O89032
SS
Gene name |
Sh3pxd2a (Fish, Sh3md1, Tks5) |
Protein name |
SH3 and PX domain-containing protein 2A |
Names |
Five SH3 domain-containing protein , SH3 multiple domains protein 1 , Tyrosine kinase substrate with five SH3 domains |
Species |
Mus musculus (Mouse) |
KEGG Pathway |
mmu:14218 |
EC number |
|
Protein Class |
|
Descriptions
The scaffold protein SH3 and PX domain-containing protein 2B (SH3PXD2B, also known as Tks4) is a member of the p47phox-related organizer superfamily and plays a key role in cell motility by affecting the formation of podosomes and invadopodia. In addition, Tks4 is involved in the epidermal growth factor (EGF) signaling pathway, in which EGF induces the translocation of Tks4 from the cytoplasm to the plasma membrane. Tks4 contains an N-terminal region: a phosphoinositide-binding PX domain is followed by two SH3 domains (tandem SH3) and a proline-rich region (PRR). The PRR is followed by a third and a fourth SH3 domain connected by a long (~420 residues) unstructured region. In the autoinhibited state, the tandem SH3 domain of Tks4 binds the PRR and thus the third SH3 domain interacts with the PX domain. The association of the PX domain and the third SH3 domain contributes to the formation of the autoinhibited conformation, and the PRR following the second SH3 domain folds back and associates with the tandem SH3, yielding a compact conformation.
Autoinhibitory domains (AIDs)
Target domain |
4-128 (PX domain) |
Relief mechanism |
PTM |
Assay |
|
Accessory elements
No accessory elements
Autoinhibited structure
Activated structure
1 structures for O89032
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-O89032-F1 | Predicted | AlphaFoldDB |
46 variants for O89032
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| rs3389545466 | 30 | V>A | No | EVA | |
| rs3389538450 | 56 | D>* | No | EVA | |
| rs3389545481 | 57 | K>M | No | EVA | |
| rs3389511508 | 65 | K>N | No | EVA | |
| rs3389538523 | 83 | R>I | No | EVA | |
| rs3409219760 | 86 | I>V | No | EVA | |
| rs36606779 | 128 | V>I | No | EVA | |
| rs3389539263 | 231 | D>A | No | EVA | |
| rs3389453503 | 237 | T>N | No | EVA | |
| rs3389538532 | 279 | S>N | No | EVA | |
| rs3389554687 | 279 | S>R | No | EVA | |
| rs213673055 | 286 | G>D | No | EVA | |
| rs3409135711 | 288 | E>* | No | EVA | |
| rs3389493223 | 303 | W>* | No | EVA | |
| rs3389493234 | 354 | K>R | No | EVA | |
| rs3389501416 | 358 | D>N | No | EVA | |
| rs3408259560 | 361 | A>T | No | EVA | |
| rs259068396 | 363 | A>S | No | EVA | |
| rs3389546210 | 487 | V>M | No | EVA | |
| rs3389560516 | 492 | K>* | No | EVA | |
| rs3389453508 | 492 | K>M | No | EVA | |
| rs3389538470 | 499 | S>* | No | EVA | |
| rs3389545491 | 563 | G>D | No | EVA | |
| rs3389544777 | 585 | P>H | No | EVA | |
| rs1132892594 | 586 | A>T | No | EVA | |
| rs39418594 | 599 | R>Q | No | EVA | |
| rs3389546203 | 618 | I>T | No | EVA | |
| rs3389557215 | 623 | G>D | No | EVA | |
| rs261293778 | 685 | S>A | No | EVA | |
| rs253918306 | 688 | S>A | No | EVA | |
| rs3389511471 | 764 | S>A | No | EVA | |
| rs39173268 | 803 | M>T | No | EVA | |
| rs3389511447 | 806 | E>D | No | EVA | |
| rs237433365 | 811 | G>C | No | EVA | |
| rs3389544696 | 815 | I>F | No | EVA | |
| rs225611615 | 820 | A>V | No | EVA | |
| rs3389557222 | 829 | K>R | No | EVA | |
| rs3389538513 | 863 | L>M | No | EVA | |
| rs864290588 | 934 | K>M | No | EVA | |
| rs3389511507 | 937 | T>S | No | EVA | |
| rs3389544791 | 939 | P>S | No | EVA | |
| rs3389560511 | 967 | A>D | No | EVA | |
| rs3389501446 | 979 | P>S | No | EVA | |
| rs3389554678 | 996 | A>P | No | EVA | |
| rs3389549393 | 1027 | A>T | No | EVA | |
| rs3389501468 | 1063 | N>Y | No | EVA |
No associated diseases with O89032
12 regional properties for O89032
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| domain | SH3 domain | 166 - 225 | IPR001452-1 |
| domain | SH3 domain | 266 - 325 | IPR001452-2 |
| domain | SH3 domain | 447 - 506 | IPR001452-3 |
| domain | SH3 domain | 833 - 892 | IPR001452-4 |
| domain | SH3 domain | 1063 - 1124 | IPR001452-5 |
| domain | Phox homology | 3 - 128 | IPR001683 |
| domain | SH3PXD2A, SH3 domain 3 | 450 - 503 | IPR035449 |
| domain | SH3PXD2A, SH3 domain 1 | 170 - 222 | IPR035450 |
| domain | SH3PXD2A, SH3 domain 2 | 269 - 322 | IPR035452 |
| domain | SH3PXD2A, SH3 domain 4 | 838 - 888 | IPR035453 |
| domain | SH3PXD2A, SH3 domain 5 | 1067 - 1123 | IPR035454 |
| domain | SH3PXD2, PX domain | 6 - 124 | IPR037961 |
4 GO annotations of cellular component
| Name | Definition |
|---|---|
| anchoring junction | A cell junction that mechanically attaches a cell (and its cytoskeleton) to neighboring cells or to the extracellular matrix. |
| cytoplasm | The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. |
| mating projection tip | The apex of the mating projection in unicellular fungi exposed to mating pheromone; site of polarized growth. |
| podosome | An actin-rich adhesion structure characterized by formation upon cell substrate contact and localization at the substrate-attached part of the cell, contain an F-actin-rich core surrounded by a ring structure containing proteins such as vinculin and talin, and have a diameter of 0.5 mm. |
9 GO annotations of molecular function
| Name | Definition |
|---|---|
| phosphatidylinositol binding | Binding to an inositol-containing glycerophospholipid, i.e. phosphatidylinositol (PtdIns) and its phosphorylated derivatives. |
| phosphatidylinositol-3,4-bisphosphate binding | Binding to phosphatidylinositol-3,4-bisphosphate, a derivative of phosphatidylinositol in which the inositol ring is phosphorylated at the 3' and 4' positions. |
| phosphatidylinositol-3-phosphate binding | Binding to phosphatidylinositol-3-phosphate, a derivative of phosphatidylinositol in which the inositol ring is phosphorylated at the 3' position. |
| phosphatidylinositol-4,5-bisphosphate binding | Binding to phosphatidylinositol-4,5-bisphosphate, a derivative of phosphatidylinositol in which the inositol ring is phosphorylated at the 4' and 5' positions. |
| phosphatidylinositol-4-phosphate binding | Binding to phosphatidylinositol-4-phosphate, a derivative of phosphatidylinositol in which the inositol ring is phosphorylated at the 4' position. |
| phosphatidylinositol-5-phosphate binding | Binding to phosphatidylinositol-5-phosphate, a derivative of phosphatidylinositol in which the inositol ring is phosphorylated at the 5' position. |
| protease binding | Binding to a protease or a peptidase. |
| protein-macromolecule adaptor activity | The binding activity of a protein that brings together two or more macromolecules in contact, permitting those molecules to function in a coordinated way. The adaptor can bring together two proteins, or a protein and another macromolecule such as a lipid or a nucleic acid. |
| superoxide-generating NADPH oxidase activator activity | Binds to and increases the activity of the enzyme superoxide-generating NADPH oxidase. |
4 GO annotations of biological process
| Name | Definition |
|---|---|
| in utero embryonic development | The process whose specific outcome is the progression of the embryo in the uterus over time, from formation of the zygote in the oviduct, to birth. An example of this process is found in Mus musculus. |
| osteoclast fusion | The plasma membrane fusion process that results in fusion of mononuclear osteoclasts to form a multinuclear osteoclast. |
| reactive oxygen species metabolic process | The chemical reactions and pathways involving a reactive oxygen species, any molecules or ions formed by the incomplete one-electron reduction of oxygen. They contribute to the microbicidal activity of phagocytes, regulation of signal transduction and gene expression, and the oxidative damage to biopolymers. |
| superoxide anion generation | The enzymatic generation of superoxide, the superoxide anion O2- (superoxide free radical), or any compound containing this species, by a cell in response to environmental stress, thereby mediating the activation of various stress-inducible signaling pathways. |
9 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| O00443 | PIK3C2A | Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit alpha | Homo sapiens (Human) | PR |
| A1X283 | SH3PXD2B | SH3 and PX domain-containing protein 2B | Homo sapiens (Human) | EV |
| Q5TCZ1 | SH3PXD2A | SH3 and PX domain-containing protein 2A | Homo sapiens (Human) | SS |
| P14598 | NCF1 | Neutrophil cytosol factor 1 | Homo sapiens (Human) | EV |
| Q61194 | Pik3c2a | Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit alpha | Mus musculus (Mouse) | PR |
| P97369 | Ncf4 | Neutrophil cytosol factor 4 | Mus musculus (Mouse) | PR |
| Q09014 | Ncf1 | Neutrophil cytosol factor 1 | Mus musculus (Mouse) | SS |
| A2AAY5 | Sh3pxd2b | SH3 and PX domain-containing protein 2B | Mus musculus (Mouse) | SS |
| F1M707 | Ncf1 | Neutrophil cytosolic factor 1 | Rattus norvegicus (Rat) | SS |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MLAYCVQDAT | VVDVEKRRSP | SKHYVYIINV | TWSDSTSQTI | YRRYSKFFDL | QMQLLDKFPI |
| 70 | 80 | 90 | 100 | 110 | 120 |
| EGGQKDPKQR | IIPFLPGKIL | FRRSHIRDVA | VKRLKPIDEY | CRALVRLPPH | ISQCDEVFRF |
| 130 | 140 | 150 | 160 | 170 | 180 |
| FEARPEDVNP | PKEDYGSSKR | KSVWLSSWAE | SPKKDVTGAD | TNAEPMILEQ | YVVVSNYKKQ |
| 190 | 200 | 210 | 220 | 230 | 240 |
| ENSELSLQAG | EVVDVIEKNE | SGWWFVSTSE | EQGWVPATYL | EAQNGTRDDS | DINTSKTGEV |
| 250 | 260 | 270 | 280 | 290 | 300 |
| SKRRKAHLRR | LDRRWTLGGM | VNRQHSREEK | YVTVQPYTSQ | SKDEIGFEKG | VTVEVIRKNL |
| 310 | 320 | 330 | 340 | 350 | 360 |
| EGWWYIRYLG | KEGWAPASYL | KKAKDDLPTR | KKNLAGPVEI | IGNIMEISNL | LNKKASGDKE |
| 370 | 380 | 390 | 400 | 410 | 420 |
| APAEGEGSEA | PITKKEISLP | ILCNASNGSA | LAIPERTTSK | LAQGSPAVAR | IAPQRAQISS |
| 430 | 440 | 450 | 460 | 470 | 480 |
| PNLRTRPPPR | RESSLGFQLP | KPPEPPSVEV | EYYTIAEFQS | CISDGISFRG | GQKAEVIDKN |
| 490 | 500 | 510 | 520 | 530 | 540 |
| SGGWWYVQIG | EKEGWAPASY | IDKRKKPNLS | RRTSTLTRPK | VPPPAPPSKP | KEAEENPVGA |
| 550 | 560 | 570 | 580 | 590 | 600 |
| CESQGSPLKV | KYEEPEYDVP | AFGFDSEPEM | NEEPSGDRGS | GDKHPAQPRR | ISPASSLQRA |
| 610 | 620 | 630 | 640 | 650 | 660 |
| HFKVGESSED | VALEEETIYE | NEGFRPYTED | TLSARGSSGD | SDSPGSSSLS | LAVKNSPKSD |
| 670 | 680 | 690 | 700 | 710 | 720 |
| SPKSSSLLKL | KAEKNAQAEL | GKNQSNISFS | SSVTISTTCS | SSSSSSSLSK | NNGDLKPRSA |
| 730 | 740 | 750 | 760 | 770 | 780 |
| SDAGIRDTPK | VGTKKDPDVK | AGLASCARAK | PSVRPKPVLN | RAESQSQEKM | DISSLRRQLR |
| 790 | 800 | 810 | 820 | 830 | 840 |
| PTGQLRGGLK | GSRSEDSELP | PQMASEGSRR | GSADIIPLTA | TTPPCVPKKE | WEGQGATYVT |
| 850 | 860 | 870 | 880 | 890 | 900 |
| CSAYQKVQDS | EISFPEGAEV | HVLEKAESGW | WYVRFGELEG | WAPSHYLVAE | ENQQPDTASK |
| 910 | 920 | 930 | 940 | 950 | 960 |
| EGDTGKSSQN | EGKSDSLEKI | EKRVQALNTV | NQSKRATPPI | PSKPPGGFGK | TSGTVAVKMR |
| 970 | 980 | 990 | 1000 | 1010 | 1020 |
| NGVRQVAVRP | QSVFVSPPPK | DNNLSCALRR | NESLTATDSL | RGVRRNSSFS | TARSAAAEAK |
| 1030 | 1040 | 1050 | 1060 | 1070 | 1080 |
| GRLAERAASQ | GSESPLLPTQ | RKGIPVSPVR | PKPIEKSQFI | HNNLKDVYIS | IADYEGDEET |
| 1090 | 1100 | 1110 | 1120 | ||
| AGFQEGVSME | VLEKNPNGWW | YCQILDEVKP | FKGWVPSNYL | EKKN |