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Protein

Inactive tyrosine-protein kinase transmembrane receptor ROR1

Gene

ROR1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Has very low kinase activity in vitro and is unlikely to function as a tyrosine kinase in vivo. May act as a receptor for wnt ligand WNT5A which may result in the inhibition of WNT3A-mediated signaling.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-protein binding Source: UniProtKB

GO - Biological processi

  • transmembrane receptor protein tyrosine kinase signaling pathway Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Receptor, Transferase

Keywords - Biological processi

Wnt signaling pathway

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS00038-MONOMER.
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

HGNCiHGNC:10256. ROR1.

Subcellular locationi

Topology

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

GO - Cellular componenti

  • cytoplasm Source: ProtInc
  • integral component of plasma membrane Source: ProtInc
  • plasma membrane Source: ProtInc
  • receptor complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Mutagenesis

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

Organism-specific databases

DisGeNETi4919.
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...)Sequence analysis1
Glycosylationi66N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi79 ↔ 131By similarity
Disulfide bondi170 ↔ 235By similarity
Disulfide bondi178 ↔ 228By similarity
Glycosylationi184N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi219 ↔ 260By similarity
Disulfide bondi248 ↔ 296By similarity
Disulfide bondi252 ↔ 282By similarity
Disulfide bondi313 ↔ 391By similarity
Glycosylationi315N-linked (GlcNAc...)Sequence 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.

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

WithEntry#Exp.IntActNotes
EGFRP005338EBI-6082337,EBI-297353
SRCP129319EBI-6082337,EBI-621482
SrcP054803EBI-6082337,EBI-298680From a different organism.

GO - Molecular functioni

  • Wnt-protein binding Source: UniProtKB

Protein-protein interaction databases

BioGridi110973. 7 interactors.
DIPiDIP-29734N.
IntActiQ01973. 9 interactors.
MINTiMINT-5004457.
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
Contains 1 FZ (frizzled) domain.PROSITE-ProRule annotation
Contains 1 kringle domain.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Immunoglobulin domain, Kringle, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IMMJ. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000118818.
HOVERGENiHBG017736.
InParanoidiQ01973.
KOiK05122.
OMAiWAEFQQE.
OrthoDBiEOG091G02W3.
PhylomeDBiQ01973.
TreeFamiTF106465.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
InterProiIPR020067. Frizzled_dom.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR011009. Kinase-like_dom.
IPR000001. Kringle.
IPR013806. Kringle-like.
IPR018056. Kringle_CS.
IPR000719. Prot_kinase_dom.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR016247. Tyr_kinase_rcpt_ROR.
[Graphical view]
PfamiPF01392. Fz. 1 hit.
PF07679. I-set. 1 hit.
PF00051. Kringle. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PIRSFiPIRSF000624. TyrPK_TMrec_ROR. 1 hit.
PRINTSiPR00109. TYRKINASE.
SMARTiSM00409. IG. 1 hit.
SM00408. IGc2. 1 hit.
SM00130. KR. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 1 hit.
SSF56112. SSF56112. 1 hit.
SSF57440. SSF57440. 1 hit.
PROSITEiPS50038. 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.
[Graphical view]

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 → M.2 PublicationsCorresponds to variant rs7527017dbSNPEnsembl.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 → R.1 PublicationCorresponds to variant rs55832740dbSNPEnsembl.1
Natural variantiVAR_041785646Y → C.1 PublicationCorresponds to variant rs34109134dbSNPEnsembl.1
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, AL161742, AL445205 Genomic DNA. Translation: CAC17591.2.
AL445205, AL137859, AL161742 Genomic DNA. Translation: CAH71705.1.
AL445205, AL137859, AL161742 Genomic DNA. Translation: CAH71706.1.
AL137859, AL445205, AL161742 Genomic DNA. Translation: CAI21732.1.
AL161742, AL137859, AL445205 Genomic DNA. Translation: CAI21931.1.
AL161742, AL445205, AL137859 Genomic DNA. Translation: CAI21932.1.
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

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M97675 mRNA. Translation: AAA60275.1.
U38894 mRNA. Translation: AAC50714.1.
AL137859, AL161742, AL445205 Genomic DNA. Translation: CAC17591.2.
AL445205, AL137859, AL161742 Genomic DNA. Translation: CAH71705.1.
AL445205, AL137859, AL161742 Genomic DNA. Translation: CAH71706.1.
AL137859, AL445205, AL161742 Genomic DNA. Translation: CAI21732.1.
AL161742, AL137859, AL445205 Genomic DNA. Translation: CAI21931.1.
AL161742, AL445205, AL137859 Genomic DNA. Translation: CAI21932.1.
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.

3D structure databases

ProteinModelPortaliQ01973.
SMRiQ01973.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110973. 7 interactors.
DIPiDIP-29734N.
IntActiQ01973. 9 interactors.
MINTiMINT-5004457.
STRINGi9606.ENSP00000360120.

PTM databases

iPTMnetiQ01973.
PhosphoSitePlusiQ01973.
SwissPalmiQ01973.

Polymorphism and mutation databases

BioMutaiROR1.
DMDMi118572711.

Proteomic databases

EPDiQ01973.
MaxQBiQ01973.
PaxDbiQ01973.
PeptideAtlasiQ01973.
PRIDEiQ01973.

Protocols and materials databases

DNASUi4919.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi4919.
DisGeNETi4919.
GeneCardsiROR1.
HGNCiHGNC:10256. ROR1.
HPAiHPA057016.
MIMi602336. gene.
neXtProtiNX_Q01973.
OpenTargetsiENSG00000185483.
PharmGKBiPA34628.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IMMJ. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000118818.
HOVERGENiHBG017736.
InParanoidiQ01973.
KOiK05122.
OMAiWAEFQQE.
OrthoDBiEOG091G02W3.
PhylomeDBiQ01973.
TreeFamiTF106465.

Enzyme and pathway databases

BioCyciZFISH:HS00038-MONOMER.
BRENDAi2.7.10.1. 2681.
ReactomeiR-HSA-5140745. WNT5A-dependent internalization of FZD2, FZD5 and ROR2.
SignaLinkiQ01973.
SIGNORiQ01973.

Miscellaneous databases

ChiTaRSiROR1. human.
GeneWikiiROR1.
GenomeRNAii4919.
PROiQ01973.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000185483.
CleanExiHS_ROR1.
ExpressionAtlasiQ01973. baseline and differential.
GenevisibleiQ01973. HS.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
InterProiIPR020067. Frizzled_dom.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR011009. Kinase-like_dom.
IPR000001. Kringle.
IPR013806. Kringle-like.
IPR018056. Kringle_CS.
IPR000719. Prot_kinase_dom.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR016247. Tyr_kinase_rcpt_ROR.
[Graphical view]
PfamiPF01392. Fz. 1 hit.
PF07679. I-set. 1 hit.
PF00051. Kringle. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PIRSFiPIRSF000624. TyrPK_TMrec_ROR. 1 hit.
PRINTSiPR00109. TYRKINASE.
SMARTiSM00409. IG. 1 hit.
SM00408. IGc2. 1 hit.
SM00130. KR. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 1 hit.
SSF56112. SSF56112. 1 hit.
SSF57440. SSF57440. 1 hit.
PROSITEiPS50038. 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.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiROR1_HUMAN
AccessioniPrimary (citable) accession number: Q01973
Secondary accession number(s): Q5VVX6, Q66K77, Q92776
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: November 28, 2006
Last modified: November 2, 2016
This is version 172 of the entry and version 2 of the sequence. [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

Caution

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

Keywords - Technical termi

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. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.