ECT2

Summary

ECT2 (epithelial cell transforming 2, HGNC:3155) is a protein-coding gene on chromosome 3q26.31, encoding Protein ECT2 (Q9H8V3). Guanine nucleotide exchange factor (GEF) that catalyzes the exchange of GDP for GTP. It is a common-essential gene (DepMap: required in 96.5% of cancer cell lines).

The protein encoded by this gene is a guanine nucleotide exchange factor and transforming protein that is related to Rho-specific exchange factors and yeast cell cycle regulators. The expression of this gene is elevated with the onset of DNA synthesis and remains elevated during G2 and M phases. In situ hybridization analysis showed that expression is at a high level in cells undergoing mitosis in regenerating liver. Thus, this protein is expressed in a cell cycle-dependent manner during liver regeneration, and is thought to have an important role in the regulation of cytokinesis. Several transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 1894 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 128 total
• Cancer dependency (DepMap): dependent in 96.5% of screened cell lines (common-essential)
• MANE Select transcript: NM_001258315

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3155
Approved symbol	ECT2
Name	epithelial cell transforming 2
Location	3q26.31
Locus type	gene with protein product
Status	Approved
Aliases	ARHGEF31
Ensembl gene	ENSG00000114346
Ensembl biotype	protein_coding
OMIM	600586
Entrez	1894

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 25 protein_coding, 3 retained_intron

ENST00000232458, ENST00000366090, ENST00000366254, ENST00000392692, ENST00000415665, ENST00000417960, ENST00000426894, ENST00000428567, ENST00000437296, ENST00000438041, ENST00000441497, ENST00000444250, ENST00000460860, ENST00000486027, ENST00000487073, ENST00000540509, ENST00000894233, ENST00000894234, ENST00000894235, ENST00000894236, ENST00000921495, ENST00000921496, ENST00000921497, ENST00000921498, ENST00000921499, ENST00000921500, ENST00000921501, ENST00000921502

RefSeq mRNA: 14 — MANE Select: NM_001258315 NM_001258315, NM_001258316, NM_001349094, NM_001349095, NM_001349096, NM_001349097, NM_001349098, NM_001349099, NM_001349100, NM_001349101, NM_001349102, NM_001349103, NM_001349104, NM_018098

CCDS: CCDS3220, CCDS58860, CCDS87168

Canonical transcript exons

ENST00000392692 — 25 exons

Exon	Start	End
ENSE00000780531	172761610	172761683
ENSE00000780534	172762910	172762972
ENSE00000826251	172762691	172762806
ENSE00000826252	172760156	172760263
ENSE00000826253	172758980	172759069
ENSE00000826254	172756983	172757165
ENSE00000826255	172755295	172755374
ENSE00001151860	172807770	172807924
ENSE00001151868	172805731	172805869
ENSE00001151881	172802616	172802694
ENSE00001151885	172786493	172786574
ENSE00001151890	172784707	172784803
ENSE00001151894	172783799	172783909
ENSE00001151898	172782163	172782231
ENSE00001151904	172773903	172774022
ENSE00001151911	172769007	172769143
ENSE00001151919	172764278	172764500
ENSE00001151940	172762416	172762546
ENSE00001203440	172754509	172754660
ENSE00001512806	172755483	172755575
ENSE00001650515	172820148	172821474
ENSE00001777018	172750726	172750857
ENSE00003669960	172816691	172816837
ENSE00003672259	172815604	172815711
ENSE00003686694	172802861	172802980

Expression profiles

Bgee: expression breadth ubiquitous, 248 present calls, max score 98.50.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 28.7465 / max 1085.8300, expressed in 1749 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
39846	25.5197	1700
39847	1.8483	1055
39845	1.1990	668
203030	0.1795	60

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	98.50	gold quality
oocyte	CL:0000023	97.97	gold quality
ventricular zone	UBERON:0003053	97.31	gold quality
ganglionic eminence	UBERON:0004023	93.68	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	92.75	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.62	gold quality
embryo	UBERON:0000922	90.73	gold quality
rectum	UBERON:0001052	87.46	gold quality
colonic epithelium	UBERON:0000397	86.18	gold quality
esophagus squamous epithelium	UBERON:0006920	85.68	gold quality
sperm	CL:0000019	84.36	gold quality
stromal cell of endometrium	CL:0002255	83.85	gold quality
adrenal tissue	UBERON:0018303	83.77	gold quality
mucosa of transverse colon	UBERON:0004991	82.51	gold quality
endometrium	UBERON:0001295	81.80	gold quality
mucosa of sigmoid colon	UBERON:0004993	81.51	gold quality
male germ cell	CL:0000015	81.46	gold quality
epithelium of nasopharynx	UBERON:0001951	81.21	gold quality
esophagus mucosa	UBERON:0002469	80.97	gold quality
bone marrow	UBERON:0002371	80.83	gold quality
islet of Langerhans	UBERON:0000006	80.76	gold quality
epithelium of esophagus	UBERON:0001976	80.64	gold quality
colonic mucosa	UBERON:0000317	80.46	gold quality
endothelial cell	CL:0000115	79.81	gold quality
testis	UBERON:0000473	79.59	gold quality
gingival epithelium	UBERON:0001949	79.47	gold quality
vermiform appendix	UBERON:0001154	79.30	gold quality
oral cavity	UBERON:0000167	79.03	gold quality
visceral pleura	UBERON:0002401	78.89	gold quality
trabecular bone tissue	UBERON:0002483	78.61	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CUX1, DMTF1, E2F1, TP53

miRNA regulators (miRDB)

96 targeting ECT2, 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-3163	100.00	77.23	8605
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-373-3P	99.84	70.68	1668
HSA-MIR-520E-3P	99.84	70.55	1698
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-372-3P	99.83	70.58	1691
HSA-MIR-520A-3P	99.83	70.59	1687

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 96.5% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• XRCC1, CLB6, and BRCT domains of ECT2 play a critical role in regulating cytokinesis (PMID:14587037)
• ECT2 regulates the polarity complex Par6/Par3/PKCzeta and possibly plays a role in epithelial cell polarity (PMID:15254234)
• BRCT domains negatively regulate Ect2 GEF activity in interphase cells, and they are also required for the proper function of Ect2 during cytokinesis (PMID:15545273)
• Ect2 regulates the activation and function of Cdc42 in mitosis. (PMID:15642749)
• Central spindle localization of ECT2 assists division plane positioning and the CYK-4 subunit of centralspindlin acts upstream of RhoA to promote furrow assembly. (PMID:16103226)
• Cdk1 inactivation is sufficient to activate a signaling pathway leading to cytokinesis, which emanates from mitotic spindles and is regulated by ECT2, MgcRacGAP, and RhoA (PMID:16118207)
• MgcRacGAP controls the initiation of cytokinesis by regulating ECT2, which in turn induces the assembly of the contractile ring and triggers the ingression of the cleavage furrow (PMID:16129829)
• a conformational change of ECT2 upon phosphorylation at T341. Therefore, ECT2 activity might be regulated by the phosphorylation status of T341. (PMID:16170345)
• ECT2 is regulated by Plk1 and CDK1, phosphorylation of ECT2 leads to accumulation of RHOA (PMID:16247472)
• Data show that RhoA accumulates at the equatorial cortex before furrow initiation and continues to concentrate at the cleavage furrow during cytokinesis, and that centralspindlin and ECT2 are required for this localization and furrowing. (PMID:16352658)
• ECT2 knockdown triggers cell cycle arrest in G1. (PMID:16778203)
• In mitotic cells Ect2 localizes to the central spindle and to the cell cortex. (PMID:16803869)
• Aberrant ECT2 expression, observed in various human tumors, could be the direct result of RB/E2F pathway deficiency, thereby contributing to cell division in cancers. (PMID:16862181)
• Late mitotic Plk1 activity promotes recruitment of Ect2 to the central spindle, triggering the initiation of cytokinesis and contributing to cleavage plane specification in human cells. (PMID:17488623)
• This gene was silenced. (PMID:17688947)
• These results suggest that equatorial Ect2 locally suppresses lamellipodia formation via RhoA activation, which indirectly contributes to restricting lamellipodia formation to polar regions during cytokinesis B. (PMID:17942602)
• Study demonstrates that FIP3 and ECT2 form mutually exclusive complexes with Cyk-4 and that dissociation of ECT2 from the mid-body at late telophase may be required for the recruitment of FIP3 and recycling endosomes to the cleavage furrow. (PMID:18511905)
• results suggest that co-regulation of Rho activity by p190RhoGAP and ECT2 in the cleavage furrow determines whether cells properly complete cytokinesis (PMID:18642445)
• Report correlation between ECT2 gene expression and methylation change of ECT2 promoter region in pancreatic cancer. (PMID:18842503)
• Data show that Trio, Ect2, and Vav3 are expressed at higher levels in glioblastoma versus low-grade glioma, and are involved in tumor cell migration and invasion. (PMID:19008376)
• study reports that mitotic complex genes Ect2, RacGAP, and MKLP1 are coordinately induced in S phase in proliferating T lymphocytes as well as in epithelial cells, depending upon activity of the CUX1 and E2F1 transcription factors (PMID:19015243)
• Immunohistochemical staining showed that a high level of ECT2 expression was associated with poor prognosis for patients with NSCLC (P = 0.0004) as well as ESCC (P = 0.0088). (PMID:19118053)
• Data showed how Plk1 promotes the central spindle recruitment of Ect2. Plk1 phosphorylates the noncatalytic N terminus of the RhoGAP HsCyk-4 at the central spindle, creating a phospho-epitope recognized by the BRCA1 C-terminal (BRCT) repeats of Ect2. (PMID:19468300)
• Data found that Plk1 binds and directly phosphorylates the HsCYK-4 at the midzone and this modification creates a major docking site for the tandem BRCT repeats of the Rho GTP exchange factor Ect2. (PMID:19468302)
• Ect2 and PKCiota are genetically and functionally linked in NSCLC, acting to coordinately drive tumor cell proliferation and invasion through formation of an oncogenic PKCiota-Par6alpha-Ect2 complex. (PMID:19617897)
• Results suggest that ECT2 is an indicator of cellular proliferation in OSCCs and that ECT2 might be a potential therapeutic target for the development of new treatments for OSCCs. (PMID:21124766)
• a model in which PKCiota-mediated phosphorylation regulates Ect2 binding to the oncogenic PKCiota-Par6 complex thereby activating Rac1 activity and driving transformed growth and invasion. (PMID:21189248)
• A mechanism involving the nuclear GEFs Ect2 and Net1 for activating RhoB after genotoxic stress, thereby facilitating cell death after treatment with DNA damaging agents. (PMID:21373644)
• Ect2 was a possible regulator of matrix-contact-side localization of invadopodia-related proteins. (PMID:21474972)
• identify Ect2 as a cell cycle-regulated protein and suggest that its ubiquitination-dependent degradation may play an important role in RhoA regulation at the time of mitosis. (PMID:21886810)
• targeting of Ect2 to the equatorial membrane represents a key step in the delivery of the cytokinetic signal to the cortex (PMID:22172673)
• Data supports an analogous function for the anillin-Ect2 complex in human cells and one hypothesis is that this complex has functionally replaced the Drosophila anillin-RacGAP50C complex. (PMID:22514687)
• ECT2 is important for tight junction function and maintenance of cell polarity. Nonfunction of this gene may cause renal tubulointerstitial injury, progressing to glomerular sclerosis. (PMID:22552385)
• RASAL2 was identified as an ECT2-interacting protein that regulates RHO activity in astrocytoma cells. (PMID:22683310)
• find that Ect2 first becomes active in prophase, when it is exported from the nucleus into the cytoplasm, activating RhoA to induce the formation of a mechanically stiff and rounded metaphase cortex (PMID:22898780)
• miR-223 functions as a tumor suppresser in osteosarcoma and miR-223/Ect2/p21 signaling is an important pathway that regulates the osteosarcoma cell cycle progression and proliferaion (PMID:23601845)
• Data suggest that ECT2 may play an oncogenic role in the pancreatic ductal adenocarcinoma (PDAC) neoplastic process. (PMID:23851435)
• Both Pbl and ECT2 repress Wg/Wnt target gene expression in cultured Drosophila and human cells. (PMID:24198276)
• Abnormality of the ECT2 gene occurs at a relatively early stage of lung adenocarcinogenesis and would be applicable as a new biomarker for prognostication of patients with lung adenocarcinoma (PMID:24484057)
• the deregulation of miR-223 and its target gene ECT2 may be associated with the aggressive tumor progression of human osteosarcoma (PMID:24784921)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ect2	ENSDARG00000007278
mus_musculus	Ect2	ENSMUSG00000027699
rattus_norvegicus	Ect2	ENSRNOG00000024365
drosophila_melanogaster	pbl	FBGN0003041
caenorhabditis_elegans		WBGENE00002297

Protein

Protein identifiers

Protein ECT2 — Q9H8V3 (reviewed: Q9H8V3)

Alternative names: Epithelial cell-transforming sequence 2 oncogene

All UniProt accessions (9): C9J0L6, C9J1C4, C9JB41, C9JDB4, C9JDV9, C9JTI2, Q9H8V3, H7C103, H7C3G1

UniProt curated annotations — full annotation on UniProt →

Function. Guanine nucleotide exchange factor (GEF) that catalyzes the exchange of GDP for GTP. Promotes guanine nucleotide exchange on the Rho family members of small GTPases, like RHOA, RHOC, RAC1 and CDC42. Required for signal transduction pathways involved in the regulation of cytokinesis. Component of the centralspindlin complex that serves as a microtubule-dependent and Rho-mediated signaling required for the myosin contractile ring formation during the cell cycle cytokinesis. Regulates the translocation of RHOA from the central spindle to the equatorial region. Plays a role in the control of mitotic spindle assembly; regulates the activation of CDC42 in metaphase for the process of spindle fibers attachment to kinetochores before chromosome congression. Involved in the regulation of epithelial cell polarity; participates in the formation of epithelial tight junctions in a polarity complex PARD3-PARD6-protein kinase PRKCQ-dependent manner. Plays a role in the regulation of neurite outgrowth. Inhibits phenobarbital (PB)-induced NR1I3 nuclear translocation. Stimulates the activity of RAC1 through its association with the oncogenic PARD6A-PRKCI complex in cancer cells, thereby acting to coordinately drive tumor cell proliferation and invasion. Also stimulates genotoxic stress-induced RHOB activity in breast cancer cells leading to their cell death.

Subunit / interactions. Homodimer. Homooligomer. Found in the centralspindlin complex. Interacts with NR1I3. Interacts (Thr-359 phosphorylated form) with PARD6A; the interaction is observed in cancer cells. Interacts (Thr-359 phosphorylated form) with PRKCI; the interaction is observed in cancer cells. Interacts with PKP4; the interaction is observed at the midbody. Interacts with RACGAP1/CYK4; the interaction is direct, occurs in a microtubule-dependent manner, occurs at anaphase and during cytokinesis, is inhibited in metaphase by phosphorylation of ECT2 on Thr-373 and is stimulated in early anaphase by dephosphorylation of ECT2 probably on Thr-373 through CDK1 activity. Interacts with PLK1; the interaction is stimulated upon its phosphorylation on Thr-444. Interacts with RHOA; the interaction results in allosteric activation of ECT2. Interacts with KIF23, PARD3, PARD6B and PRKCQ. Interacts with NEDD9/HEF1.

Subcellular location. Nucleus. Cytoplasm. Cytoskeleton. Spindle. Cleavage furrow. Midbody. Cell junction. Tight junction. Microtubule organizing center. Centrosome.

Tissue specificity. Expressed in lung epithelial cells (at protein level). Expressed in squamous cell carcinoma, primary non-small cell lung cancer tumors and lung adenocarcinoma.

Post-translational modifications. Phosphorylated by PLK1 in vitro. Hyperphosphorylated during the G2 phase of the cell cycle. Phosphorylation at Thr-373 occurs during the G2/M phase, relieves its auto-inhibition status and stimulates its GEF activity. Phosphorylation at Thr-444 in G2/M phase is required for subsequent binding with PLK1 and Rho exchange activation. Dephosphorylated at the time of cytokinesis. Phosphorylation at Thr-359 is required for its transformation activity in cancer cells.

Activity regulation. Autoinhibited by the C-terminal PH domain which folds back and binds to the surface of the DH domain, blocking binding of RHOA to the catalytic center of the DH domain. The 2nd BRCT domain is also involved in inhibition, probably by helping to impede RHOA binding. Allosterically activated by binding of activated GTP-bound RHOA to the PH domain which stimulates the release of PH inhibition and promotes the binding of substrate RHOA to the catalytic center. Binding of phosphorylated RACGAP1 to the N-terminal BRCT domain-containing region also releases autoinhibition.

Domain organisation. The BRCT domains 1 and 2 are required for intramolecular interaction, but not for intermolecular oligomerization. The BRCT domains negatively inhibit its GEF activity in interphase cells. The same BRCT domains may act as a positive regulatory motif for the completion of cytokinesis after the breakdown of nuclear membrane during mitosis.

Induction. Up-regulated by calcium in cells forming cell-cell contact sites. Up-regulated by DNA damaging agents like H(2)O(2) or ionizing radiation (IR).

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9H8V3-1	1	yes
Q9H8V3-2	2
Q9H8V3-3	3
Q9H8V3-4	4

RefSeq proteins (14): NP_001245244, NP_001245245, NP_001336023, NP_001336024, NP_001336025, NP_001336026, NP_001336027, NP_001336028, NP_001336029, NP_001336030, NP_001336031, NP_001336032, NP_001336033, NP_060568 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000219	DH_dom	Domain
IPR001331	GDS_CDC24_CS	Conserved_site
IPR001357	BRCT_dom	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR026817	Ect2	Family
IPR035899	DBL_dom_sf	Homologous_superfamily
IPR036420	BRCT_dom_sf	Homologous_superfamily
IPR049395	ECT2_PH	Domain
IPR049396	ECT2_BRCT0	Domain

Pfam: PF00533, PF00621, PF12738, PF21242, PF21243

UniProt features (106 total): helix 28, mutagenesis site 23, strand 18, modified residue 12, turn 4, domain 4, splice variant 3, sequence conflict 3, compositionally biased region 2, sequence variant 2, region of interest 2, short sequence motif 2, initiator methionine 1, chain 1, cross-link 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
3L46	X-RAY DIFFRACTION	1.48
6L30	X-RAY DIFFRACTION	2.8
4N40	X-RAY DIFFRACTION	3.11

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H8V3-F1	71.17	0.27

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 (13): 2, 359, 367, 370, 373, 376, 444, 716, 842, 846, 861, 866, 611

Mutagenesis-validated functional residues (23):

Position	Phenotype
184	inhibits interaction with racgap1. abolishes targeting to the central spindle.
226	inhibits interaction with racgap1. abolishes targeting to the central spindle.
336	inhibits homodimerization. increases binding with rhoa and gef activity.
338	2-fold increase in gef activity.
359	inhibits its phosphorylation and anchorage-independent growth and invasion in cancer cells. does not inhibit its gef act
373	does not inhibit its rho exchange activity. increases interaction with racgap1. does not inhibit anchorage-independent g
373	does not inhibit subcellular localization or homodimerization. enhances its rho exchange activity.
379–381	shows both nuclear and cytoplasmic localization and activates its transforming activity.
402–404	shows both nuclear and cytoplasmic localization and activates its transforming activity.
444	diminishes its phosphorylation status. reduces its interaction with plk1 and rho exchange activity. does not change its
444	does not reduce its interaction with plk1, change its subcellular localization and rho exchange activity.
488	partially releases inhibition.
570	2-fold increase in gef activity.
573	2-fold increase in gef activity.
586	complete loss of gef activity and failure to support cytokinesis.
596–599	inhibits activation of the transforming activity.
601	complete loss of gef activity and failure to support cytokinesis.
652	no effect on gef activity but severely decreases ect2 activation by rhoa. localizes correctly but fails to rescue the cy
656	no effect on gef activity but severely decreases ect2 activation by rhoa. fails to rescue the cytokinesis defect caused
670	marked increase in gef activity and rescues the cytokinesis defect caused by depletion of endogenous ect2. when expresse
734	more than 10-fold increase in gef activity. overexpression causes noticeable changes in interphase cell morphology such
796	more than 10-fold increase in gef activity. overexpression causes noticeable changes in interphase cell morphology such
846	diminishes its phosphorylation status.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-193648	NRAGE signals death through JNK
R-HSA-416482	G alpha (12/13) signalling events
R-HSA-8980692	RHOA GTPase cycle
R-HSA-9013026	RHOB GTPase cycle
R-HSA-9013148	CDC42 GTPase cycle
R-HSA-9013149	RAC1 GTPase cycle

MSigDB gene sets: 437 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GOBP_MITOTIC_CYTOKINESIS, RRAGTTGT_UNKNOWN, GOBP_ATTACHMENT_OF_SPINDLE_MICROTUBULES_TO_KINETOCHORE, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_RESPONSE_TO_IONIZING_RADIATION, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, SEMBA_FHIT_TARGETS_DN, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, PAL_PRMT5_TARGETS_UP, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_CHROMOSOME_LOCALIZATION, GOBP_POSITIVE_REGULATION_OF_NEURON_DIFFERENTIATION, GOBP_ACTIVATION_OF_GTPASE_ACTIVITY

GO Biological Process (25): mitotic cytokinesis (GO:0000281), cell morphogenesis (GO:0000902), nervous system development (GO:0007399), protein transport (GO:0015031), cell differentiation (GO:0030154), activation of protein kinase activity (GO:0032147), positive regulation of cytokinesis (GO:0032467), intracellular signal transduction (GO:0035556), positive regulation of protein import into nucleus (GO:0042307), positive regulation of apoptotic process (GO:0043065), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), positive regulation of GTPase activity (GO:0043547), positive regulation of neuron differentiation (GO:0045666), regulation of protein kinase activity (GO:0045859), regulation of small GTPase mediated signal transduction (GO:0051056), protein homooligomerization (GO:0051260), regulation of attachment of spindle microtubules to kinetochore (GO:0051988), cellular response to hydrogen peroxide (GO:0070301), bicellular tight junction assembly (GO:0070830), cellular response to calcium ion (GO:0071277), cellular response to ionizing radiation (GO:0071479), activation of GTPase activity (GO:0090630), positive regulation of mitotic cytokinetic process (GO:1903438), regulation of cytokinesis, actomyosin contractile ring assembly (GO:2000431), cell division (GO:0051301)

GO Molecular Function (5): guanyl-nucleotide exchange factor activity (GO:0005085), GTPase activator activity (GO:0005096), small GTPase binding (GO:0031267), protein homodimerization activity (GO:0042803), protein binding (GO:0005515)

GO Cellular Component (16): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), centrosome (GO:0005813), cytosol (GO:0005829), cell-cell junction (GO:0005911), bicellular tight junction (GO:0005923), cell cortex (GO:0005938), nuclear body (GO:0016604), midbody (GO:0030496), cleavage furrow (GO:0032154), mitotic spindle (GO:0072686), centralspindlin complex (GO:0097149), spindle (GO:0005819), cytoskeleton (GO:0005856), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
RHO GTPase cycle	4
Cell death signalling via NRAGE, NRIF and NADE	1
GPCR downstream signalling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
intracellular membraneless organelle	3
intracellular anatomical structure	2
GTPase activity	2
GTPase regulator activity	2
cytoplasm	2
mitotic cell cycle	1
cytoskeleton-dependent cytokinesis	1
mitotic cell cycle process	1
anatomical structure morphogenesis	1
system development	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
cellular developmental process	1
positive regulation of protein kinase activity	1
cytokinesis	1
regulation of cytokinesis	1
positive regulation of cell division	1
positive regulation of cell cycle process	1
signal transduction	1
protein import into nucleus	1
regulation of protein import into nucleus	1
positive regulation of nucleocytoplasmic transport	1
positive regulation of intracellular protein transport	1
positive regulation of protein localization to nucleus	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
regulation of GTPase activity	1
positive regulation of hydrolase activity	1
neuron differentiation	1
positive regulation of cell differentiation	1
regulation of neuron differentiation	1
regulation of protein phosphorylation	1
protein kinase activity	1
regulation of kinase activity	1

Protein interactions and networks

STRING

3268 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ECT2	RACGAP1	Q9H0H5	999
ECT2	ANLN	Q9NQW6	987
ECT2	KIF23	Q02241	970
ECT2	RHOA	P06749	915
ECT2	PLK1	P53350	889
ECT2	CDK1	P06493	838
ECT2	PKP4	Q99569	830
ECT2	CDC42	P21181	817
ECT2	RABIF	P47224	809
ECT2	PRKCI	P41743	774
ECT2	CCNB1	P14635	768
ECT2	AURKB	Q96GD4	754
ECT2	PLK4	O00444	710
ECT2	KIF20A	O95235	690
ECT2	ARHGAP1	Q07960	687

IntAct

71 interactions, top by confidence:

A	B	Type	Score
ECT2	RACGAP1	psi-mi:“MI:0407”(direct interaction)	0.880
ECT2	RACGAP1	psi-mi:“MI:0915”(physical association)	0.880
RACGAP1	ECT2	psi-mi:“MI:0915”(physical association)	0.880
CDH1	CTNNA1	psi-mi:“MI:0914”(association)	0.800
CTNNA1	CDH1	psi-mi:“MI:0914”(association)	0.800
RACGAP1	PLK1	psi-mi:“MI:0914”(association)	0.710
PLK4	ECT2	psi-mi:“MI:0915”(physical association)	0.600
PLK4	ECT2	psi-mi:“MI:0217”(phosphorylation reaction)	0.600
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
ECT2	KIF23	psi-mi:“MI:0915”(physical association)	0.560
ECT2	KIF23	psi-mi:“MI:0914”(association)	0.560
PNMA2	CCDC85C	psi-mi:“MI:0914”(association)	0.530
FOXM1	PES1	psi-mi:“MI:0914”(association)	0.500
ECT2	CDH1	psi-mi:“MI:0915”(physical association)	0.500
ECT2	CDH1	psi-mi:“MI:0914”(association)	0.500
ECT2	CTNNA1	psi-mi:“MI:0915”(physical association)	0.500
ECT2	GRB2	psi-mi:“MI:0915”(physical association)	0.400
ECT2	NCK1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (978): ECT2 (Affinity Capture-Western), ECT2 (Biochemical Activity), ECT2 (Affinity Capture-MS), ECT2 (Affinity Capture-MS), ECT2 (Affinity Capture-MS), ECT2 (Affinity Capture-MS), ECT2 (Affinity Capture-MS), ECT2 (Affinity Capture-MS), ECT2 (Affinity Capture-MS), ECT2 (Affinity Capture-Western), ECT2 (Affinity Capture-MS), ECT2 (Affinity Capture-MS), ECT2 (Affinity Capture-MS), RPGRIP1L (Affinity Capture-MS), ECT2 (Affinity Capture-MS)

ESM2 similar proteins: A0A1D5P556, A0A3Q1LSX9, A2A5R2, A2APV2, B0DOB5, B2RQE8, D3ZYR1, D4A631, F1LVW7, F1M775, F4IUX6, G3X9K3, O08808, O46382, O60308, O60610, O75674, O95466, Q07139, Q0IHV1, Q0JRZ9, Q3UQN2, Q4S6U8, Q5MIZ7, Q5R807, Q5SP90, Q6DFT3, Q6IN85, Q6INN7, Q6NTV6, Q6NXC0, Q6P2K6, Q6ZPF4, Q7TSU1, Q7ZX60, Q801Q7, Q80U19, Q86T65, Q8BPM0, Q8IVF7

Diamond homologs: A2AWP8, E9PSK7, O15013, P34609, P52734, P98174, Q07139, Q1ZXH8, Q29RM4, Q58A65, Q5R5M3, Q8C033, Q9ESN9, Q9H8V3, Q9HCE6, Q9UPT6, A0A0G2JTR4, A6QNS3, Q12979, Q5SSL4, Q6ZQF0, Q800K6, Q92547, A1L390, A5D7D1, D3ZHA0, D3ZHV2, L7UZ85, O13728, O42287, O43707, O75369, O75689, O76329, O88387, O88990, P05094, P05095, P11277, P11533

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
CDK1	down-regulates	ECT2	phosphorylation
CDK1	up-regulates	ECT2	phosphorylation
PRKCI	up-regulates	ECT2	phosphorylation
CyclinB/CDK1	down-regulates	ECT2	phosphorylation
CyclinB/CDK1	up-regulates	ECT2	phosphorylation
ECT2	“up-regulates activity”	RHOA	“guanine nucleotide exchange factor”
PLK1	“up-regulates activity”	ECT2	phosphorylation
DMTF1	“down-regulates quantity by repression”	ECT2	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	92
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

4921 predictions. Top by Δscore:

Variant	Effect	Δscore
3:172754500:T:G	acceptor_gain	1.0000
3:172754507:A:AG	acceptor_gain	1.0000
3:172754507:AGCT:A	acceptor_gain	1.0000
3:172754508:G:GG	acceptor_gain	1.0000
3:172754508:GCT:G	acceptor_gain	1.0000
3:172754508:GCTG:G	acceptor_gain	1.0000
3:172754656:AGAAG:A	donor_loss	1.0000
3:172754657:GAAGG:G	donor_loss	1.0000
3:172754658:AAGGT:A	donor_loss	1.0000
3:172754659:AGGT:A	donor_loss	1.0000
3:172754660:GGTA:G	donor_loss	1.0000
3:172754661:G:T	donor_loss	1.0000
3:172754662:T:A	donor_loss	1.0000
3:172755285:A:AG	acceptor_gain	1.0000
3:172755286:T:G	acceptor_gain	1.0000
3:172755290:A:AG	acceptor_gain	1.0000
3:172755291:A:G	acceptor_gain	1.0000
3:172755293:A:AG	acceptor_gain	1.0000
3:172755294:G:GG	acceptor_gain	1.0000
3:172755294:GA:G	acceptor_gain	1.0000
3:172755294:GAA:G	acceptor_gain	1.0000
3:172755294:GAAGA:G	acceptor_gain	1.0000
3:172755372:AAGGT:A	donor_loss	1.0000
3:172755373:AGGTA:A	donor_loss	1.0000
3:172755375:G:GG	donor_gain	1.0000
3:172755375:GTA:G	donor_loss	1.0000
3:172755376:T:G	donor_loss	1.0000
3:172756966:A:AG	acceptor_gain	1.0000
3:172756967:A:G	acceptor_gain	1.0000
3:172756970:A:AG	acceptor_gain	1.0000

AlphaMissense

6045 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:172761649:T:A	W242R	1.000
3:172761649:T:C	W242R	1.000
3:172762910:T:A	W336R	1.000
3:172762910:T:C	W336R	1.000
3:172769094:T:C	L460P	1.000
3:172784753:T:C	L592P	1.000
3:172784765:C:A	P596Q	1.000
3:172784772:G:C	Q598H	1.000
3:172784772:G:T	Q598H	1.000
3:172784774:G:C	R599T	1.000
3:172784774:G:T	R599M	1.000
3:172784775:G:C	R599S	1.000
3:172784775:G:T	R599S	1.000
3:172784792:T:C	L605S	1.000
3:172784795:T:C	L606P	1.000
3:172802662:T:C	F652L	1.000
3:172802664:T:A	F652L	1.000
3:172802664:T:G	F652L	1.000
3:172802883:G:C	R670P	1.000
3:172802970:A:T	D699V	1.000
3:172802976:T:C	L701P	1.000
3:172761614:C:A	A230D	0.999
3:172762796:T:A	V332D	0.999
3:172762914:T:C	F337S	0.999
3:172762916:T:A	W338R	0.999
3:172762916:T:C	W338R	0.999
3:172762922:A:C	S340R	0.999
3:172762924:C:A	S340R	0.999
3:172762924:C:G	S340R	0.999
3:172769073:G:T	R453M	0.999

dbSNP variants (sampled 300 via entrez): RS1000025914 (3:172754149 G>A,T), RS1000027206 (3:172777976 T>C), RS1000053279 (3:172829297 T>C,G), RS1000062501 (3:172794778 G>A), RS1000111085 (3:172812134 C>T), RS1000248980 (3:172802229 C>T), RS1000316028 (3:172816261 G>A,C,T), RS1000342012 (3:172763564 C>T), RS1000374761 (3:172763853 A>G), RS1000403280 (3:172759336 G>A,T), RS1000412511 (3:172765800 C>G,T), RS1000460684 (3:172809259 T>C), RS1000495891 (3:172784883 T>C,G), RS1000501138 (3:172802514 T>C), RS1000516851 (3:172795128 T>A)

Disease associations

OMIM: gene MIM:600586 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): breast ductal adenocarcinoma (MONDO:0005590)

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001762_664	Obesity-related traits	8.000000e-06
GCST90002404_67	Red cell distribution width	6.000000e-11

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0009188	Red cell distribution width

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
Tetrachlorodibenzodioxin	affects expression, decreases expression	3
Cyclosporine	increases expression, decreases expression	3
bisphenol A	decreases expression, increases expression	2
trichostatin A	affects cotreatment, decreases expression	2
cobaltous chloride	decreases expression	2
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	2
perfluorooctane sulfonic acid	decreases expression	2
Acetaminophen	decreases expression, increases expression	2
Acrolein	increases abundance, affects cotreatment, increases expression	2
Cisplatin	decreases expression, increases reaction, affects cotreatment	2
Doxorubicin	increases cleavage, decreases expression, decreases reaction	2
Ozone	increases expression, increases abundance, affects cotreatment	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
testosterone enanthate	affects expression	1
methylmercuric chloride	decreases expression	1
alpha-pinene	increases expression, increases abundance, affects cotreatment	1
deoxynivalenol	increases expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, decreases reaction	1
perfluorooctanoic acid	decreases expression	1
ochratoxin A	decreases acetylation, decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT00637364	PHASE1/PHASE2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	PHASE1/PHASE2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974	Not specified	ACTIVE_NOT_RECRUITING	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery