JUNB

Summary

JUNB (JunB proto-oncogene, AP-1 transcription factor subunit, HGNC:6205) is a protein-coding gene on chromosome 19p13.13, encoding Transcription factor JunB (P17275). Transcription factor involved in regulating gene activity following the primary growth factor response. It is a selective cancer dependency (DepMap: 17.4% of cell lines).

Enables sequence-specific double-stranded DNA binding activity. Involved in positive regulation of transcription by RNA polymerase II. Located in nucleoplasm. Part of transcription factor AP-1 complex. Implicated in head and neck squamous cell carcinoma and melanoma. Biomarker of gastrointestinal system cancer (multiple); lung non-small cell carcinoma; and lymphoma (multiple).

Source: NCBI Gene 3726 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 12 total
• Cancer dependency (DepMap): dependent in 17.4% of screened cell lines
• Transcription factor: yes — 122 downstream targets (CollecTRI)
• MANE Select transcript: NM_002229

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6205
Approved symbol	JUNB
Name	JunB proto-oncogene, AP-1 transcription factor subunit
Location	19p13.13
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000171223
Ensembl biotype	protein_coding
OMIM	165161
Entrez	3726

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000302754

RefSeq mRNA: 1 — MANE Select: NM_002229 NM_002229

CCDS: CCDS12280

Canonical transcript exons

ENST00000302754 — 1 exons

Exon	Start	End
ENSE00001129119	12791486	12793315

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 99.70.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 544.6085 / max 21829.6800, expressed in 1826 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
174023	544.6085	1826

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of stomach	UBERON:0001199	99.70	gold quality
left uterine tube	UBERON:0001303	99.66	gold quality
granulocyte	CL:0000094	99.58	gold quality
monocyte	CL:0000576	99.49	gold quality
tibial artery	UBERON:0007610	99.43	gold quality
popliteal artery	UBERON:0002250	99.42	gold quality
vena cava	UBERON:0004087	99.40	gold quality
mononuclear cell	CL:0000842	99.33	gold quality
saphenous vein	UBERON:0007318	99.32	gold quality
leukocyte	CL:0000738	99.31	gold quality
aorta	UBERON:0000947	99.21	gold quality
left ovary	UBERON:0002119	99.20	gold quality
nipple	UBERON:0002030	99.19	gold quality
trachea	UBERON:0003126	99.18	gold quality
omental fat pad	UBERON:0010414	99.13	gold quality
peritoneum	UBERON:0002358	99.08	gold quality
right ovary	UBERON:0002118	99.05	gold quality
ascending aorta	UBERON:0001496	99.04	gold quality
skin of abdomen	UBERON:0001416	99.01	gold quality
lower esophagus mucosa	UBERON:0035834	99.01	gold quality
thoracic aorta	UBERON:0001515	98.99	gold quality
pharyngeal mucosa	UBERON:0000355	98.88	gold quality
descending thoracic aorta	UBERON:0002345	98.81	gold quality
adenohypophysis	UBERON:0002196	98.72	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.63	gold quality
nerve	UBERON:0001021	98.56	gold quality
tibial nerve	UBERON:0001323	98.56	gold quality
skin of leg	UBERON:0001511	98.54	gold quality
upper leg skin	UBERON:0004262	98.53	gold quality
penis	UBERON:0000989	98.50	gold quality

Single-cell (SCXA)

Detected in 43 experiment(s), a significant marker in 27.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	7630.50
E-MTAB-8322	yes	6484.66
E-GEOD-134144	yes	6152.68
E-CURD-88	yes	6040.65
E-CURD-122	yes	6029.23
E-MTAB-8142	yes	4692.94
E-CURD-79	yes	4674.14
E-GEOD-70580	yes	4550.24
E-MTAB-10287	yes	4358.64
E-CURD-97	yes	1588.61
E-HCAD-31	yes	1362.43
E-HCAD-30	yes	1023.39
E-GEOD-89232	yes	785.16
E-MTAB-7052	yes	562.52
E-MTAB-8498	yes	333.32

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

122 targets.

Target	Regulation
ADCYAP1
ALB	Repression
ALK
AP1	Activation
APOC3	Repression
APOM	Unknown
BAX
BCL2
BGLAP	Activation
CAT
CCL2	Activation
CCL5	Activation
CCNA2	Activation
CCND1	Unknown
CCR4
CD68
CD82	Activation
CDKN1A	Unknown
CDKN2A	Unknown
CHUK
CKM
CLU	Unknown
COL1A2	Activation
CSF2
CSF3
CYP11B2
CYP19A1
DCN
DMP1	Unknown
DNAJB4

JASPAR motifs

Motif	Name	Family
MA0490.1	JUNB	Jun-related
MA0490.2	JUNB	Jun-related
MA0490.3	JUNB	Jun-related
MA1132.1	JUN::JUNB	Jun-related
MA1132.2	JUN::JUNB	Jun-related
MA1133.1	JUN::JUNB	Jun-related
MA1133.2	JUN::JUNB	Jun-related
MA1134.1	FOS::JUNB	Fos-related::Jun-related
MA1134.2	FOS::JUNB	Fos-related::Jun-related
MA1135.1	FOSB::JUNB	Fos-related::Jun-related
MA1135.2	FOSB::JUNB	Fos-related::Jun-related
MA1136.1	FOSB::JUNB	Fos-related::Jun-related
MA1137.1	FOSL1::JUNB	Fos-related::Jun-related
MA1137.2	FOSL1::JUNB	Fos-related::Jun-related
MA1138.1	FOSL2::JUNB	Fos-related::Jun-related
MA1138.2	FOSL2::JUNB	Fos-related::Jun-related
MA1139.1	FOSL2::JUNB	Fos-related::Jun-related
MA1139.2	FOSL2::JUNB	Fos-related::Jun-related
MA1140.1	JUNB	Jun-related
MA1140.2	JUNB	Jun-related
MA1140.3	JUNB	Jun-related

JASPAR matrix evidence (PMIDs): PMID:21526160, PMID:15240010, PMID:11988758, PMID:21703547, PMID:14585541

Upstream regulators (CollecTRI, top): CEBPA, DMTF1, ELK1, ESR1, ETS1, ETS2, FOS, FOSL1, GLI2, HBP1, HMGA2, IRF6, JUNB, JUND, MAPK12, MAPK14, MYC, NFKB1, NFKB, NFYA, PGR, RBMX, RELA, SMAD1, SOX9, STAT1, STAT3, WT1

miRNA regulators (miRDB)

51 targeting JUNB, 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-656-3P	100.00	72.15	2788
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-2681-5P	99.75	67.64	1655
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-1825	99.72	68.11	1089
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-1303	99.65	69.77	1662
HSA-MIR-199A-5P	99.51	69.71	1107
HSA-MIR-199B-5P	99.51	69.74	1098
HSA-MIR-548B-3P	99.38	67.26	1000

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 17.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• JunB is an important regulator of erythroid differentiation (PMID:11726656)
• JunB potentiates function of BRCA1 activation domain 1 (AD1) through a coiled-coil-mediated interaction (PMID:12080089)
• Aberrantly expressed c-Jun and JunB are a hallmark of Hodgkin lymphoma cells, stimulate proliferation and synergize with NF-kappa B. (PMID:12145210)
• demonstrated that a functional AP-1 site mediates MMP-2 transcription in cardiac cells through the binding of distinctive Fra1-JunB and FosB-JunB heterodimers. The synthesis of MMP-2 is considered to be independent of the AP-1 transcriptional complex (PMID:12371906)
• results have revealed, for the first time, amplification and expression patterns of JUNB in primary cutaneous lymphomas (PMID:12393503)
• Real-time RT-PCR gave further insights into the role of JunB in human CML. The expression levels were significantly impaired in CML cases. In the promoter area, most of the CpG sites were methylated only in CML cases. (PMID:12506033)
• C/EBPalpha and PKC/delta affect expression of this gene and monocyte differentiation. (PMID:12522006)
• Expression of junB was induced by TPA and Saikosaponin a during 30 min to 6 h of treatment. (PMID:12592382)
• JunB was strongly expressed in T-cell lymphomas, but non-Hodgkin B-cell lymphomas do not or only weakly express JunB. (PMID:12907453)
• Transcription factor c-Jun plays a principal role in down-regulation of mdr-1 expression and induction of apoptosis in salvicine-treated human MDR K562/A02 cells. (PMID:12907627)
• c-jun, junD, junB, and c-fos and Notch2 are expressed in splenic marginal zone lymphoma (PMID:15507668)
• The IGFBP3, hRas, JunB, Egr-1, Id1 and MIDA1 genes were up-regulated in psoriatic involved skin compared with uninvolved skin. (PMID:16552541)
• 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole sensitivity-inducing factor (DSIF)- and NELF-mediated transcriptional pausing has a dual function in regulating immediate-early expression of the human junB gene. (PMID:16880520)
• JunB and JunD contribute opposing effects; JunB activated whereas JunD repressed heme oxygenase-1 expression in human renal epithelial cells (PMID:17204476)
• results suggest that HTLV-I HBZ-SP1- mediated sequestration of JunB to the HBZ-SP1 nuclear bodies may be causing the repression of JunB activity in vivo (PMID:17306025)
• Coordinated down- and up-regulation of the various AP-1 subunits in the course of epidermal wound healing is important for its undisturbed progress, putatively by influencing inflammation and cell-cell communication. (PMID:17495958)
• Dimerization with the Jun proteins inhibits c-Fos nuclear exit. (PMID:17681951)
• JunB is a critical target of mTOR and is translationally regulated in NPM-ALK-positive lymphomas. (PMID:17690253)
• constitutive action of aberrantly expressed JunB on hypomethylated CD30 CpG islands of lymphocytes triggers CD30 induction and initiates activation of the JunB-CD30-JunB loop, essential to the pathogenesis of HL and ALCL (PMID:17965727)
• JunB levels, which are high in S phase, drop during mid- to late G2 phase due to accelerated phosphorylation-dependent degradation by the proteasome, and are required for subsequent reduction of cyclin A2 levels in prometaphase (PMID:18391017)
• sumoylation of JunB regulates its ability to induce cytokine gene transcription and likely plays a critical role in T cell activation. (PMID:18424718)
• JunB plays an important role in controlling prostate carcinogenesis and may be a new target for cancer prevention and therapy. (PMID:18628455)
• results establish a role for JunB in normal erythropoiesis and indicate that JunB may play a major role in the development of JAK2 V617F myeloproliferative disorders. (PMID:18843287)
• confirmed the downregulation of the FOS-JUNB pathway at transcriptional and protein level (PMID:19151755)
• JUNB downregulation is a DNA methylation-independent phenomenon encountered in chronic lymphocytic leukemia only in advanced phases. (PMID:19409613)
• When p53 dysfunction and low expression of JunB are simultaneous, they may play an important role in down-regulating the expression of KAI1 by synergism in hepatocellular carcinoma. (PMID:19666408)
• Chromatin immunoprecipitation assays confirmed that JunB/Fra-1 proteins interact in vivo with the beta4-integrin promoter and that JunB/Fra-1 promoter occupancy is reduced during keratinocyte differentiation as well as in HPV8 E2 positive keratinocytes (PMID:19923172)
• This analysis shows that the overwhelming majority of JUNB alleles in both chronic phase and blast crisis samples remain unmethylated (PMID:20006998)
• The methylation of JunB and CDH13 gene promoters probably plays a role in the pathogenesis of chronic myelogenous leukemia and may have clinical significance in predicting prognosis of CML. (PMID:20030915)
• JunB functions as a transcriptional factor and up-regulates the expression of VEGF. (PMID:20056077)
• The increase in JunB expression attenuated nuclear relocation of apoptosis-inducing factor and mitochondrial Bcl-2 reduction that occurred following hydrogen peroxide exposure. (PMID:20132737)
• Monoammonium glycyrrhizinate highly stimulated JUNB expression in a human hepatoma cell line, HepG2. (PMID:21225234)
• JunB and c-Jun have opposite roles in human epidermal neoplasia and that their functional specificities are dependent on both N- and C-terminal domains. (PMID:21289643)
• JunB is a direct transcriptional activator of GzB and that GzB transcription is also promoted by NPM-ALK. (PMID:21326808)
• JunB activates aromatase promoters by maintaining JunD expression (PMID:21393445)
• Study confirmed that JunB was upregulated in VHL-defective clear-cell renal-cell carcinoma (ccRCC) specimens by immunostaining. Short-hairpin RNA (shRNA)-mediated knockdown of JunB in 786-O and A498 VHL null ccRCC cells suppressed their invasiveness. (PMID:22020339)
• up-regulation of JunB induced by HGF might play an important role in the regulation of cell proliferation and cell invasion through MMP-9 expression. (PMID:22252121)
• Different mechanisms preserve translation of programmed cell death 8 and JunB in poliovirus-infected endothelial cells. (PMID:22328780)
• A novel mechanism by which mitosis progression and chromatid cohesion are regulated through GSK3/SCF(FBXW7)-mediated proteolysis of JunB. (PMID:22710716)
• Apoptosis rate of HepG2 cells transformed with pEGFP-C1-wtp53/JunB was significantly higher. (PMID:23259178)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	junba	ENSDARG00000074378
danio_rerio	junbb	ENSDARG00000104773
mus_musculus	Junb	ENSMUSG00000052837
rattus_norvegicus	Junb	ENSRNOG00000065682
drosophila_melanogaster	Jra	FBGN0001291
caenorhabditis_elegans		WBGENE00008945

Paralogs (2): JUND (ENSG00000130522), JUN (ENSG00000177606)

Protein

Protein identifiers

Transcription factor JunB — P17275 (reviewed: P17275)

Alternative names: Transcription factor AP-1 subunit JunB

All UniProt accessions (2): P17275, Q5U079

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor involved in regulating gene activity following the primary growth factor response. Binds to the DNA sequence 5’-TGA[GC]TCA-3’. Heterodimerizes with proteins of the FOS family to form an AP-1 transcription complex, thereby enhancing its DNA binding activity to an AP-1 consensus sequence and its transcriptional activity.

Subunit / interactions. Binds DNA as a homodimer or as a heterodimer with another member of the Jun/Fos family. Component of an AP-1 transcription factor complex composed of JUN-FOS heterodimers composed of JUN-FOS heterodimers. As part of the AP-1 transcription factor complex, forms heterodimers with FOSB, thereby binding to the AP-1 consensus sequence and stimulating transcription. Interacts with ITCH (via its WW domains).

Subcellular location. Nucleus.

Post-translational modifications. Ubiquitinated by ITCH, leading to its degradation.

Induction. By growth factors.

Similarity. Belongs to the bZIP family. Jun subfamily.

RefSeq proteins (1): NP_002220* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002112	Leuzip_Jun	Family
IPR004827	bZIP	Domain
IPR005643	JNK	Domain
IPR008917	TF_DNA-bd_sf	Homologous_superfamily
IPR046347	bZIP_sf	Homologous_superfamily
IPR050946	AP-1_TF_bZIP	Family

Pfam: PF00170, PF03957

UniProt features (25 total): cross-link 8, modified residue 7, region of interest 4, compositionally biased region 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-P17275-F1	61.35	0.22

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 (15): 117, 240, 251, 255, 259, 4, 33, 36, 81, 141, 240, 240, 343, 102, 104

Function

Pathways and Gene Ontology

Reactome pathways

22 pathways

ID	Pathway
R-HSA-2173796	SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription
R-HSA-6785807	Interleukin-4 and Interleukin-13 signaling
R-HSA-9031628	NGF-stimulated transcription
R-HSA-9725371	Nuclear events stimulated by ALK signaling in cancer
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-162582	Signal Transduction
R-HSA-1643685	Disease
R-HSA-166520	Signaling by NTRKs
R-HSA-168256	Immune System
R-HSA-170834	Signaling by TGF-beta Receptor Complex
R-HSA-187037	Signaling by NTRK1 (TRKA)
R-HSA-198725	Nuclear Events (kinase and transcription factor activation)
R-HSA-212436	Generic Transcription Pathway
R-HSA-2173793	Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer
R-HSA-449147	Signaling by Interleukins
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases
R-HSA-9006936	Signaling by TGFB family members
R-HSA-9700206	Signaling by ALK in cancer
R-HSA-9725370	Signaling by ALK fusions and activated point mutants

MSigDB gene sets: 641 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GSE45365_NK_CELL_VS_CD11B_DC_DN, GSE45365_NK_CELL_VS_BCELL_UP, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_LABYRINTHINE_LAYER_DEVELOPMENT, MODULE_52, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, CHIBA_RESPONSE_TO_TSA_UP, REACTOME_SIGNALING_BY_TGF_BETA_RECEPTOR_COMPLEX, GOBP_REGULATION_OF_ALPHA_BETA_T_CELL_ACTIVATION, AMIT_DELAYED_EARLY_GENES, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, DORN_ADENOVIRUS_INFECTION_12HR_UP, GOBP_T_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE

GO Biological Process (21): vasculogenesis (GO:0001570), osteoblast differentiation (GO:0001649), trophectodermal cell differentiation (GO:0001829), osteoclast proliferation (GO:0002158), regulation of transcription by RNA polymerase II (GO:0006357), osteoclast differentiation (GO:0030316), osteoblast proliferation (GO:0033687), regulation of cell population proliferation (GO:0042127), positive regulation of cell differentiation (GO:0045597), positive regulation of transcription by RNA polymerase II (GO:0045944), decidualization (GO:0046697), response to steroid hormone (GO:0048545), regulation of cell cycle (GO:0051726), embryonic process involved in female pregnancy (GO:0060136), labyrinthine layer blood vessel development (GO:0060716), cellular response to calcium ion (GO:0071277), integrated stress response signaling (GO:0140467), regulation of T-helper 17 cell differentiation (GO:2000319), in utero embryonic development (GO:0001701), regulation of DNA-templated transcription (GO:0006355), cell differentiation (GO:0030154)

GO Molecular Function (9): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA binding (GO:0003677), sequence-specific double-stranded DNA binding (GO:1990837), RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), double-stranded DNA binding (GO:0003690), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515)

GO Cellular Component (6): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription regulator complex (GO:0005667), transcription factor AP-1 complex (GO:0035976), RNA polymerase II transcription regulator complex (GO:0090575)

Reactome top-level categories

Rollup of top-16 pathways:

Category	Pathways
Signal Transduction	2
Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer	1
Signaling by Interleukins	1
Nuclear Events (kinase and transcription factor activation)	1
Signaling by ALK fusions and activated point mutants	1
Immune System	1
Signaling by Receptor Tyrosine Kinases	1
Signaling by TGFB family members	1
Signaling by NTRKs	1
Signaling by NTRK1 (TRKA)	1
RNA Polymerase II Transcription	1
Signaling by TGF-beta Receptor Complex	1
Generic Transcription Pathway	1
Cytokine Signaling in Immune system	1
Disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell differentiation	4
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of DNA-templated transcription	2
transcription by RNA polymerase II	2
cell population proliferation	2
regulation of cellular process	2
regulation of transcription by RNA polymerase II	2
transcription cis-regulatory region binding	2
cellular anatomical structure	2
blood vessel morphogenesis	1
ossification	1
blastocyst formation	1
leukocyte proliferation	1
myeloid leukocyte differentiation	1
regulation of cell differentiation	1
positive regulation of cellular process	1
positive regulation of developmental process	1
positive regulation of DNA-templated transcription	1
maternal placenta development	1
developmental process involved in reproduction	1
tissue development	1
response to hormone	1
response to lipid	1
cell cycle	1
female pregnancy	1
embryo development	1
embryo development ending in birth or egg hatching	1
multicellular organismal reproductive process	1
embryonic organ development	1
placenta blood vessel development	1
labyrinthine layer development	1
response to calcium ion	1
cellular response to metal ion	1
cellular response to stress	1
intracellular signaling cassette	1
regulation of immune effector process	1
regulation of T-helper cell differentiation	1
T-helper 17 cell differentiation	1
regulation of T-helper 17 type immune response	1
chordate embryonic development	1

Protein interactions and networks

STRING

2352 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
JUNB	FOSB	P53539	996
JUNB	FOSL2	P15408	996
JUNB	FOSL1	P15407	996
JUNB	FOS	P01100	995
JUNB	JUND	P17535	984
JUNB	JUN	P05412	983
JUNB	BATF	Q16520	924
JUNB	JDP2	Q8WYK2	849
JUNB	ATF3	P18847	755
JUNB	IRF4	Q15306	689
JUNB	MAF	O75444	664
JUNB	EGR1	P18146	658
JUNB	MAFB	Q9Y5Q3	634
JUNB	MAFG	O15525	620
JUNB	IL1B	P01584	609

IntAct

186 interactions, top by confidence:

A	B	Type	Score
FOS	JUN	psi-mi:“MI:0914”(association)	0.980
JUNB	BATF	psi-mi:“MI:0915”(physical association)	0.970
BATF	JUNB	psi-mi:“MI:0915”(physical association)	0.970
JUNB	BATF	psi-mi:“MI:0407”(direct interaction)	0.970
BATF	JUNB	psi-mi:“MI:0407”(direct interaction)	0.970
JUNB	BATF	psi-mi:“MI:2364”(proximity)	0.970

BioGRID (208): JUNB (Two-hybrid), BATF (Two-hybrid), JUNB (Affinity Capture-MS), JUNB (Affinity Capture-MS), JUNB (Affinity Capture-MS), NINL (Two-hybrid), FOSL1 (Two-hybrid), JUNB (Co-fractionation), JUNB (Two-hybrid), JUNB (Affinity Capture-MS), JUNB (Affinity Capture-MS), JUNB (Affinity Capture-MS), JUNB (Affinity Capture-MS), JUNB (Affinity Capture-MS), JUNB (Affinity Capture-MS)

ESM2 similar proteins: A6NKD9, A7YY54, D3ZLB7, E9Q1P8, E9Q6B2, O00287, O35779, O77627, O77628, O97676, P03966, P04198, P05411, P05412, P05627, P09450, P10158, P11939, P12981, P13346, P15066, P15407, P17275, P17325, P17535, P18870, P23050, P24898, P26014, P27921, P48755, P52909, P53539, P54864, P56432, Q0VBZ5, Q2VPU4, Q61127, Q61976, Q63379

Diamond homologs: A0A0A2J9B3, A7YY54, B8NLU5, O77627, O93602, P05411, P05412, P05627, P09450, P11939, P12981, P15066, P15336, P16951, P17275, P17325, P17535, P17544, P18870, P23050, P24898, P27921, P52890, P52909, P54864, P56432, P78962, P79703, Q00969, Q02100, Q02930, Q09771, Q09926, Q0VBZ5, Q2U616, Q4WVQ7, Q59VR1, Q5R9C9, Q8K1L0, Q8R0S1

SIGNOR signaling

16 interactions.

A	Effect	B	Mechanism
MAPK14	up-regulates	JUNB	phosphorylation
(-)-anisomycin	up-regulates	JUNB	“chemical activation”
JUNB	“up-regulates quantity by expression”	IL4	“transcriptional regulation”
JUNB	“down-regulates quantity by repression”	LORICRIN	“transcriptional regulation”
“Integrator complex”	“down-regulates quantity by repression”	JUNB	“transcriptional regulation”
GSK3B	“down-regulates quantity by destabilization”	JUNB	phosphorylation
MAPK9	down-regulates	JUNB	binding
SMAD3/SMAD4	“up-regulates quantity by expression”	JUNB	“transcriptional regulation”
MAPK12	“up-regulates quantity by expression”	JUNB	“transcriptional regulation”
MAPK14	“up-regulates quantity by expression”	JUNB	“transcriptional regulation”
MAPK8	“up-regulates activity”	JUNB	phosphorylation
DMTF1	“up-regulates quantity by expression”	JUNB	“transcriptional regulation”
ITCH	“down-regulates quantity by destabilization”	JUNB	polyubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 78 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
NGF-stimulated transcription	5	27.4×	5e-04
Response of EIF2AK4 (GCN2) to amino acid deficiency	6	12.8×	2e-03
PIP3 activates AKT signaling	7	9.0×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
integrated stress response signaling	9	92.9×	1e-13
positive regulation of miRNA transcription	5	21.4×	5e-04
transcription by RNA polymerase II	7	7.3×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	12
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

59 predictions. Top by Δscore:

Variant	Effect	Δscore
19:12792796:TC:T	donor_gain	0.7500
19:12792755:C:A	donor_gain	0.6100
19:12792734:GGCCC:G	donor_gain	0.5800
19:12792670:TG:T	donor_gain	0.5600
19:12792756:A:AG	donor_gain	0.5600
19:12793085:G:C	acceptor_gain	0.4900
19:12792802:G:T	donor_gain	0.4800
19:12792754:TC:T	donor_gain	0.4700
19:12793083:AGGG:A	acceptor_gain	0.4500
19:12793084:GGGG:G	acceptor_gain	0.4500
19:12792629:G:GT	donor_gain	0.4200
19:12793086:G:A	acceptor_gain	0.4000
19:12792092:A:T	donor_gain	0.3800
19:12792982:C:G	donor_gain	0.3800
19:12792733:T:TA	donor_gain	0.3600
19:12792886:G:GT	donor_gain	0.3600
19:12792091:G:T	donor_gain	0.3400
19:12792984:TTTAC:T	donor_gain	0.3400
19:12792561:G:GT	donor_gain	0.3100
19:12792767:C:A	donor_gain	0.3100
19:12792492:G:GT	donor_gain	0.3000
19:12792635:G:GT	donor_gain	0.3000
19:12792672:A:AG	donor_gain	0.3000
19:12792094:A:AG	donor_gain	0.2900
19:12792095:G:GG	donor_gain	0.2900
19:12792980:G:GT	donor_gain	0.2900
19:12792940:G:GT	donor_gain	0.2800
19:12791557:A:T	donor_gain	0.2700
19:12792671:GA:G	donor_gain	0.2700
19:12793078:CAGGG:C	acceptor_gain	0.2700

AlphaMissense

2204 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:12792174:T:C	F135L	1.000
19:12792175:T:C	F135S	1.000
19:12792175:T:G	F135C	1.000
19:12792176:C:A	F135L	1.000
19:12792176:C:G	F135L	1.000
19:12792186:T:C	F139L	1.000
19:12792187:T:C	F139S	1.000
19:12792187:T:G	F139C	1.000
19:12792188:T:A	F139L	1.000
19:12792188:T:G	F139L	1.000
19:12792199:T:A	L143Q	1.000
19:12792199:T:C	L143P	1.000
19:12792208:T:C	L146P	1.000
19:12792579:A:G	K270E	1.000
19:12792581:A:C	K270N	1.000
19:12792581:A:T	K270N	1.000
19:12792588:C:A	R273S	1.000
19:12792589:G:C	R273P	1.000
19:12792591:A:G	K274E	1.000
19:12792593:G:C	K274N	1.000
19:12792593:G:T	K274N	1.000
19:12792595:G:C	R275P	1.000
19:12792598:T:C	L276P	1.000
19:12792601:G:C	R277P	1.000
19:12792603:A:C	N278H	1.000
19:12792603:A:G	N278D	1.000
19:12792604:A:C	N278T	1.000
19:12792604:A:G	N278S	1.000
19:12792604:A:T	N278I	1.000
19:12792605:C:A	N278K	1.000

dbSNP variants (sampled 300 via entrez): RS1000901426 (19:12790070 C>T), RS1001278645 (19:12793554 T>C,G), RS1001569409 (19:12793185 T>C), RS1002071250 (19:12792427 C>T), RS1002097621 (19:12792999 T>A,C), RS1002693397 (19:12791646 G>T), RS1003150413 (19:12791389 G>A,C,T), RS1003528681 (19:12790995 G>A), RS1003963182 (19:12790920 A>G), RS1004076399 (19:12791396 C>T), RS1004337603 (19:12790867 C>T), RS1005752745 (19:12793023 T>C), RS1005755553 (19:12789629 G>T), RS1006092655 (19:12792686 C>A,G,T), RS1007861949 (19:12790491 A>C)

Disease associations

OMIM: gene MIM:165161 | 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)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases expression, decreases expression, increases activity, increases phosphorylation (+2 more)	7
Estradiol	affects cotreatment, increases expression, decreases expression	6
Cadmium Chloride	affects cotreatment, increases expression, decreases expression, increases abundance	6
Tetrachlorodibenzodioxin	increases expression, affects expression	5
Benzo(a)pyrene	increases expression, increases methylation	4
Tetradecanoylphorbol Acetate	decreases reaction, increases expression, affects binding, increases reaction	4
Cyclosporine	decreases expression, increases expression	4
(+)-JQ1 compound	decreases expression, increases expression	3
Decitabine	affects methylation, decreases expression, decreases reaction, affects expression	3
Arsenic Trioxide	increases expression, increases reaction, decreases expression	3
Air Pollutants	decreases expression, increases expression, affects expression, increases abundance	3
Cadmium	increases abundance, increases expression, decreases reaction, decreases expression	3
Cisplatin	increases reaction, increases expression, affects cotreatment, decreases expression	3
Valproic Acid	decreases expression, increases expression	3
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	3
Aflatoxin B1	affects expression, decreases expression, increases expression, increases methylation, decreases reaction	3
Particulate Matter	decreases expression, increases abundance, increases expression	3
nickel sulfate	increases expression	2
polyhexamethyleneguanidine	increases expression	2
cylindrospermopsin	increases expression	2
Acetaminophen	increases expression	2
Calcitriol	increases expression	2
Fluorouracil	increases expression, affects cotreatment, decreases response to substance	2
Hydrogen Peroxide	affects expression, increases expression	2
Quercetin	increases expression	2
Dronabinol	decreases expression, increases expression	2
Tobacco Smoke Pollution	affects expression	2
Tretinoin	increases expression	2
aristolochic acid I	increases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1

Cellosaurus cell lines

6 cell lines: 3 embryonic stem cell, 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A3J8	SEES3-1V human JUNB, clone1	Embryonic stem cell	Male
CVCL_A3J9	SEES3-1V human JUNB, clone2	Embryonic stem cell	Male
CVCL_A3K0	SEES3-1V human JUNB, clone3	Embryonic stem cell	Male
CVCL_AW30	K562 eGFP-JUNB	Cancer cell line	Female
CVCL_D1X5	Abcam A-549 JUNB KO	Cancer cell line	Male
CVCL_D2BE	Abcam HCT 116 JUNB KO	Cancer cell line	Male

Clinical trials (associated diseases)

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