GeneCards; ATF5; -.
DR HGNC; HGNC:790; ATF5.
DR HPA; ENSG00000169136; Tissue enriched (liver).
DR MIM; 606398; gene.
DR neXtProt; NX_Q9Y2D1; -.
DR OpenTargets; ENSG00000169136; -.
DR PharmGKB; PA25090; -.
DR VEuPathDB; HostDB:ENSG00000169136; -.
DR eggNOG; KOG4571; Eukaryota.
DR GeneTree; ENSGT00530000063801; -.
DR HOGENOM; CLU_083640_0_0_1; -.
DR InParanoid; Q9Y2D1; -.
DR OMA; KIPGHYE; -.
DR OrthoDB; 1524842at2759; -.
DR PhylomeDB; Q9Y2D1; -.
DR TreeFam; TF316136; -.
DR PathwayCommons; Q9Y2D1; -.
DR Reactome; R-HSA-9648895; Response of EIF2AK1 (HRI) to heme deficiency.
DR SignaLink; Q9Y2D1; -.
DR SIGNOR; Q9Y2D1; -.
DR BioGRID-ORCS; 22809; 21 hits in 1109 CRISPR screens.
DR ChiTaRS; ATF5; human.
DR GeneWiki; ATF5; -.
DR GenomeRNAi; 22809; -.
DR Pharos; Q9Y2D1; Tbio.
DR PRO; PR:Q9Y2D1; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q9Y2D1; protein.
DR Bgee; ENSG00000169136; Expressed in right lobe of liver and 115 other tissues.
DR ExpressionAtlas; Q9Y2D1; baseline and differential.
DR Genevisible; Q9Y2D1; HS.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; IPI:ComplexPortal.
DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA: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; ISA:NTNU_SB.
DR GO; GO:0019900; F:kinase binding; IPI:UniProtKB.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IMP:NTNU_SB.
DR GO; GO:0043565; F:sequence-specific DNA binding; ISS:UniProtKB.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISS:UniProtKB.
DR GO; GO:0015631; F:tubulin binding; IDA:UniProtKB.
DR GO; GO:0021930; P:cerebellar granule cell precursor proliferation; ISS:UniProtKB.
DR GO; GO:0007623; P:circadian rhythm; IEA:Ensembl.
DR GO; GO:0045444; P:fat cell differentiation; IMP:UniProtKB.
DR GO; GO:0035264; P:multicellular organism growth; IEA:Ensembl.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:1902750; P:negative regulation of cell cycle G2/M phase transition; IDA:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0021891; P:olfactory bulb interneuron development; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0009791; P:post-embryonic development; IEA:Ensembl.
DR GO; GO:0046605; P:regulation of centrosome cycle; IDA:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:UniProtKB.
DR InterPro; IPR029855; ATF5.
DR InterPro; IPR004827; bZIP.
DR InterPro; IPR046347; bZIP_sf.
DR PANTHER; PTHR13044:SF3; PTHR13044:SF3; 1.
DR Pfam; PF00170; bZIP_1; 1.
DR SMART; SM00338; BRLZ; 1.
DR SUPFAM; SSF57959; SSF57959; 1.
DR PROSITE; PS50217; BZIP; 1.
PE 1: Evidence at protein level;
KW Acetylation; Activator; Cytoplasm; Cytoskeleton; DNA-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1..282
FT /note="Cyclic AMP-dependent transcription factor ATF-5"
FT /id="PRO_0000076586"
FT DOMAIN 208..271
FT /note="bZIP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 1..21
FT /note="Required for protein stabilization induced by IL1B"
FT /evidence="ECO:0000269|PubMed:24379400"
FT REGION 116..152
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 119..217
FT /note="Interaction with PTP4A1"
FT REGION 173..238
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 210..230
FT /note="Basic motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 236..250
FT /note="Leucine-zipper"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT COMPBIAS 118..149
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 176..199
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 206..238
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 29
FT /note="N6-acetyllysine; by EP300"
FT /evidence="ECO:0000250|UniProtKB:O70191"
FT MOD_RES 256
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VARIANT 121
FT /note="P -> L (in dbSNP:rs283526)"
FT /evidence="ECO:0000269|PubMed:15221005,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_022786"
FT MUTAGEN 3..25
FT /note="LLATLGLELDRALLPASGLGWLV->AAATAGAEADRAAAPASGAGWAA:
FT Highly increases protein levels. No effect on protein
FT stability enhanced by IL1B."
FT /evidence="ECO:0000269|PubMed:24379400"
FT MUTAGEN 3..4
FT /note="LL->AA: Increases protein levels. No effect on
FT protein stability enhanced by IL1B."
FT /evidence="ECO:0000269|PubMed:24379400"
FT MUTAGEN 3..4
FT /note="LL->II: Decreases protein levels."
FT /evidence="ECO:0000269|PubMed:24379400"
FT MUTAGEN 3..4
FT /note="LL->VV: No effect on protein levels. No effect on
FT protein stability enhanced by IL1B."
FT /evidence="ECO:0000269|PubMed:24379400"
FT MUTAGEN 7
FT /note="L->A: Increases protein levels."
FT /evidence="ECO:0000269|PubMed:24379400"
FT MUTAGEN 9..11
FT /note="LEL->AEA: Increases protein levels."
FT /evidence="ECO:0000269|PubMed:24379400"
FT MUTAGEN 15..16
FT /note="LL->AA: Increases protein levels."
FT /evidence="ECO:0000269|PubMed:24379400"
FT MUTAGEN 21..25
FT /note="LGWLV->AGWAA: Increases protein levels."
FT /evidence="ECO:0000269|PubMed:24379400"
FT MUTAGEN 92..94
FT /note="SPT->APA: Not phosphorylated; when associated with
FT A-126 and A-190."
FT MUTAGEN 126
FT /note="S->A: Not phosphorylated; when associated with 92-
FT A--A-94 and A-190."
FT MUTAGEN 157
FT /note="D->A: Resistant to cleavage by CASP3."
FT /evidence="ECO:0000269|PubMed:22528486"
FT MUTAGEN 190
FT /note="S->A: Not phosphorylated; when associated with 92-
FT A--A-94 and A-126."
FT CONFLICT 161..163
FT /note="LLA -> RHE (in Ref. 8; AAD28370)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 282 AA; 30674 MW; DDB2F907CA0215A0 CRC64;
MSLLATLGLE LDRALLPASG LGWLVDYGKL PPAPAPLAPY EVLGGALEGG LPVGGEPLAG
DGFSDWMTER VDFTALLPLE PPLPPGTLPQ PSPTPPDLEA MASLLKKELE QMEDFFLDAP
PLPPPSPPPL PPPPLPPAPS LPLSLPSFDL PQPPVLDTLD LLAIYCRNEA GQEEVGMPPL
PPPQQPPPPS PPQPSRLAPY PHPATTRGDR KQKKRDQNKS AALRYRQRKR AEGEALEGEC
QGLEARNREL KERAESVERE IQYVKDLLIE VYKARSQRTR SC
