ID SEM2A_CAEEL Reviewed; 658 AA.
AC Q95XP4; Q86LT8; Q9NI38; W6RTP3; W6SBL1;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 27-MAR-2024, entry version 152.
DE RecName: Full=Semaphorin-2A;
DE Short=Sema-2a;
DE AltName: Full=Protein male abnormal 20;
DE Flags: Precursor;
GN Name=mab-20 {ECO:0000312|WormBase:Y71G12B.20a};
GN ORFNames=Y71G12B.20 {ECO:0000312|WormBase:Y71G12B.20a};
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 [MRNA] (ISOFORM A), FUNCTION, TISSUE SPECIFICITY, AND
RP DISRUPTION PHENOTYPE.
RX PubMed=10648234; DOI=10.1242/dev.127.4.755;
RA Roy P.J., Zheng H., Warren C.E., Culotti J.G.;
RT "mab-20 encodes Semaphorin-2a and is required to prevent ectopic cell
RT contacts during epidermal morphogenesis in Caenorhabditis elegans.";
RL Development 127:755-767(2000).
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.
RX PubMed=12403719; DOI=10.1242/dev.00122;
RA Chin-Sang I.D., Moseley S.L., Ding M., Harrington R.J., George S.E.,
RA Chisholm A.D.;
RT "The divergent C. elegans ephrin EFN-4 functions in embryonic morphogenesis
RT in a pathway independent of the VAB-1 Eph receptor.";
RL Development 129:5499-5510(2002).
RN [4]
RP FUNCTION.
RX PubMed=12679110; DOI=10.1016/s0012-1606(02)00129-x;
RA Hahn A.C., Emmons S.W.;
RT "The roles of an ephrin and a semaphorin in patterning cell-cell contacts
RT in C. elegans sensory organ development.";
RL Dev. Biol. 256:379-388(2003).
RN [5]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-65, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC STRAIN=Bristol N2;
RX PubMed=12754521; DOI=10.1038/nbt829;
RA Kaji H., Saito H., Yamauchi Y., Shinkawa T., Taoka M., Hirabayashi J.,
RA Kasai K., Takahashi N., Isobe T.;
RT "Lectin affinity capture, isotope-coded tagging and mass spectrometry to
RT identify N-linked glycoproteins.";
RL Nat. Biotechnol. 21:667-672(2003).
RN [6]
RP FUNCTION, AND INTERACTION WITH PLX-2.
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 [7]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-65 AND ASN-275, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=Bristol N2;
RX PubMed=17761667; DOI=10.1074/mcp.m600392-mcp200;
RA Kaji H., Kamiie J., Kawakami H., Kido K., Yamauchi Y., Shinkawa T.,
RA Taoka M., Takahashi N., Isobe T.;
RT "Proteomics reveals N-linked glycoprotein diversity in Caenorhabditis
RT elegans and suggests an atypical translocation mechanism for integral
RT membrane proteins.";
RL Mol. Cell. Proteomics 6:2100-2109(2007).
RN [8]
RP FUNCTION.
RX PubMed=25358863; DOI=10.1038/ncomms6325;
RA Nakamura F., Kumeta K., Hida T., Isono T., Nakayama Y.,
RA Kuramata-Matsuoka E., Yamashita N., Uchida Y., Ogura K., Gengyo-Ando K.,
RA Mitani S., Ogino T., Goshima Y.;
RT "Amino- and carboxyl-terminal domains of Filamin-A interact with CRMP1 to
RT mediate Sema3A signalling.";
RL Nat. Commun. 5:5325-5325(2014).
RN [9]
RP FUNCTION, AND MUTAGENESIS OF ARG-247.
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).
CC -!- FUNCTION: Regulates the formation or stabilization of cell-cell
CC contacts at several stages of epithelial morphogenesis
CC (PubMed:10648234, PubMed:12403719, PubMed:17761667). In early embryonic
CC development, required for proper ventral closure of the epidermis
CC (PubMed:12403719). During male tail morphogenesis, regulates precursor
CC cell sorting and allows the formation of distinct sensory rays
CC (PubMed:12679110). Seems to control cell-cell contact formation through
CC 2 parallel pathways, one involving efn-4 and one involving plx-2 and
CC unc-129 (PubMed:15030761). Involved in follower axon guidance
CC (PubMed:25358863, 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). Probably by
CC binding receptor plx-2, regulates fln-1-mediated remodeling of the
CC actin cytoskeleton and thus axon guidance and/or fasciculation of DD/VD
CC neurons (PubMed:25358863). {ECO:0000269|PubMed:10648234,
CC ECO:0000269|PubMed:12403719, ECO:0000269|PubMed:12679110,
CC ECO:0000269|PubMed:15030761, ECO:0000269|PubMed:17761667,
CC ECO:0000269|PubMed:25358863, ECO:0000269|PubMed:28846083}.
CC -!- FUNCTION: [Isoform a]: Required for the guidance of axons from neurons,
CC including AIY interneurons, into the nerve ring.
CC {ECO:0000269|PubMed:28846083}.
CC -!- SUBUNIT: Interacts with plx-2. {ECO:0000269|PubMed:15030761}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=a {ECO:0000312|WormBase:Y71G12B.20a};
CC IsoId=Q95XP4-1; Sequence=Displayed;
CC Name=c {ECO:0000312|WormBase:Y71G12B.20c};
CC IsoId=Q95XP4-3; Sequence=VSP_060648;
CC Name=d {ECO:0000312|WormBase:Y71G12B.20d};
CC IsoId=Q95XP4-4; Sequence=VSP_060647;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC {ECO:0000269|PubMed:10648234}.
CC -!- DISRUPTION PHENOTYPE: Worms have defects both in early embryonic
CC morphogenesis and in postembryonic male tail morphogenesis.
CC {ECO:0000269|PubMed:10648234}.
CC -!- SIMILARITY: Belongs to the semaphorin family. {ECO:0000305}.
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DR EMBL; AF216968; AAF60253.2; -; mRNA.
DR EMBL; BX284601; CCD67974.1; -; Genomic_DNA.
DR EMBL; BX284601; CDM63583.1; -; Genomic_DNA.
DR EMBL; BX284601; CDM63584.1; -; Genomic_DNA.
DR RefSeq; NP_001293443.1; NM_001306514.1. [Q95XP4-3]
DR RefSeq; NP_001293444.1; NM_001306515.1. [Q95XP4-4]
DR RefSeq; NP_490875.1; NM_058474.4. [Q95XP4-1]
DR AlphaFoldDB; Q95XP4; -.
DR SMR; Q95XP4; -.
DR BioGRID; 37220; 5.
DR IntAct; Q95XP4; 1.
DR STRING; 6239.Y71G12B.20a.1; -.
DR GlyCosmos; Q95XP4; 4 sites, No reported glycans.
DR iPTMnet; Q95XP4; -.
DR EPD; Q95XP4; -.
DR PaxDb; 6239-Y71G12B-20a; -.
DR PeptideAtlas; Q95XP4; -.
DR EnsemblMetazoa; Y71G12B.20a.1; Y71G12B.20a.1; WBGene00003111. [Q95XP4-1]
DR EnsemblMetazoa; Y71G12B.20c.1; Y71G12B.20c.1; WBGene00003111. [Q95XP4-3]
DR EnsemblMetazoa; Y71G12B.20d.1; Y71G12B.20d.1; WBGene00003111. [Q95XP4-4]
DR GeneID; 171727; -.
DR KEGG; cel:CELE_Y71G12B.20; -.
DR UCSC; Y71G12B.20a; c. elegans. [Q95XP4-1]
DR AGR; WB:WBGene00003111; -.
DR WormBase; Y71G12B.20a; CE22926; WBGene00003111; mab-20. [Q95XP4-1]
DR WormBase; Y71G12B.20c; CE49604; WBGene00003111; mab-20. [Q95XP4-3]
DR WormBase; Y71G12B.20d; CE49534; WBGene00003111; mab-20. [Q95XP4-4]
DR eggNOG; KOG3611; Eukaryota.
DR HOGENOM; CLU_009051_10_0_1; -.
DR InParanoid; Q95XP4; -.
DR OMA; HKVVQWI; -.
DR OrthoDB; 5399685at2759; -.
DR PhylomeDB; Q95XP4; -.
DR Reactome; R-CEL-399954; Sema3A PAK dependent Axon repulsion.
DR Reactome; R-CEL-399955; SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion.
DR Reactome; R-CEL-399956; CRMPs in Sema3A signaling.
DR Reactome; R-CEL-416550; Sema4D mediated inhibition of cell attachment and migration.
DR Reactome; R-CEL-416572; Sema4D induced cell migration and growth-cone collapse.
DR Reactome; R-CEL-416700; Other semaphorin interactions.
DR PRO; PR:Q95XP4; -.
DR Proteomes; UP000001940; Chromosome I.
DR Bgee; WBGene00003111; Expressed in embryo and 3 other cell types or tissues.
DR ExpressionAtlas; Q95XP4; baseline and differential.
DR GO; GO:0009986; C:cell surface; IDA:WormBase.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0045499; F:chemorepellent activity; IBA:GO_Central.
DR GO; GO:0030215; F:semaphorin receptor binding; IPI:WormBase.
DR GO; GO:0007411; P:axon guidance; IMP:WormBase.
DR GO; GO:0007413; P:axonal fasciculation; IMP:WormBase.
DR GO; GO:0010172; P:embryonic body morphogenesis; IMP:WormBase.
DR GO; GO:0016331; P:morphogenesis of embryonic epithelium; IMP:WormBase.
DR GO; GO:0050919; P:negative chemotaxis; IBA:GO_Central.
DR GO; GO:0048843; P:negative regulation of axon extension involved in axon guidance; IBA:GO_Central.
DR GO; GO:0090597; P:nematode male tail mating organ morphogenesis; IMP:UniProtKB.
DR GO; GO:0045138; P:nematode male tail tip morphogenesis; IMP:WormBase.
DR GO; GO:0030335; P:positive regulation of cell migration; IBA:GO_Central.
DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; IMP:WormBase.
DR GO; GO:1902667; P:regulation of axon guidance; IMP:UniProtKB.
DR GO; GO:0030155; P:regulation of cell adhesion; IMP:WormBase.
DR GO; GO:0030334; P:regulation of cell migration; IMP:WormBase.
DR GO; GO:0071526; P:semaphorin-plexin signaling pathway; IBA:GO_Central.
DR CDD; cd11238; Sema_2A; 1.
DR Gene3D; 2.60.40.10; Immunoglobulins; 1.
DR Gene3D; 2.130.10.10; YVTN repeat-like/Quinoprotein amine dehydrogenase; 1.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR001627; Semap_dom.
DR InterPro; IPR036352; Semap_dom_sf.
DR InterPro; IPR027231; Semaphorin.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR PANTHER; PTHR11036; SEMAPHORIN; 1.
DR PANTHER; PTHR11036:SF139; SEMAPHORIN-2A; 1.
DR Pfam; PF01403; Sema; 1.
DR SMART; SM00630; Sema; 1.
DR SUPFAM; SSF48726; Immunoglobulin; 1.
DR SUPFAM; SSF101912; Sema domain; 1.
DR PROSITE; PS51004; SEMA; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Developmental protein; Disulfide bond; Glycoprotein;
KW Immunoglobulin domain; Reference proteome; Secreted; Signal.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..658
FT /note="Semaphorin-2A"
FT /id="PRO_0000248547"
FT DOMAIN 20..476
FT /note="Sema"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
FT DOMAIN 478..527
FT /note="PSI"
FT DOMAIN 556..592
FT /note="Ig-like"
FT CARBOHYD 65
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:12754521,
FT ECO:0000269|PubMed:17761667"
FT CARBOHYD 153
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 275
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:17761667"
FT CARBOHYD 653
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 87..97
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
FT DISULFID 252..360
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
FT DISULFID 276..320
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
FT DISULFID 479..494
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
FT DISULFID 488..503
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
FT VAR_SEQ 1..177
FT /note="Missing (in isoform d)"
FT /evidence="ECO:0000305"
FT /id="VSP_060647"
FT VAR_SEQ 1..120
FT /note="Missing (in isoform c)"
FT /evidence="ECO:0000305"
FT /id="VSP_060648"
FT MUTAGEN 247
FT /note="R->H: In ns789; impairs nerve ring assembly due to
FT non-commissural interneurons AIY failing to extend dorsally
FT and enter the nerve ring. This phenotype is enhanced in a
FT chin-1 ns399 mutant background."
FT /evidence="ECO:0000269|PubMed:28846083"
FT CONFLICT 87
FT /note="C -> Y (in Ref. 1; AAF60253)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 658 AA; 73328 MW; F2AE83F7667D4F6E CRC64;
MRNFLVFSVI FIAYNSCEAA NIQADNTFAD PNIGEFRELL IDPKAGALFV GSEGAIFRLW
AYNINDTGEN VFAKKQLVLS ESEESECRST ASDERLCRPS TRFLAFTNNL DSIYVCSSVG
MRPEIRVLDS LSLRDQQEPR TEIGICVVDP TFNFTAVVVD SGNPEDATSV YSGIRTGMGG
ENHLIYRPPL TKNGKQLHAS IRTIYSDNKW LNEPQFVGSF DVGQHVFFFF REIAHDNSFG
ERIVHSRVAR VCKKDIGGRN VLRQVWTSFV KARLNCSVSA NFPFYFDHIQ SVKRVDKHGE
TYFYATFSTS ETAFTSSAIC MFQLSSINHL LDTGLLMEET ANGQFSVTAD EIPAHRPGTC
SQNSHSISDT DLHFAKTHLL VSDSISGGTP ILPLRDHVFT HIVVDQLPNQ NVIFAFDSAN
RRVWKISHWK EGNEWKSNLI EEKSLKIAAS RINDVALLPA EFFFVTSGAG VSQFSVARCS
EQPSCALCSL DPYCSWNAVN SKCSLKTKTN EKSVGWISSS WAGRISPECS AVEKLTVKDV
YLGDGLRLVG AKNGVWQKDG RSVESGQRHV VTRNGELVVL DAQLEDAGTY ECLRDNIILV
RARIVVHENC ARPTSVAEYR SCQREWCKKA DAYKAALNIW SDSNKKNVQC KANTSSAH
//
