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 17-JUN-2020, entry version 170. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 SMR; P17945; -. DR BioGRID; 246610; 2. DR MINT; P17945; -. DR STRING; 10116.ENSRNOP00000009764; -. DR MEROPS; S01.978; -. DR PaxDb; P17945; -. DR PRIDE; P17945; -. DR Ensembl; ENSRNOT00000009763; ENSRNOP00000009764; ENSRNOG00000007027. DR GeneID; 24446; -. DR KEGG; rno:24446; -. DR CTD; 3082; -. DR RGD; 2794; Hgf. DR eggNOG; ENOG410IDXR; Eukaryota. DR eggNOG; COG5640; LUCA. DR GeneTree; ENSGT00940000156019; -. DR HOGENOM; CLU_017565_1_0_1; -. DR InParanoid; P17945; -. DR KO; K05460; -. DR OMA; TNIPQCG; -. 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 PRO; PR:P17945; -. DR Proteomes; UP000002494; Chromosome 4. DR Bgee; ENSRNOG00000007027; Expressed in liver and 8 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:0004252; F:serine-type endopeptidase activity; IBA:GO_Central. DR GO; GO:0000187; P:activation of MAPK activity; ISO:RGD. 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:0030212; P:hyaluronan metabolic process; IEP: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: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: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 CDD; cd00108; KR; 4. DR CDD; cd00190; Tryp_SPc; 1. DR Gene3D; 2.40.20.10; -; 4. DR InterPro; IPR027284; Hepatocyte_GF. DR InterPro; IPR024174; HGF-like. 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; 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 //