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netrin receptor UNC5A (Unc-5 homolog A, Unc-5 homolog 1, UNC5A, UNC5H1, KIAA1976)

Function: 1) receptor for netrin 2) involved in axon guidance 3) mediates axon repulsion of neuronal growth cones in developing nervous system 4) association with DCC (cytoplasmic domain) may trigger signaling for axonal repulsion 6) apoptosis induction when NOT associated with netrin 7) interacts with MAGED1 mediated by ZU5 domain - participates in the induction of apoptosis 8) interacts with PRKCABP, - regulates its surface expression & leads to its removal from surface of neurons & growth cones 9) phosphorylated on different cytoplasmic Tyr 10) phosphorylated by PKC in vitro 11) phosphorylation of Tyr-568 leads to an interaction with PTPN11 phosphatase (netrin-dependent) 12) proteolytic cleavage by caspases during apoptosis does NOT occur associated with netrin ligand 13) cleavage by caspases is required to induce apoptosis Compartment: membrane Alternative splicing: named isoforms=3 Expression: - expressed in brain, kidney - not expressed in developing or adult lung Pathology: - down-regulated in multiple cancers including: - colorectal cancer - breast cancer - ovarian cancer - uterine cancer - stomach cancer - lung cancer - kidney cancer

Related

netrin

General

glycoprotein phosphoprotein UNC5 homolog protein

Properties

SIZE: MW = 93 kD entity length = 842 aa COMPARTMENT: plasma membrane MOTIF: signal sequence {1-25} immunoglobulin superfamily domain {44-141} MOTIF: cysteine residue {C65} MODIFICATION: cysteine residue {C124} N-glycosylation site {N107} cysteine residue {C124} MODIFICATION: cysteine residue {C65} immunoglobulin superfamily domain {155-234} MOTIF: cysteine residue {C170} MODIFICATION: cysteine residue {C221} N-glycosylation site {N218} cysteine residue {C221} MODIFICATION: cysteine residue {C170} TSP TYPE-1 {242-294} MOTIF: N-glycosylation site {N287} transmembrane domain {307-327} proteolytic site {340-341} ZU5 {439-545} binding site SITE: 605-623 FOR-BINDING-OF: netrin receptor DCC death domain NAME: death domain SITE: 761-841

Database Correlations

OMIM 607869 UniProt Q6ZN44 PFAM correlations Entrez Gene 90249 Kegg hsa:90249

References

  1. Leonardo ED et al. Vertebrate homologues of C. elegans UNC-5 are candidate netrin receptors. Nature 386:833-8 1997 PMID: 9126742
  2. UniProt :accession Q6ZN44