ATF4 - activating transcription factor 4 Gene

Homo sapiens

Also known as CREB2; TXREB; CREB-2; TAXREB67

Gene ID: 468 | Gene type: protein coding

About ATF4

Cytogenetic location: 22q13.1 Genomic coordinates (GRCh38): 22:39,520,559-39,522,686 (from NCBI)

This gene has 11 transcripts (splice variants), 269 orthologues and 1 paralogue. Ubiquitous expression in bone marrow (RPKM 183.9), fat (RPKM 87.6) and 25 other tissues.

Summary

This gene encodes a transcription factor that was originally identified as a widely expressed mammalian DNA binding protein that could bind a tax-responsive enhancer element in the LTR of HTLV-1. The encoded protein was also isolated and characterized as the cAMP-response element binding protein 2 (CREB-2). The protein encoded by this gene belongs to a family of DNA-binding proteins that includes the AP-1 family of transcription factors, cAMP-response element binding proteins (CREBs) and CREB-like proteins. These transcription factors share a leucine zipper region that is involved in protein-protein interactions, located C-terminal to a stretch of basic Amino acids that functions as a DNA binding domain. Two alternative transcripts encoding the same protein have been described. Two pseudogenes are located on the X chromosome at q28 in a region containing a large inverted duplication. [provided by RefSeq, Sep 2011]

ATF4 Products(2)

mRNA	Protein	Name
NM_001675.4	NP_001666.2	cyclic AMP-dependent transcription factor ATF-4
NM_182810.3	NP_877962.1	cyclic AMP-dependent transcription factor ATF-4

Gene Ontology

Molecular Function
Biological Process
Cellular Component

Molecular Function GO Annotation	Evidence	Reference	Source
enables DNA binding	IDA IDA: Inferred from direct assay	15788408	GOA
enables DNA-binding transcription factor activity	IDA IDA: Inferred from direct assay	11960987	GOA
enables DNA-binding transcription factor activity, RNA polymerase II-specific	IDA IDA: Inferred from direct assay	11478948	GOA
enables RNA polymerase II-specific DNA-binding transcription factor binding	IPI IPI: Inferred from physical interaction	11478948	GOA
enables identical protein binding	IPI IPI: Inferred from physical interaction	16343488	GOA
enables leucine zipper domain binding	IDA IDA: Inferred from direct assay	11478948	GOA
enables promoter-specific chromatin binding	IDA IDA: Inferred from direct assay	17267404	GOA
enables protein binding	IPI IPI: Inferred from physical interaction	9488481	GOA
enables protein kinase binding	IPI IPI: Inferred from physical interaction	20873783	GOA
enables sequence-specific DNA binding	IDA IDA: Inferred from direct assay	22915762	GOA
enables sequence-specific double-stranded DNA binding	IDA IDA: Inferred from direct assay	28473536	GOA
contributes to transcription cis-regulatory region binding	IDA IDA: Inferred from direct assay	12871976	GOA
enables transcription cis-regulatory region binding	IDA IDA: Inferred from direct assay	21113145	GOA

Biological Process GO Annotation	Evidence	Reference	Source
involved in HRI-mediated signaling	IDA IDA: Inferred from direct assay	32132706	GOA
involved in L-asparagine metabolic process	IDA IDA: Inferred from direct assay	11960987	GOA
involved in cellular response to glucose starvation	IMP IMP: Inferred from mutant phenotype	22915762	GOA
involved in cellular response to leucine starvation	IDA IDA: Inferred from direct assay	17267404	GOA
involved in cellular response to oxidative stress	IMP IMP: Inferred from mutant phenotype	21113145	GOA
involved in integrated stress response signaling	IDA IDA: Inferred from direct assay	32132707	GOA
involved in negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway	IGI IGI: Inferred from genetic interaction	23392669	GOA
involved in positive regulation of DNA-templated transcription	IDA IDA: Inferred from direct assay	15775988	GOA
involved in positive regulation of DNA-templated transcription	IMP IMP: Inferred from mutant phenotype	11960987	GOA
involved in positive regulation of gene expression	IMP IMP: Inferred from mutant phenotype	16445384	GOA
involved in positive regulation of transcription by RNA polymerase I	IMP IMP: Inferred from mutant phenotype	22915762	GOA
involved in positive regulation of transcription by RNA polymerase II	IDA IDA: Inferred from direct assay	11478948	GOA
involved in positive regulation of transcription by RNA polymerase II	IMP IMP: Inferred from mutant phenotype	15788408	GOA
involved in positive regulation of vascular endothelial growth factor production	IMP IMP: Inferred from mutant phenotype	22915762	GOA
involved in regulation of osteoblast differentiation	IDA IDA: Inferred from direct assay	15109498	GOA
involved in response to endoplasmic reticulum stress	IDA IDA: Inferred from direct assay	12871976	GOA
involved in response to endoplasmic reticulum stress	IMP IMP: Inferred from mutant phenotype	21113145	GOA
involved in response to nutrient levels	IDA IDA: Inferred from direct assay	11960987	GOA

Cellular Component GO Annotation	Evidence	Reference	Source
part of ATF1-ATF4 transcription factor complex	IDA IDA: Inferred from direct assay	12871976	GOA
part of ATF4-CREB1 transcription factor complex	IDA IDA: Inferred from direct assay	12871976	GOA
part of CHOP-ATF4 complex	IDA IDA: Inferred from direct assay	11478948	GOA
part of CHOP-ATF4 complex	IPI IPI: Inferred from physical interaction	18940792	GOA
located in Lewy body core	IDA IDA: Inferred from direct assay	23392669	GOA
part of RNA polymerase II transcription regulator complex	IPI IPI: Inferred from physical interaction	20102225	GOA
colocalizes with centrosome	IDA IDA: Inferred from direct assay	20873783	GOA
located in cytoplasm	IDA IDA: Inferred from direct assay	23392669	GOA
located in neuron projection	IDA IDA: Inferred from direct assay	23392669	GOA
located in nuclear periphery	IDA IDA: Inferred from direct assay	23392669	GOA
located in nucleus	IDA IDA: Inferred from direct assay	11478948	GOA
part of protein-containing complex	IDA IDA: Inferred from direct assay	20873783	GOA

EXP: Inferred from Experiment IDA: Inferred from direct assay IPI: Inferred from physical interaction IMP: Inferred from mutant phenotype IGI: Inferred from genetic interaction IEP: Inferred from expression pattern

ATF4 Protein Structure

bZIP_1

0
100
200
300
351 a.a.

Protein Preferred Names

Protein Names

cyclic AMP-dependent transcription factor ATF-4

DNA-binding protein TAXREB67

Related Diseases

Diseases

Alias

Coffin-Lowry Syndrome

CLS	Coffin Syndrome 1
Coffin Syndrome	Intellectual Disability With Osteocartilaginous Abnormalities
Dwarfism, Lean Spastic Type	Lean Spastic Dwarfism
Mental Retardation With Osteocartilaginous Abnormalities	Coffin Lowry Syndrome

Fatty Liver Disease

Alcoholic Fatty Liver	Fatty Liver
Fatty Liver, Alcoholic	Fatty Change Of Liver
Hepatic Lipidosis	Steatosis Of Liver
Fatty Liver Alcoholic	Steatohepatitis
Etoh Fatty Liver	Etoh Fatty Liver Metamorphosis
Fatty Etoh Liver Necrosis

Liver Disease

Liver Failure	Liver Diseases
Abnormality Of The Liver	Liver Dysfunction
Disorder Of Liver	Hepatic Disorder
Hepatic Disease	Disease Of Bilirubin Metabolism
Disorder Of Bilirubin Metabolism	Liver Decompensation
Liver Function Failure	Hepatic Failure Nos
Liver Failure Nos	End Stage Liver Disease
Decompensated Liver Failure	Decompensation Of Liver Function
Hepatic Decompensation	Hepatic Insufficiency
Liver Cell Necrosis With Hepatic Failure	Liver Insufficiency
Decompensated Liver Disease	End Stage Liver Failure
Liver Necrosis With Hepatic Failure

Epiphyseal Dysplasia, Multiple, With Early-Onset Diabetes Mellitus

Wolcott-Rallison Syndrome	Med-Iddm Syndrome
Iddm-Med Syndrome	Wolcott Rallison Syndrome
WRS	Epiphyseal Dysplasia Multiple With Early-Onset Diabetes Mellitus
Early-Onset Diabetes Mellitus With Multiple Epiphyseal Dysplasia	Multiple Epiphyseal Dysplasia With Early-Onset Diabetes Mellitus

Leukodystrophy

Leukodystrophies

T-Cell Acute Lymphoblastic Leukemia

T-Cell Leukemia	Acute T Cell Leukemia
Precursor T Lymphoblastic Leukemia	Precursor T-Lymphoblastic Lymphoma/Leukemia
T Acute Lymphoblastic Leukemia	T-Cell Acute Lymphocytic Leukaemia
T-Cell Lymphoblastic Leukemia/Lymphoma	Leukemia T-Cell
Leukemia, T-Cell	Leukemia, Acute, Lymphoblastic, T-Cell
Leukemia, T-Cell Acute Lymphoblastic	Leukemia, Acute T-Cell
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma	Precursor T-Cell Lymphoblastic Lymphoma
Precursor T Cell Lymphoblastic Leukemia/Lymphoblastic Lymphoma

Leukoencephalopathy With Vanishing White Matter

Cree Leukoencephalopathy	Vanishing White Matter Disease
Ovarioleukodystrophy	Vanishing White Matter Leukodystrophy
Childhood Ataxia With Central Nervous System Hypomyelinization	Cach
Cach Syndrome	Myelinosis Centralis Diffusa
VWM	Cle
Childhood Ataxia With Central Nervous System Hypomyelination	Childhood Ataxia With Diffuse Central Nervous System Hypomyelination
Cach/Vwm	Cach/Vwm Syndrome
Childhood Ataxia With Central Nervous System Hypomyelination/Vanishing White Matter	Cree Leukoencehalopathy
Late Infantile Cach Syndrome	Juvenile Or Adult Cach Syndrome
Congenital Or Early Infantile Cach Syndrome	Leukodystrophy With Vanishing White Matter

Pancreatic Cancer

Pancreatic Carcinoma	Carcinoma Of Pancreas
Familial Pancreatic Carcinoma	Pancreatic Neoplasm
Pancreatic Carcinoma, Familial	Malignant Neoplasm Of Pancreas
Pancreatic Acinar Carcinoma	Pancreatic Tumor
Familial Pancreatic Cancer	Neoplasm Of The Pancreas
Cancer Of The Pancreas	Pancreatic Carcinoma, Somatic
Pancreatic Cancer, Somatic	Ca Body Of Pancreas
Ca Head Of Pancreas	Ca Tail Of Pancreas
Malignant Neoplasm Of Body Of Pancreas	Malignant Neoplasm Of Head Of Pancreas
Malignant Neoplasm Of Tail Of Pancreas	Pancreas Neoplasm
Exocrine Cancer	Exocrine Pancreas Carcinoma
Hereditary Pancreatic Cancer	Hereditary Pancreatic Carcinoma
PNCA	Pancreatic Cancer, Susceptibility To
Carcinoma Of Head Of Pancreas	Pancreatic Neoplasms
Pancreatic Tumors	Cancer, Pancreatic
Cancer Of Pancreas	Mixed Islet Cell With Exocrine Carcinoma Of Unspecified Site

Basal Cell Carcinoma

Basal Cell Cancer	Basal Cell Neoplasm
Basal Cell Carcinoma Of Skin	Malignant Basal Cell Tumor
Basal Cell Tumor	Epithelioma Basal Cell
Malignant Basal Cell Neoplasm	Rodent Ulcer
Carcinoma Basal Cell	Neoplasms, Basal Cell
Basal Cell Carcinomas	Experimental Organism Basal Cell Carcinoma
Nodulo-Ulcerative Basal Cell Carcinoma	Basalioma
Basal Cell Epithelioma Of Skin	Bcc - [Basal Cell Carcinoma] Of Skin
Rodent Ulcer Of Skin	Rodent Ulcer Of Unspecified Site
Basal Cell Epithelioma Of Unspecified Site

Retinitis Pigmentosa

RP	Rod-Cone Dystrophy
Autosomal Recessive Retinitis Pigmentosa	Non-Syndromic Retinitis Pigmentosa
Pericentral Pigmentary Retinopathy	Pigmentary Retinopathy
Tapetoretinal Degeneration	Rcd
Retinitis Pigmentosa Autosomal Recessive	ARRP
Retinitis Pigmentosa, Autosomal Recessive	Retinitis Pigmentosa 1

Diseases	Alias
Waldenstroem'S Macroglobulinemia	Waldenstroem'S Macroglobulinemia Waldenstroem'S Macroglobulinemia Macroglobulinemia Of Waldenstrom Lymphoplasmacytic Lymphoma With Igm Gammopathy Lymphoplasmacytic Lymphoma Waldenstroem'S Macroglobulinemia Waldenstroem'S Macroglobulinemia Macroglobulinemia Of Waldenstrom Lymphoplasmacytic Lymphoma With Igm Gammopathy Lymphoplasmacytic Lymphoma

Related Agents

Clinical Phase

Bioactive Molecules (1)

Cat. No.	Product Name	Effect	Purity	Phase
HY-13559	Atiprimod		/	Phase 2

Pre-clinical Phase

Bioactive Molecules (19)

Cat. No.	Product Name	Effect	Purity	Rare Diseases
HY-100548	GSK621		98.02%	Unkown
HY-153339	E235		98.85%	Unkown
HY-153340	I-152	Activator	98.78%	Unkown
HY-153074	ISR-IN-1		98.25%	Unkown
HY-158201	ATF4-IN-1	Activator	98.02%	Unkown
HY-124646	KIRA-7	Inhibitor	98.33%	Unkown
HY-153075	ISR-IN-2		98.21%	Unkown
HY-121337	Flurochloridone		99.61%	Unkown
HY-158202	ATF4-IN-2		/	Unkown
HY-158204	CNB-001	Inhibitor	/	Unkown
HY-149918	Antiproliferative agent-23		/	Unkown
HY-117938	T-3861174	Inhibitor	/	Unkown
HY-158195	DPP23		/	Unkown
HY-158196	PERK/eIF2α activator 1	Activator	/	Unkown
HY-158203	BMP agonist 2		99.26%	Unkown
HY-158205	HPO-DAEE		/	Unkown
HY-162886	BSO-07	Activator	/	Unkown
HY-RS01130	ATF4 Human Pre-designed siRNA Set A	Pre-designed Sets	/	Unkown
HY-112654A	GCN2iB acetate		/	Unkown

Orthologs Information

Species	Symbol	Source	ID
Rattus norvegicus	ATF4	RGD	RGD:621863
Mus musculus	ATF4	MGD	MGI:88096
Canis familiaris	ATF4	VGNC	VGNC:38210
Bos taurus	ATF4	VGNC	VGNC:26242
Macaca mulatta	ATF4	VGNC	VGNC:107770
Felis catus	ATF4	VGNC	VGNC:68509

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