O08721

SS
Gene name
Unc5a (Unc5h1)
Protein name
Netrin receptor UNC5A
Names
Protein unc-5 homolog 1 , Protein unc-5 homolog A
Species
Rattus norvegicus (Rat)
KEGG Pathway
rno:60629
EC number
Protein Class

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. <br>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)

495-641 (ZU5 domain) SS

Target domain

495-895 (ZU5-UPA-DD)

Relief mechanism

Ligand binding

Assay

642-782 (UPA domain) SS

Target domain

495-895 (ZU5-UPA-DD)

Relief mechanism

Ligand binding

Assay

806-895 (Death domain, DD domain) SS

Target domain

495-895 (ZU5-UPA-DD)

Relief mechanism

Ligand binding

Assay

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

1 structures for O08721

Entry ID Method Resolution Chain Position Source
AF-O08721-F1 Predicted AlphaFoldDB

No variants for O08721

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for O08721

No associated diseases with O08721

9 regional properties for O08721

Type Name Position InterPro Accession
domain Death domain 805 - 896 IPR000488
repeat Thrombospondin type-1 (TSP1) repeat 242 - 296 IPR000884-1
repeat Thrombospondin type-1 (TSP1) repeat 298 - 350 IPR000884-2
domain ZU5 domain 495 - 640 IPR000906
domain Immunoglobulin subtype 155 - 240 IPR003599
domain Immunoglobulin-like domain 155 - 238 IPR007110
domain Immunoglobulin I-set 150 - 237 IPR013098
domain UPA domain 645 - 783 IPR033772
domain UNC5A, death domain 811 - 894 IPR042155

Functions

Description
EC Number
Subcellular Localization
  • Cell membrane ; Single-pass type I membrane protein
  • Membrane raft
  • Cell projection, neuron projection
  • The interaction with PRKCABP regulates its surface expression and leads to its removal from the surface of neurons and growth cones (PubMed:14672991)
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

4 GO annotations of cellular component

Name Definition
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.
neuron projection membrane The portion of the plasma membrane surrounding a neuron projection.
neuronal cell body membrane The plasma membrane of a neuron cell body - excludes the plasma membrane of cell projections such as axons and dendrites.
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.

5 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.
netrin-activated signaling pathway The series of molecular signals initiated by the binding of a netrin protein to its receptor on the surface of the target cell, and ending with the regulation of a downstream cellular process, e.g. transcription. Netrins can act as chemoattractant signals for some cells and chemorepellent signals for others. Netrins also have roles outside of cell and axon guidance.
neuron projection development The process whose specific outcome is the progression of a neuron projection over time, from its formation to the mature structure. A neuron projection is any process extending from a neural cell, such as axons or dendrites (collectively called neurites).

12 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
Q7T2Z5 UNC5C Netrin receptor UNC5C Gallus gallus (Chicken) SS
Q8IZJ1 UNC5B Netrin receptor UNC5B Homo sapiens (Human) SS
Q6UXZ4 UNC5D Netrin receptor UNC5D Homo sapiens (Human) SS
O95185 UNC5C Netrin receptor UNC5C Homo sapiens (Human) SS
Q6ZN44 UNC5A Netrin receptor UNC5A Homo sapiens (Human) SS
Q8K1S3 Unc5b Netrin receptor UNC5B Mus musculus (Mouse) SS
O08747 Unc5c Netrin receptor UNC5C Mus musculus (Mouse) SS
Q8K1S2 Unc5d Netrin receptor UNC5D Mus musculus (Mouse) SS
Q8K1S4 Unc5a Netrin receptor UNC5A Mus musculus (Mouse) SS
O08722 Unc5b Netrin receptor UNC5B Rattus norvegicus (Rat) EV
F1LW30 Unc5d Netrin receptor UNC5D Rattus norvegicus (Rat) SS
Q761X5 Unc5c Netrin receptor UNC5C Rattus norvegicus (Rat) SS
10 20 30 40 50 60
MAVRPGLWPV LLGIVLAAWL RGSGAQQSAT VANPVPGANP DLLPHFLVEP EDVYIVKNKP
70 80 90 100 110 120
VLLVCKAVPA TQIFFKCNGE WVRQVDHVIE RSTDSSSGLP TMEVRINVSR QQVEKVFGLE
130 140 150 160 170 180
EYWCQCVAWS SSGTTKSQKA YIRIAYLRKN FEQEPLAKEV SLEQGIVLPC RPPEGIPPAE
190 200 210 220 230 240
VEWLRNEDLV DPSLDPNVYI TREHSLVVRQ ARLADTANYT CVAKNIVARR RSTSAAVIVY
250 260 270 280 290 300
VNGGWSTWTE WSVCSASCGR GWQKRSRSCT NPAPLNGGAF CEGQNVQKTA CATLCPVDGS
310 320 330 340 350 360
WSSWSKWSAC GLDCTHWRSR ECSDPAPRNG GEECRGADLD TRNCTSDLCL HTASCPEDVA
370 380 390 400 410 420
LYIGLVAVAV CLFLLLLALG LIYCRKKEGL DSDVADSSIL TSGFQPVSIK PSKADNPHLL
430 440 450 460 470 480
TIQPDLSTTT TTYQGSLCSR QDGPSPKFQL SNGHLLSPLG SGRHTLHHSS PTSEAEDFVS
490 500 510 520 530 540
RLSTQNYFRS LPRGTSNMAY GTFNFLGGRL MIPNTGISLL IPPDAIPRGK IYEIYLTLHK
550 560 570 580 590 600
PEDVRLPLAG CQTLLSPVVS CGPPGVLLTR PVILAMDHCG EPSPDSWSLR LKKQSCEGSW
610 620 630 640 650 660
EDVLHLGEES PSHLYYCQLE AGACYVFTEQ LGRFALVGEA LSVAATKRLR LLLFAPVACT
670 680 690 700 710 720
SLEYNIRVYC LHDTHDALKE VVQLEKQLGG QLIQEPRVLH FKDSYHNLRL SIHDVPSSLW
730 740 750 760 770 780
KSKLLVSYQE IPFYHIWNGT QQYLHCTFTL ERINASTSDL ACKVWVWQVE GDGQSFNINF
790 800 810 820 830 840
NITKDTRFAE LLALESEGGV PALVGPSAFK IPFLIRQKII ASLDPPCSRG ADWRTLAQKL
850 860 870 880 890
HLDSHLSFFA SKPSPTAMIL NLWEARHFPN GNLGQLAAAV AGLGQPDAGL FTVSEAEC