HGF_RAT
ID HGF_RAT Reviewed; 728 AA.
AC P17945;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1990, sequence version 1.
DT 03-AUG-2022, entry version 177.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RC STRAIN=Wistar; TISSUE=Liver;
RX PubMed=2139229; DOI=10.1073/pnas.87.8.3200;
RA Toshiro K., Hagiya M., Nishizawa T., Seki T., Shimonishi M., Shimizu S.,
RA Nakamura T.;
RT "Deduced primary structure of rat hepatocyte growth factor and expression
RT of the mRNA in rat tissues.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:3200-3204(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Wistar; TISSUE=Liver;
RX PubMed=2146117; DOI=10.1111/j.1432-1033.1990.tb19349.x;
RA Okajima A., Miyazawa K., Kitamura N.;
RT "Primary structure of rat hepatocyte growth factor and induction of its
RT mRNA during liver regeneration following hepatic injury.";
RL Eur. J. Biochem. 193:375-381(1990).
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.
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; D90102; BAA14133.1; -; mRNA.
DR EMBL; X54400; CAA38266.1; -; mRNA.
DR PIR; A35644; A35644.
DR RefSeq; NP_058713.1; NM_017017.2.
DR AlphaFoldDB; P17945; -.
DR SMR; P17945; -.
DR BioGRID; 246610; 2.
DR MINT; P17945; -.
DR STRING; 10116.ENSRNOP00000009764; -.
DR MEROPS; S01.978; -.
DR GlyGen; P17945; 4 sites.
DR PaxDb; P17945; -.
DR PRIDE; P17945; -.
DR GeneID; 24446; -.
DR KEGG; rno:24446; -.
DR CTD; 3082; -.
DR RGD; 2794; Hgf.
DR VEuPathDB; HostDB:ENSRNOG00000007027; -.
DR eggNOG; ENOG502QR40; Eukaryota.
DR HOGENOM; CLU_017565_1_0_1; -.
DR InParanoid; P17945; -.
DR OMA; CNIKVCE; -.
DR OrthoDB; 164039at2759; -.
DR PhylomeDB; P17945; -.
DR TreeFam; TF329901; -.
DR Reactome; R-RNO-114608; Platelet degranulation.
DR Reactome; R-RNO-1257604; PIP3 activates AKT signaling.
DR Reactome; R-RNO-5673001; RAF/MAP kinase cascade.
DR Reactome; R-RNO-6806942; MET Receptor Activation.
DR Reactome; R-RNO-6807004; Negative regulation of MET activity.
DR Reactome; R-RNO-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR Reactome; R-RNO-8851805; MET activates RAS signaling.
DR Reactome; R-RNO-8851907; MET activates PI3K/AKT signaling.
DR Reactome; R-RNO-8865999; MET activates PTPN11.
DR Reactome; R-RNO-8874081; MET activates PTK2 signaling.
DR Reactome; R-RNO-8875513; MET interacts with TNS proteins.
DR Reactome; R-RNO-8875555; MET activates RAP1 and RAC1.
DR Reactome; R-RNO-8875656; MET receptor recycling.
DR Reactome; R-RNO-8875791; MET activates STAT3.
DR Reactome; R-RNO-9734091; Drug-mediated inhibition of MET activation.
DR PRO; PR:P17945; -.
DR Proteomes; UP000002494; Chromosome 4.
DR Bgee; ENSRNOG00000007027; Expressed in liver and 16 other tissues.
DR Genevisible; P17945; RN.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0042056; F:chemoattractant activity; ISO:RGD.
DR GO; GO:0008083; F:growth factor activity; IMP:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:RGD.
DR GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR GO; GO:0031100; P:animal organ regeneration; IEP:RGD.
DR GO; GO:0060326; P:cell chemotaxis; ISO:RGD.
DR GO; GO:0000902; P:cell morphogenesis; ISO:RGD.
DR GO; GO:0035729; P:cellular response to hepatocyte growth factor stimulus; ISO:RGD.
DR GO; GO:0050673; P:epithelial cell proliferation; ISO:RGD.
DR GO; GO:0048012; P:hepatocyte growth factor receptor signaling pathway; ISO:RGD.
DR GO; GO:0001889; P:liver development; ISO:RGD.
DR GO; GO:0051450; P:myoblast proliferation; ISO:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:RGD.
DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISO:RGD.
DR GO; GO:1902042; P:negative regulation of extrinsic apoptotic signaling pathway via death domain receptors; ISO:RGD.
DR GO; GO:1901299; P:negative regulation of hydrogen peroxide-mediated programmed cell death; ISO:RGD.
DR GO; GO:0050728; P:negative regulation of inflammatory response; ISO:RGD.
DR GO; GO:0032715; P:negative regulation of interleukin-6 production; ISO:RGD.
DR GO; GO:0033137; P:negative regulation of peptidyl-serine phosphorylation; ISO:RGD.
DR GO; GO:0090201; P:negative regulation of release of cytochrome c from mitochondria; ISO:RGD.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IDA:RGD.
DR GO; GO:0030335; P:positive regulation of cell migration; ISO:RGD.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; TAS:RGD.
DR GO; GO:2000573; P:positive regulation of DNA biosynthetic process; ISO:RGD.
DR GO; GO:0032733; P:positive regulation of interleukin-10 production; ISO:RGD.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISO:RGD.
DR GO; GO:0031643; P:positive regulation of myelination; IDA:RGD.
DR GO; GO:0070572; P:positive regulation of neuron projection regeneration; IDA:RGD.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISO:RGD.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; ISO:RGD.
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; ISO:RGD.
DR GO; GO:1900744; P:regulation of p38MAPK cascade; ISO:RGD.
DR GO; GO:1902947; P:regulation of tau-protein kinase activity; ISO:RGD.
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 1: Evidence at protein level;
KW Direct protein sequencing; Disulfide bond; Glycoprotein; Growth factor;
KW Kringle; Pyrrolidone carboxylic acid; Reference proteome; Repeat;
KW Serine protease homolog; Signal.
FT SIGNAL 1..32
FT /evidence="ECO:0000250"
FT CHAIN 33..495
FT /note="Hepatocyte growth factor alpha chain"
FT /id="PRO_0000028095"
FT CHAIN 496..728
FT /note="Hepatocyte growth factor beta chain"
FT /id="PRO_0000028096"
FT DOMAIN 38..124
FT /note="PAN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00315"
FT DOMAIN 129..207
FT /note="Kringle 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DOMAIN 212..289
FT /note="Kringle 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DOMAIN 306..384
FT /note="Kringle 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DOMAIN 392..470
FT /note="Kringle 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DOMAIN 496..724
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT MOD_RES 33
FT /note="Pyrrolidone carboxylic acid"
FT /evidence="ECO:0000250|UniProtKB:P14210"
FT CARBOHYD 295
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 403
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 569
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 656
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 71..97
FT /evidence="ECO:0000250"
FT DISULFID 75..85
FT /evidence="ECO:0000250"
FT DISULFID 129..207
FT /evidence="ECO:0000250"
FT DISULFID 150..190
FT /evidence="ECO:0000250"
FT DISULFID 178..202
FT /evidence="ECO:0000250"
FT DISULFID 212..289
FT /evidence="ECO:0000250"
FT DISULFID 233..272
FT /evidence="ECO:0000250"
FT DISULFID 261..284
FT /evidence="ECO:0000250"
FT DISULFID 306..384
FT /evidence="ECO:0000250"
FT DISULFID 327..366
FT /evidence="ECO:0000250"
FT DISULFID 355..378
FT /evidence="ECO:0000250"
FT DISULFID 392..470
FT /evidence="ECO:0000250"
FT DISULFID 413..453
FT /evidence="ECO:0000250"
FT DISULFID 441..465
FT /evidence="ECO:0000250"
FT DISULFID 488..607
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 520..536
FT /evidence="ECO:0000250"
FT DISULFID 615..682
FT /evidence="ECO:0000250"
FT DISULFID 645..661
FT /evidence="ECO:0000250"
FT DISULFID 672..700
FT /evidence="ECO:0000250"
SQ SEQUENCE 728 AA; 82906 MW; 3E0BF1F96ADCEDFF CRC64;
MMWGTKLLPV LLLQHVLLHL LLLPVTIPYA EGQKKRRNTL HEFKKSAKTT LTKEDPLVKI
KTKKVNSADE CANRCIRNKG FPFTCKAFVF DKSRKRCYWY PFNSMSSGVK KGFGHEFDLY
ENKDYIRNCI IGKGGSYKGT VSITKSGIKC QPWNSMIPHE HSFLPSSYRG KDLQENYCRN
PRGEEGGPWC FTSNPEVRYE VCDIPQCSEV ECMTCNGESY RGPMDHTESG KTCQRWDQQT
PHRHKFLPER YPDKGFDDNY CRNPDGKPRP WCYTLDPDTP WEYCAIKMCA HSAVNETDVP
METTECIKGQ GEGYRGTTNT IWNGIPCQRW DSQYPHKHDI TPENFKCKDL RENYCRNPDG
AESPWCFTTD PNIRVGYCSQ IPKCDVSSGQ DCYRGNGKNY MGNLSKTRSG LTCSMWDKNM
EDLHRHIFWE PDASKLTKNY CRNPDDDAHG PWCYTGNPLV PWDYCPISRC EGDTTPTIVN
LDHPVISCAK TKQLRVVNGI PTQTTVGWMV SLKYRNKHIC GGSLIKESWV LTARQCFPAR
NKDLKDYEAW LGIHDVHERG EEKRKQILNI SQLVYGPEGS DLVLLKLARP AILDNFVSTI
DLPSYGCTIP EKTTCSIYGW GYTGLINADG LLRVAHLYIM GNEKCSQHHQ GKVTLNESEL
CAGAEKIGSG PCEGDYGGPL ICEQHKMRMV LGVIVPGRGC AIPNRPGIFV RVAYYAKWIH
KVILTYKL
