Primary Information |
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| BoMiProt ID | Bomi6226 |
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| Protein Name | Hepatocyte growth factor receptor/HGF/SF receptor/Proto-oncogene c-Met/Scatter factor receptor/Tyrosine-protein kinase Met |
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| Organism | Bos taurus |
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| Uniprot ID | Q769I5 |
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| Milk Fraction | Whey |
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| Ref Sequence ID | NP_001013017.2 |
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| Aminoacid Length | 1384 |
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| Molecular Weight | 154814 |
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| FASTA Sequence |
Download |
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| Gene Name | MET |
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| Gene ID | 280855 |
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| Protein Existence Status | reviewed |
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Secondary Information |
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| Protein Function | C-Met plays a role in regulating a cell fate program during embryonic development, wound healing, and in tumor invasion known as epithelial-mesenchymal transition (EMT). |
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| Biochemical Properties | . Met shares similar structural features with the receptor for MST1 (MST1R; also known as Ron/CD136 or as STK in mice). The mature form of Met comprises the extracellular 50 kDa α-chain and the transmembrane-passing 145 kDa β-chain. The so-called Sema domain constituted by the α-chain and the amino-terminal end of the β-chain is required for HGF binding and activation of Met signaling. |
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| Significance in milk | role in development of bovine mammary gland. |
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| PTMs | Disulfide bond formation, N-Linked Glycosylation at Asn, Phosphorylation at Ser/Thr, Ubl conjugation,Ubiquitination |
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Site(s) of PTM(s)
N-glycosylation,
O-glycosylation,
Phosphorylation
| >sp|Q769I5|MET_BOVIN Hepatocyte growth factor receptor OS=Bos taurus OX=9913 GN=MET PE=2 SV=1
MKAPAVLAPGILVLLFTFVQKSNGECKEALVKSRMNVNMQYQLPN*45FTAETSIQNVVLHKH
HIYLGAINYIYVLNDKDLQKVAEYKTGPVLEHPDCFPCQDCSHKAN*106LSGGVWKDNINMAL
LVDTYYDDQLISCGSVHRGTCQRHVLPPN*149NTADIESEVHCMYSPQADEETNQCPDCVVSA
LGTKVLLSEKDRFINFFVGNTIN*203SSYLPDYILHSISVRRLKETQDGFKFLTDQSYIDVLP
ELRDSYPIKYVHAFESNHFIYFLTVQRETLDAQTFHTRIIRFCSADSGLHSYMEMPLECI
LTEKRRKRSTKQEVFNILQAAYVSKPGAQLARQIGASLNDDILYGVFAQSKPDSSEPMN*359R
SAVCAFPVKYVNEFFNKIVNKNNVRCLQHFYGPNHEHCFN*400RTLLRN*406SSGCEVRNDEYRTE
FTTALPRVDLFTGQFNQVLLTSISTFIKGDLTIANLGTSEGRFMQVVVSRSGSLTPHVNF
HLDSHPVSPEVIVEHPLNQNGYTLVVTGKKITKIPLNGLGCEHFQSCSQCLSAPSFVQCG
WCHDKCVRLEECSSGTWTQETCLPTIYKVFPTSAPLEGGTTLTVCGWDFGFKRNNKFDLK
KTRVLLGN*608ESCTLTLTESTTNMLKCTVGPAMNEHFN*636MSIVISNSRGSVEYSAFSYVDPII
TSISPNYGPKTGGTLLTLTGKHLNSGNSRHISIGGKTCTLKSVSHSILECYTPAQSAPTE
FSVKLKIDLANREVNSFIYREDPIVYEIHPTKSFISGGSTITGVGKNLNSVSVLRMVINV
HEAGRN*786FTVACQHRSNSEIICCTTPSIEQLNLQLPLKTKAFFMLDGIHSKYFDLIYVHNP
VFKPFEKPVMISVGNENVLEIKGNDIDPEAVKGEVLKVGN*880KSCENIHSHSEAVLCTVPSD
LLKLNSELNIEWKQAISSTVLGKVIVQPDQN*931FTGLIVGVVSISIILLLLLGLFLWLKKRK
QIKDLGS*967ELVRYDARVHT*978PHLDRLVSARSVS*991PTTEMVS*998NES*1001VDY*1004RATFPEDQFPNASQNGSCRQVQYPLTDLSPILTSGDSDISSPLLQNTIHIDLSALNPELVQAVQHVVIGPSSLIVH
FNEVIGRGHFGCVYHGTLLDNDDKKIHCAVKSLNRITDIGEVSQFLTEGIIMKDFSHPNV
LSLLGICLRSEGSPLVVLPYMKHGDLRNFIRNETHNPTVKDLIGFGLQVAKGMEYLASKK
FVHRDLAARNCMLDEKFTVKVADFGLARDVY*1231DKEY*1235Y*1236SVHNKTGAKLPVKWMALESLQTQK
FTTKSDVWSFGVLLWELMTRGAPPYPDVNT*1290FDITVYLLQGRRLLQPEYCPDPLYEVMLKC
WHPKAELRPSFSELVSRISVIFSTFIGEHY*1350VHVNATY*1357VNVKCVAPY*1366PSLLSSQDNVSGED
DDDT |
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| Predicted Disorder Regions | 1371-1379 |
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| DisProt Annotation | |
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| TM Helix Prediction | 1TMH; (934-956) |
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| Significance of PTMs | 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.Ubiquitination by CBL regulates the receptor stability and activity through proteasomal degradation. |
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| Additional Comments | Met signaling in skin resident DCs(dendritic cell) including LCs(Langerhans cells) appears to be a critical determinant for maintaining normal immune function and as an important constituent that interlaces tissue regenerative functions with the appropriate immune responses that must be accomplished after tissue injury, infection, or inflammation. |
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| Bibliography | 1.Sagi Z, Hieronymus T. The Impact of the Epithelial-Mesenchymal Transition Regulator Hepatocyte Growth Factor Receptor/Met on Skin Immunity by Modulating Langerhans Cell Migration. Front Immunol. 2018 Mar 16;9:517. doi: 10.3389/fimmu.2018.00517. PMID: 29616031; PMCID: PMC5864859. 2.Manning G, Whyte DB, Martinez R, Hunter T, Sudarsanam S. The protein
kinase complement of the human genome. Science (2002) 298(5600):1912–34.
doi:10.1126/science.1075762. 3.. Hieronymus T, Zenke M, Baek JH, Sere K. The clash of Langerhans cell homeostasis in skin: should I stay or should I go? Semin Cell Dev Biol (2015) 41:30–8. doi:10.1016/j.semcdb.2014.02.009. 4.Gherardi E, Youles ME, Miguel RN, Blundell TL, Iamele L, Gough J, et al. Functional map and domain structure of MET, the product of the c-met protooncogene and receptor for hepatocyte growth factor/scatter factor. Proc Natl Acad Sci U S A (2003) 100(21):12039–44. doi:10.1073/pnas.2034936100. 4.Yamaji D, Kimura K, Watanabe A, Kon Y, Iwanaga T, Soliman MM, Ahmed MM, Saito M. Bovine hepatocyte growth factor and its receptor c-Met: cDNA cloning and expression analysis in the mammary gland. Domest Anim Endocrinol. 2006 Mar;30(3):239-46. doi: 10.1016/j.domaniend.2005.08.005. Epub 2005 Sep 21. PMID: 16207523. |
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