ID   HGF_HUMAN      STANDARD;      PRT;   728 AA.
AC   P14210; Q9BYL9; Q9UDU6;
DT   01-JAN-1990 (Rel. 13, Created)
DT   01-AUG-1991 (Rel. 19, Last sequence update)
DT   15-MAR-2004 (Rel. 43, Last annotation update)
DE   Hepatocyte growth factor precursor (Scatter factor) (SF)
DE   (Hepatopoeitin A).
GN   HGF OR HPTA.
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   SEQUENCE FROM N.A.
RX   MEDLINE=91340155; PubMed=1831432;
RA   Seki T., Hagiya M., Shimonishi M., Nakamura T., Shimizu S.;
RT   "Organization of the human hepatocyte growth factor-encoding gene.";
RL   Gene 102:213-219(1991).
RN   [2]
RP   SEQUENCE FROM N.A.
RC   TISSUE=Placenta;
RX   MEDLINE=89392017; PubMed=2528952;
RA   Miyazawa K., Tsubouchi H., Naka D., Takahashi K., Okigaki M.,
RA   Arakaki N., Nakayama H., Hirono S., Sakiyama O., Takahashi K.,
RA   Gohda E., Daikuhara Y., Kitamura N.;
RT   "Molecular cloning and sequence analysis of cDNA for human hepatocyte
RT   growth factor.";
RL   Biochem. Biophys. Res. Commun. 163:967-973(1989).
RN   [3]
RP   SEQUENCE FROM N.A.
RC   TISSUE=Leukocyte;
RX   MEDLINE=91025062; PubMed=2145836;
RA   Seki T., Ihara I., Sugimura A., Shimonishi M., Nishizawa T.,
RA   Asami O., Hagiya M., Nakamura T., Shimizu S.;
RT   "Isolation and expression of cDNA for different forms of hepatocyte
RT   growth factor from human leukocyte.";
RL   Biochem. Biophys. Res. Commun. 172:321-327(1990).
RN   [4]
RP   SEQUENCE FROM N.A., AND SEQUENCE OF 55-73 AND 495-520.
RC   TISSUE=Liver;
RX   MEDLINE=90066676; PubMed=2531289;
RA   Nakamura T., Nishizawa T., Hagiya M., Seki T., Shimonishi M.,
RA   Sugimura A., Tashiro K., Shimizu S.;
RT   "Molecular cloning and expression of human hepatocyte growth factor.";
RL   Nature 342:440-443(1989).
RN   [5]
RP   SEQUENCE FROM N.A.
RC   TISSUE=Embryonic fibroblast;
RX   MEDLINE=91334393; PubMed=1831266;
RA   Weidner K.M., Arakaki N., Hartmann G., Vandekerckhove J., Weingart S.,
RA   Rieder H., Fonatsch C., Tsubouchi H., Hishida T., Daikuhara Y.,
RA   Birchmeier W.;
RT   "Evidence for the identity of human scatter factor and human
RT   hepatocyte growth factor.";
RL   Proc. Natl. Acad. Sci. U.S.A. 88:7001-7005(1991).
RN   [6]
RP   SEQUENCE FROM N.A.
RA   Rieder M.J., Livingston R.J., Daniels M.R., Chung M.-W.,
RA   Miyamoto K.E., Nguyen C.P., Nguyen D.A., Poel C.L., Robertson P.D.,
RA   Schackwitz W.S., Sherwood J.K., Witrak L.A., Nickerson D.A.;
RL   Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases.
RN   [7]
RP   SEQUENCE FROM N.A.
RA   Courtney L., Elliot G., Angell S.;
RL   Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases.
RN   [8]
RP   SEQUENCE OF 249-695 FROM N.A.
RX   MEDLINE=91369928; PubMed=1832556;
RA   Miyazawa K., Kitamura A., Kitamura N.;
RT   "Structural organization and the transcription initiation site of the
RT   human hepatocyte growth factor gene.";
RL   Biochemistry 30:9170-9176(1991).
RN   [9]
RP   SIGNAL SEQUENCE CLEAVAGE SITE.
RX   MEDLINE=91207365; PubMed=1826837;
RA   Yoshiyama Y., Arakakai N., Naka D., Takahashi K., Hirono S., Kondo J.,
RA   Nakayama H., Gohda E., Kitamura N., Tsubouchi H., Ishii T.,
RA   Hishida T., Daikuhara Y.;
RT   "Identification of the N-terminal residue of the heavy chain of both
RT   native and recombinant human hepatocyte growth factor.";
RL   Biochem. Biophys. Res. Commun. 175:660-667(1991).
RN   [10]
RP   CARBOHYDRATE-LINKAGE SITE THR-476.
RX   MEDLINE=93129192; PubMed=1482348;
RA   Shimizu N., Hara H., Sogabe T., Sakai H., Ihara I., Inoue H.,
RA   Nakamura T., Shimizu S.;
RT   "Hepatocyte growth factor is linked by O-glycosylated oligosaccharide
RT   on the alpha chain.";
RL   Biochem. Biophys. Res. Commun. 189:1329-1335(1992).
RN   [11]
RP   MUTAGENESIS.
RX   MEDLINE=92331602; PubMed=1321034;
RA   Lokker N.A., Mark M.R., Luis E.A., Bennett G.L., Robbins K.A.,
RA   Baker J.B., Godowski P.J.;
RT   "Structure-function analysis of hepatocyte growth factor:
RT   identification of variants that lack mitogenic activity yet retain
RT   high affinity receptor binding.";
RL   EMBO J. 11:2503-2510(1992).
RN   [12]
RP   STRUCTURE BY NMR OF 31-127.
RX   MEDLINE=98154323; PubMed=9493272;
RA   Zhou H., Mazzulla M.J., Kaufman J.D., Stahl S.J., Wingfield P.T.,
RA   Rubin J.S., Bottaro D.P., Byrd R.A.;
RT   "The solution structure of the N-terminal domain of hepatocyte growth
RT   factor reveals a potential heparin-binding site.";
RL   Structure 6:109-116(1998).
RN   [13]
RP   X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 35-210.
RX   MEDLINE=99036858; PubMed=9817840;
RA   Ultsch M., Lokker N.A., Godowski P.J., de Vos A.M.;
RT   "Crystal structure of the NK1 fragment of human hepatocyte growth
RT   factor at 2.0-A resolution.";
RL   Structure 6:1383-1393(1998).
CC   -!- FUNCTION: HGF is a potent mitogen for mature parenchymal
CC       hepatocyte cells, seems to be an hepatotrophic factor, and acts
CC       as growth factor for a broad spectrum of tissues and cell types.
CC       It has no detectable protease activity.
CC   -!- SUBUNIT: Dimer of an alpha chain and a beta chain linked by a
CC       disulfide bond.
CC   -!- SIMILARITY: Belongs to peptidase family S1. Plasminogen subfamily.
CC   -!- SIMILARITY: Contains 4 kringle domains.
CC   -!- SIMILARITY: Contains 1 PAN domain.
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DR   EMBL; D90334; BAA14348.1; -.
DR   EMBL; D90318; BAA14348.1; JOINED.
DR   EMBL; D90319; BAA14348.1; JOINED.
DR   EMBL; D90320; BAA14348.1; JOINED.
DR   EMBL; D90322; BAA14348.1; JOINED.
DR   EMBL; D90323; BAA14348.1; JOINED.
DR   EMBL; D90324; BAA14348.1; JOINED.
DR   EMBL; D90325; BAA14348.1; JOINED.
DR   EMBL; D90326; BAA14348.1; JOINED.
DR   EMBL; D90327; BAA14348.1; JOINED.
DR   EMBL; D90328; BAA14348.1; JOINED.
DR   EMBL; D90329; BAA14348.1; JOINED.
DR   EMBL; D90330; BAA14348.1; JOINED.
DR   EMBL; D90331; BAA14348.1; JOINED.
DR   EMBL; D90332; BAA14348.1; JOINED.
DR   EMBL; D90333; BAA14348.1; JOINED.
DR   EMBL; M29145; AAA52650.1; -.
DR   EMBL; M60718; AAA52648.1; -.
DR   EMBL; X16323; CAA34387.1; -.
DR   EMBL; M73239; AAA64239.1; -.
DR   EMBL; M73240; AAA64297.1; -.
DR   EMBL; AY246560; AAO61091.1; -.
DR   EMBL; AC004960; AAC71655.1; -.
DR   EMBL; M75983; AAG53460.1; -.
DR   EMBL; M75972; AAG53460.1; JOINED.
DR   EMBL; M75973; AAG53460.1; JOINED.
DR   EMBL; M75974; AAG53460.1; JOINED.
DR   EMBL; M75975; AAG53460.1; JOINED.
DR   EMBL; M75976; AAG53460.1; JOINED.
DR   EMBL; M75977; AAG53460.1; JOINED.
DR   EMBL; M75978; AAG53460.1; JOINED.
DR   EMBL; M75979; AAG53460.1; JOINED.
DR   EMBL; M75980; AAG53460.1; JOINED.
DR   EMBL; M75981; AAG53460.1; JOINED.
DR   EMBL; M75982; AAG53460.1; JOINED.
DR   PIR; JH0579; JH0579.
DR   PDB; 1GP9; 24-JUN-03.
DR   PDB; 2HGF; 24-JUN-98.
DR   PDB; 1BHT; 18-NOV-98.
DR   PDB; 1NK1; 29-DEC-99.
DR   MEROPS; S01.976; -.
DR   GlycoSuiteDB; P14210; -.
DR   Genew; HGNC:4893; HGF.
DR   MIM; 142409; -.
DR   GO; GO:0008083; F:growth factor activity; NAS.
DR   GO; GO:0007067; P:mitosis; NAS.
DR   InterPro; IPR009003; Cys_Ser_trypsin.
DR   InterPro; IPR000001; Kringle.
DR   InterPro; IPR003014; PAN.
DR   InterPro; IPR003609; Pan_app.
DR   InterPro; IPR001254; Peptidase_S1.
DR   InterPro; IPR001314; Peptidase_S1A.
DR   Pfam; PF00051; kringle; 4.
DR   Pfam; PF00024; PAN; 1.
DR   Pfam; PF00089; trypsin; 1.
DR   PRINTS; PR00722; CHYMOTRYPSIN.
DR   PRINTS; PR00018; KRINGLE.
DR   ProDom; PD000395; Kringle; 4.
DR   SMART; SM00130; KR; 4.
DR   SMART; SM00473; PAN_AP; 1.
DR   SMART; SM00020; Tryp_SPc; 1.
DR   PROSITE; PS00021; KRINGLE_1; 4.
DR   PROSITE; PS50070; KRINGLE_2; 4.
DR   PROSITE; PS50948; PAN; 1.
DR   PROSITE; PS50240; TRYPSIN_DOM; 1.
KW   Growth factor; Kringle; Glycoprotein; Serine protease homolog; Repeat;
KW   Signal; 3D-structure; Polymorphism; Pyrrolidone carboxylic acid.
FT   SIGNAL        1     31
FT   CHAIN        32    494       HEPATOCYTE GROWTH FACTOR ALPHA CHAIN.
FT   CHAIN       495    728       HEPATOCYTE GROWTH FACTOR BETA CHAIN.
FT   MOD_RES      32     32       PYRROLIDONE CARBOXYLIC ACID.
FT   DOMAIN       37    123       PAN.
FT   DOMAIN      128    206       KRINGLE 1.
FT   DOMAIN      211    288       KRINGLE 2.
FT   DOMAIN      305    383       KRINGLE 3.
FT   DOMAIN      391    469       KRINGLE 4.
FT   DOMAIN      495    728       SERINE PROTEASE-LIKE.
FT   DISULFID     70     96
FT   DISULFID     74     84
FT   DISULFID    128    206
FT   DISULFID    149    189
FT   DISULFID    177    201
FT   DISULFID    487    604       INTERCHAIN (BY SIMILARITY).
FT   CARBOHYD    294    294       N-LINKED (GLCNAC...) (COMPLEX).
FT                                /FTId=CAR_000021.
FT   CARBOHYD    402    402       N-LINKED (GLCNAC...) (COMPLEX).
FT                                /FTId=CAR_000022.
FT   CARBOHYD    476    476       O-LINKED (GALNAC...).
FT                                /FTId=CAR_000023.
FT   CARBOHYD    566    566       N-LINKED (GLCNAC...) (COMPLEX).
FT                                /FTId=CAR_000024.
FT   CARBOHYD    653    653       N-LINKED (GLCNAC...) (COMPLEX).
FT                                /FTId=CAR_000025.
FT   VARIANT     153    153       S -> I (in dbSNP:17566).
FT                                /FTId=VAR_014570.
FT   CONFLICT     32     33       QR -> HK (in Ref. 4).
FT   CONFLICT     78     78       K -> N (in Ref. 4).
FT   CONFLICT    162    166       Missing (in Ref. 7).
FT   CONFLICT    293    293       M -> V (in Ref. 4).
FT   CONFLICT    300    300       L -> M (in Ref. 4).
FT   CONFLICT    317    317       V -> A (in Ref. 4).
FT   CONFLICT    336    336       E -> K (in Ref. 4).
FT   CONFLICT    387    387       H -> N (in Ref. 4).
FT   CONFLICT    416    416       D -> N (in Ref. 4).
FT   CONFLICT    505    505       I -> V (in Ref. 4).
FT   CONFLICT    509    509       V -> I (in Ref. 4).
FT   CONFLICT    558    558       D -> E (in Ref. 4).
FT   CONFLICT    561    561       C -> R (in Ref. 4).
FT   CONFLICT    595    595       S -> N (in Ref. 4).
FT   HELIX        39     41
FT   STRAND       42     51
FT   TURN         55     56
FT   STRAND       60     63
FT   HELIX        67     75
FT   TURN         76     77
FT   STRAND       86     90
FT   TURN         91     94
FT   STRAND       95     99
FT   TURN        103    104
FT   TURN        106    107
FT   STRAND      109    121
FT   HELIX       122    124
FT   STRAND      129    129
FT   TURN        131    132
FT   TURN        134    135
FT   STRAND      142    142
FT   TURN        144    145
FT   STRAND      148    149
FT   TURN        152    153
FT   HELIX       164    166
FT   TURN        168    169
FT   TURN        174    175
FT   STRAND      178    178
FT   TURN        180    181
FT   TURN        184    185
FT   STRAND      188    191
FT   TURN        194    195
FT   STRAND      198    200
FT   STRAND      205    205
FT   TURN        206    207
SQ   SEQUENCE   728 AA;  83133 MW;  2D997938295ADD2F CRC64;
     MWVTKLLPAL LLQHVLLHLL LLPIAIPYAE GQRKRRNTIH EFKKSAKTTL IKIDPALKIK
     TKKVNTADQC ANRCTRNKGL PFTCKAFVFD KARKQCLWFP FNSMSSGVKK EFGHEFDLYE
     NKDYIRNCII GKGRSYKGTV SITKSGIKCQ PWSSMIPHEH SFLPSSYRGK DLQENYCRNP
     RGEEGGPWCF TSNPEVRYEV CDIPQCSEVE CMTCNGESYR GLMDHTESGK ICQRWDHQTP
     HRHKFLPERY PDKGFDDNYC RNPDGQPRPW CYTLDPHTRW EYCAIKTCAD NTMNDTDVPL
     ETTECIQGQG EGYRGTVNTI WNGIPCQRWD SQYPHEHDMT PENFKCKDLR ENYCRNPDGS
     ESPWCFTTDP NIRVGYCSQI PNCDMSHGQD CYRGNGKNYM GNLSQTRSGL TCSMWDKNME
     DLHRHIFWEP DASKLNENYC RNPDDDAHGP WCYTGNPLIP WDYCPISRCE GDTTPTIVNL
     DHPVISCAKT KQLRVVNGIP TRTNIGWMVS LRYRNKHICG GSLIKESWVL TARQCFPSRD
     LKDYEAWLGI HDVHGRGDEK CKQVLNVSQL VYGPEGSDLV LMKLARPAVL DDFVSTIDLP
     NYGCTIPEKT SCSVYGWGYT GLINYDGLLR VAHLYIMGNE KCSQHHRGKV TLNESEICAG
     AEKIGSGPCE GDYGGPLVCE QHKMRMVLGV IVPGRGCAIP NRPGIFVRVA YYAKWIHKII
     LTYKVPQS
//