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UN129_CAEEL
ID   UN129_CAEEL             Reviewed;         407 AA.
AC   G5EBY8;
DT   10-FEB-2021, integrated into UniProtKB/Swiss-Prot.
DT   14-DEC-2011, sequence version 1.
DT   03-AUG-2022, entry version 95.
DE   RecName: Full=BMP-like protein unc-129 {ECO:0000305};
DE   AltName: Full=Uncoordinated protein 129 {ECO:0000312|WormBase:C53D6.2};
DE   Flags: Precursor;
GN   Name=unc-129 {ECO:0000312|WormBase:C53D6.2};
GN   ORFNames=C53D6.2 {ECO:0000312|WormBase:C53D6.2};
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:AAC48376.1}
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, DEVELOPMENTAL STAGE, AND MUTAGENESIS
RP   OF ASP-163; 242-TYR--LEU-407 AND 327-ASP--LEU-407.
RC   STRAIN=Bristol N2 {ECO:0000312|EMBL:AAC48376.1};
RX   PubMed=9685266; DOI=10.1126/science.281.5377.706;
RA   Colavita A., Krishna S., Zheng H., Padgett R.W., Culotti J.G.;
RT   "Pioneer axon guidance by UNC-129, a C. elegans TGF-beta.";
RL   Science 281:706-709(1998).
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 327-ASP--LEU-407.
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 MUTAGENESIS OF 327-ASP--LEU-407.
RX   PubMed=11018016; DOI=10.1101/gad.831500;
RA   Nash B., Colavita A., Zheng H., Roy P.J., Culotti J.G.;
RT   "The forkhead transcription factor UNC-130 is required for the graded
RT   spatial expression of the UNC-129 TGF-beta guidance factor in C. elegans.";
RL   Genes Dev. 14:2486-2500(2000).
RN   [5] {ECO:0000305}
RP   FUNCTION, AND MUTAGENESIS OF 327-ASP--LEU-407.
RX   PubMed=15030761; DOI=10.1016/s1534-5807(04)00057-7;
RA   Ikegami R., Zheng H., Ong S.-H., Culotti J.G.;
RT   "Integration of semaphorin-2A/MAB-20, ephrin-4, and UNC-129 TGF-beta
RT   signaling pathways regulates sorting of distinct sensory rays in C.
RT   elegans.";
RL   Dev. Cell 6:383-395(2004).
RN   [6] {ECO:0000305}
RP   FUNCTION, INTERACTION WITH UNC-5, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP   327-ASP--LEU-407.
RX   PubMed=19169249; DOI=10.1038/nn.2256;
RA   MacNeil L.T., Hardy W.R., Pawson T., Wrana J.L., Culotti J.G.;
RT   "UNC-129 regulates the balance between UNC-40 dependent and independent
RT   UNC-5 signaling pathways.";
RL   Nat. Neurosci. 12:150-155(2009).
RN   [7] {ECO:0000305}
RP   DEVELOPMENTAL STAGE.
RX   PubMed=27341757; DOI=10.1016/j.ydbio.2016.06.029;
RA   Kersey R.K., Brodigan T.M., Fukushige T., Krause M.W.;
RT   "Regulation of UNC-130/FOXD-mediated mesodermal patterning in C. elegans.";
RL   Dev. Biol. 416:300-311(2016).
CC   -!- FUNCTION: Required for the migration of axonal growth-cones and distal
CC       tip cells (DTC) along the dorsal-ventral axis of the body wall
CC       (PubMed:9685266, PubMed:19169249, PubMed:9473333). Acts cell
CC       nonautonomously and independently of the classical daf-4, sma-6 or daf-
CC       1 TGFbeta receptor signaling (PubMed:9685266, PubMed:11018016,
CC       PubMed:19169249). During axon migration, facilitates long-range
CC       repulsive guidance of unc-6/netrin by enhancing unc-5-unc-40 signaling
CC       at the expense of unc-5 alone signaling, probably through direct
CC       interaction with receptor unc-5 (PubMed:19169249, PubMed:9473333).
CC       Involved in cell-cell contact formation in sensory rays in the
CC       developing male tail, via a pathway involving plx-2 and mab-
CC       20/semaphorin-2A (PubMed:15030761). {ECO:0000269|PubMed:11018016,
CC       ECO:0000269|PubMed:15030761, ECO:0000269|PubMed:19169249,
CC       ECO:0000269|PubMed:9473333, ECO:0000269|PubMed:9685266}.
CC   -!- SUBUNIT: Interacts with netrin receptor unc-5; the interaction is
CC       direct. {ECO:0000269|PubMed:19169249}.
CC   -!- SUBCELLULAR LOCATION: Secreted, extracellular space
CC       {ECO:0000269|PubMed:19169249}.
CC   -!- DEVELOPMENTAL STAGE: Expressed first at late gastrulation stage in
CC       cells that include descendants of the AB and E lineages
CC       (PubMed:9685266). Expression detected in dorsal body wall muscle (BWM)
CC       at the 1.5-to 2-fold stage of embryogenesis; also in some of cells in
CC       the head, including one ventral muscle (PubMed:9685266,
CC       PubMed:27341757). Between 520 min and hatching, expressed in the DA and
CC       DB motor neurons, excluding DA8 and DA9 (PubMed:9685266). This pattern
CC       of expression persists into adulthood (PubMed:9685266).
CC       {ECO:0000269|PubMed:27341757, ECO:0000269|PubMed:9685266}.
CC   -!- SIMILARITY: Belongs to the TGF-beta family.
CC       {ECO:0000255|RuleBase:RU000354}.
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DR   EMBL; AF029887; AAC48376.1; -; mRNA.
DR   EMBL; BX284604; CAB61007.1; -; Genomic_DNA.
DR   PIR; T37242; T37242.
DR   RefSeq; NP_501566.1; NM_069165.5.
DR   AlphaFoldDB; G5EBY8; -.
DR   IntAct; G5EBY8; 1.
DR   STRING; 6239.C53D6.2; -.
DR   EPD; G5EBY8; -.
DR   PaxDb; G5EBY8; -.
DR   PeptideAtlas; G5EBY8; -.
DR   EnsemblMetazoa; C53D6.2.1; C53D6.2.1; WBGene00006852.
DR   GeneID; 177719; -.
DR   KEGG; cel:CELE_C53D6.2; -.
DR   CTD; 177719; -.
DR   WormBase; C53D6.2; CE24863; WBGene00006852; unc-129.
DR   eggNOG; KOG3900; Eukaryota.
DR   GeneTree; ENSGT00940000160223; -.
DR   HOGENOM; CLU_055885_0_0_1; -.
DR   InParanoid; G5EBY8; -.
DR   OMA; IETSFCK; -.
DR   OrthoDB; 744135at2759; -.
DR   PhylomeDB; G5EBY8; -.
DR   Reactome; R-CEL-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR   Reactome; R-CEL-8957275; Post-translational protein phosphorylation.
DR   Proteomes; UP000001940; Chromosome IV.
DR   Bgee; WBGene00006852; Expressed in embryo and 3 other tissues.
DR   GO; GO:0005576; C:extracellular region; ISS:WormBase.
DR   GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR   GO; GO:0005125; F:cytokine activity; IBA:GO_Central.
DR   GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR   GO; GO:0005102; F:signaling receptor binding; IPI:WormBase.
DR   GO; GO:0005160; F:transforming growth factor beta receptor binding; ISS:WormBase.
DR   GO; GO:0043057; P:backward locomotion; IMP:WormBase.
DR   GO; GO:0033563; P:dorsal/ventral axon guidance; IMP:WormBase.
DR   GO; GO:0040039; P:inductive cell migration; IMP:WormBase.
DR   GO; GO:0040011; P:locomotion; IMP:WormBase.
DR   GO; GO:0008045; P:motor neuron axon guidance; IMP:WormBase.
DR   GO; GO:0045138; P:nematode male tail tip morphogenesis; IGI:WormBase.
DR   GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; IBA:GO_Central.
DR   GO; GO:0060395; P:SMAD protein signal transduction; IBA:GO_Central.
DR   Gene3D; 2.10.90.10; -; 1.
DR   InterPro; IPR029034; Cystine-knot_cytokine.
DR   InterPro; IPR001839; TGF-b_C.
DR   InterPro; IPR015615; TGF-beta-rel.
DR   PANTHER; PTHR11848; PTHR11848; 1.
DR   Pfam; PF00019; TGF_beta; 1.
DR   SMART; SM00204; TGFB; 1.
DR   SUPFAM; SSF57501; SSF57501; 1.
DR   PROSITE; PS51362; TGF_BETA_2; 1.
PE   1: Evidence at protein level;
KW   Glycoprotein; Growth factor; Neurogenesis; Reference proteome; Secreted;
KW   Signal.
FT   SIGNAL          1..18
FT                   /evidence="ECO:0000255"
FT   CHAIN           19..407
FT                   /note="BMP-like protein unc-129"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000451997"
FT   REGION          252..283
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        252..270
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CARBOHYD        27
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   CARBOHYD        42
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   CARBOHYD        211
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   CARBOHYD        395
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   MUTAGEN         163
FT                   /note="D->N: In ev566; axon guidance defects, but at a
FT                   lower frequency than in ev557 or ev554 mutants."
FT                   /evidence="ECO:0000269|PubMed:9685266"
FT   MUTAGEN         242..407
FT                   /note="Missing: In ev557; axon guidance defects."
FT                   /evidence="ECO:0000269|PubMed:9685266"
FT   MUTAGEN         327..407
FT                   /note="Missing: In ev554; uncoordinated movement defects
FT                   whereby animals exhibit a kink in the normal wavelike
FT                   motion during backwards movements. Axon guidance defects.
FT                   The axons of DD and VD motorneurons do not reach the dorsal
FT                   cord and instead extend along longitudinal paths at aberant
FT                   axial levels. The axons of DA and DB motorneurons do not
FT                   grow to their targets in the dorsal cord and instead extend
FT                   along subdorsal longitudinal paths. Some motorneurons
FT                   display excessive branching and disorganized trajectories.
FT                   Does not have distal tip cell (DTC) migration defects and
FT                   partially suppresses DTC migration defects when on an unc-
FT                   130 mutant background. Similar frequency of DA and DB motor
FT                   axon guidance defects on the unc-130 or unc-40 mutant
FT                   backgrounds. Exhibit similar locomotion defects on a daf-4
FT                   mutant background. Enhances ray fusion defects on an efn-4
FT                   mutant background. Suppresses the anterior touch neuron
FT                   axon guidance defects in an unc-5 over-expression mutant
FT                   background."
FT                   /evidence="ECO:0000269|PubMed:11018016,
FT                   ECO:0000269|PubMed:15030761, ECO:0000269|PubMed:19169249,
FT                   ECO:0000269|PubMed:9473333, ECO:0000269|PubMed:9685266"
SQ   SEQUENCE   407 AA;  47339 MW;  1A6C9243C298EF6A CRC64;
     MRRLPIVLLL SVFSIANCAK VDVDLINETI RDLLHFKSSD PNVTSFHRSS HTLTEHMKNL
     YENFIDEDSN EDGNLVRAIE PAVGKFEGQE VLVFDVEGFD SHESIMRAEL HFYLRRRDSF
     ARRRSRQIRA KSVCVNEYCR QQTLKKIRVG GDENLEEYKV IWDATKSVFD SYHLDAKQAV
     FRITREHSKM RPYAEMIRKS TPFLVIYSKV NHTLDTVSVM KQTEQTKRKR RDLGNEELRE
     YYNYNSIPLD NDDREPIKRK NGKKNSLSEE ISSEDVWQGF GEETSREERE RIANEELAND
     VRVVLLQNKN RCHKEGVLVS LKHFGWDRYV IEPKTIETSF CKGKCAKPML TSGKASNHAM
     LQSLFAAEPV CCAPTNLKSL NFWYRDEKGR TVIRNYSKML IGSCSCL
 
 
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