DDIT3 DNA damage inducible transcript 3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: DDIT3provided by HGNC
Official Full Name: DNA damage inducible transcript 3provided by HGNC
Primary source: HGNC:HGNC:2726
See related: Ensembl:ENSG00000175197 MIM:126337; AllianceGenome:HGNC:2726
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: CHOP; CEBPZ; CHOP10; CHOP-10; GADD153; AltDDIT3; C/EBPzeta
Summary: This gene encodes a member of the CCAAT/enhancer-binding protein (C/EBP) family of transcription factors. The protein functions as a dominant-negative inhibitor by forming heterodimers with other C/EBP members, such as C/EBP and LAP (liver activator protein), and preventing their DNA binding activity. The protein is implicated in adipogenesis and erythropoiesis, is activated by endoplasmic reticulum stress, and promotes apoptosis. Fusion of this gene and FUS on chromosome 16 or EWSR1 on chromosome 22 induced by translocation generates chimeric proteins in myxoid liposarcomas or Ewing sarcoma. Multiple alternatively spliced transcript variants encoding two isoforms with different length have been identified. [provided by RefSeq, Aug 2010]
Annotation information: Note: CEBPZ (Gene ID: 10153) and DDIT3 (Gene ID: 1649) share the CEBPZ symbol/alias. CEBPZ is a widely used alternative name for DNA damage inducible transcript 3 (DDIT3), which can be confused with the official symbol for CEBPZ (CCAAT enhancer binding protein zeta, GeneID: 10153). [12 Nov 2020]
Expression: Broad expression in thyroid (RPKM 74.2), bone marrow (RPKM 47.3) and 24 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 12q13.3

Exon count:: 4

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	12	NC_000012.12 (57516588..57520517, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	12	NC_060936.1 (57484816..57488745, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	12	NC_000012.11 (57910371..57914300, complement)

Chromosome 12 - NC_000012.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Integrated Bioinformatics Analysis Identified ASNS and DDIT3 as the Therapeutic Target in Castrate-Resistant Prostate Cancer.
Title: Integrated Bioinformatics Analysis Identified ASNS and DDIT3 as the Therapeutic Target in Castrate-Resistant Prostate Cancer.
C/EBPalpha-p30 confers AML cell susceptibility to the terminal unfolded protein response and resistance to Venetoclax by activating DDIT3 transcription.
Title: C/EBPα-p30 confers AML cell susceptibility to the terminal unfolded protein response and resistance to Venetoclax by activating DDIT3 transcription.
CHOP upregulation and dysregulation of the mature form of the SNAT2 amino acid transporter in the placentas from small for gestational age newborns.
Title: CHOP upregulation and dysregulation of the mature form of the SNAT2 amino acid transporter in the placentas from small for gestational age newborns.
Endoplasmic Reticulum Stress Promotes the Expression of TNF-alpha in THP-1 Cells by Mechanisms Involving ROS/CHOP/HIF-1alpha and MAPK/NF-kappaB Pathways.
Title: Endoplasmic Reticulum Stress Promotes the Expression of TNF-α in THP-1 Cells by Mechanisms Involving ROS/CHOP/HIF-1α and MAPK/NF-κB Pathways.
Some Macrophages With High Expression of CHOP Undergo Necroptosis in Chronic Rhinosinusitis.
Title: Some Macrophages With High Expression of CHOP Undergo Necroptosis in Chronic Rhinosinusitis.
The transcription factor DDIT3 is a potential driver of dyserythropoiesis in myelodysplastic syndromes.
Title: The transcription factor DDIT3 is a potential driver of dyserythropoiesis in myelodysplastic syndromes.
Riboflavin (Vitamin B2) Deficiency Induces Apoptosis Mediated by Endoplasmic Reticulum Stress and the CHOP Pathway in HepG2 Cells.
Title: Riboflavin (Vitamin B2) Deficiency Induces Apoptosis Mediated by Endoplasmic Reticulum Stress and the CHOP Pathway in HepG2 Cells.
Epigenetic Silencing of CHOP Expression by the Histone Methyltransferase EHMT1 Regulates Apoptosis in Colorectal Cancer Cells.
Title: Epigenetic Silencing of CHOP Expression by the Histone Methyltransferase EHMT1 Regulates Apoptosis in Colorectal Cancer Cells.
Diterpenoid Vinigrol specifically activates ATF4/DDIT3-mediated PERK arm of unfolded protein response to drive non-apoptotic death of breast cancer cells.
Title: Diterpenoid Vinigrol specifically activates ATF4/DDIT3-mediated PERK arm of unfolded protein response to drive non-apoptotic death of breast cancer cells.
CHOP Increases TRIB3-Dependent miR-208 Expression to Potentiate Vascular Smooth Muscle Cell Proliferation and Migration by Downregulating TIMP3 in Atherosclerosis.
Title: CHOP Increases TRIB3-Dependent miR-208 Expression to Potentiate Vascular Smooth Muscle Cell Proliferation and Migration by Downregulating TIMP3 in Atherosclerosis.

Submit: New GeneRIF Correction See all GeneRIFs (222)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 Env gp120 upregulates DDIT3 (CHOP) in SVGA cells and human fetal astrocytes via IRE1a, JNK, and AP-1	PubMed
Tat	tat	HIV-1 Tat induces endoplasmic reticulum (ER) stress response proteins CASP12 (Caspase 12), DDIT3 (CHOP), ROS1, ERN-1 (p-IRE1), EIF2AK3 (p-PERK), and ATF6 in human brain microvascular endothelial cells (HBMECs)	PubMed
	tat	HIV-1 Tat is dependent on DDIT3 (CHOP) to induce apoptosis in Human Brain Microvascular Endothelial Cells (HBMECs) as shown through DDIT3 siRNA knockdown	PubMed
	tat	Expression of Rad51 enhances basal- and HIV-1 Tat-induced transcription of the HIV-1 LTR promoter; this event requires cooperativity from the C/EBP family of transcription factors including C/EBPbeta and C/EBPbeta homologous protein (CHOP)	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

GDB:434012 (e-PCR)
- UniSTS:157204

GDB:438520 (e-PCR)
- UniSTS:157278

D1S1423 (e-PCR)
- UniSTS:149619

D1S1425 (e-PCR)
- UniSTS:149621

G35510 (e-PCR)
- UniSTS:44150

D12S1943 (e-PCR)
- UniSTS:7319

RH17412 (e-PCR)
- UniSTS:9638

PMC150726P8 (e-PCR)
- UniSTS:271080

RH17902 (e-PCR)
- UniSTS:68333

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription activator activity, RNA polymerase II-specific	IBA Inferred from Biological aspect of Ancestor more info
enables DNA-binding transcription activator activity, RNA polymerase II-specific	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription factor activity	IGI Inferred from Genetic Interaction more info	PubMed
enables DNA-binding transcription factor activity	ISS Inferred from Sequence or Structural Similarity more info
enables DNA-binding transcription factor activity, RNA polymerase II-specific	ISA Inferred from Sequence Alignment more info
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables RNA polymerase II-specific DNA-binding transcription factor binding	IPI Inferred from Physical Interaction more info	PubMed
enables cAMP response element binding protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables cAMP response element binding protein binding	ISS Inferred from Sequence or Structural Similarity more info
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables leucine zipper domain binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein heterodimerization activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein heterodimerization activity	IPI Inferred from Physical Interaction more info	PubMed
enables protein homodimerization activity	IDA Inferred from Direct Assay more info	PubMed
enables transcription cis-regulatory region binding	IC Inferred by Curator more info	PubMed
enables transcription cis-regulatory region binding	IDA Inferred from Direct Assay more info	PubMed
enables transcription cis-regulatory region binding	ISS Inferred from Sequence or Structural Similarity more info
enables transcription corepressor activity	IDA Inferred from Direct Assay more info	PubMed
enables transcription corepressor activity	IGI Inferred from Genetic Interaction more info	PubMed
enables transcription factor binding	IBA Inferred from Biological aspect of Ancestor more info
enables transcription regulator activator activity	ISS Inferred from Sequence or Structural Similarity more info
enables transcription regulator inhibitor activity	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
involved_in ATF6-mediated unfolded protein response	TAS Traceable Author Statement more info	PubMed
involved_in DNA damage response	TAS Traceable Author Statement more info	PubMed
involved_in ER overload response	IBA Inferred from Biological aspect of Ancestor more info
involved_in PERK-mediated unfolded protein response	TAS Traceable Author Statement more info	PubMed
involved_in Wnt signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in anterior/posterior axis specification	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in artery development	IEA Inferred from Electronic Annotation more info
involved_in blood vessel maturation	IEA Inferred from Electronic Annotation more info
involved_in cell cycle	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within cell redox homeostasis	IDA Inferred from Direct Assay more info	PubMed
involved_in endoplasmic reticulum unfolded protein response	ISS Inferred from Sequence or Structural Similarity more info
involved_in establishment of protein localization to mitochondrion	IEA Inferred from Electronic Annotation more info
involved_in gene expression	IEA Inferred from Electronic Annotation more info
involved_in integrated stress response signaling	NAS Non-traceable Author Statement more info	PubMed
involved_in intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress	IBA Inferred from Biological aspect of Ancestor more info
involved_in intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress	IDA Inferred from Direct Assay more info	PubMed
involved_in intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress	TAS Traceable Author Statement more info	PubMed
involved_in intrinsic apoptotic signaling pathway in response to nitrosative stress	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of DNA-binding transcription factor activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of canonical Wnt signaling pathway	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in negative regulation of cold-induced thermogenesis	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in negative regulation of determination of dorsal identity	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of fat cell differentiation	IEA Inferred from Electronic Annotation more info
acts_upstream_of negative regulation of interleukin-17 production	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of negative regulation of interleukin-4 production	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of myoblast differentiation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within negative regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of transcription by RNA polymerase II	IGI Inferred from Genetic Interaction more info	PubMed
involved_in negative regulation of transcription by RNA polymerase II	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of transcription by RNA polymerase II	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of negative regulation of type II interferon production	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of DNA-binding transcription factor activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of interleukin-8 production	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of intrinsic apoptotic signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of neuron apoptotic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	ISS Inferred from Sequence or Structural Similarity more info
involved_in proteasome-mediated ubiquitin-dependent protein catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of DNA-templated transcription	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of autophagy	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of cell cycle	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of transcription by RNA polymerase II	NAS Non-traceable Author Statement more info	PubMed
involved_in release of sequestered calcium ion into cytosol	IEA Inferred from Electronic Annotation more info
involved_in response to endoplasmic reticulum stress	IDA Inferred from Direct Assay more info	PubMed
involved_in response to endoplasmic reticulum stress	IGI Inferred from Genetic Interaction more info	PubMed
involved_in response to platelet-derived growth factor	IEA Inferred from Electronic Annotation more info
involved_in response to starvation	IEA Inferred from Electronic Annotation more info
involved_in response to unfolded protein	IDA Inferred from Direct Assay more info	PubMed
involved_in response to wounding	IEA Inferred from Electronic Annotation more info
involved_in sensory perception of sound	IEA Inferred from Electronic Annotation more info
involved_in vascular associated smooth muscle cell migration	IEA Inferred from Electronic Annotation more info
involved_in vascular associated smooth muscle cell proliferation	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
part_of CHOP-ATF3 complex	IBA Inferred from Biological aspect of Ancestor more info
part_of CHOP-ATF3 complex	IDA Inferred from Direct Assay more info	PubMed
part_of CHOP-ATF4 complex	IBA Inferred from Biological aspect of Ancestor more info
part_of CHOP-ATF4 complex	IDA Inferred from Direct Assay more info	PubMed
part_of CHOP-ATF4 complex	IPI Inferred from Physical Interaction more info	PubMed
part_of CHOP-C/EBP complex	IBA Inferred from Biological aspect of Ancestor more info
part_of CHOP-C/EBP complex	IPI Inferred from Physical Interaction more info	PubMed
part_of CHOP-C/EBP complex	ISS Inferred from Sequence or Structural Similarity more info
part_of CHOP-C/EBP complex	TAS Traceable Author Statement more info	PubMed
part_of RNA polymerase II transcription regulator complex	IPI Inferred from Physical Interaction more info	PubMed
part_of chromatin	ISA Inferred from Sequence Alignment more info
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info	PubMed
located_in late endosome	IEA Inferred from Electronic Annotation more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	NAS Non-traceable Author Statement more info	PubMed
part_of protein-DNA complex	IDA Inferred from Direct Assay more info	PubMed
part_of transcription regulator complex	NAS Non-traceable Author Statement more info	PubMed

General protein information

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Preferred Names: DNA damage-inducible transcript 3 protein

Names: C/EBP zeta; CCAAT/enhancer-binding protein homologous protein; alternative DDIT3 protein; c/EBP-homologous protein 10; growth arrest and DNA damage-inducible protein GADD153

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_027674.1 RefSeqGene

Range

5004..8925

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001195053.1 → NP_001181982.1 DNA damage-inducible transcript 3 protein isoform 1

See identical proteins and their annotated locations for NP_001181982.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longer isoform (1).

Source sequence(s)

AY461580, BM464290

Consensus CDS

CCDS55838.1

UniProtKB/Swiss-Prot

P35638

Related

ENSP00000448665.1, ENST00000551116.5

Conserved Domains (2) summary

smart00338
Location:119 → 182

BRLZ; basic region leucin zipper

cd14686
Location:122 → 176

bZIP; coiled coil [structural motif]
NM_001195054.1 → NP_001181983.1 DNA damage-inducible transcript 3 protein isoform 1

See identical proteins and their annotated locations for NP_001181983.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an internal segment in the 5' UTR, as compared to variant 1. Variants 1-4 encode the same isoform 1.

Source sequence(s)

AY461580, BM464290, BU664077

Consensus CDS

CCDS55838.1

UniProtKB/Swiss-Prot

P35638

Conserved Domains (2) summary

smart00338
Location:119 → 182

BRLZ; basic region leucin zipper

cd14686
Location:122 → 176

bZIP; coiled coil [structural motif]
NM_001195055.1 → NP_001181984.1 DNA damage-inducible transcript 3 protein isoform 1

See identical proteins and their annotated locations for NP_001181984.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks an internal segment in the 5' UTR, as compared to variant 1. Variants 1-4 encode the same isoform 1.

Source sequence(s)

AA054097, AY461580, BM464290

Consensus CDS

CCDS55838.1

UniProtKB/Swiss-Prot

P35638

Conserved Domains (2) summary

smart00338
Location:119 → 182

BRLZ; basic region leucin zipper

cd14686
Location:122 → 176

bZIP; coiled coil [structural motif]
NM_001195056.1 → NP_001181985.1 DNA damage-inducible transcript 3 protein isoform 1

See identical proteins and their annotated locations for NP_001181985.1

Status: REVIEWED

Description

Transcript Variant: This variant (4) has an additional segment in the 5' UTR, as compared to variant 1. Variants 1-4 encode the same isoform 1.

Source sequence(s)

AK316581, AY461580, BM464290

Consensus CDS

CCDS55838.1

UniProtKB/TrEMBL

Q53YD1

Related

ENSP00000447803.1, ENST00000552740.5

Conserved Domains (2) summary

smart00338
Location:119 → 182

BRLZ; basic region leucin zipper

cd14686
Location:122 → 176

bZIP; coiled coil [structural motif]
NM_001195057.1 → NP_001181986.1 DNA damage-inducible transcript 3 protein isoform 2

See identical proteins and their annotated locations for NP_001181986.1

Status: REVIEWED

Description

Transcript Variant: This variant (6) lacks an internal segment in the 5' region, resulting in a downstream AUG start codon, as compared to variant 1. The resulting isoform (2) is shorter at the N-terminus, as compared to isoform 1. Variants 5-8 all encode the same isoform (2).

Source sequence(s)

AY461580, BM464290, CN482428

Consensus CDS

CCDS8943.1

UniProtKB/Swiss-Prot

F8VS99, P35638

UniProtKB/TrEMBL

Q53YD1

Related

ENSP00000447188.1, ENST00000547303.5

Conserved Domains (3) summary

smart00338
Location:96 → 159

BRLZ; basic region leucin zipper

cd14686
Location:102 → 153

bZIP; coiled coil [structural motif]

pfam02724
Location:17 → 125

CDC45; CDC45-like protein
NM_001413641.1 → NP_001400570.1 DNA damage-inducible transcript 3 protein isoform 2

Status: REVIEWED

Source sequence(s)

AC022506

UniProtKB/Swiss-Prot

F8VS99, P35638

UniProtKB/TrEMBL

Q53YD1
NM_001413642.1 → NP_001400571.1 DNA damage-inducible transcript 3 protein isoform 2

Status: REVIEWED

Source sequence(s)

AC022506

UniProtKB/Swiss-Prot

F8VS99, P35638

UniProtKB/TrEMBL

Q53YD1
NM_004083.6 → NP_004074.2 DNA damage-inducible transcript 3 protein isoform 2

See identical proteins and their annotated locations for NP_004074.2

Status: REVIEWED

Description

Transcript Variant: This variant (5) lacks an internal segment in the 5' region, resulting in a downstream AUG start codon, as compared to variant 1. The resulting isoform (2) is shorter at the N-terminus, as compared to isoform 1. Variants 5-8 all encode the same isoform (2).

Source sequence(s)

AC022506

Consensus CDS

CCDS8943.1

UniProtKB/Swiss-Prot

F8VS99, P35638

UniProtKB/TrEMBL

Q53YD1

Related

ENSP00000340671.3, ENST00000346473.8

Conserved Domains (3) summary

smart00338
Location:96 → 159

BRLZ; basic region leucin zipper

cd14686
Location:102 → 153

bZIP; coiled coil [structural motif]

pfam02724
Location:17 → 125

CDC45; CDC45-like protein