ELK1

Summary

ELK1 (ETS transcription factor ELK1, HGNC:3321) is a protein-coding gene on chromosome Xp11.23, encoding ETS domain-containing protein Elk-1 (P19419). Transcription factor that binds to purine-rich DNA sequences.

This gene is a member of the Ets family of transcription factors and of the ternary complex factor (TCF) subfamily. Proteins of the TCF subfamily form a ternary complex by binding to the the serum response factor and the serum response element in the promoter of the c-fos proto-oncogene. The protein encoded by this gene is a nuclear target for the ras-raf-MAPK signaling cascade. This gene produces multiple isoforms by using alternative translational start codons and by alternative splicing. Related pseudogenes have been identified on chromosomes 7 and 14.

Source: NCBI Gene 2002 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 80 total
• Druggable target: yes
• Transcription factor: yes — 74 downstream targets (CollecTRI)
• MANE Select transcript: NM_001114123

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3321
Approved symbol	ELK1
Name	ETS transcription factor ELK1
Location	Xp11.23
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000126767
Ensembl biotype	protein_coding
OMIM	311040
Entrez	2002

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 13 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000247161, ENST00000343894, ENST00000376983, ENST00000468956, ENST00000879539, ENST00000879540, ENST00000879541, ENST00000879542, ENST00000935083, ENST00000935084, ENST00000935085, ENST00000969565, ENST00000969566, ENST00000969567

RefSeq mRNA: 3 — MANE Select: NM_001114123 NM_001114123, NM_001257168, NM_005229

CCDS: CCDS14283, CCDS59165

Canonical transcript exons

ENST00000376983 — 7 exons

Exon	Start	End
ENSE00000867044	47637013	47637114
ENSE00000867045	47637751	47638182
ENSE00000867046	47638895	47639338
ENSE00001472335	47649921	47650026
ENSE00003678048	47641232	47641475
ENSE00003848232	47650423	47650563
ENSE00004034703	47635521	47636927

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 98.49.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 33.2916 / max 211.7490, expressed in 1818 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
199139	30.0571	1816
199140	3.2344	1582

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
olfactory bulb	UBERON:0002264	98.49	silver quality
type B pancreatic cell	CL:0000169	98.29	silver quality
diaphragm	UBERON:0001103	96.36	silver quality
vena cava	UBERON:0004087	95.84	gold quality
gluteal muscle	UBERON:0002000	95.73	gold quality
cardia of stomach	UBERON:0001162	95.55	gold quality
body of tongue	UBERON:0011876	94.77	gold quality
triceps brachii	UBERON:0001509	93.87	silver quality
tongue	UBERON:0001723	93.77	gold quality
tongue squamous epithelium	UBERON:0006919	93.66	silver quality
cervix squamous epithelium	UBERON:0006922	93.55	silver quality
lateral globus pallidus	UBERON:0002476	93.35	gold quality
cerebellar vermis	UBERON:0004720	93.33	gold quality
pylorus	UBERON:0001166	93.30	gold quality
pharyngeal mucosa	UBERON:0000355	93.17	gold quality
nasal cavity epithelium	UBERON:0005384	93.15	gold quality
nucleus accumbens	UBERON:0001882	93.13	gold quality
ventral tegmental area	UBERON:0002691	93.06	gold quality
superior surface of tongue	UBERON:0007371	93.02	gold quality
pericardium	UBERON:0002407	92.88	gold quality
nipple	UBERON:0002030	92.71	gold quality
right hemisphere of cerebellum	UBERON:0014890	92.70	gold quality
hair follicle	UBERON:0002073	92.69	gold quality
subthalamic nucleus	UBERON:0001906	92.57	gold quality
pons	UBERON:0000988	92.54	gold quality
right frontal lobe	UBERON:0002810	92.37	gold quality
saphenous vein	UBERON:0007318	92.34	gold quality
cerebellar cortex	UBERON:0002129	92.23	gold quality
cerebellar hemisphere	UBERON:0002245	92.20	gold quality
cervix epithelium	UBERON:0004801	92.15	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.65

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

74 targets.

Target	Regulation
ACTA2	Unknown
ADAMTS13	Unknown
AGTR1
APOA1
BAX
BRF1	Unknown
CCN5	Unknown
CCT8	Unknown
CDKN1A	Unknown
CDKN1B	Unknown
CITED2	Unknown
DAP3	Unknown
DDIT4	Unknown
DLST
DPP3	Unknown
EGR1	Unknown
EIF2AK1	Activation
EIF3K
ERBB2	Unknown
EZH2	Activation
F2	Unknown
FOS	Unknown
FOSL1	Activation
FUT1	Unknown
FUT4	Unknown
FZD8
HMOX1	Activation
IER2	Unknown
JUNB	Unknown
KATNB1	Unknown

JASPAR motifs

Motif	Name	Family
MA0028.1	ELK1	Ets-related
MA0028.2	ELK1	Ets-related
MA0028.3	ELK1	Ets-related
MA1931.1	ELK1::HOXA1	Ets-related::HOX-related factors
MA1932.1	ELK1::HOXB13	Ets-related::HOX-related factors
MA1932.2	ELK1::HOXB13	Ets-related::HOX-related factors
MA1933.1	ELK1::SREBF2	Ets-related::bHLH-ZIP
MA1933.2	ELK1::SREBF2	Ets-related::bHLH-ZIP
MA1954.1	FOXO1::ELK1	FOX::Ets-related
MA1954.2	FOXO1::ELK1	FOX::Ets-related
MA1957.1	HOXB2::ELK1	HOX::Ets-related
MA1958.1	HOXD12::ELK1	HOX::Ets-related
MA1958.2	HOXD12::ELK1	HOX::Ets-related

JASPAR matrix evidence (PMIDs): PMID:1425594, PMID:24218641, PMID:23050235, PMID:31913281

Upstream regulators (CollecTRI, top): EGR1, HLX, LMO2, MYC, NR3C1

miRNA regulators (miRDB)

143 targeting ELK1, 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-3613-3P	100.00	76.36	7965
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-7845-5P	99.88	64.88	771
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-3121-3P	99.82	71.96	3630

Literature-anchored findings (GeneRIF, showing 40)

• Complexities in Elk-1 transcription factor function and regulation (PMID:12023815)
• The Elk-1 R motif and the p300 CRD1 motif represent a new class of repression domains that are regulated in a context-dependent manner. (PMID:12077333)
• Interaction of serum response factor (SRF) with the Elk-1 B box inhibits RhoA-actin signaling to SRF and potentiates transcriptional activation by Elk-1 (PMID:12242287)
• Bombesin-dependent activation of the transcription factor Elk-1 and significant increase of cell proliferation in prostate cancer cell lines (PMID:12409226)
• role in signal cascade in immediate-early gene induction by anisomycin and arsenite (PMID:12660819)
• ERK pathway activation leads to both phosphorylation of Elk-1 and loss of SUMO conjugation. This reciprocal regulation of activation and repression are coupled by MAP kinase modification of Elk-1. (PMID:12887893)
• SUMO conjugation is a novel regulator of Elk-1 function through the control of its nuclear-cytoplasmic shuttling. (PMID:15210726)
• transcriptional activities of ElK-1 and AP-1 are inhibited by TRIM45, a novel human RBCC/TRIM protein (PMID:15351693)
• Deletion analyses of the Egr-1 promoter identify a minimal estradiol-responsive region of the promoter containing a serum response element which binds Elk-1 and serum response factor. (PMID:15449318)
• H. pylori induction of villin in the stomach correlates with activation and cooperative binding of Elk-1 and the SRF to the proximal promoter of villin (PMID:15576363)
• Basal and inducible phosphorylation of Elk-1 is impaired in a patient with premature aging syndrome and insulin resistance. (PMID:15772901)
• Data suggest that residues distal to the binding interface of DNA and Elk-1/SAP-1 may indirectly modulate the binding affinity by stabilizing the protein scaffold required for efficient DNA interaction. (PMID:15808854)
• PKCalpha expression may be modulated by Elk-1 and MZF-1 at the transcriptional level. (PMID:16297876)
• PI3K through p21-activated kinase 1 regulates FRA-1 proto-oncogene induction by cigarette smoke and the subsequent activation of the Elk1 and cAMP-response element-binding protein transcription factors (PMID:16490785)
• JNK1 and JNK2 differentially regulate TBP through Elk-1, controlling c-Jun expression and cell proliferation (PMID:17074809)
• PKC-eta-mediated glioblastoma proliferation involves MEK/mitogen-activated protein (MAP) kinase phosphorylation, activation of ERK and subsequently of Elk-1. (PMID:17146445)
• Increased expression of transcription factor Elk-1 may play an important role in esophageal carcinogenesis. (PMID:17203534)
• Human Rev7 (hRev7)/MAD2B/MAD2L2 is an interaction partner for Elk-1 and hRev7 acts to promote Elk-1 phosphorylation by the c-Jun N-terminal protein kinase (JNK) MAP kinases. (PMID:17296730)
• Elk1 transcription factor targets a binding site in the TBP promoter and its occupancy of this region is reciprocal with that of Mif1. (PMID:17499043)
• The 5’ UTR controls ribosomal access to the ELK-1 AUG initiation codon. (PMID:17591614)
• BFGF activates the MAPK and NFkappB pathways that converge on ELK1 to control production of MMP13 by articular chondrocytes. (PMID:17724016)
• Elk-1 exerted opposite effects on hSlu7 transcription:Elk-1 protein represses transcription in a dose-dependent manner (PMID:17804646)
• Elk-1 activated transcription of the HTLV-1 long terminal repeat (LTR), and mutations within either of the TCF sites or the CArG box reduced responsiveness of the LTR to Elk-1. (PMID:17898074)
• Hemin activated Elk-1, SRF, and NF-kappaB and promoted their interaction with the Egr-1 promoter (PMID:17967787)
• MDMX basal promoter activity requires c-Ets-1 and Elk-1. c-Ets-1 and Elk-1 control MDMX transcription and contribute to the suppression of p53 activity. (PMID:18172009)
• These results strongly support that Elk-1 protein is a novel binding-protein partner for FAK, a finding that significantly broadens the potential functioning of FAK and Elk-1. (PMID:18247360)
• ERK and JNK MAPK/Elk-1/Egr-1 signal cascade is required for p53-independent transcriptional activation of p21(Waf1/Cip1) in response to curcumin in U-87MG human glioblastoma cells (PMID:18316600)
• the early growth response 1 gene is repressed by Elk1 in normally cycling SH-SY5Y neuroblastoma cell line (PMID:18434015)
• Results suggest that Elk-1 is anchored to neuronal microtubules in resting or unstimulated cells, and upon stimulation is phosphorylated, which relocalizes phospho-Elk-1 to the nucleus in neurons. (PMID:19013529)
• Elk-1 is involved in upregulating HRI expression during stress along with a co-activator p300, while MZF-1 along with HDAC-1 is instrumental in its downregulation during hemin treatment. (PMID:19133234)
• Constitutive androstane receptor expression may be mediated by phosphorylated Elk-1 via the SAPK signaling pathway (PMID:19302787)
• FcgammaRIIIB, but not FcgammaRIIA, activates a unique signaling pathway leading to the nuclear-restricted phosphorylation of ERK and Elk-1, independently of Syk, PI3K, or MEK (PMID:19342628)
• polymorphism rs968567 influences FADS2 gene promoter activity and alters DNA binding affinity of the transcription factor ELK1. (PMID:19546342)
• Data show that a significant overlaps between the ELK1- and SRF-binding regions, and between ELK1- and GABPA-binding regions. (PMID:19687146)
• Data show that T417(+) Elk-1 uniquely associates with several types of inclusions present in Lewy body Disease, Alzheimer’s disease, and Huntington’s Disease. (PMID:20126313)
• The authors now show that the inactivation of either the Elk-1 or serum response factor (SRF) binding site within the enhancer also reduces major immediate-early promoter activation and viral replication of human cytomegalovirus in fibroblasts. (PMID:20147408)
• preferential activation of PTPRZ1 by HIF-2 results at least in part from cooperative binding of HIF-2 and ELK1 to nearby sites on the PTPRZ1 promoter region (PMID:20224786)
• Results demonstrate that SENP1 is the most efficient SUMO protease acting on Elk-1, and that SENP3 has little effect on Elk-1. SENP2 has an intermediate effect, but its ability to activate Elk-1 is independent from its SUMO-deconjugating activity. (PMID:20337593)
• findings suggest that MLL-AF4 family fusion oncoproteins can activate Elk-1 through Ras/MEK/extracellular signal-regulated kinase (ERK) pathway and strongly support the role of Ras signaling in the pathogenesis of MLL-rearranged leukemia (PMID:20362031)
• AC3-33 is a novel member of the secretory family and inhibits Elk1 transcriptional activity via ERK1/2 MAP (PMID:20680465)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	elk1	ENSDARG00000078066
mus_musculus	Elk1	ENSMUSG00000009406
rattus_norvegicus	Elk1	ENSRNOG00000010171

Paralogs (28): ETV1 (ENSG00000006468), ETV7 (ENSG00000010030), SPI1 (ENSG00000066336), ELF4 (ENSG00000102034), ETV2 (ENSG00000105672), ERF (ENSG00000105722), ELF2 (ENSG00000109381), ELK3 (ENSG00000111145), ETV3 (ENSG00000117036), ELF1 (ENSG00000120690), SPDEF (ENSG00000124664), ETS1 (ENSG00000134954), EHF (ENSG00000135373), ELF5 (ENSG00000135374), ETV6 (ENSG00000139083), FLI1 (ENSG00000151702), GABPA (ENSG00000154727), ERG (ENSG00000157554), ETS2 (ENSG00000157557), ELK4 (ENSG00000158711), ELF3 (ENSG00000163435), FEV (ENSG00000163497), SPIC (ENSG00000166211), ETV4 (ENSG00000175832), ETV5 (ENSG00000244405), ETV3L (ENSG00000253831), ERFL (ENSG00000268041), SPIB (ENSG00000269404)

Protein

Protein identifiers

ETS domain-containing protein Elk-1 — P19419 (reviewed: P19419)

All UniProt accessions (1): P19419

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor that binds to purine-rich DNA sequences. Forms a ternary complex with SRF and the ETS and SRF motifs of the serum response element (SRE) on the promoter region of immediate early genes such as FOS and IER2. Induces target gene transcription upon JNK and MAPK-signaling pathways stimulation.

Subunit / interactions. Interacts in its sumoylated form with PIAS2/PIASX which enhances its transcriptional activator activity. Interacts with MAD2L2; the interaction is direct and promotes phosphorylation by the kinases MAPK8 and/or MAPK9. Interacts with POU1F1.

Subcellular location. Nucleus.

Tissue specificity. Lung and testis.

Post-translational modifications. Sumoylation represses transcriptional activator activity as it results in recruitment of HDAC2 to target gene promoters which leads to decreased histone acetylation and reduced transactivator activity. It also regulates nuclear retention. On mitogenic stimulation, phosphorylated on C-terminal serine and threonine residues by MAPK1. Ser-383 and Ser-389 are the preferred sites for MAPK1. In vitro, phosphorylation by MAPK1 potentiates ternary complex formation with the serum responses factors, SRE and SRF. Also phosphorylated on Ser-383 by MAPK8 and/or MAKP9. Phosphorylation leads to loss of sumoylation and restores transcriptional activator activity. Phosphorylated and activated by CAMK4, MAPK11, MAPK12 and MAPK14. Upon bFGF stimulus, phosphorylated by PAK1. Phosphorylated by PRP4K at Thr-417; phosphorylation activation ELK1 transcriptional activity.

Similarity. Belongs to the ETS family.

Isoforms (2)

UniProt ID	Names	Canonical?
P19419-1	1	yes
P19419-2	2, ELKV

RefSeq proteins (3): NP_001107595, NP_001244097, NP_005220 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000418	Ets_dom	Domain
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily
IPR046328	ETS_fam	Family

Pfam: PF00178

UniProt features (49 total): mutagenesis site 12, modified residue 9, strand 5, region of interest 4, cross-link 3, sequence variant 3, helix 3, turn 3, splice variant 2, compositionally biased region 2, chain 1, DNA-binding region 1, glycosylation site 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
1DUX	X-RAY DIFFRACTION	2.1
5VVT	X-RAY DIFFRACTION	2.8
9F6Y	ELECTRON MICROSCOPY	2.98

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P19419-F1	60.14	0.26

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 (12): 353, 363, 368, 383, 389, 417, 422, 230, 249, 254, 324, 336

Glycosylation sites (1): 381

Mutagenesis-validated functional residues (12):

Position	Phenotype
230	9-fold increase in transcriptional activator activity; when associated with r-249. reduction in sumoylation.
249	9-fold increase in transcriptional activator activity; when associated with r-230. reduction in sumoylation.
254	reduction in sumoylation.
324	no effect on ternary complex formation but loss of transcriptional activity positive regulation by mad2l2.
336	no effect on ternary complex formation.
353	no effect on ternary complex formation.
363	no effect on ternary complex formation.
368	no effect on ternary complex formation.
383	17% reduction in ternary complex formation.
389	34% reduction in ternary complex formation.
417	no effect on ternary complex formation.
422	slight reduction in ternary complex formation.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-198753	ERK/MAPK targets
R-HSA-9031628	NGF-stimulated transcription
R-HSA-9609690	HCMV Early Events
R-HSA-9634638	Estrogen-dependent nuclear events downstream of ESR-membrane signaling

MSigDB gene sets: 319 (showing top): PID_BCR_5PATHWAY, RNGTGGGC_UNKNOWN, GOBP_RESPONSE_TO_ETHANOL, GOBP_HEPATICOBILIARY_SYSTEM_DEVELOPMENT, GOBP_RESPONSE_TO_IONIZING_RADIATION, BIOCARTA_FMLP_PATHWAY, REACTOME_INNATE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_CELLULAR_RESPONSE_TO_LIPID, KEGG_MAPK_SIGNALING_PATHWAY, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, AAGCCAT_MIR135A_MIR135B, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN

GO Biological Process (15): liver development (GO:0001889), regulation of transcription by RNA polymerase II (GO:0006357), response to light stimulus (GO:0009416), gene expression (GO:0010467), cell differentiation (GO:0030154), lung development (GO:0030324), response to ethanol (GO:0045471), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), cellular response to testosterone stimulus (GO:0071394), cellular response to gamma radiation (GO:0071480), response to fibroblast growth factor (GO:0071774), hippocampal neuron apoptotic process (GO:0110088), regulation of DNA-templated transcription (GO:0006355), cellular response to lipid (GO:0071396)

GO Molecular Function (15): transcription cis-regulatory region binding (GO:0000976), 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), chromatin binding (GO:0003682), DNA-binding transcription factor activity (GO:0003700), mediator complex binding (GO:0036033), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), transcription regulator inhibitor activity (GO:0140416), transcription regulator activator activity (GO:0140537), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), double-stranded DNA binding (GO:0003690), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565)

GO Cellular Component (7): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), dendrite (GO:0030425), mitochondrial membrane (GO:0031966), neuronal cell body (GO:0043025), axon terminus (GO:0043679)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Nuclear Events (kinase and transcription factor activation)	2
MAPK targets/ Nuclear events mediated by MAP kinases	1
HCMV Infection	1
Extra-nuclear estrogen signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	3
regulation of gene expression	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
transcription regulator activity	3
transcription by RNA polymerase II	2
DNA-templated transcription	2
regulation of transcription by RNA polymerase II	2
binding	2
DNA binding	2
cellular anatomical structure	2
gland development	1
hepaticobiliary system development	1
response to radiation	1
macromolecule biosynthetic process	1
cellular developmental process	1
respiratory tube development	1
animal organ development	1
respiratory system development	1
response to alcohol	1
positive regulation of RNA biosynthetic process	1
positive regulation of DNA-templated transcription	1
response to testosterone	1
cellular response to lipid	1
cellular response to ketone	1
response to gamma radiation	1
cellular response to ionizing radiation	1
response to growth factor	1
neuron apoptotic process	1
regulation of RNA biosynthetic process	1
response to lipid	1
cellular response to chemical stimulus	1
transcription regulatory region nucleic acid binding	1
sequence-specific double-stranded DNA binding	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
transcription cis-regulatory region binding	1

Protein interactions and networks

STRING

656 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ELK1	MED23	Q9ULK4	870
ELK1	KCNH3	Q9ULD8	768
ELK1	TBC1D25	Q3MII6	761
ELK1	MYOCD	Q8IZQ8	614
ELK1	SRF	P11831	610
ELK1	HNF4A	P41235	443
ELK1	GTF2A1	P52655	405
ELK1	ATF2	P15336	326
ELK1	FOS	P01100	325
ELK1	MISO1	Q6P1S2	310
ELK1	MYB	P10242	296
ELK1	SNCG	O76070	287
ELK1	ITGB6	P18564	283
ELK1	MAPK1	P28482	263
ELK1	EFR3A	Q14156	254

IntAct

69 interactions, top by confidence:

A	B	Type	Score
UBE2I	ELK1	psi-mi:“MI:0566”(sumoylation reaction)	0.730
UBE2I	ELK1	psi-mi:“MI:0407”(direct interaction)	0.730
ELK1	UBE2I	psi-mi:“MI:0407”(direct interaction)	0.730
UBE2I	ELK1	psi-mi:“MI:0915”(physical association)	0.730
ELK1	UBE2I	psi-mi:“MI:0915”(physical association)	0.730
SUMO1	ELK1	psi-mi:“MI:0915”(physical association)	0.660
FOXE1	ELK1	psi-mi:“MI:0915”(physical association)	0.630
ELK1	FOXE1	psi-mi:“MI:0915”(physical association)	0.630
	ELK1	psi-mi:“MI:0915”(physical association)	0.630
ELK1	MAPK3	psi-mi:“MI:2364”(proximity)	0.570
ELK1	MAPK3	psi-mi:“MI:0217”(phosphorylation reaction)	0.570
FMR1	ELK1	psi-mi:“MI:0915”(physical association)	0.560
APP	ELK1	psi-mi:“MI:0915”(physical association)	0.560
ELK1		psi-mi:“MI:0407”(direct interaction)	0.560

BioGRID (167): ELK1 (Affinity Capture-Western), UBE2I (Reconstituted Complex), ELK1 (Biochemical Activity), ELK1 (Far Western), ELK1 (Reconstituted Complex), ELK1 (Two-hybrid), ELK1 (Two-hybrid), ELK1 (Co-localization), ELK1 (Biochemical Activity), ELK1 (Biochemical Activity), DOK4 (Affinity Capture-Western), EPAS1 (Affinity Capture-Western), ELK1 (Biochemical Activity), ELK1 (Biochemical Activity), ELK1 (Biochemical Activity)

ESM2 similar proteins: A0A1W2PQ73, A1YF16, A1YG93, A2RU54, A5PKG8, O02786, O14813, O15353, O35602, O43638, O57601, P13297, P19419, P28360, P35548, P41969, P42580, P43687, P49640, P50223, P50548, P52946, P52950, P63156, P63157, P70459, P78413, Q03358, Q14549, Q2VL78, Q2VL79, Q2VL82, Q2VL83, Q2VL84, Q2VL85, Q2VL86, Q2VL87, Q2VL88, Q5NSW5, Q61575

Diamond homologs: A0A1W2PQ73, A0JN51, A1A4L6, A1YF15, A1YG61, A1YG91, A2D4Z7, A2T737, A2T762, A3FEM2, A4GTP4, A8WFJ9, O00321, O01519, O70132, O70273, O95238, P01105, P10157, P11308, P11536, P13474, P14921, P15036, P15037, P15062, P18755, P18756, P19102, P19419, P20105, P26323, P27577, P28322, P28324, P29773, P29774, P29775, P29776, P32519

SIGNOR signaling

40 interactions.

A	Effect	B	Mechanism
PELI3	up-regulates	ELK1
MAPK14	up-regulates	ELK1	phosphorylation
ELK1	up-regulates	Cell_growth
ERK1/2	“up-regulates activity”	ELK1	phosphorylation
MAPK8	“up-regulates activity”	ELK1	phosphorylation
TAOK2	“up-regulates activity”	ELK1	phosphorylation
MAPK9	“up-regulates activity”	ELK1	phosphorylation
ERK1/2	up-regulates	ELK1	phosphorylation
ELK1	“up-regulates quantity by expression”	MUC4	“transcriptional regulation”
ELK1	“up-regulates quantity by expression”	PRKCA	“transcriptional regulation”
AKT	“up-regulates activity”	ELK1	phosphorylation
HLX	“up-regulates quantity by expression”	ELK1	“transcriptional regulation”
Gbeta	up-regulates	ELK1	phosphorylation
FBXO25	“down-regulates quantity by destabilization”	ELK1	binding
“Cullin 1-RBX1-Skp1”	“down-regulates quantity by destabilization”	ELK1	polyubiquitination
MAPK3	up-regulates	ELK1	phosphorylation
MAPK8	up-regulates	ELK1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 29 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
MITF-M-regulated melanocyte development	5	27.2×	3e-04
Cellular responses to stress	6	10.5×	4e-04
Cytokine Signaling in Immune system	5	9.7×	1e-03
Cellular responses to stimuli	6	9.0×	6e-04
Cell Cycle	5	8.6×	1e-03
Infectious disease	6	7.1×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	38
Likely benign	4
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

1122 predictions. Top by Δscore:

Variant	Effect	Δscore
X:47639335:TGTT:T	acceptor_gain	1.0000
X:47641227:TGTA:T	donor_loss	1.0000
X:47641228:GTACC:G	donor_loss	1.0000
X:47641229:TACCT:T	donor_loss	1.0000
X:47650418:CTCA:C	donor_loss	1.0000
X:47636756:T:TA	donor_gain	0.9900
X:47636928:C:CC	acceptor_gain	0.9900
X:47637008:CCTAC:C	donor_loss	0.9900
X:47637009:CTACC:C	donor_loss	0.9900
X:47637010:TACC:T	donor_loss	0.9900
X:47637011:ACCT:A	donor_loss	0.9900
X:47637012:CC:C	donor_loss	0.9900
X:47637112:GGTC:G	acceptor_loss	0.9900
X:47637113:GTCT:G	acceptor_loss	0.9900
X:47637114:TCTGT:T	acceptor_loss	0.9900
X:47637115:C:CC	acceptor_gain	0.9900
X:47637115:C:T	acceptor_loss	0.9900
X:47637116:T:G	acceptor_loss	0.9900
X:47637744:CACT:C	donor_loss	0.9900
X:47637745:ACTC:A	donor_loss	0.9900
X:47637746:CTCA:C	donor_loss	0.9900
X:47637747:TCA:T	donor_loss	0.9900
X:47637748:CAC:C	donor_loss	0.9900
X:47637749:A:AC	donor_gain	0.9900
X:47637749:A:C	donor_loss	0.9900
X:47637750:C:CA	donor_loss	0.9900
X:47637750:C:CC	donor_gain	0.9900
X:47638073:T:TA	donor_gain	0.9900
X:47638890:CTTA:C	donor_loss	0.9900
X:47638891:TTACC:T	donor_loss	0.9900

AlphaMissense

2726 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:47637052:A:C	S383R	1.000
X:47637052:A:T	S383R	1.000
X:47637054:T:G	S383R	1.000
X:47639294:A:C	F85L	1.000
X:47639294:A:T	F85L	1.000
X:47639295:A:C	F85C	1.000
X:47639295:A:G	F85S	1.000
X:47639296:A:G	F85L	1.000
X:47639301:T:C	Y83C	1.000
X:47639302:A:C	Y83D	1.000
X:47639302:A:G	Y83H	1.000
X:47639302:A:T	Y83N	1.000
X:47639304:A:T	V82D	1.000
X:47639306:G:C	F81L	1.000
X:47639306:G:T	F81L	1.000
X:47639307:A:C	F81C	1.000
X:47639307:A:G	F81S	1.000
X:47639308:A:C	F81V	1.000
X:47639308:A:G	F81L	1.000
X:47639308:A:T	F81I	1.000
X:47639309:C:A	K80N	1.000
X:47639309:C:G	K80N	1.000
X:47639310:T:A	K80M	1.000
X:47639311:T:C	K80E	1.000
X:47639313:T:G	Q79P	1.000
X:47639316:C:A	G78V	1.000
X:47639316:C:T	G78D	1.000
X:47639317:C:A	G78C	1.000
X:47639317:C:G	G78R	1.000
X:47639324:C:A	K75N	1.000

dbSNP variants (sampled 300 via entrez): RS1000619237 (X:47647816 C>G), RS1001208258 (X:47640417 A>T), RS1001269818 (X:47641900 A>C,G), RS1001624677 (X:47650323 C>T), RS1001639648 (X:47639929 A>T), RS1001696660 (X:47649787 A>G), RS1001709293 (X:47644393 C>T), RS1001990012 (X:47644910 C>T), RS1002239473 (X:47642169 C>T), RS1002606552 (X:47642700 G>A), RS1002702711 (X:47651167 G>A), RS1003199784 (X:47650601 C>A,G), RS1003201153 (X:47644912 G>T), RS1003756321 (X:47650885 G>A), RS1003878113 (X:47646339 G>A)

Disease associations

OMIM: gene MIM:311040 | 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: yes

ChEMBL targets (1): CHEMBL4453 (SINGLE PROTEIN)

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

PubChem BioAssay actives

5 with measured affinity, of 11 total; 5 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
1-(4-bromophenyl)-1-[(4-hydroxy-3-methoxyphenyl)methyl]-3-phenylurea	1803132: Cell-Based Enzyme Inhibition Assay (ELISA) from Article 10.3109/14756366.2011.608665: “Synthesis and biological evaluation of novel N, N’-disubstituted urea and thiourea derivatives as potential anti-melanoma agents.”	ic50	1.2400	uM
1-(4-bromophenyl)-1-[(4-hydroxy-3-methoxyphenyl)methyl]-3-phenylthiourea	1803132: Cell-Based Enzyme Inhibition Assay (ELISA) from Article 10.3109/14756366.2011.608665: “Synthesis and biological evaluation of novel N, N’-disubstituted urea and thiourea derivatives as potential anti-melanoma agents.”	ic50	1.5300	uM
1-(4-fluorophenyl)-1-[(4-hydroxy-3-methoxyphenyl)methyl]-3-phenylthiourea	1803132: Cell-Based Enzyme Inhibition Assay (ELISA) from Article 10.3109/14756366.2011.608665: “Synthesis and biological evaluation of novel N, N’-disubstituted urea and thiourea derivatives as potential anti-melanoma agents.”	ic50	1.9500	uM
1-[(4-hydroxy-3-methoxyphenyl)methyl]-1-(4-methoxyphenyl)-3-phenylthiourea	1803132: Cell-Based Enzyme Inhibition Assay (ELISA) from Article 10.3109/14756366.2011.608665: “Synthesis and biological evaluation of novel N, N’-disubstituted urea and thiourea derivatives as potential anti-melanoma agents.”	ic50	2.4200	uM
1-(4-chlorophenyl)-1-[(4-hydroxy-3-methoxyphenyl)methyl]-3-phenylthiourea	1803132: Cell-Based Enzyme Inhibition Assay (ELISA) from Article 10.3109/14756366.2011.608665: “Synthesis and biological evaluation of novel N, N’-disubstituted urea and thiourea derivatives as potential anti-melanoma agents.”	ic50	2.4700	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects expression, increases reaction, decreases reaction, affects binding, increases activity (+4 more)	6
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	decreases reaction, increases phosphorylation, increases activity, affects cotreatment	6
U 0126	increases reaction, decreases reaction, increases activity, increases phosphorylation	6
SB 203580	affects cotreatment, decreases reaction, increases phosphorylation	3
pyrazolanthrone	increases phosphorylation, decreases reaction	3
Benzo(a)pyrene	affects methylation, decreases methylation, increases methylation, increases mutagenesis	3
Estradiol	increases expression, increases activity, increases phosphorylation, affects reaction	3
Quercetin	decreases expression, decreases phosphorylation, increases expression, decreases reaction, increases phosphorylation	3
tetrachlorodian	decreases reaction, increases expression	2
Erlotinib Hydrochloride	increases activity, increases phosphorylation, decreases reaction	2
Resveratrol	increases activity, affects reaction, increases expression, decreases reaction	2
Benzene	decreases expression	2
Curcumin	decreases reaction, increases expression, increases phosphorylation	2
Oxygen	affects cotreatment, decreases expression, decreases reaction, increases expression	2
Tetradecanoylphorbol Acetate	increases activity, increases phosphorylation	2
Valproic Acid	decreases reaction, increases activity, increases reaction, decreases methylation	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
dicrotophos	increases expression	1
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
androstane-3,17-dione	increases expression, decreases reaction	1
baicalein	decreases reaction, increases phosphorylation	1
deoxynivalenol	increases expression	1
titanium dioxide	decreases methylation	1
trichostatin A	increases activity, decreases reaction	1
mancozeb	increases phosphorylation	1
methoxyacetic acid	increases activity, increases reaction, decreases reaction	1
arsenite	affects binding, increases reaction, increases activity	1
o,p’-DDT	increases activity	1
cobaltous chloride	affects expression, affects cotreatment	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1042544	Binding	Inhibition of Elk1 phosphorylation in PMA-stimulated human U937 cells at 50 uM after 3 hrs by Western blotting	Structure-activity relationship (SAR) studies of 3-(2-amino-ethyl)-5-(4-ethoxy-benzylidene)-thiazolidine-2,4-dione: development of potential substrate-specific ERK1/2 inhibitors. — Bioorg Med Chem Lett

Cellosaurus cell lines

12 cell lines: 9 cancer cell line, 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A1I3	SEES3-1V human ELK1, clone1	Embryonic stem cell	Male
CVCL_A1I4	SEES3-1V human ELK1, clone2	Embryonic stem cell	Male
CVCL_A1I5	SEES3-1V human ELK1, clone3	Embryonic stem cell	Male
CVCL_B1QZ	Abcam HeLa ELK1 KO	Cancer cell line	Female
CVCL_B8F8	Abcam HCT 116 ELK1 KO	Cancer cell line	Male
CVCL_B9HG	Abcam A-549 ELK1 KO	Cancer cell line	Male
CVCL_D2F0	Abcam MCF-7 ELK1 KO	Cancer cell line	Female
CVCL_D7PC	Ubigene A-549 ELK1 KO	Cancer cell line	Male
CVCL_GZ82	K562 eGFP-ELK1	Cancer cell line	Female
CVCL_KB19	HLR-Elk1	Cancer cell line	Female

Clinical trials (associated diseases)

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