Reviewed, UniProtKB/Swiss-Prot Q04912 (RON_HUMAN)

Names and origin

Protein names

Recommended name:
    Macrophage-stimulating protein receptor
      Short name=MSP receptor
    EC=2.7.10.1
Alternative name(s):
    p185-Ron
    CDw136
    CD_antigen=CD136
Cleaved into the following 2 chains:
    1- Recommended name:
            Macrophage-stimulating protein receptor alpha chain
    2- Recommended name:
            Macrophage-stimulating protein receptor beta chain

Gene names

Name:	MST1R
Synonyms:	PTK8, RON

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1400 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Receptor for macrophage stimulating protein (MSP). Has a tyrosine-protein kinase activity. Ref.3
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Subunit structure	Heterodimer formed of an alpha chain and a beta chain which are disulfide linked. Binds PLXNB1. Associates with and is negatively regulated by HYAL2.
Subcellular location	Membrane; Single-pass type I membrane protein.
Tissue specificity	Keratinocytes and lung.
Post-translational modification	Proteolytic processing yields the two subunits. Phosphorylated in response to ligand binding Probable.
Sequence similarities	Belongs to the protein kinase superfamily. Tyr protein kinase family. Contains 3 IPT/TIG domains. Contains 1 protein kinase domain. Contains 1 Sema domain.

Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat Signal Transmembrane
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Receptor Transferase Tyrosine-protein kinase
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein Phosphoprotein
Gene Ontology (GO)
Biological process	cell motion Traceable author statement. Source: ProtInc defense response Traceable author statement. Source: ProtInc multicellular organismal development Inferred from electronic annotation. Source: InterPro positive regulation of cell proliferation Traceable author statement. Source: ProtInc protein amino acid phosphorylation Inferred from electronic annotation. Source: InterPro signal transduction Ref.3 Traceable author statement. Source: ProtInc single fertilization Traceable author statement. Source: ProtInc
Cellular component	integral to plasma membrane Ref.3 Traceable author statement. Source: ProtInc
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW macrophage colony stimulating factor receptor activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform RON (identifier: Q04912-1)

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.

Isoform Delta-RON (identifier: Q04912-2)

The sequence of this isoform differs from the canonical sequence as follows:
     884-932: Missing.

Note: Lacks part of the extracellular domain, oligomerizes and is constitutively activated.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 24	24	Potential
	Chain	25 – 1400	1376	Macrophage-stimulating protein receptor		PRO_0000024452
	Chain	25 – 304	280	Macrophage-stimulating protein receptor alpha chain Potential		PRO_0000024453
	Chain	310 – 1400	1091	Macrophage-stimulating protein receptor beta chain Potential		PRO_0000024454
Regions
	Topological domain	25 – 957	933	Extracellular Potential
	Transmembrane	958 – 978	21	Potential
	Topological domain	979 – 1400	422	Cytoplasmic Potential
	Domain	31 – 522	492	Sema
	Domain	569 – 671	103	IPT/TIG 1
	Domain	684 – 767	84	IPT/TIG 2
	Domain	770 – 860	91	IPT/TIG 3
	Domain	1082 – 1345	264	Protein kinase
	Nucleotide binding	1088 – 1096	9	ATP By similarity
	Compositional bias	306 – 309	4	Poly-Arg
Sites
	Active site	1208	1	Proton acceptor By similarity
	Binding site	1114	1	ATP By similarity
Amino acid modifications
	Modified residue	1353	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	1360	1	Phosphotyrosine; by autocatalysis By similarity
	Glycosylation	66	1	N-linked (GlcNAc...) Potential
	Glycosylation	419	1	N-linked (GlcNAc...) Potential
	Glycosylation	458	1	N-linked (GlcNAc...) Potential
	Glycosylation	488	1	N-linked (GlcNAc...) Potential
	Glycosylation	654	1	N-linked (GlcNAc...) Potential
	Glycosylation	720	1	N-linked (GlcNAc...) Potential
	Glycosylation	841	1	N-linked (GlcNAc...) Potential
	Glycosylation	897	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	884 – 932	49	Missing in isoform Delta-RON.		VSP_005007
	Natural variant	75	1	R → S Ref.6		VAR_041768
	Natural variant	95	1	P → T Ref.6		VAR_041769
	Natural variant	185	1	R → C Ref.6		VAR_041770
	Natural variant	322	1	Q → R Ref.6		VAR_006350
	Natural variant	356	1	G → D Ref.6		VAR_041771
	Natural variant	434	1	S → L: dbSNP rs2230591. Ref.6		VAR_029238
	Natural variant	440	1	N → S: dbSNP rs2230592.		VAR_029239
	Natural variant	465	1	G → D Ref.6		VAR_041772
	Natural variant	504	1	R → C Ref.6		VAR_041773
	Natural variant	523	1	R → Q Ref.6		VAR_041774
	Natural variant	613	1	Q → P Ref.6		VAR_041775
	Natural variant	900	1	V → M Ref.6		VAR_041776
	Natural variant	1304	1	R → G Ref.6		VAR_041777
	Natural variant	1335	1	R → G: dbSNP rs1062633. Ref.6		VAR_024577
	Natural variant	1360	1	Y → C Ref.6		VAR_041778

Sequences

	Sequence		Length	Mass (Da)
	Isoform RON [UniParc]. Last modified October 1, 1994. Version 1. Checksum: EE782D07E4D2568A	FASTA	1,400	152,227
	10 20 30 40 50 60 MELLPPLPQS FLLLLLLPAK PAAGEDWQCP RTPYAASRDF DVKYVVPSFS AGGLVQAMVT 70 80 90 100 110 120 YEGDRNESAV FVAIRNRLHV LGPDLKSVQS LATGPAGDPG CQTCAACGPG PHGPPGDTDT 130 140 150 160 170 180 KVLVLDPALP ALVSCGSSLQ GRCFLHDLEP QGTAVHLAAP ACLFSAHHNR PDDCPDCVAS 190 200 210 220 230 240 PLGTRVTVVE QGQASYFYVA SSLDAAVAGS FSPRSVSIRR LKADASGFAP GFVALSVLPK 250 260 270 280 290 300 HLVSYSIEYV HSFHTGAFVY FLTVQPASVT DDPSALHTRL ARLSATEPEL GDYRELVLDC 310 320 330 340 350 360 RFAPKRRRRG APEGGQPYPV LQVAHSAPVG AQLATELSIA EGQEVLFGVF VTGKDGGPGV 370 380 390 400 410 420 GPNSVVCAFP IDLLDTLIDE GVERCCESPV HPGLRRGLDF FQSPSFCPNP PGLEALSPNT 430 440 450 460 470 480 SCRHFPLLVS SSFSRVDLFN GLLGPVQVTA LYVTRLDNVT VAHMGTMDGR ILQVELVRSL 490 500 510 520 530 540 NYLLYVSNFS LGDSGQPVQR DVSRLGDHLL FASGDQVFQV PIRGPGCRHF LTCGRCLRAW 550 560 570 580 590 600 HFMGCGWCGN MCGQQKECPG SWQQDHCPPK LTEFHPHSGP LRGSTRLTLC GSNFYLHPSG 610 620 630 640 650 660 LVPEGTHQVT VGQSPCRPLP KDSSKLRPVP RKDFVEEFEC ELEPLGTQAV GPTNVSLTVT 670 680 690 700 710 720 NMPPGKHFRV DGTSVLRGFS FMEPVLIAVQ PLFGPRAGGT CLTLEGQSLS VGTSRAVLVN 730 740 750 760 770 780 GTECLLARVS EGQLLCATPP GATVASVPLS LQVGGAQVPG SWTFQYREDP VVLSISPNCG 790 800 810 820 830 840 YINSHITICG QHLTSAWHLV LSFHDGLRAV ESRCERQLPE QQLCRLPEYV VRDPQGWVAG 850 860 870 880 890 900 NLSARGDGAA GFTLPGFRFL PPPHPPSANL VPLKPEEHAI KFEYIGLGAV ADCVGINVTV 910 920 930 940 950 960 GGESCQHEFR GDMVVCPLPP SLQLGQDGAP LQVCVDGECH ILGRVVRPGP DGVPQSTLLG 970 980 990 1000 1010 1020 ILLPLLLLVA ALATALVFSY WWRRKQLVLP PNLNDLASLD QTAGATPLPI LYSGSDYRSG 1030 1040 1050 1060 1070 1080 LALPAIDGLD STTCVHGASF SDSEDESCVP LLRKESIQLR DLDSALLAEV KDVLIPHERV 1090 1100 1110 1120 1130 1140 VTHSDRVIGK GHFGVVYHGE YIDQAQNRIQ CAIKSLSRIT EMQQVEAFLR EGLLMRGLNH 1150 1160 1170 1180 1190 1200 PNVLALIGIM LPPEGLPHVL LPYMCHGDLL QFIRSPQRNP TVKDLISFGL QVARGMEYLA 1210 1220 1230 1240 1250 1260 EQKFVHRDLA ARNCMLDESF TVKVADFGLA RDILDREYYS VQQHRHARLP VKWMALESLQ 1270 1280 1290 1300 1310 1320 TYRFTTKSDV WSFGVLLWEL LTRGAPPYRH IDPFDLTHFL AQGRRLPQPE YCPDSLYQVM 1330 1340 1350 1360 1370 1380 QQCWEADPAV RPTFRVLVGE VEQIVSALLG DHYVQLPATY MNLGPSTSHE MNVRPEQPQF 1390 1400 SPMPGNVRRP RPLSEPPRPT
	Isoform Delta-RON. Checksum: C1B6B6B73E93BEF3	FASTA	1,351	147,233
	10 20 30 40 50 60 MELLPPLPQS FLLLLLLPAK PAAGEDWQCP RTPYAASRDF DVKYVVPSFS AGGLVQAMVT 70 80 90 100 110 120 YEGDRNESAV FVAIRNRLHV LGPDLKSVQS LATGPAGDPG CQTCAACGPG PHGPPGDTDT 130 140 150 160 170 180 KVLVLDPALP ALVSCGSSLQ GRCFLHDLEP QGTAVHLAAP ACLFSAHHNR PDDCPDCVAS 190 200 210 220 230 240 PLGTRVTVVE QGQASYFYVA SSLDAAVAGS FSPRSVSIRR LKADASGFAP GFVALSVLPK 250 260 270 280 290 300 HLVSYSIEYV HSFHTGAFVY FLTVQPASVT DDPSALHTRL ARLSATEPEL GDYRELVLDC 310 320 330 340 350 360 RFAPKRRRRG APEGGQPYPV LQVAHSAPVG AQLATELSIA EGQEVLFGVF VTGKDGGPGV 370 380 390 400 410 420 GPNSVVCAFP IDLLDTLIDE GVERCCESPV HPGLRRGLDF FQSPSFCPNP PGLEALSPNT 430 440 450 460 470 480 SCRHFPLLVS SSFSRVDLFN GLLGPVQVTA LYVTRLDNVT VAHMGTMDGR ILQVELVRSL 490 500 510 520 530 540 NYLLYVSNFS LGDSGQPVQR DVSRLGDHLL FASGDQVFQV PIRGPGCRHF LTCGRCLRAW 550 560 570 580 590 600 HFMGCGWCGN MCGQQKECPG SWQQDHCPPK LTEFHPHSGP LRGSTRLTLC GSNFYLHPSG 610 620 630 640 650 660 LVPEGTHQVT VGQSPCRPLP KDSSKLRPVP RKDFVEEFEC ELEPLGTQAV GPTNVSLTVT 670 680 690 700 710 720 NMPPGKHFRV DGTSVLRGFS FMEPVLIAVQ PLFGPRAGGT CLTLEGQSLS VGTSRAVLVN 730 740 750 760 770 780 GTECLLARVS EGQLLCATPP GATVASVPLS LQVGGAQVPG SWTFQYREDP VVLSISPNCG 790 800 810 820 830 840 YINSHITICG QHLTSAWHLV LSFHDGLRAV ESRCERQLPE QQLCRLPEYV VRDPQGWVAG 850 860 870 880 890 900 NLSARGDGAA GFTLPGFRFL PPPHPPSANL VPLKPEEHAI KFEVCVDGEC HILGRVVRPG 910 920 930 940 950 960 PDGVPQSTLL GILLPLLLLV AALATALVFS YWWRRKQLVL PPNLNDLASL DQTAGATPLP 970 980 990 1000 1010 1020 ILYSGSDYRS GLALPAIDGL DSTTCVHGAS FSDSEDESCV PLLRKESIQL RDLDSALLAE 1030 1040 1050 1060 1070 1080 VKDVLIPHER VVTHSDRVIG KGHFGVVYHG EYIDQAQNRI QCAIKSLSRI TEMQQVEAFL 1090 1100 1110 1120 1130 1140 REGLLMRGLN HPNVLALIGI MLPPEGLPHV LLPYMCHGDL LQFIRSPQRN PTVKDLISFG 1150 1160 1170 1180 1190 1200 LQVARGMEYL AEQKFVHRDL AARNCMLDES FTVKVADFGL ARDILDREYY SVQQHRHARL 1210 1220 1230 1240 1250 1260 PVKWMALESL QTYRFTTKSD VWSFGVLLWE LLTRGAPPYR HIDPFDLTHF LAQGRRLPQP 1270 1280 1290 1300 1310 1320 EYCPDSLYQV MQQCWEADPA VRPTFRVLVG EVEQIVSALL GDHYVQLPAT YMNLGPSTSH 1330 1340 1350 EMNVRPEQPQ FSPMPGNVRR PRPLSEPPRP T

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A novel putative receptor protein tyrosine kinase of the met family." Ronsin C., Muscatelli F., Mattei M.-G., Breathnach R. Oncogene 8:1195-1202(1993) [PubMed: 8386824] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Keratinocyte.
[2]	"A splicing variant of the RON transcript induces constitutive tyrosine kinase activity and an invasive phenotype." Collesi C., Santoro M.M., Gaudino G., Comoglio P.M. Mol. Cell. Biol. 16:5518-5526(1996) [PubMed: 8816464] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING.
[3]	"Identification of the ron gene product as the receptor for the human macrophage stimulating protein." Wang M.-H., Ronsin C., Gesnel M.-C., Coupey L., Skeel A., Leonard E.J., Breatnach R. Science 266:117-119(1994) [PubMed: 7939629] [Abstract] Cited for: FUNCTION.
[4]	"Hyaluronidase 2 negatively regulates RON receptor tyrosine kinase and mediates transformation of epithelial cells by jaagsiekte sheep retrovirus." Danilkovitch-Miagkova A., Duh F.-M., Kuzmin I., Angeloni D., Liu S.-L., Miller A.D., Lerman M.I. Proc. Natl. Acad. Sci. U.S.A. 100:4580-4585(2003) [PubMed: 12676986] [Abstract] Cited for: INTERACTION WITH HYAL2.
[5]	"Interplay between scatter factor receptors and B plexins controls invasive growth." Conrotto P., Corso S., Gamberini S., Comoglio P.M., Giordano S. Oncogene 23:5131-5137(2004) [PubMed: 15184888] [Abstract] Cited for: INTERACTION WITH PLXNB1.
[6]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] SER-75; THR-95; CYS-185; ARG-322; ASP-356; LEU-434; ASP-465; CYS-504; GLN-523; PRO-613; MET-900; GLY-1304; GLY-1335 AND CYS-1360.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases
EMBLGenBankDDBJ	X70040 mRNA. Translation: CAA49634.1.
IPI	IPI00030273. IPI00219706.
PIR	I38185.
RefSeq	NP_002438.2.
UniGene	Hs.517973
3D structure databases
HSSP	HSSP built from PDB template 1FGK based on UniProtKB P11362.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP:6029N.
PTM databases
PhosphoSite	Q04912.
Proteomic databases
PRIDE	Q04912.
Genome annotation databases
Ensembl	ENSG00000164078. Homo sapiens. [Contig view]
GeneID	4486.
KEGG	hsa:4486.
Organism-specific databases
GeneCards	GC03M049899.
H-InvDB	HIX0030873.
HGNC	HGNC:7381. MST1R.
HPA	CAB008972. HPA007657. HPA008180.
MIM	600168. gene.
PharmGKB	PA31186.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q04912.
HOVERGEN	Q04912.
Enzyme and pathway databases
BRENDA	2.7.10.1. 247.
Pathway_Interaction_DB	a6b1_a6b4_integrin_pathway. a6b1 and a6b4 Integrin signaling. amb2_neutrophils_pathway. amb2 Integrin signaling.
Gene expression databases
ArrayExpress	Q04912.
Bgee	Q04912.
CleanEx	HS_MST1R.
GermOnline	ENSG00000164078. Homo sapiens.
Family and domain databases
InterPro	IPR002909. IPT_TIG_rcpt. IPR003659. Plexin-like. IPR002165. Plexin_repeat. IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_BS. IPR001627. Semaphorin/CD100_Ag. IPR001245. Tyr_pkinase. IPR008266. Tyr_pkinase_AS. IPR016244. TyrPK_HGF-R. [Graphical view]
Pfam	PF07714. Pkinase_Tyr. 1 hit. PF01437. PSI. 1 hit. PF01403. Sema. 1 hit. PF01833. TIG. 3 hits. [Graphical view]
PIRSF	PIRSF000617. TyrPK_HGF-R. 1 hit.
PRINTS	PR00109. TYRKINASE.
ProDom	PD000001. Prot_kinase. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00429. IPT. 3 hits. SM00423. PSI. 1 hit. SM00630. Sema. 1 hit. SM00219. TyrKc. 1 hit. [Graphical view]
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00109. PROTEIN_KINASE_TYR. 1 hit. PS51004. SEMA. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	17355.
SOURCE	Search...

Entry information

Entry name

RON_HUMAN

Accession

Primary (citable) accession number: Q04912

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1994
Last sequence update:	October 1, 1994
Last modified:	June 16, 2009
This is version 103 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)