O08722
Gene name |
Unc5b (Unc5h2) |
Protein name |
Netrin receptor UNC5B |
Names |
Protein unc-5 homolog 2, Protein unc-5 homolog B |
Species |
Rattus norvegicus (Rat) |
KEGG Pathway |
rno:60630 |
EC number |
|
Protein Class |
NETRIN RECEPTOR UNC5 (PTHR12582) |
Descriptions
The UNC5 family proteins, initially discovered in C. elegans as an axonal guidance transmembrane receptor. The cytoplasmic domains of UNC5b are responsible for its netrin-mediated signaling events in axonal migrations, blood vessel patterning, and apoptosis. The domain organization pattern of the cytoplasmic portion of UNC5 (i.e., ZU5-UPA-DD) is also found in ankyrins, a large family of scaffold proteins responsible for the assembly of specialized membrane microdomain structures that contain ion channels, cell adhesion molecules, and cytoskeletons in diverse cells.
The three domains (ZU5, UPA, and DD) form a structural supramoldule, thereby locking the ZU5-UPA-DD supramodule in a closed conformation and suppressing the biological activity of UNC5b. Release of the closed conformation of the ZU5-UPA-DD supramodule leads to the activation of the receptor in the promotion of apoptosis and blood vessel patterning.
Autoinhibitory domains (AIDs)
Target domain |
541-942 (ZU5-UPA-DD) |
Relief mechanism |
Ligand binding |
Assay |
Structural analysis, Deletion assay |
Target domain |
541-942 (ZU5-UPA-DD) |
Relief mechanism |
Ligand binding |
Assay |
Structural analysis, Deletion assay |
Target domain |
541-942 (ZU5-UPA-DD) |
Relief mechanism |
Ligand binding |
Assay |
Structural analysis, Deletion assay |
Accessory elements
No accessory elements
Autoinhibited structure
Activated structure
2 structures for O08722
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| 3G5B | X-ray | 200 A | A | 541-945 | PDB |
| AF-O08722-F1 | Predicted | AlphaFoldDB |
No variants for O08722
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| No variants for O08722 | |||||
No associated diseases with O08722
11 regional properties for O08722
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| domain | Death domain | 852 - 943 | IPR000488 |
| repeat | Thrombospondin type-1 (TSP1) repeat | 246 - 300 | IPR000884-1 |
| repeat | Thrombospondin type-1 (TSP1) repeat | 302 - 354 | IPR000884-2 |
| domain | ZU5 domain | 541 - 686 | IPR000906 |
| domain | Immunoglobulin subtype 2 | 165 - 232 | IPR003598 |
| domain | Immunoglobulin subtype | 54 - 149 | IPR003599-1 |
| domain | Immunoglobulin subtype | 159 - 244 | IPR003599-2 |
| domain | Immunoglobulin-like domain | 172 - 242 | IPR007110 |
| domain | Immunoglobulin I-set | 154 - 243 | IPR013098 |
| domain | UPA domain | 691 - 830 | IPR033772 |
| domain | UNC5B, death domain | 858 - 941 | IPR042156 |
Functions
| Description | ||
|---|---|---|
| EC Number | ||
| Subcellular Localization |
|
|
| PANTHER Family | PTHR12582 | NETRIN RECEPTOR UNC5 |
| PANTHER Subfamily | PTHR12582:SF6 | NETRIN RECEPTOR UNC5B |
| PANTHER Protein Class | transmembrane signal receptor | |
| PANTHER Pathway Category |
Axon guidance mediated by netrin UNC-5 |
|
3 GO annotations of cellular component
| Name | Definition |
|---|---|
| integral component of membrane | The component of a membrane consisting of the gene products and protein complexes having at least some part of their peptide sequence embedded in the hydrophobic region of the membrane. |
| membrane raft | Any of the small (10-200 nm), heterogeneous, highly dynamic, sterol- and sphingolipid-enriched membrane domains that compartmentalize cellular processes. Small rafts can sometimes be stabilized to form larger platforms through protein-protein and protein-lipid interactions. |
| plasma membrane | The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins. |
1 GO annotations of molecular function
| Name | Definition |
|---|---|
| netrin receptor activity | Combining with a netrin signal and transmitting the signal from one side of the membrane to the other to initiate a change in cell activity. |
7 GO annotations of biological process
| Name | Definition |
|---|---|
| anterior/posterior axon guidance | The process in which the migration of an axon growth cone is directed to a specific target site along the anterior-posterior body axis in response to a combination of attractive and repulsive cues. The anterior-posterior axis is defined by a line that runs from the head or mouth of an organism to the tail or opposite end of the organism. |
| apoptotic process | A programmed cell death process which begins when a cell receives an internal (e.g. DNA damage) or external signal (e.g. an extracellular death ligand), and proceeds through a series of biochemical events (signaling pathway phase) which trigger an execution phase. The execution phase is the last step of an apoptotic process, and is typically characterized by rounding-up of the cell, retraction of pseudopodes, reduction of cellular volume (pyknosis), chromatin condensation, nuclear fragmentation (karyorrhexis), plasma membrane blebbing and fragmentation of the cell into apoptotic bodies. When the execution phase is completed, the cell has died. |
| axon guidance | The chemotaxis process that directs the migration of an axon growth cone to a specific target site in response to a combination of attractive and repulsive cues. |
| negative regulation of extrinsic apoptotic signaling pathway in absence of ligand | Any process that stops, prevents or reduces the frequency, rate or extent of extrinsic apoptotic signaling pathway in absence of ligand. |
| negative regulation of neuron apoptotic process | Any process that stops, prevents, or reduces the frequency, rate or extent of cell death by apoptotic process in neurons. |
| positive regulation of extrinsic apoptotic signaling pathway in absence of ligand | Any process that activates or increases the frequency, rate or extent of extrinsic apoptotic signaling pathway in absence of ligand. |
| positive regulation of phosphatidylinositol 3-kinase signaling | Any process that activates or increases the frequency, rate or extent of signal transduction mediated by the phosphatidylinositol 3-kinase cascade. |
12 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| Q7T2Z5 | UNC5C | Netrin receptor UNC5C | Gallus gallus (Chicken) | SS |
| Q6ZN44 | UNC5A | Netrin receptor UNC5A | Homo sapiens (Human) | SS |
| Q6UXZ4 | UNC5D | Netrin receptor UNC5D | Homo sapiens (Human) | SS |
| O95185 | UNC5C | Netrin receptor UNC5C | Homo sapiens (Human) | SS |
| Q8IZJ1 | UNC5B | Netrin receptor UNC5B | Homo sapiens (Human) | SS |
| Q8K1S4 | Unc5a | Netrin receptor UNC5A | Mus musculus (Mouse) | SS |
| O08747 | Unc5c | Netrin receptor UNC5C | Mus musculus (Mouse) | SS |
| Q8K1S2 | Unc5d | Netrin receptor UNC5D | Mus musculus (Mouse) | SS |
| Q8K1S3 | Unc5b | Netrin receptor UNC5B | Mus musculus (Mouse) | SS |
| O08721 | Unc5a | Netrin receptor UNC5A | Rattus norvegicus (Rat) | SS |
| F1LW30 | Unc5d | Netrin receptor UNC5D | Rattus norvegicus (Rat) | SS |
| Q761X5 | Unc5c | Netrin receptor UNC5C | Rattus norvegicus (Rat) | SS |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MRARSGARGA | LLLALLLCWD | PTPSLAGIDS | GGQALPDSFP | SAPAEQLPHF | LLEPEDAYIV |
| 70 | 80 | 90 | 100 | 110 | 120 |
| KNKPVELHCR | AFPATQIYFK | CNGEWVSQKG | HVTQESLDEA | TGLRIREVQI | EVSRQQVEEL |
| 130 | 140 | 150 | 160 | 170 | 180 |
| FGLEDYWCQC | VAWSSSGTTK | SRRAYIRIAY | LRKNFDQEPL | AKEVPLDHEV | LLQCRPPEGV |
| 190 | 200 | 210 | 220 | 230 | 240 |
| PVAEVEWLKN | EDVIDPAQDT | NFLLTIDHNL | IIRQARLSDT | ANYTCVAKNI | VAKRRSTTAT |
| 250 | 260 | 270 | 280 | 290 | 300 |
| VIVYVNGGWS | SWAEWSPCSN | RCGRGWQKRT | RTCTNPAPLN | GGAFCEGQAC | QKTACTTVCP |
| 310 | 320 | 330 | 340 | 350 | 360 |
| VDGAWTEWSK | WSACSTECAH | WRSRECMAPP | PQNGGRDCSG | TLLDSKNCTD | GLCVLNQRTL |
| 370 | 380 | 390 | 400 | 410 | 420 |
| NDPKSRPLEP | SGDVALYAGL | VVAVFVVLAV | LMAVGVIVYR | RNCRDFDTDI | TDSSAALTGG |
| 430 | 440 | 450 | 460 | 470 | 480 |
| FHPVNFKTAR | PSNPQLLHPS | APPDLTASAG | IYRGPVYALQ | DSADKIPMTN | SPLLDPLPSL |
| 490 | 500 | 510 | 520 | 530 | 540 |
| KIKVYDSSTI | GSGAGLADGA | DLLGVLPPGT | YPGDFSRDTH | FLHLRSASLG | SQHLLGLPRD |
| 550 | 560 | 570 | 580 | 590 | 600 |
| PSSSVSGTFG | CLGGRLTIPG | TGVSLLVPNG | AIPQGKFYDL | YLRINKTEST | LPLSEGSQTV |
| 610 | 620 | 630 | 640 | 650 | 660 |
| LSPSVTCGPT | GLLLCRPVVL | TVPHCAEVIA | GDWIFQLKTQ | AHQGHWEEVV | TLDEETLNTP |
| 670 | 680 | 690 | 700 | 710 | 720 |
| CYCQLEAKSC | HILLDQLGTY | VFTGESYSRS | AVKRLQLAIF | APALCTSLEY | SLRVYCLEDT |
| 730 | 740 | 750 | 760 | 770 | 780 |
| PAALKEVLEL | ERTLGGYLVE | EPKTLLFKDS | YHNLRLSLHD | IPHAHWRSKL | LAKYQEIPFY |
| 790 | 800 | 810 | 820 | 830 | 840 |
| HVWNGSQKAL | HCTFTLERHS | LASTEFTCKV | CVRQVEGEGQ | IFQLHTTLAE | TPAGSLDALC |
| 850 | 860 | 870 | 880 | 890 | 900 |
| SAPGNAATTQ | LGPYAFKIPL | SIRQKICNSL | DAPNSRGNDW | RLLAQKLSMD | RYLNYFATKA |
| 910 | 920 | 930 | 940 | ||
| SPTGVILDLW | EARQQDDGDL | NSLASALEEM | GKSEMLVAMT | TDGDC |