UNC40_CAEEL
ID UNC40_CAEEL Reviewed; 1415 AA.
AC G5EF96;
DT 07-APR-2021, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 1.
DT 03-AUG-2022, entry version 100.
DE RecName: Full=Netrin receptor unc-40 {ECO:0000303|PubMed:11454756};
DE AltName: Full=Uncoordinated protein 40 {ECO:0000305};
DE Flags: Precursor;
GN Name=unc-40 {ECO:0000312|WormBase:T19B4.7};
GN ORFNames=T19B4.7 {ECO:0000312|WormBase:T19B4.7};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|EMBL:AAB17088.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH UNC-6, DEVELOPMENTAL
RP STAGE, AND MUTAGENESIS OF 157-ARG--LYS-1415.
RX PubMed=8861903; DOI=10.1016/s0092-8674(00)81337-9;
RA Chan S.S.-Y., Zheng H., Su M.-W., Wilk R., Killeen M.T., Hedgecock E.M.,
RA Culotti J.G.;
RT "UNC-40, a C. elegans homolog of DCC (Deleted in Colorectal Cancer), is
RT required in motile cells responding to UNC-6 netrin cues.";
RL Cell 87:187-195(1996).
RN [2] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [3]
RP FUNCTION, AND MUTAGENESIS OF 157-ARG--LYS-1415.
RX PubMed=9473333; DOI=10.1006/dbio.1997.8790;
RA Colavita A., Culotti J.G.;
RT "Suppressors of ectopic UNC-5 growth cone steering identify eight genes
RT involved in axon guidance in Caenorhabditis elegans.";
RL Dev. Biol. 194:72-85(1998).
RN [4] {ECO:0000305}
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=11454756; DOI=10.1093/genetics/158.3.1071;
RA Merz D.C., Zheng H., Killeen M.T., Krizus A., Culotti J.G.;
RT "Multiple signaling mechanisms of the UNC-6/netrin receptors UNC-5 and UNC-
RT 40/DCC in vivo.";
RL Genetics 158:1071-1080(2001).
RN [5] {ECO:0000305}
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=16520734; DOI=10.1038/nn1666;
RA Adler C.E., Fetter R.D., Bargmann C.I.;
RT "UNC-6/Netrin induces neuronal asymmetry and defines the site of axon
RT formation.";
RL Nat. Neurosci. 9:511-518(2006).
RN [6] {ECO:0000305}
RP FUNCTION, AND INTERACTION WITH UNC-6.
RX PubMed=22426253; DOI=10.1038/nn.3065;
RA Smith C.J., Watson J.D., VanHoven M.K., Colon-Ramos D.A., Miller D.M. III;
RT "Netrin (UNC-6) mediates dendritic self-avoidance.";
RL Nat. Neurosci. 15:731-737(2012).
RN [7] {ECO:0000305}
RP FUNCTION.
RX PubMed=24004945; DOI=10.1242/dev.095190;
RA Dalpe G., Tarsitano M., Persico M.G., Zheng H., Culotti J.;
RT "C. elegans PVF-1 inhibits permissive UNC-40 signalling through CED-10
RT GTPase to position the male ray 1 sensillum.";
RL Development 140:4020-4030(2013).
RN [8] {ECO:0000305}
RP FUNCTION, INTERACTION WITH DRAG-1, DOMAIN, AND MUTAGENESIS OF
RP 628-GLN--LYS-1415.
RX PubMed=24004951; DOI=10.1242/dev.099838;
RA Tian C., Shi H., Xiong S., Hu F., Xiong W.C., Liu J.;
RT "The neogenin/DCC homolog UNC-40 promotes BMP signaling via the RGM protein
RT DRAG-1 in C. elegans.";
RL Development 140:4070-4080(2013).
RN [9] {ECO:0000305}
RP FUNCTION, AND INTERACTION WITH EVA-1.
RX PubMed=25122090; DOI=10.1371/journal.pgen.1004521;
RA Chan K.K., Seetharaman A., Bagg R., Selman G., Zhang Y., Kim J., Roy P.J.;
RT "EVA-1 functions as an UNC-40 Co-receptor to enhance attraction to the
RT MADD-4 guidance cue in Caenorhabditis elegans.";
RL PLoS Genet. 10:E1004521-E1004521(2014).
CC -!- FUNCTION: Receptor for netrin unc-6 required for asymmetric axon
CC formation, axon guidance and cell migrations (PubMed:16520734,
CC PubMed:8861903, PubMed:11454756, PubMed:22426253, PubMed:9473333).
CC Required during axon formation, in response to unc-6, to initiate,
CC maintain and orient asymmetric neuronal growth, and may signal via
CC phosphoinositide 3-kinase (PI3K) (PubMed:16520734). Mediates axon
CC attraction of neuronal growth cones in the developing nervous system
CC upon ligand binding (PubMed:8861903, PubMed:11454756, PubMed:22426253,
CC PubMed:9473333). Axon migration is mediated by the secreted unc-6,
CC which promotes attraction of neurons and axons through binding to the
CC unc-40 receptor, while repulsion requires both unc-5 and unc-40
CC receptors (PubMed:8861903, PubMed:11454756, PubMed:22426253,
CC PubMed:9473333). Involved in dendritic morphogenesis; may act by
CC localizing unc-6 at the tips of growing dendrites for interaction with
CC unc-5 on the apposing branch to induce mutual repulsion
CC (PubMed:22426253). Involved in the ventral-dorsal and anterior-
CC posterior migration of gonadal distal tip cells (DTCs) along the body
CC (PubMed:11454756). Involved in the positioning of ray 1, the most
CC anterior ray sensilium, in the male tail (PubMed:24004945). Positively
CC modulates a TGF-beta-like signaling pathway, independent of its role in
CC unc-6 mediated axon guidance, in association with RGM drag-1
CC (PubMed:24004951). Mediates attraction of muscle plasma membrane
CC extensions, known as muscle arms, towards the secreted madd-4 guidance
CC cue, enhanced by interaction with the coreceptor eva-1
CC (PubMed:25122090). {ECO:0000269|PubMed:11454756,
CC ECO:0000269|PubMed:16520734, ECO:0000269|PubMed:22426253,
CC ECO:0000269|PubMed:24004945, ECO:0000269|PubMed:24004951,
CC ECO:0000269|PubMed:25122090, ECO:0000269|PubMed:8861903,
CC ECO:0000269|PubMed:9473333}.
CC -!- SUBUNIT: Interacts with netrin unc-6 (PubMed:22426253, PubMed:8861903).
CC Interacts with eva-1 (PubMed:25122090). Interacts (via fibronectin
CC type-III domain) with drag-1 (PubMed:24004951).
CC {ECO:0000269|PubMed:22426253, ECO:0000269|PubMed:24004951,
CC ECO:0000269|PubMed:25122090, ECO:0000269|PubMed:8861903}.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane
CC protein.
CC -!- DEVELOPMENTAL STAGE: Expressed on the surface of motile cells and
CC pioneering axons (PubMed:8861903). Expressed at the onset of
CC gastrulation (at about 100 minutes (min) after first cell cleavage) on
CC the surface of all cells, and then gradually diminishes
CC (PubMed:8861903). Highly expressed in the neurula (at about 400 min),
CC on ventral cord motorneurons, including cell bodies and axons,
CC undergoing axonogenesis (PubMed:8861903). Expressed in stage L1 larvae
CC in ventral epidermoblasts as they undergo planar movements within the
CC epithelium and in neuroblasts QL and QR and their descendants as they
CC migrate longitudinally along the epidermis (PubMed:8861903). Expressed
CC in L2 and later stage larvae in distal tip cells (DTCs) of
CC hermaphrodites as they migrate along the body wall (PubMed:8861903).
CC Expressed in the DTCs beginning at the time of the ventral-to-dorsal
CC second migration (PubMed:11454756). Expression on the immature
CC hermaphrodite specific neuron (HSN) is localized to the ventral surface
CC beginning at the early L2 stage (PubMed:16520734).
CC {ECO:0000269|PubMed:11454756, ECO:0000269|PubMed:16520734,
CC ECO:0000269|PubMed:8861903}.
CC -!- DOMAIN: Fibronectin type-III 6 motif is essential for the role of unc-
CC 40 in a TGF-beta-like signaling pathway. {ECO:0000269|PubMed:24004951}.
CC -!- SIMILARITY: Belongs to the immunoglobulin superfamily. DCC family.
CC {ECO:0000305}.
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DR EMBL; U70618; AAB17088.1; -; mRNA.
DR EMBL; BX284601; CCD62978.1; -; Genomic_DNA.
DR PIR; T25892; T25892.
DR RefSeq; NP_491664.1; NM_059263.7.
DR AlphaFoldDB; G5EF96; -.
DR SMR; G5EF96; -.
DR IntAct; G5EF96; 1.
DR STRING; 6239.T19B4.7; -.
DR EPD; G5EF96; -.
DR PaxDb; G5EF96; -.
DR PeptideAtlas; G5EF96; -.
DR EnsemblMetazoa; T19B4.7.1; T19B4.7.1; WBGene00006776.
DR GeneID; 172233; -.
DR KEGG; cel:CELE_T19B4.7; -.
DR CTD; 172233; -.
DR WormBase; T19B4.7; CE25115; WBGene00006776; unc-40.
DR eggNOG; KOG4221; Eukaryota.
DR HOGENOM; CLU_004256_2_0_1; -.
DR InParanoid; G5EF96; -.
DR OMA; SYRTIPS; -.
DR OrthoDB; 217780at2759; -.
DR PhylomeDB; G5EF96; -.
DR Reactome; R-CEL-373752; Netrin-1 signaling.
DR Reactome; R-CEL-376176; Signaling by ROBO receptors.
DR Reactome; R-CEL-418885; DCC mediated attractive signaling.
DR Reactome; R-CEL-418889; Caspase activation via Dependence Receptors in the absence of ligand.
DR Reactome; R-CEL-428542; Regulation of commissural axon pathfinding by SLIT and ROBO.
DR SignaLink; G5EF96; -.
DR Proteomes; UP000001940; Chromosome I.
DR Bgee; WBGene00006776; Expressed in germ line (C elegans) and 7 other tissues.
DR GO; GO:0044295; C:axonal growth cone; IDA:UniProtKB.
DR GO; GO:0031253; C:cell projection membrane; IDA:WormBase.
DR GO; GO:0009986; C:cell surface; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:WormBase.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:WormBase.
DR GO; GO:0043235; C:receptor complex; IPI:WormBase.
DR GO; GO:0005042; F:netrin receptor activity; IMP:UniProtKB.
DR GO; GO:0019904; F:protein domain specific binding; IPI:WormBase.
DR GO; GO:0007411; P:axon guidance; IBA:GO_Central.
DR GO; GO:0016199; P:axon midline choice point recognition; IGI:UniProtKB.
DR GO; GO:0048858; P:cell projection morphogenesis; IMP:UniProtKB.
DR GO; GO:0098609; P:cell-cell adhesion; IBA:GO_Central.
DR GO; GO:0061643; P:chemorepulsion of axon; IMP:UniProtKB.
DR GO; GO:0048813; P:dendrite morphogenesis; IMP:UniProtKB.
DR GO; GO:0035545; P:determination of left/right asymmetry in nervous system; IMP:WormBase.
DR GO; GO:0097628; P:distal tip cell migration; IMP:UniProtKB.
DR GO; GO:0033563; P:dorsal/ventral axon guidance; IMP:WormBase.
DR GO; GO:0035262; P:gonad morphogenesis; IMP:UniProtKB.
DR GO; GO:0008045; P:motor neuron axon guidance; IMP:UniProtKB.
DR GO; GO:0048843; P:negative regulation of axon extension involved in axon guidance; IGI:UniProtKB.
DR GO; GO:1905490; P:negative regulation of sensory neuron axon guidance; IGI:UniProtKB.
DR GO; GO:0045138; P:nematode male tail tip morphogenesis; IMP:WormBase.
DR GO; GO:0038007; P:netrin-activated signaling pathway; IMP:UniProtKB.
DR GO; GO:0097402; P:neuroblast migration; IMP:WormBase.
DR GO; GO:0001764; P:neuron migration; IMP:WormBase.
DR GO; GO:0031175; P:neuron projection development; IMP:WormBase.
DR GO; GO:0030513; P:positive regulation of BMP signaling pathway; IGI:WormBase.
DR GO; GO:0040017; P:positive regulation of locomotion; IMP:UniProtKB.
DR GO; GO:0040018; P:positive regulation of multicellular organism growth; IMP:UniProtKB.
DR GO; GO:0051965; P:positive regulation of synapse assembly; IMP:UniProtKB.
DR GO; GO:0030334; P:regulation of cell migration; IMP:WormBase.
DR GO; GO:1905815; P:regulation of dorsal/ventral axon guidance; IMP:UniProtKB.
DR GO; GO:0042661; P:regulation of mesodermal cell fate specification; IGI:UniProtKB.
DR GO; GO:1905812; P:regulation of motor neuron axon guidance; IGI:UniProtKB.
DR GO; GO:0097374; P:sensory neuron axon guidance; IMP:UniProtKB.
DR GO; GO:1901048; P:transforming growth factor beta receptor signaling pathway involved in regulation of multicellular organism growth; IGI:UniProtKB.
DR CDD; cd00063; FN3; 6.
DR Gene3D; 2.60.40.10; -; 10.
DR InterPro; IPR003961; FN3_dom.
DR InterPro; IPR036116; FN3_sf.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR013098; Ig_I-set.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR003598; Ig_sub2.
DR Pfam; PF00041; fn3; 6.
DR Pfam; PF07679; I-set; 3.
DR SMART; SM00060; FN3; 6.
DR SMART; SM00409; IG; 4.
DR SMART; SM00408; IGc2; 4.
DR SUPFAM; SSF48726; SSF48726; 4.
DR SUPFAM; SSF49265; SSF49265; 4.
DR PROSITE; PS50853; FN3; 6.
DR PROSITE; PS50835; IG_LIKE; 4.
PE 1: Evidence at protein level;
KW Cell membrane; Disulfide bond; Immunoglobulin domain; Membrane;
KW Neurogenesis; Reference proteome; Repeat; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..1415
FT /note="Netrin receptor unc-40"
FT /evidence="ECO:0000255"
FT /id="PRO_5015091971"
FT TOPO_DOM 23..1082
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1083..1103
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1104..1415
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT DOMAIN 41..130
FT /note="Ig-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DOMAIN 148..235
FT /note="Ig-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DOMAIN 244..331
FT /note="Ig-like 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DOMAIN 336..421
FT /note="Ig-like 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DOMAIN 442..532
FT /note="Fibronectin type-III 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 538..630
FT /note="Fibronectin type-III 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 635..730
FT /note="Fibronectin type-III 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 739..830
FT /note="Fibronectin type-III 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 851..944
FT /note="Fibronectin type-III 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 947..1046
FT /note="Fibronectin type-III 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT REGION 612..658
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 830..853
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 940..970
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1112..1136
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1178..1274
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 612..650
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1184..1218
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1228..1243
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT DISULFID 63..118
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 169..218
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 266..315
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 357..405
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT MUTAGEN 157..1415
FT /note="Missing: In e1430; defects in dorsal pathfinding.
FT The axons of DA and DB motorneurons do not grow to their
FT targets in the dorsal cord and instead extend along
FT subdorsal longitudinal paths."
FT /evidence="ECO:0000269|PubMed:8861903,
FT ECO:0000269|PubMed:9473333"
FT MUTAGEN 628..1415
FT /note="Missing: In jj59; significantly smaller body size;
FT suppression of the mesodermal M lineage phenotype on a sma-
FT 9 mutant background."
FT /evidence="ECO:0000269|PubMed:24004951"
SQ SEQUENCE 1415 AA; 154437 MW; B2D90F76F9FEB6A9 CRC64;
MILRHFGFIL IILTVYLSST HATTRKHHRR SIDNDARNLG FQFVMEPRRN VTVMESSSHL
LECSYVLAHE RLVHDVRIEW KRDGVLLSER TSSRIKVMSN GSLWIESVSS AEEGTYQCAV
HVTTKSDQTS DTWTFLSRKA TLRLADLAKF ELQAIDRTLA KGQPTAFHCL INSKPTPTAV
WLHNDEPIVN GGEYHILPVS NTLEISSTQS RHEGTYRCTV EGAGKRRSSQ TARLTVTTET
VSNELVFITT PRLQVVEQGD EFLLECLVAS LIRPQVRWLK DSRQIIVDGV RIRRVGVSSI
LVSRASIEDT GLYTCRASNN DDSIDRAVSV EVRAPPRITT RPTTKVAVET ADVELECGTA
AARPEARVNW YKNGEAIIGS EYFVIEPNRL RILGVVRADQ AIYQCIAEND VGSEQASAQL
LVDAPDSSSV AASSGVPMTS SAPLGLRSTS SGSRFINVEW DPPVQRNGNI MRYHIFYKDN
LIDRERMINS SSTSATLTSL QPSTMYLIRV TAENEAGMGK FSDSLKVTTN KEQAVPGKVA
SLTTTATGPE TIDIRWSPPS GGQPALRYKI FYSHDPLEKN EKETLITTST THYTLHGMDK
YTGYQIRIEA EGSNGSGLSS DTVKVRTQSD EPSAPPVNIQ AEADSSTSVR VSWDEPEEES
VNGEITGYRL KYKTKARGAK GNTLVIDATA REYTMGNLEP NTQYLIRMAV VNHNGTGPFS
DWVSIDTPGQ DKEERTLGAP REIRPHAGID YILVSWLPPA DEQNLVRGYQ IGWGLSVPDT
ETIRVTASTT QYKIARLHSE RDYVISLRAF NNLGSGFPIY ETVRTLSRET PSHFNEDSDS
DDSDVGSSES TPVGVRAEAI SATSIRVMWT ESDETAFNTQ YTVRYSTAVD GNQHRYVNST
ETWATVEGLR PATEYEFAVR AVASNGQLST WSMATRNRTL AAPPSSAPRD LTVLPAESGD
PHSSSLHWQP PKYSNGEIEE YLVFYTDRAS LADKDWTINY VAGDKLSHQV SNLLPKANYF
FKIQARNEKG HGPFSSVVGY TPSGGAILSG KDRHNARGHG SAASGDTVSL VDQLQSLLHS
NPLYLILLAA FALILILTLI LIIMCCWKRS SGGGRKNGYQ SGKKTSAGAG SGGGIGGLGG
PPNDLWINGT GSHMRAGASD YMVDGLATAH LTAADIESPT PRYHHLQGQG TLTRSYHQSS
QSLEGRQRTP QVVYTGTGRH QPIQRIDFES PYGSSSAIGS ASTPPLPMQA PPSGPPTVID
GYRTLRGTPP NSSAANALRS FTQLAGATPP PPHSAASSSS RPTIIAAGGR QVPVGRATAQ
PRVNVANIYS PFASCSASSD AGESDKKSGE CMEMRETTPI KSNTAGSSNG EKMNTNMNPS
HSAEDLNAHL ENLDTMLDDL QQLQHNLHFE TSMDK
