ATF5

Summary

ATF5 (activating transcription factor 5, HGNC:790) is a protein-coding gene on chromosome 19q13.33, encoding Cyclic AMP-dependent transcription factor ATF-5 (Q9Y2D1). Transcription factor that either stimulates or represses gene transcription through binding of different DNA regulatory elements such as cAMP response element (CRE) (consensus: 5’-GTGACGT[AC][AG]-3’), ATF5-specific response element (ARE) (consensus: 5’-C[CT]TCT[CT]CCTT[AT]-3’) b….

Enables several functions, including DNA-binding transcription activator activity, RNA polymerase II-specific; RNA polymerase II transcription regulatory region sequence-specific DNA binding activity; and tubulin binding activity. Involved in several processes, including fat cell differentiation; regulation of DNA-templated transcription; and regulation of cell cycle process. Located in centrosome; cytosol; and nucleoplasm. Part of RNA polymerase II transcription regulator complex.

Source: NCBI Gene 22809 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 29 total
• Transcription factor: yes — 35 downstream targets (CollecTRI)
• MANE Select transcript: NM_001193646

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:790
Approved symbol	ATF5
Name	activating transcription factor 5
Location	19q13.33
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000169136
Ensembl biotype	protein_coding
OMIM	606398
Entrez	22809

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 10 protein_coding

ENST00000423777, ENST00000595125, ENST00000596658, ENST00000597227, ENST00000600336, ENST00000858032, ENST00000858033, ENST00000858034, ENST00000858035, ENST00000858036

RefSeq mRNA: 3 — MANE Select: NM_001193646 NM_001193646, NM_001290746, NM_012068

CCDS: CCDS12789

Canonical transcript exons

ENST00000423777 — 3 exons

Exon	Start	End
ENSE00001125999	49930732	49931028
ENSE00001662627	49932422	49933935
ENSE00003132147	49929205	49929400

Expression profiles

Bgee: expression breadth ubiquitous, 167 present calls, max score 99.70.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 149.1976 / max 9451.1783, expressed in 1820 samples.

FANTOM5 promoters (16 alternative TSS)

Promoter ID	TPM avg	Samples expressed
177101	140.2251	1820
177100	3.1168	353
177112	1.2619	484
177098	0.7957	445
177116	0.7116	333
177097	0.6907	343
177099	0.4656	136
177115	0.4129	159
177113	0.3934	150
177110	0.3492	112

Top tissues by expression

237 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	99.70	gold quality
liver	UBERON:0002107	95.57	gold quality
right adrenal gland cortex	UBERON:0035827	94.92	gold quality
mucosa of stomach	UBERON:0001199	94.70	gold quality
right adrenal gland	UBERON:0001233	94.41	gold quality
left adrenal gland	UBERON:0001234	94.20	gold quality
left adrenal gland cortex	UBERON:0035825	93.95	gold quality
adrenal cortex	UBERON:0001235	93.52	gold quality
left testis	UBERON:0004533	92.36	gold quality
vena cava	UBERON:0004087	92.16	silver quality
nasal cavity epithelium	UBERON:0005384	92.15	gold quality
left ventricle myocardium	UBERON:0006566	92.09	gold quality
right testis	UBERON:0004534	91.98	gold quality
adrenal gland	UBERON:0002369	91.92	gold quality
cardiac muscle of right atrium	UBERON:0003379	91.66	gold quality
myocardium	UBERON:0002349	91.29	gold quality
kidney epithelium	UBERON:0004819	91.01	gold quality
monocyte	CL:0000576	90.73	gold quality
vermiform appendix	UBERON:0001154	90.71	gold quality
leukocyte	CL:0000738	90.34	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	90.21	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	90.10	gold quality
testis	UBERON:0000473	89.83	gold quality
granulocyte	CL:0000094	89.73	gold quality
upper arm skin	UBERON:0004263	89.58	gold quality
caecum	UBERON:0001153	89.46	gold quality
hindlimb stylopod muscle	UBERON:0004252	88.94	gold quality
body of stomach	UBERON:0001161	88.76	gold quality
subcutaneous adipose tissue	UBERON:0002190	88.50	gold quality
gastrocnemius	UBERON:0001388	88.47	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	78.66
E-HCAD-9	yes	57.48
E-HCAD-13	yes	23.07
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

35 targets.

Target	Regulation
APRT
ASNS	Activation
ATF5
ATF7IP
BCL2	Activation
CCND3	Activation
CEBPA
CEBPB
CREB1	Activation
CREBBP
CYP2B6	Activation
DDIT3	Unknown
DISC1	Unknown
EBP
EGR1	Unknown
EYA1
GFAP
GNAS
HNRNPD
HNRNPH1
HSPB1
ID1	Repression
IL1B
KIR3DL1
LRP6
MCL1	Activation
NOTCH1
NPM1
PPARGC1A	Activation
SAA1

Upstream regulators (CollecTRI, top): ATF4, ATF5, BMAL1, CEBPB, CLOCK, CREB1, DDIT3, EBF1, NPM1

miRNA regulators (miRDB)

30 targeting ATF5, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-4753-5P	99.54	68.51	1356
HSA-MIR-29A-5P	99.08	68.59	1813
HSA-MIR-6506-5P	99.04	65.66	1386
HSA-MIR-3926	98.95	69.26	1438
HSA-MIR-5589-5P	98.34	64.82	1148
HSA-MIR-4483	98.09	64.12	1642
HSA-MIR-6847-5P	97.93	66.74	1808
HSA-MIR-610	96.84	67.98	905
HSA-MIR-5194	96.77	63.91	1021
HSA-MIR-500B-3P	96.49	65.40	1087
HSA-MIR-1293	96.16	64.69	916
HSA-MIR-3679-5P	94.75	66.46	862
HSA-MIR-1185-5P	94.47	65.95	725
HSA-MIR-11400	94.03	67.12	81

Literature-anchored findings (GeneRIF, showing 40)

• activating transcription factor 5 (ATF5) is a new interacting partner of cyclin D3 (PMID:15358120)
• recruitment of ATFx to the HTLV-1 LTR serves to link viral transcription with critical events in cellular homeostasis (PMID:15890932)
• Overexpression of the bZIP protein ATF5, a transcriptional activator, stimulates asparagine synthetase promoter/reporter gene transcription via the nutrient-sensing response unit. (PMID:16164412)
• The widespread expression of ATF5 in glioblastomas (PMID:16170340)
• ATF5 increases cisplatin-induced apoptosis through up-regulation of Cyclin D3 transcription, which elicits survival signals in HeLa cells (PMID:16300731)
• Contribution of common variations of ATF4 and ATF5 to the pathophysiology of bipolar disorder may be minimal if any. (PMID:17346882)
• translation of ATF5 is regulated by the alternative 5’-UTR region of its mRNA, and ATF5 may play a role in protecting cells from amino acid limitation or arsenite-induced oxidative stress (PMID:18055463)
• ATF4 contributes to basal ATF5 transcription, and eIF2 kinases direct the translational expression of multiple transcription regulators by a mechanism involving delayed translation reinitiation (PMID:18195013)
• ATF5 is abundant in the liver, activates CYP2B6, and cooperates with the constitutive androstane receptor in sustaining the hepatic-specific expression of this P450 in human hepatocytes and hepatoma cells. (PMID:18332083)
• cisplatin increased ATF5 protein expression via preventing its ubiquitin-dependent degradation, which might be associated with its promoting the nucleus-to-cytoplasm translocation of E2 ubiquitin-conjugating enzyme Cdc34 (PMID:18458088)
• Loss of ATF5 is associated with hepatocellular carcinoma (PMID:18701499)
• The down-regulation of the SAP gene by ATF5 may represent a common mechanism for the pathogenesis of Hemophagocytic syndrome that is associated with either Epstein-Barr virus infection or immune disorders with dysregulated T-cell activation. (PMID:18832568)
• These results indicate that ATF5 is targeted for degradation by the ubiquitin-proteasome pathway, and that cadmium slows the rate of ATF5 degradation via a post-ubiquitination mechanism. (PMID:19285020)
• Identified a novel ATF5 consensus DNA binding sequence. Demonstrate in C6 glioma and MCF-7 breast cancer cells that ATF5 occupies this sequence and that ATF5 activates reporter gene expression driven by this site. (PMID:19531563)
• our studies not only provided molecular basis of ATF5 transcriptional regulation, but also identified ATF5 as a target gene of EBF1 transcription factor. (PMID:20423929)
• BCL-2 is an essential mediator for the cancer-specific cell survival function of ATF5 in glioblastoma and breast cancer cells (PMID:21212266)
• an essential role for HSP70 in maintaining high levels of ATF5 expression in glioma cells and support the conclusion that ATF5 is an important substrate protein of HSP70 that mediates HSP70-promoted cell survival in glioma cells. (PMID:21521685)
• coordinated actions by ATF5, p300, Elk-1, and ERK/mitogen-activated protein kinase are essential for ATF5-dependent Egr-1 activation and cell proliferation and survival (PMID:21791614)
• ATF5 polymorphisms influence ATF function and response to treatment in children with childhood acute lymphoblastic leukemia. (PMID:21972289)
• The evidence suggests a role for ATF5 in the regulation of osteogenic differentiation in adipose-derived stem cells. (PMID:22442021)
• a mechanistic link between elevated NPM1 expression and depressed ATF5 in HCC and suggests that regulation of ATF5 by NPM1 plays an important role in the proliferation and survival of HCC. (PMID:22528486)
• demonstrated that interference with the function of ATF5 could markedly increase the apoptosis of ovarian cancer cells and identified B-cell leukemia lymphoma-2 as an ATF5-targeted apoptosis-related gene (PMID:23018213)
• The 5’-untranslated region regulates ATF5 mRNA stability via nonsense-mediated mRNA decay in response to environmental stress. (PMID:23876217)
• ATF5 promotes the proliferation of HSV-1 via a potential mechanism by which ATF5 enhances the transcription of viral genes during the course of an HSV-1 infection (PMID:24302293)
• N-terminal hydrophobic amino acids play an important role in the regulation of ATF5 protein expression in IL-1beta-mediated immune response and that ATF5 is a negative regulator for IL-1beta-induced expression of SAA1 and SAA2 in HepG2 cells. (PMID:24379400)
• Low expression level of ATF5 in hepatocellular carcinoma indicated aggressive tumor behavior and predicted a worse clinical outcome. (PMID:25294425)
• the TAK1-NLK pathway is a novel regulator of basal or IL-1beta-triggered C/EBP activation though stabilization of ATF5 (PMID:25512613)
• Report a global loss of 5hmC identified three new genes (ECM1, ATF5, and EOMES) with potential anti-cancer functions that may promote the understanding of the molecular mechanisms of hepatocellular carcinoma development and progression. (PMID:25517360)
• Activating transcription factor 5 enhances radioresistance and malignancy in cancer. (PMID:25682872)
• Data show that ATF5 is an essential structural protein that is required for the interaction between the mother centriole and the pericentriolar material. (PMID:26213385)
• This study provides the first evidence that the methylation level of ATF5 decreased, and its mRNA expression was evidently up-regulated in glioma. (PMID:26365117)
• These results suggest that the hepatic functions of the human iPS-HLCs could be enhanced by ATF5, c/EBPalpha, and PROX1 transduction. (PMID:26679606)
• Our results suggest that ATF5 promotes invasion by inducing the expression of integrin-alpha2 and integrin-beta1 in several human cancer cell lines. (PMID:27125458)
• ATF5 expression can rescue UPR(mt) signaling in atfs-1-deficient worms requiring the same UPR(mt) promoter element identified in C. elegans. Furthermore, mammalian cells require ATF5 to maintain mitochondrial activity during mitochondrial stress and promote organelle recovery. Combined, these data suggest that regulation of the UPR(mt) is conserved from worms to mammals. (PMID:27426517)
• Study reports that reduced levels of ATF5 in brain of Huntington’s disease patients, probably due to its sequestration into the characteristic PolyQ containing neuronal inclusion bodies, correlates with decreased levels of the antiapoptotic protein MCL1, a transcriptional target of ATF5. Also provides evidence of decreased ATF5 being deleterious by rendering neurons more vulnerable to polyQ-induced apoptosis. (PMID:28861715)
• Data suggest that ATF5 is modified by SUMO2/3 at a conserved SUMO-targeting consensus site; this SUMOylation of ATF5 appears to be required for transport of ATF5 to centrosome. (ATF5 = activating transcription factor-5; SUMO = small ubiquitin-like modifier) (PMID:29326161)
• Dominant-Negative ATF5 Compromises Cancer Cell Survival by Targeting CEBPB and CEBPD. (PMID:31676720)
• ATF5 involved in radioresistance in nasopharyngeal carcinoma by promoting epithelial-to-mesenchymal phenotype transition. (PMID:32342199)
• Expression of activating transcription factor 5 (ATF5) is mediated by microRNA-520b-3p under diverse cellular stress in cancer cells. (PMID:32603335)
• Maf1 suppression of ATF5-dependent mitochondrial unfolded protein response contributes to rapamycin-induced radio-sensitivity in lung cancer cell line A549. (PMID:33640883)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	atf5a	ENSDARG00000068096
danio_rerio	atf5b	ENSDARG00000077785
mus_musculus	Atf5	ENSMUSG00000038539
rattus_norvegicus	Atf5	ENSRNOG00000020060
caenorhabditis_elegans		WBGENE00000221
caenorhabditis_elegans		WBGENE00013878

Paralogs (1): ATF4 (ENSG00000128272)

Protein

Protein identifiers

Cyclic AMP-dependent transcription factor ATF-5 — Q9Y2D1 (reviewed: Q9Y2D1)

Alternative names: Activating transcription factor 5, Transcription factor ATFx

All UniProt accessions (4): Q9Y2D1, M0QZD2, M0R040, M0R0D5

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor that either stimulates or represses gene transcription through binding of different DNA regulatory elements such as cAMP response element (CRE) (consensus: 5’-GTGACGT[AC][AG]-3’), ATF5-specific response element (ARE) (consensus: 5’-C[CT]TCT[CT]CCTT[AT]-3’) but also the amino acid response element (AARE), present in many viral and cellular promoters. Critically involved, often in a cell type-dependent manner, in cell survival, proliferation, and differentiation. Its transcriptional activity is enhanced by CCND3 and slightly inhibited by CDK4. Important regulator of the cerebral cortex formation, functions in cerebral cortical neuroprogenitor cells to maintain proliferation and to block differentiation into neurons. Must be down-regulated in order for such cells to exit the cycle and differentiate. Participates in the pathways by which SHH promotes cerebellar granule neuron progenitor cells proliferation. Critical for survival of mature olfactory sensory neurons (OSN), directs expression of OSN-specific genes. May be involved in osteogenic differentiation. Promotes cell proliferation and survival by inducing the expression of EGR1 sinergistically with ELK1. Once acetylated by EP300, binds to ARE sequences on target genes promoters, such as BCL2 and EGR1. Plays an anti-apoptotic role through the transcriptional regulation of BCL2, this function seems to be cell type-dependent. Cooperates with NR1I3/CAR in the transcriptional activation of CYP2B6 in liver. In hepatic cells, represses CRE-dependent transcription and inhibits proliferation by blocking at G2/M phase. May act as a negative regulator of IL1B transduction pathway in liver. Upon IL1B stimulus, cooperates with NLK to activate the transactivation activity of C/EBP subfamily members. Besides its function of transcription factor, acts as a cofactor of CEBPB to activate CEBPA and promote adipocyte differentiation. Regulates centrosome dynamics in a cell-cycle- and centriole-age-dependent manner. Forms 9-foci symmetrical ring scaffold around the mother centriole to control centrosome function and the interaction between centrioles and pericentriolar material.

Subunit / interactions. Binds DNA as a dimer. Interacts with PTP4A1/PRL-1. Interacts with CCND3, but not with CCND1 or CCND2. Interacts with HSPA1A or HSPA1B; the interaction protects ATF5 from degradation via proteasome-dependent and caspase-dependent processes. Interacts (via C-terminal region) with NPM1 (via C-terminal region); the interaction leads to loss of association between HSPA1A or HSPA1B and ATF5 and promotes ATF5 degradation via proteasome-dependent and caspase-dependent processes. Interacts with NLK; the interaction stabilizes ATF5 at the protein level in a kinase-independent manner. Interacts with alpha-tubulin, gamma-tubulin members TUBGCP2 and TUBGCP4, PCNT; the ATF5:PCNT:polyglutamylated tubulin (PGT) tripartite unites the mother centriole and the pericentriolar material (PCM) in the centrosome. Interacts with CEBPB and EP300; EP300 is required for ATF5 and CEBPB interaction and DNA binding.

Subcellular location. Cytoplasm. Nucleus. Cytoskeleton. Microtubule organizing center. Centrosome.

Tissue specificity. Widely expressed with higher expression levels in liver.

Post-translational modifications. Ubiquitinated by CDC34 and UBE2B in order to be degraded by the proteasome. Cisplatin inhibits ubiquitination and proteasome-mediated degradation by inhibiting the interaction with CDC34. Ubiquitination and degradation by the proteasome are inhibited by NLK in a kinase-independent manner. Phosphorylated by NLK, probably at Ser-92, Thr-94, Ser-126 and Ser-190. Acetylated at Lys-29 by EP300, the acetylation enhances the interaction with CEBPB, DNA-binding and transactivation activity.

Induction. Down-regulated by pro-apoptotic stimuli. However, the pro-apoptotic cisplatin increases protein levels by inhibiting polyubiquitination. IL1B increases protein levels through protein stabilization and increase of translation efficiency.

Similarity. Belongs to the bZIP family.

RefSeq proteins (3): NP_001180575, NP_001277675, NP_036200 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004827	bZIP	Domain
IPR046347	bZIP_sf	Homologous_superfamily

Pfam: PF00170

UniProt features (27 total): mutagenesis site 12, region of interest 6, compositionally biased region 3, modified residue 2, chain 1, domain 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y2D1-F1	69.00	0.29

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 29, 256

Mutagenesis-validated functional residues (12):

Position	Phenotype
3–25	highly increases protein levels. no effect on protein stability enhanced by il1b.
3–4	increases protein levels. no effect on protein stability enhanced by il1b.
3–4	decreases protein levels.
3–4	no effect on protein levels. no effect on protein stability enhanced by il1b.
7	increases protein levels.
9–11	increases protein levels.
15–16	increases protein levels.
21–25	increases protein levels.
92–94	not phosphorylated; when associated with a-126 and a-190.
126	not phosphorylated; when associated with 92-a–a-94 and a-190.
157	resistant to cleavage by casp3.
190	not phosphorylated; when associated with 92-a–a-94 and a-126.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-9648895	Response of EIF2AK1 (HRI) to heme deficiency
R-HSA-9841251	Mitochondrial unfolded protein response (UPRmt)
R-HSA-2262752	Cellular responses to stress
R-HSA-8953897	Cellular responses to stimuli

MSigDB gene sets: 331 (showing top): GOBP_CIRCADIAN_RHYTHM, GOBP_FOREBRAIN_NEURON_DEVELOPMENT, E2F_Q4, GOBP_HINDBRAIN_DEVELOPMENT, GOBP_OLFACTORY_BULB_INTERNEURON_DIFFERENTIATION, MULLIGHAN_NPM1_SIGNATURE_3_UP, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, E2F4DP1_01, GNF2_GSTM1, CMYB_01, GNF2_HPN, PID_PRL_SIGNALING_EVENTS_PATHWAY, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_GROWTH, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN

GO Biological Process (19): regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), circadian rhythm (GO:0007623), negative regulation of cell population proliferation (GO:0008285), post-embryonic development (GO:0009791), olfactory bulb interneuron development (GO:0021891), cerebellar granule cell precursor proliferation (GO:0021930), multicellular organism growth (GO:0035264), negative regulation of apoptotic process (GO:0043066), fat cell differentiation (GO:0045444), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of centrosome cycle (GO:0046605), negative regulation of cell cycle G2/M phase transition (GO:1902750), regulation of gene expression (GO:0010468), olfactory bulb interneuron differentiation (GO:0021889), olfactory lobe development (GO:0021988), regulation of apoptotic process (GO:0042981)

GO Molecular Function (11): transcription cis-regulatory region binding (GO:0000976), RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), chromatin binding (GO:0003682), DNA-binding transcription factor activity (GO:0003700), tubulin binding (GO:0015631), kinase binding (GO:0019900), sequence-specific DNA binding (GO:0043565), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (9): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), centrosome (GO:0005813), cytosol (GO:0005829), RNA polymerase II transcription regulator complex (GO:0090575), transcription regulator complex (GO:0005667), cytoplasm (GO:0005737), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Cellular responses to stress	2
Cellular responses to stimuli	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	4
cellular anatomical structure	4
DNA-templated transcription	3
transcription by RNA polymerase II	2
multicellular organismal process	2
apoptotic process	2
regulation of transcription by RNA polymerase II	2
transcription cis-regulatory region binding	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
binding	2
regulation of gene expression	1
regulation of RNA biosynthetic process	1
rhythmic process	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
multicellular organism development	1
forebrain neuron development	1
olfactory bulb interneuron differentiation	1
cell proliferation in external granule layer	1
developmental growth	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
cell differentiation	1
negative regulation of RNA biosynthetic process	1
positive regulation of RNA biosynthetic process	1
positive regulation of DNA-templated transcription	1
centrosome cycle	1
regulation of cell cycle process	1
regulation of microtubule-based process	1
regulation of cellular component organization	1
cell cycle G2/M phase transition	1
negative regulation of cell cycle phase transition	1
regulation of cell cycle G2/M phase transition	1
gene expression	1
regulation of macromolecule biosynthetic process	1
olfactory bulb development	1
forebrain neuron differentiation	1
telencephalon development	1
anatomical structure development	1

Protein interactions and networks

STRING

1014 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATF5	ATF6	P18850	932
ATF5	CREB3L2	Q70SY1	806
ATF5	IFT54	Q8TDR0	769
ATF5	ATF7	P17544	750
ATF5	BATF	Q16520	742
ATF5	GABBR1	Q9UBS5	713
ATF5	DISC1	Q9NRI5	700
ATF5	ATF6B	Q99941	680
ATF5	PDE4B	Q07343	675
ATF5	CDC34	P49427	673
ATF5	FEZ2	Q9UHY8	668
ATF5	MCL1	Q07820	659
ATF5	LONP1	P36776	655
ATF5	PTP4A1	Q93096	649
ATF5	CEBPG	P53567	645

IntAct

51 interactions, top by confidence:

A	B	Type	Score
ATF5	CEBPG	psi-mi:“MI:0407”(direct interaction)	0.820
CEBPG	ATF5	psi-mi:“MI:0915”(physical association)	0.820
CEBPG	ATF5	psi-mi:“MI:0407”(direct interaction)	0.820
ATF5	CEBPA	psi-mi:“MI:0407”(direct interaction)	0.620
CEBPA	ATF5	psi-mi:“MI:0407”(direct interaction)	0.620
TTR	ATF5	psi-mi:“MI:0915”(physical association)	0.560
CCDC6	ATF5	psi-mi:“MI:0915”(physical association)	0.560
	ATF5	psi-mi:“MI:0915”(physical association)	0.560
EIF2B1	ATF5	psi-mi:“MI:0915”(physical association)	0.560
GPS2	ATF5	psi-mi:“MI:0915”(physical association)	0.560
ATF5	DISC1	psi-mi:“MI:0915”(physical association)	0.540
DISC1	ATF5	psi-mi:“MI:0915”(physical association)	0.540
DISC1	ATF5	psi-mi:“MI:0403”(colocalization)	0.540
ATF5	BATF	psi-mi:“MI:0407”(direct interaction)	0.440
CEBPE	ATF5	psi-mi:“MI:0407”(direct interaction)	0.440
ATF5	KEAP1	psi-mi:“MI:0915”(physical association)	0.400
rep	ATF5	psi-mi:“MI:0915”(physical association)	0.370
ATF5	CCND3	psi-mi:“MI:0915”(physical association)	0.370
EP300	ATF5	psi-mi:“MI:0915”(physical association)	0.370
ATF5	GIT2	psi-mi:“MI:0915”(physical association)	0.370
ATF5	TRIB3	psi-mi:“MI:0915”(physical association)	0.370
ATXN1	ATF5	psi-mi:“MI:0915”(physical association)	0.370
CDC34	ATF5	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (31): EP300 (Affinity Capture-Western), ATF5 (Biochemical Activity), ATF5 (Two-hybrid), ATF5 (Biochemical Activity), ATF5 (Two-hybrid), CCND3 (Reconstituted Complex), CCND3 (Affinity Capture-Western), ATF5 (Two-hybrid), ATF5 (Affinity Capture-Western), ATF5 (Two-hybrid), ATF5 (Two-hybrid), ATF5 (Two-hybrid), ATF5 (Two-hybrid), ATF5 (Two-hybrid), ATF5 (Two-hybrid)

ESM2 similar proteins: A6NEQ2, A7MB34, A8MYZ6, O02754, O02755, O02756, O70191, O77728, P05554, P16443, P17676, P19532, P49715, P49716, P50548, P53566, P54845, P54846, P56261, P70459, Q00322, Q01094, Q03484, Q05826, Q05B92, Q10586, Q15744, Q15784, Q32PF6, Q5TGY3, Q60843, Q60925, Q61660, Q62414, Q63247, Q63689, Q64092, Q64305, Q64731, Q6NW59

Diamond homologs: O70191, P18848, Q06507, Q6NW59, Q6P788, Q9ES19, Q9Y2D1, Q3ZCH6, Q9GPH3, Q22156

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
ATF5	“up-regulates quantity by expression”	CYP2B6	“transcriptional regulation”
“TOM40 complex”	“down-regulates activity”	ATF5	relocalization

Disease & clinical

Clinical variants and AI predictions

ClinVar

29 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	20
Likely benign	0
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1281 predictions. Top by Δscore:

Variant	Effect	Δscore
19:49929401:G:GG	donor_gain	1.0000
19:49929001:G:T	donor_gain	0.9900
19:49929397:TGGA:T	donor_gain	0.9900
19:49929398:GGA:G	donor_gain	0.9900
19:49929398:GGAG:G	donor_gain	0.9900
19:49929399:GA:G	donor_gain	0.9900
19:49929399:GAG:G	donor_gain	0.9900
19:49929396:ATGGA:A	donor_gain	0.9800
19:49929400:AGT:A	donor_loss	0.9800
19:49929405:G:GG	donor_gain	0.9800
19:49929857:G:GA	donor_gain	0.9800
19:49930903:C:G	donor_gain	0.9800
19:49928888:G:GT	donor_gain	0.9700
19:49929403:GAGTA:G	donor_loss	0.9700
19:49929404:A:AG	donor_gain	0.9700
19:49929404:AGT:A	donor_loss	0.9700
19:49929416:CCT:C	donor_gain	0.9700
19:49929782:TGTA:T	donor_gain	0.9700
19:49929856:T:TA	donor_gain	0.9700
19:49930902:GCTA:G	donor_gain	0.9700
19:49932264:T:A	acceptor_gain	0.9700
19:49932580:G:GT	donor_gain	0.9700
19:49927693:CCG:C	donor_gain	0.9600
19:49928667:A:AC	donor_gain	0.9600
19:49928668:A:C	donor_gain	0.9600
19:49929001:G:GT	donor_gain	0.9600
19:49929411:GCTTA:G	donor_loss	0.9600
19:49929412:CTTAC:C	donor_loss	0.9600
19:49929413:TTACC:T	donor_loss	0.9600
19:49929414:T:TG	donor_loss	0.9600

AlphaMissense

1768 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:49932895:A:G	N218D	1.000
19:49932898:A:G	K219E	1.000
19:49932900:G:C	K219N	1.000
19:49932900:G:T	K219N	1.000
19:49932908:C:A	A222D	1.000
19:49932914:G:T	R224M	1.000
19:49932916:T:C	Y225H	1.000
19:49932916:T:G	Y225D	1.000
19:49932917:A:G	Y225C	1.000
19:49932919:C:A	R226S	1.000
19:49932930:G:C	K229N	1.000
19:49932930:G:T	K229N	1.000
19:49932992:T:C	L250P	1.000
19:49933003:G:C	A254P	1.000
19:49933034:T:A	V264D	1.000
19:49933043:T:C	L267P	1.000
19:49933046:T:C	L268P	1.000
19:49932439:T:A	W66R	0.999
19:49932439:T:C	W66R	0.999
19:49932883:A:G	K214E	0.999
19:49932885:G:C	K214N	0.999
19:49932885:G:T	K214N	0.999
19:49932887:G:C	R215T	0.999
19:49932888:A:C	R215S	0.999
19:49932888:A:T	R215S	0.999
19:49932893:A:C	Q217P	0.999
19:49932894:G:C	Q217H	0.999
19:49932894:G:T	Q217H	0.999
19:49932895:A:C	N218H	0.999
19:49932896:A:C	N218T	0.999

dbSNP variants (sampled 300 via entrez): RS1000223412 (19:49932305 A>AGTTGTTTT), RS1000359557 (19:49930602 C>G,T), RS1000913718 (19:49929422 C>T), RS1001272530 (19:49929717 C>T), RS1001661048 (19:49930171 A>G), RS1001818136 (19:49931615 G>A), RS1002183501 (19:49928953 A>C,G), RS1002421066 (19:49930219 G>A,T), RS1003258656 (19:49934018 A>G), RS1003275116 (19:49927438 T>C), RS1003736231 (19:49933193 G>T), RS1004440324 (19:49928911 C>T), RS1004838056 (19:49929611 G>A,C), RS1005191272 (19:49929821 C>T), RS1005202098 (19:49927519 C>T)

Disease associations

OMIM: gene MIM:606398 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs8667	ATF5		0.00	0

CTD chemical–gene interactions

79 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects expression	4
sodium arsenite	affects reaction, increases expression	3
Cadmium Chloride	decreases expression, increases abundance, increases expression, affects reaction	3
lead acetate	affects reaction, increases abundance, increases expression, affects response to substance, decreases response to substance	2
methylselenic acid	decreases expression	2
trichostatin A	affects expression, decreases expression	2
entinostat	increases expression, affects cotreatment	2
Vorinostat	affects cotreatment, decreases expression	2
Cadmium	decreases expression, increases abundance, increases expression, affects reaction	2
Nickel	increases expression	2
Plant Extracts	affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	increases expression	2
Tunicamycin	increases expression	2
Cyclosporine	increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
aristolochic acid I	increases expression	1
methylmercuric chloride	increases expression	1
bisphenol A	increases methylation	1
arsenite	affects expression	1
cobaltous chloride	decreases expression	1
periodate-oxidized adenosine	affects expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
S-(1,2-dichlorovinyl)cysteine	increases expression	1
beta-methylcholine	affects expression	1
azoxystrobin	decreases expression	1
CGP 52608	increases reaction, affects binding	1
polyglutamine	affects localization, decreases expression	1
AM 251	increases expression	1
deguelin	increases expression	1
fenpyroximate	increases expression	1

Cellosaurus cell lines

8 cell lines: 8 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B7W2	Abcam Raji ATF5 KO	Cancer cell line	Male
CVCL_B9WK	Abcam THP-1 ATF5 KO	Cancer cell line	Male
CVCL_C6YL	Abcam PC-3 ATF5 KO	Cancer cell line	Male
CVCL_C8SU	HeLa S3 ATF5 KO	Cancer cell line	Female
CVCL_C8SX	HeLa S3 CHOP/ATF4/ATF5 triple KO	Cancer cell line	Female
CVCL_SD84	HAP1 ATF5 (-) 1	Cancer cell line	Male
CVCL_SD85	HAP1 ATF5 (-) 2	Cancer cell line	Male
CVCL_XL68	HAP1 ATF5 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.