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Protein

Netrin receptor UNC5A

Gene

UNC5A

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

Miscellaneous

Down-regulated in multiple cancers including colorectal, breast, ovary, uterus, stomach, lung, or kidney cancers.1 Publication

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionDevelopmental protein, Receptor
Biological processApoptosis

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
SIGNORiQ6ZN44

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

EuPathDBiHostDB:ENSG00000113763.10
HGNCiHGNC:12567 UNC5A
MIMi607869 gene
neXtProtiNX_Q6ZN44

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 domaini26 – 306ExtracellularSequence analysisAdd BLAST281
Transmembranei307 – 327HelicalSequence analysisAdd BLAST21
Topological domaini328 – 842CytoplasmicSequence analysisAdd BLAST515

Keywords - Cellular componenti

Cell membrane, Cell projection, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi90249
OpenTargetsiENSG00000113763
PharmGKBiPA37204

Polymorphism and mutation databases

BioMutaiUNC5A
DMDMi296453000

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 25Sequence analysisAdd BLAST25
ChainiPRO_000003606826 – 842Netrin receptor UNC5AAdd BLAST817

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi65 ↔ 126Combined sources
Disulfide bondi77 ↔ 124Combined sources
Glycosylationi107N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi170 ↔ 221Combined sources
Glycosylationi218N-linked (GlcNAc...) asparagineSequence analysisCombined sources1
Disulfide bondi254 ↔ 288Combined sources
Disulfide bondi258 ↔ 293Combined sources
Disulfide bondi266 ↔ 278Combined sources
Glycosylationi287N-linked (GlcNAc...) asparagineSequence analysis1

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)DescriptionActionsGraphical viewLength
Sitei340 – 341Cleavage; by caspase-3By similarity2

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ6ZN44
PeptideAtlasiQ6ZN44
PRIDEiQ6ZN44
ProteomicsDBi67973
67974 [Q6ZN44-2]
67975 [Q6ZN44-3]

PTM databases

iPTMnetiQ6ZN44
PhosphoSitePlusiQ6ZN44

Expressioni

Inductioni

By p53/TP53.1 Publication

Gene expression databases

BgeeiENSG00000113763 Expressed in 88 organ(s), highest expression level in endothelial cell
CleanExiHS_UNC5A
ExpressionAtlasiQ6ZN44 baseline and differential
GenevisibleiQ6ZN44 HS

Organism-specific databases

HPAiHPA071450

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) (By similarity).By similarity1 Publication

Protein-protein interaction databases

BioGridi124683, 4 interactors
STRINGi9606.ENSP00000332737

Structurei

Secondary structure

1842
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ6ZN44
SMRiQ6ZN44
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini44 – 141Ig-likeAdd BLAST98
Domaini155 – 234Ig-like C2-typeAdd BLAST80
Domaini242 – 294TSP type-1PROSITE-ProRule annotationAdd BLAST53
Domaini441 – 584ZU5PROSITE-ProRule annotationAdd BLAST144
Domaini761 – 841DeathAdd BLAST81

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni605 – 623Interaction with DCCBy similarityAdd BLAST19

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

Keywords - Domaini

Immunoglobulin domain, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1480 Eukaryota
ENOG410XRS6 LUCA
GeneTreeiENSGT00920000149006
HOGENOMiHOG000060306
HOVERGENiHBG056483
InParanoidiQ6ZN44
KOiK07521
OMAiLIRQKIC
OrthoDBiEOG091G040Q
PhylomeDBiQ6ZN44
TreeFamiTF316767

Family and domain databases

Gene3Di2.20.100.10, 1 hit
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
IPR000884 TSP1_rpt
IPR036383 TSP1_rpt_sf
IPR037936 UNC5
IPR033772 UPA
IPR000906 ZU5_dom
PANTHERiPTHR12582 PTHR12582, 2 hits
PfamiView protein in Pfam
PF00531 Death, 1 hit
PF07679 I-set, 1 hit
PF17217 UPA, 1 hit
PF00791 ZU5, 1 hit
SMARTiView protein in SMART
SM00005 DEATH, 1 hit
SM00409 IG, 1 hit
SM00209 TSP1, 1 hit
SM00218 ZU5, 1 hit
SUPFAMiSSF47986 SSF47986, 1 hit
SSF48726 SSF48726, 2 hits
SSF82895 SSF82895, 1 hit
PROSITEiView protein in PROSITE
PS50835 IG_LIKE, 1 hit
PS50092 TSP1, 1 hit
PS51145 ZU5, 1 hit

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

This entry has 3 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q6ZN44-1) [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 LLGIVLAAWL 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 VDGSWSPWSK
260 270 280 290 300
WSACGLDCTH WRSRECSDPA PRNGGEECQG TDLDTRNCTS DLCVHTASGP
310 320 330 340 350
EDVALYVGLI AVAVCLVLLL LVLILVYCRK KEGLDSDVAD SSILTSGFQP
360 370 380 390 400
VSIKPSKADN PHLLTIQPDL STTTTTYQGS LCPRQDGPSP KFQLTNGHLL
410 420 430 440 450
SPLGGGRHTL HHSSPTSEAE EFVSRLSTQN YFRSLPRGTS NMTYGTFNFL
460 470 480 490 500
GGRLMIPNTG ISLLIPPDAI PRGKIYEIYL TLHKPEDVRL PLAGCQTLLS
510 520 530 540 550
PIVSCGPPGV LLTRPVILAM DHCGEPSPDS WSLRLKKQSC EGSWEDVLHL
560 570 580 590 600
GEEAPSHLYY CQLEASACYV FTEQLGRFAL VGEALSVAAA KRLKLLLFAP
610 620 630 640 650
VACTSLEYNI RVYCLHDTHD ALKEVVQLEK QLGGQLIQEP RVLHFKDSYH
660 670 680 690 700
NLRLSIHDVP SSLWKSKLLV SYQEIPFYHI WNGTQRYLHC TFTLERVSPS
710 720 730 740 750
TSDLACKLWV WQVEGDGQSF SINFNITKDT RFAELLALES EAGVPALVGP
760 770 780 790 800
SAFKIPFLIR QKIISSLDPP CRRGADWRTL AQKLHLDSHL SFFASKPSPT
810 820 830 840
AMILNLWEAR HFPNGNLSQL AAAVAGLGQP DAGLFTVSEA EC
Note: No experimental confirmation available.
Length:842
Mass (Da):92,932
Last modified:May 18, 2010 - v3
Checksum:i7B209042977FE524
GO
Isoform 2 (identifier: Q6ZN44-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     296-301: TASGPE → SESSLP
     302-842: Missing.

Note: No experimental confirmation available.
Show »
Length:301
Mass (Da):33,342
Checksum:i255472A1B083799A
GO
Isoform 3 (identifier: Q6ZN44-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-97: MAVRPGLWPA...VIERSTDGSS → MAGTSERSLI...PKPETFCGQT

Note: No experimental confirmation available.
Show »
Length:802
Mass (Da):88,640
Checksum:i122B6B66DBE9AE29
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H0Y8R2H0Y8R2_HUMAN
Netrin receptor UNC5A
UNC5A
898Annotation score:
H0Y9G2H0Y9G2_HUMAN
Netrin receptor UNC5A
UNC5A
84Annotation score:

Sequence cautioni

The sequence BAB85562 differs from that shown. Intron retention.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti97S → N in BAD18531 (PubMed:14702039).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0116931 – 97MAVRP…TDGSS → MAGTSERSLISSISQPKAIE CFEVKKKAFLTHGRYHGSGA TPPKTKDPKPETFCGQT in isoform 3. 1 PublicationAdd BLAST97
Alternative sequenceiVSP_011694296 – 301TASGPE → SESSLP in isoform 2. 1 Publication6
Alternative sequenceiVSP_011695302 – 842Missing in isoform 2. 1 PublicationAdd BLAST541

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK131380 mRNA Translation: BAD18531.1
AC027318 Genomic DNA No translation available.
AC091897 Genomic DNA No translation available.
AC091902 Genomic DNA No translation available.
BC009333 mRNA Translation: AAH09333.2
BC033727 mRNA No translation available.
BC157824 mRNA Translation: AAI57825.1
AB075856 mRNA Translation: BAB85562.1 Sequence problems.
CCDSiCCDS34299.1 [Q6ZN44-1]
RefSeqiNP_588610.2, NM_133369.2 [Q6ZN44-1]
UniGeneiHs.33191

Genome annotation databases

EnsembliENST00000329542; ENSP00000332737; ENSG00000113763 [Q6ZN44-1]
GeneIDi90249
KEGGihsa:90249
UCSCiuc003mey.4 human [Q6ZN44-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK131380 mRNA Translation: BAD18531.1
AC027318 Genomic DNA No translation available.
AC091897 Genomic DNA No translation available.
AC091902 Genomic DNA No translation available.
BC009333 mRNA Translation: AAH09333.2
BC033727 mRNA No translation available.
BC157824 mRNA Translation: AAI57825.1
AB075856 mRNA Translation: BAB85562.1 Sequence problems.
CCDSiCCDS34299.1 [Q6ZN44-1]
RefSeqiNP_588610.2, NM_133369.2 [Q6ZN44-1]
UniGeneiHs.33191

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4V2AX-ray2.40A1-303[»]
ProteinModelPortaliQ6ZN44
SMRiQ6ZN44
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi124683, 4 interactors
STRINGi9606.ENSP00000332737

PTM databases

iPTMnetiQ6ZN44
PhosphoSitePlusiQ6ZN44

Polymorphism and mutation databases

BioMutaiUNC5A
DMDMi296453000

Proteomic databases

PaxDbiQ6ZN44
PeptideAtlasiQ6ZN44
PRIDEiQ6ZN44
ProteomicsDBi67973
67974 [Q6ZN44-2]
67975 [Q6ZN44-3]

Protocols and materials databases

DNASUi90249
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000329542; ENSP00000332737; ENSG00000113763 [Q6ZN44-1]
GeneIDi90249
KEGGihsa:90249
UCSCiuc003mey.4 human [Q6ZN44-1]

Organism-specific databases

CTDi90249
DisGeNETi90249
EuPathDBiHostDB:ENSG00000113763.10
GeneCardsiUNC5A
H-InvDBiHIX0005448
HGNCiHGNC:12567 UNC5A
HPAiHPA071450
MIMi607869 gene
neXtProtiNX_Q6ZN44
OpenTargetsiENSG00000113763
PharmGKBiPA37204
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1480 Eukaryota
ENOG410XRS6 LUCA
GeneTreeiENSGT00920000149006
HOGENOMiHOG000060306
HOVERGENiHBG056483
InParanoidiQ6ZN44
KOiK07521
OMAiLIRQKIC
OrthoDBiEOG091G040Q
PhylomeDBiQ6ZN44
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
SIGNORiQ6ZN44

Miscellaneous databases

ChiTaRSiUNC5A human
GeneWikiiUNC5A
GenomeRNAii90249
PROiPR:Q6ZN44
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000113763 Expressed in 88 organ(s), highest expression level in endothelial cell
CleanExiHS_UNC5A
ExpressionAtlasiQ6ZN44 baseline and differential
GenevisibleiQ6ZN44 HS

Family and domain databases

Gene3Di2.20.100.10, 1 hit
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
IPR000884 TSP1_rpt
IPR036383 TSP1_rpt_sf
IPR037936 UNC5
IPR033772 UPA
IPR000906 ZU5_dom
PANTHERiPTHR12582 PTHR12582, 2 hits
PfamiView protein in Pfam
PF00531 Death, 1 hit
PF07679 I-set, 1 hit
PF17217 UPA, 1 hit
PF00791 ZU5, 1 hit
SMARTiView protein in SMART
SM00005 DEATH, 1 hit
SM00409 IG, 1 hit
SM00209 TSP1, 1 hit
SM00218 ZU5, 1 hit
SUPFAMiSSF47986 SSF47986, 1 hit
SSF48726 SSF48726, 2 hits
SSF82895 SSF82895, 1 hit
PROSITEiView protein in PROSITE
PS50835 IG_LIKE, 1 hit
PS50092 TSP1, 1 hit
PS51145 ZU5, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiUNC5A_HUMAN
AccessioniPrimary (citable) accession number: Q6ZN44
Secondary accession number(s): B2RXE6, Q8TF26, Q96GP4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 11, 2004
Last sequence update: May 18, 2010
Last modified: November 7, 2018
This is version 150 of the entry and version 3 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
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