DDRB_CAEEL
ID DDRB_CAEEL Reviewed; 797 AA.
AC Q95ZV7; Q95ZV6;
DT 14-OCT-2015, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Discoidin domain-containing receptor tyrosine kinase B {ECO:0000305};
DE EC=2.7.10.1 {ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000269|PubMed:27984580, ECO:0000269|PubMed:31371405};
DE AltName: Full=Discoidin domain-containing receptor B {ECO:0000303|PubMed:23147028};
DE Flags: Precursor;
GN Name=ddr-2 {ECO:0000312|WormBase:F11D5.3a};
GN Synonyms=svh-4 {ECO:0000303|PubMed:27984580,
GN ECO:0000312|WormBase:F11D5.3a};
GN ORFNames=F11D5.3 {ECO:0000312|WormBase:F11D5.3a};
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|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 [2] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=23147028; DOI=10.1016/j.ydbio.2012.11.001;
RA Unsoeld T., Park J.O., Hutter H.;
RT "Discoidin domain receptors guide axons along longitudinal tracts in C.
RT elegans.";
RL Dev. Biol. 374:142-152(2013).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH SHC-1, SUBCELLULAR LOCATION,
RP TISSUE SPECIFICITY, PHOSPHORYLATION, DISRUPTION PHENOTYPE, AND MUTAGENESIS
RP OF ARG-100 AND LYS-554.
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, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, PHOSPHORYLATION,
RP GLYCOSYLATION AT ASN-141, AND MUTAGENESIS OF ASN-141; ASN-167; ASN-264;
RP ASN-353 AND LYS-554.
RX PubMed=31371405; DOI=10.1534/genetics.119.302492;
RA Shimizu T., Kato Y., Sakai Y., Hisamoto N., Matsumoto K.;
RT "N-Glycosylation of the Discoidin Domain Receptor Is Required for Axon
RT Regeneration in Caenorhabditis elegans.";
RL Genetics 213:491-500(2019).
CC -!- FUNCTION: Tyrosine-protein kinase receptor which, together with ddr-1,
CC is involved in axon guidance to establish the tracts for the ventral
CC and dorsal nerve cords during nervous system development
CC (PubMed:23147028). Acts upstream of the adapter shc-1, and the tyrosine
CC kinase receptors svh-1 and svh-2 to regulate axon regeneration
CC following injury in D-type motor neurons (PubMed:27984580,
CC PubMed:31371405). May mediate axon regeneration in association with the
CC collagen emb-9 (PubMed:27984580). {ECO:0000269|PubMed:23147028,
CC ECO:0000269|PubMed:27984580, ECO:0000269|PubMed:31371405}.
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:0000255|PROSITE-ProRule:PRU00159,
CC ECO:0000269|PubMed:27984580, ECO:0000269|PubMed:31371405};
CC -!- SUBUNIT: Interacts with shc-1. {ECO:0000269|PubMed:27984580}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:27984580};
CC Single-pass type I membrane protein {ECO:0000305}. Cell projection,
CC axon {ECO:0000269|PubMed:23147028, ECO:0000269|PubMed:27984580,
CC ECO:0000269|PubMed:31371405}. Perikaryon {ECO:0000269|PubMed:23147028}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=a {ECO:0000312|WormBase:F11D5.3a};
CC IsoId=Q95ZV7-1; Sequence=Displayed;
CC Name=b {ECO:0000312|WormBase:F11D5.3b};
CC IsoId=Q95ZV7-2; Sequence=VSP_057892;
CC -!- TISSUE SPECIFICITY: Expressed in some neurons in head and tail, some
CC motoneurons in ventral nerve cord, in PVP interneurons, seam cells,
CC rectal gland cells, vulva cells and some non-neuronal cells in the tail
CC (PubMed:23147028). Expressed in D-type motor neurons (PubMed:27984580).
CC {ECO:0000269|PubMed:23147028, ECO:0000269|PubMed:27984580}.
CC -!- DEVELOPMENTAL STAGE: Expression begins during late gastrulation in seam
CC cells and in few head neurons. {ECO:0000269|PubMed:23147028}.
CC -!- PTM: Autophosphorylated on tyrosine residues.
CC {ECO:0000269|PubMed:23147028, ECO:0000269|PubMed:31371405}.
CC -!- PTM: N-glycosylation at Asn-141 is required for axon regeneration after
CC injury but is dispensable for kinase activity and axon localization.
CC {ECO:0000269|PubMed:31371405}.
CC -!- DISRUPTION PHENOTYPE: Viable. Normal morphology of D-type motor
CC neurons, but 24 hours following injury of D-type motor neurons there is
CC reduced axon regeneration. Double knockout with ddr-1 results in a more
CC enhanced axon regeneration defect of D-type motor neurons as compared
CC to the svh-4 and ddr-1 single mutants. {ECO:0000269|PubMed:27984580}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. Insulin receptor subfamily. {ECO:0000305}.
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DR EMBL; BX284606; CCD69233.1; -; Genomic_DNA.
DR EMBL; BX284606; CCD69234.1; -; Genomic_DNA.
DR RefSeq; NP_508572.1; NM_076171.4. [Q95ZV7-1]
DR RefSeq; NP_508573.1; NM_076172.4. [Q95ZV7-2]
DR AlphaFoldDB; Q95ZV7; -.
DR SMR; Q95ZV7; -.
DR DIP; DIP-27423N; -.
DR STRING; 6239.F11D5.3a; -.
DR EPD; Q95ZV7; -.
DR PaxDb; Q95ZV7; -.
DR EnsemblMetazoa; F11D5.3a.1; F11D5.3a.1; WBGene00017381. [Q95ZV7-1]
DR EnsemblMetazoa; F11D5.3b.1; F11D5.3b.1; WBGene00017381. [Q95ZV7-2]
DR EnsemblMetazoa; F11D5.3b.2; F11D5.3b.2; WBGene00017381. [Q95ZV7-2]
DR GeneID; 180622; -.
DR KEGG; cel:CELE_F11D5.3; -.
DR UCSC; F11D5.3b.3; c. elegans.
DR CTD; 180622; -.
DR WormBase; F11D5.3a; CE27950; WBGene00017381; ddr-2. [Q95ZV7-1]
DR WormBase; F11D5.3b; CE27951; WBGene00017381; ddr-2. [Q95ZV7-2]
DR eggNOG; KOG1094; Eukaryota.
DR GeneTree; ENSGT00940000169525; -.
DR InParanoid; Q95ZV7; -.
DR OMA; QILRCHF; -.
DR OrthoDB; 227725at2759; -.
DR PhylomeDB; Q95ZV7; -.
DR PRO; PR:Q95ZV7; -.
DR Proteomes; UP000001940; Chromosome X.
DR Bgee; WBGene00017381; Expressed in pharyngeal muscle cell (C elegans) and 3 other tissues.
DR GO; GO:0030424; C:axon; IDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005518; F:collagen binding; IBA:GO_Central.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IDA:UniProtKB.
DR GO; GO:0038062; F:protein tyrosine kinase collagen receptor activity; IBA:GO_Central.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0097376; P:interneuron axon guidance; IMP:UniProtKB.
DR GO; GO:0008045; P:motor neuron axon guidance; IMP:UniProtKB.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:UniProtKB.
DR GO; GO:0048680; P:positive regulation of axon regeneration; IMP:UniProtKB.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR InterPro; IPR000421; FA58C.
DR InterPro; IPR008979; Galactose-bd-like_sf.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR Pfam; PF00754; F5_F8_type_C; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00231; FA58C; 1.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF49785; SSF49785; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS01285; FA58C_1; 1.
DR PROSITE; PS01286; FA58C_2; 1.
DR PROSITE; PS50022; FA58C_3; 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; Cell projection;
KW Disulfide bond; Glycoprotein; Kinase; Membrane; Neurogenesis;
KW Nucleotide-binding; Receptor; Reference proteome; Repeat; Signal;
KW Transferase; Transmembrane; Transmembrane helix; Tyrosine-protein kinase.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..797
FT /note="Discoidin domain-containing receptor tyrosine kinase
FT B"
FT /evidence="ECO:0000305"
FT /id="PRO_0000434039"
FT TOPO_DOM 20..384
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 385..405
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 406..797
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 25..181
FT /note="F5/8 type C"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00081"
FT DOMAIN 527..785
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 46..66
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 645
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 533..541
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 554
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT SITE 100
FT /note="May be required for collagen binding"
FT /evidence="ECO:0000303|PubMed:27984580"
FT CARBOHYD 141
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:31371405"
FT CARBOHYD 167
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 264
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 353
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 25..181
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00081"
FT VAR_SEQ 1..30
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_057892"
FT MUTAGEN 100
FT /note="R->A: Does not rescue the axon regeneration defect
FT in the svh-4 loss of function mutant (ok564) following
FT injury to D-type motor neurons."
FT /evidence="ECO:0000269|PubMed:27984580"
FT MUTAGEN 141
FT /note="N->A: Loss of N-glycosylation. Impairs axon
FT regeneration following axon injury. No effect on axon
FT localization and kinase activity."
FT /evidence="ECO:0000269|PubMed:31371405"
FT MUTAGEN 167
FT /note="N->A: Partially impairs axon regeneration following
FT axon injury."
FT /evidence="ECO:0000269|PubMed:31371405"
FT MUTAGEN 264
FT /note="N->A: No effect on axon regeneration following axon
FT injury."
FT /evidence="ECO:0000269|PubMed:31371405"
FT MUTAGEN 353
FT /note="N->A: No effect on axon regeneration following axon
FT injury."
FT /evidence="ECO:0000269|PubMed:31371405"
FT MUTAGEN 554
FT /note="K->E: Abolishes kinase activity and abolishes
FT autophosphorylation. Does not rescue the axon regeneration
FT defect in the svh-4 loss of function mutant (ok564)
FT following injury to D-type motor neurons."
FT /evidence="ECO:0000269|PubMed:27984580,
FT ECO:0000269|PubMed:31371405"
SQ SEQUENCE 797 AA; 90303 MW; C96D16AFE144899E CRC64;
MKLLLYLFGV TFHSNTVVAL ELRECSHQLG MSNRKIRDEQ ISASSSFDLQ STGPQHARAH
QESGSGAWCP KNQINSLSKE WLQISFSVDT VITSVETQGR FDDGRGMEYA TAFKIQYWRP
SLNAWASYKD DFELETIPAN NDTEHAIRRH LDRAIIARRI RIVPVSNSTR TVCMRVEVFG
CPFDDSLVFY NVDQGDLQSG ISYHDFSYDG NLANSPHLTG GIGKLYDGEV GKNNVFVNHH
KWVGWRRKRN GNVKLAFEFS ELRNISGILI HTSNEFKKSA KAFSSATVLF SINGKDFSDT
IVHFNNPEDT ESEVPRWIRI PVNNRIAKVA KIRLNFGTDS DWLFISEVNF ESNHTNIELL
NDDVVIPDSV SYFSVTEHDD GTSMFAFIIF FFMFLIVAVI ILTVLYRKRE YRVKASSPSP
NAKREILLTI DGNTIKHHVS PSTYQMARDN LQNALIEKMP MSPIISDYAE PDISVCSDVT
ANTPLLYGID GPYDTQKRSN PLSSMVKYSD YGEVYCTTLP EIARDKLICV SRIGQGEFGE
VDLCQLENRK VAVKKLHGIS QADEFSFHRE IRVLGSLKHP NVVEVVGVCT IQKPILCIME
YMENGDLKSY ILKNPTIQTS QCISICTQLA AGLAYLESCN FVHRDIAARN CLVDGEGNVK
IADFGMARSL YSQEYYKVEG KFVLPIRWMA WEALLLGKFS TASDVWGFGV TMWEIFSLCS
EKPYSDMTDD DVVENLQSMS STGSLKQVLS RPRMCPSKLY NEQILPCWNY ESSRRPSFEN
VHLHLQSLVH TSPHIHF
