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

543-940 (ZU5-UPA-DD)

Relief mechanism

Ligand binding

Assay

Target domain

543-940 (ZU5-UPA-DD)

Relief mechanism

Ligand binding

Assay

Target domain

543-940 (ZU5-UPA-DD)

Relief mechanism

Ligand binding

Assay

Accessory elements

No accessory elements

Autoinhibited structure

Activated structure

8 structures for F1LW30

Entry ID Method Resolution Chain Position Source
4V2B X-ray 200 A A/B 1-161 PDB
4V2C X-ray 400 A B/D 1-161 PDB
5FTT X-ray 340 A A/E 32-307 PDB
5FTU X-ray 601 A A/E/I 32-161 PDB
7ZA1 X-ray 410 A E/F/G/H 46-307 PDB
7ZA2 X-ray 460 A E/F/G/H 46-307 PDB
7ZA3 X-ray 400 A E/F/G/H 46-307 PDB
AF-F1LW30-F1 Predicted AlphaFoldDB

1 variants for F1LW30

Variant ID(s) Position Change Description Diseaes Association Provenance
rs3322988502 532 Y>F No EVA

No associated diseases with F1LW30

10 regional properties for F1LW30

Type Name Position InterPro Accession
domain Death domain 850 - 941 IPR000488
repeat Thrombospondin type-1 (TSP1) repeat 250 - 304 IPR000884-1
repeat Thrombospondin type-1 (TSP1) repeat 306 - 358 IPR000884-2
domain ZU5 domain 543 - 685 IPR000906
domain Immunoglobulin subtype 2 169 - 236 IPR003598
domain Immunoglobulin subtype 163 - 248 IPR003599
domain Immunoglobulin-like domain 164 - 242 IPR007110
domain Immunoglobulin I-set 158 - 246 IPR013098
domain UPA domain 690 - 829 IPR033772
domain UNC5D, Death domain 856 - 953 IPR042058

Functions

Description
EC Number
Subcellular Localization
  • Cell membrane ; Single-pass type I membrane protein
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

2 GO annotations of cellular component

Name Definition
cell surface The external part of the cell wall and/or plasma membrane.
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
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.
cell-cell adhesion via plasma-membrane adhesion molecules The attachment of one cell to another cell via adhesion molecules that are at least partially embedded in the plasma membrane.
pyramidal neuron differentiation The process in which a neuroblast or one of its progeny commits to a pyramidal neuron fate, migrates from the ventricular zone to the appropriate layer in the cortex and develops into a mature neuron.
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
O95185 UNC5C Netrin receptor UNC5C Homo sapiens (Human) SS
Q6UXZ4 UNC5D Netrin receptor UNC5D Homo sapiens (Human) SS
Q8K1S4 Unc5a Netrin receptor UNC5A Mus musculus (Mouse) 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
O08721 Unc5a Netrin receptor UNC5A Rattus norvegicus (Rat) SS
O08722 Unc5b Netrin receptor UNC5B Rattus norvegicus (Rat) EV
Q761X5 Unc5c Netrin receptor UNC5C Rattus norvegicus (Rat) SS
10 20 30 40 50 60
MGTGAADRSR GARWWLPWLG LCFWAAGAEA ARGADSGEVL PDSIPSAPGT LPHFIEEPED
70 80 90 100 110 120
AYIIKSNPIA LRCKARPAMQ IFFKCNGEWV HQNEHVSEES LDESSGLKVR EVFINVTRQQ
130 140 150 160 170 180
VEDFHGPEDY WCQCVAWSHL GTSKSRKASV RIAYLRKNFE QDPQGREVPI EGMIVLHCRP
190 200 210 220 230 240
PEGVPAAEVE WLKNEEPIDS EQDENIDTRA DHNLIIRQAR LSDSGNYTCM AANIVAKRRS
250 260 270 280 290 300
LSATVVVYVN GGWSSWTEWS ACNVRCGRGW QKRSRTCTNP APLNGGAFCE GMSVQKITCT
310 320 330 340 350 360
ALCPVDGSWE VWSEWSVCSP ECEHLRIREC TAPPPRNGGK FCEGLSQESE NCTDGLCILD
370 380 390 400 410 420
KKPLHEIKPQ RWSRRGIENA SDIALYSGLG AAVVAVAVLV IGVTLYRRSH SDYGVDVIDS
430 440 450 460 470 480
SALTGGFQTF NFKTVRQGNS LLLNPAMHPD LTVSRTYSGP ICLQDPLDKE LMTESSLFNP
490 500 510 520 530 540
LSDIKVKVQS SFMVSLGVSE RAEYHGKNHS GTFPHGNNRG FSTIHPRNKT PYIQNLSSLP
550 560 570 580 590 600
TRTELRTTGV FGHLGGRLVM PNTGVSLLIP HGAIPEENSW EIYMSINQGE PSLQSDGSEV
610 620 630 640 650 660
LLSPEVTCGP PDMLVTTPFA LTIPHCADVS SEHWNIHLKK RTQQGKWEEV MSVEDESTSC
670 680 690 700 710 720
YCLLDPFACH VLLDSFGTYA LTGEPITDCA VKQLKVAVFG CMSCNSLDYN LRVYCVDNTP
730 740 750 760 770 780
CAFQEVVSDE RHQGGQLLEE PKLLHFKGNT FSLQISVLDI PPFLWRIKPF TACQEVPFSR
790 800 810 820 830 840
VWSSNRQPLH CAFSLERYTP TTTQLSCKIC IRQLKGHEQI LQVQTSILES ERETITFFAQ
850 860 870 880 890 900
EDSTFPAQTG PKAFKIPYSI RQRICATFDT PNAKGKDWQM LAQKNSINRN LSYFATQSSP
910 920 930 940 950
SAVILNLWEA RHQQDGDLDS LACALEEIGR THTKLSNITE PQLDDTDFNY SRQNGL