UniProtKB - Q8IZJ1 (UNC5B_HUMAN)
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Protein
Netrin receptor UNC5B
Gene
UNC5B
Organism
Homo sapiens (Human)
Status
Functioni
Receptor for netrin required for axon guidance. Mediates axon repulsion of neuronal growth cones in the developing nervous system upon ligand binding. Axon repulsion in growth cones may be caused by its association with DCC that may trigger signaling for repulsion (By similarity). Functions as netrin receptor that negatively regulates vascular branching during angiogenesis. Mediates retraction of tip cell filopodia on endothelial growth cones in response to netrin (By similarity). It also acts as a dependence receptor required for apoptosis induction when not associated with netrin ligand (PubMed:12598906). Mediates apoptosis by activating DAPK1. In the absence of NTN1, activates DAPK1 by reducing its autoinhibitory phosphorylation at Ser-308 thereby increasing its catalytic activity (By similarity).By similarity1 Publication
Miscellaneous
Down-regulated in multiple cancers including colorectal, breast, ovary, uterus, stomach, lung, or kidney cancers.
GO - Molecular functioni
- netrin receptor activity Source: InterPro
GO - Biological processi
- angiogenesis Source: UniProtKB-KW
- anterior/posterior axon guidance Source: Ensembl
- apoptotic process Source: UniProtKB-KW
- negative regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: UniProtKB
- negative regulation of neuron apoptotic process Source: UniProtKB
- positive regulation of phosphatidylinositol 3-kinase signaling Source: UniProtKB
Keywordsi
Molecular function | Developmental protein, Receptor |
Biological process | Angiogenesis, Apoptosis |
Enzyme and pathway databases
Reactomei | R-HSA-373752. Netrin-1 signaling. R-HSA-418886. Netrin mediated repulsion signals. R-HSA-418889. Ligand-independent caspase activation via DCC. |
Names & Taxonomyi
Protein namesi | Recommended name: Netrin receptor UNC5BAlternative name(s): Protein unc-5 homolog 2 Protein unc-5 homolog B p53-regulated receptor for death and life protein 11 Publication Short name: p53RDL11 Publication |
Gene namesi | Name:UNC5B Synonyms:P53RDL11 Publication, UNC5H21 Publication ORF Names:UNQ1883/PRO4326 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000107731.12. |
HGNCi | HGNC:12568. UNC5B. |
MIMi | 607870. gene. |
neXtProti | NX_Q8IZJ1. |
Subcellular locationi
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 27 – 377 | ExtracellularSequence analysisAdd BLAST | 351 | |
Transmembranei | 378 – 398 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 399 – 945 | CytoplasmicSequence analysisAdd BLAST | 547 |
Keywords - Cellular componenti
Cell membrane, MembranePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 412 | D → N: Abolishes cleavage by caspase-3 and subsequent induction of apoptosis. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 219699. |
OpenTargetsi | ENSG00000107731. |
PharmGKBi | PA37205. |
Polymorphism and mutation databases
BioMutai | UNC5B. |
DMDMi | 54036589. |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 26 | Sequence analysisAdd BLAST | 26 | |
ChainiPRO_0000036071 | 27 – 945 | Netrin receptor UNC5BAdd BLAST | 919 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 69 ↔ 130 | By similarity | ||
Disulfide bondi | 81 ↔ 128 | By similarity | ||
Disulfide bondi | 174 ↔ 225 | By similarity | ||
Glycosylationi | 222 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 258 ↔ 295 | By similarity | ||
Disulfide bondi | 262 ↔ 299 | By similarity | ||
Disulfide bondi | 273 ↔ 285 | By similarity | ||
Disulfide bondi | 314 ↔ 348 | By similarity | ||
Disulfide bondi | 318 ↔ 353 | By similarity | ||
Disulfide bondi | 326 ↔ 338 | By similarity | ||
Glycosylationi | 347 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Lipidationi | 403 | S-palmitoyl cysteineBy similarity | 1 | |
Modified residuei | 581 | PhosphotyrosineBy similarity | 1 |
Post-translational modificationi
Phosphorylated on cytoplasmic tyrosine residues.By similarity
Proteolytically cleaved by caspases during apoptosis. The cleavage does not take place when the receptor is associated with netrin ligand. Its cleavage by caspases is required to induce apoptosis.1 Publication
Palmitoylation is required for pro-apoptotic activity, but not for location at lipid rafts.By similarity
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 412 – 413 | Cleavage; by caspase-31 Publication | 2 |
Keywords - PTMi
Disulfide bond, Glycoprotein, Lipoprotein, Palmitate, PhosphoproteinProteomic databases
MaxQBi | Q8IZJ1. |
PaxDbi | Q8IZJ1. |
PeptideAtlasi | Q8IZJ1. |
PRIDEi | Q8IZJ1. |
PTM databases
iPTMneti | Q8IZJ1. |
PhosphoSitePlusi | Q8IZJ1. |
SwissPalmi | Q8IZJ1. |
Miscellaneous databases
PMAP-CutDBi | Q8IZJ1. |
Expressioni
Tissue specificityi
Highly expressed in brain. Also expressed at lower level in developing lung, cartilage, kidney and hematopoietic and immune tissues.1 Publication
Inductioni
By p53/TP53.
Gene expression databases
Bgeei | ENSG00000107731. |
CleanExi | HS_UNC5B. |
Genevisiblei | Q8IZJ1. HS. |
Interactioni
Subunit structurei
Interacts with the cytoplasmic part of DCC (By similarity). Interacts with GNAI2 via its cytoplasmic part (PubMed:12359238). Interacts (via death domain) with DAPK1 (via death domain) (PubMed:15729359, PubMed:18582460). Interacts (via extracellular domain) with FLRT3 (via extracellular domain); the interaction is direct (PubMed:26235030). Interacts (via extracellular domain) with FLRT2 and FLRT3 (via extracellular domain), but has higher affinity for FLRT3 (PubMed:25374360). Identified in a complex with FLRT3 and ADGRL3; does not interact with ADGRL3 by itself (PubMed:26235030).By similarity4 Publications
Binary interactionsi
Protein-protein interaction databases
BioGridi | 128567. 10 interactors. |
CORUMi | Q8IZJ1. |
DIPi | DIP-46275N. |
IntActi | Q8IZJ1. 6 interactors. |
STRINGi | 9606.ENSP00000334329. |
Structurei
3D structure databases
ProteinModelPortali | Q8IZJ1. |
SMRi | Q8IZJ1. |
ModBasei | Search... |
MobiDBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 48 – 145 | Ig-likeAdd BLAST | 98 | |
Domaini | 147 – 242 | Ig-like C2-typeAdd BLAST | 96 | |
Domaini | 246 – 300 | TSP type-1 1PROSITE-ProRule annotationAdd BLAST | 55 | |
Domaini | 302 – 354 | TSP type-1 2PROSITE-ProRule annotationAdd BLAST | 53 | |
Domaini | 543 – 686 | ZU5PROSITE-ProRule annotationAdd BLAST | 144 | |
Domaini | 865 – 943 | DeathAdd BLAST | 79 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 689 – 838 | UPA domainBy similarityAdd BLAST | 150 | |
Regioni | 707 – 725 | Interaction with DCCBy similarityAdd BLAST | 19 |
Sequence similaritiesi
Belongs to the unc-5 family.Curated
Keywords - Domaini
Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG1480. Eukaryota. ENOG410XRS6. LUCA. |
GeneTreei | ENSGT00910000144013. |
HOGENOMi | HOG000060306. |
HOVERGENi | HBG056483. |
InParanoidi | Q8IZJ1. |
KOi | K07521. |
OMAi | HEVLLQC. |
OrthoDBi | EOG091G040Q. |
PhylomeDBi | Q8IZJ1. |
TreeFami | TF316767. |
Family and domain databases
Gene3Di | 2.20.100.10. 2 hits. 2.60.40.10. 2 hits. |
InterProi | View protein in InterPro IPR011029. DEATH-like_dom_sf. IPR000488. Death_domain. IPR007110. Ig-like_dom. IPR036179. Ig-like_dom_sf. IPR013783. Ig-like_fold. IPR013098. Ig_I-set. IPR003599. Ig_sub. IPR003598. Ig_sub2. IPR000884. TSP1_rpt. IPR036383. TSP1_rpt_sf. IPR037936. UNC5. IPR033772. UPA. IPR000906. ZU5_dom. |
PANTHERi | PTHR12582. PTHR12582. 1 hit. |
Pfami | View protein in Pfam PF00531. Death. 1 hit. PF07679. I-set. 1 hit. PF00090. TSP_1. 2 hits. PF17217. UPA. 1 hit. PF00791. ZU5. 1 hit. |
SMARTi | View protein in SMART SM00005. DEATH. 1 hit. SM00409. IG. 2 hits. SM00408. IGc2. 1 hit. SM00209. TSP1. 2 hits. SM00218. ZU5. 1 hit. |
SUPFAMi | SSF47986. SSF47986. 1 hit. SSF48726. SSF48726. 2 hits. SSF82895. SSF82895. 2 hits. |
PROSITEi | View protein in PROSITE PS50835. IG_LIKE. 1 hit. PS50092. TSP1. 2 hits. PS51145. ZU5. 1 hit. |
s (2)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basket
Isoform 1 (identifier: Q8IZJ1-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
10 20 30 40 50
MGARSGARGA LLLALLLCWD PRLSQAGTDS GSEVLPDSFP SAPAEPLPYF
60 70 80 90 100
LQEPQDAYIV KNKPVELRCR AFPATQIYFK CNGEWVSQND HVTQEGLDEA
110 120 130 140 150
TGLRVREVQI EVSRQQVEEL FGLEDYWCQC VAWSSAGTTK SRRAYVRIAY
160 170 180 190 200
LRKNFDQEPL GKEVPLDHEV LLQCRPPEGV PVAEVEWLKN EDVIDPTQDT
210 220 230 240 250
NFLLTIDHNL IIRQARLSDT ANYTCVAKNI VAKRRSTTAT VIVYVNGGWS
260 270 280 290 300
SWAEWSPCSN RCGRGWQKRT RTCTNPAPLN GGAFCEGQAF QKTACTTICP
310 320 330 340 350
VDGAWTEWSK WSACSTECAH WRSRECMAPP PQNGGRDCSG TLLDSKNCTD
360 370 380 390 400
GLCMQNKKTL SDPNSHLLEA SGDAALYAGL VVAIFVVVAI LMAVGVVVYR
410 420 430 440 450
RNCRDFDTDI TDSSAALTGG FHPVNFKTAR PSNPQLLHPS VPPDLTASAG
460 470 480 490 500
IYRGPVYALQ DSTDKIPMTN SPLLDPLPSL KVKVYSSSTT GSGPGLADGA
510 520 530 540 550
DLLGVLPPGT YPSDFARDTH FLHLRSASLG SQQLLGLPRD PGSSVSGTFG
560 570 580 590 600
CLGGRLSIPG TGVSLLVPNG AIPQGKFYEM YLLINKAEST LPLSEGTQTV
610 620 630 640 650
LSPSVTCGPT GLLLCRPVIL TMPHCAEVSA RDWIFQLKTQ AHQGHWEEVV
660 670 680 690 700
TLDEETLNTP CYCQLEPRAC HILLDQLGTY VFTGESYSRS AVKRLQLAVF
710 720 730 740 750
APALCTSLEY SLRVYCLEDT PVALKEVLEL ERTLGGYLVE EPKPLMFKDS
760 770 780 790 800
YHNLRLSLHD LPHAHWRSKL LAKYQEIPFY HIWSGSQKAL HCTFTLERHS
810 820 830 840 850
LASTELTCKI CVRQVEGEGQ IFQLHTTLAE TPAGSLDTLC SAPGSTVTTQ
860 870 880 890 900
LGPYAFKIPL SIRQKICNSL DAPNSRGNDW RMLAQKLSMD RYLNYFATKA
910 920 930 940
SPTGVILDLW EALQQDDGDL NSLASALEEM GKSEMLVAVA TDGDC
Sequence cautioni
The sequence BAB14276 differs from that shown. Reason: Erroneous initiation.Curated
The sequence BAC04382 differs from that shown. Reason: Erroneous initiation.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 483 | K → E in BAC04382 (PubMed:12975309).Curated | 1 | |
Sequence conflicti | 851 | L → P in BAB14276 (PubMed:12975309).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_052472 | 242 | I → V. Corresponds to variant dbSNP:rs34957097Ensembl. | 1 | |
Natural variantiVAR_019730 | 516 | A → T. Corresponds to variant dbSNP:rs10509332Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_011698 | 356 – 367 | NKKTL…PNSHL → M in isoform 2. 1 PublicationAdd BLAST | 12 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AY126437 mRNA. Translation: AAM95701.1. AB096256 mRNA. Translation: BAC57998.1. AY358351 mRNA. Translation: AAQ88717.1. AK022859 mRNA. Translation: BAB14276.1. Different initiation. AK094595 mRNA. Translation: BAC04382.1. Different initiation. AK128132 mRNA. Translation: BAG54634.1. AL359384 Genomic DNA. No translation available. AL359832 Genomic DNA. No translation available. CH471083 Genomic DNA. Translation: EAW54420.1. CH471083 Genomic DNA. Translation: EAW54421.1. |
CCDSi | CCDS58083.1. [Q8IZJ1-2] CCDS7309.1. [Q8IZJ1-1] |
RefSeqi | NP_001231818.1. NM_001244889.1. [Q8IZJ1-2] NP_734465.2. NM_170744.4. [Q8IZJ1-1] |
UniGenei | Hs.522997. |
Genome annotation databases
Ensembli | ENST00000335350; ENSP00000334329; ENSG00000107731. [Q8IZJ1-1] ENST00000373192; ENSP00000362288; ENSG00000107731. [Q8IZJ1-2] |
GeneIDi | 219699. |
KEGGi | hsa:219699. |
UCSCi | uc001jro.4. human. [Q8IZJ1-1] |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar proteinsi
Entry informationi
Entry namei | UNC5B_HUMAN | |
Accessioni | Q8IZJ1Primary (citable) accession number: Q8IZJ1 Secondary accession number(s): Q5T3R9 Q9H9F3 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | October 11, 2004 |
Last sequence update: | October 11, 2004 | |
Last modified: | March 28, 2018 | |
This is version 145 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |