Descriptions
MCF2 protein is the prototype member of a large family of guanine nucleotide exchange factors (GEFs) that modulates the Rho family of GTPases. Removal of the N-terminal region results in a significant increase of MCF2 activity. Specifically, the autoinhibitory region binds to the PH domain, and limits the access of Rho GTPases to the catalytic DH domain and masks the intracellular targeting function of the PH domain.
Autoinhibitory domains (AIDs)
Target domain |
824-948 (PH domain) |
Relief mechanism |
Cleavage |
Assay |
|
Accessory elements
No accessory elements
Autoinhibited structure
Activated structure
5 structures for Q64096
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| 1KZ7 | X-ray | 240 A | A/C | 623-967 | PDB |
| 1KZG | X-ray | 260 A | A/C | 623-967 | PDB |
| 1LB1 | X-ray | 281 A | A/C/E/G | 623-967 | PDB |
| 1RJ2 | X-ray | 300 A | A/D/G/J | 623-968 | PDB |
| AF-Q64096-F1 | Predicted | AlphaFoldDB |
No variants for Q64096
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| No variants for Q64096 | |||||
No associated diseases with Q64096
9 regional properties for Q64096
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| domain | Dbl homology (DH) domain | 632 - 812 | IPR000219 |
| domain | CRAL-TRIO lipid binding domain | 52 - 224 | IPR001251 |
| conserved_site | Guanine-nucleotide dissociation stimulator, CDC24, conserved site | 761 - 786 | IPR001331 |
| domain | SH3 domain | 1055 - 1116 | IPR001452 |
| domain | Pleckstrin homology domain | 830 - 948 | IPR001849 |
| repeat | Spectrin repeat | 355 - 454 | IPR002017 |
| repeat | Spectrin/alpha-actinin | 352 - 554 | IPR018159 |
| domain | DBS, SH3 domain | 1059 - 1113 | IPR035532 |
| domain | DBS, PH domain | 817 - 948 | IPR035534 |
5 GO annotations of cellular component
| Name | Definition |
|---|---|
| cytoplasm | The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. |
| extrinsic component of membrane | The component of a membrane consisting of gene products and protein complexes that are loosely bound to one of its surfaces, but not integrated into the hydrophobic region. |
| lamellipodium | A thin sheetlike process extended by the leading edge of a migrating cell or extending cell process; contains a dense meshwork of actin filaments. |
| membrane | A lipid bilayer along with all the proteins and protein complexes embedded in it and attached to it. |
| plasma membrane | The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins. |
2 GO annotations of molecular function
| Name | Definition |
|---|---|
| 1-phosphatidylinositol binding | Binding to a phosphatidylinositol, a glycophospholipid with its sn-glycerol 3-phosphate residue is esterified to the 1-hydroxyl group of 1D-myo-inositol. |
| guanyl-nucleotide exchange factor activity | Stimulates the exchange of GDP to GTP on a signaling GTPase, changing its conformation to its active form. Guanine nucleotide exchange factors (GEFs) act by stimulating the release of guanosine diphosphate (GDP) to allow binding of guanosine triphosphate (GTP), which is more abundant in the cell under normal cellular physiological conditions. |
4 GO annotations of biological process
| Name | Definition |
|---|---|
| intracellular signal transduction | The process in which a signal is passed on to downstream components within the cell, which become activated themselves to further propagate the signal and finally trigger a change in the function or state of the cell. |
| positive regulation of Rho protein signal transduction | Any process that activates or increases the frequency, rate or extent of Rho protein signal transduction. |
| positive regulation of transcription by RNA polymerase II | Any process that activates or increases the frequency, rate or extent of transcription from an RNA polymerase II promoter. |
| Rho protein signal transduction | The series of molecular signals within the cell that are mediated by a member of the Rho family of proteins switching to a GTP-bound active state. |
12 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| O60229 | KALRN | Kalirin | Homo sapiens (Human) | SS |
| Q86YR7 | MCF2L2 | Probable guanine nucleotide exchange factor MCF2L2 | Homo sapiens (Human) | SS |
| O75962 | TRIO | Triple functional domain protein | Homo sapiens (Human) | EV |
| P10911 | MCF2 | Proto-oncogene DBL | Homo sapiens (Human) | EV |
| O15068 | MCF2L | Guanine nucleotide exchange factor DBS | Homo sapiens (Human) | SS |
| A2CG49 | Kalrn | Kalirin | Mus musculus (Mouse) | SS |
| Q0KL02 | Trio | Triple functional domain protein | Mus musculus (Mouse) | SS |
| Q9CWR0 | Arhgef25 | Rho guanine nucleotide exchange factor 25 | Mus musculus (Mouse) | SS |
| F1M0Z1 | Trio | Triple functional domain protein | Rattus norvegicus (Rat) | SS |
| P97924 | Kalrn | Kalirin | Rattus norvegicus (Rat) | SS |
| Q63406 | Mcf2l | Guanine nucleotide exchange factor DBS | Rattus norvegicus (Rat) | SS |
| Q1LUA6 | trio | Triple functional domain protein | Danio rerio (Zebrafish) (Brachydanio rerio) | SS |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MSDCWCFIFC | KEHVRSNPLS | PQHDGASREE | ADHQVDVSDG | IRLVPDKAEA | TAATASDEIM |
| 70 | 80 | 90 | 100 | 110 | 120 |
| HQDIVPLCAA | DIQEQLKKRF | AYLSGGRGQD | GSPVITFPDY | PAFSEIPDKE | FQNVMTYLTS |
| 130 | 140 | 150 | 160 | 170 | 180 |
| IPSLQDAGIG | FILVIDRRQD | KWTSVKASVL | RIAASFPANL | QLVLVLRPTG | FFQRTLSDIA |
| 190 | 200 | 210 | 220 | 230 | 240 |
| FKFNRDEFKM | KVPVMMLSSV | PELHGYIDKS | QLTEDLGGTL | DYCHSRWLCH | RTAIESFALM |
| 250 | 260 | 270 | 280 | 290 | 300 |
| VKQTAQMLQA | FGTELAETEL | PNDVQSTSLV | LSAHTEKKAK | VKEDLQLALK | EGNSILESLR |
| 310 | 320 | 330 | 340 | 350 | 360 |
| EPLAESAAHS | VNQDQLDNQA | TVQRLLAQLN | ETEAAFDEFW | AKHQQKLEQC | LQLRHFEQGF |
| 370 | 380 | 390 | 400 | 410 | 420 |
| REVKTTLDSM | SQKIAAFTDV | GNSLAHVQHL | LKDLTAFEEK | SSVAVDKARA | LSLEGQQLIE |
| 430 | 440 | 450 | 460 | 470 | 480 |
| NRHYAVDSIH | PKCEELQHLC | DHFASEVTRR | RGLLSKSLEL | HSLLETSMKW | SDEGIFLLAS |
| 490 | 500 | 510 | 520 | 530 | 540 |
| QPVDKCQSQD | GAEAALQEIE | KFLETGAENK | IQELNEIYKE | YECILNQDLL | EHVQKVFQKQ |
| 550 | 560 | 570 | 580 | 590 | 600 |
| ESTEEMFHRR | QASLKKLAAK | QTRPVQPVAP | RPEALTKSPS | PSPGSWRSSE | NSSSEGNALR |
| 610 | 620 | 630 | 640 | 650 | 660 |
| RGPYRRAKSE | MSEPRQGRTS | STGEEEESLA | ILRRHVMNEL | LDTERAYVEE | LLCVLEGYAA |
| 670 | 680 | 690 | 700 | 710 | 720 |
| EMDNPLMAHL | ISTGLQNKKN | ILFGNMEEIY | HFHNRNIPAG | LESCIDCPEL | VGRCFLERME |
| 730 | 740 | 750 | 760 | 770 | 780 |
| EFQIYEKYCQ | NKPRSESLWR | QCSDCPFFQE | CQKKLDHKLS | LDSYLLKPVQ | RITKYQLLLK |
| 790 | 800 | 810 | 820 | 830 | 840 |
| EMLKYSKHCE | GAEDLQEALS | SILGILKAVN | DSMHLIAITG | YDGNLGDLGK | LLMQGSFSVW |
| 850 | 860 | 870 | 880 | 890 | 900 |
| TDHKKGHTKV | KELARFKPMQ | RHLFLHEKAV | LFCKKREENG | EGYEKAPSYS | YKQSLNMTAV |
| 910 | 920 | 930 | 940 | 950 | 960 |
| GITENVKGDT | KKFEIWYNAR | EEVYIIQAPT | PEIKAAWVNE | IRKVLTSQLQ | ACREASQHRA |
| 970 | 980 | 990 | 1000 | 1010 | 1020 |
| LEQSHSLPLP | TPSSTSPTKG | NTRNVKKLED | RKTDPLSLEG | YVSSSLPKPP | EKGKGWSKTS |
| 1030 | 1040 | 1050 | 1060 | 1070 | 1080 |
| HSLEAPEEDG | GWSSAEELIN | SSDAEEDGGV | GPKKLVPGKY | TVVMDDEKGG | PDTLAMRSGD |
| 1090 | 1100 | 1110 | 1120 | 1130 | 1140 |
| MVEVVEEGAE | GLWYVRDLTS | SKEGWVPASS | LSTLLGKSSS | AQCLSSSGKI | HCARQLCPEP |
| AEILSPEPV |