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Protein

Netrin receptor UNC5A

Gene

Unc5a

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Receptor for netrin required for axon guidance (PubMed:9126742, PubMed:10399920). Functions in the netrin signaling pathway and promotes neurite outgrowth in response to NTN1 (PubMed:19755150). Mediates axon repulsion of neuronal growth cones in the developing nervous system in response to netrin (PubMed:10399920). Axon repulsion in growth cones may be mediated by its association with DCC that may trigger signaling for repulsion (PubMed:10399920). It also acts as a dependence receptor required for apoptosis induction when not associated with netrin ligand (PubMed:11387206, PubMed:12598531).1 Publication4 Publications

GO - Molecular functioni

  • netrin receptor activity Source: RGD

GO - Biological processi

  • apoptotic process Source: UniProtKB-KW
  • axon guidance Source: RGD
  • netrin-activated signaling pathway Source: UniProtKB
  • neuron projection development Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Receptor

Keywords - Biological processi

Apoptosis

Names & Taxonomyi

Protein namesi
Recommended name:
Netrin receptor UNC5A
Alternative name(s):
Protein unc-5 homolog 1
Protein unc-5 homolog A
Gene namesi
Name:Unc5a
Synonyms:Unc5h13 Publications
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi621755. Unc5a.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini26 – 361336ExtracellularSequence analysisAdd
BLAST
Transmembranei362 – 38221HelicalSequence analysisAdd
BLAST
Topological domaini383 – 898516CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • integral component of membrane Source: UniProtKB-KW
  • intrinsic component of plasma membrane Source: UniProtKB
  • membrane raft Source: UniProtKB-SubCell
  • neuronal cell body membrane Source: UniProtKB
  • neuron projection membrane Source: UniProtKB
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi896 – 8983Missing : Abolishes interaction with PRKCABP. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2525Sequence analysisAdd
BLAST
Chaini26 – 898873Netrin receptor UNC5APRO_0000036070Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi65 ↔ 126By similarity
Disulfide bondi77 ↔ 124By similarity
Glycosylationi107 – 1071N-linked (GlcNAc...)Sequence analysis
Disulfide bondi170 ↔ 221By similarity
Glycosylationi218 – 2181N-linked (GlcNAc...)Sequence analysis
Disulfide bondi254 ↔ 291By similarity
Disulfide bondi258 ↔ 295By similarity
Disulfide bondi269 ↔ 281By similarity
Disulfide bondi310 ↔ 344By similarity
Disulfide bondi314 ↔ 349By similarity
Disulfide bondi322 ↔ 334By similarity
Glycosylationi343 – 3431N-linked (GlcNAc...)Sequence analysis

Post-translational modificationi

Phosphorylated on cytoplasmic tyrosine residues (By similarity). Phosphorylated by PKC in vitro.By similarity1 Publication
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
Sitei396 – 3972Cleavage; by caspase-31 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiO08721.

PTM databases

iPTMnetiO08721.
PhosphoSiteiO08721.

Expressioni

Tissue specificityi

Mainly expressed in regions of differentiating neurons. Expressed at early stages of neural tube development in the ventral spinal cord. In developing hindbrain, it colocalizes with a number of cranial motor neuron subpopulations from embryonic E11 to E14, while DCC is expressed by motor neurons at E12. Also expressed in non-neural structures, such as the basal plane of the hindbrain and midbrain, in the developing hypothalamus, thalamus and in the pallidum.2 Publications

Interactioni

Subunit structurei

Homodimer and homooligomer (PubMed:19755150). Interacts with the cytoplasmic part of DCC (PubMed:10399920). Interacts with MAGED1 (PubMed:12598531). Interacts with PRKCABP, possibly mediating some interaction with PKC (PubMed:14672991). Interacts (via extracellular domain) with FLRT2 (via extracellular domain) (By similarity). Interacts (via extracellular domain) with FLRT3 (via extracellular domain) (By similarity).By similarity3 Publications

Protein-protein interaction databases

DIPiDIP-60742N.
STRINGi10116.ENSRNOP00000032250.

Structurei

3D structure databases

ProteinModelPortaliO08721.
SMRiO08721. Positions 808-895.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini44 – 14198Ig-likeAdd
BLAST
Domaini155 – 23884Ig-like C2-typeAdd
BLAST
Domaini242 – 29655TSP type-1 1PROSITE-ProRule annotationAdd
BLAST
Domaini298 – 35053TSP type-1 2PROSITE-ProRule annotationAdd
BLAST
Domaini495 – 601107ZU5PROSITE-ProRule annotationAdd
BLAST
Domaini817 – 89781DeathAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni661 – 67919Interaction with DCCBy similarityAdd
BLAST

Domaini

The ZU5 domain mediates the interaction with MAGED1, which participates in the induction of apoptosis.1 Publication

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.
HOGENOMiHOG000060306.
HOVERGENiHBG056483.
InParanoidiO08721.
KOiK07521.
PhylomeDBiO08721.

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.
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.
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]

Sequencei

Sequence statusi: Complete.

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

O08721-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAVRPGLWPV LLGIVLAAWL RGSGAQQSAT VANPVPGANP DLLPHFLVEP
60 70 80 90 100
EDVYIVKNKP VLLVCKAVPA TQIFFKCNGE WVRQVDHVIE RSTDSSSGLP
110 120 130 140 150
TMEVRINVSR QQVEKVFGLE EYWCQCVAWS SSGTTKSQKA YIRIAYLRKN
160 170 180 190 200
FEQEPLAKEV SLEQGIVLPC RPPEGIPPAE VEWLRNEDLV DPSLDPNVYI
210 220 230 240 250
TREHSLVVRQ ARLADTANYT CVAKNIVARR RSTSAAVIVY VNGGWSTWTE
260 270 280 290 300
WSVCSASCGR GWQKRSRSCT NPAPLNGGAF CEGQNVQKTA CATLCPVDGS
310 320 330 340 350
WSSWSKWSAC GLDCTHWRSR ECSDPAPRNG GEECRGADLD TRNCTSDLCL
360 370 380 390 400
HTASCPEDVA LYIGLVAVAV CLFLLLLALG LIYCRKKEGL DSDVADSSIL
410 420 430 440 450
TSGFQPVSIK PSKADNPHLL TIQPDLSTTT TTYQGSLCSR QDGPSPKFQL
460 470 480 490 500
SNGHLLSPLG SGRHTLHHSS PTSEAEDFVS RLSTQNYFRS LPRGTSNMAY
510 520 530 540 550
GTFNFLGGRL MIPNTGISLL IPPDAIPRGK IYEIYLTLHK PEDVRLPLAG
560 570 580 590 600
CQTLLSPVVS CGPPGVLLTR PVILAMDHCG EPSPDSWSLR LKKQSCEGSW
610 620 630 640 650
EDVLHLGEES PSHLYYCQLE AGACYVFTEQ LGRFALVGEA LSVAATKRLR
660 670 680 690 700
LLLFAPVACT SLEYNIRVYC LHDTHDALKE VVQLEKQLGG QLIQEPRVLH
710 720 730 740 750
FKDSYHNLRL SIHDVPSSLW KSKLLVSYQE IPFYHIWNGT QQYLHCTFTL
760 770 780 790 800
ERINASTSDL ACKVWVWQVE GDGQSFNINF NITKDTRFAE LLALESEGGV
810 820 830 840 850
PALVGPSAFK IPFLIRQKII ASLDPPCSRG ADWRTLAQKL HLDSHLSFFA
860 870 880 890
SKPSPTAMIL NLWEARHFPN GNLGQLAAAV AGLGQPDAGL FTVSEAEC
Length:898
Mass (Da):98,841
Last modified:July 1, 1997 - v1
Checksum:i7A3CBCB9E7ACA135
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U87305 mRNA. Translation: AAB57678.1.
RefSeqiNP_071542.1. NM_022206.1.
UniGeneiRn.44433.

Genome annotation databases

GeneIDi60629.
KEGGirno:60629.
UCSCiRGD:621755. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U87305 mRNA. Translation: AAB57678.1.
RefSeqiNP_071542.1. NM_022206.1.
UniGeneiRn.44433.

3D structure databases

ProteinModelPortaliO08721.
SMRiO08721. Positions 808-895.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-60742N.
STRINGi10116.ENSRNOP00000032250.

PTM databases

iPTMnetiO08721.
PhosphoSiteiO08721.

Proteomic databases

PaxDbiO08721.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi60629.
KEGGirno:60629.
UCSCiRGD:621755. rat.

Organism-specific databases

CTDi90249.
RGDi621755. Unc5a.

Phylogenomic databases

eggNOGiKOG1480. Eukaryota.
ENOG410XRS6. LUCA.
HOGENOMiHOG000060306.
HOVERGENiHBG056483.
InParanoidiO08721.
KOiK07521.
PhylomeDBiO08721.

Miscellaneous databases

PROiO08721.

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.
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.
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

  1. "Vertebrate homologues of C. elegans UNC-5 are candidate netrin receptors."
    Leonardo E.D., Hinck L., Masu M., Keino-Masu K., Ackerman S.L., Tessier-Lavigne M.
    Nature 386:833-838(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
    Tissue: Ventral spinal cord.
  2. "A ligand-gated association between cytoplasmic domains of UNC5 and DCC family receptors converts netrin-induced growth cone attraction to repulsion."
    Hong K., Hinck L., Nishiyama M., Poo M.-M., Tessier-Lavigne M., Stein E.
    Cell 97:927-941(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH DCC.
  3. "Expression patterns of the netrin receptor UNC5H1 among developing motor neurons in the embryonic rat hindbrain."
    Barrett C., Guthrie S.
    Mech. Dev. 106:163-166(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  4. "Netrin-1 acts as a survival factor via its receptors UNC5H and DCC."
    Llambi F., Causeret F., Bloch-Gallego E., Mehlen P.
    EMBO J. 20:2715-2722(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, PROTEOLYTIC CLEAVAGE.
  5. "UNC5H1 induces apoptosis via its juxtamembrane region through an interaction with NRAGE."
    Williams M.E., Strickland P., Watanabe K., Hinck L.
    J. Biol. Chem. 278:17483-17490(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH MAGED1, DOMAIN.
  6. "Surface expression of the netrin receptor UNC5H1 is regulated through a protein kinase C-interacting protein/protein kinase-dependent mechanism."
    Williams M.E., Wu S.C.-Y., McKenna W.L., Hinck L.
    J. Neurosci. 23:11279-11288(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH PRKCABP, PHOSPHORYLATION, MUTAGENESIS OF 896-ALA--CYS-898.
  7. "Lipid raft localization and palmitoylation: identification of two requirements for cell death induction by the tumor suppressors UNC5H."
    Maisse C., Rossin A., Cahuzac N., Paradisi A., Klein C., Haillot M.L., Herincs Z., Mehlen P., Hueber A.O.
    Exp. Cell Res. 314:2544-2552(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
  8. "Spatial and temporal activation of the small GTPases RhoA and Rac1 by the netrin-1 receptor UNC5a during neurite outgrowth."
    Picard M., Petrie R.J., Antoine-Bertrand J., Saint-Cyr-Proulx E., Villemure J.F., Lamarche-Vane N.
    Cell. Signal. 21:1961-1973(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBUNIT, SUBCELLULAR LOCATION.

Entry informationi

Entry nameiUNC5A_RAT
AccessioniPrimary (citable) accession number: O08721
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 11, 2004
Last sequence update: July 1, 1997
Last modified: June 8, 2016
This is version 122 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 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.