Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Netrin receptor UNC5B

Gene

UNC5B

Organism
Homo sapiens (Human)
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. 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

GO - Biological processi

Keywordsi

Molecular functionDevelopmental protein, Receptor
Biological processAngiogenesis, Apoptosis

Enzyme and pathway databases

ReactomeiR-HSA-373752 Netrin-1 signaling
R-HSA-418886 Netrin mediated repulsion signals
R-HSA-418889 via Dependence Receptors in the absence of ligand

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

EuPathDBiHostDB:ENSG00000107731.12
HGNCiHGNC:12568 UNC5B
MIMi607870 gene
neXtProtiNX_Q8IZJ1

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

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...) 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
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

EPDiQ8IZJ1
MaxQBiQ8IZJ1
PaxDbiQ8IZJ1
PeptideAtlasiQ8IZJ1
PRIDEiQ8IZJ1
ProteomicsDBi71355
71356 [Q8IZJ1-2]

PTM databases

iPTMnetiQ8IZJ1
PhosphoSitePlusiQ8IZJ1
SwissPalmiQ8IZJ1

Miscellaneous databases

PMAP-CutDBiQ8IZJ1

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 Expressed in 220 organ(s), highest expression level in inferior vagus X ganglion
CleanExiHS_UNC5B
GenevisibleiQ8IZJ1 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

BioGridi128567, 10 interactors
CORUMiQ8IZJ1
DIPiDIP-46275N
IntActiQ8IZJ1, 10 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
Domaini543 – 686ZU5PROSITE-ProRule annotationAdd BLAST144
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

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1480 Eukaryota
ENOG410XRS6 LUCA
GeneTreeiENSGT00920000149006
HOGENOMiHOG000060306
HOVERGENiHBG056483
InParanoidiQ8IZJ1
KOiK07521
OMAiGPMYALQ
OrthoDBiEOG091G040Q
PhylomeDBiQ8IZJ1
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
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: 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 dbSNP:rs34957097Ensembl.1
Natural variantiVAR_019730516A → T. Corresponds to variant dbSNP:rs10509332Ensembl.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 Genomic DNA No translation available.
AL359832 Genomic DNA No translation available.
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

Similar proteinsi

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 Genomic DNA No translation available.
AL359832 Genomic DNA No translation available.
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, 10 interactors
CORUMiQ8IZJ1
DIPiDIP-46275N
IntActiQ8IZJ1, 10 interactors
STRINGi9606.ENSP00000334329

PTM databases

iPTMnetiQ8IZJ1
PhosphoSitePlusiQ8IZJ1
SwissPalmiQ8IZJ1

Polymorphism and mutation databases

BioMutaiUNC5B
DMDMi54036589

Proteomic databases

EPDiQ8IZJ1
MaxQBiQ8IZJ1
PaxDbiQ8IZJ1
PeptideAtlasiQ8IZJ1
PRIDEiQ8IZJ1
ProteomicsDBi71355
71356 [Q8IZJ1-2]

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
EuPathDBiHostDB:ENSG00000107731.12
GeneCardsiUNC5B
HGNCiHGNC:12568 UNC5B
MIMi607870 gene
neXtProtiNX_Q8IZJ1
OpenTargetsiENSG00000107731
PharmGKBiPA37205
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1480 Eukaryota
ENOG410XRS6 LUCA
GeneTreeiENSGT00920000149006
HOGENOMiHOG000060306
HOVERGENiHBG056483
InParanoidiQ8IZJ1
KOiK07521
OMAiGPMYALQ
OrthoDBiEOG091G040Q
PhylomeDBiQ8IZJ1
TreeFamiTF316767

Enzyme and pathway databases

ReactomeiR-HSA-373752 Netrin-1 signaling
R-HSA-418886 Netrin mediated repulsion signals
R-HSA-418889 via Dependence Receptors in the absence of ligand

Miscellaneous databases

ChiTaRSiUNC5B human
GenomeRNAii219699
PMAP-CutDBiQ8IZJ1
PROiPR:Q8IZJ1
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000107731 Expressed in 220 organ(s), highest expression level in inferior vagus X ganglion
CleanExiHS_UNC5B
GenevisibleiQ8IZJ1 HS

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
PS50835 IG_LIKE, 1 hit
PS50092 TSP1, 2 hits
PS51145 ZU5, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiUNC5B_HUMAN
AccessioniPrimary (citable) accession number: Q8IZJ1
Secondary accession number(s): Q5T3R9
, Q5T3S0, Q86SN3, Q8N1Y2, Q9H9F3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 11, 2004
Last sequence update: October 11, 2004
Last modified: November 7, 2018
This is version 150 of the entry and version 2 of the sequence. See 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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again