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Protein

Netrin receptor UNC5B

Gene

UNC5B

Organism
Homo sapiens (Human)
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 (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

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
  • signal transduction Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Receptor

Keywords - Biological processi

Angiogenesis, Apoptosis

Enzyme and pathway databases

ReactomeiR-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 UNC5B
Alternative 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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

HGNCiHGNC:12568. 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

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi412D → N: Abolishes cleavage by caspase-3 and subsequent induction of apoptosis. 1 Publication1

Organism-specific databases

DisGeNETi219699.
OpenTargetsiENSG00000107731.
PharmGKBiPA37205.

Polymorphism and mutation databases

BioMutaiUNC5B.
DMDMi54036589.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 26Sequence analysisAdd BLAST26
ChainiPRO_000003607127 – 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 cysteineBy similarity1
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.By similarity

Sites

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

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

MaxQBiQ8IZJ1.
PaxDbiQ8IZJ1.
PeptideAtlasiQ8IZJ1.
PRIDEiQ8IZJ1.

PTM databases

iPTMnetiQ8IZJ1.
PhosphoSitePlusiQ8IZJ1.
SwissPalmiQ8IZJ1.

Miscellaneous databases

PMAP-CutDBQ8IZJ1.

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

BgeeiENSG00000107731.
CleanExiHS_UNC5B.
GenevisibleiQ8IZJ1. HS.

Organism-specific databases

HPAiHPA011141.

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

WithEntry#Exp.IntActNotes
Agap2Q8CGU49EBI-4409075,EBI-4409108From a different organism.
NTN1O956312EBI-10832046,EBI-2678626

Protein-protein interaction databases

BioGridi128567. 9 interactors.
DIPiDIP-46275N.
IntActiQ8IZJ1. 5 interactors.
STRINGi9606.ENSP00000334329.

Structurei

3D structure databases

ProteinModelPortaliQ8IZJ1.
SMRiQ8IZJ1.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini48 – 145Ig-likeAdd BLAST98
Domaini147 – 242Ig-like C2-typeAdd BLAST96
Domaini246 – 300TSP type-1 1PROSITE-ProRule annotationAdd BLAST55
Domaini302 – 354TSP type-1 2PROSITE-ProRule annotationAdd BLAST53
Domaini544 – 688ZU5PROSITE-ProRule annotationAdd BLAST145
Domaini865 – 943DeathAdd 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
Contains 1 death domain.Curated
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.
GeneTreeiENSGT00850000132260.
HOGENOMiHOG000060306.
HOVERGENiHBG056483.
InParanoidiQ8IZJ1.
KOiK07521.
OMAiQEIPFCH.
OrthoDBiEOG091G040Q.
PhylomeDBiQ8IZJ1.
TreeFamiTF316767.

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.
PROSITEiPS50835. IG_LIKE. 1 hit.
PS50092. TSP1. 2 hits.
PS51145. ZU5. 1 hit.
[Graphical view]

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: 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.

« Hide

        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
Length:945
Mass (Da):103,638
Last modified:October 11, 2004 - v2
Checksum:i56064E335F323447
GO
Isoform 2 (identifier: Q8IZJ1-2) [UniParc]FASTAAdd to basket

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

Show »
Length:934
Mass (Da):102,434
Checksum:i225B3F506D52B780
GO

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 keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti483K → E in BAC04382 (PubMed:12975309).Curated1
Sequence conflicti851L → P in BAB14276 (PubMed:12975309).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_052472242I → V.Corresponds to variant rs34957097dbSNPEnsembl.1
Natural variantiVAR_019730516A → T.Corresponds to variant rs10509332dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_011698356 – 367NKKTL…PNSHL → M in isoform 2. 1 PublicationAdd BLAST12

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, AL359832 Genomic DNA. Translation: CAI16089.1.
AL359384, AL359832 Genomic DNA. Translation: CAI16090.1.
AL359832, AL359384 Genomic DNA. Translation: CAI16737.1.
AL359832, AL359384 Genomic DNA. Translation: CAI16738.1.
CH471083 Genomic DNA. Translation: EAW54420.1.
CH471083 Genomic DNA. Translation: EAW54421.1.
CCDSiCCDS58083.1. [Q8IZJ1-2]
CCDS7309.1. [Q8IZJ1-1]
RefSeqiNP_001231818.1. NM_001244889.1. [Q8IZJ1-2]
NP_734465.2. NM_170744.4. [Q8IZJ1-1]
UniGeneiHs.522997.

Genome annotation databases

EnsembliENST00000335350; ENSP00000334329; ENSG00000107731. [Q8IZJ1-1]
ENST00000373192; ENSP00000362288; ENSG00000107731. [Q8IZJ1-2]
GeneIDi219699.
KEGGihsa:219699.
UCSCiuc001jro.4. human. [Q8IZJ1-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

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, AL359832 Genomic DNA. Translation: CAI16089.1.
AL359384, AL359832 Genomic DNA. Translation: CAI16090.1.
AL359832, AL359384 Genomic DNA. Translation: CAI16737.1.
AL359832, AL359384 Genomic DNA. Translation: CAI16738.1.
CH471083 Genomic DNA. Translation: EAW54420.1.
CH471083 Genomic DNA. Translation: EAW54421.1.
CCDSiCCDS58083.1. [Q8IZJ1-2]
CCDS7309.1. [Q8IZJ1-1]
RefSeqiNP_001231818.1. NM_001244889.1. [Q8IZJ1-2]
NP_734465.2. NM_170744.4. [Q8IZJ1-1]
UniGeneiHs.522997.

3D structure databases

ProteinModelPortaliQ8IZJ1.
SMRiQ8IZJ1.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi128567. 9 interactors.
DIPiDIP-46275N.
IntActiQ8IZJ1. 5 interactors.
STRINGi9606.ENSP00000334329.

PTM databases

iPTMnetiQ8IZJ1.
PhosphoSitePlusiQ8IZJ1.
SwissPalmiQ8IZJ1.

Polymorphism and mutation databases

BioMutaiUNC5B.
DMDMi54036589.

Proteomic databases

MaxQBiQ8IZJ1.
PaxDbiQ8IZJ1.
PeptideAtlasiQ8IZJ1.
PRIDEiQ8IZJ1.

Protocols and materials databases

DNASUi219699.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000335350; ENSP00000334329; ENSG00000107731. [Q8IZJ1-1]
ENST00000373192; ENSP00000362288; ENSG00000107731. [Q8IZJ1-2]
GeneIDi219699.
KEGGihsa:219699.
UCSCiuc001jro.4. human. [Q8IZJ1-1]

Organism-specific databases

CTDi219699.
DisGeNETi219699.
GeneCardsiUNC5B.
HGNCiHGNC:12568. UNC5B.
HPAiHPA011141.
MIMi607870. gene.
neXtProtiNX_Q8IZJ1.
OpenTargetsiENSG00000107731.
PharmGKBiPA37205.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1480. Eukaryota.
ENOG410XRS6. LUCA.
GeneTreeiENSGT00850000132260.
HOGENOMiHOG000060306.
HOVERGENiHBG056483.
InParanoidiQ8IZJ1.
KOiK07521.
OMAiQEIPFCH.
OrthoDBiEOG091G040Q.
PhylomeDBiQ8IZJ1.
TreeFamiTF316767.

Enzyme and pathway databases

ReactomeiR-HSA-373752. Netrin-1 signaling.
R-HSA-418886. Netrin mediated repulsion signals.
R-HSA-418889. Ligand-independent caspase activation via DCC.

Miscellaneous databases

ChiTaRSiUNC5B. human.
GenomeRNAii219699.
PMAP-CutDBQ8IZJ1.
PROiQ8IZJ1.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000107731.
CleanExiHS_UNC5B.
GenevisibleiQ8IZJ1. HS.

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.
PROSITEiPS50835. IG_LIKE. 1 hit.
PS50092. TSP1. 2 hits.
PS51145. ZU5. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiUNC5B_HUMAN
AccessioniPrimary (citable) accession number: Q8IZJ1
Secondary accession number(s): Q5T3R9
, Q5T3S0, Q86SN3, Q8N1Y2, Q9H9F3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 11, 2004
Last sequence update: October 11, 2004
Last modified: November 30, 2016
This is version 134 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Miscellaneous

Down-regulated in multiple cancers including colorectal, breast, ovary, uterus, stomach, lung, or kidney cancers.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. 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.