Search by BoMiProt ID - Bomi6226


Primary Information

BoMiProt ID Bomi6226
Protein Name Hepatocyte growth factor receptor/HGF/SF receptor/Proto-oncogene c-Met/Scatter factor receptor/Tyrosine-protein kinase Met
Organism Bos taurus
Uniprot IdQ769I5
Milk FractionWhey
Ref Sequence Id NP_001013017.2
Aminoacid Length 1384
Molecular Weight 154814
Fasta Sequence https://www.uniprot.org/uniprot/Q769I5.fasta
Gene Name MET
Gene Id 280855
Protein Existence Status reviewed

Secondary Information

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).
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.
Significance in milk role in development of bovine mammary gland.
PTMs Disulfide bond formation, N-Linked Glycosylation at Asn, Phosphorylation at Ser/Thr, Ubl conjugation,Ubiquitination
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
Predicted Disorder Regions 1371-1379
DisProt Annotation
TM Helix Prediction 1TMH; (934-956)
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.
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.
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.