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)

Target domain

528-928 (ZU5-UPA-DD)

Relief mechanism

Ligand binding

Assay

Target domain

528-928 (ZU5-UPA-DD)

Relief mechanism

Ligand binding

Assay

Target domain

528-928 (ZU5-UPA-DD)

Relief mechanism

Ligand binding

Assay

Accessory elements

No accessory elements

Autoinhibited structure

Activated structure

1 structures for Q761X5

Entry ID Method Resolution Chain Position Source
AF-Q761X5-F1 Predicted AlphaFoldDB

No variants for Q761X5

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for Q761X5

1 associated diseases with Q761X5

Without disease ID

10 regional properties for Q761X5

Type Name Position InterPro Accession
domain Death domain 838 - 929 IPR000488
repeat Thrombospondin type-1 (TSP1) repeat 260 - 314 IPR000884-1
repeat Thrombospondin type-1 (TSP1) repeat 316 - 368 IPR000884-2
domain ZU5 domain 528 - 673 IPR000906
domain Immunoglobulin subtype 2 179 - 246 IPR003598
domain Immunoglobulin subtype 173 - 258 IPR003599
domain Immunoglobulin-like domain 175 - 256 IPR007110
domain Immunoglobulin I-set 168 - 257 IPR013098
domain UPA domain 678 - 817 IPR033772
domain UNC5C, death domain 844 - 926 IPR042154

Functions

Description
EC Number
Subcellular Localization
  • Cell membrane ; Single-pass type I membrane protein
  • Cell surface
  • Synapse, synaptosome
  • Cell projection, axon
  • Cell projection, dendrite
  • Cell projection, growth cone
  • Cell projection, lamellipodium
  • Cell projection, filopodium
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

9 GO annotations of cellular component

Name Definition
axon The long process of a neuron that conducts nerve impulses, usually away from the cell body to the terminals and varicosities, which are sites of storage and release of neurotransmitter.
cell surface The external part of the cell wall and/or plasma membrane.
dendrite A neuron projection that has a short, tapering, morphology. Dendrites receive and integrate signals from other neurons or from sensory stimuli, and conduct nerve impulses towards the axon or the cell body. In most neurons, the impulse is conveyed from dendrites to axon via the cell body, but in some types of unipolar neuron, the impulse does not travel via the cell body.
filopodium Thin, stiff, actin-based protrusion extended by the leading edge of a motile cell such as a crawling fibroblast or amoeba, or an axonal or dendritic growth cone, or a dendritic shaft.
growth cone The migrating motile tip of a growing neuron projection, where actin accumulates, and the actin cytoskeleton is the most dynamic.
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.
neuronal cell body The portion of a neuron that includes the nucleus, but excludes 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.
synapse The junction between an axon of one neuron and a dendrite of another neuron, a muscle fiber or a glial cell. As the axon approaches the synapse it enlarges into a specialized structure, the presynaptic terminal bouton, which contains mitochondria and synaptic vesicles. At the tip of the terminal bouton is the presynaptic membrane; facing it, and separated from it by a minute cleft (the synaptic cleft) is a specialized area of membrane on the receiving cell, known as the postsynaptic membrane. In response to the arrival of nerve impulses, the presynaptic terminal bouton secretes molecules of neurotransmitters into the synaptic cleft. These diffuse across the cleft and transmit the signal to the postsynaptic membrane.

4 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.
netrin receptor activity involved in chemorepulsion Combining with a netrin signal and transmitting the signal from one side of the membrane to the other to contribute to the directed movement of a motile cell away from a higher concentration of netrin.
protein kinase binding Binding to a protein kinase, any enzyme that catalyzes the transfer of a phosphate group, usually from ATP, to a protein substrate.
tubulin binding Binding to monomeric or multimeric forms of tubulin, including microtubules.

13 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.
brain development The process whose specific outcome is the progression of the brain over time, from its formation to the mature structure. Brain development begins with patterning events in the neural tube and ends with the mature structure that is the center of thought and emotion. The brain is responsible for the coordination and control of bodily activities and the interpretation of information from the senses (sight, hearing, smell, etc.).
chemorepulsion of axon The process in which a neuron growth cone is directed to a specific target site in response to a repulsive chemical cue.
dorsal root ganglion development The process whose specific outcome is the progression of a dorsal root ganglion over time, from its formation to the mature structure.
ectopic germ cell programmed cell death Programmed cell death of an errant germ line cell that is outside the normal migratory path or ectopic to the gonad. This is an important mechanism of regulating germ cell survival within the embryo.
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.
positive regulation of apoptotic process Any process that activates or increases the frequency, rate or extent of cell death by apoptotic process.
positive regulation of developmental process Any process that activates or increases the rate or extent of development, the biological process whose specific outcome is the progression of an organism over time from an initial condition (e.g. a zygote, or a young adult) to a later condition (e.g. a multicellular animal or an aged adult).
positive regulation of reproductive process Any process that activates or increases the frequency, rate or extent of reproductive process.
regulation of cell migration Any process that modulates the frequency, rate or extent of cell migration.
regulation of neuron migration Any process that modulates the frequency, rate or extent of neuron migration.

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
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
Q8K1S4 Unc5a Netrin receptor UNC5A Mus musculus (Mouse) SS
Q8K1S3 Unc5b Netrin receptor UNC5B Mus musculus (Mouse) SS
Q8K1S2 Unc5d Netrin receptor UNC5D Mus musculus (Mouse) SS
O08747 Unc5c Netrin receptor UNC5C Mus musculus (Mouse) SS
O08721 Unc5a Netrin receptor UNC5A Rattus norvegicus (Rat) SS
O08722 Unc5b Netrin receptor UNC5B Rattus norvegicus (Rat) EV
F1LW30 Unc5d Netrin receptor UNC5D Rattus norvegicus (Rat) SS
10 20 30 40 50 60
MRKGLRATAA RCGLGLGYLL QMLVLPALAL LSASGTGSAA QDDDFFHELP ETFPSDPPEP
70 80 90 100 110 120
LPHFLIEPEE AYIVKNKPVN LYCKASPATQ IYFKCNSEWV HQKDHVVDER VDETSGLIVR
130 140 150 160 170 180
EVSIEISRQQ VEELFGPEDY WCQCVAWSSA GTTKSRKAYV RIAYLRKTFE QEPLGKEVSL
190 200 210 220 230 240
EQEVLLQCRP PEGIPMAEVE WLKNEDIIDP VEDRNFYITI DHNLIIKQAR LSDTANYTCV
250 260 270 280 290 300
AKNIVAKRKS TTATVIVYVN GGWSTWAEWS VCNSRCGRGY QKRTRTCTNP APLNGGAFCE
310 320 330 340 350 360
GQSVQKIACT TLCPVDGRWT SWSKWSTCGT ECTHWRRREC TAPAPKNGGK DCDGLVLQSK
370 380 390 400 410 420
NCTDGLCMQA APDSDDVALY VGIVIAVTVC LAITVVVALF VYRKNHRDFE SNIIDSSALN
430 440 450 460 470 480
GGFQPVNIKA ARQDLLAVPP DLTSAAAMYR GPVYALHDVS DKIPMTNSPI LDPLPNLKIK
490 500 510 520 530 540
VYNSSGAVTP QDDLAEFSSK LSPQMTQSLL ENEALNLKNQ SLARQTDPSC TAFGTFNSLG
550 560 570 580 590 600
GHLIIPNSGV SLLIPAGAIP QGRVYEMYVT VHRKENMRPP MEDSQTLLTP VVSCGPPGAL
610 620 630 640 650 660
LTRPVILTLH HCADPNTEDW KIQLKNQAVQ GQWEDVVVVG EENFTTPCYI QLDAEACHIL
670 680 690 700 710 720
TENLSTYALV GQSTTKAAAK RLKLAIFGPL CCSSLEYSIR VYCLDDTQDA LKEVLQLERQ
730 740 750 760 770 780
MGGQLLEEPK ALHFKGSIHN LRLSIHDITH SLWKSKLLAK YQEIPFYHIW SGSQRNLHCT
790 800 810 820 830 840
FTLERLSLNT VELVCKLCVR QVEGEGQIFQ LNCTVSEEPT GIDLPLLDPA STITTVTGPS
850 860 870 880 890 900
AFSIPLPIRQ KLCSSLDAPQ TRGHDWRMLA HKLNLDRYLN YFATKSSPTG VILDLWEAQN
910 920 930
FPDGNLSMLA AVLEEMGRHE TVVSLAAEGQ Y