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Protein

Netrin receptor UNC5B

Gene

Unc5b

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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 (By similarity). Functions as netrin receptor that negatively regulates vascular branching during angiogenesis (PubMed:15510105). Mediates retraction of tip cell filopodia on endothelial growth cones in response to netrin (PubMed:15510105). It also acts as a dependence receptor required for apoptosis induction when not associated with netrin ligand. 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

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionDevelopmental protein, Receptor
Biological processAngiogenesis, Apoptosis

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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:894703 Unc5b

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

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

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Disruption phenotypei

Complete embryonic lethality, due to defects in blood vessel development that lead to heart failure. Mutant embryos display increased branching of the internal carotid artery and of blood vessels in the nervous system, including thinner and more highly branched brain capillaries. Endothelial tip cells present an increased number of filopodia.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 26Sequence analysisAdd BLAST26
ChainiPRO_000003607227 – 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...) asparagineSequence 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...) asparagineSequence analysis1
Lipidationi403S-palmitoyl cysteineBy similarity1
Modified residuei581PhosphotyrosineBy similarity1

Post-translational modificationi

Phosphorylated on cytoplasmic tyrosine residues.By similarity
Palmitoylation is required for pro-apoptotic activity, but not for location at lipid rafts.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.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei412 – 413Cleavage; by caspase-3By similarity2

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

PaxDbiQ8K1S3
PRIDEiQ8K1S3

PTM databases

iPTMnetiQ8K1S3
PhosphoSitePlusiQ8K1S3

Expressioni

Tissue specificityi

Highly expressed in brain. Expressed in lung during late development. Expressed during early blood vessel formation, in the semicircular canal and in a dorsal to ventral gradient in the retina.3 Publications

Gene expression databases

BgeeiENSMUSG00000020099
CleanExiMM_UNC5B
GenevisibleiQ8K1S3 MM

Interactioni

Subunit structurei

Interacts with the cytoplasmic part of DCC (By similarity). Interacts with GNAI2 via its cytoplasmic part. Interacts (via death domain) with DAPK1 (via death domain) (By similarity). Interacts (via extracellular domain) with FLRT2 and FLRT3 (via extracellular domain), but has higher affinity for FLRT3 (PubMed:19492039, PubMed:21673655, PubMed:22405201, PubMed:25374360). Identified in a complex with FLRT3 and ADGRL3; does not interact with ADGRL3 by itself (By similarity).By similarity4 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi223296, 5 interactors
IntActiQ8K1S3, 3 interactors
STRINGi10090.ENSMUSP00000077080

Structurei

Secondary structure

1945
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi860 – 871Combined sources12
Helixi873 – 875Combined sources3
Helixi880 – 886Combined sources7
Helixi890 – 892Combined sources3
Helixi893 – 897Combined sources5
Helixi902 – 913Combined sources12
Turni917 – 919Combined sources3
Helixi920 – 929Combined sources10
Helixi933 – 941Combined sources9

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1WMGX-ray2.10A/B/C/D/E/F854-943[»]
ProteinModelPortaliQ8K1S3
SMRiQ8K1S3
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ8K1S3

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
Domaini543 – 686ZU5PROSITE-ProRule annotationAdd BLAST144
Domaini865 – 943DeathPROSITE-ProRule annotationAdd BLAST79

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni689 – 838UPA domainBy similarityAdd BLAST150
Regioni707 – 725Interaction with DCCBy similarityAdd BLAST19

Sequence similaritiesi

Belongs to the unc-5 family.Curated

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1480 Eukaryota
ENOG410XRS6 LUCA
GeneTreeiENSGT00910000144013
HOGENOMiHOG000060306
HOVERGENiHBG056483
InParanoidiQ8K1S3
KOiK07521
OMAiHEVLLQC
OrthoDBiEOG091G040Q
PhylomeDBiQ8K1S3
TreeFamiTF316767

Family and domain databases

Gene3Di2.20.100.10, 2 hits
2.60.40.10, 2 hits
InterProiView 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
PANTHERiPTHR12582 PTHR12582, 1 hit
PfamiView 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
SMARTiView protein in SMART
SM00005 DEATH, 1 hit
SM00409 IG, 2 hits
SM00408 IGc2, 1 hit
SM00209 TSP1, 2 hits
SM00218 ZU5, 1 hit
SUPFAMiSSF47986 SSF47986, 1 hit
SSF48726 SSF48726, 2 hits
SSF82895 SSF82895, 2 hits
PROSITEiView protein in PROSITE
PS50017 DEATH_DOMAIN, 1 hit
PS50835 IG_LIKE, 1 hit
PS50092 TSP1, 2 hits
PS51145 ZU5, 1 hit

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8K1S3-1) [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.

« Hide

        10         20         30         40         50
MRARSGVRSA LLLALLLCWD PTPSLAGVDS AGQVLPDSYP SAPAEQLPYF
60 70 80 90 100
LLEPQDAYIV KNKPVELHCR AFPATQIYFK CNGEWVSQND HVTQESLDEA
110 120 130 140 150
TGLRVREVQI 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 GGAFCEGQAF QKTACTTVCP
310 320 330 340 350
VDGAWTEWSK WSACSTECAH WRSRECMAPP PQNGGRDCSG TLLDSKNCTD
360 370 380 390 400
GLCVLNQRTL NDPKSHPLET SGDVALYAGL VVAVFVVVAV LMAVGVIVYR
410 420 430 440 450
RNCRDFDTDI TDSSAALTGG FHPVNFKTAR PNNPQLLHPS APPDLTASAG
460 470 480 490 500
IYRGPVYALQ DSADKIPMTN SPLLDPLPSL KIKVYNSSTI GSGSGLADGA
510 520 530 540 550
DLLGVLPPGT YPGDFSRDTH FLHLRSASLG SQHLLGLPRD PSSSVSGTFG
560 570 580 590 600
CLGGRLSLPG TGVSLLVPNG AIPQGKFYDL YLHINKAEST LPLSEGSQTV
610 620 630 640 650
LSPSVTCGPT GLLLCRPVVL TVPHCAEVIA GDWIFQLKTQ AHQGHWEEVV
660 670 680 690 700
TLDEETLNTP CYCQLEAKSC HILLDQLGTY VFMGESYSRS AVKRLQLAIF
710 720 730 740 750
APALCTSLEY SLRVYCLEDT PVALKEVLEL ERTLGGYLVE EPKPLLFKDS
760 770 780 790 800
YHNLRLSLHD IPHAHWRSKL LAKYQEIPFY HVWNGSQRAL HCTFTLERHS
810 820 830 840 850
LASTEFTCKV CVRQVEGEGQ IFQLHTTLAE TPAGSLDALC SAPGNAITTQ
860 870 880 890 900
LGPYAFKIPL SIRQKICSSL DAPNSRGNDW RLLAQKLSMD RYLNYFATKA
910 920 930 940
SPTGVILDLW EARQQDDGDL NSLASALEEM GKSEMLVAMA TDGDC
Length:945
Mass (Da):103,739
Last modified:October 1, 2002 - v1
Checksum:i80E896F0F0E06012
GO
Isoform 2 (identifier: Q8K1S3-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     356-367: NQRTLNDPKSHP → T

Show »
Length:934
Mass (Da):102,452
Checksum:iE92DB6288F013C98
GO

Sequence cautioni

The sequence AAH48162 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti238T → A in BAB31108 (PubMed:16141072).Curated1
Sequence conflicti394V → E in BAB31108 (PubMed:16141072).Curated1
Sequence conflicti679T → S in BAB31108 (PubMed:16141072).Curated1
Sequence conflicti874N → D in BAB31108 (PubMed:16141072).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_011699356 – 367NQRTL…PKSHP → T in isoform 2. 1 PublicationAdd BLAST12

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ487853 mRNA Translation: CAD32251.1
AK018177 mRNA Translation: BAB31108.1
AK154271 mRNA Translation: BAE32479.1
BC048162 mRNA Translation: AAH48162.1 Different initiation.
BC057560 mRNA Translation: AAH57560.1
CCDSiCCDS23872.1 [Q8K1S3-1]
RefSeqiNP_084046.2, NM_029770.2 [Q8K1S3-1]
XP_006513091.1, XM_006513028.3
UniGeneiMm.290433

Genome annotation databases

EnsembliENSMUST00000077925; ENSMUSP00000077080; ENSMUSG00000020099 [Q8K1S3-1]
ENSMUST00000218637; ENSMUSP00000151251; ENSMUSG00000020099 [Q8K1S3-2]
GeneIDi107449
KEGGimmu:107449
UCSCiuc007ffd.1 mouse [Q8K1S3-2]
uc007ffe.1 mouse [Q8K1S3-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiUNC5B_MOUSE
AccessioniPrimary (citable) accession number: Q8K1S3
Secondary accession number(s): Q3U4F2
, Q6PFH0, Q80Y85, Q9D398
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 11, 2004
Last sequence update: October 1, 2002
Last modified: April 25, 2018
This is version 136 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

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