HGF_CANLF
ID HGF_CANLF Reviewed; 730 AA.
AC Q867B7;
DT 06-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 115.
DE RecName: Full=Hepatocyte growth factor;
DE AltName: Full=Hepatopoietin-A;
DE AltName: Full=Scatter factor;
DE Short=SF;
DE Contains:
DE RecName: Full=Hepatocyte growth factor alpha chain;
DE Contains:
DE RecName: Full=Hepatocyte growth factor beta chain;
DE Flags: Precursor;
GN Name=HGF;
OS Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Beagle;
RX PubMed=12963274; DOI=10.1016/s0165-2427(03)00118-1;
RA Miyake M., Saze K., Yaguchi T., Wang J., Suzuta Y., Haga Y.,
RA Takahashi S.Y., Yamamoto Y., Iwabuchi S.;
RT "Canine hepatocyte growth factor: molecular cloning and characterization of
RT the recombinant protein.";
RL Vet. Immunol. Immunopathol. 95:135-143(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Liao A.T., Chien M.B., London C.A.;
RT "Characterization of the receptor tyrosine kinase Met and its autocrine
RT loop in canine osteosarcoma cell lines.";
RL Submitted (FEB-2004) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Potent mitogen for mature parenchymal hepatocyte cells, seems
CC to be a hepatotrophic factor, and acts as a growth factor for a broad
CC spectrum of tissues and cell types. Activating ligand for the receptor
CC tyrosine kinase MET by binding to it and promoting its dimerization (By
CC similarity). {ECO:0000250}.
CC -!- SUBUNIT: Dimer of an alpha chain and a beta chain linked by a disulfide
CC bond. Interacts with SRPX2; the interaction increases HGF mitogenic
CC activity (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. Plasminogen subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU00274}.
CC -!- CAUTION: Has lost two of the three essential catalytic residues and so
CC probably has no enzymatic activity. {ECO:0000305}.
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DR EMBL; AB090353; BAC57560.1; -; mRNA.
DR EMBL; AY543632; AAS48570.1; -; mRNA.
DR RefSeq; NP_001002964.1; NM_001002964.1.
DR AlphaFoldDB; Q867B7; -.
DR SMR; Q867B7; -.
DR STRING; 9615.ENSCAFP00000009539; -.
DR MEROPS; S01.976; -.
DR PaxDb; Q867B7; -.
DR PRIDE; Q867B7; -.
DR Ensembl; ENSCAFT00030017776; ENSCAFP00030015521; ENSCAFG00030009302.
DR Ensembl; ENSCAFT00040036906; ENSCAFP00040032140; ENSCAFG00040019820.
DR Ensembl; ENSCAFT00845046191; ENSCAFP00845036270; ENSCAFG00845025968.
DR GeneID; 403441; -.
DR KEGG; cfa:403441; -.
DR CTD; 3082; -.
DR VEuPathDB; HostDB:ENSCAFG00845025968; -.
DR eggNOG; ENOG502QR40; Eukaryota.
DR GeneTree; ENSGT00940000156019; -.
DR HOGENOM; CLU_017565_1_0_1; -.
DR InParanoid; Q867B7; -.
DR OMA; CNIKVCE; -.
DR OrthoDB; 164039at2759; -.
DR TreeFam; TF329901; -.
DR Reactome; R-CFA-114608; Platelet degranulation.
DR Reactome; R-CFA-1257604; PIP3 activates AKT signaling.
DR Reactome; R-CFA-5673001; RAF/MAP kinase cascade.
DR Reactome; R-CFA-6806942; MET Receptor Activation.
DR Reactome; R-CFA-6807004; Negative regulation of MET activity.
DR Reactome; R-CFA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR Reactome; R-CFA-8851805; MET activates RAS signaling.
DR Reactome; R-CFA-8851907; MET activates PI3K/AKT signaling.
DR Reactome; R-CFA-8865999; MET activates PTPN11.
DR Reactome; R-CFA-8874081; MET activates PTK2 signaling.
DR Reactome; R-CFA-8875555; MET activates RAP1 and RAC1.
DR Reactome; R-CFA-8875656; MET receptor recycling.
DR Proteomes; UP000002254; Chromosome 18.
DR Bgee; ENSCAFG00000006370; Expressed in metanephros cortex and 42 other tissues.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0042056; F:chemoattractant activity; IEA:Ensembl.
DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR GO; GO:0060326; P:cell chemotaxis; IEA:Ensembl.
DR GO; GO:0000902; P:cell morphogenesis; IEA:Ensembl.
DR GO; GO:0035729; P:cellular response to hepatocyte growth factor stimulus; IEA:Ensembl.
DR GO; GO:0050673; P:epithelial cell proliferation; IEA:Ensembl.
DR GO; GO:0048012; P:hepatocyte growth factor receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0001889; P:liver development; IEA:Ensembl.
DR GO; GO:0051450; P:myoblast proliferation; IEA:Ensembl.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IBA:GO_Central.
DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; IEA:Ensembl.
DR GO; GO:1902042; P:negative regulation of extrinsic apoptotic signaling pathway via death domain receptors; IEA:Ensembl.
DR GO; GO:1901299; P:negative regulation of hydrogen peroxide-mediated programmed cell death; IEA:Ensembl.
DR GO; GO:0050728; P:negative regulation of inflammatory response; IEA:Ensembl.
DR GO; GO:0032715; P:negative regulation of interleukin-6 production; IEA:Ensembl.
DR GO; GO:0033137; P:negative regulation of peptidyl-serine phosphorylation; IEA:Ensembl.
DR GO; GO:0090201; P:negative regulation of release of cytochrome c from mitochondria; IEA:Ensembl.
DR GO; GO:0030335; P:positive regulation of cell migration; IEA:Ensembl.
DR GO; GO:2000573; P:positive regulation of DNA biosynthetic process; IEA:Ensembl.
DR GO; GO:0032733; P:positive regulation of interleukin-10 production; IEA:Ensembl.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IEA:Ensembl.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IEA:Ensembl.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; IEA:Ensembl.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IBA:GO_Central.
DR GO; GO:0006508; P:proteolysis; IEA:InterPro.
DR GO; GO:0060665; P:regulation of branching involved in salivary gland morphogenesis by mesenchymal-epithelial signaling; IEA:Ensembl.
DR GO; GO:1900744; P:regulation of p38MAPK cascade; IEA:Ensembl.
DR GO; GO:1902947; P:regulation of tau-protein kinase activity; IEA:Ensembl.
DR GO; GO:0014856; P:skeletal muscle cell proliferation; IEA:Ensembl.
DR CDD; cd00108; KR; 4.
DR CDD; cd00190; Tryp_SPc; 1.
DR Gene3D; 2.40.10.10; -; 2.
DR Gene3D; 2.40.20.10; -; 4.
DR InterPro; IPR027284; Hepatocyte_GF.
DR InterPro; IPR024174; HGF/MST1.
DR InterPro; IPR000001; Kringle.
DR InterPro; IPR013806; Kringle-like.
DR InterPro; IPR018056; Kringle_CS.
DR InterPro; IPR038178; Kringle_sf.
DR InterPro; IPR003609; Pan_app.
DR InterPro; IPR009003; Peptidase_S1_PA.
DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR InterPro; IPR001314; Peptidase_S1A.
DR InterPro; IPR001254; Trypsin_dom.
DR Pfam; PF00051; Kringle; 4.
DR Pfam; PF00024; PAN_1; 1.
DR Pfam; PF00089; Trypsin; 1.
DR PIRSF; PIRSF500183; Hepatocyte_GF; 1.
DR PIRSF; PIRSF001152; HGF_MST1; 1.
DR PRINTS; PR00722; CHYMOTRYPSIN.
DR SMART; SM00130; KR; 4.
DR SMART; SM00473; PAN_AP; 1.
DR SMART; SM00020; Tryp_SPc; 1.
DR SUPFAM; SSF50494; SSF50494; 1.
DR SUPFAM; SSF57440; SSF57440; 4.
DR PROSITE; PS00021; KRINGLE_1; 4.
DR PROSITE; PS50070; KRINGLE_2; 4.
DR PROSITE; PS50948; PAN; 1.
DR PROSITE; PS50240; TRYPSIN_DOM; 1.
PE 2: Evidence at transcript level;
KW Disulfide bond; Glycoprotein; Growth factor; Kringle;
KW Pyrrolidone carboxylic acid; Reference proteome; Repeat;
KW Serine protease homolog; Signal.
FT SIGNAL 1..31
FT /evidence="ECO:0000250"
FT CHAIN 32..494
FT /note="Hepatocyte growth factor alpha chain"
FT /id="PRO_0000274199"
FT CHAIN 495..730
FT /note="Hepatocyte growth factor beta chain"
FT /id="PRO_0000274200"
FT DOMAIN 37..123
FT /note="PAN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00315"
FT DOMAIN 128..206
FT /note="Kringle 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DOMAIN 211..288
FT /note="Kringle 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DOMAIN 305..383
FT /note="Kringle 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DOMAIN 391..469
FT /note="Kringle 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DOMAIN 495..723
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT MOD_RES 32
FT /note="Pyrrolidone carboxylic acid"
FT /evidence="ECO:0000250|UniProtKB:P14210"
FT CARBOHYD 294
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 402
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 568
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 655
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 70..96
FT /evidence="ECO:0000250"
FT DISULFID 74..84
FT /evidence="ECO:0000250"
FT DISULFID 128..206
FT /evidence="ECO:0000250"
FT DISULFID 149..189
FT /evidence="ECO:0000250"
FT DISULFID 177..201
FT /evidence="ECO:0000250"
FT DISULFID 211..288
FT /evidence="ECO:0000250"
FT DISULFID 232..271
FT /evidence="ECO:0000250"
FT DISULFID 260..283
FT /evidence="ECO:0000250"
FT DISULFID 305..383
FT /evidence="ECO:0000250"
FT DISULFID 326..365
FT /evidence="ECO:0000250"
FT DISULFID 354..377
FT /evidence="ECO:0000250"
FT DISULFID 391..469
FT /evidence="ECO:0000250"
FT DISULFID 412..452
FT /evidence="ECO:0000250"
FT DISULFID 440..464
FT /evidence="ECO:0000250"
FT DISULFID 487..606
FT /note="Interchain (between alpha and beta chains)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121,
FT ECO:0000255|PROSITE-ProRule:PRU00274, ECO:0000255|PROSITE-
FT ProRule:PRU00315"
FT DISULFID 519..535
FT /evidence="ECO:0000250"
FT DISULFID 614..681
FT /evidence="ECO:0000250"
FT DISULFID 644..660
FT /evidence="ECO:0000250"
FT DISULFID 671..699
FT /evidence="ECO:0000250"
SQ SEQUENCE 730 AA; 83398 MW; 4E83F9EA8BFF6DB1 CRC64;
MWVTKLLPLL VLQQLLLHLL LLPVAVPRAE GQKKRRNTLH EFKKSAKTTL IKEDPLLKIK
TKKMNTADQC ANRCIRNKGL PFTCKAFVFD KARKRCLWFP FNSMTSGVKK EFGHEFDLYE
NKDYIRNCII GKGGSYKGTV SITKSGIKCQ PWNSMIPHEH SFLPSSYRGK DLQENYCRNP
RGEEGGPWCF TSNPEVRYEV CDIPQCSEVE CMTCNGESYR GPMDHTESGK ICQRWDHQTP
HRHKFLPERY PDKGFDDNYC RNPDGKPRPW CYTLDPDTPW EYCAIKMCAH STMNDTDVPM
ETTECIQGQG EGYRGTINTI WNGVPCQRWD SQYPHQHDIT PENFKCKDLR ENYCRNPDGA
ESPWCFTTDP NIRVGYCSQI PKCDVSSGQD CYRGNGKNYM GNLSKTRSGL TCSMWEKNME
DLHRHIFWEP DASKLNKNYC RNPDDDAHGP WCYTGNPLIP WDYCPIFRCE GDTTPTIVNL
DHPVISCAKT KQLRVVNGIP TRTNVGWMVS LKYRNKHICG GSLIKESWIL TARQCFPSRN
RDLKDYEAWL GIHDVHGKGD EKRKQVLNVS QLVYGPEGSD LVLLKLARPA ILDDFVSTID
LPNYGCTIPE KTTCSVYGWG YTGSINFDGL LRVAHLYIMG NEKCSQYHQG KVTLNESEIC
AGAENIVSGP CEGDYGGPLV CEQHKMRMVL GVIVPGRGCA IPNRPGIFVR VAYYAKWIHK
IILTYKIQQS
