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Protein

Netrin receptor UNC5D

Gene

UNC5D

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Receptor for the netrin NTN4 that promotes neuronal cell survival (By similarity). Plays a role in cell-cell adhesion and cell guidance. Receptor for netrin involved in cell migration. Plays a role in axon guidance by mediating axon repulsion of neuronal growth cones in the developing nervous system upon ligand binding (By similarity). May play a role in apoptosis in response to DNA damage (PubMed:24691657). It also acts as a dependence receptor required for apoptosis induction when not associated with netrin ligand (PubMed:24519068). Mediates cell-cell adhesion via its interaction with FLRT3 on an adjacent cell (By similarity).By similarity2 Publications

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Receptor

Keywords - Biological processi

Apoptosis

Enzyme and pathway databases

ReactomeiR-HSA-418886. Netrin mediated repulsion signals.

Names & Taxonomyi

Protein namesi
Recommended name:
Netrin receptor UNC5D
Alternative name(s):
Protein unc-5 homolog 4
Protein unc-5 homolog D
Gene namesi
Name:UNC5D
Synonyms:KIAA1777, UNC5H41 Publication
ORF Names:UNQ6012/PRO34692
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

HGNCiHGNC:18634. UNC5D.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini33 – 379347ExtracellularSequence analysisAdd
BLAST
Transmembranei380 – 40021HelicalSequence analysisAdd
BLAST
Topological domaini401 – 953553CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA38612.

Polymorphism and mutation databases

BioMutaiUNC5D.
DMDMi54036576.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 3232Sequence analysisAdd
BLAST
Chaini33 – 953921Netrin receptor UNC5DPRO_0000036079Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi75 ↔ 136By similarity
Disulfide bondi87 ↔ 134By similarity
Glycosylationi117 – 1171N-linked (GlcNAc...)Sequence analysis
Disulfide bondi180 ↔ 231By similarity
Glycosylationi228 – 2281N-linked (GlcNAc...)Sequence analysis
Disulfide bondi264 ↔ 301By similarity
Disulfide bondi268 ↔ 305By similarity
Disulfide bondi279 ↔ 291By similarity
Disulfide bondi320 ↔ 354By similarity
Disulfide bondi324 ↔ 359By similarity
Disulfide bondi332 ↔ 344By similarity
Glycosylationi353 – 3531N-linked (GlcNAc...)Sequence analysis
Glycosylationi376 – 3761N-linked (GlcNAc...)Sequence analysis

Post-translational modificationi

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei416 – 4172Cleavage; by caspase-3Curated

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ6UXZ4.
PeptideAtlasiQ6UXZ4.
PRIDEiQ6UXZ4.

PTM databases

iPTMnetiQ6UXZ4.
PhosphoSiteiQ6UXZ4.

Expressioni

Inductioni

Up-regulated by p53/TP53 in response to DNA damage.1 Publication

Gene expression databases

BgeeiQ6UXZ4.
CleanExiHS_UNC5D.
ExpressionAtlasiQ6UXZ4. baseline and differential.
GenevisibleiQ6UXZ4. HS.

Organism-specific databases

HPAiHPA042940.

Interactioni

Subunit structurei

Interacts (via extracellular domain) with FLRT2 (via extracellular domain); the interaction is direct (By similarity). Interacts (via extracellular domain) with FLRT3 (via extracellular domain); the interaction is direct (PubMed:26235030). Identified in a complex with FLRT3 and ADGRL3; does not interact with ADGRL3 by itself (PubMed:26235030).By similarity1 Publication

Protein-protein interaction databases

STRINGi9606.ENSP00000385143.

Structurei

3D structure databases

ProteinModelPortaliQ6UXZ4.
SMRiQ6UXZ4. Positions 52-364, 545-928.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini54 – 15198Ig-likeAdd
BLAST
Domaini153 – 24492Ig-like C2-typeAdd
BLAST
Domaini252 – 30655TSP type-1 1PROSITE-ProRule annotationAdd
BLAST
Domaini308 – 36053TSP type-1 2PROSITE-ProRule annotationAdd
BLAST
Domaini540 – 645106ZU5PROSITE-ProRule annotationAdd
BLAST
Domaini859 – 93678DeathAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni91 – 933Important for interaction with FLRT2By similarity

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.
GeneTreeiENSGT00840000129679.
HOGENOMiHOG000060306.
HOVERGENiHBG056483.
InParanoidiQ6UXZ4.
KOiK07521.
OrthoDBiEOG7BGHJX.
PhylomeDBiQ6UXZ4.
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.
IPR000906. ZU5_dom.
[Graphical view]
PfamiPF00531. Death. 1 hit.
PF07679. I-set. 1 hit.
PF00090. TSP_1. 2 hits.
PF00791. ZU5. 1 hit.
[Graphical view]
SMARTiSM00005. DEATH. 1 hit.
SM00409. IG. 1 hit.
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: Q6UXZ4-1) [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
MGRAAATAGG GGGARRWLPW LGLCFWAAGT AAARGTDNGE ALPESIPSAP
60 70 80 90 100
GTLPHFIEEP DDAYIIKSNP IALRCKARPA MQIFFKCNGE WVHQNEHVSE
110 120 130 140 150
ETLDESSGLK VREVFINVTR QQVEDFHGPE DYWCQCVAWS HLGTSKSRKA
160 170 180 190 200
SVRIAYLRKN FEQDPQGREV PIEGMIVLHC RPPEGVPAAE VEWLKNEEPI
210 220 230 240 250
DSEQDENIDT RADHNLIIRQ ARLSDSGNYT CMAANIVAKR RSLSATVVVY
260 270 280 290 300
VNGGWSSWTE WSACNVRCGR GWQKRSRTCT NPAPLNGGAF CEGMSVQKIT
310 320 330 340 350
CTSLCPVDGS WEVWSEWSVC SPECEHLRIR ECTAPPPRNG GKFCEGLSQE
360 370 380 390 400
SENCTDGLCI LDKKPLHEIK PQSIENASDI ALYSGLGAAV VAVAVLVIGV
410 420 430 440 450
TLYRRSQSDY GVDVIDSSAL TGGFQTFNFK TVRQGNSLLL NSAMQPDLTV
460 470 480 490 500
SRTYSGPICL QDPLDKELMT ESSLFNPLSD IKVKVQSSFM VSLGVSERAE
510 520 530 540 550
YHGKNHSRTF PHGNNHSFST MHPRNKMPYI QNLSSLPTRT ELRTTGVFGH
560 570 580 590 600
LGGRLVMPNT GVSLLIPHGA IPEENSWEIY MSINQGEPSL QSDGSEVLLS
610 620 630 640 650
PEVTCGPPDM IVTTPFALTI PHCADVSSEH WNIHLKKRTQ QGKWEEVMSV
660 670 680 690 700
EDESTSCYCL LDPFACHVLL DSFGTYALTG EPITDCAVKQ LKVAVFGCMS
710 720 730 740 750
CNSLDYNLRV YCVDNTPCAF QEVVSDERHQ GGQLLEEPKL LHFKGNTFSL
760 770 780 790 800
QISVLDIPPF LWRIKPFTAC QEVPFSRVWC SNRQPLHCAF SLERYTPTTT
810 820 830 840 850
QLSCKICIRQ LKGHEQILQV QTSILESERE TITFFAQEDS TFPAQTGPKA
860 870 880 890 900
FKIPYSIRQR ICATFDTPNA KGKDWQMLAQ KNSINRNLSY FATQSSPSAV
910 920 930 940 950
ILNLWEARHQ HDGDLDSLAC ALEEIGRTHT KLSNISESQL DEADFNYSRQ

NGL
Length:953
Mass (Da):105,880
Last modified:July 5, 2004 - v1
Checksum:i5F893B9DF746F731
GO
Isoform 2 (identifier: Q6UXZ4-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-34: MGRAAATAGGGGGARRWLPWLGLCFWAAGTAAAR → MILVLVKALSDVCAGTSGFLLDFSSQTSP

Note: No experimental confirmation available.
Show »
Length:948
Mass (Da):105,491
Checksum:iBBC5C40290CDF21C
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti728 – 7281R → K.
Corresponds to variant rs35487923 [ dbSNP | Ensembl ].
VAR_059848

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 3434MGRAA…TAAAR → MILVLVKALSDVCAGTSGFL LDFSSQTSP in isoform 2. 1 PublicationVSP_011703Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB055056 mRNA. Translation: BAB83663.1.
AY358147 mRNA. Translation: AAQ88514.1.
CCDSiCCDS6093.2. [Q6UXZ4-1]
RefSeqiNP_001309747.1. NM_001322818.1.
NP_543148.2. NM_080872.3. [Q6UXZ4-1]
UniGeneiHs.238889.
Hs.720206.

Genome annotation databases

EnsembliENST00000404895; ENSP00000385143; ENSG00000156687. [Q6UXZ4-1]
ENST00000453357; ENSP00000394303; ENSG00000156687. [Q6UXZ4-2]
GeneIDi137970.
KEGGihsa:137970.
UCSCiuc003xjr.3. human. [Q6UXZ4-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB055056 mRNA. Translation: BAB83663.1.
AY358147 mRNA. Translation: AAQ88514.1.
CCDSiCCDS6093.2. [Q6UXZ4-1]
RefSeqiNP_001309747.1. NM_001322818.1.
NP_543148.2. NM_080872.3. [Q6UXZ4-1]
UniGeneiHs.238889.
Hs.720206.

3D structure databases

ProteinModelPortaliQ6UXZ4.
SMRiQ6UXZ4. Positions 52-364, 545-928.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000385143.

PTM databases

iPTMnetiQ6UXZ4.
PhosphoSiteiQ6UXZ4.

Polymorphism and mutation databases

BioMutaiUNC5D.
DMDMi54036576.

Proteomic databases

PaxDbiQ6UXZ4.
PeptideAtlasiQ6UXZ4.
PRIDEiQ6UXZ4.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000404895; ENSP00000385143; ENSG00000156687. [Q6UXZ4-1]
ENST00000453357; ENSP00000394303; ENSG00000156687. [Q6UXZ4-2]
GeneIDi137970.
KEGGihsa:137970.
UCSCiuc003xjr.3. human. [Q6UXZ4-1]

Organism-specific databases

CTDi137970.
GeneCardsiUNC5D.
HGNCiHGNC:18634. UNC5D.
HPAiHPA042940.
MIMi616466. gene.
neXtProtiNX_Q6UXZ4.
PharmGKBiPA38612.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1480. Eukaryota.
ENOG410XRS6. LUCA.
GeneTreeiENSGT00840000129679.
HOGENOMiHOG000060306.
HOVERGENiHBG056483.
InParanoidiQ6UXZ4.
KOiK07521.
OrthoDBiEOG7BGHJX.
PhylomeDBiQ6UXZ4.
TreeFamiTF316767.

Enzyme and pathway databases

ReactomeiR-HSA-418886. Netrin mediated repulsion signals.

Miscellaneous databases

ChiTaRSiUNC5D. human.
GenomeRNAii137970.
PROiQ6UXZ4.
SOURCEiSearch...

Gene expression databases

BgeeiQ6UXZ4.
CleanExiHS_UNC5D.
ExpressionAtlasiQ6UXZ4. baseline and differential.
GenevisibleiQ6UXZ4. 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.
IPR000906. ZU5_dom.
[Graphical view]
PfamiPF00531. Death. 1 hit.
PF07679. I-set. 1 hit.
PF00090. TSP_1. 2 hits.
PF00791. ZU5. 1 hit.
[Graphical view]
SMARTiSM00005. DEATH. 1 hit.
SM00409. IG. 1 hit.
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...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
  2. "Identification of unc5H4 gene."
    Nakajima D., Nakayama M., Nagase T., Ohara O.
    Submitted (JAN-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
    Tissue: Brain.
  3. "Unc5D regulates p53-dependent apoptosis in neuroblastoma cells."
    Wang H., Wu Q., Li S., Zhang B., Chi Z., Hao L.
    Mol. Med. Report. 9:2411-2416(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION BY DNA DAMAGE, FUNCTION.
  4. "Overexpression of the dependence receptor UNC5H4 inhibits cell migration and invasion, and triggers apoptosis in neuroblastoma cell."
    Wang H., Zhang B., Gu M., Li S., Chi Z., Hao L.
    Tumor Biol. 35:5417-5425(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, PROTEOLYTIC CLEAVAGE.
  5. "Structural basis of latrophilin-FLRT-UNC5 interaction in cell adhesion."
    Lu Y.C., Nazarko O.V., Sando R. III, Salzman G.S., Suedhof T.C., Arac D.
    Structure 23:1678-1691(2015) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH FLRT3, SUBUNIT, SUBCELLULAR LOCATION.

Entry informationi

Entry nameiUNC5D_HUMAN
AccessioniPrimary (citable) accession number: Q6UXZ4
Secondary accession number(s): Q8WYP7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 11, 2004
Last sequence update: July 5, 2004
Last modified: July 6, 2016
This is version 121 of the entry and version 1 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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: 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.