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Protein

Receptor tyrosine-protein kinase let-23

Gene

let-23

Organism
Caenorhabditis elegans
Status
Reviewed-Annotation score: -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
  • transmembrane receptor protein tyrosine kinase activity Source: GO_Central
  • transmembrane signaling receptor activity Source: GO_Central
  • Wnt-protein binding Source: GO_Central

GO - Biological processi

Keywordsi

Molecular functionDevelopmental protein, Kinase, Receptor, Transferase, Tyrosine-protein kinase
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.1 1045
ReactomeiR-CEL-1227986 Signaling by ERBB2
R-CEL-1250196 SHC1 events in ERBB2 signaling
R-CEL-1251985 Nuclear signaling by ERBB4
R-CEL-1253288 Downregulation of ERBB4 signaling
R-CEL-177929 Signaling by EGFR
R-CEL-179812 GRB2 events in EGFR signaling
R-CEL-180292 GAB1 signalosome
R-CEL-180336 SHC1 events in EGFR signaling
R-CEL-182971 EGFR downregulation
R-CEL-212718 EGFR interacts with phospholipase C-gamma
R-CEL-2179392 EGFR Transactivation by Gastrin
R-CEL-445144 Signal transduction by L1
R-CEL-5673001 RAF/MAP kinase cascade
R-CEL-6785631 ERBB2 Regulates Cell Motility
R-CEL-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-CEL-8856825 Cargo recognition for clathrin-mediated endocytosis
R-CEL-8856828 Clathrin-mediated endocytosis
R-CEL-8863795 Downregulation of ERBB2 signaling
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 lineageiEukaryotaMetazoaEcdysozoaNematodaChromadoreaRhabditidaRhabditinaRhabditomorphaRhabditoideaRhabditidaePeloderinaeCaenorhabditis
Proteomesi
  • UP000001940 Componenti: Chromosome II

Organism-specific databases

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

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

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

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...) asparagineSequence analysis1
Glycosylationi169N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi220 ↔ 228By similarity
Disulfide bondi224 ↔ 236By similarity
Disulfide bondi244 ↔ 251By similarity
Disulfide bondi248 ↔ 262By similarity
Glycosylationi255N-linked (GlcNAc...) asparagineSequence 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...) asparagine1 Publication1
Disulfide bondi520 ↔ 529By similarity
Disulfide bondi524 ↔ 537By similarity
Disulfide bondi540 ↔ 549By similarity
Disulfide bondi553 ↔ 567By similarity
Glycosylationi561N-linked (GlcNAc...) asparagineSequence 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...) asparagineSequence analysis1
Disulfide bondi670 ↔ 693Sequence analysis
Disulfide bondi696 ↔ 703Sequence analysis
Disulfide bondi700 ↔ 715Sequence analysis
Disulfide bondi717 ↔ 731Sequence analysis
Disulfide bondi735 ↔ 750Sequence analysis
Glycosylationi746N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi753 ↔ 763Sequence analysis
Disulfide bondi757 ↔ 771Sequence analysis
Disulfide bondi774 ↔ 787Sequence analysis
Glycosylationi776N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi791 ↔ 805Sequence analysis

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiP24348
PRIDEiP24348

PTM databases

iPTMnetiP24348

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 Expressed in 4 organ(s), highest expression level in adult organism

Interactioni

GO - Molecular functioni

Protein-protein interaction databases

BioGridi39787, 105 interactors
DIPiDIP-1014N
IntActiP24348, 2 interactors
MINTiP24348
STRINGi6239.ZK1067.1c

Structurei

Secondary structure

11323
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

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

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1025 Eukaryota
ENOG410XNSR LUCA
GeneTreeiENSGT00760000118799
HOGENOMiHOG000016236
InParanoidiP24348
PhylomeDBiP24348

Family and domain databases

CDDicd00064 FU, 5 hits
Gene3Di3.80.20.20, 2 hits
InterProiView protein in InterPro
IPR006211 Furin-like_Cys-rich_dom
IPR006212 Furin_repeat
IPR032778 GF_recep_IV
IPR009030 Growth_fac_rcpt_cys_sf
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR000494 Rcpt_L-dom
IPR036941 Rcpt_L-dom_sf
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
IPR008266 Tyr_kinase_AS
IPR020635 Tyr_kinase_cat_dom
PfamiView protein in Pfam
PF00757 Furin-like, 1 hit
PF14843 GF_recep_IV, 1 hit
PF07714 Pkinase_Tyr, 1 hit
PF01030 Recep_L_domain, 2 hits
PRINTSiPR00109 TYRKINASE
SMARTiView protein in SMART
SM00261 FU, 7 hits
SM00219 TyrKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
SSF57184 SSF57184, 3 hits
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00109 PROTEIN_KINASE_TYR, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 3 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
B5BM27B5BM27_CAEEL
Receptor protein-tyrosine kinase
let-23 CELE_ZK1067.1, ZK1067.1
1,328Annotation score:
B5BM28B5BM28_CAEEL
Receptor protein-tyrosine kinase
let-23 CELE_ZK1067.1, ZK1067.1
1,262Annotation score:
A0A0K3AX35A0A0K3AX35_CAEEL
Receptor protein-tyrosine kinase
let-23 CELE_ZK1067.1, ZK1067.1
1,335Annotation score:

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

Similar proteinsi

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

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5WNOX-ray2.39A866-1191[»]
ProteinModelPortaliP24348
SMRiP24348
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi39787, 105 interactors
DIPiDIP-1014N
IntActiP24348, 2 interactors
MINTiP24348
STRINGi6239.ZK1067.1c

PTM databases

iPTMnetiP24348

Proteomic databases

PaxDbiP24348
PRIDEiP24348

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
ReactomeiR-CEL-1227986 Signaling by ERBB2
R-CEL-1250196 SHC1 events in ERBB2 signaling
R-CEL-1251985 Nuclear signaling by ERBB4
R-CEL-1253288 Downregulation of ERBB4 signaling
R-CEL-177929 Signaling by EGFR
R-CEL-179812 GRB2 events in EGFR signaling
R-CEL-180292 GAB1 signalosome
R-CEL-180336 SHC1 events in EGFR signaling
R-CEL-182971 EGFR downregulation
R-CEL-212718 EGFR interacts with phospholipase C-gamma
R-CEL-2179392 EGFR Transactivation by Gastrin
R-CEL-445144 Signal transduction by L1
R-CEL-5673001 RAF/MAP kinase cascade
R-CEL-6785631 ERBB2 Regulates Cell Motility
R-CEL-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-CEL-8856825 Cargo recognition for clathrin-mediated endocytosis
R-CEL-8856828 Clathrin-mediated endocytosis
R-CEL-8863795 Downregulation of ERBB2 signaling
SignaLinkiP24348

Miscellaneous databases

PROiPR:P24348

Gene expression databases

BgeeiWBGene00002299 Expressed in 4 organ(s), highest expression level in adult organism

Family and domain databases

CDDicd00064 FU, 5 hits
Gene3Di3.80.20.20, 2 hits
InterProiView protein in InterPro
IPR006211 Furin-like_Cys-rich_dom
IPR006212 Furin_repeat
IPR032778 GF_recep_IV
IPR009030 Growth_fac_rcpt_cys_sf
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR000494 Rcpt_L-dom
IPR036941 Rcpt_L-dom_sf
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
IPR008266 Tyr_kinase_AS
IPR020635 Tyr_kinase_cat_dom
PfamiView protein in Pfam
PF00757 Furin-like, 1 hit
PF14843 GF_recep_IV, 1 hit
PF07714 Pkinase_Tyr, 1 hit
PF01030 Recep_L_domain, 2 hits
PRINTSiPR00109 TYRKINASE
SMARTiView protein in SMART
SM00261 FU, 7 hits
SM00219 TyrKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
SSF57184 SSF57184, 3 hits
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00109 PROTEIN_KINASE_TYR, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiLET23_CAEEL
AccessioniPrimary (citable) accession number: P24348
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 1, 1992
Last sequence update: July 25, 2006
Last modified: November 7, 2018
This is version 187 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programCaenorhabditis annotation project

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Caenorhabditis elegans
    Caenorhabditis elegans: entries, gene names and cross-references to WormBase
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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Main funding by: National Institutes of Health

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