ID   ROR2_HUMAN              Reviewed;         943 AA.
AC   Q01974; Q59GF5; Q5SPI5; Q9HAY7; Q9HB61;
DT   27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT   07-MAR-2006, sequence version 2.
DT   27-MAR-2024, entry version 230.
DE   RecName: Full=Tyrosine-protein kinase transmembrane receptor ROR2;
DE            EC=2.7.10.1 {ECO:0000269|PubMed:17717073};
DE   AltName: Full=Neurotrophic tyrosine kinase, receptor-related 2;
DE   Flags: Precursor;
GN   Name=ROR2; Synonyms=NTRKR2;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ALA-245.
RX   PubMed=1334494; DOI=10.1016/s0021-9258(18)35733-8;
RA   Masiakowski P., Carroll R.D.;
RT   "A novel family of cell surface receptors with tyrosine kinase-like
RT   domain.";
RL   J. Biol. Chem. 267:26181-26190(1992).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15164053; DOI=10.1038/nature02465;
RA   Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA   Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA   Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA   Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA   Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA   Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA   Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA   Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA   Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA   Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA   Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA   Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA   Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA   Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA   Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA   Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA   Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA   Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA   McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA   Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA   Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA   Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA   Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA   West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA   Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA   Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA   Dunham I.;
RT   "DNA sequence and analysis of human chromosome 9.";
RL   Nature 429:369-374(2004).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 33-943, AND VARIANTS ALA-245 AND
RP   ILE-819.
RC   TISSUE=Brain;
RA   Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA   Ohara O., Nagase T., Kikuno R.F.;
RL   Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 34-943, AND VARIANTS ALA-245 AND
RP   ILE-819.
RX   PubMed=10700182; DOI=10.1038/73495;
RA   Oldridge M., Fortuna A.M., Maringa M., Propping P., Mansour S., Pollitt C.,
RA   DeChiara T.M., Kimble R.B., Valenzuela D.M., Yancopoulos G.D.,
RA   Wilkie A.O.M.;
RT   "Dominant mutations in ROR2, encoding an orphan receptor tyrosine kinase,
RT   cause brachydactyly type B.";
RL   Nat. Genet. 24:275-278(2000).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 34-574, AND VARIANT ALA-245.
RX   PubMed=10986040; DOI=10.1086/303084;
RA   Schwabe G.C., Tinschert S., Buschow C., Meinecke P., Wolff G.,
RA   Gillessen-Kaesbach G., Oldridge M., Wilkie A.O.M., Koemec R., Mundlos S.;
RT   "Distinct mutations in the receptor tyrosine kinase gene ROR2 cause
RT   brachydactyly type B.";
RL   Am. J. Hum. Genet. 67:822-831(2000).
RN   [6]
RP   PROTEIN SEQUENCE OF 465-474, SULFATION AT SER-469 AND SER-471, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY.
RX   PubMed=14752058; DOI=10.1074/mcp.m300140-mcp200;
RA   Medzihradszky K.F., Darula Z., Perlson E., Fainzilber M., Chalkley R.J.,
RA   Ball H., Greenbaum D., Bogyo M., Tyson D.R., Bradshaw R.A.,
RA   Burlingame A.L.;
RT   "O-sulfonation of serine and threonine: mass spectrometric detection and
RT   characterization of a new posttranslational modification in diverse
RT   proteins throughout the eukaryotes.";
RL   Mol. Cell. Proteomics 3:429-440(2004).
RN   [7]
RP   FUNCTION, CATALYTIC ACTIVITY, COFACTOR, INTERACTION WITH YWHAB, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY.
RX   PubMed=17717073; DOI=10.1210/me.2007-0323;
RA   Liu Y., Ross J.F., Bodine P.V.N., Billiard J.;
RT   "Homodimerization of Ror2 tyrosine kinase receptor induces 14-3-3(beta)
RT   phosphorylation and promotes osteoblast differentiation and bone
RT   formation.";
RL   Mol. Endocrinol. 21:3050-3061(2007).
RN   [8]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA   Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA   Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT   "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT   site occupancy during mitosis.";
RL   Sci. Signal. 3:RA3-RA3(2010).
RN   [9]
RP   FUNCTION, LACK OF CATALYTIC ACTIVITY, AND MUTAGENESIS OF ASP-482.
RX   PubMed=25029443; DOI=10.1371/journal.pone.0102695;
RA   Bainbridge T.W., DeAlmeida V.I., Izrael-Tomasevic A., Chalouni C., Pan B.,
RA   Goldsmith J., Schoen A.P., Quinones G.A., Kelly R., Lill J.R., Sandoval W.,
RA   Costa M., Polakis P., Arnott D., Rubinfeld B., Ernst J.A.;
RT   "Evolutionary divergence in the catalytic activity of the CAM-1, ROR1 and
RT   ROR2 kinase domains.";
RL   PLoS ONE 9:E102695-E102695(2014).
RN   [10]
RP   INTERACTION WITH TMEM67.
RX   PubMed=26035863; DOI=10.1242/dmm.019083;
RA   Abdelhamed Z.A., Natarajan S., Wheway G., Inglehearn C.F., Toomes C.,
RA   Johnson C.A., Jagger D.J.;
RT   "The Meckel-Gruber syndrome protein TMEM67 controls basal body positioning
RT   and epithelial branching morphogenesis in mice via the non-canonical Wnt
RT   pathway.";
RL   Dis. Model. Mech. 8:527-541(2015).
RN   [11]
RP   VARIANTS RRS1 CYS-184; TRP-189; TRP-366 AND LYS-620.
RX   PubMed=10932186; DOI=10.1038/78107;
RA   Afzal A.R., Rajab A., Fenske C.D., Oldridge M., Elanko N.,
RA   Ternes-Pereira E., Tueysuez B., Murday V.A., Patton M.A., Wilkie A.O.M.,
RA   Jeffery S.;
RT   "Recessive Robinow syndrome, allelic to dominant brachydactyly type B, is
RT   caused by mutation of ROR2.";
RL   Nat. Genet. 25:419-422(2000).
RN   [12]
RP   VARIANT RRS1 TYR-182.
RX   PubMed=10932187; DOI=10.1038/78113;
RA   van Bokhoven H., Celli J., Kayserili H., van Beusekom E., Balci S.,
RA   Brussel W., Skovby F., Kerr B., Percin E.F., Akarsu N., Brunner H.G.;
RT   "Mutation of the gene encoding the ROR2 tyrosine kinase causes autosomal
RT   recessive Robinow syndrome.";
RL   Nat. Genet. 25:423-426(2000).
RN   [13]
RP   ERRATUM OF PUBMED:10932187.
RX   PubMed=11062486; DOI=10.1038/81722;
RA   van Bokhoven H., Celli J., Kayserili H., van Beusekom E., Balci S.,
RA   Brussel W., Skovby F., Kerr B., Percin E.F., Akarsu N., Brunner H.G.;
RL   Nat. Genet. 26:383-383(2000).
RN   [14]
RP   VARIANTS [LARGE SCALE ANALYSIS] GLN-244; ALA-245; ASP-349; ALA-490;
RP   GLN-530; MET-542; SER-548; LEU-557; ASN-644; ASN-672; ARG-695; CYS-738;
RP   LEU-762; ILE-819 AND GLU-935.
RX   PubMed=17344846; DOI=10.1038/nature05610;
RA   Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA   Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA   Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA   Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA   Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA   Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA   Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA   Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA   Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA   Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA   Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA   Futreal P.A., Stratton M.R.;
RT   "Patterns of somatic mutation in human cancer genomes.";
RL   Nature 446:153-158(2007).
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 (By similarity). Phosphorylates
CC       YWHAB, leading to induction of osteogenesis and bone formation
CC       (PubMed:17717073). 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       (PubMed:25029443). {ECO:0000250|UniProtKB:Q9Z138,
CC       ECO:0000269|PubMed:17717073, ECO:0000269|PubMed:25029443}.
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:PRU10028,
CC         ECO:0000269|PubMed:17717073};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000269|PubMed:17717073};
CC   -!- SUBUNIT: Homodimer; promotes osteogenesis. Binds YWHAB
CC       (PubMed:17717073). Interacts with WTIP (By similarity). Interacts with
CC       ROR2 (PubMed:26035863). {ECO:0000250|UniProtKB:Q9Z138,
CC       ECO:0000269|PubMed:17717073, ECO:0000269|PubMed:26035863}.
CC   -!- INTERACTION:
CC       Q01974; Q5BKX5-3: ACTMAP; NbExp=3; IntAct=EBI-6422642, EBI-11976299;
CC       Q01974; Q9NP73-4: ALG13; NbExp=3; IntAct=EBI-6422642, EBI-10186621;
CC       Q01974; Q03989: ARID5A; NbExp=3; IntAct=EBI-6422642, EBI-948603;
CC       Q01974; O14503: BHLHE40; NbExp=3; IntAct=EBI-6422642, EBI-711810;
CC       Q01974; Q5SWW7: C10orf55; NbExp=3; IntAct=EBI-6422642, EBI-12809220;
CC       Q01974; Q6P1W5: C1orf94; NbExp=3; IntAct=EBI-6422642, EBI-946029;
CC       Q01974; Q03060-25: CREM; NbExp=3; IntAct=EBI-6422642, EBI-12884642;
CC       Q01974; O43186: CRX; NbExp=4; IntAct=EBI-6422642, EBI-748171;
CC       Q01974; Q15038: DAZAP2; NbExp=8; IntAct=EBI-6422642, EBI-724310;
CC       Q01974; A1KXE4-2: FAM168B; NbExp=3; IntAct=EBI-6422642, EBI-12193763;
CC       Q01974; P53539: FOSB; NbExp=3; IntAct=EBI-6422642, EBI-2806743;
CC       Q01974; P08238: HSP90AB1; NbExp=2; IntAct=EBI-6422642, EBI-352572;
CC       Q01974; Q2M1V0: ISX; NbExp=3; IntAct=EBI-6422642, EBI-6426064;
CC       Q01974; A4D0Q3: KIAA1218; NbExp=3; IntAct=EBI-6422642, EBI-14308786;
CC       Q01974; Q3SYF9: KRTAP19-7; NbExp=3; IntAct=EBI-6422642, EBI-10241353;
CC       Q01974; Q3LI66: KRTAP6-2; NbExp=3; IntAct=EBI-6422642, EBI-11962084;
CC       Q01974; Q8IUC3: KRTAP7-1; NbExp=3; IntAct=EBI-6422642, EBI-18394498;
CC       Q01974; Q9UPM6: LHX6; NbExp=3; IntAct=EBI-6422642, EBI-10258746;
CC       Q01974; P35548: MSX2; NbExp=3; IntAct=EBI-6422642, EBI-6447480;
CC       Q01974; P78337: PITX1; NbExp=3; IntAct=EBI-6422642, EBI-748265;
CC       Q01974; O15496: PLA2G10; NbExp=3; IntAct=EBI-6422642, EBI-726466;
CC       Q01974; Q16633: POU2AF1; NbExp=3; IntAct=EBI-6422642, EBI-943588;
CC       Q01974; O43741: PRKAB2; NbExp=3; IntAct=EBI-6422642, EBI-1053424;
CC       Q01974; P86480: PRR20D; NbExp=3; IntAct=EBI-6422642, EBI-12754095;
CC       Q01974; Q8N813: PRR23E; NbExp=3; IntAct=EBI-6422642, EBI-18115268;
CC       Q01974; O95416: SOX14; NbExp=5; IntAct=EBI-6422642, EBI-9087806;
CC       Q01974; Q6ZVD7: STOX1; NbExp=3; IntAct=EBI-6422642, EBI-3923644;
CC       Q01974; O43711: TLX3; NbExp=3; IntAct=EBI-6422642, EBI-3939165;
CC       Q01974; O95231: VENTX; NbExp=3; IntAct=EBI-6422642, EBI-10191303;
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Single-pass type I
CC       membrane protein {ECO:0000250}.
CC   -!- DEVELOPMENTAL STAGE: Expressed at high levels during early embryonic
CC       development. The expression levels drop strongly around day 16 and
CC       there are only very low levels in adult tissues.
CC   -!- DISEASE: Brachydactyly B1 (BDB1) [MIM:113000]: A form of brachydactyly.
CC       Brachydactyly defines a group of inherited malformations characterized
CC       by shortening of the digits due to abnormal development of the
CC       phalanges and/or the metacarpals. In brachydactyly type B1 the middle
CC       phalanges are short but in addition the terminal phalanges are
CC       rudimentary or absent. Both fingers and toes are affected. The thumbs
CC       and big toes are usually deformed. Symphalangism is also a feature.
CC       Note=The disease is caused by variants affecting the gene represented
CC       in this entry.
CC   -!- DISEASE: Robinow syndrome, autosomal recessive 1 (RRS1) [MIM:268310]: A
CC       recessive form of Robinow syndrome, a disease characterized by short-
CC       limb dwarfism, costovertebral segmentation defects and abnormalities of
CC       the head, face and external genitalia. The clinical signs are generally
CC       far more severe in recessive cases, particularly skeletal
CC       abnormalities. All patients with the recessive form suffer from
CC       vertebral segmentation abnormalities, resulting in scoliosis and chest
CC       deformities. Rib fusions are considered to be characteristic of the
CC       autosomal recessive form. Patients can also present brachydactyly, with
CC       extensive aplasia/hypoplasia of the phalanges and
CC       metacarpals/metatarsals, and brachy-syn-polydactyly of the hands and
CC       oligodactyly of the feet. {ECO:0000269|PubMed:10932186,
CC       ECO:0000269|PubMed:10932187}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC       kinase family. ROR subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}.
CC   -!- CAUTION: The catalytic activity of the kinase domain is controversial.
CC       {ECO:0000269|PubMed:17717073, ECO:0000269|PubMed:25029443}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAD92391.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC   -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC       Haematology;
CC       URL="https://atlasgeneticsoncology.org/gene/43476/ROR2";
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DR   EMBL; M97639; AAA60276.1; -; mRNA.
DR   EMBL; AL391219; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL928802; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL583841; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AB209154; BAD92391.1; ALT_INIT; mRNA.
DR   EMBL; AH009681; AAG01184.2; -; Genomic_DNA.
DR   EMBL; AH010002; AAG33132.1; -; Genomic_DNA.
DR   CCDS; CCDS6691.1; -.
DR   PIR; B45082; B45082.
DR   RefSeq; NP_001305133.1; NM_001318204.1.
DR   RefSeq; NP_004551.2; NM_004560.3.
DR   PDB; 3ZZW; X-ray; 2.90 A; A/B=464-751.
DR   PDB; 4GT4; X-ray; 2.41 A; A/B=452-753.
DR   PDB; 6OSH; X-ray; 1.12 A; K=314-394.
DR   PDB; 6OSN; X-ray; 1.08 A; A=314-394.
DR   PDB; 6OSV; X-ray; 1.34 A; K=314-394.
DR   PDBsum; 3ZZW; -.
DR   PDBsum; 4GT4; -.
DR   PDBsum; 6OSH; -.
DR   PDBsum; 6OSN; -.
DR   PDBsum; 6OSV; -.
DR   AlphaFoldDB; Q01974; -.
DR   SMR; Q01974; -.
DR   BioGRID; 110974; 382.
DR   IntAct; Q01974; 209.
DR   MINT; Q01974; -.
DR   STRING; 9606.ENSP00000364860; -.
DR   ChEMBL; CHEMBL2375201; -.
DR   GlyCosmos; Q01974; 4 sites, 1 glycan.
DR   GlyGen; Q01974; 5 sites, 3 O-linked glycans (2 sites).
DR   iPTMnet; Q01974; -.
DR   PhosphoSitePlus; Q01974; -.
DR   BioMuta; ROR2; -.
DR   DMDM; 90110767; -.
DR   CPTAC; CPTAC-2781; -.
DR   EPD; Q01974; -.
DR   jPOST; Q01974; -.
DR   MassIVE; Q01974; -.
DR   MaxQB; Q01974; -.
DR   PaxDb; 9606-ENSP00000364860; -.
DR   PeptideAtlas; Q01974; -.
DR   ProteomicsDB; 58028; -.
DR   Pumba; Q01974; -.
DR   ABCD; Q01974; 6 sequenced antibodies.
DR   Antibodypedia; 13579; 815 antibodies from 40 providers.
DR   DNASU; 4920; -.
DR   Ensembl; ENST00000375708.4; ENSP00000364860.3; ENSG00000169071.15.
DR   GeneID; 4920; -.
DR   KEGG; hsa:4920; -.
DR   MANE-Select; ENST00000375708.4; ENSP00000364860.3; NM_004560.4; NP_004551.2.
DR   UCSC; uc004arj.3; human.
DR   AGR; HGNC:10257; -.
DR   CTD; 4920; -.
DR   DisGeNET; 4920; -.
DR   GeneCards; ROR2; -.
DR   GeneReviews; ROR2; -.
DR   HGNC; HGNC:10257; ROR2.
DR   HPA; ENSG00000169071; Low tissue specificity.
DR   MalaCards; ROR2; -.
DR   MIM; 113000; phenotype.
DR   MIM; 268310; phenotype.
DR   MIM; 602337; gene.
DR   neXtProt; NX_Q01974; -.
DR   OpenTargets; ENSG00000169071; -.
DR   Orphanet; 1507; Autosomal recessive Robinow syndrome.
DR   Orphanet; 572385; Brachydactyly type B1.
DR   PharmGKB; PA34629; -.
DR   VEuPathDB; HostDB:ENSG00000169071; -.
DR   eggNOG; KOG1026; Eukaryota.
DR   GeneTree; ENSGT00940000153947; -.
DR   HOGENOM; CLU_000288_30_4_1; -.
DR   InParanoid; Q01974; -.
DR   OMA; QYLASHH; -.
DR   OrthoDB; 1614410at2759; -.
DR   PhylomeDB; Q01974; -.
DR   TreeFam; TF106465; -.
DR   BRENDA; 2.7.10.1; 2681.
DR   PathwayCommons; Q01974; -.
DR   Reactome; R-HSA-4086400; PCP/CE pathway.
DR   Reactome; R-HSA-5140745; WNT5A-dependent internalization of FZD2, FZD5 and ROR2.
DR   SignaLink; Q01974; -.
DR   SIGNOR; Q01974; -.
DR   BioGRID-ORCS; 4920; 9 hits in 1192 CRISPR screens.
DR   ChiTaRS; ROR2; human.
DR   GeneWiki; ROR2; -.
DR   GenomeRNAi; 4920; -.
DR   Pharos; Q01974; Tbio.
DR   PRO; PR:Q01974; -.
DR   Proteomes; UP000005640; Chromosome 9.
DR   RNAct; Q01974; Protein.
DR   Bgee; ENSG00000169071; Expressed in muscle layer of sigmoid colon and 125 other cell types or tissues.
DR   ExpressionAtlas; Q01974; baseline and differential.
DR   GO; GO:0009986; C:cell surface; IEA:Ensembl.
DR   GO; GO:0030669; C:clathrin-coated endocytic vesicle membrane; TAS:Reactome.
DR   GO; GO:0030425; C:dendrite; IEA:Ensembl.
DR   GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR   GO; GO:0005874; C:microtubule; IEA:Ensembl.
DR   GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR   GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR   GO; GO:0098794; C:postsynapse; IEA:Ensembl.
DR   GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0015026; F:coreceptor activity; TAS:ParkinsonsUK-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:UniProtKB.
DR   GO; GO:0014002; P:astrocyte development; IEA:Ensembl.
DR   GO; GO:0030282; P:bone mineralization; IEA:Ensembl.
DR   GO; GO:1905517; P:macrophage migration; IEA:Ensembl.
DR   GO; GO:0030539; P:male genitalia development; IEA:Ensembl.
DR   GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR   GO; GO:0030335; P:positive regulation of cell migration; IDA:UniProtKB.
DR   GO; GO:0045651; P:positive regulation of macrophage differentiation; IEA:Ensembl.
DR   GO; GO:0010976; P:positive regulation of neuron projection development; IBA:GO_Central.
DR   GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IBA:GO_Central.
DR   GO; GO:0051968; P:positive regulation of synaptic transmission, glutamatergic; IEA:Ensembl.
DR   GO; GO:0099175; P:regulation of postsynapse organization; IEA:Ensembl.
DR   GO; GO:0150045; P:regulation of synaptic signaling by nitric oxide; IEA:Ensembl.
DR   GO; GO:0007165; P:signal transduction; IMP:UniProtKB.
DR   GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR   GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR   CDD; cd07468; CRD_TK_ROR2; 1.
DR   CDD; cd00108; KR; 1.
DR   CDD; cd05091; PTKc_Ror2; 1.
DR   Gene3D; 1.10.2000.10; Frizzled cysteine-rich domain; 1.
DR   Gene3D; 2.60.40.10; Immunoglobulins; 1.
DR   Gene3D; 2.40.20.10; Plasminogen Kringle 4; 1.
DR   Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
DR   IDEAL; IID00560; -.
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   PANTHER; PTHR24416; TYROSINE-PROTEIN KINASE RECEPTOR; 1.
DR   PANTHER; PTHR24416:SF132; TYROSINE-PROTEIN KINASE TRANSMEMBRANE RECEPTOR ROR2; 1.
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; PR00018; KRINGLE.
DR   PRINTS; PR00109; TYRKINASE.
DR   SMART; SM00409; IG; 1.
DR   SMART; SM00408; IGc2; 1.
DR   SMART; SM00130; KR; 1.
DR   SUPFAM; SSF48726; Immunoglobulin; 1.
DR   SUPFAM; SSF57440; Kringle-like; 1.
DR   SUPFAM; SSF56112; Protein kinase-like (PK-like); 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.
DR   Genevisible; Q01974; HS.
PE   1: Evidence at protein level;
KW   3D-structure; ATP-binding; Cell membrane; Developmental protein;
KW   Direct protein sequencing; Disease variant; Disulfide bond; Dwarfism;
KW   Glycoprotein; Immunoglobulin domain; Kinase; Kringle; Magnesium; Membrane;
KW   Metal-binding; Methylation; Nucleotide-binding; Phosphoprotein; Receptor;
KW   Reference proteome; Signal; Sulfation; Transferase; Transmembrane;
KW   Transmembrane helix; Tyrosine-protein kinase; Wnt signaling pathway.
FT   SIGNAL          1..33
FT                   /evidence="ECO:0000255"
FT   CHAIN           34..943
FT                   /note="Tyrosine-protein kinase transmembrane receptor ROR2"
FT                   /id="PRO_0000024460"
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..943
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..796
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          850..931
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        757..786
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        856..886
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         469
FT                   /note="Sulfoserine; partial"
FT                   /evidence="ECO:0000269|PubMed:14752058"
FT   MOD_RES         471
FT                   /note="Sulfoserine; partial"
FT                   /evidence="ECO:0000269|PubMed:14752058"
FT   MOD_RES         646
FT                   /note="Phosphotyrosine; by autocatalysis"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         785
FT                   /note="Asymmetric dimethylarginine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Z138"
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   VARIANT         182
FT                   /note="C -> Y (in RRS1)"
FT                   /evidence="ECO:0000269|PubMed:10932187"
FT                   /id="VAR_010911"
FT   VARIANT         184
FT                   /note="R -> C (in RRS1; dbSNP:rs121909084)"
FT                   /evidence="ECO:0000269|PubMed:10932186"
FT                   /id="VAR_010768"
FT   VARIANT         189
FT                   /note="R -> W (in RRS1; dbSNP:rs199975149)"
FT                   /evidence="ECO:0000269|PubMed:10932186"
FT                   /id="VAR_010769"
FT   VARIANT         244
FT                   /note="R -> Q (in dbSNP:rs55737262)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041787"
FT   VARIANT         245
FT                   /note="T -> A (in dbSNP:rs10820900)"
FT                   /evidence="ECO:0000269|PubMed:10700182,
FT                   ECO:0000269|PubMed:10986040, ECO:0000269|PubMed:1334494,
FT                   ECO:0000269|PubMed:17344846, ECO:0000269|Ref.3"
FT                   /id="VAR_010912"
FT   VARIANT         349
FT                   /note="H -> D (in dbSNP:rs55983376)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041788"
FT   VARIANT         366
FT                   /note="R -> W (in RRS1)"
FT                   /evidence="ECO:0000269|PubMed:10932186"
FT                   /id="VAR_010770"
FT   VARIANT         490
FT                   /note="G -> A (in dbSNP:rs56197744)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041789"
FT   VARIANT         530
FT                   /note="R -> Q (in dbSNP:rs35852786)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041790"
FT   VARIANT         542
FT                   /note="V -> M (in a colorectal adenocarcinoma sample;
FT                   somatic mutation; dbSNP:rs140213020)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041791"
FT   VARIANT         548
FT                   /note="P -> S (in dbSNP:rs35764413)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041792"
FT   VARIANT         557
FT                   /note="S -> L (in dbSNP:rs56099091)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041793"
FT   VARIANT         620
FT                   /note="N -> K (in RRS1)"
FT                   /evidence="ECO:0000269|PubMed:10932186"
FT                   /id="VAR_010771"
FT   VARIANT         644
FT                   /note="D -> N (in dbSNP:rs55798732)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041794"
FT   VARIANT         672
FT                   /note="D -> N (in dbSNP:rs55651110)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041795"
FT   VARIANT         695
FT                   /note="G -> R (in dbSNP:rs34431454)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041796"
FT   VARIANT         738
FT                   /note="R -> C (in dbSNP:rs56231927)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041797"
FT   VARIANT         762
FT                   /note="S -> L (in dbSNP:rs34491822)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041798"
FT   VARIANT         819
FT                   /note="V -> I (in dbSNP:rs10761129)"
FT                   /evidence="ECO:0000269|PubMed:10700182,
FT                   ECO:0000269|PubMed:17344846, ECO:0000269|Ref.3"
FT                   /id="VAR_010913"
FT   VARIANT         935
FT                   /note="D -> E (in dbSNP:rs41277835)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041799"
FT   MUTAGEN         482
FT                   /note="D->G: Slight increase in kinase activity."
FT                   /evidence="ECO:0000269|PubMed:25029443"
FT   STRAND          344..346
FT                   /evidence="ECO:0007829|PDB:6OSN"
FT   TURN            352..354
FT                   /evidence="ECO:0007829|PDB:6OSN"
FT   HELIX           356..358
FT                   /evidence="ECO:0007829|PDB:6OSN"
FT   HELIX           368..370
FT                   /evidence="ECO:0007829|PDB:6OSN"
FT   STRAND          372..381
FT                   /evidence="ECO:0007829|PDB:6OSN"
FT   STRAND          385..389
FT                   /evidence="ECO:0007829|PDB:6OSN"
FT   HELIX           470..472
FT                   /evidence="ECO:0007829|PDB:4GT4"
FT   STRAND          473..481
FT                   /evidence="ECO:0007829|PDB:4GT4"
FT   STRAND          486..492
FT                   /evidence="ECO:0007829|PDB:4GT4"
FT   STRAND          502..508
FT                   /evidence="ECO:0007829|PDB:4GT4"
FT   HELIX           518..530
FT                   /evidence="ECO:0007829|PDB:4GT4"
FT   STRAND          539..543
FT                   /evidence="ECO:0007829|PDB:4GT4"
FT   STRAND          545..548
FT                   /evidence="ECO:0007829|PDB:4GT4"
FT   STRAND          550..554
FT                   /evidence="ECO:0007829|PDB:4GT4"
FT   HELIX           561..566
FT                   /evidence="ECO:0007829|PDB:4GT4"
FT   HELIX           589..608
FT                   /evidence="ECO:0007829|PDB:4GT4"
FT   HELIX           618..620
FT                   /evidence="ECO:0007829|PDB:4GT4"
FT   STRAND          621..623
FT                   /evidence="ECO:0007829|PDB:4GT4"
FT   HELIX           625..627
FT                   /evidence="ECO:0007829|PDB:4GT4"
FT   STRAND          629..631
FT                   /evidence="ECO:0007829|PDB:4GT4"
FT   HELIX           639..644
FT                   /evidence="ECO:0007829|PDB:4GT4"
FT   STRAND          648..652
FT                   /evidence="ECO:0007829|PDB:4GT4"
FT   HELIX           656..658
FT                   /evidence="ECO:0007829|PDB:4GT4"
FT   HELIX           661..666
FT                   /evidence="ECO:0007829|PDB:4GT4"
FT   HELIX           671..686
FT                   /evidence="ECO:0007829|PDB:4GT4"
FT   TURN            687..689
FT                   /evidence="ECO:0007829|PDB:4GT4"
FT   TURN            692..695
FT                   /evidence="ECO:0007829|PDB:4GT4"
FT   HELIX           698..706
FT                   /evidence="ECO:0007829|PDB:4GT4"
FT   HELIX           719..728
FT                   /evidence="ECO:0007829|PDB:4GT4"
FT   HELIX           733..735
FT                   /evidence="ECO:0007829|PDB:4GT4"
FT   HELIX           739..747
FT                   /evidence="ECO:0007829|PDB:4GT4"
SQ   SEQUENCE   943 AA;  104757 MW;  F926FB681A8312FE CRC64;
     MARGSALPRR PLLCIPAVWA AAALLLSVSR TSGEVEVLDP NDPLGPLDGQ DGPIPTLKGY
     FLNFLEPVNN ITIVQGQTAI LHCKVAGNPP PNVRWLKNDA PVVQEPRRII IRKTEYGSRL
     RIQDLDTTDT GYYQCVATNG MKTITATGVL FVRLGPTHSP NHNFQDDYHE DGFCQPYRGI
     ACARFIGNRT IYVDSLQMQG EIENRITAAF TMIGTSTHLS DQCSQFAIPS FCHFVFPLCD
     ARSRTPKPRE LCRDECEVLE SDLCRQEYTI ARSNPLILMR LQLPKCEALP MPESPDAANC
     MRIGIPAERL GRYHQCYNGS GMDYRGTAST TKSGHQCQPW ALQHPHSHHL SSTDFPELGG
     GHAYCRNPGG QMEGPWCFTQ NKNVRMELCD VPSCSPRDSS KMGILYILVP SIAIPLVIAC
     LFFLVCMCRN KQKASASTPQ RRQLMASPSQ DMEMPLINQH KQAKLKEISL SAVRFMEELG
     EDRFGKVYKG HLFGPAPGEQ TQAVAIKTLK DKAEGPLREE FRHEAMLRAR LQHPNVVCLL
     GVVTKDQPLS MIFSYCSHGD LHEFLVMRSP HSDVGSTDDD RTVKSALEPP DFVHLVAQIA
     AGMEYLSSHH VVHKDLATRN VLVYDKLNVK ISDLGLFREV YAADYYKLLG NSLLPIRWMA
     PEAIMYGKFS IDSDIWSYGV VLWEVFSYGL QPYCGYSNQD VVEMIRNRQV LPCPDDCPAW
     VYALMIECWN EFPSRRPRFK DIHSRLRAWG NLSNYNSSAQ TSGASNTTQT SSLSTSPVSN
     VSNARYVGPK QKAPPFPQPQ FIPMKGQIRP MVPPPQLYVP VNGYQPVPAY GAYLPNFYPV
     QIPMQMAPQQ VPPQMVPKPS SHHSGSGSTS TGYVTTAPSN TSMADRAALL SEGADDTQNA
     PEDGAQSTVQ EAEEEEEGSV PETELLGDCD TLQVDEAQVQ LEA
//