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Protein

Netrin receptor UNC5B

Gene

Unc5b

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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 (PubMed:10399920, PubMed:9126742). 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:11387206). Mediates apoptosis by activating DAPK1 (PubMed:18582460). In the absence of NTN1, activates DAPK1 by reducing its autoinhibitory phosphorylation at Ser-308 thereby increasing its catalytic activity (PubMed:15729359).By similarity1 Publication4 Publications

GO - Molecular functioni

  • netrin receptor activity Source: RGD

GO - Biological processi

  • apoptotic process Source: UniProtKB-KW
  • axon guidance Source: RGD
  • positive regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Receptor

Keywords - Biological processi

Apoptosis

Enzyme and pathway databases

ReactomeiR-RNO-373752. Netrin-1 signaling.

Names & Taxonomyi

Protein namesi
Recommended name:
Netrin receptor UNC5B
Alternative name(s):
Protein unc-5 homolog 2
Protein unc-5 homolog B
Gene namesi
Name:Unc5b
Synonyms:Unc5h2
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi621756. Unc5b.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini27 – 377ExtracellularSequence analysisAdd BLAST351
Transmembranei378 – 398HelicalSequence analysisAdd BLAST21
Topological domaini399 – 945CytoplasmicSequence analysisAdd BLAST547

GO - Cellular componenti

  • integral component of membrane Source: UniProtKB-KW
  • membrane raft Source: UniProtKB
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi403C → V: Abolishes palmitoylation. Impairs interaction with DAPK1. No effect on location on lipid rafts. 1 Publication1
Mutagenesisi412D → N: Abolishes cleavage by caspase-3 and subsequent induction of apoptosis. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 26Sequence analysisAdd BLAST26
ChainiPRO_000003607327 – 945Netrin receptor UNC5BAdd BLAST919

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi69 ↔ 130By similarity
Disulfide bondi81 ↔ 128By similarity
Disulfide bondi174 ↔ 225By similarity
Glycosylationi222N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi258 ↔ 295By similarity
Disulfide bondi262 ↔ 299By similarity
Disulfide bondi273 ↔ 285By similarity
Disulfide bondi314 ↔ 348By similarity
Disulfide bondi318 ↔ 353By similarity
Disulfide bondi326 ↔ 338By similarity
Glycosylationi347N-linked (GlcNAc...)Sequence analysis1
Lipidationi403S-palmitoyl cysteine1 Publication1
Modified residuei581PhosphotyrosineBy similarity1

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.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei412 – 413Cleavage; by caspase-31 Publication2

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

PaxDbiO08722.
PRIDEiO08722.

PTM databases

iPTMnetiO08722.
PhosphoSitePlusiO08722.

Miscellaneous databases

PMAP-CutDBO08722.

Expressioni

Tissue specificityi

Mainly expressed in regions of differentiating neurons. Expressed in the developing sensory ganglia that flank the spinal cord from E12, peaking at E14. Expressed in the roof plate region of the spinal cord from E14.1 Publication

Interactioni

Subunit structurei

Interacts with the cytoplasmic part of DCC (PubMed:10399920). Interacts with GNAI2 via its cytoplasmic part (By similarity). 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. Interacts (via extracellular domain) with FLRT2 and FLRT3 (via extracellular domain), but has higher affinity for FLRT3. Identified in a complex with FLRT3 and ADGRL3; does not interact with ADGRL3 by itself (By similarity).By similarity3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Agap2Q8CGU46EBI-4404185,EBI-4409108
PPP2R1BP301544EBI-4404185,EBI-357094From a different organism.

Protein-protein interaction databases

DIPiDIP-60743N.
IntActiO08722. 3 interactors.
STRINGi10116.ENSRNOP00000034951.

Structurei

Secondary structure

1945
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi544 – 549Combined sources6
Beta strandi554 – 558Combined sources5
Turni559 – 562Combined sources4
Beta strandi563 – 567Combined sources5
Beta strandi578 – 584Combined sources7
Helixi587 – 593Combined sources7
Beta strandi598 – 600Combined sources3
Beta strandi605 – 608Combined sources4
Beta strandi618 – 623Combined sources6
Beta strandi629 – 631Combined sources3
Beta strandi634 – 642Combined sources9
Beta strandi646 – 651Combined sources6
Beta strandi660 – 665Combined sources6
Beta strandi667 – 676Combined sources10
Beta strandi678 – 685Combined sources8
Beta strandi692 – 703Combined sources12
Beta strandi707 – 720Combined sources14
Helixi721 – 734Combined sources14
Beta strandi736 – 738Combined sources3
Beta strandi743 – 751Combined sources9
Beta strandi754 – 759Combined sources6
Turni763 – 765Combined sources3
Beta strandi766 – 768Combined sources3
Beta strandi771 – 773Combined sources3
Beta strandi775 – 777Combined sources3
Helixi779 – 783Combined sources5
Beta strandi791 – 800Combined sources10
Beta strandi805 – 814Combined sources10
Beta strandi819 – 827Combined sources9
Beta strandi849 – 851Combined sources3
Turni852 – 855Combined sources4
Helixi860 – 870Combined sources11
Helixi880 – 886Combined sources7
Turni891 – 893Combined sources3
Helixi894 – 897Combined sources4
Helixi902 – 914Combined sources13
Helixi920 – 929Combined sources10
Helixi934 – 940Combined sources7

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3G5BX-ray2.00A541-945[»]
ProteinModelPortaliO08722.
SMRiO08722.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO08722.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini48 – 145Ig-likeAdd BLAST98
Domaini153 – 242Ig-like C2-typeAdd BLAST90
Domaini246 – 300TSP type-1 1PROSITE-ProRule annotationAdd BLAST55
Domaini302 – 354TSP type-1 2PROSITE-ProRule annotationAdd BLAST53
Domaini544 – 688ZU5PROSITE-ProRule annotationAdd BLAST145
Domaini865 – 943DeathPROSITE-ProRule annotationAdd BLAST79

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni689 – 838UPA domainAdd BLAST150
Regioni707 – 725Interaction with DCC1 PublicationAdd BLAST19

Sequence similaritiesi

Belongs to the unc-5 family.Curated
Contains 1 death domain.PROSITE-ProRule annotation
Contains 2 TSP type-1 domains.PROSITE-ProRule annotation
Contains 1 ZU5 domain.PROSITE-ProRule annotation

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1480. Eukaryota.
ENOG410XRS6. LUCA.
HOGENOMiHOG000060306.
HOVERGENiHBG056483.
InParanoidiO08722.
KOiK07521.
PhylomeDBiO08722.

Family and domain databases

Gene3Di1.10.533.10. 1 hit.
2.60.40.10. 2 hits.
InterProiIPR011029. DEATH-like_dom.
IPR000488. Death_domain.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR000884. TSP1_rpt.
IPR033772. UPA.
IPR000906. ZU5_dom.
[Graphical view]
PfamiPF00531. Death. 1 hit.
PF07679. I-set. 1 hit.
PF00090. TSP_1. 2 hits.
PF17217. UPA. 1 hit.
PF00791. ZU5. 1 hit.
[Graphical view]
SMARTiSM00005. DEATH. 1 hit.
SM00409. IG. 2 hits.
SM00408. IGc2. 1 hit.
SM00209. TSP1. 2 hits.
SM00218. ZU5. 1 hit.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
SSF48726. SSF48726. 2 hits.
SSF82895. SSF82895. 2 hits.
PROSITEiPS50017. DEATH_DOMAIN. 1 hit.
PS50835. IG_LIKE. 1 hit.
PS50092. TSP1. 2 hits.
PS51145. ZU5. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

O08722-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRARSGARGA LLLALLLCWD PTPSLAGIDS GGQALPDSFP SAPAEQLPHF
60 70 80 90 100
LLEPEDAYIV KNKPVELHCR AFPATQIYFK CNGEWVSQKG HVTQESLDEA
110 120 130 140 150
TGLRIREVQI EVSRQQVEEL FGLEDYWCQC VAWSSSGTTK SRRAYIRIAY
160 170 180 190 200
LRKNFDQEPL AKEVPLDHEV LLQCRPPEGV PVAEVEWLKN EDVIDPAQDT
210 220 230 240 250
NFLLTIDHNL IIRQARLSDT ANYTCVAKNI VAKRRSTTAT VIVYVNGGWS
260 270 280 290 300
SWAEWSPCSN RCGRGWQKRT RTCTNPAPLN GGAFCEGQAC QKTACTTVCP
310 320 330 340 350
VDGAWTEWSK WSACSTECAH WRSRECMAPP PQNGGRDCSG TLLDSKNCTD
360 370 380 390 400
GLCVLNQRTL NDPKSRPLEP SGDVALYAGL VVAVFVVLAV LMAVGVIVYR
410 420 430 440 450
RNCRDFDTDI TDSSAALTGG FHPVNFKTAR PSNPQLLHPS APPDLTASAG
460 470 480 490 500
IYRGPVYALQ DSADKIPMTN SPLLDPLPSL KIKVYDSSTI GSGAGLADGA
510 520 530 540 550
DLLGVLPPGT YPGDFSRDTH FLHLRSASLG SQHLLGLPRD PSSSVSGTFG
560 570 580 590 600
CLGGRLTIPG TGVSLLVPNG AIPQGKFYDL YLRINKTEST LPLSEGSQTV
610 620 630 640 650
LSPSVTCGPT GLLLCRPVVL TVPHCAEVIA GDWIFQLKTQ AHQGHWEEVV
660 670 680 690 700
TLDEETLNTP CYCQLEAKSC HILLDQLGTY VFTGESYSRS AVKRLQLAIF
710 720 730 740 750
APALCTSLEY SLRVYCLEDT PAALKEVLEL ERTLGGYLVE EPKTLLFKDS
760 770 780 790 800
YHNLRLSLHD IPHAHWRSKL LAKYQEIPFY HVWNGSQKAL HCTFTLERHS
810 820 830 840 850
LASTEFTCKV CVRQVEGEGQ IFQLHTTLAE TPAGSLDALC SAPGNAATTQ
860 870 880 890 900
LGPYAFKIPL SIRQKICNSL DAPNSRGNDW RLLAQKLSMD RYLNYFATKA
910 920 930 940
SPTGVILDLW EARQQDDGDL NSLASALEEM GKSEMLVAMT TDGDC
Length:945
Mass (Da):103,521
Last modified:July 1, 1997 - v1
Checksum:i6E9C2A262E560B9B
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U87306 mRNA. Translation: AAB57679.1.
RefSeqiNP_071543.1. NM_022207.1.
UniGeneiRn.34617.

Genome annotation databases

GeneIDi60630.
KEGGirno:60630.
UCSCiRGD:621756. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U87306 mRNA. Translation: AAB57679.1.
RefSeqiNP_071543.1. NM_022207.1.
UniGeneiRn.34617.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3G5BX-ray2.00A541-945[»]
ProteinModelPortaliO08722.
SMRiO08722.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-60743N.
IntActiO08722. 3 interactors.
STRINGi10116.ENSRNOP00000034951.

PTM databases

iPTMnetiO08722.
PhosphoSitePlusiO08722.

Proteomic databases

PaxDbiO08722.
PRIDEiO08722.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi60630.
KEGGirno:60630.
UCSCiRGD:621756. rat.

Organism-specific databases

CTDi219699.
RGDi621756. Unc5b.

Phylogenomic databases

eggNOGiKOG1480. Eukaryota.
ENOG410XRS6. LUCA.
HOGENOMiHOG000060306.
HOVERGENiHBG056483.
InParanoidiO08722.
KOiK07521.
PhylomeDBiO08722.

Enzyme and pathway databases

ReactomeiR-RNO-373752. Netrin-1 signaling.

Miscellaneous databases

EvolutionaryTraceiO08722.
PMAP-CutDBO08722.
PROiO08722.

Family and domain databases

Gene3Di1.10.533.10. 1 hit.
2.60.40.10. 2 hits.
InterProiIPR011029. DEATH-like_dom.
IPR000488. Death_domain.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR000884. TSP1_rpt.
IPR033772. UPA.
IPR000906. ZU5_dom.
[Graphical view]
PfamiPF00531. Death. 1 hit.
PF07679. I-set. 1 hit.
PF00090. TSP_1. 2 hits.
PF17217. UPA. 1 hit.
PF00791. ZU5. 1 hit.
[Graphical view]
SMARTiSM00005. DEATH. 1 hit.
SM00409. IG. 2 hits.
SM00408. IGc2. 1 hit.
SM00209. TSP1. 2 hits.
SM00218. ZU5. 1 hit.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
SSF48726. SSF48726. 2 hits.
SSF82895. SSF82895. 2 hits.
PROSITEiPS50017. DEATH_DOMAIN. 1 hit.
PS50835. IG_LIKE. 1 hit.
PS50092. TSP1. 2 hits.
PS51145. ZU5. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiUNC5B_RAT
AccessioniPrimary (citable) accession number: O08722
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 11, 2004
Last sequence update: July 1, 1997
Last modified: November 30, 2016
This is version 124 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.