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Details on Person UniProt:Q9H8V3 ECT2

Class:IdReferenceGeneProduct:195054
_chainChangeLoginitiator methionine:1 added on Sat February 7 2015;chain:2-914 added on Sat February 7 2015;initiator methionine:1 for 195054 removed on Fri Nov 03 2023;initiator methionine: for 195054 added on Fri Nov 03 2023;initiator methionine: for 195054 removed on Fri Aug 15 2025;initiator methionine:1 for 195054 added on Fri Aug 15 2025
_displayNameUniProt:Q9H8V3 ECT2
_timestamp2025-08-15 20:59:20
chaininitiator methionine:1
chain:2-914
checksumF40FC4F982FB8C78
commentFUNCTION 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.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 (PubMed:31888991). The 2nd BRCT domain is also involved in inhibition, probably by helping to impede RHOA binding (PubMed:31888991). 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 (PubMed:31888991). Binding of phosphorylated RACGAP1 to the N-terminal BRCT domain-containing region also releases autoinhibition (PubMed:25068414).SUBUNIT Homodimer (PubMed:14645260, PubMed:15545273, PubMed:16170345). Homooligomer (PubMed:15545273). Found in the centralspindlin complex (PubMed:16236794). Interacts with NR1I3 (By similarity). Interacts (Thr-359 phosphorylated form) with PARD6A; the interaction is observed in cancer cells (PubMed:15254234, PubMed:19617897). Interacts (Thr-359 phosphorylated form) with PRKCI; the interaction is observed in cancer cells (PubMed:19617897). Interacts with PKP4; the interaction is observed at the midbody (PubMed:22814378). 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 (PubMed:16103226, PubMed:16129829, PubMed:16236794, PubMed:19468300, PubMed:19468302, PubMed:25068414). Interacts with PLK1; the interaction is stimulated upon its phosphorylation on Thr-444 (PubMed:16247472). Interacts with RHOA; the interaction results in allosteric activation of ECT2 (PubMed:31888991). Interacts with KIF23, PARD3, PARD6B and PRKCQ (PubMed:15254234, PubMed:16236794). Interacts with NEDD9/HEF1 (PubMed:16394104).INTERACTION Sequestered within the nucleus during interphase (PubMed:10579713). Dispersed throughout the cytoplasm upon breakdown of the nuclear envelope during mitosis (PubMed:10579713). Colocalizes with the centralspindlin complex to the mitotic spindles during anaphase/metaphase, the cleavage furrow during telophase and at the midbody at the end of cytokinesis (PubMed:10579713). Colocalized with RhoA at the midbody (PubMed:10579713). Its subcellular localization to tight junction is increased by calcium (PubMed:15254234).ALTERNATIVE PRODUCTS Expressed in lung epithelial cells (at protein level). Expressed in squamous cell carcinoma, primary non-small cell lung cancer tumors and lung adenocarcinoma.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).DOMAIN The BRCT domains 1 and 2 are required for intramolecular interaction, but not for intermolecular oligomerization (PubMed:15545273). The BRCT domains negatively inhibit its GEF activity in interphase cells (PubMed:15545273, PubMed:31888991). The same BRCT domains may act as a positive regulatory motif for the completion of cytokinesis after the breakdown of nuclear membrane during mitosis (PubMed:15545273).PTM 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.MISCELLANEOUS May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.SEQUENCE CAUTION Truncated N-terminus.
created[InstanceEdit:195029] Gopinathrao, G, 2007-04-02 17:19:01
descriptionrecommendedName: Protein ECT2 alternativeName: Epithelial cell-transforming sequence 2 oncogene
geneNameECT2
identifierQ9H8V3
isSequenceChangedFALSE
keyword3D-structure
Acetylation
Alternative splicing
Cell cycle
Cell division
Cell junction
Cytoplasm
Cytoskeleton
Differentiation
Guanine-nucleotide releasing factor
Isopeptide bond
Neurogenesis
Nucleus
Oncogene
Phosphoprotein
Protein transport
Proteomics identification
Reference proteome
Repeat
Tight junction
Transport
Ubl conjugation
modified[InstanceEdit:9836292] Weiser, Joel, 2023-05-25
[InstanceEdit:9852000] Weiser, Joel, 2023-11-03
[InstanceEdit:9917590] Weiser, Joel, 2024-08-09
[InstanceEdit:9926675] Weiser, Joel, 2024-11-03
[InstanceEdit:9963647] Weiser, Joel, 2025-08-15
nameECT2
referenceDatabase[ReferenceDatabase:2] UniProt
referenceGene[ReferenceDNASequence:8998276] ENSEMBL:ENSG00000114346 ECT2 [Homo sapiens]
secondaryIdentifierECT2_HUMAN
Q0MT80
Q2M269
Q6U836
Q9NSV8
Q9NVW9
sequenceLength914
species[Species:48887] Homo sapiens
(isoformParent)[ReferenceIsoform:384939] UniProt:Q9H8V3-2 ECT2 [Homo sapiens]
[ReferenceIsoform:414333] UniProt:Q9H8V3-1 ECT2 [Homo sapiens]
[ReferenceIsoform:8974660] UniProt:Q9H8V3-3 ECT2 [Homo sapiens]
[ReferenceIsoform:8974661] UniProt:Q9H8V3-4 ECT2 [Homo sapiens]
(referenceEntity)[EntityWithAccessionedSequence:195036] ECT2 [cytosol] [Homo sapiens]
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