Q04912 (RON_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Macrophage-stimulating protein receptor
Short name=MSP receptor
EC=2.7.10.1

Alternative name(s):
CDw136
Protein-tyrosine kinase 8
p185-Ron
CD_antigen=CD136

Cleaved into the following 2 chains:

1. Macrophage-stimulating protein receptor alpha chain
2. Macrophage-stimulating protein receptor beta chain

Gene names

Name:	MST1R
Synonyms:	PTK8, RON

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › 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 tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to MST1 ligand. Regulates many physiological processes including cell survival, migration and differentiation. Ligand binding at the cell surface induces autophosphorylation of RON on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with the PI3-kinase subunit PIK3R1, PLCG1 or the adapter GAB1. Recruitment of these downstream effectors by RON leads to the activation of several signaling cascades including the RAS-ERK, PI3 kinase-AKT, or PLCgamma-PKC. RON signaling activates the wound healing response by promoting epithelial cell migration, proliferation as well as survival at the wound site. Plays also a role in the innate immune response by regulating the migration and phagocytic activity of macrophages. Alternatively, RON can also promote signals such as cell migration and proliferation in response to growth factors other than MST1 ligand. Ref.7 Ref.8 Ref.16
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Enzyme regulation	In its inactive state, the C-terminal tail interacts with the catalytic domain and inhibits the kinase activity. Upon ligand binding, the C-terminal tail is displaced and becomes phosphorylated, thus increasing the kinase activity. Ref.15
Subunit structure	Heterodimer of an alpha chain and a beta chain which are disulfide linked. Binds PLXNB1. Associates with and is negatively regulated by HYAL2. Interacts when phosphorylated with downstream effectors including PIK3R1, PCLG1, GRB2 and GAB1. Interacts with integrin beta1/ITGB1 in a ligand-independent fashion. Ref.5 Ref.9 Ref.10 Ref.13 Ref.14 Ref.18
Subcellular location	Membrane; Single-pass type I membrane protein.
Tissue specificity	Expressed in colon, skin, lung and bone marrow. Ref.6
Post-translational modification	Proteolytic processing yields the two subunits. Autophosphorylated in response to ligand binding on Tyr-1238 and Tyr-1239 in the kinase domain leading to further phosphorylation of Tyr-1353 and Tyr-1360 in the C-terminal multifunctional docking site. Ref.15 Ref.19 Ubiquitinated. Ubiquitination by CBL regulates the receptor stability and activity through proteasomal degradation. Ref.12
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
Biological process	Immunity Innate immunity
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat Signal Transmembrane Transmembrane helix
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Receptor Transferase Tyrosine-protein kinase
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular component movement Traceable author statement PubMed 9045873. Source: ProtInc defense response Traceable author statement PubMed 9045873. Source: ProtInc innate immune response Inferred from electronic annotation. Source: UniProtKB-KW multicellular organismal development Inferred from electronic annotation. Source: InterPro positive regulation of MAP kinase activity Inferred from direct assay Ref.13. Source: UniProtKB positive regulation of cell proliferation Traceable author statement PubMed 10871856. Source: ProtInc positive regulation of protein kinase B signaling cascade Inferred from direct assay Ref.13. Source: UniProtKB response to virus Inferred from direct assay Ref.13. Source: UniProtKB single fertilization Traceable author statement PubMed 9045873. Source: ProtInc transmembrane receptor protein tyrosine kinase signaling pathway Inferred from electronic annotation. Source: InterPro
Cellular_component	integral to plasma membrane Traceable author statement Ref.7. Source: ProtInc stress fiber Inferred from electronic annotation. Source: Compara
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW macrophage colony-stimulating factor receptor activity Traceable author statement PubMed 9045873. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PLXNB1	O43157	3	EBI-2637518,EBI-1111488
PLXNB2	O15031	2	EBI-2637518,EBI-722004
PLXNB3	Q9ULL4	2	EBI-2637518,EBI-311073

Alternative products

This entry describes 6 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.

Isoform RON-1 (identifier: Q04912-3)

The sequence of this isoform differs from the canonical sequence as follows:
     475-495: ELVRSLNYLLYVSNFSLGDSG → GPHPHSPLALGPCLHPHFAHI
     496-1400: Missing.

Isoform RON-2 (identifier: Q04912-4)

The sequence of this isoform differs from the canonical sequence as follows:
     411-516: Missing.
     628-647: PVPRKDFVEEFECELEPLGT → YNLVPPLPFPEGGNQAAPSP
     648-1400: Missing.

Isoform RON-3 (identifier: Q04912-5)

The sequence of this isoform differs from the canonical sequence as follows:
     884-907: YIGLGAVADCVGINVTVGGESCQH → VSVRDRGRDSWGSESRGQPTGWSS
     908-1400: Missing.

Isoform RON-4 (identifier: Q04912-6)

The sequence of this isoform differs from the canonical sequence as follows:
     628-647: PVPRKDFVEEFECELEPLGT → YNLVPPLPFPEGGNQAAPSP
     648-1400: Missing.

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

Helical; 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

Nucleotide binding

1161 – 1164

4

ATP

Compositional bias

306 – 309

4

Poly-Arg

Compositional bias

962 – 968

7

Poly-Leu

Sites

Active site

1208

1

Proton acceptor Probable

Binding site

1114

1

ATP

Binding site

1212

1

ATP

Amino acid modifications

Modified residue

1238

1

Phosphotyrosine; by autocatalysis Probable

Modified residue

1239

1

Phosphotyrosine; by autocatalysis Probable

Modified residue

1353

1

Phosphotyrosine; by autocatalysis

Modified residue

1360

1

Phosphotyrosine; by autocatalysis

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...) Ref.20

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

Disulfide bond

101 ↔ 104

Ref.20

Disulfide bond

107 ↔ 162

Ref.20

Disulfide bond

135 ↔ 143

Ref.20

Disulfide bond

174 ↔ 177

Ref.20

Disulfide bond

300 ↔ 367

Ref.20

Disulfide bond

385 ↔ 407

Ref.20

Disulfide bond

386 ↔ 422

Ref.20

Disulfide bond

527 ↔ 545

Ref.20

Disulfide bond

533 ↔ 567

Ref.20

Disulfide bond

536 ↔ 552

Ref.20

Disulfide bond

548 ↔ 558

Ref.20

Natural variations

Alternative sequence

411 – 516

106

Missing in isoform RON-2.

VSP_038919

Alternative sequence

475 – 495

21

ELVRS…LGDSG → GPHPHSPLALGPCLHPHFAH I in isoform RON-1.

VSP_038920

Alternative sequence

496 – 1400

905

Missing in isoform RON-1.

VSP_038921

Alternative sequence

628 – 647

20

PVPRK…EPLGT → YNLVPPLPFPEGGNQAAPSP in isoform RON-2 and isoform RON-4.

VSP_038922

Alternative sequence

648 – 1400

753

Missing in isoform RON-2 and isoform RON-4.

VSP_038923

Alternative sequence

884 – 932

49

Missing in isoform Delta-RON.

VSP_005007

Alternative sequence

884 – 907

24

YIGLG…ESCQH → VSVRDRGRDSWGSESRGQPT GWSS in isoform RON-3.

VSP_038924

Alternative sequence

908 – 1400

493

Missing in isoform RON-3.

VSP_038925

Natural variant

75

1

R → S. Ref.21
Corresponds to variant rs35887539 [ dbSNP | Ensembl ].

VAR_041768

Natural variant

95

1

P → T. Ref.21
Corresponds to variant rs55908300 [ dbSNP | Ensembl ].

VAR_041769

Natural variant

185

1

R → C. Ref.21
Corresponds to variant rs55633379 [ dbSNP | Ensembl ].

VAR_041770

Natural variant

322

1

R → Q. Ref.1 Ref.21
Corresponds to variant rs2230593 [ dbSNP | Ensembl ].

VAR_006350

Natural variant

356

1

G → D. Ref.21
Corresponds to variant rs35924402 [ dbSNP | Ensembl ].

VAR_041771

Natural variant

434

1

S → L. Ref.21
Corresponds to variant rs2230591 [ dbSNP | Ensembl ].

VAR_029238

Natural variant

440

1

N → S.
Corresponds to variant rs2230592 [ dbSNP | Ensembl ].

VAR_029239

Natural variant

465

1

G → D. Ref.21
Corresponds to variant rs34564898 [ dbSNP | Ensembl ].

VAR_041772

Natural variant

504

1

R → C. Ref.21
Corresponds to variant rs34350470 [ dbSNP | Ensembl ].

VAR_041773

Natural variant

523

1

Q → R. Ref.1 Ref.21
Corresponds to variant rs2230590 [ dbSNP | Ensembl ].

VAR_041774

Natural variant

613

1

Q → P. Ref.21
Corresponds to variant rs35986685 [ dbSNP | Ensembl ].

VAR_041775

Natural variant

900

1

V → M. Ref.21
Corresponds to variant rs56091918 [ dbSNP | Ensembl ].

VAR_041776

Natural variant

1195

1

S → G. Ref.1
Corresponds to variant rs7433231 [ dbSNP | Ensembl ].

VAR_061749

Natural variant

1304

1

R → G. Ref.21

VAR_041777

Natural variant

1335

1

R → G. Ref.21
Corresponds to variant rs1062633 [ dbSNP | Ensembl ].

VAR_024577

Natural variant

1360

1

Y → C. Ref.21
Corresponds to variant rs56330223 [ dbSNP | Ensembl ].

VAR_041778

Experimental info

Sequence conflict

209

1

A → G in CAA49634. Ref.1

Sequence conflict

813

1

R → RQ in ACF47620. Ref.3

Secondary structure

1

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1400

Helix Strand Turn

Details...

Beta strand

43 – 45

3

Beta strand

48 – 50

3

Beta strand

55 – 62

8

Beta strand

68 – 74

7

Beta strand

77 – 81

5

Beta strand

87 – 92

6

Helix

102 – 105

4

Beta strand

108 – 110

3

Beta strand

120 – 126

7

Turn

127 – 130

4

Beta strand

131 – 138

8

Helix

139 – 141

3

Beta strand

143 – 151

9

Beta strand

154 – 157

4

Beta strand

184 – 191

8

Beta strand

194 – 201

8

Helix

205 – 208

4

Beta strand

209 – 211

3

Beta strand

215 – 221

7

Beta strand

233 – 235

3

Helix

239 – 242

4

Beta strand

248 – 255

8

Beta strand

258 – 268

11

Beta strand

275 – 288

14

Beta strand

294 – 302

9

Beta strand

316 – 318

3

Beta strand

320 – 328

9

Helix

331 – 337

7

Beta strand

344 – 351

8

Beta strand

365 – 370

6

Helix

371 – 386

16

Beta strand

387 – 389

3

Turn

399 – 401

3

Helix

422 – 424

3

Beta strand

433 – 436

4

Turn

438 – 445

8

Beta strand

448 – 456

9

Beta strand

459 – 466

8

Beta strand

469 – 475

7

Beta strand

485 – 491

7

Beta strand

503 – 505

3

Beta strand

508 – 513

6

Beta strand

516 – 521

6

Helix

527 – 529

3

Helix

533 – 538

6

Helix

541 – 543

3

Beta strand

549 – 553

5

Helix

555 – 557

3

Turn

559 – 561

3

Helix

1064 – 1069

6

Helix

1071 – 1073

3

Helix

1077 – 1079

3

Beta strand

1080 – 1091

12

Beta strand

1094 – 1102

9

Beta strand

1104 – 1106

3

Beta strand

1108 – 1116

9

Helix

1122 – 1136

15

Beta strand

1148 – 1150

3

Beta strand

1153 – 1155

3

Beta strand

1158 – 1161

4

Helix

1169 – 1174

6

Helix

1182 – 1201

20

Helix

1211 – 1213

3

Beta strand

1214 – 1216

3

Beta strand

1222 – 1224

3

Turn

1232 – 1235

4

Helix

1236 – 1239

4

Helix

1250 – 1253

4

Helix

1256 – 1259

4

Helix

1266 – 1282

17

Turn

1287 – 1290

4

Helix

1293 – 1295

3

Helix

1296 – 1301

6

Helix

1314 – 1323

10

Helix

1328 – 1330

3

Helix

1334 – 1347

14

Sequences

	Sequence		Length	Mass (Da)
	Isoform RON [UniParc]. Last modified April 20, 2010. Version 2. Checksum: EB5CA79ABC69A882	FASTA	1,400	152,271
	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 SSLDAAVAAS FSPRSVSIRR LKADASGFAP GFVALSVLPK 250 260 270 280 290 300 HLVSYSIEYV HSFHTGAFVY FLTVQPASVT DDPSALHTRL ARLSATEPEL GDYRELVLDC 310 320 330 340 350 360 RFAPKRRRRG APEGGQPYPV LRVAHSAPVG 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 PIQGPGCRHF 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 QVARSMEYLA 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 [UniParc]. Checksum: 23ACE5B9330EEA0B	FASTA	1,351	147,277
	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 SSLDAAVAAS FSPRSVSIRR LKADASGFAP GFVALSVLPK 250 260 270 280 290 300 HLVSYSIEYV HSFHTGAFVY FLTVQPASVT DDPSALHTRL ARLSATEPEL GDYRELVLDC 310 320 330 340 350 360 RFAPKRRRRG APEGGQPYPV LRVAHSAPVG 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 PIQGPGCRHF 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 LQVARSMEYL 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
	Isoform RON-1 [UniParc]. Checksum: 3F99D0A454B25721	FASTA	495	52,519
	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 SSLDAAVAAS FSPRSVSIRR LKADASGFAP GFVALSVLPK 250 260 270 280 290 300 HLVSYSIEYV HSFHTGAFVY FLTVQPASVT DDPSALHTRL ARLSATEPEL GDYRELVLDC 310 320 330 340 350 360 RFAPKRRRRG APEGGQPYPV LRVAHSAPVG 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 ILQVGPHPHS 490 PLALGPCLHP HFAHI
	Isoform RON-2 [UniParc]. Checksum: 9BC028F4170B1BFC	FASTA	541	57,721
	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 SSLDAAVAAS FSPRSVSIRR LKADASGFAP GFVALSVLPK 250 260 270 280 290 300 HLVSYSIEYV HSFHTGAFVY FLTVQPASVT DDPSALHTRL ARLSATEPEL GDYRELVLDC 310 320 330 340 350 360 RFAPKRRRRG APEGGQPYPV LRVAHSAPVG AQLATELSIA EGQEVLFGVF VTGKDGGPGV 370 380 390 400 410 420 GPNSVVCAFP IDLLDTLIDE GVERCCESPV HPGLRRGLDF FQSPSFCPNP VFQVPIQGPG 430 440 450 460 470 480 CRHFLTCGRC LRAWHFMGCG WCGNMCGQQK ECPGSWQQDH CPPKLTEFHP HSGPLRGSTR 490 500 510 520 530 540 LTLCGSNFYL HPSGLVPEGT HQVTVGQSPC RPLPKDSSKL RYNLVPPLPF PEGGNQAAPS P
	Isoform RON-3 [UniParc]. Checksum: DDC3A5776146ECCB	FASTA	907	97,315
	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 SSLDAAVAAS FSPRSVSIRR LKADASGFAP GFVALSVLPK 250 260 270 280 290 300 HLVSYSIEYV HSFHTGAFVY FLTVQPASVT DDPSALHTRL ARLSATEPEL GDYRELVLDC 310 320 330 340 350 360 RFAPKRRRRG APEGGQPYPV LRVAHSAPVG 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 PIQGPGCRHF 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 KFEVSVRDRG RDSWGSESRG QPTGWSS
	Isoform RON-4 [UniParc]. Checksum: BE4234918FE98C33	FASTA	647	69,265
	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 SSLDAAVAAS FSPRSVSIRR LKADASGFAP GFVALSVLPK 250 260 270 280 290 300 HLVSYSIEYV HSFHTGAFVY FLTVQPASVT DDPSALHTRL ARLSATEPEL GDYRELVLDC 310 320 330 340 350 360 RFAPKRRRRG APEGGQPYPV LRVAHSAPVG 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 PIQGPGCRHF LTCGRCLRAW 550 560 570 580 590 600 HFMGCGWCGN MCGQQKECPG SWQQDHCPPK LTEFHPHSGP LRGSTRLTLC GSNFYLHPSG 610 620 630 640 LVPEGTHQVT VGQSPCRPLP KDSSKLRYNL VPPLPFPEGG NQAAPSP

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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM RON), VARIANTS GLN-322; ARG-523 AND GLY-1195. 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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING.
[3]	"Novel splice variants derived from the receptor tyrosine kinase superfamily are potential therapeutics for rheumatoid arthritis." Jin P., Zhang J., Sumariwalla P.F., Ni I., Jorgensen B., Crawford D., Phillips S., Feldmann M., Shepard H.M., Paleolog E.M. Arthritis Res. Ther. 10:R73-R73(2008) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS RON-1; RON-2; RON-3 AND RON-4).
[4]	"The DNA sequence, annotation and analysis of human chromosome 3." Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A. Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"A novel recognition motif for phosphatidylinositol 3-kinase binding mediates its association with the hepatocyte growth factor/scatter factor receptor." Ponzetto C., Bardelli A., Maina F., Longati P., Panayotou G., Dhand R., Waterfield M.D., Comoglio P.M. Mol. Cell. Biol. 13:4600-4608(1993) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PIK3R1.
[6]	"RON is a heterodimeric tyrosine kinase receptor activated by the HGF homologue MSP." Gaudino G., Follenzi A., Naldini L., Collesi C., Santoro M., Gallo K.A., Godowski P.J., Comoglio P.M. EMBO J. 13:3524-3532(1994) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[7]	"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] [Europe PMC] [Abstract] Cited for: FUNCTION.
[8]	"Proteolytic cleavage and activation of pro-macrophage-stimulating protein and upregulation of its receptor in tissue injury." Nanney L.B., Skeel A., Luan J., Polis S., Richmond A., Wang M.H., Leonard E.J. J. Invest. Dermatol. 111:573-581(1998) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN WOUND HEALING RESPONSE.
[9]	"Macrophage stimulating protein-induced epithelial cell adhesion is mediated by a PI3-K-dependent, but FAK-independent mechanism." Danilkovitch A., Skeel A., Leonard E.J. Exp. Cell Res. 248:575-582(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ITGB1.
[10]	"Interaction of macrophage-stimulating protein with its receptor. Residues critical for beta chain binding and evidence for independent alpha chain binding." Danilkovitch A., Miller M., Leonard E.J. J. Biol. Chem. 274:29937-29943(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MST1.
[11]	"Macrophage-stimulating protein and RON receptor tyrosine kinase: potential regulators of macrophage inflammatory activities." Wang M.H., Zhou Y.Q., Chen Y.Q. Scand. J. Immunol. 56:545-553(2002) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION.
[12]	"c-Cbl is a critical modulator of the Ron tyrosine kinase receptor." Penengo L., Rubin C., Yarden Y., Gaudino G. Oncogene 22:3669-3679(2003) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION.
[13]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HYAL2.
[14]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PLXNB1.
[15]	"The C terminus of RON tyrosine kinase plays an autoinhibitory role." Yokoyama N., Ischenko I., Hayman M.J., Miller W.T. J. Biol. Chem. 280:8893-8900(2005) [PubMed] [Europe PMC] [Abstract] Cited for: AUTOPHOSPHORYLATION, ENZYME REGULATION.
[16]	"The RON receptor tyrosine kinase promotes MSP-independent cell spreading and survival in breast epithelial cells." Feres K.J., Ischenko I., Hayman M.J. Oncogene 28:279-288(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[17]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[18]	"Distinct involvement of the Gab1 and Grb2 adaptor proteins in signal transduction by the related receptor tyrosine kinases RON and MET." Chaudhuri A., Xie M.H., Yang B., Mahapatra K., Liu J., Marsters S., Bodepudi S., Ashkenazi A. J. Biol. Chem. 286:32762-32774(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH GAB1 AND GRB2.
[19]	"The crystal structure of a constitutively active mutant RON kinase suggests an intramolecular autophosphorylation hypothesis." Wang J., Steinbacher S., Augustin M., Schreiner P., Epstein D., Mulvihill M.J., Crew A.P. Biochemistry 49:7972-7974(2010) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.24 ANGSTROMS) OF 1060-1357 IN COMPLEX WITH AMP-PNP AND MAGNESIUM, ACTIVE SITE, PHOSPHORYLATION AT TYR-1238.
[20]	"Crystal structure of the Sema-PSI extracellular domain of human RON receptor tyrosine kinase." Chao K.L., Tsai I.W., Chen C., Herzberg O. PLoS ONE 7:E41912-E41912(2012) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 42-568, GLYCOSYLATION AT ASN-488, DISULFIDE BONDS.
[21]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] SER-75; THR-95; CYS-185; GLN-322; ASP-356; LEU-434; ASP-465; CYS-504; ARG-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

EMBL
GenBank
DDBJ

X70040 mRNA. Translation: CAA49634.1.
EU826582 mRNA. Translation: ACF47618.1.
EU826583 mRNA. Translation: ACF47619.1.
EU826584 mRNA. Translation: ACF47620.1.
EU826585 mRNA. Translation: ACF47621.1.
AC105935 Genomic DNA. No translation available.

IPI

IPI00030273.
IPI00219706.
IPI00910383.
IPI00926020.
IPI00956299.
IPI00956695.

PIR

I38185.

RefSeq

NP_001231866.1. NM_001244937.1.
NP_002438.2. NM_002447.2.

UniGene

Hs.517973.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3PLS	X-ray	2.24	A	1060-1357	[»]
4FWW	X-ray	1.85	A	42-568	[»]

ProteinModelPortal

Q04912.

SMR

Q04912. Positions 42-769, 1060-1377.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-6029N.

IntAct

Q04912. 5 interactions.

MINT

MINT-6539690.

STRING

9606.ENSP00000296474.

PTM databases

PhosphoSite

Q04912.

Polymorphism databases

DMDM

294862462.

Proteomic databases

PaxDb

Q04912.

PRIDE

Q04912.

Protocols and materials databases

DNASU

4486.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000296474; ENSP00000296474; ENSG00000164078.
ENST00000344206; ENSP00000341325; ENSG00000164078.

GeneID

4486.

KEGG

hsa:4486.

UCSC

uc003cxy.4. human.
uc011bdc.2. human.
uc011bdd.2. human.
uc011bde.1. human.
uc011bdf.1. human.
uc011bdg.2. human.

Organism-specific databases

CTD

4486.

GeneCards

GC03M049924.

HGNC

HGNC:7381. MST1R.

HPA

CAB008972.
HPA007657.
HPA008180.

MIM

600168. gene.

neXtProt

NX_Q04912.

PharmGKB

PA31186.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

HOGENOM

HOG000220900.

HOVERGEN

HBG104342.

InParanoid

Q04912.

KO

K05100.

OMA

EQKFVHR.

OrthoDB

EOG4M65GR.

PhylomeDB

Q04912.

Enzyme and pathway databases

BRENDA

2.7.10.1. 2681.

Pathway_Interaction_DB

a6b1_a6b4_integrin_pathway. a6b1 and a6b4 Integrin signaling.
amb2_neutrophils_pathway. amb2 Integrin signaling.

Gene expression databases

Bgee

Q04912.

CleanEx

HS_MST1R.

Genevestigator

Q04912.

GermOnline

ENSG00000164078. Homo sapiens.

Family and domain databases

Gene3D

2.130.10.10. 1 hit.
2.60.40.10. 4 hits.

InterPro

IPR013783. Ig-like_fold.
IPR014756. Ig_E-set.
IPR002909. IPT_TIG_rcpt.
IPR011009. Kinase-like_dom.
IPR003659. Plexin-like.
IPR016201. Plexin-like_fold.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001627. Semaphorin/CD100_Ag.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR016244. Tyr_kinase_HGF/MSP_rcpt.
IPR015943. WD40/YVTN_repeat-like_dom.
[Graphical view]

Pfam

PF07714. Pkinase_Tyr. 1 hit.
PF01403. Sema. 1 hit.
PF01833. TIG. 2 hits.
[Graphical view]

PIRSF

PIRSF000617. TyrPK_HGF-R. 1 hit.

PRINTS

PR00109. TYRKINASE.

SMART

SM00429. IPT. 3 hits.
SM00423. PSI. 1 hit.
SM00630. Sema. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]

SUPFAM

SSF81296. Ig_E-set. 3 hits.
SSF56112. Kinase_like. 1 hit.
SSF103575. Plexin-like_fold. 1 hit.
SSF101912. Sema. 1 hit.

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

BindingDB

Q04912.

ChEMBL

CHEMBL2689.

ChiTaRS

MST1R. human.

GenomeRNAi

4486.

NextBio

17355.

SOURCE

Search...

Entry information

Entry name

RON_HUMAN

Accession

Primary (citable) accession number: Q04912
Secondary accession number(s): B5A944 , B5A945, B5A946, B5A947

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1994
Last sequence update:	April 20, 2010
Last modified:	May 1, 2013
This is version 144 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.