A2AAY5
SS
Gene name |
Sh3pxd2b (Fad49, Tks4) |
Protein name |
SH3 and PX domain-containing protein 2B |
Names |
Factor for adipocyte differentiation 49 , Tyrosine kinase substrate with four SH3 domains |
Species |
Mus musculus (Mouse) |
KEGG Pathway |
mmu:268396 |
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 |
5-129 (PX domain) |
Relief mechanism |
PTM |
Assay |
|
Accessory elements
No accessory elements
Autoinhibited structure
Activated structure
1 structures for A2AAY5
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-A2AAY5-F1 | Predicted | AlphaFoldDB |
42 variants for A2AAY5
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| rs3389144230 | 44 | R>H | No | EVA | |
| rs3389144198 | 45 | Y>H | No | EVA | |
| rs3413053470 | 47 | K>E | No | EVA | |
| rs3401821172 | 48 | F>* | No | EVA | |
| rs3401684312 | 49 | F>* | No | EVA | |
| rs3402136003 | 49 | F>L | No | EVA | |
| rs3389149365 | 71 | R>S | No | EVA | |
| rs3389113138 | 101 | Y>F | No | EVA | |
| rs3389154550 | 120 | Q>H | No | EVA | |
| rs3389142442 | 124 | T>A | No | EVA | |
| rs3389113104 | 154 | L>M | No | EVA | |
| rs3402042969 | 174 | S>N | No | EVA | |
| rs3389144146 | 197 | E>V | No | EVA | |
| rs3389086820 | 209 | Q>H | No | EVA | |
| rs3389124746 | 236 | D>V | No | EVA | |
| rs3389135643 | 269 | W>* | No | EVA | |
| rs3389144140 | 301 | D>V | No | EVA | |
| rs3389113070 | 322 | D>G | No | EVA | |
| rs3402042999 | 346 | P>L | No | EVA | |
| rs3389149760 | 441 | P>S | No | EVA | |
| rs223992445 | 464 | V>M | No | EVA | |
| rs3389149772 | 475 | H>Y | No | EVA | |
| rs3389156998 | 488 | W>* | No | EVA | |
| rs3389149778 | 549 | G>D | No | EVA | |
| rs3389124722 | 552 | P>A | No | EVA | |
| rs1132781934 | 610 | R>W | No | EVA | |
| rs3389147016 | 679 | D>G | No | EVA | |
| rs3389146746 | 682 | S>N | No | EVA | |
| rs3389142435 | 693 | L>I | No | EVA | |
| rs3389148056 | 699 | P>L | No | EVA | |
| rs228897117 | 749 | L>Q | No | EVA | |
| rs3389142436 | 759 | R>K | No | EVA | |
| rs243453318 | 783 | Q>H | No | EVA | |
| rs3412977733 | 787 | S>C | No | EVA | |
| rs26862535 | 790 | A>T | No | EVA | |
| rs3389144157 | 807 | L>I | No | EVA | |
| rs26862534 | 817 | M>I | No | EVA | |
| rs243514057 | 827 | V>I | No | EVA | |
| rs3389120608 | 829 | G>S | No | EVA | |
| rs3389142472 | 832 | G>* | No | EVA | |
| rs3389148023 | 866 | S>R | No | EVA | |
| rs3548549013 | 905 | R>Q | No | EVA |
No associated diseases with A2AAY5
5 regional properties for A2AAY5
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| domain | Cation-transporting P-type ATPase, N-terminal | 47 - 123 | IPR004014 |
| domain | Cation-transporting P-type ATPase, C-terminal | 858 - 1036 | IPR006068 |
| ptm | P-type ATPase, phosphorylation site | 454 - 460 | IPR018303 |
| domain | Plasma membrane calcium transporting P-type ATPase, C-terminal | 1081 - 1127 | IPR022141 |
| domain | P-type ATPase, haloacid dehalogenase domain | 434 - 825 | IPR044492 |
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. |
| cell projection | A prolongation or process extending from a cell, e.g. a flagellum or axon. |
| cytoplasm | The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. |
| 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. |
6 GO annotations of molecular function
| Name | Definition |
|---|---|
| phosphatidylinositol-3,5-bisphosphate binding | Binding to phosphatidylinositol-3,5-bisphosphate, a derivative of phosphatidylinositol in which the inositol ring is phosphorylated at the 3' and 5' 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-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. |
| SH2 domain binding | Binding to a SH2 domain (Src homology 2) of a protein, a protein domain of about 100 amino-acid residues and belonging to the alpha + beta domain class. |
| superoxide-generating NADPH oxidase activator activity | Binds to and increases the activity of the enzyme superoxide-generating NADPH oxidase. |
18 GO annotations of biological process
| Name | Definition |
|---|---|
| adipose tissue development | The process whose specific outcome is the progression of adipose tissue over time, from its formation to the mature structure. Adipose tissue is specialized tissue that is used to store fat. |
| bone development | The process whose specific outcome is the progression of bone over time, from its formation to the mature structure. Bone is the hard skeletal connective tissue consisting of both mineral and cellular components. |
| cranial skeletal system development | The process whose specific outcome is the progression of a cranial skeletal system over time, from its formation to the mature structure. The cranial skeletal system is the skeletal subdivision of the head, and includes the skull (cranium plus mandible), pharyngeal and/or hyoid apparatus. |
| eye development | The process whose specific outcome is the progression of the eye over time, from its formation to the mature structure. The eye is the organ of sight. |
| heart development | The process whose specific outcome is the progression of the heart over time, from its formation to the mature structure. The heart is a hollow, muscular organ, which, by contracting rhythmically, keeps up the circulation of the blood. |
| osteoblast fate commitment | The commitment of mesenchymal cells to the specific cell fate of an osteoblast. An osteoblast is a bone-forming cell which secretes an extracellular matrix. Hydroxyapatite crystals are then deposited into the matrix to form bone. |
| podosome assembly | The aggregation, arrangement and bonding together of a set of components to form a podosome, an actin-rich adhesion structure characterized by formation upon cell substrate contact and localization at the substrate-attached part of the cell. |
| positive regulation of adipose tissue development | Any process that activates or increases the frequency, rate or extent of adipose tissue development. |
| positive regulation of fat cell differentiation | Any process that activates or increases the frequency, rate or extent of adipocyte differentiation. |
| positive regulation of gene expression | Any process that increases the frequency, rate or extent of gene expression. Gene expression is the process in which a gene's coding sequence is converted into a mature gene product (protein or RNA). |
| positive regulation of multicellular organism growth | Any process that activates or increases the frequency, rate or extent of growth of an organism to reach its usual body size. |
| positive regulation of stress fiber assembly | Any process that activates or increases the frequency, rate or extent of the assembly of a stress fiber, a bundle of microfilaments and other proteins found in fibroblasts. |
| protein localization to membrane | A process in which a protein is transported to, or maintained in, a specific location in a membrane. |
| regulation of brood size | Any process that modulates brood size. Brood size is the number of progeny that survive embryogenesis and are cared for at one time. |
| skeletal system development | The process whose specific outcome is the progression of the skeleton over time, from its formation to the mature structure. The skeleton is the bony framework of the body in vertebrates (endoskeleton) or the hard outer envelope of insects (exoskeleton or dermoskeleton). |
| skeletal system morphogenesis | The process in which the anatomical structures of the skeleton are generated and organized. |
| 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. |
| superoxide metabolic process | The chemical reactions and pathways involving superoxide, the superoxide anion O2- (superoxide free radical), or any compound containing this species. |
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 |
| Q5TCZ1 | SH3PXD2A | SH3 and PX domain-containing protein 2A | Homo sapiens (Human) | SS |
| A1X283 | SH3PXD2B | SH3 and PX domain-containing protein 2B | Homo sapiens (Human) | EV |
| 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 |
| O89032 | Sh3pxd2a | SH3 and PX domain-containing protein 2A | Mus musculus (Mouse) | SS |
| F1M707 | Ncf1 | Neutrophil cytosolic factor 1 | Rattus norvegicus (Rat) | SS |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MPPRRSIVEV | KVLDVQKRRV | PNKHYVYIIR | VTWSSGATEA | IYRRYSKFFD | LQMQMLDKFP |
| 70 | 80 | 90 | 100 | 110 | 120 |
| MEGGQKDPKQ | RIIPFLPGKI | LFRRSHIRDV | AVKRLIPIDE | YCKALIQLPP | YISQCDEVLQ |
| 130 | 140 | 150 | 160 | 170 | 180 |
| FFETRPEDLN | PPKEEHIGKK | KSGNDPTSVD | PMVLEQYVVV | ADYQKQESSE | ISLSVGQVVD |
| 190 | 200 | 210 | 220 | 230 | 240 |
| IIEKNESGWW | FVSTAEEQGW | VPATCLEGQD | GVQDEFSLQP | EEEEKYTVIY | PYTARDQDEM |
| 250 | 260 | 270 | 280 | 290 | 300 |
| NLERGAVVEV | VQKNLEGWWK | IRYQGKEGWA | PASYLKKNSG | EPLPPKLGPS | SPAHSGALDL |
| 310 | 320 | 330 | 340 | 350 | 360 |
| DGVSRHQNAM | GREKELLNNQ | RDGRFEGRLV | PDGDVKQRSP | KMRQRPPPRR | DMTIPRGLNL |
| 370 | 380 | 390 | 400 | 410 | 420 |
| PKPPIPPQVE | EEYYTIAEFQ | TTIPDGISFQ | AGLKVEVIEK | SLSGWWYIQM | EDKEGWAPAT |
| 430 | 440 | 450 | 460 | 470 | 480 |
| FIDKYKKTSS | ASRPNFLAPL | PHEMTQLRLG | DAAATENNTG | PEAVGPSRPL | PEAPHGAVDS |
| 490 | 500 | 510 | 520 | 530 | 540 |
| GMLWSKDWKG | GKEAPRKASS | DLSASTGYEE | ISDPTQEEKP | SLPPRKESII | KSEEELLERE |
| 550 | 560 | 570 | 580 | 590 | 600 |
| RQKMEPLRGS | SPKPPGMILP | MIPAKHAPLA | RDSRKPEPKL | DKSKFPLRND | MGLECGHKVL |
| 610 | 620 | 630 | 640 | 650 | 660 |
| AKEVKKPNLR | PISRSKAELS | EEKVDPTSQN | LFMKSRPQVR | PKPTPSPKTE | PAQSEDHVDI |
| 670 | 680 | 690 | 700 | 710 | 720 |
| YNLRSKLRPA | KSQEKALLDG | ESHHAAGSHD | TALSRSFLPG | EGPGHGQDRS | GRQDGLSPKE |
| 730 | 740 | 750 | 760 | 770 | 780 |
| TPCRAPPRPA | KTTDPGPKNV | PVPVQEATLQ | QRPVVPPRRP | PPPKKTSSSP | LSCRPLPEVR |
| 790 | 800 | 810 | 820 | 830 | 840 |
| GAQREESRVA | PAAGRALLVP | PKAKPFLSNS | SVGQDDMRGK | GGLGPRVTGK | VGETREKAAS |
| 850 | 860 | 870 | 880 | 890 | 900 |
| FLNADGPKDS | LYVAVANFEG | DEDTSSFQEG | TVFEVREKNS | SGWWFCQVLS | GAPSWEGWIP |
| SNYLRKKP |