ROR2_MOUSE
ID ROR2_MOUSE Reviewed; 944 AA.
AC Q9Z138; E9QKB3;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 186.
DE RecName: Full=Tyrosine-protein kinase transmembrane receptor ROR2;
DE Short=mROR2;
DE EC=2.7.10.1 {ECO:0000250|UniProtKB:Q01974};
DE AltName: Full=Neurotrophic tyrosine kinase, receptor-related 2;
DE Flags: Precursor;
GN Name=Ror2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10231392; DOI=10.1046/j.1365-2443.1999.00234.x;
RA Oishi I., Takeuchi S., Hashimoto R., Nagabukuro A., Ueda T., Liu Z.J.,
RA Hatta T., Akira S., Matsuda Y., Yamamura H., Otani H., Minami Y.;
RT "Spatio-temporally regulated expression of receptor tyrosine kinases,
RT mRor1, mRor2, during mouse development: implications in development and
RT function of the nervous system.";
RL Genes Cells 4:41-56(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP FUNCTION.
RX PubMed=10700181; DOI=10.1038/73488;
RA DeChiara T.M., Kimble R.B., Poueymirou W.T., Rojas J., Masiakowski P.,
RA Valenzuela D.M., Yancopoulos G.D.;
RT "Ror2, encoding a receptor-like tyrosine kinase, is required for cartilage
RT and growth plate development.";
RL Nat. Genet. 24:271-274(2000).
RN [4]
RP INTERACTION WITH WTIP, SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
RX PubMed=19785987; DOI=10.1016/j.bbrc.2009.09.086;
RA van Wijk N.V., Witte F., Feike A.C., Schambony A., Birchmeier W.,
RA Mundlos S., Stricker S.;
RT "The LIM domain protein Wtip interacts with the receptor tyrosine kinase
RT Ror2 and inhibits canonical Wnt signalling.";
RL Biochem. Biophys. Res. Commun. 390:211-216(2009).
RN [5]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-785, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryo;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
CC -!- FUNCTION: Tyrosine-protein kinase receptor which may be involved in the
CC early formation of the chondrocytes. It seems to be required for
CC cartilage and growth plate development (PubMed:10700181).
CC Phosphorylates YWHAB, leading to induction of osteogenesis and bone
CC formation. In contrast, has also been shown to have very little
CC tyrosine kinase activity in vitro. May act as a receptor for wnt ligand
CC WNT5A which may result in the inhibition of WNT3A-mediated signaling
CC (By similarity). {ECO:0000250|UniProtKB:Q01974,
CC ECO:0000269|PubMed:10700181}.
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:0000250|UniProtKB:Q01974, ECO:0000255|PROSITE-
CC ProRule:PRU10028};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q01974};
CC -!- SUBUNIT: Homodimer; promotes osteogenesis. Binds YWHAB (By similarity).
CC Interacts with WTIP (PubMed:19785987). {ECO:0000250|UniProtKB:Q01974,
CC ECO:0000269|PubMed:19785987}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:19785987};
CC Single-pass type I membrane protein {ECO:0000269|PubMed:19785987}.
CC -!- DEVELOPMENTAL STAGE: From 9.5 to 11.5 dpc, expressed in the branchial
CC arches, otic vesicle, limb buds, somites, craniofacial mesenchyme and
CC tail buds. At 14.5 dpc, expressed in the developing tongue, nasal
CC cavity, palate, adrenal gland, in the forebrain, dorsal root ganglia
CC and in the somites. At 14.5 dpc, also detected in lung, rib cartilage,
CC kidney and intestine (at protein level). {ECO:0000269|PubMed:19785987}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. ROR subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}.
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DR EMBL; AB010384; BAA75481.1; -; mRNA.
DR EMBL; AC111017; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS26520.1; -.
DR AlphaFoldDB; Q9Z138; -.
DR SMR; Q9Z138; -.
DR CORUM; Q9Z138; -.
DR IntAct; Q9Z138; 1.
DR STRING; 10090.ENSMUSP00000021918; -.
DR GlyGen; Q9Z138; 3 sites.
DR iPTMnet; Q9Z138; -.
DR PhosphoSitePlus; Q9Z138; -.
DR SwissPalm; Q9Z138; -.
DR EPD; Q9Z138; -.
DR MaxQB; Q9Z138; -.
DR PaxDb; Q9Z138; -.
DR PRIDE; Q9Z138; -.
DR ProteomicsDB; 260831; -.
DR Antibodypedia; 13579; 691 antibodies from 39 providers.
DR MGI; MGI:1347521; Ror2.
DR VEuPathDB; HostDB:ENSMUSG00000021464; -.
DR eggNOG; KOG1026; Eukaryota.
DR InParanoid; Q9Z138; -.
DR PhylomeDB; Q9Z138; -.
DR TreeFam; TF106465; -.
DR Reactome; R-MMU-5140745; WNT5A-dependent internalization of FZD2, FZD5 and ROR2.
DR ChiTaRS; Ror2; mouse.
DR PRO; PR:Q9Z138; -.
DR Proteomes; UP000000589; Chromosome 13.
DR RNAct; Q9Z138; protein.
DR ExpressionAtlas; Q9Z138; baseline and differential.
DR Genevisible; Q9Z138; MM.
DR GO; GO:0009986; C:cell surface; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0030425; C:dendrite; ISO:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:MGI.
DR GO; GO:0005874; C:microtubule; ISO:MGI.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005109; F:frizzled binding; IPI:BHF-UCL.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0031435; F:mitogen-activated protein kinase kinase kinase binding; IPI:WormBase.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0017147; F:Wnt-protein binding; IPI:MGI.
DR GO; GO:0014002; P:astrocyte development; ISO:MGI.
DR GO; GO:0030509; P:BMP signaling pathway; IMP:MGI.
DR GO; GO:0001502; P:cartilage condensation; IMP:MGI.
DR GO; GO:0045165; P:cell fate commitment; IMP:MGI.
DR GO; GO:0002062; P:chondrocyte differentiation; IMP:MGI.
DR GO; GO:0042733; P:embryonic digit morphogenesis; IMP:MGI.
DR GO; GO:0030538; P:embryonic genitalia morphogenesis; IMP:MGI.
DR GO; GO:0042472; P:inner ear morphogenesis; IMP:MGI.
DR GO; GO:0007254; P:JNK cascade; IDA:MGI.
DR GO; GO:1905517; P:macrophage migration; ISO:MGI.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IGI:MGI.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IDA:BHF-UCL.
DR GO; GO:0030335; P:positive regulation of cell migration; ISO:MGI.
DR GO; GO:0043507; P:positive regulation of JUN kinase activity; ISO:MGI.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:0045651; P:positive regulation of macrophage differentiation; ISO:MGI.
DR GO; GO:0010976; P:positive regulation of neuron projection development; IBA:GO_Central.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; IBA:GO_Central.
DR GO; GO:1900020; P:positive regulation of protein kinase C activity; ISO:MGI.
DR GO; GO:0051968; P:positive regulation of synaptic transmission, glutamatergic; ISO:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:BHF-UCL.
DR GO; GO:0060828; P:regulation of canonical Wnt signaling pathway; IMP:MGI.
DR GO; GO:0007165; P:signal transduction; ISO:MGI.
DR GO; GO:0001501; P:skeletal system development; IMP:MGI.
DR GO; GO:0060395; P:SMAD protein signal transduction; IMP:MGI.
DR GO; GO:0007224; P:smoothened signaling pathway; IMP:MGI.
DR GO; GO:0001756; P:somitogenesis; IMP:MGI.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR GO; GO:0007223; P:Wnt signaling pathway, calcium modulating pathway; IPI:MGI.
DR GO; GO:0060071; P:Wnt signaling pathway, planar cell polarity pathway; IMP:MGI.
DR CDD; cd00108; KR; 1.
DR Gene3D; 1.10.2000.10; -; 1.
DR Gene3D; 2.40.20.10; -; 1.
DR Gene3D; 2.60.40.10; -; 1.
DR InterPro; IPR020067; Frizzled_dom.
DR InterPro; IPR036790; Frizzled_dom_sf.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR013098; Ig_I-set.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR003598; Ig_sub2.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000001; Kringle.
DR InterPro; IPR013806; Kringle-like.
DR InterPro; IPR018056; Kringle_CS.
DR InterPro; IPR038178; Kringle_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR016247; Tyr_kinase_rcpt_ROR.
DR Pfam; PF01392; Fz; 1.
DR Pfam; PF07679; I-set; 1.
DR Pfam; PF00051; Kringle; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR PIRSF; PIRSF000624; TyrPK_TMrec_ROR; 1.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00409; IG; 1.
DR SMART; SM00408; IGc2; 1.
DR SMART; SM00130; KR; 1.
DR SUPFAM; SSF48726; SSF48726; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR SUPFAM; SSF57440; SSF57440; 1.
DR PROSITE; PS50038; FZ; 1.
DR PROSITE; PS50835; IG_LIKE; 1.
DR PROSITE; PS00021; KRINGLE_1; 1.
DR PROSITE; PS50070; KRINGLE_2; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cell membrane; Developmental protein; Disulfide bond;
KW Glycoprotein; Immunoglobulin domain; Kinase; Kringle; Magnesium; Membrane;
KW Metal-binding; Methylation; Nucleotide-binding; Phosphoprotein; Receptor;
KW Reference proteome; Signal; Transferase; Transmembrane;
KW Transmembrane helix; Wnt signaling pathway.
FT SIGNAL 1..33
FT /evidence="ECO:0000255"
FT CHAIN 34..944
FT /note="Tyrosine-protein kinase transmembrane receptor ROR2"
FT /id="PRO_0000024461"
FT TOPO_DOM 34..403
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 404..424
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 425..944
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 55..145
FT /note="Ig-like C2-type"
FT DOMAIN 169..303
FT /note="FZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DOMAIN 316..394
FT /note="Kringle"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DOMAIN 473..746
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 757..779
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 850..879
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 898..929
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 856..879
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 908..923
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 615
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 479..487
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 507
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 646
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 785
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT CARBOHYD 70
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 188
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 318
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 83..135
FT /evidence="ECO:0000250"
FT DISULFID 174..239
FT /evidence="ECO:0000250"
FT DISULFID 182..232
FT /evidence="ECO:0000250"
FT DISULFID 223..264
FT /evidence="ECO:0000250"
FT DISULFID 252..300
FT /evidence="ECO:0000250"
FT DISULFID 256..286
FT /evidence="ECO:0000250"
FT DISULFID 316..394
FT /evidence="ECO:0000250"
FT DISULFID 337..377
FT /evidence="ECO:0000250"
FT DISULFID 365..389
FT /evidence="ECO:0000250"
FT CONFLICT 110
FT /note="I -> V (in Ref. 1; BAA75481)"
FT /evidence="ECO:0000305"
FT CONFLICT 242
FT /note="R -> C (in Ref. 1; BAA75481)"
FT /evidence="ECO:0000305"
FT CONFLICT 372
FT /note="V -> M (in Ref. 1; BAA75481)"
FT /evidence="ECO:0000305"
FT CONFLICT 398
FT /note="D -> Y (in Ref. 1; BAA75481)"
FT /evidence="ECO:0000305"
FT CONFLICT 612
FT /note="V -> C (in Ref. 1; BAA75481)"
FT /evidence="ECO:0000305"
FT CONFLICT 897
FT /note="A -> V (in Ref. 1; BAA75481)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 944 AA; 105005 MW; 03B00784CFFF4489 CRC64;
MARGWVRPSR VPLCARAVWT AAALLLWTPW TAGEVEDSEA IDTLGQPDGP DSPLPTLKGY
FLNFLEPVNN ITIVQGQTAI LHCKVAGNPP PNVRWLKNDA PVVQEPRRVI IRKTEYGSRL
RIQDLDTTDT GYYQCVATNG LKTITATGVL YVRLGPTHSP NHNFQDDDQE DGFCQPYRGI
ACARFIGNRT IYVDSLQMQG EIENRITAAF TMIGTSTQLS DQCSQFAIPS FCHFVFPLCD
ARSRAPKPRE LCRDECEVLE NDLCRQEYTI ARSNPLILMR LQLPKCEALP MPESPDAANC
MRIGIPAERL GRYHQCYNGS GADYRGMAST TKSGHQCQPW ALQHPHSHRL SSTEFPELGG
GHAYCRNPGG QVEGPWCFTQ NKNVRVELCD VPPCSPRDGS KMGILYILVP SIAIPLVIAC
LFFLVCMCRN KQKASASTPQ RRQLMASPSQ DMEMPLISQH KQAKLKEISL STVRFMEELG
EDRFGKVYKG HLFGPAPGEP TQAVAIKTLK DKAEGPLREE FRQEAMLRAR LQHPNIVCLL
GVVTKDQPLS MIFSYCSHGD LHEFLVMRSP HSDVGSTDDD RTVKSALEPP DFVHVVAQIA
AGMEFLSSHH VVHKDLATRN VLVYDKLNVR ISDLGLFREV YSADYYKLMG NSLLPIRWMS
PEAVMYGKFS IDSDIWSYGV VLWEVFSYGL QPYCGYSNQD VVEMIRSRQV LPCPDDCPAW
VYALMIECWN EFPSRRPRFK DIHSRLRSWG NLSNYNSSAQ TSGASNTTQT SSLSTSPVSN
VSNARYMAPK QKAQPFPQPQ FIPMKGQIRP LVPPAQLYIP VNGYQPVPAY GAYLPNFYPV
QIPMQMAPQQ VPPQMVPKPS SHHSGSGSTS TGYVTTAPSN TSVADRAALL SEGTEDAQNI
AEDVAQSPVQ EAEEEEEGSV PETELLGDND TLQVTEAAHV QLEA
