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Protein

Receptor tyrosine-protein kinase let-23

Gene

let-23

Organism
Caenorhabditis elegans
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Tyrosine-protein kinase receptor which, upon binding ligand lin-3, activates 2 signaling cascades: the let-60/Ras and MAP kinase signaling pathway and the let-60-independent phospholipase C-mediated Ca2+ signaling pathway. Each pathway regulates distinct functions. By activating let-60/Ras, regulates larval development, induction of vulva cell precursors during vulva development, male spicule formation and posterior development of the epidermis (PubMed:2071015, PubMed:8313880, PubMed:9491893). Probably by activating phospholipase plc-3 and inositol 1,4,5-trisphosphate receptor itr-1 signaling cascade downstream of ligand lin-3, plays a role in ovulation by promoting ovulatory gonadal sheath cell contractions (PubMed:9491893, PubMed:15194811). Probably by regulating neuronal transmission in ALA neurons, mediates, independently of let-60/Ras, the decrease in pharyngeal pumping and locomotion during the quiescent state that precedes each larval molt, downstream of lin-3 and upstream of plc-3 (PubMed:17891142).5 Publications

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei919ATPPROSITE-ProRule annotation1
Active sitei1010Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi891 – 899ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • epidermal growth factor-activated receptor activity Source: WormBase

GO - Biological processi

  • epidermal growth factor receptor signaling pathway Source: WormBase
  • male genitalia development Source: WormBase
  • nematode larval development Source: WormBase
  • ovulation Source: WormBase
  • positive regulation of vulval development Source: WormBase
  • sleep Source: WormBase
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Kinase, Receptor, Transferase, Tyrosine-protein kinase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.1. 1045.
SignaLinkiP24348.

Names & Taxonomyi

Protein namesi
Recommended name:
Receptor tyrosine-protein kinase let-23 (EC:2.7.10.1)
Alternative name(s):
Lethal protein 23
Gene namesi
Name:let-23
Synonyms:kin-7
ORF Names:ZK1067.1
OrganismiCaenorhabditis elegans
Taxonomic identifieri6239 [NCBI]
Taxonomic lineageiEukaryotaMetazoaEcdysozoaNematodaChromadoreaRhabditidaRhabditoideaRhabditidaePeloderinaeCaenorhabditis
Proteomesi
  • UP000001940 Componenti: Chromosome II

Organism-specific databases

WormBaseiZK1067.1a; CE03840; WBGene00002299; let-23.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini21 – 818ExtracellularSequence analysisAdd BLAST798
Transmembranei819 – 839HelicalSequence analysisAdd BLAST21
Topological domaini840 – 1323CytoplasmicSequence analysisAdd BLAST484

GO - Cellular componenti

  • apical plasma membrane Source: WormBase
  • basolateral plasma membrane Source: WormBase
  • cell-cell junction Source: WormBase
  • integral component of membrane Source: UniProtKB-KW
  • lateral plasma membrane Source: WormBase
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Disruption phenotypei

Larval lethality, lack of vulva formation, infertility and lack of male spicule formation (PubMed:2071015). RNAi-mediated knockdown causes sterility, a small decrease in the peak rate of sheath cell contractions and a delay in the onset of ovulatory contractions (PubMed:15194811). Restores normal pharyngeal pumping rate in 30 percent of animals overexpressing lin-3 (PubMed:17891142).3 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi368C → Y in sy10; severe larval lethality, lack of vulva induction, infertile and lack of male spicule formation. Impaired ovulation characterized by a delay in the initiation of ovulatory sheath cell contractions and prolonged ovulatory contractions. 3 Publications1
Mutagenesisi469G → R in mn216; larval lethality. 1 Publication1
Mutagenesisi700C → W in mn23; larval lethality. 1 Publication1
Mutagenesisi753C → Y in SY11. 1 Publication1
Mutagenesisi1065T → I in sy16; larval lethality and lack of vulva induction. Viability, vulva induction but not fertility are restored in a let-60 (n1046gf) mutant background. Viability is not restored in a lfe-1 (sy290) or lfe-2 (sy326) mutant background. Fertility is restored in a let-60 (n1046gf) and lfe-1 (sy290) mutant background. 2 Publications1
Mutagenesisi1074G → E in SY7. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 20Sequence analysisAdd BLAST20
ChainiPRO_000001667721 – 1323Receptor tyrosine-protein kinase let-23Add BLAST1303

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi91N-linked (GlcNAc...)Sequence analysis1
Glycosylationi169N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi220 ↔ 228By similarity
Disulfide bondi224 ↔ 236By similarity
Disulfide bondi244 ↔ 251By similarity
Disulfide bondi248 ↔ 262By similarity
Glycosylationi255N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi263 ↔ 271By similarity
Disulfide bondi267 ↔ 279By similarity
Disulfide bondi282 ↔ 291By similarity
Disulfide bondi295 ↔ 322By similarity
Disulfide bondi326 ↔ 337By similarity
Disulfide bondi341 ↔ 356By similarity
Disulfide bondi359 ↔ 364By similarity
Glycosylationi376N-linked (GlcNAc...)1 Publication1
Disulfide bondi520 ↔ 529By similarity
Disulfide bondi524 ↔ 537By similarity
Disulfide bondi540 ↔ 549By similarity
Disulfide bondi553 ↔ 567By similarity
Glycosylationi561N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi570 ↔ 577By similarity
Disulfide bondi574 ↔ 585By similarity
Disulfide bondi588 ↔ 604By similarity
Disulfide bondi608 ↔ 620By similarity
Disulfide bondi623 ↔ 632By similarity
Disulfide bondi627 ↔ 644By similarity
Disulfide bondi647 ↔ 660Sequence analysis
Glycosylationi655N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi670 ↔ 693Sequence analysis
Disulfide bondi696 ↔ 703Sequence analysis
Disulfide bondi700 ↔ 715Sequence analysis
Disulfide bondi717 ↔ 731Sequence analysis
Disulfide bondi735 ↔ 750Sequence analysis
Glycosylationi746N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi753 ↔ 763Sequence analysis
Disulfide bondi757 ↔ 771Sequence analysis
Disulfide bondi774 ↔ 787Sequence analysis
Glycosylationi776N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi791 ↔ 805Sequence analysis

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiP24348.

Expressioni

Tissue specificityi

Expressed in vulval precursor cells (at protein level) (PubMed:10359617). Expressed in ALA neurons, 2 ventral head neurons, a single neuron in the tail, pharyngeal-intestinal valve and posterior arcade epithelial cells (PubMed:17891142).2 Publications

Developmental stagei

Expressed during L2 and L3 larval stages.1 Publication

Gene expression databases

BgeeiWBGene00002299.
ExpressionAtlasiP24348. differential.

Interactioni

Protein-protein interaction databases

BioGridi39787. 105 interactors.
DIPiDIP-1014N.
IntActiP24348. 2 interactors.
MINTiMINT-1515688.
STRINGi6239.ZK1067.1c.

Structurei

3D structure databases

ProteinModelPortaliP24348.
SMRiP24348.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini885 – 1152Protein kinasePROSITE-ProRule annotationAdd BLAST268

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. EGF receptor subfamily.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1025. Eukaryota.
ENOG410XNSR. LUCA.
GeneTreeiENSGT00760000118799.
HOGENOMiHOG000016236.
InParanoidiP24348.
PhylomeDBiP24348.

Family and domain databases

Gene3Di3.80.20.20. 2 hits.
InterProiIPR006211. Furin-like_Cys-rich_dom.
IPR006212. Furin_repeat.
IPR032778. GF_recep_IV.
IPR009030. Growth_fac_rcpt_.
IPR011009. Kinase-like_dom.
IPR032675. L_dom-like.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR000494. Rcpt_L-dom.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
[Graphical view]
PfamiPF00757. Furin-like. 1 hit.
PF14843. GF_recep_IV. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PF01030. Recep_L_domain. 2 hits.
[Graphical view]
PRINTSiPR00109. TYRKINASE.
SMARTiSM00261. FU. 7 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF52058. SSF52058. 2 hits.
SSF56112. SSF56112. 1 hit.
SSF57184. SSF57184. 3 hits.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P24348-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRYPPSIGSI LLIIPIFLTF FGNSNAQLWK RCVSPQDCLC SGTTNGISRY
60 70 80 90 100
GTGNILEDLE TMYRGCRRVY GNLEITWIEA NEIKKWREST NSTVDPKNED
110 120 130 140 150
SPLKSINFFD NLEEIRGSLI IYRANIQKIS FPRLRVIYGD EVFHDNALYI
160 170 180 190 200
HKNDKVHEVV MRELRVIRNG SVTIQDNPKM CYIGDKIDWK ELLYDPDVQK
210 220 230 240 250
VETTNSHQHC YQNGKSMAKC HESCNDKCWG SGDNDCQRVY RSVCPKSCSQ
260 270 280 290 300
CFYSNSTSSY ECCDSACLGG CTGHGPKNCI ACSKYELDGI CIETCPSRKI
310 320 330 340 350
FNHKTGRLVF NPDGRYQNGN HCVKECPPEL LIENDVCVRH CSDGHHYDAT
360 370 380 390 400
KDVRECEKCR SSSCPKICTV DGHLTNETLK NLEGCEQIDG HLIIEHAFTY
410 420 430 440 450
EQLKVLETVK IVSEYITIVQ QNFYDLKFLK NLQIIEGRKL HNVRWALAIY
460 470 480 490 500
QCDDLEELSL NSLKLIKTGA VLIMKNHRLC YVSKIDWSSI ITSKGKDNKP
510 520 530 540 550
SLAIAENRDS KLCETEQRVC DKNCNKRGCW GKEPEDCLEC KTWKSVGTCV
560 570 580 590 600
EKCDTKGFLR NQTSMKCERC SPECETCNGL GELDCLTCRH KTLYNSDFGN
610 620 630 640 650
RMECVHDCPV SHFPTQKNVC EKCHPTCYDN GCTGPDSNLG YGGCKQCKYA
660 670 680 690 700
VKYENDTIFC LQSSGMNNVC VENDLPNYYI STYDTEGVIE THCEKCSISC
710 720 730 740 750
KTCSSAGRNV VQNKCVCKHV EYQPNPSERI CMDQCPVNSF MVPDTNNTVC
760 770 780 790 800
KKCHHECDQN YHCANGQSTG CQKCKNFTVF KGDIAQCVSE CPKNLPFSNP
810 820 830 840 850
ANGECLDYDI ASRQRKTRMV IIGSVLFGFA VMFLFILLVY WRCQRIGKKL
860 870 880 890 900
KIAEMVDMPE LTPIDASVRP NMSRICLIPS SELQTKLDKK LGAGAFGTVF
910 920 930 940 950
AGIYYPKRAK NVKIPVAIKV FQTDQSQTDE MLEEATNMFR LRHDNLLKII
960 970 980 990 1000
GFCMHDDGLK IVTIYRPLGN LQNFLKLHKE NLGAREQVLY CYQIASGMQY
1010 1020 1030 1040 1050
LEKQRVVHRD LATRNVLVKK FNHVEITDFG LSKILKHDAD SITIKSGKVA
1060 1070 1080 1090 1100
IKWLAIEIFS KHCYTHASDV WAFGVTCWEI ITFGQSPYQG MSTDSIHNFL
1110 1120 1130 1140 1150
KDGNRLSQPP NCSQDLYQEL LRCWMADPKS RPGFEILYER FKEFCKVPQL
1160 1170 1180 1190 1200
FLENSNKISE SDLSAEERFQ TERIREMFDG NIDPQMYFDQ GSLPSMPSSP
1210 1220 1230 1240 1250
TSMATFTIPH GDLMNRMQSV NSSRYKTEPF DYGSTAQEDN SYLIPKTKEV
1260 1270 1280 1290 1300
QQSAVLYTAV TNEDGQTELS PSNGDYYNQP NTPSSSSGYY NEPHLKTKKP
1310 1320
ETSEEAEAVQ YENEEVSQKE TCL
Length:1,323
Mass (Da):150,511
Last modified:July 25, 2006 - v3
Checksum:i6B0307EE53EEFA99
GO

Sequence cautioni

The sequence BAA09729 differs from that shown. Reason: Erroneous gene model prediction.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti1179D → H in CAA40919 (PubMed:1979659).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X57767 mRNA. Translation: CAA40919.1.
D63426 Genomic DNA. Translation: BAA09729.1. Sequence problems.
Z70038 Genomic DNA. Translation: CAA93882.3.
PIRiE88257.
S70712.
RefSeqiNP_495962.2. NM_063561.4.
UniGeneiCel.16858.

Genome annotation databases

EnsemblMetazoaiZK1067.1a; ZK1067.1a; WBGene00002299.
GeneIDi174462.
UCSCiZK1067.1. c. elegans.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X57767 mRNA. Translation: CAA40919.1.
D63426 Genomic DNA. Translation: BAA09729.1. Sequence problems.
Z70038 Genomic DNA. Translation: CAA93882.3.
PIRiE88257.
S70712.
RefSeqiNP_495962.2. NM_063561.4.
UniGeneiCel.16858.

3D structure databases

ProteinModelPortaliP24348.
SMRiP24348.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi39787. 105 interactors.
DIPiDIP-1014N.
IntActiP24348. 2 interactors.
MINTiMINT-1515688.
STRINGi6239.ZK1067.1c.

Proteomic databases

PaxDbiP24348.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblMetazoaiZK1067.1a; ZK1067.1a; WBGene00002299.
GeneIDi174462.
UCSCiZK1067.1. c. elegans.

Organism-specific databases

CTDi174462.
WormBaseiZK1067.1a; CE03840; WBGene00002299; let-23.

Phylogenomic databases

eggNOGiKOG1025. Eukaryota.
ENOG410XNSR. LUCA.
GeneTreeiENSGT00760000118799.
HOGENOMiHOG000016236.
InParanoidiP24348.
PhylomeDBiP24348.

Enzyme and pathway databases

BRENDAi2.7.10.1. 1045.
SignaLinkiP24348.

Miscellaneous databases

PROiP24348.

Gene expression databases

BgeeiWBGene00002299.
ExpressionAtlasiP24348. differential.

Family and domain databases

Gene3Di3.80.20.20. 2 hits.
InterProiIPR006211. Furin-like_Cys-rich_dom.
IPR006212. Furin_repeat.
IPR032778. GF_recep_IV.
IPR009030. Growth_fac_rcpt_.
IPR011009. Kinase-like_dom.
IPR032675. L_dom-like.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR000494. Rcpt_L-dom.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
[Graphical view]
PfamiPF00757. Furin-like. 1 hit.
PF14843. GF_recep_IV. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PF01030. Recep_L_domain. 2 hits.
[Graphical view]
PRINTSiPR00109. TYRKINASE.
SMARTiSM00261. FU. 7 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF52058. SSF52058. 2 hits.
SSF56112. SSF56112. 1 hit.
SSF57184. SSF57184. 3 hits.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiLET23_CAEEL
AccessioniPrimary (citable) accession number: P24348
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 1, 1992
Last sequence update: July 25, 2006
Last modified: November 30, 2016
This is version 169 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programCaenorhabditis annotation project

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Caenorhabditis elegans
    Caenorhabditis elegans: entries, gene names and cross-references to WormBase
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.