VAB1_CAEEL
ID VAB1_CAEEL Reviewed; 1122 AA.
AC O61460; Q21477;
DT 19-JUL-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 1.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=Ephrin receptor 1;
DE EC=2.7.10.1 {ECO:0000269|PubMed:19853560};
DE AltName: Full=Tyrosine-protein kinase Eph receptor;
DE AltName: Full=Variable abnormal protein 1;
DE Flags: Precursor;
GN Name=vab-1 {ECO:0000312|WormBase:M03A1.1a};
GN ORFNames=M03A1.1 {ECO:0000312|WormBase:M03A1.1a};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|EMBL:AAC38970.1};
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, TISSUE SPECIFICITY, AND
RP MUTAGENESIS OF GLU-62; THR-63; GLU-195; GLY-917 AND CYS-966.
RC STRAIN=Bristol N2;
RX PubMed=9506518; DOI=10.1016/s0092-8674(00)81131-9;
RA George S.E., Simokat K., Hardin J., Chisholm A.D.;
RT "The VAB-1 Eph receptor tyrosine kinase functions in neural and epithelial
RT morphogenesis in C. elegans.";
RL Cell 92:633-643(1998).
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, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE,
RP AND MUTAGENESIS OF GLU-62; THR-63 AND GLY-917.
RX PubMed=12533508; DOI=10.1101/gad.1028303;
RA Miller M.A., Ruest P.J., Kosinski M., Hanks S.K., Greenstein D.;
RT "An Eph receptor sperm-sensing control mechanism for oocyte meiotic
RT maturation in Caenorhabditis elegans.";
RL Genes Dev. 17:187-200(2003).
RN [4]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-238, AND IDENTIFICATION BY MASS
RP 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 [5]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, INTERACTION WITH DAF-18,
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, PHOSPHORYLATION, AND MUTAGENESIS
RP OF GLY-917.
RX PubMed=19853560; DOI=10.1016/j.devcel.2009.08.009;
RA Brisbin S., Liu J., Boudreau J., Peng J., Evangelista M., Chin-Sang I.;
RT "A role for C. elegans Eph RTK signaling in PTEN regulation.";
RL Dev. Cell 17:459-469(2009).
RN [6]
RP FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND MUTAGENESIS OF
RP THR-63 AND GLY-917.
RX PubMed=25529479; DOI=10.1002/dvdy.24244;
RA Praslicka B., Gissendanner C.R.;
RT "The C. elegans NR4A nuclear receptor gene nhr-6 promotes cell cycle
RT progression in the spermatheca lineage.";
RL Dev. Dyn. 244:417-430(2015).
RN [7]
RP FUNCTION.
RX PubMed=26903502; DOI=10.1242/dev.128934;
RA Dong B., Moseley-Alldredge M., Schwieterman A.A., Donelson C.J.,
RA McMurry J.L., Hudson M.L., Chen L.;
RT "EFN-4 functions in LAD-2-mediated axon guidance in Caenorhabditis
RT elegans.";
RL Development 143:1182-1191(2016).
CC -!- FUNCTION: Receptor for members of the ephrin family (By similarity).
CC Receptor for major sperm proteins (MSPs), that functions as sperm-
CC sensing checkpoint which inhibits oocyte meiotic maturation and
CC ovulation when sperm are not available for fertilization
CC (PubMed:12533508). Specifically, functions to negatively regulates
CC oocyte maturation and MAPK activation in the absence of MSPs
CC (PubMed:12533508, PubMed:19853560). Required for the MSP-mediated
CC increase in the basal sheath cell contraction rate in somatic cells
CC (PubMed:12533508). Phosphorylates phosphatase daf-18/PTEN which
CC probably promotes daf-18 degradation (PubMed:19853560). By inactivating
CC daf-18, regulates positively insulin-like daf-2 signaling cascade
CC (PubMed:9506518). Involved in interactions between neuronal substrate
CC cells and a migrating epithelial sheet in head epidermis morphogenesis
CC (PubMed:9506518). Also required for cell movements following
CC gastrulation and during ventral closure of the epidermis
CC (PubMed:9506518). Might play a role in spermatheca morphogenesis
CC (PubMed:25529479). Involved in axon guidance of SDQL neurons during
CC neurogenesis (PubMed:26903502). {ECO:0000250|UniProtKB:Q62413,
CC ECO:0000269|PubMed:12533508, ECO:0000269|PubMed:19853560,
CC ECO:0000269|PubMed:25529479, ECO:0000269|PubMed:26903502,
CC ECO:0000269|PubMed:9506518}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1;
CC Evidence={ECO:0000269|PubMed:19853560};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000305};
CC -!- ACTIVITY REGULATION: Dephosphorylated by daf-18.
CC {ECO:0000269|PubMed:19853560}.
CC -!- SUBUNIT: Interacts (via kinase domain) with daf-18 (via C-terminus);
CC the interaction is independent of vab-1 kinase activity.
CC {ECO:0000269|PubMed:19853560}.
CC -!- INTERACTION:
CC O61460; G5EE01: daf-18; NbExp=3; IntAct=EBI-1788319, EBI-2914422;
CC O61460; O44782: vpr-1; NbExp=2; IntAct=EBI-1788319, EBI-320991;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12533508,
CC ECO:0000269|PubMed:19853560}; Single-pass type I membrane protein
CC {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=a {ECO:0000312|WormBase:M03A1.1a};
CC IsoId=O61460-1; Sequence=Displayed;
CC Name=b {ECO:0000312|WormBase:M03A1.1b};
CC IsoId=O61460-2; Sequence=VSP_050207;
CC -!- TISSUE SPECIFICITY: During ventral enclosure of the epidermis,
CC expression is seen in clusters of presumptive head neuronal cells and
CC several cells in the tail region. Early larvae show expression in the
CC nerve ring and ventral nerve cord. Strong expression is also seen in
CC the procorpus and terminal bulb of the pharynx. Expression in the
CC nervous system is seen through to adulthood (PubMed:9506518,
CC PubMed:19853560). Expressed in Z2/Z3 germline precursor cells and in
CC oocytes (at protein level). Expressed in the vulva and in the
CC spermatheca with accumulation in the apical regions of the organ
CC (PubMed:25529479). Expressed in oocytes and sheath cells
CC (PubMed:12533508). {ECO:0000269|PubMed:12533508,
CC ECO:0000269|PubMed:19853560, ECO:0000269|PubMed:25529479,
CC ECO:0000269|PubMed:9506518}.
CC -!- DEVELOPMENTAL STAGE: Expressed in larval stage L4.
CC {ECO:0000269|PubMed:25529479}.
CC -!- PTM: Autophosphorylated. {ECO:0000269|PubMed:19853560}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown results in impaired
CC inhibition of oocyte maturation and ovulation in the presence of
CC reduced numbers of self-derived sperm (PubMed:12533508). As a result,
CC hermaphrodites lay increased numbers of unfertilized oocytes
CC (PubMed:12533508). Reduced sheath cell contraction rate in somatic
CC cells (PubMed:12533508). {ECO:0000269|PubMed:12533508}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. Ephrin receptor subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
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DR EMBL; AF040269; AAC38970.1; -; Genomic_DNA.
DR EMBL; BX284602; CCD70550.1; -; Genomic_DNA.
DR EMBL; BX284602; CCD70551.1; -; Genomic_DNA.
DR PIR; T42400; T42400.
DR RefSeq; NP_494806.1; NM_062405.5.
DR RefSeq; NP_494807.1; NM_062406.3. [O61460-2]
DR AlphaFoldDB; O61460; -.
DR SMR; O61460; -.
DR BioGRID; 39149; 56.
DR IntAct; O61460; 2.
DR STRING; 6239.M03A1.1b; -.
DR iPTMnet; O61460; -.
DR EPD; O61460; -.
DR PaxDb; O61460; -.
DR PeptideAtlas; O61460; -.
DR EnsemblMetazoa; M03A1.1.1; M03A1.1.1; WBGene00006868. [O61460-2]
DR GeneID; 173794; -.
DR KEGG; cel:CELE_M03A1.1; -.
DR UCSC; M03A1.1a; c. elegans. [O61460-1]
DR CTD; 173794; -.
DR WormBase; M03A1.1a; CE25060; WBGene00006868; vab-1. [O61460-2]
DR WormBase; M03A1.1b; CE28617; WBGene00006868; vab-1. [O61460-1]
DR eggNOG; KOG0196; Eukaryota.
DR GeneTree; ENSGT00940000165255; -.
DR InParanoid; O61460; -.
DR OMA; IGWTTHP; -.
DR OrthoDB; 933071at2759; -.
DR PhylomeDB; O61460; -.
DR BRENDA; 2.7.10.1; 1045.
DR SignaLink; O61460; -.
DR PRO; PR:O61460; -.
DR Proteomes; UP000001940; Chromosome II.
DR Bgee; WBGene00006868; Expressed in pharyngeal muscle cell (C elegans) and 4 other tissues.
DR GO; GO:0030424; C:axon; IDA:WormBase.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:WormBase.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005003; F:ephrin receptor activity; IDA:WormBase.
DR GO; GO:0019904; F:protein domain specific binding; IPI:WormBase.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IDA:WormBase.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0005005; F:transmembrane-ephrin receptor activity; IBA:GO_Central.
DR GO; GO:0007411; P:axon guidance; IMP:WormBase.
DR GO; GO:0007409; P:axonogenesis; IMP:WormBase.
DR GO; GO:0009792; P:embryo development ending in birth or egg hatching; IMP:WormBase.
DR GO; GO:0010172; P:embryonic body morphogenesis; IMP:UniProtKB.
DR GO; GO:0016331; P:morphogenesis of embryonic epithelium; IMP:UniProtKB.
DR GO; GO:0001556; P:oocyte maturation; IMP:WormBase.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:WormBase.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:1902667; P:regulation of axon guidance; IMP:UniProtKB.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR CDD; cd00063; FN3; 2.
DR Gene3D; 2.60.40.10; -; 2.
DR InterPro; IPR027936; Eph_TM.
DR InterPro; IPR001090; Ephrin_rcpt_lig-bd_dom.
DR InterPro; IPR003961; FN3_dom.
DR InterPro; IPR036116; FN3_sf.
DR InterPro; IPR008979; Galactose-bd-like_sf.
DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR Pfam; PF14575; EphA2_TM; 1.
DR Pfam; PF01404; Ephrin_lbd; 1.
DR Pfam; PF00041; fn3; 2.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00615; EPH_lbd; 1.
DR SMART; SM00060; FN3; 2.
DR SUPFAM; SSF49265; SSF49265; 1.
DR SUPFAM; SSF49785; SSF49785; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR SUPFAM; SSF57184; SSF57184; 1.
DR PROSITE; PS51550; EPH_LBD; 1.
DR PROSITE; PS50853; FN3; 2.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Cell membrane; Developmental protein;
KW Glycoprotein; Kinase; Membrane; Neurogenesis; Nucleotide-binding;
KW Phosphoprotein; Receptor; Reference proteome; Repeat; Signal; Transferase;
KW Transmembrane; Transmembrane helix; Tyrosine-protein kinase.
FT SIGNAL 1..29
FT /evidence="ECO:0000255"
FT CHAIN 30..1122
FT /note="Ephrin receptor 1"
FT /id="PRO_0000016839"
FT TOPO_DOM 30..559
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 560..580
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 581..1122
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 31..217
FT /note="Eph LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00883"
FT DOMAIN 341..445
FT /note="Fibronectin type-III 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 451..537
FT /note="Fibronectin type-III 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 692..988
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1091..1122
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 1120..1122
FT /note="PDZ-binding"
FT /evidence="ECO:0000255"
FT COMPBIAS 1092..1109
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 849
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 698..706
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 748
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 667
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000255"
FT MOD_RES 673
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000255"
FT MOD_RES 885
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000255"
FT MOD_RES 1048
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000255"
FT CARBOHYD 172
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 238
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:17761667"
FT CARBOHYD 244
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 499
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 554
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 843..847
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_050207"
FT MUTAGEN 62
FT /note="E->K: In ju8; most die as larvae. Animals lay an
FT increased number of unfertilized oocytes compared to wild-
FT type. No effect on major sperm protein (MSP) binding."
FT /evidence="ECO:0000269|PubMed:12533508,
FT ECO:0000269|PubMed:9506518"
FT MUTAGEN 63
FT /note="T->I: In e699; most die as larvae. Animals lay an
FT increased number of unfertilized oocytes compared to wild-
FT type. Reduced brood size. No effect on major sperm protein
FT (MSP) binding. In a RNAi-mediated nhr-6 knockdown
FT background, enhanced reduction in brood size."
FT /evidence="ECO:0000269|PubMed:12533508,
FT ECO:0000269|PubMed:25529479, ECO:0000269|PubMed:9506518"
FT MUTAGEN 195
FT /note="E->K: In e856; most die as larvae."
FT /evidence="ECO:0000269|PubMed:9506518"
FT MUTAGEN 917
FT /note="G->E: In e2; about 80% animals reach adulthood. No
FT effect on interaction with daf-18. Increased daf-18 protein
FT levels in embryos. May lack kinase activity. Animals lay an
FT increased number of unfertilized oocytes compared to wild-
FT type. Reduced brood size. No effect on major sperm protein
FT (MSP) binding. In a RNAi-mediated nhr-6 knockdown
FT background, enhanced reduction in brood size."
FT /evidence="ECO:0000269|PubMed:12533508,
FT ECO:0000269|PubMed:19853560, ECO:0000269|PubMed:25529479,
FT ECO:0000269|PubMed:9506518"
FT MUTAGEN 966
FT /note="C->F: In ju22; about 80% animals reach adulthood."
FT /evidence="ECO:0000269|PubMed:9506518"
FT MUTAGEN 966
FT /note="C->Y: In e1063; about 80% animals reach adulthood."
FT /evidence="ECO:0000269|PubMed:9506518"
SQ SEQUENCE 1122 AA; 125264 MW; 6E4A3037BB92A1D0 CRC64;
MRLYNSRILN PHQSIFILVL QCLITIVTSH QEVLFDLSKV GSDLKWDQVS LRHDRDDVWM
EETWRNPAAT DEKHANQRAY VTCNYDMINP SNWLFSHFIE VKTARRIYIE LLFNTRDCDA
YLNPKSCKET FSVYLKQFKT SRPGSTKIEK ERFSEDIDNW KNIGRLARSN SNMTTETLGM
EIDSDTKTIR IAFEEQGICL SLLNVKIYYR ICDEFTDQLV YFRPQVTGPK ETDMVRMNGS
CIPNASKKIP GVDLIGLCMS TGSGIKTSGE CVCDSGYSQI ADSNGARCES CPTNTYKPKG
QSLCKSCPSN SISSEAASSC RCLNGYFRAE DELISMPCTQ PPSRPIKLVA NAITATSTRL
SWNEPSSLGG RPEIWYEVKC SGRGECGTVV MTPGDKKLST RSVQINGLRP SSDYTFLVFA
KNKVSAQFPE FSEKNAVIDI RTRSEEEDVP PVSHLRVDAS QSDGITIAWS VSDSDVSDFE
VEVRPAIVKK RTFETRHVNM TYTTFIGLNP ETVYQFRVRI RDDLRWSQPI SYQLGRGLMS
SPSSNEVEES QFLNQTGSAL LIIIALILIV IAVALCMIVV QKKSKNRKQM SDLDVLDTYK
QDSMTPDYHT TSRHHHHQGN LPATLHEQLR STTKLNAPLI PSFGSPISQP PPYYGGVHPN
SGKYKTYVDP TTYEDPYQAL IEFTFDISPN DVFITQVIGG GEFGDVCLGG LSKNSPAAAK
WSVSNTTMGR GGGGGGYESE PYETVAIKTL KSGSSAKAKA EFLTEATIMG QFSHPNVIRL
IGVVTSAEPV MIVAEYMANG SLDQFLRNTD QRGEKVHWEK ITEMLYGIAS GMKYLTDMGY
VHRVSFLRDL AARNVLLDME LRCKIADFGL SRGVRSEGSS VEPEYTTNGG KIPVRWTAPE
AITHRKFTPS SDVWSFGVVI WEVCSFGERP YWDWTNQKVI SEVMIGYRLP PPMDCPMGLY
RIAQWCWKME RHERPTFTQL LATFHKYILQ PTLIEHDPGE LPRRVQSQSA LNTYGSVNVG
VVPTPPSSAA PMPSLDDFLR QIGLNHVYGQ LVSNNIHSVS DLANTSHLDL LAYGLMSAEC
STVRDGLNGR ISGSPPGSSG TIHATTRGTR TTRPPREEGF FV
