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tyrosine-protein kinase transmembrane receptor ROR1; neurotrophic tyrosine kinase, receptor-related 1 (ROR1, NTRKR1)
Function:
- tyrosine-protein kinase receptor
- orphan receptor
- function not well understood
Structure:
- belongs to the protein kinase superfamily, Tyr protein kinase family, ROR subfamily
- contains 1 FZ (frizzled) domain
- contains 1 Ig-like C2-type domain (immunoglobulin-like)
- contains 1 kringle domain
- contains 1 protein kinase domain
Compartment: membrane
Alternative splicing: named isoforms=2
Expression:
- expressed strongly in human heart, lung, & kidney, but weakly in the CNS
- expressed at high levels during early embryonic development
- expression levels drop strongly around day 16 & there are only very low levels in adult tissues
- short isoform is strongly expressed in fetal & adult CNS & in a variety of human cancers, including those originating from CNS or PNS neuroectoderm
Pathology:
- upregulated with metastases [2]
- lung adenocarcinoma
- breast cancer
- chronic lymphocytic leukemia (CLL)
- melanoma
General
glycoprotein
tyrosine kinase receptor (RTK)
Properties
SIZE: entity length = 937 aa
MW = 104 kD
COMPARTMENT: cellular membrane
STATE: active state
MOTIF: signal sequence {1-29}
immunoglobulin superfamily domain {42-147}
MOTIF: N-glycosylation site {N47}
N-glycosylation site {N66}
cysteine residue {C79}
MODIFICATION: cysteine residue {C131}
cysteine residue {C131}
MODIFICATION: cysteine residue {C79}
frizzled domain {165-299}
MOTIF: cysteine residue {C170}
MODIFICATION: cysteine residue {C235}
cysteine residue {C178}
MODIFICATION: cysteine residue {C228}
N-glycosylation site {N184}
cysteine residue {C219}
MODIFICATION: cysteine residue {C260}
cysteine residue {C228}
MODIFICATION: cysteine residue {C178}
cysteine residue {C235}
MODIFICATION: cysteine residue {C170}
cysteine residue {C248}
MODIFICATION: cysteine residue {C296}
cysteine residue {C252}
MODIFICATION: cysteine residue {C282}
cysteine residue {C260}
MODIFICATION: cysteine residue {C219}
cysteine residue {C282}
MODIFICATION: cysteine residue {C252}
cysteine residue {C296}
MODIFICATION: cysteine residue {C248}
Kringle {312-391}
MOTIF: cysteine residue {C313}
MODIFICATION: cysteine residue {C391}
N-glycosylation site {N315}
cysteine residue {C334}
MODIFICATION: cysteine residue {C374}
cysteine residue {C362}
MODIFICATION: cysteine residue {C386}
cysteine residue {C374}
MODIFICATION: cysteine residue {C334}
cysteine residue {C386}
MODIFICATION: cysteine residue {C362}
cysteine residue {C391}
MODIFICATION: cysteine residue {C313}
transmembrane domain {407-427}
kinase domain
SITE: 473-746
MOTIF: ATP-binding site
NAME: ATP-binding site
SITE: 479-487
ATP-binding site
NAME: ATP-binding site
SITE: 506-506
aspartate residue {D615}
Tyr phosphorylation site {Y645}
threonine-rich region {753-782}
MOTIF: threonine residue (SEVERAL)
proline-rich region
SITE: 784-851
MOTIF: proline residue (SEVERAL)
threonine-rich region {853-876}
MOTIF: threonine residue (SEVERAL)
Database Correlations
OMIM 602336
UniProt Q01973
PFAM correlations
ENZYME 2.7.10.1
References
- UniProt :accession Q01973
- Cui B, Zhang S, Chen L et al
Targeting ROR1 Inhibits Epithelial-Mesenchymal Transition and
Metastasis.
Cancer Res. 2013 Jun 15;73(12):3649-60
PMID: 23771907
- Hojjat-Farsangi M, Ghaemimanesh F, Daneshmanesh AH et al
Inhibition of the receptor tyrosine kinase ROR1 by anti-ROR1
monoclonal antibodies and siRNA induced apoptosis of melanoma
cells.
PLoS One. 2013 Apr 8;8(4):e61167
PMID: 23593420
- Rebagay G, Yan S, Liu C, Cheung NK.
ROR1 and ROR2 in human malignancies: potentials for targeted
therapy.
Front Oncol. 2012;2:34.
PMID: 22655270
- Zhang S, Chen L, Cui B, Chuang HY et al
ROR1 is expressed in human breast cancer and associated with
enhanced tumor-cell growth.
PLoS One. 2012;7(3):e31127
PMID: 22403610