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FLASH GENE
Symbol ROR2 contributors: shn/ - updated : 24-06-2018
HGNC name receptor tyrosine kinase-like orphan receptor 2
HGNC id 10257
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • an extracellular immunoglobulin-like domain
  • one frizzled-like cysteine rich domain (CRD)
  • a kringle domain
  • a transmembrane and intracellular tyrosine kinase
  • a serine/threonine-rich and proline-rich domains
    • conjugated GlycoP
    HOMOLOGY
    interspecies ortholog to Ror2, Mus musculus
    ortholog to ror2, Danio rerio
    ortholog to Ror2, Rattus norvegicus
    ortholog to ROR2, Pan troglodytes
    Homologene
    FAMILY
  • protein kinase superfamily
  • Ror-family receptor tyrosine kinases
  • ROR subfamily
    • CATEGORY enzyme , receptor
    SUBCELLULAR LOCALIZATION     plasma membrane
    basic FUNCTION
  • encodes a receptor-like tyrosine kinase that is particularly important for the chondrocyte lineage
  • may be involved in the early formation of the chondrocytes and may be required for cartilage and growth plate development
  • Ror2 plays essential roles in the development of the heart and in limb/tail formation, in cardiac septal formation and ossification of distal portions of limbs and tails
  • Ror1 and Ror2 are functionally redundant and that they interact genetically in skeletal and cardiac development
  • Ror2 is involved in genital development
  • Ror2 has a role in cartilage formation, chondrocyte differentiation and joint formation
  • play crucial roles in the development of various organs and tissues
  • ROR1, and ROR2, play a key role in WNT-5A-activated signaling pathways leading to synapse formation in the mammalian CNS
  • regulates WNT5A-induced polymerization of Dishevelled (Dvl) and ROR2-mediated regulation of Dvl is independent of the cytoplasmic region of ROR2
  • WNT5A and ROR2 signaling are of substantial importance for BMP2-mediated osteoblastic differentiation
  • ANPEP and ROR2 are cell-surface markers capable of selecting early cardiac mesoderm emerging during embryonic stem cells (hESCs) differentiation
  • signaling through the ROR2 receptor tyrosine kinase promotes invadopodia formation for tumor invasion
  • may act as a tumor suppressor in endometrioid endometrial cancer, similar to its role in colorectal cancer
  • ROR1/ROR2 are essential for the progression of myofibroblast differentiation and for the adaptive remodeling of the heart in response to pressure overload
    • CELLULAR PROCESS cell life, differentiation
    cell life, proliferation/growth
    PHYSIOLOGICAL PROCESS cardiovascular , ossification
    PATHWAY
    metabolism
    signaling
  • WNT5A/ROR2 signaling appears to be involved in BMP2-mediated osteoblast differentiation in a Smad independent pathway
    • a component ROR2/FZD7 receptor complex plays an important role in WNT5a/RAC1/AP-1 pathway by regulating polymerization of DVL2
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • bone morphogenetic protein receptor type Ib (BRIb) with the extracellular CRD domain of ROR2
  • modulates the canonical Wnt signaling in lung epithelial cells through cooperation with FZD2
  • act as a receptor or coreceptor for WNT5A to mediate noncanonical Wnt signaling
  • intracellular interaction partner of WTIP
  • can associate with FZD7 via its extracellular cysteine-rich domain to form a receptor complex that is required for the regulation of Dvl and activation of the AP-1 promoter after WNT5A stimulation
  • binds to WNT5A directly through its Fz-like CRD and may serve as a co-receptor in WNT5A-induced signaling
  • WNT5A-ROR2 signaling might be required for expression of MMP13 gene during the development of the cartilaginous tissue
  • acts autonomously to permit the polarized response of primordial germ cells (PGCs) to KITLG
  • WNT5A potentiates PGC chemotaxis toward secreted KITLG by redistribution of ROR2 within the cell
  • WNT5A activates noncanonical WNT signaling through ROR2
  • TWIST1-binding sequences associated with CHST11, LITAF, ROR2, and SPATA5 also bound the potential TWIST1 cofactor RREB1
  • stimulated by the hyperphosphorylation of DVL3 by CNSK1E, ROR2 has been shown to interact with DVL3
  • ROR2 signaling is required for local upregulation of GFD6 and activation of BMP signaling at the neural plate border
  • IFT20 mediates the ability of ROR2 signaling to induce the invasiveness of the tumors that lack primary cilia
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) BDB1 , DEL9Q22 , RBNS
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    hypoxia-inducible factor target in von hippel-Lindau-associated RCC
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    WNT5a-ROR2 signaling can be a target of cancer therapies to prevent cancer cells from undergoing invasion and metastasis
    cancerbrainglioma/neuroblstoma
    ROR1 and ROR2 could serve as novel targets for immunotherapy in neuroblastoma
    cancerreproductiveovary
    targeting both ROR1 and ROR2 may be a powerful approach to treating ovarian cancer
    ANIMAL & CELL MODELS
  • Disruption of mouse Ror2 leads to profound skeletal abnormalities with essentially all endochondrally derived bones foreshortened or misshapen
  • Ror2-deficient mice had cardiac septal defects and skeletal abnormalities, including shorter limbs, vertebrae, and facial structure, with a particular defect in their distal portions and died after birth
  • Ror1/Ror2 double-mutant mice showed skeletal abnormalities including a sternal defect and dysplasia of the symphysis of the pubic bone