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Protein

Netrin receptor UNC5A

Gene

UNC5A

Organism
Homo sapiens (Human)
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

Miscellaneous

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

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. Ligand-independent caspase activation via DCC.
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.

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

EPDiQ6ZN44.
PaxDbiQ6ZN44.
PeptideAtlasiQ6ZN44.
PRIDEiQ6ZN44.

PTM databases

iPTMnetiQ6ZN44.
PhosphoSitePlusiQ6ZN44.

Expressioni

Inductioni

By p53/TP53.1 Publication

Gene expression databases

BgeeiENSG00000113763.
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. 3 interactors.
STRINGi9606.ENSP00000332737.

Structurei

Secondary structure

1842
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi45 – 48Combined sources4
Beta strandi61 – 69Combined sources9
Beta strandi71 – 77Combined sources7
Turni84 – 86Combined sources3
Beta strandi88 – 93Combined sources6
Beta strandi95 – 98Combined sources4
Beta strandi100 – 108Combined sources9
Helixi110 – 115Combined sources6
Beta strandi118 – 120Combined sources3
Beta strandi123 – 129Combined sources7
Beta strandi134 – 136Combined sources3
Beta strandi158 – 163Combined sources6
Beta strandi166 – 168Combined sources3
Beta strandi180 – 185Combined sources6
Turni192 – 194Combined sources3
Beta strandi196 – 200Combined sources5
Beta strandi206 – 208Combined sources3
Beta strandi211 – 214Combined sources4
Beta strandi216 – 224Combined sources9
Beta strandi229 – 231Combined sources3
Beta strandi235 – 241Combined sources7
Helixi256 – 258Combined sources3
Beta strandi259 – 263Combined sources5
Beta strandi282 – 287Combined sources6

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...

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.
GeneTreeiENSGT00850000132260.
HOGENOMiHOG000060306.
HOVERGENiHBG056483.
InParanoidiQ6ZN44.
KOiK07521.
OMAiGTSNMTY.
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.
IPR000488. Death_domain.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003599. Ig_sub.
IPR000884. TSP1_rpt.
IPR033772. UPA.
IPR000906. ZU5_dom.
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

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

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

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: September 27, 2017
This is version 141 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. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  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. SIMILARITY comments
    Index of protein domains and families