SVH2_CAEEL
ID SVH2_CAEEL Reviewed; 1086 AA.
AC H2KZU7; H1AGA1; Q6AHP3;
DT 14-OCT-2015, integrated into UniProtKB/Swiss-Prot.
DT 21-MAR-2012, sequence version 1.
DT 03-AUG-2022, entry version 76.
DE RecName: Full=Tyrosine-protein kinase receptor svh-2 {ECO:0000305};
DE EC=2.7.10.1 {ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000305|PubMed:22388962, ECO:0000305|PubMed:27984580};
DE AltName: Full=Met/Ron-like receptor tyrosine kinase svh-2 {ECO:0000303|PubMed:22388962};
DE AltName: Full=Suppressor of vhp-1 deletion lethality protein svh-2 {ECO:0000312|WormBase:T14E8.1a};
DE Flags: Precursor;
GN Name=svh-2 {ECO:0000312|WormBase:T14E8.1a};
GN ORFNames=T14E8.1 {ECO:0000312|WormBase:T14E8.1a};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|EMBL:BAL45942.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B), FUNCTION, INTERACTION WITH MLK-1,
RP TISSUE SPECIFICITY, PHOSPHORYLATION AT TYR-890, AND MUTAGENESIS OF LYS-767
RP AND TYR-890.
RX PubMed=22388962; DOI=10.1038/nn.3052;
RA Li C., Hisamoto N., Nix P., Kanao S., Mizuno T., Bastiani M., Matsumoto K.;
RT "The growth factor SVH-1 regulates axon regeneration in C. elegans via the
RT JNK MAPK cascade.";
RL Nat. Neurosci. 15:551-557(2012).
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, CATALYTIC ACTIVITY, INTERACTION WITH SHC-1, DISRUPTION PHENOTYPE,
RP AND MUTAGENESIS OF LYS-767.
RX PubMed=27984580; DOI=10.1371/journal.pgen.1006475;
RA Hisamoto N., Nagamori Y., Shimizu T., Pastuhov S.I., Matsumoto K.;
RT "The C. elegans discoidin domain receptor DDR-2 modulates the Met-like RTK-
RT JNK signaling pathway in axon regeneration.";
RL PLoS Genet. 12:E1006475-E1006475(2016).
RN [4]
RP FUNCTION, AND INTERACTION WITH TNS-1.
RX PubMed=31109965; DOI=10.1523/jneurosci.2059-18.2019;
RA Hisamoto N., Shimizu T., Asai K., Sakai Y., Pastuhov S.I., Hanafusa H.,
RA Matsumoto K.;
RT "C. elegans Tensin Promotes Axon Regeneration by Linking the Met-like SVH-2
RT and Integrin Signaling Pathways.";
RL J. Neurosci. 39:5662-5672(2019).
CC -!- FUNCTION: Receptor tyrosine kinase which may phosphorylate mlk-1, a
CC component of the mlk-1, mek-1 and kgb-1 pathway (PubMed:22388962).
CC Involved in axon regeneration after injury by promoting the generation
CC of productive and stable growth cones (PubMed:22388962,
CC PubMed:27984580, PubMed:31109965). {ECO:0000269|PubMed:22388962,
CC ECO:0000269|PubMed:27984580, ECO:0000269|PubMed:31109965}.
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:0000305|PubMed:22388962, ECO:0000305|PubMed:27984580};
CC -!- SUBUNIT: Interacts (via cytoplasmic domain) with mlk-1
CC (PubMed:22388962). Interacts with shc-1 (via SH2 domain)
CC (PubMed:27984580). May interact (when tyrosine-phosphorylated) with
CC tns-1 (via SH2 domain) (PubMed:31109965). {ECO:0000269|PubMed:22388962,
CC ECO:0000269|PubMed:27984580, ECO:0000269|PubMed:31109965}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Single-pass membrane
CC protein {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=a {ECO:0000312|WormBase:T14E8.1a};
CC IsoId=H2KZU7-1; Sequence=Displayed;
CC Name=b {ECO:0000312|WormBase:T14E8.1b};
CC IsoId=H2KZU7-2; Sequence=VSP_057916, VSP_057918;
CC Name=c {ECO:0000312|WormBase:T14E8.1c};
CC IsoId=H2KZU7-3; Sequence=VSP_057917, VSP_057919;
CC -!- TISSUE SPECIFICITY: Expressed in body wall and vulva muscles, pharynx,
CC intestine, excretory canals, distal tip cells and some neurons.
CC Expressed in D-type motor neurons upon axon injury.
CC {ECO:0000269|PubMed:22388962}.
CC -!- PTM: May be autophosphorylated on Tyr-890 following dimerization.
CC {ECO:0000269|PubMed:22388962}.
CC -!- DISRUPTION PHENOTYPE: Viable. Reduced axon regeneration 24 hours
CC following injury of D-type motor neurons.
CC {ECO:0000269|PubMed:27984580}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. {ECO:0000255|PROSITE-ProRule:PRU00159}.
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DR EMBL; AB693147; BAL45942.1; -; mRNA.
DR EMBL; BX284606; CCD83400.1; -; Genomic_DNA.
DR EMBL; BX284606; CCD83401.1; -; Genomic_DNA.
DR EMBL; BX284606; CCD83402.1; -; Genomic_DNA.
DR RefSeq; NP_001024906.1; NM_001029735.3. [H2KZU7-3]
DR RefSeq; NP_509104.1; NM_076703.6. [H2KZU7-1]
DR RefSeq; NP_509105.1; NM_076704.4.
DR AlphaFoldDB; H2KZU7; -.
DR SMR; H2KZU7; -.
DR STRING; 6239.T14E8.1a; -.
DR iPTMnet; H2KZU7; -.
DR EPD; H2KZU7; -.
DR PaxDb; H2KZU7; -.
DR PeptideAtlas; H2KZU7; -.
DR EnsemblMetazoa; T14E8.1a.1; T14E8.1a.1; WBGene00020504. [H2KZU7-1]
DR EnsemblMetazoa; T14E8.1b.1; T14E8.1b.1; WBGene00020504. [H2KZU7-2]
DR EnsemblMetazoa; T14E8.1b.2; T14E8.1b.2; WBGene00020504. [H2KZU7-2]
DR EnsemblMetazoa; T14E8.1c.1; T14E8.1c.1; WBGene00020504. [H2KZU7-3]
DR GeneID; 180929; -.
DR KEGG; cel:CELE_T14E8.1; -.
DR UCSC; T14E8.1c; c. elegans.
DR CTD; 180929; -.
DR WormBase; T14E8.1a; CE28667; WBGene00020504; svh-2. [H2KZU7-1]
DR WormBase; T14E8.1b; CE29341; WBGene00020504; svh-2. [H2KZU7-2]
DR WormBase; T14E8.1c; CE37148; WBGene00020504; svh-2. [H2KZU7-3]
DR eggNOG; KOG1095; Eukaryota.
DR GeneTree; ENSGT00940000168249; -.
DR InParanoid; H2KZU7; -.
DR OMA; ACKTIDS; -.
DR OrthoDB; 163404at2759; -.
DR Reactome; R-CEL-109704; PI3K Cascade.
DR Reactome; R-CEL-1257604; PIP3 activates AKT signaling.
DR Reactome; R-CEL-186763; Downstream signal transduction.
DR Reactome; R-CEL-186797; Signaling by PDGF.
DR Reactome; R-CEL-210993; Tie2 Signaling.
DR Reactome; R-CEL-5673001; RAF/MAP kinase cascade.
DR Reactome; R-CEL-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR Reactome; R-CEL-9607240; FLT3 Signaling.
DR PRO; PR:H2KZU7; -.
DR Proteomes; UP000001940; Chromosome X.
DR Bgee; WBGene00020504; Expressed in pharyngeal muscle cell (C elegans) and 3 other tissues.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; ISS:WormBase.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0031435; F:mitogen-activated protein kinase kinase kinase binding; IPI:UniProtKB.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IDA:UniProtKB.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IMP:UniProtKB.
DR GO; GO:0031103; P:axon regeneration; IMP:WormBase.
DR GO; GO:0038083; P:peptidyl-tyrosine autophosphorylation; IMP:UniProtKB.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IMP:UniProtKB.
DR GO; GO:0048680; P:positive regulation of axon regeneration; IDA:UniProtKB.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IGI:WormBase.
DR GO; GO:0006468; P:protein phosphorylation; IMP:UniProtKB.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR Gene3D; 2.130.10.10; -; 1.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR036352; Semap_dom_sf.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF101912; SSF101912; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Cell membrane; Glycoprotein; Kinase;
KW Membrane; Nucleotide-binding; Phosphoprotein; Receptor; Reference proteome;
KW Signal; Transferase; Transmembrane; Transmembrane helix;
KW Tyrosine-protein kinase.
FT SIGNAL 1..34
FT /evidence="ECO:0000255"
FT CHAIN 35..1086
FT /note="Tyrosine-protein kinase receptor svh-2"
FT /evidence="ECO:0000305"
FT /id="PRO_0000434163"
FT TOPO_DOM 35..651
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 652..672
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 673..1086
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 735..996
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1056..1086
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 858
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 741..749
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 767
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT SITE 767
FT /note="Required for shc-1 interaction"
FT /evidence="ECO:0000269|PubMed:27984580"
FT MOD_RES 890
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:22388962"
FT CARBOHYD 276
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 299
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 461
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 554
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 617
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT VAR_SEQ 1017..1030
FT /note="SRFLSLSRHDPAFP -> ELVTSRPSISNLSE (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_057916"
FT VAR_SEQ 1018
FT /note="R -> F (in isoform c)"
FT /evidence="ECO:0000305"
FT /id="VSP_057917"
FT VAR_SEQ 1019..1086
FT /note="Missing (in isoform c)"
FT /evidence="ECO:0000305"
FT /id="VSP_057919"
FT VAR_SEQ 1031..1086
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_057918"
FT MUTAGEN 767
FT /note="K->R: Abolished interaction with shc-1. Probable
FT loss of kinase activity. Loss of phosphorylation at Y-890.
FT Impaired axon regeneration following injury."
FT /evidence="ECO:0000269|PubMed:22388962,
FT ECO:0000269|PubMed:27984580"
FT MUTAGEN 890
FT /note="Y->F: Abolishes phosphorylation. Impaired axon
FT regeneration following injury."
FT /evidence="ECO:0000269|PubMed:22388962"
SQ SEQUENCE 1086 AA; 122895 MW; 58BD2277423F77E0 CRC64;
MVLGSSQSSA KELTTQSSIF RFLVLLLCFT SATGGQINGK LLNGNGVFVS RDELQNKNVL
GVITGFDLLV VATHSRFQVF ENNEERRTVG HVSLDMHPRT KFLELKLFSK SEIFYCDESS
CGLCTYSGVT SSCSTFMLNG DEPKIQEILS SSAVKIENLG QIMLAISFKN EEDPDNPRTM
ILRYNAQDTG TVIPTAYHAD SSFIHNNHAL TGFEREGFVY FVMTASQIFE PEVFLHDQSN
NKVTVTKVIR FCATDQTADL ASKISILVGC DQEFRNISSR GETAVYDHAN DLINIVMFNH
TSMNHLMCRF KMANIEKRFK TIWSTCQETS FSGSTAKTTR CKYPQIFDQM KVKKGCLTYS
RLDDESSPTL CVRYGRGDAL DNCQLHTAKS NSYRYGWLED YNVLQGELMM RIPYPFFGIA
ESLITDGKSY FAAVSGEFDM SDVLRFSASE SADIRPHWRT NISVVGKFSI TKTKENQLLY
TTVEGLQSLD ISCKGLYPNC QTLRQGGWED PLECSWCADD NAQRTITSSE VSSCKNNLKH
ECPPSMRWIH KYNNNSGFTA VVDGFRALKN PKLNACGTNC VVTVVDSSSI QCDTNPDEVI
GDSCKQVFLS GMIGDKNYSF PFDYQQADRG TQTDVKNSQV DDKKGSSPGW KIAIAIISVM
TIILIVAIIV YYMRNRFPRI KTHVRPPIGQ RIENEYDMGH MAGRQAQLAI NGDNYVKVFR
SMRPDLKVDF KNLRVDKLDP IGQGHYGVVY KAMYSPSKSL EEKVVCKYLK EGKISEFYEE
ARTMSEFDHP NILKLIGVAL DDSSHLPIII TEYMAKGDLK SFIENVENTI KMRDLFEFAF
DIAKGMNYMH SKKFIHRDLA CRNCLLDEHL RVKIADFGLC RKVDIETELY VQMHERDLPV
RWFPPEISEQ GFGITSDIWS FGVVIWELFT RGSTPYSNMA SWILILPWLK ESETNRLRKP
PYCPEKLYTD VMLACWKANP AERPQFSDLV TIIPNVVKYM EGYDRSQLQA GYERVSSRFL
SLSRHDPAFP IYQNEMPNTP LLANCQNDTN DSKTLAELPS DSPSTSTAIP QSTPYQLLSE
CSETSV
