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Q108U6

- MET_LOXAF

UniProt

Q108U6 - MET_LOXAF

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Protein

Hepatocyte growth factor receptor

Gene

MET

Organism
Loxodonta africana (African elephant)
Status
Reviewed - Annotation score: 5 out of 5- Protein inferred from homologyi

Functioni

Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand. Regulates many physiological processes including proliferation, scattering, morphogenesis and survival. Ligand binding at the cell surface induces autophosphorylation of MET on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with the PI3-kinase subunit PIK3R1, PLCG1, SRC, GRB2, STAT3 or the adapter GAB1. Recruitment of these downstream effectors by MET leads to the activation of several signaling cascades including the RAS-ERK, PI3 kinase-AKT, or PLCgamma-PKC. The RAS-ERK activation is associated with the morphogenetic effects while PI3K/AKT coordinates prosurvival effects. During embryonic development, MET signaling plays a role in gastrulation, development and migration of muscles and neuronal precursors, angiogenesis and kidney formation. In adults, participates in wound healing as well as organ regeneration and tissue remodeling. Promotes also differentiation and proliferation of hematopoietic cells (By similarity).By similarity

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation

Enzyme regulationi

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 (By similarity).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei308 – 3092CleavageSequence Analysis
Binding sitei1111 – 11111ATPPROSITE-ProRule annotation
Active sitei1205 – 12051Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi1085 – 10939ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. hepatocyte growth factor-activated receptor activity Source: Ensembl

GO - Biological processi

  1. activation of MAPK activity Source: Ensembl
  2. adult behavior Source: Ensembl
  3. brain development Source: Ensembl
  4. branching morphogenesis of an epithelial tube Source: Ensembl
  5. glucose homeostasis Source: Ensembl
  6. liver development Source: Ensembl
  7. muscle cell migration Source: Ensembl
  8. myoblast proliferation Source: Ensembl
  9. myotube differentiation Source: Ensembl
  10. negative regulation of hydrogen peroxide-mediated programmed cell death Source: Ensembl
  11. placenta development Source: Ensembl
  12. positive chemotaxis Source: UniProtKB
  13. positive regulation of endothelial cell chemotaxis Source: UniProtKB
  14. positive regulation of glucose transport Source: Ensembl
  15. positive regulation of transcription from RNA polymerase II promoter Source: Ensembl
  16. protein autophosphorylation Source: Ensembl
  17. regulation of branching involved in salivary gland morphogenesis by mesenchymal-epithelial signaling Source: Ensembl
  18. semaphorin-plexin signaling pathway Source: UniProtKB
  19. skeletal muscle tissue development Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Receptor, Transferase, Tyrosine-protein kinase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Hepatocyte growth factor receptor (EC:2.7.10.1)
Short name:
HGF receptor
Alternative name(s):
HGF/SF receptor
Proto-oncogene c-Met
Scatter factor receptor
Short name:
SF receptor
Tyrosine-protein kinase Met
Gene namesi
Name:MET
OrganismiLoxodonta africana (African elephant)
Taxonomic identifieri9785 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaAfrotheriaProboscideaElephantidaeLoxodonta
ProteomesiUP000007646: Unplaced

Subcellular locationi

Membrane By similarity; Single-pass type I membrane protein By similarity

GO - Cellular componenti

  1. basal plasma membrane Source: Ensembl
  2. integral component of membrane Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Keywords - Diseasei

Proto-oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2424Sequence AnalysisAdd
BLAST
Chaini25 – 13821358Hepatocyte growth factor receptorPRO_0000250465Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi45 – 451N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi95 ↔ 101PROSITE-ProRule annotation
Disulfide bondi98 ↔ 160PROSITE-ProRule annotation
Glycosylationi106 – 1061N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi133 ↔ 141PROSITE-ProRule annotation
Disulfide bondi173 ↔ 176PROSITE-ProRule annotation
Glycosylationi203 – 2031N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi299 ↔ 364PROSITE-ProRule annotation
Glycosylationi359 – 3591N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi386 ↔ 398PROSITE-ProRule annotation
Glycosylationi400 – 4001N-linked (GlcNAc...)Sequence Analysis
Glycosylationi406 – 4061N-linked (GlcNAc...)Sequence Analysis
Glycosylationi450 – 4501N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi521 ↔ 539PROSITE-ProRule annotation
Disulfide bondi527 ↔ 562PROSITE-ProRule annotation
Disulfide bondi530 ↔ 546PROSITE-ProRule annotation
Disulfide bondi542 ↔ 552PROSITE-ProRule annotation
Glycosylationi608 – 6081N-linked (GlcNAc...)Sequence Analysis
Glycosylationi636 – 6361N-linked (GlcNAc...)Sequence Analysis
Glycosylationi751 – 7511N-linked (GlcNAc...)Sequence Analysis
Glycosylationi786 – 7861N-linked (GlcNAc...)Sequence Analysis
Glycosylationi880 – 8801N-linked (GlcNAc...)Sequence Analysis
Glycosylationi931 – 9311N-linked (GlcNAc...)Sequence Analysis
Modified residuei978 – 9781PhosphothreonineBy similarity
Modified residuei991 – 9911PhosphoserineBy similarity
Modified residuei998 – 9981PhosphoserineBy similarity
Modified residuei1001 – 10011PhosphoserineBy similarity
Modified residuei1004 – 10041PhosphotyrosineBy similarity
Modified residuei1231 – 12311PhosphotyrosineBy similarity
Modified residuei1235 – 12351Phosphotyrosine; by autocatalysisBy similarity
Modified residuei1236 – 12361Phosphotyrosine; by autocatalysisBy similarity
Modified residuei1290 – 12901PhosphothreonineBy similarity
Modified residuei1350 – 13501Phosphotyrosine; by autocatalysisBy similarity
Modified residuei1357 – 13571Phosphotyrosine; by autocatalysisBy similarity
Modified residuei1366 – 13661PhosphotyrosineBy similarity

Post-translational modificationi

Autophosphorylated in response to ligand binding on Tyr-1235 and Tyr-1236 in the kinase domain leading to further phosphorylation of Tyr-1350 and Tyr-1357 in the C-terminal multifunctional docking site. Dephosphorylated by PTPRJ at Tyr-1350 and Tyr-1366. Dephosphorylated by PTPN1 and PTPN2 (By similarity).By similarity
Ubiquitinated. Ubiquitination by CBL regulates the receptor stability and activity through proteasomal degradation (By similarity).By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

Interactioni

Subunit structurei

Heterodimer made of an alpha chain (50 kDa) and a beta chain (145 kDa) which are disulfide linked. Binds PLXNB1. Interacts when phosphorylated with downstream effectors including STAT3, PIK3R1, SRC, PCLG1, GRB2 and GAB1. Interacts with SPSB1, SPSB2 and SPSB4. Interacts with INPP5D/SHIP1. When phosphorylated at Tyr-1357, interacts with INPPL1/SHIP2. Interacts with RANBP9 and RANBP10, as well as SPSB1, SPSB2, SPSB3 and SPSB4. SPSB1 binding occurs in the presence and in the absence of HGF, however HGF treatment has a positive effect on this interaction. Interacts with MUC20; prevents interaction with GRB2 and suppresses hepatocyte growth factor-induced cell proliferation. Interacts with GRB10 (By similarity). Interacts with PTPN1 and PTPN2 (By similarity).By similarity

Structurei

3D structure databases

ProteinModelPortaliQ108U6.
SMRiQ108U6. Positions 40-742, 1047-1347.
ModBaseiSearch...
MobiDBiSearch...

Topological domain

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini25 – 935911ExtracellularSequence AnalysisAdd
BLAST
Topological domaini957 – 1382426CytoplasmicSequence AnalysisAdd
BLAST

Transmembrane

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei936 – 95621HelicalSequence AnalysisAdd
BLAST

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini27 – 516490SemaPROSITE-ProRule annotationAdd
BLAST
Domaini564 – 65693IPT/TIG 1Add
BLAST
Domaini658 – 74083IPT/TIG 2Add
BLAST
Domaini743 – 83795IPT/TIG 3Add
BLAST
Domaini1079 – 1346268Protein kinasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1213 – 1382170Interaction with RANBP9By similarityAdd
BLAST
Regioni1321 – 136040Interaction with MUC20By similarityAdd
BLAST

Domaini

The kinase domain is involved in SPSB1 binding.By similarity
The beta-propeller Sema domain mediates binding to HGF.By similarity

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family.PROSITE-ProRule annotation
Contains 3 IPT/TIG domains.Curated
Contains 1 protein kinase domain.PROSITE-ProRule annotation
Contains 1 Sema domain.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

HOGENOMiHOG000220900.
HOVERGENiHBG006348.
InParanoidiQ108U6.

Family and domain databases

Gene3Di2.130.10.10. 1 hit.
2.60.40.10. 3 hits.
InterProiIPR013783. Ig-like_fold.
IPR014756. Ig_E-set.
IPR002909. IPT.
IPR011009. Kinase-like_dom.
IPR016201. Plexin-like_fold.
IPR002165. Plexin_repeat.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001627. Semap_dom.
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]
PfamiPF07714. Pkinase_Tyr. 1 hit.
PF01437. PSI. 1 hit.
PF01403. Sema. 1 hit.
PF01833. TIG. 3 hits.
[Graphical view]
PIRSFiPIRSF000617. TyrPK_HGF-R. 1 hit.
PRINTSiPR00109. TYRKINASE.
SMARTiSM00429. IPT. 4 hits.
SM00423. PSI. 1 hit.
SM00630. Sema. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF101912. SSF101912. 1 hit.
SSF103575. SSF103575. 1 hit.
SSF56112. SSF56112. 1 hit.
SSF81296. SSF81296. 3 hits.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS51004. SEMA. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

Q108U6-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MKAPAVLAPG VLVLLFTLVR KSHGECEEAL AKSKMNVNMK YQLPNFTADT
60 70 80 90 100
PIQNVVLHEH HIFLGAINNI YVLNDKDLQK VAEYKTGPVL EHPDCLPCQD
110 120 130 140 150
CSSKANLSGS VWKDNINMAL LVDTYYDDQL ITCGSVNRGT CQRHVLPPDN
160 170 180 190 200
PADIHSKVHC MYSPQADEEP SKCPDCVVSA LGTKVLLTEK DRFINFFVGN
210 220 230 240 250
TVNSSYLPDH SLHSISVRRL KETQDGFKFL TDQSYIDVLP EFRDSYPIKY
260 270 280 290 300
VHAFKHNQFI YFLTVQRETL ESQTFHTRII RFCSVDSGLH SYMEMPLECI
310 320 330 340 350
LTEKRRKRSA REEVFNILQA AYVSKPGAYL AKQIGALPDD DILYGVFAQS
360 370 380 390 400
KLDSAEPMNR SAVCAFPIKY VNDFFNKIVN KNNVRCLQHF YGPNHEHCFN
410 420 430 440 450
RTLLRNSSGC EVRRDEYRTE FTTALQRVDL FTGQFNQVLL TSISTFIKGN
460 470 480 490 500
LTIANLGTSE GRFMQVVVSR SGLTTPHVNF RLDSHAVSPE VILEHPLNQN
510 520 530 540 550
GYTLVITGKK ITKIPLDGLG CDHFQSCSQC LSAPSFVQCG WCHNKCARAE
560 570 580 590 600
ECPNGMWTQE ICLPTIYEVF PTSAPLEGGT TLTVCGWDFG FRRNNKFDLK
610 620 630 640 650
KTRVLIGNDS CTLTLSESTT NTLKCTVGPA MNKHFNLSII ISNGRGTARY
660 670 680 690 700
RTFSYVEPVI TSISPSYGPK AGGTLVTLTG KYLNSGNSRH ISIGGKTCTL
710 720 730 740 750
KSVSDSVLEC YTPAQSISTD FPVKLKIDLA NREAYSFSYQ EDPTVYEIHP
760 770 780 790 800
NKSFISGGST ITGIGKNLNS VSVPRMVINV QEAGRNFTVA CQHRSNSEII
810 820 830 840 850
CCTTPSLQQL NLQLPLKTKA FFMLDGIHSN YFDLIYVHNP VFKPFKKPVM
860 870 880 890 900
ISMGNENVLE IKGDYIDPEA VKGEVLKVGN KSCENIHLQS EAVLCTVPND
910 920 930 940 950
LLKLNSELNI EWKQAVSSTV LGKVIVQPDQ NFTGLIVGVV SISIILLLLL
960 970 980 990 1000
GLFLWLKKRK QIKDLGSELV RYDARVHTPH LDRLVSARSV SPTTEMVSNE
1010 1020 1030 1040 1050
SVDYRATFPE DQFPNSSQNG SCRQVQYPLT DMSPILTNGD SDSSIPLLQN
1060 1070 1080 1090 1100
NVHIDLSALN PELVQAVQHV VIGPSSLIVH FNEVIGRGHF GCVYHGTLLD
1110 1120 1130 1140 1150
NGDKKIHCAV KSLNRITDIG EVSQFLTEGI IMKDFSHPNV LSLLGICLRS
1160 1170 1180 1190 1200
EGSPLVVLPY MKHGDLRNFI RNETHNPTVK DLIGFGLQVA KGMKYLASKK
1210 1220 1230 1240 1250
FVHRDLAARN CMLDEKFTVK VADFGLARDV YDKEYYSVHN KTGAKLPVKW
1260 1270 1280 1290 1300
MALESLQTQK FTTKSDVWSF GVLLWELMTR GAPPYPDVNT FDITVYLLQG
1310 1320 1330 1340 1350
RRLLQPEYCP DPLYEVMLKC WHPKAEMRPS FSELVSRISA IFSTFIGEHY
1360 1370 1380
VHVNTTYVNV KCVAPYPSLL SSQDSVDDEV DT
Length:1,382
Mass (Da):154,684
Last modified:August 22, 2006 - v1
Checksum:iB22F334F1CC126BC
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
DP000087 Genomic DNA. Translation: ABG66646.1.
RefSeqiXP_003407277.1. XM_003407229.1.

Genome annotation databases

GeneIDi100656285.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
DP000087 Genomic DNA. Translation: ABG66646.1 .
RefSeqi XP_003407277.1. XM_003407229.1.

3D structure databases

ProteinModelPortali Q108U6.
SMRi Q108U6. Positions 40-742, 1047-1347.
ModBasei Search...
MobiDBi Search...

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 100656285.

Phylogenomic databases

HOGENOMi HOG000220900.
HOVERGENi HBG006348.
InParanoidi Q108U6.

Family and domain databases

Gene3Di 2.130.10.10. 1 hit.
2.60.40.10. 3 hits.
InterProi IPR013783. Ig-like_fold.
IPR014756. Ig_E-set.
IPR002909. IPT.
IPR011009. Kinase-like_dom.
IPR016201. Plexin-like_fold.
IPR002165. Plexin_repeat.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001627. Semap_dom.
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 ]
Pfami PF07714. Pkinase_Tyr. 1 hit.
PF01437. PSI. 1 hit.
PF01403. Sema. 1 hit.
PF01833. TIG. 3 hits.
[Graphical view ]
PIRSFi PIRSF000617. TyrPK_HGF-R. 1 hit.
PRINTSi PR00109. TYRKINASE.
SMARTi SM00429. IPT. 4 hits.
SM00423. PSI. 1 hit.
SM00630. Sema. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view ]
SUPFAMi SSF101912. SSF101912. 1 hit.
SSF103575. SSF103575. 1 hit.
SSF56112. SSF56112. 1 hit.
SSF81296. SSF81296. 3 hits.
PROSITEi PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS51004. SEMA. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  1. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].

Entry informationi

Entry nameiMET_LOXAF
AccessioniPrimary (citable) accession number: Q108U6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 3, 2006
Last sequence update: August 22, 2006
Last modified: October 29, 2014
This is version 69 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3