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Protein

Inactive tyrosine-protein kinase transmembrane receptor ROR1

Gene

ROR1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Has very low kinase activity in vitro and is unlikely to function as a tyrosine kinase in vivo (PubMed:25029443). Receptor for ligand WNT5A which activate downstream NFkB signaling pathway and may result in the inhibition of WNT3A-mediated signaling (PubMed:25029443, PubMed:27162350). In inner ear, crucial for spiral ganglion neurons to innervate auditory hair cells (PubMed:27162350).2 Publications

Caution

The kinase domain has very low catalytic activity in vitro.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei506ATPPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi479 – 487ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • coreceptor activity involved in Wnt signaling pathway, planar cell polarity pathway Source: ParkinsonsUK-UCL
  • transmembrane receptor protein tyrosine kinase activity Source: ProtInc
  • Wnt-activated receptor activity Source: UniProtKB
  • Wnt-protein binding Source: UniProtKB

GO - Biological processi

  • astrocyte development Source: Ensembl
  • inner ear development Source: UniProtKB
  • positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  • positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
  • sensory perception of sound Source: UniProtKB
  • transmembrane receptor protein tyrosine kinase signaling pathway Source: ProtInc

Keywordsi

Molecular functionKinase, Receptor, Transferase
Biological processWnt signaling pathway
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.1 2681
ReactomeiR-HSA-5140745 WNT5A-dependent internalization of FZD2, FZD5 and ROR2
SignaLinkiQ01973
SIGNORiQ01973

Names & Taxonomyi

Protein namesi
Recommended name:
Inactive tyrosine-protein kinase transmembrane receptor ROR1Curated
Alternative name(s):
Neurotrophic tyrosine kinase, receptor-related 1
Gene namesi
Name:ROR1
Synonyms:NTRKR1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000185483.11
HGNCiHGNC:10256 ROR1
MIMi602336 gene
neXtProtiNX_Q01973

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini30 – 406ExtracellularSequence analysisAdd BLAST377
Transmembranei407 – 427HelicalSequence analysisAdd BLAST21
Topological domaini428 – 937CytoplasmicSequence analysisAdd BLAST510

Keywords - Cellular componenti

Cell projection, Membrane

Pathology & Biotechi

Involvement in diseasei

Deafness, autosomal recessive, 108 (DFNB108)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
See also OMIM:617654
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_079530736R → T in DFNB108; impairs plasma membrane location; abolishes downstream NFkB activation. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi482C → G: No effect on kinase activity. 1 Publication1

Keywords - Diseasei

Deafness, Disease mutation, Non-syndromic deafness

Organism-specific databases

DisGeNETi4919
MalaCardsiROR1
MIMi617654 phenotype
OpenTargetsiENSG00000185483
PharmGKBiPA34628

Polymorphism and mutation databases

BioMutaiROR1
DMDMi118572711

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 29Sequence analysisAdd BLAST29
ChainiPRO_000002445830 – 937Inactive tyrosine-protein kinase transmembrane receptor ROR1Add BLAST908

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi47N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi66N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi79 ↔ 131By similarity
Disulfide bondi170 ↔ 235By similarity
Disulfide bondi178 ↔ 228By similarity
Glycosylationi184N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi219 ↔ 260By similarity
Disulfide bondi248 ↔ 296By similarity
Disulfide bondi252 ↔ 282By similarity
Disulfide bondi313 ↔ 391By similarity
Glycosylationi315N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi334 ↔ 374By similarity
Disulfide bondi362 ↔ 386By similarity
Modified residuei645Phosphotyrosine; by autocatalysisBy similarity1

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiQ01973
MaxQBiQ01973
PaxDbiQ01973
PeptideAtlasiQ01973
PRIDEiQ01973
ProteomicsDBi58025
58026 [Q01973-2]
58027 [Q01973-3]

PTM databases

iPTMnetiQ01973
PhosphoSitePlusiQ01973
SwissPalmiQ01973

Expressioni

Tissue specificityi

Expressed strongly in human heart, lung and kidney, but weakly in the CNS. Isoform Short is strongly expressed in fetal and adult CNS and in a variety of human cancers, including those originating from CNS or PNS neuroectoderm.

Developmental stagei

Expressed at high levels during early embryonic development. The expression levels drop strongly around day 16 and there are only very low levels in adult tissues.

Gene expression databases

BgeeiENSG00000185483
CleanExiHS_ROR1
ExpressionAtlasiQ01973 baseline and differential
GenevisibleiQ01973 HS

Organism-specific databases

HPAiHPA057016

Interactioni

Binary interactionsi

Show more details

GO - Molecular functioni

  • Wnt-protein binding Source: UniProtKB

Protein-protein interaction databases

BioGridi110973, 23 interactors
DIPiDIP-29734N
IntActiQ01973, 10 interactors
STRINGi9606.ENSP00000360120

Structurei

3D structure databases

ProteinModelPortaliQ01973
SMRiQ01973
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini42 – 147Ig-like C2-typeAdd BLAST106
Domaini165 – 299FZPROSITE-ProRule annotationAdd BLAST135
Domaini312 – 391KringlePROSITE-ProRule annotationAdd BLAST80
Domaini473 – 746Protein kinasePROSITE-ProRule annotationAdd BLAST274

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi753 – 782Ser/Thr-richAdd BLAST30
Compositional biasi784 – 851Pro-richAdd BLAST68
Compositional biasi853 – 876Ser/Thr-richAdd BLAST24

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. ROR subfamily.PROSITE-ProRule annotation

Keywords - Domaini

Immunoglobulin domain, Kringle, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IMMJ Eukaryota
COG0515 LUCA
GeneTreeiENSGT00760000118818
HOVERGENiHBG017736
InParanoidiQ01973
KOiK05122
OMAiECWHEQS
OrthoDBiEOG091G02W3
PhylomeDBiQ01973
TreeFamiTF106465

Family and domain databases

Gene3Di1.10.2000.10, 1 hit
2.40.20.10, 1 hit
2.60.40.10, 1 hit
InterProiView protein in InterPro
IPR020067 Frizzled_dom
IPR036790 Frizzled_dom_sf
IPR007110 Ig-like_dom
IPR036179 Ig-like_dom_sf
IPR013783 Ig-like_fold
IPR013098 Ig_I-set
IPR003599 Ig_sub
IPR003598 Ig_sub2
IPR011009 Kinase-like_dom_sf
IPR000001 Kringle
IPR013806 Kringle-like
IPR018056 Kringle_CS
IPR038178 Kringle_sf
IPR000719 Prot_kinase_dom
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
IPR008266 Tyr_kinase_AS
IPR016247 Tyr_kinase_rcpt_ROR
PfamiView protein in Pfam
PF01392 Fz, 1 hit
PF07679 I-set, 1 hit
PF00051 Kringle, 1 hit
PF07714 Pkinase_Tyr, 1 hit
PIRSFiPIRSF000624 TyrPK_TMrec_ROR, 1 hit
PRINTSiPR00109 TYRKINASE
SMARTiView protein in SMART
SM00409 IG, 1 hit
SM00408 IGc2, 1 hit
SM00130 KR, 1 hit
SUPFAMiSSF48726 SSF48726, 1 hit
SSF56112 SSF56112, 1 hit
SSF57440 SSF57440, 1 hit
PROSITEiView protein in PROSITE
PS50038 FZ, 1 hit
PS50835 IG_LIKE, 1 hit
PS00021 KRINGLE_1, 1 hit
PS50070 KRINGLE_2, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00109 PROTEIN_KINASE_TYR, 1 hit

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform Long (identifier: Q01973-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MHRPRRRGTR PPLLALLAAL LLAARGAAAQ ETELSVSAEL VPTSSWNISS
60 70 80 90 100
ELNKDSYLTL DEPMNNITTS LGQTAELHCK VSGNPPPTIR WFKNDAPVVQ
110 120 130 140 150
EPRRLSFRST IYGSRLRIRN LDTTDTGYFQ CVATNGKEVV SSTGVLFVKF
160 170 180 190 200
GPPPTASPGY SDEYEEDGFC QPYRGIACAR FIGNRTVYME SLHMQGEIEN
210 220 230 240 250
QITAAFTMIG TSSHLSDKCS QFAIPSLCHY AFPYCDETSS VPKPRDLCRD
260 270 280 290 300
ECEILENVLC QTEYIFARSN PMILMRLKLP NCEDLPQPES PEAANCIRIG
310 320 330 340 350
IPMADPINKN HKCYNSTGVD YRGTVSVTKS GRQCQPWNSQ YPHTHTFTAL
360 370 380 390 400
RFPELNGGHS YCRNPGNQKE APWCFTLDEN FKSDLCDIPA CDSKDSKEKN
410 420 430 440 450
KMEILYILVP SVAIPLAIAL LFFFICVCRN NQKSSSAPVQ RQPKHVRGQN
460 470 480 490 500
VEMSMLNAYK PKSKAKELPL SAVRFMEELG ECAFGKIYKG HLYLPGMDHA
510 520 530 540 550
QLVAIKTLKD YNNPQQWTEF QQEASLMAEL HHPNIVCLLG AVTQEQPVCM
560 570 580 590 600
LFEYINQGDL HEFLIMRSPH SDVGCSSDED GTVKSSLDHG DFLHIAIQIA
610 620 630 640 650
AGMEYLSSHF FVHKDLAARN ILIGEQLHVK ISDLGLSREI YSADYYRVQS
660 670 680 690 700
KSLLPIRWMP PEAIMYGKFS SDSDIWSFGV VLWEIFSFGL QPYYGFSNQE
710 720 730 740 750
VIEMVRKRQL LPCSEDCPPR MYSLMTECWN EIPSRRPRFK DIHVRLRSWE
760 770 780 790 800
GLSSHTSSTT PSGGNATTQT TSLSASPVSN LSNPRYPNYM FPSQGITPQG
810 820 830 840 850
QIAGFIGPPI PQNQRFIPIN GYPIPPGYAA FPAAHYQPTG PPRVIQHCPP
860 870 880 890 900
PKSRSPSSAS GSTSTGHVTS LPSSGSNQEA NIPLLPHMSI PNHPGGMGIT
910 920 930
VFGNKSQKPY KIDSKQASLL GDANIHGHTE SMISAEL
Length:937
Mass (Da):104,283
Last modified:November 28, 2006 - v2
Checksum:i0EC0E4762A90C6C7
GO
Isoform Short (identifier: Q01973-2) [UniParc]FASTAAdd to basket
Also known as: T-ROR1

The sequence of this isoform differs from the canonical sequence as follows:
     1-549: Missing.

Show »
Length:388
Mass (Da):42,833
Checksum:i8DC1D0BA14085BD2
GO
Isoform 3 (identifier: Q01973-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     392-393: DS → GK
     394-937: Missing.

Note: No experimental confirmation available.
Show »
Length:393
Mass (Da):43,826
Checksum:i1F93DCBBBBF53855
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_041779144G → E in a metastatic melanoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_041780150F → L in an ovarian mucinous carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_041781301I → V in a renal clear cell carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_041782518T → M2 PublicationsCorresponds to variant dbSNP:rs7527017Ensembl.1
Natural variantiVAR_035713562E → D in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_041783567R → I in a colorectal adenocarcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_041784624G → R1 PublicationCorresponds to variant dbSNP:rs55832740Ensembl.1
Natural variantiVAR_041785646Y → C1 PublicationCorresponds to variant dbSNP:rs34109134Ensembl.1
Natural variantiVAR_079530736R → T in DFNB108; impairs plasma membrane location; abolishes downstream NFkB activation. 1 Publication1
Natural variantiVAR_041786776S → N in a colorectal adenocarcinoma sample; somatic mutation. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0050081 – 549Missing in isoform Short. 1 PublicationAdd BLAST549
Alternative sequenceiVSP_043663392 – 393DS → GK in isoform 3. 1 Publication2
Alternative sequenceiVSP_043664394 – 937Missing in isoform 3. 1 PublicationAdd BLAST544

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M97675 mRNA Translation: AAA60275.1
U38894 mRNA Translation: AAC50714.1
AL137859 Genomic DNA No translation available.
AL161742 Genomic DNA No translation available.
AL445205 Genomic DNA No translation available.
AL138793 Genomic DNA No translation available.
AL353713 Genomic DNA No translation available.
AL808029 Genomic DNA No translation available.
AL808030 Genomic DNA No translation available.
CH471059 Genomic DNA Translation: EAX06556.1
BC080541 mRNA Translation: AAH80541.1
CCDSiCCDS41344.1 [Q01973-3]
CCDS626.1 [Q01973-1]
PIRiA45082
RefSeqiNP_001077061.1, NM_001083592.1 [Q01973-3]
NP_005003.2, NM_005012.3 [Q01973-1]
UniGeneiHs.128753

Genome annotation databases

EnsembliENST00000371079; ENSP00000360120; ENSG00000185483 [Q01973-1]
ENST00000371080; ENSP00000360121; ENSG00000185483 [Q01973-3]
GeneIDi4919
KEGGihsa:4919
UCSCiuc001dbi.5 human [Q01973-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiROR1_HUMAN
AccessioniPrimary (citable) accession number: Q01973
Secondary accession number(s): Q5VVX6, Q66K77, Q92776
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: November 28, 2006
Last modified: July 18, 2018
This is version 189 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

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