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Protein

Netrin receptor UNC5D

Gene

UNC5D

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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 - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionDevelopmental protein, Receptor
Biological processApoptosis

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

EuPathDBiHostDB:ENSG00000156687.10
HGNCiHGNC:18634 UNC5D
MIMi616466 gene
neXtProtiNX_Q6UXZ4

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 domaini33 – 379ExtracellularSequence analysisAdd BLAST347
Transmembranei380 – 400HelicalSequence analysisAdd BLAST21
Topological domaini401 – 953CytoplasmicSequence analysisAdd BLAST553

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi137970
OpenTargetsiENSG00000156687
PharmGKBiPA38612

Polymorphism and mutation databases

BioMutaiUNC5D
DMDMi54036576

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 32Sequence analysisAdd BLAST32
ChainiPRO_000003607933 – 953Netrin receptor UNC5DAdd BLAST921

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi75 ↔ 136By similarity
Disulfide bondi87 ↔ 134By similarity
Glycosylationi117N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi180 ↔ 231By similarity
Glycosylationi228N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi264 ↔ 301By similarity
Disulfide bondi268 ↔ 305By similarity
Disulfide bondi279 ↔ 291By similarity
Disulfide bondi320 ↔ 354By similarity
Disulfide bondi324 ↔ 359By similarity
Disulfide bondi332 ↔ 344By similarity
Glycosylationi353N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi376N-linked (GlcNAc...) asparagineSequence analysis1

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)DescriptionActionsGraphical viewLength
Sitei416 – 417Cleavage; by caspase-3Curated2

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ6UXZ4
PeptideAtlasiQ6UXZ4
PRIDEiQ6UXZ4

PTM databases

iPTMnetiQ6UXZ4
PhosphoSitePlusiQ6UXZ4

Expressioni

Inductioni

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

Gene expression databases

BgeeiENSG00000156687
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

CORUMiQ6UXZ4
STRINGi9606.ENSP00000385143

Structurei

3D structure databases

ProteinModelPortaliQ6UXZ4
SMRiQ6UXZ4
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini54 – 151Ig-likeAdd BLAST98
Domaini153 – 244Ig-like C2-typeAdd BLAST92
Domaini252 – 306TSP type-1 1PROSITE-ProRule annotationAdd BLAST55
Domaini308 – 360TSP type-1 2PROSITE-ProRule annotationAdd BLAST53
Domaini542 – 682ZU5PROSITE-ProRule annotationAdd BLAST141
Domaini859 – 936DeathAdd BLAST78

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni91 – 93Important for interaction with FLRT2By similarity3

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
InParanoidiQ6UXZ4
KOiK07521
PhylomeDBiQ6UXZ4
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, 1 hit
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: 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)DescriptionActionsGraphical viewLength
Natural variantiVAR_059848728R → K. Corresponds to variant dbSNP:rs35487923Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0117031 – 34MGRAA…TAAAR → MILVLVKALSDVCAGTSGFL LDFSSQTSP in isoform 2. 1 PublicationAdd BLAST34

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]
CCDS83279.1 [Q6UXZ4-2]
RefSeqiNP_001309747.1, NM_001322818.1 [Q6UXZ4-2]
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

Similar proteinsi

Entry informationi

Entry nameiUNC5D_HUMAN
AccessioniPrimary (citable) accession number: Q6UXZ4
Secondary accession number(s): Q8WYP7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 11, 2004
Last sequence update: July 5, 2004
Last modified: March 28, 2018
This is version 134 of the entry and version 1 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. 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

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