UNC6_CAEEL
ID UNC6_CAEEL Reviewed; 612 AA.
AC P34710;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1994, sequence version 1.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Netrin unc-6;
DE AltName: Full=Uncoordinated protein 6;
DE Flags: Precursor;
GN Name=unc-6 {ECO:0000312|WormBase:F41C6.1};
GN Synonyms=unc-106 {ECO:0000312|WormBase:F41C6.1};
GN ORFNames=F41C6.1 {ECO:0000312|WormBase:F41C6.1};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=1329863; DOI=10.1016/0896-6273(92)90240-e;
RA Ishii N., Wadsworth W.G., Stern B.D., Culotti J.G., Hedgecock E.M.;
RT "UNC-6, a laminin-related protein, guides cell and pioneer axon migrations
RT in C. elegans.";
RL Neuron 9:873-881(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
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 INTERACTION WITH UNC-5.
RX PubMed=8332188; DOI=10.1038/364327a0;
RA Hamelin M., Zhou Y., Su M.-W., Scott I.M., Culotti J.G.;
RT "Expression of the UNC-5 guidance receptor in the touch neurons of C.
RT elegans steers their axons dorsally.";
RL Nature 364:327-330(1993).
RN [4]
RP FUNCTION, AND INTERACTION WITH UNC-40.
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 [5]
RP FUNCTION, AND MUTAGENESIS OF 99-GLN--TYR-612.
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 [6]
RP FUNCTION, AND MUTAGENESIS OF 99-GLN--TYR-612.
RX PubMed=17716643; DOI=10.1016/j.ydbio.2007.07.014;
RA Zheng H., Coudiere L., Camia C., Colavita A., Culotti J.G., Merz D.C.;
RT "C. elegans seu-1 encodes novel nuclear proteins that regulate responses to
RT UNC-6/netrin guidance cues.";
RL Dev. Biol. 310:44-53(2007).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=22732572; DOI=10.1016/j.ydbio.2012.06.011;
RA Martynovsky M., Wong M.C., Byrd D.T., Kimble J., Schwarzbauer J.E.;
RT "mig-38, a novel gene that regulates distal tip cell turning during
RT gonadogenesis in C. elegans hermaphrodites.";
RL Dev. Biol. 368:404-414(2012).
RN [8] {ECO:0000305}
RP FUNCTION, AND INTERACTION WITH UNC-40.
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 [9]
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 [10]
RP FUNCTION, AND MUTAGENESIS OF ARG-30; 99-GLN--TYR-612; ARG-307 AND LYS-598.
RX PubMed=28846083; DOI=10.1038/nn.4630;
RA Rapti G., Li C., Shan A., Lu Y., Shaham S.;
RT "Glia initiate brain assembly through noncanonical Chimaerin-Furin axon
RT guidance in C. elegans.";
RL Nat. Neurosci. 20:1350-1360(2017).
RN [11]
RP FUNCTION, AND MUTAGENESIS OF 99-GLN--TYR-612.
RX PubMed=29742100; DOI=10.1371/journal.pgen.1007312;
RA Varshney A., Benedetti K., Watters K., Shankar R., Tatarakis D.,
RA Coto Villa D., Magallanes K., Agenor V., Wung W., Farah F., Ali N., Le N.,
RA Pyle J., Farooqi A., Kieu Z., Bremer M., VanHoven M.;
RT "The receptor protein tyrosine phosphatase CLR-1 is required for synaptic
RT partner recognition.";
RL PLoS Genet. 14:E1007312-E1007312(2018).
CC -!- FUNCTION: Component of an extracellular matrix cue that guides
CC dorsoventral migrations on the epidermis (PubMed:8861903). Required for
CC the guidance of pioneer axons and migrating cells along the body wall
CC (PubMed:8332188, PubMed:28846083). In particular, it is required for
CC the guidance of axons from neurons, including SubL neurons and AIY
CC interneurons, into the nerve ring (PubMed:28846083, PubMed:9473333).
CC During gonad morphogenesis, involved in distal tip cell (DTC) migration
CC from the dorsal side of the hermaphrodite body to the midbody to allow
CC for formation of gonad arms (PubMed:22732572, PubMed:17716643). Its
CC association with either unc-40 or unc-5 receptors will lead to axon
CC attraction or repulsion, respectively (PubMed:8332188, PubMed:8861903,
CC PubMed:9473333). Involved in dendritic morphogenesis; may act by
CC association with unc-40 at the tips of growing dendrites for
CC interaction with unc-5 on the apposing branch to induce mutual
CC repulsion (PubMed:22426253). Involved in the positioning of ray 1, the
CC most anterior ray sensilium, in the male tail (PubMed:24004945).
CC Required for the formation of synapses between the AVA interneurons and
CC the PHB sensory neurons (PubMed:29742100).
CC {ECO:0000269|PubMed:17716643, ECO:0000269|PubMed:22426253,
CC ECO:0000269|PubMed:22732572, ECO:0000269|PubMed:24004945,
CC ECO:0000269|PubMed:28846083, ECO:0000269|PubMed:29742100,
CC ECO:0000269|PubMed:8332188, ECO:0000269|PubMed:8861903,
CC ECO:0000269|PubMed:9473333}.
CC -!- SUBUNIT: Binds to unc-5 and unc-40 receptors.
CC {ECO:0000269|PubMed:22426253, ECO:0000269|PubMed:8861903}.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix, basement membrane. Note=Epidermal basal lamina.
CC -!- DOMAIN: Mutations that delete the second laminin EGF-like repeat impair
CC only dorsal migrations of mesodermal cells and axons.
CC -!- DISRUPTION PHENOTYPE: Defective gonad distal tip cell (DTC) migration
CC whereby DTCs migrate towards the midbody of the hermaphrodite on the
CC ventral side rather than the dorsal side of the body resulting in
CC ventrally located gonad arms. Double knockout with mig-38 RNAi results
CC in failed gonad DTC migration to the midbody of the hermaphrodite.
CC {ECO:0000269|PubMed:22732572}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; M80241; AAA28157.1; -; Genomic_DNA.
DR EMBL; BX284606; CCD67895.1; -; Genomic_DNA.
DR PIR; JH0799; JH0799.
DR RefSeq; NP_509165.1; NM_076764.3.
DR AlphaFoldDB; P34710; -.
DR SMR; P34710; -.
DR BioGRID; 45889; 4.
DR DIP; DIP-24693N; -.
DR STRING; 6239.F41C6.1.1; -.
DR EPD; P34710; -.
DR PaxDb; P34710; -.
DR PeptideAtlas; P34710; -.
DR EnsemblMetazoa; F41C6.1.1; F41C6.1.1; WBGene00006746.
DR EnsemblMetazoa; F41C6.1.2; F41C6.1.2; WBGene00006746.
DR GeneID; 180961; -.
DR KEGG; cel:CELE_F41C6.1; -.
DR UCSC; F41C6.1.1; c. elegans.
DR CTD; 180961; -.
DR WormBase; F41C6.1; CE04538; WBGene00006746; unc-6.
DR eggNOG; KOG3512; Eukaryota.
DR GeneTree; ENSGT00940000153882; -.
DR HOGENOM; CLU_018213_2_0_1; -.
DR InParanoid; P34710; -.
DR OMA; YFSQFSM; -.
DR OrthoDB; 858946at2759; -.
DR PhylomeDB; P34710; -.
DR Reactome; R-CEL-373752; Netrin-1 signaling.
DR Reactome; R-CEL-418885; DCC mediated attractive signaling.
DR PRO; PR:P34710; -.
DR Proteomes; UP000001940; Chromosome X.
DR Bgee; WBGene00006746; Expressed in hermaphroditic organism and 18 other tissues.
DR GO; GO:0030424; C:axon; IDA:WormBase.
DR GO; GO:0005604; C:basement membrane; IDA:WormBase.
DR GO; GO:0005737; C:cytoplasm; IDA:WormBase.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005102; F:signaling receptor binding; ISS:WormBase.
DR GO; GO:0009887; P:animal organ morphogenesis; IBA:GO_Central.
DR GO; GO:0007411; P:axon guidance; IMP:WormBase.
DR GO; GO:0016358; P:dendrite development; IBA:GO_Central.
DR GO; GO:0048813; P:dendrite morphogenesis; IMP:UniProtKB.
DR GO; GO:0033563; P:dorsal/ventral axon guidance; IMP:UniProtKB.
DR GO; GO:0030950; P:establishment or maintenance of actin cytoskeleton polarity; IMP:UniProtKB.
DR GO; GO:0035262; P:gonad morphogenesis; IMP:UniProtKB.
DR GO; GO:0097376; P:interneuron axon guidance; IMP:UniProtKB.
DR GO; GO:0008078; P:mesodermal cell migration; IMP:WormBase.
DR GO; GO:0008045; P:motor neuron axon guidance; IMP:UniProtKB.
DR GO; GO:0031115; P:negative regulation of microtubule polymerization; IMP: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:0031175; P:neuron projection development; IMP:WormBase.
DR GO; GO:1905488; P:positive regulation of anterior/posterior axon guidance; IMP:UniProtKB.
DR GO; GO:0040017; P:positive regulation of locomotion; 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:1905812; P:regulation of motor neuron axon guidance; IGI:UniProtKB.
DR GO; GO:1905489; P:regulation of sensory neuron axon guidance; IGI:UniProtKB.
DR GO; GO:0097374; P:sensory neuron axon guidance; IMP:UniProtKB.
DR GO; GO:0009888; P:tissue development; IBA:GO_Central.
DR GO; GO:0007419; P:ventral cord development; IMP:UniProtKB.
DR CDD; cd00055; EGF_Lam; 3.
DR Gene3D; 2.40.50.120; -; 1.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR008211; Laminin_N.
DR InterPro; IPR002049; LE_dom.
DR InterPro; IPR001134; Netrin_domain.
DR InterPro; IPR018933; Netrin_module_non-TIMP.
DR InterPro; IPR008993; TIMP-like_OB-fold.
DR Pfam; PF00053; Laminin_EGF; 3.
DR Pfam; PF00055; Laminin_N; 1.
DR Pfam; PF01759; NTR; 1.
DR SMART; SM00643; C345C; 1.
DR SMART; SM00180; EGF_Lam; 3.
DR SMART; SM00136; LamNT; 1.
DR SUPFAM; SSF50242; SSF50242; 1.
DR PROSITE; PS00022; EGF_1; 2.
DR PROSITE; PS01248; EGF_LAM_1; 3.
DR PROSITE; PS50027; EGF_LAM_2; 3.
DR PROSITE; PS51117; LAMININ_NTER; 1.
DR PROSITE; PS50189; NTR; 1.
PE 1: Evidence at protein level;
KW Basement membrane; Disulfide bond; Extracellular matrix; Glycoprotein;
KW Laminin EGF-like domain; Neurogenesis; Reference proteome; Repeat;
KW Secreted; Signal.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..612
FT /note="Netrin unc-6"
FT /id="PRO_0000017090"
FT DOMAIN 43..290
FT /note="Laminin N-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00466"
FT DOMAIN 291..346
FT /note="Laminin EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00460"
FT DOMAIN 347..409
FT /note="Laminin EGF-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00460"
FT DOMAIN 410..459
FT /note="Laminin EGF-like 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00460"
FT DOMAIN 478..604
FT /note="NTR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT CARBOHYD 114
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 128
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 268
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 368
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 423
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 564
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 117..149
FT /evidence="ECO:0000250"
FT DISULFID 291..300
FT /evidence="ECO:0000250"
FT DISULFID 293..310
FT /evidence="ECO:0000250"
FT DISULFID 312..321
FT /evidence="ECO:0000250"
FT DISULFID 324..344
FT /evidence="ECO:0000250"
FT DISULFID 347..356
FT /evidence="ECO:0000250"
FT DISULFID 349..374
FT /evidence="ECO:0000250"
FT DISULFID 377..386
FT /evidence="ECO:0000250"
FT DISULFID 389..407
FT /evidence="ECO:0000250"
FT DISULFID 410..422
FT /evidence="ECO:0000250"
FT DISULFID 412..429
FT /evidence="ECO:0000250"
FT DISULFID 431..440
FT /evidence="ECO:0000250"
FT DISULFID 443..457
FT /evidence="ECO:0000250"
FT DISULFID 478..547
FT /evidence="ECO:0000250"
FT DISULFID 494..604
FT /evidence="ECO:0000250"
FT MUTAGEN 30
FT /note="Missing: Partially rescues the AIY axon guidance
FT defects of the unc-6 ev400 mutant."
FT /evidence="ECO:0000269|PubMed:28846083"
FT MUTAGEN 99..612
FT /note="Missing: In ev400; reduces synapse formation between
FT the PHB and AVA neurons. Defective guidance of the AIY axon
FT into the nerve ring, which impairs nerve ring assembly.
FT Anterior touch neuron axons fail to extend in a dorsal
FT direction. The axons of DA and DB motorneurons do not grow
FT to their targets in the dorsal cord and instead extend
FT along subdorsal longitudinal paths. Distal tip cell
FT migration defects. The distal tip cell migration defects
FT are enhanced in seu-1 ev520 or seu-1 ev529 mutants."
FT /evidence="ECO:0000269|PubMed:17716643,
FT ECO:0000269|PubMed:28846083, ECO:0000269|PubMed:29742100,
FT ECO:0000269|PubMed:9473333"
FT MUTAGEN 307
FT /note="Missing: Partially rescues the AIY axon guidance
FT defects of the unc-6 ev400 mutant."
FT /evidence="ECO:0000269|PubMed:28846083"
FT MUTAGEN 598
FT /note="Missing: Does not rescue the AIY axon guidance
FT defects of the unc-6 ev400 mutant."
FT /evidence="ECO:0000269|PubMed:28846083"
SQ SEQUENCE 612 AA; 68442 MW; 30920E15BF177953 CRC64;
MITSVLRYVL ALYFCMGIAH GAYFSQFSMR APDHDPCHDH TGRPVRCVPE FINAAFGKPV
IASDTCGTNR PDKYCTVKEG PDGIIREQCD TCDARNHFQS HPASLLTDLN SIGNMTCWVS
TPSLSPQNVS LTLSLGKKFE LTYVSMHFCS RLPDSMALYK SADFGKTWTP FQFYSSECRR
IFGRDPDVSI TKSNEQEAVC TASHIMGPGG NRVAFPFLEN RPSAQNFENS PVLQDWVTAT
DIKVVFSRLS PDQAELYGLS NDVNSYGNET DDEVKQRYFY SMGELAVGGR CKCNGHASRC
IFDKMGRYTC DCKHNTAGTE CEMCKPFHYD RPWGRATANS ANSCVACNCN QHAKRCRFDA
ELFRLSGNRS GGVCLNCRHN TAGRNCHLCK PGFVRDTSLP MTHRKACKSC GCHPVGSLGK
SCNQSSGQCV CKPGVTGTTC NRCAKGYQQS RSTVTPCIKI PTKADFIGSS HSEEQDQCSK
CRIVPKRLNQ KKFCKRDHAV QMVVVSREMV DGWAKYKIVV ESVFKRGTEN MQRGETSLWI
SPQGVICKCP KLRVGRRYLL LGKNDSDHER DGLMVNPQTV LVEWEDDIMD KVLRFSKKDK
LGQCPEITSH RY
