ECT2
entrez
1894
canonical
uniprot
Q9H8V3
canonical
ensembl
ENSG00000114346
resolver
ensp
ENSP00000232458
resolver
ensp
ENSP00000376457
resolver
ensp
ENSP00000412259
resolver
ensp
ENSP00000415876
resolver
ensp
ENSP00000443160
resolver
ensp
ENSP00000564292
resolver
ensp
ENSP00000745011
resolver
genesymbol
ECT2
resolver
hgnc
HGNC:3155
resolver
uniprot
Q0MT80
resolver
uniprot
Q2M269
resolver
uniprot
Q6U836
resolver
uniprot
Q9NSV8
resolver
uniprot
Q9NVW9
resolver
uniprot_entry
ECT2_HUMAN
resolver
uniprot_sec
Q0MT80
resolver
uniprot_sec
Q2M269
resolver
uniprot_sec
Q6U836
resolver
uniprot_sec
Q9NSV8
resolver
uniprot_sec
Q9NVW9
resolver
activity_regulation
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). {ECO:0000269|PubMed:25068414, ECO:0000269|PubMed:31888991}.
uniprot
proteins
amino_acid_sequence
MAENSVLTSTTGRTSLADSSIFDSKVTEISKENLLIGSTSYVEEEMPQIETRVILVQEAGKQEELIKALKTIKIMEVPVIKIKESCPGKSDEKLIKSVINMDIKVGFVKMESVEEFEGLDSPEFENVFVVTDFQDSVFNDLYKADCRVIGPPVVLNCSQKGEPLPFSCRPLYCTSMMNLVLCFTGFRKKEELVRLVTLVHHMGGVIRKDFNSKVTHLVANCTQGEKFRVAVSLGTPIMKPEWIYKAWERRNEQDFYAAVDDFRNEFKVPPFQDCILSFLGFSDEEKTNMEEMTEMQGGKYLPLGDERCTHLVVEENIVKDLPFEPSKKLYVVKQEWFWGSIQMDARAGETMYLYEKANTPELKKSVSMLSLNTPNSNRKRRRLKETLAQLSRETDVSPFPPRKRPSAEHSLSIGSLLDISNTPESSINYGDTPKSCTKSSKSSTPVPSKQSARWQVAKELYQTESNYVNILATIIQLFQVPLEEEGQRGGPILAPEEIKTIFGSIPDIFDVHTKIKDDLEDLIVNWDESKSIGDIFLKYSKDLVKTYPPFVNFFEMSKETIIKCEKQKPRFHAFLKINQAKPECGRQSLVELLIRPVQRLPSVALLLNDLKKHTADENPDKSTLEKAIGSLKEVMTHINEDKRKTEAQKQIFDVVYEVDGCPANLLSSHRSLVQRVETISLGEHPCDRGEQVTLFLFNDCLEIARKRHKVIGTFRSPHGQTRPPASLKHIHLMPLSQIKKVLDIRETEDCHNAFALLVRPPTEQANVLLSFQMTSDELPKENWLKMLCRHVANTICKADAENLIYTADPESFEVNTKDMDSTLSRASRAIKKTSKKVTRAFSFSKTPKRALRRALMTSHGSVEGRSPSSNDKHVMSRLSSTSSLAGIPSPSLVSLPSFFERRSHTLSRSTTHLI
uniprot
proteins
function
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. {ECO:0000269|PubMed:10579713, ECO:0000269|PubMed:14645260, ECO:0000269|PubMed:15254234, ECO:0000269|PubMed:15545273, ECO:0000269|PubMed:15642749, ECO:0000269|PubMed:16103226, ECO:0000269|PubMed:16170345, ECO:0000269|PubMed:16236794, ECO:0000269|PubMed:16495035, ECO:0000269|PubMed:19129481, ECO:0000269|PubMed:19468300, ECO:0000269|PubMed:19617897, ECO:0000269|PubMed:21189248, ECO:0000269|PubMed:21373644, ECO:0000269|PubMed:25068414, ECO:0000269|PubMed:31888991}.
uniprot
proteins
mass_dalton
103505
uniprot
proteins
mutagenesis
MUTAGEN 184; /note="T->A: Inhibits interaction with RACGAP1. Abolishes targeting to the central spindle."; /evidence="ECO:0000269|PubMed:19468300, ECO:0000269|PubMed:25068414"; MUTAGEN 226; /note="K->A: Inhibits interaction with RACGAP1. Abolishes targeting to the central spindle."; /evidence="ECO:0000269|PubMed:19468300, ECO:0000269|PubMed:25068414"; MUTAGEN 336; /note="W->R: Inhibits homodimerization. Increases binding with RhoA and GEF activity."; /evidence="ECO:0000269|PubMed:15545273"; MUTAGEN 338; /note="W->A: 2-fold increase in GEF activity."; /evidence="ECO:0000269|PubMed:31888991"; MUTAGEN 359; /note="T->A: Inhibits its phosphorylation and anchorage-independent growth and invasion in cancer cells. Does not inhibit its GEF activity."; /evidence="ECO:0000269|PubMed:21189248"; MUTAGEN 373; /note="T->A: Does not inhibit its Rho exchange activity. Increases interaction with RACGAP1. Does not inhibit anchorage-independent growth and invasion in cancer cells."; /evidence="ECO:0000269|PubMed:16103226, ECO:0000269|PubMed:16170345"; MUTAGEN 373; /note="T->D: Does not inhibit subcellular localization or homodimerization. Enhances its Rho exchange activity."; /evidence="ECO:0000269|PubMed:16103226, ECO:0000269|PubMed:16170345"; MUTAGEN 379..381; /note="KRR->AAA: Shows both nuclear and cytoplasmic localization and activates its transforming activity."; /evidence="ECO:0000269|PubMed:14645260"; MUTAGEN 402..404; /note="RKR->AKA: Shows both nuclear and cytoplasmic localization and activates its transforming activity."; /evidence="ECO:0000269|PubMed:14645260"; MUTAGEN 444; /note="T->A: Diminishes its phosphorylation status. Reduces its interaction with PLK1 and Rho exchange activity. Does not change its subcellular localization. Does not inhibit anchorage-independent growth and invasion in cancer cells."; /evidence="ECO:0000269|PubMed:16247472"; MUTAGEN 444; /note="T->D: Does not reduce its interaction with PLK1, change its subcellular localization and Rho exchange activity."; /evidence="ECO:0000269|PubMed:16247472"; MUTAGEN 488; /note="R->C: Partially releases inhibition."; /evidence="ECO:0000269|PubMed:31888991"; MUTAGEN 570; /note="R->D: 2-fold increase in GEF activity."; /evidence="ECO:0000269|PubMed:31888991"; MUTAGEN 573; /note="A->D: 2-fold increase in GEF activity."; /evidence="ECO:0000269|PubMed:31888991"; MUTAGEN 586; /note="R->Q: Complete loss of GEF activity and failure to support cytokinesis."; /evidence="ECO:0000269|PubMed:31888991"; MUTAGEN 596..599; /note="PVQR->AAAA: Inhibits activation of the transforming activity."; /evidence="ECO:0000269|PubMed:14645260"; MUTAGEN 601; /note="P->S: Complete loss of GEF activity and failure to support cytokinesis."; /evidence="ECO:0000269|PubMed:31888991"; MUTAGEN 652; /note="F->A: No effect on GEF activity but severely decreases ECT2 activation by RHOA. Localizes correctly but fails to rescue the cytokinesis defect caused by knockdown of endogenous ECT2 in contrast to the wild-type protein which rescues this defect."; /evidence="ECO:0000269|PubMed:31888991"; MUTAGEN 656; /note="Y->A: No effect on GEF activity but severely decreases ECT2 activation by RHOA. Fails to rescue the cytokinesis defect caused by knockdown of endogenous ECT2 in contrast to the wild-type protein which rescues this defect."; /evidence="ECO:0000269|PubMed:31888991"; MUTAGEN 670; /note="R->Q: Marked increase in GEF activity and rescues the cytokinesis defect caused by depletion of endogenous ECT2. When expressed in a cancer cell line, causes faster cell proliferation than the wild-type protein."; /evidence="ECO:0000269|PubMed:31888991"; MUTAGEN 734; /note="P->D: More than 10-fold increase in GEF activity. Overexpression causes noticeable changes in interphase cell morphology such as cell rounding and formation of stress fibers, suggesting ectopic RhoA activation."; /evidence="ECO:0000269|PubMed:31888991"; MUTAGEN 796; /note="C->K: More than 10-fold increase in GEF activity. Overexpression causes noticeable changes in interphase cell morphology such as cell rounding and formation of stress fibers, suggesting ectopic RHOA activation."; /evidence="ECO:0000269|PubMed:31888991"; MUTAGEN 846; /note="T->A: Diminishes its phosphorylation status."; /evidence="ECO:0000269|PubMed:16247472
uniprot
proteins
post_translational_modification
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. {ECO:0000269|PubMed:10579713, ECO:0000269|PubMed:16170345, ECO:0000269|PubMed:16247472, ECO:0000269|PubMed:21189248}.
uniprot
proteins
pubmed
10579713
uniprot
proteins
pubmed
14587037
uniprot
proteins
pubmed
14645260
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15254234
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15545273
uniprot
proteins
pubmed
15642749
uniprot
proteins
pubmed
16103226
uniprot
proteins
pubmed
16129829
uniprot
proteins
pubmed
16170345
uniprot
proteins
pubmed
16236794
uniprot
proteins
pubmed
16247472
uniprot
proteins
pubmed
16394104
uniprot
proteins
pubmed
16495035
uniprot
proteins
pubmed
16641997
uniprot
proteins
pubmed
16959974
uniprot
proteins
pubmed
17115030
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
18220336
uniprot
proteins
pubmed
18511905
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
19129481
uniprot
proteins
pubmed
19468300
uniprot
proteins
pubmed
19468302
uniprot
proteins
pubmed
19617897
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
21189248
uniprot
proteins
pubmed
21373644
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
22814378
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
25068414
uniprot
proteins
pubmed
28112733
uniprot
proteins
pubmed
31888991
uniprot
proteins
sequence_length
914
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10579713, ECO:0000269|PubMed:14645260, ECO:0000269|PubMed:15254234, ECO:0000269|PubMed:16103226, ECO:0000269|PubMed:16495035, ECO:0000269|PubMed:19617897}. Cytoplasm {ECO:0000269|PubMed:10579713, ECO:0000269|PubMed:16236794, ECO:0000269|PubMed:16394104}. Cytoplasm, cytoskeleton, spindle {ECO:0000269|PubMed:10579713, ECO:0000269|PubMed:16103226, ECO:0000269|PubMed:16236794, ECO:0000269|PubMed:17115030, ECO:0000269|PubMed:19468300}. Cleavage furrow {ECO:0000269|PubMed:10579713}. Midbody {ECO:0000269|PubMed:15254234, ECO:0000269|PubMed:16394104, ECO:0000269|PubMed:17115030}. Cell junction {ECO:0000269|PubMed:15254234, ECO:0000269|PubMed:16495035}. Cell junction, tight junction {ECO:0000269|PubMed:15254234}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269|PubMed:17115030}. Note=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). {ECO:0000269|PubMed:10579713, ECO:0000269|PubMed:15254234}.
uniprot
proteins