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Protein

Netrin receptor UNC5A

Gene

Unc5a

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Receptor for netrin required for axon guidance. Functions in the netrin signaling pathway and promotes neurite outgrowth in response to NTN1. Mediates axon repulsion of neuronal growth cones in the developing nervous system in response to netrin. Axon repulsion in growth cones may be mediated by its association with DCC that may trigger signaling for repulsion. It also acts as a dependence receptor required for apoptosis induction when not associated with netrin ligand.By similarity

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Receptor

Keywords - Biological processi

Apoptosis

Enzyme and pathway databases

ReactomeiR-MMU-373752. Netrin-1 signaling.
R-MMU-418889. Ligand-independent caspase activation via DCC.

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:Kiaa1976, Unc5h1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 13

Organism-specific databases

MGIiMGI:894682. Unc5a.

Subcellular locationi

  • Cell membrane By similarity; Single-pass type I membrane protein By similarity
  • Membrane raft By similarity
  • Cell projection By similarity

  • Note: The interaction with PRKCABP regulates its surface expression and leads to its removal from the surface of neurons and growth cones. Detected in neurites.By similarity

Topology

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

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2525Sequence analysisAdd
BLAST
Chaini26 – 898873Netrin receptor UNC5APRO_0000036069Add
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 similarity).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.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei396 – 3972Cleavage; by caspase-3By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiQ8K1S4.
PaxDbiQ8K1S4.
PRIDEiQ8K1S4.

PTM databases

iPTMnetiQ8K1S4.
PhosphoSiteiQ8K1S4.

Expressioni

Tissue specificityi

Restricted to central nervous system.1 Publication

Gene expression databases

BgeeiQ8K1S4.
CleanExiMM_UNC5A.
ExpressionAtlasiQ8K1S4. baseline and differential.
GenevisibleiQ8K1S4. MM.

Interactioni

Subunit structurei

Homodimer and homooligomer. Interacts with the cytoplasmic part of DCC. Interacts with MAGED1. Interacts with PRKCABP, possibly mediating some interaction with PKC (By similarity). Interacts (via extracellular domain) with FLRT2 (via extracellular domain) (PubMed:25374360). Interacts (via extracellular domain) with FLRT3 (via extracellular domain) (PubMed:22405201).By similarity2 Publications

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000026994.

Structurei

3D structure databases

ProteinModelPortaliQ8K1S4.
SMRiQ8K1S4. Positions 43-349, 501-887.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini44 – 14198Ig-likeAdd
BLAST
Domaini155 – 23480Ig-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.By 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.
InParanoidiQ8K1S4.
KOiK07521.
OMAiCQLEAET.
OrthoDBiEOG7BGHJX.
PhylomeDBiQ8K1S4.
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.
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]

Sequences (3)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8K1S4-1) [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
MAVRPGLWPA LLGIVLTAWL RGSGAQQSAT VANPVPGANP DLLPHFLVEP
60 70 80 90 100
EDVYIVKNKP VLLVCKAVPA TQIFFKCNGE WVRQVDHVIE RSTDGSSGLP
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 RSASAAVIVY VNGGWSTWTE
260 270 280 290 300
WSVCSASCGR GWQKRSRSCT NPAPLNGGAF CEGQNVQKTA CATLCPVDGS
310 320 330 340 350
WSPWSKWSAC GLDCTHWRSR ECSDPAPRNG GEECRGADLD TRNCTSDLCL
360 370 380 390 400
HTSSGPEDVA LYIGLVAVAV CLILLLLVLV LIYCRKKEGL DSDVADSSIL
410 420 430 440 450
TSGFQPVSIK PSKADNPHLL TIQPDLSTTT TTYQGSLCPR 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
CQTLLSPIVS 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
ERVNASTSDL ACKVWVWQVE GDGQSFNINF NITKDTRFAE MLALESEGGV
810 820 830 840 850
PALVGPSAFK IPFLIRQKII TSLDPPCSRG ADWRTLAQKL HLDSHLSFFA
860 870 880 890
SKPSPTAMIL NLWEARHFPN GNLGQLAAAV AGLGQPDAGL FTVSEAEC
Length:898
Mass (Da):98,857
Last modified:October 1, 2002 - v1
Checksum:i59F04BA2E196C1DB
GO
Isoform 2 (identifier: Q8K1S4-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     241-296: Missing.

Note: No experimental confirmation available.
Show »
Length:842
Mass (Da):92,924
Checksum:i2D106FCA22D7AE44
GO
Isoform 3 (identifier: Q8K1S4-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-790: Missing.

Note: No experimental confirmation available.
Show »
Length:108
Mass (Da):11,482
Checksum:i2B7D02D006FB166D
GO

Sequence cautioni

The sequence BAC65857.1 differs from that shown. Reason: Erroneous initiation. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti217 – 2171A → P in AAH58084 (PubMed:15489334).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 790790Missing in isoform 3. 1 PublicationVSP_011696Add
BLAST
Alternative sequencei241 – 29656Missing in isoform 2. 1 PublicationVSP_011697Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ487852 mRNA. Translation: CAD32250.1.
AK122575 mRNA. Translation: BAC65857.1. Different initiation.
BC058084 mRNA. Translation: AAH58084.1.
CCDSiCCDS26537.1. [Q8K1S4-1]
CCDS79188.1. [Q8K1S4-2]
RefSeqiNP_001298057.1. NM_001311128.1. [Q8K1S4-2]
NP_694771.1. NM_153131.3. [Q8K1S4-1]
UniGeneiMm.23573.

Genome annotation databases

EnsembliENSMUST00000026994; ENSMUSP00000026994; ENSMUSG00000025876. [Q8K1S4-1]
ENSMUST00000109994; ENSMUSP00000105621; ENSMUSG00000025876. [Q8K1S4-2]
GeneIDi107448.
KEGGimmu:107448.
UCSCiuc007qpp.1. mouse. [Q8K1S4-1]
uc007qpq.1. mouse. [Q8K1S4-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ487852 mRNA. Translation: CAD32250.1.
AK122575 mRNA. Translation: BAC65857.1. Different initiation.
BC058084 mRNA. Translation: AAH58084.1.
CCDSiCCDS26537.1. [Q8K1S4-1]
CCDS79188.1. [Q8K1S4-2]
RefSeqiNP_001298057.1. NM_001311128.1. [Q8K1S4-2]
NP_694771.1. NM_153131.3. [Q8K1S4-1]
UniGeneiMm.23573.

3D structure databases

ProteinModelPortaliQ8K1S4.
SMRiQ8K1S4. Positions 43-349, 501-887.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000026994.

PTM databases

iPTMnetiQ8K1S4.
PhosphoSiteiQ8K1S4.

Proteomic databases

MaxQBiQ8K1S4.
PaxDbiQ8K1S4.
PRIDEiQ8K1S4.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000026994; ENSMUSP00000026994; ENSMUSG00000025876. [Q8K1S4-1]
ENSMUST00000109994; ENSMUSP00000105621; ENSMUSG00000025876. [Q8K1S4-2]
GeneIDi107448.
KEGGimmu:107448.
UCSCiuc007qpp.1. mouse. [Q8K1S4-1]
uc007qpq.1. mouse. [Q8K1S4-2]

Organism-specific databases

CTDi90249.
MGIiMGI:894682. Unc5a.
RougeiSearch...

Phylogenomic databases

eggNOGiKOG1480. Eukaryota.
ENOG410XRS6. LUCA.
GeneTreeiENSGT00840000129679.
HOGENOMiHOG000060306.
HOVERGENiHBG056483.
InParanoidiQ8K1S4.
KOiK07521.
OMAiCQLEAET.
OrthoDBiEOG7BGHJX.
PhylomeDBiQ8K1S4.
TreeFamiTF316767.

Enzyme and pathway databases

ReactomeiR-MMU-373752. Netrin-1 signaling.
R-MMU-418889. Ligand-independent caspase activation via DCC.

Miscellaneous databases

PROiQ8K1S4.
SOURCEiSearch...

Gene expression databases

BgeeiQ8K1S4.
CleanExiMM_UNC5A.
ExpressionAtlasiQ8K1S4. baseline and differential.
GenevisibleiQ8K1S4. MM.

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

« Hide 'large scale' publications
  1. "Cloning of three mouse Unc5 genes and their expression patterns at mid-gestation."
    Engelkamp D.
    Mech. Dev. 118:191-197(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
  2. "Prediction of the coding sequences of mouse homologues of KIAA gene: II. The complete nucleotide sequences of 400 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries."
    Okazaki N., Kikuno R., Ohara R., Inamoto S., Aizawa H., Yuasa S., Nakajima D., Nagase T., Ohara O., Koga H.
    DNA Res. 10:35-48(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
    Tissue: Brain.
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
    Strain: C57BL/6J.
    Tissue: Brain.
  4. "FLRT proteins are endogenous latrophilin ligands and regulate excitatory synapse development."
    O'Sullivan M.L., de Wit J., Savas J.N., Comoletti D., Otto-Hitt S., Yates J.R. III, Ghosh A.
    Neuron 73:903-910(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH FLRT3.
  5. "FLRT structure: balancing repulsion and cell adhesion in cortical and vascular development."
    Seiradake E., del Toro D., Nagel D., Cop F., Haertl R., Ruff T., Seyit-Bremer G., Harlos K., Border E.C., Acker-Palmer A., Jones E.Y., Klein R.
    Neuron 84:370-385(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH FLRT2.

Entry informationi

Entry nameiUNC5A_MOUSE
AccessioniPrimary (citable) accession number: Q8K1S4
Secondary accession number(s): Q6PEF7, Q80T71
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 11, 2004
Last sequence update: October 1, 2002
Last modified: June 8, 2016
This is version 119 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. 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.