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Reviewed, UniProtKB/Swiss-Prot Q04756 (HGFA_HUMAN)

Last modified June 16, 2009. Version 97. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Hepatocyte growth factor activator
      Short name=HGF activator
      Short name=HGFA
    EC=3.4.21.-
Cleaved into the following 2 chains:
    1- Recommended name:
            Hepatocyte growth factor activator short chain
    2- Recommended name:
            Hepatocyte growth factor activator long chain
Gene names
Name: HGFAC
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length655 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Activates hepatocyte growth factor (HGF) by converting it from a single chain to a heterodimeric form.

Subunit structure

Heterodimer of a short chain and a long chain linked by a disulfide bond.

Subcellular location

Secreted. Note: Secreted as an inactive single-chain precursor and is then activated to a heterodimeric form.

Tissue specificity

Liver.

Sequence similarities

Belongs to the peptidase S1 family.

Contains 2 EGF-like domains.

Contains 1 fibronectin type-I domain.

Contains 1 fibronectin type-II domain.

Contains 1 kringle domain.

Contains 1 peptidase S1 domain.

Caution

It is uncertain whether Met-1 is the initiator.

Ontologies

Keywords
   Cellular componentSecreted
   Coding sequence diversityPolymorphism
   DomainEGF-like domain
Kringle
Repeat
Signal
   Molecular functionHydrolase
Protease
Serine protease
   PTMDisulfide bond
Glycoprotein
Zymogen
   Technical term3D-structure
Direct protein sequencing
Gene Ontology (GO)
   Biological processproteolysis

Traceable author statement. Source: ProtInc

   Cellular componentextracellular space

Inferred from electronic annotation. Source: InterPro

   Molecular functionprotein binding Ref.9

Inferred from physical interaction. Source: IntAct

serine-type endopeptidase activity Ref.1

Traceable author statement. Source: ProtInc

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

SPINT1O432781EBI-1041722,EBI-953990

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3535 Ref.6
Propeptide36 – 372337Removed in mature form
PRO_0000027911
Chain373 – 40735Hepatocyte growth factor activator short chain
PRO_0000027912
Chain408 – 655248Hepatocyte growth factor activator long chain
PRO_0000027913

Regions

Domain103 – 15048Fibronectin type-II
Domain160 – 19839EGF-like 1
Domain200 – 24041Fibronectin type-I
Domain241 – 27939EGF-like 2
Domain286 – 36782Kringle
Domain408 – 646239Peptidase S1

Sites

Active site4471Charge relay system
Active site4971Charge relay system
Active site5981Charge relay system

Amino acid modifications

Glycosylation481N-linked (GlcNAc...) Potential
Glycosylation2901N-linked (GlcNAc...) Potential
Glycosylation4681N-linked (GlcNAc...) Ref.7
Glycosylation4921N-linked (GlcNAc...) Potential
Glycosylation5461N-linked (GlcNAc...) Potential
Disulfide bond108 ↔ 133 By similarity
Disulfide bond122 ↔ 148 By similarity
Disulfide bond164 ↔ 175 By similarity
Disulfide bond169 ↔ 186 By similarity
Disulfide bond188 ↔ 197 By similarity
Disulfide bond202 ↔ 230 By similarity
Disulfide bond228 ↔ 237 By similarity
Disulfide bond245 ↔ 256 By similarity
Disulfide bond250 ↔ 267 By similarity
Disulfide bond269 ↔ 278 By similarity
Disulfide bond286 ↔ 367 By similarity
Disulfide bond307 ↔ 349 By similarity
Disulfide bond338 ↔ 362 By similarity
Disulfide bond394 ↔ 521Interchain (between short and long chains)
Disulfide bond432 ↔ 448
Disulfide bond440 ↔ 510
Disulfide bond535 ↔ 604
Disulfide bond567 ↔ 583
Disulfide bond594 ↔ 622

Natural variations

Natural variant2181A → S: dbSNP rs3748034.
VAR_051851
Natural variant2251V → M: dbSNP rs16844370.
VAR_033651
Natural variant2311F → L: dbSNP rs1987546. Ref.5
VAR_033652
Natural variant5091R → H: dbSNP rs16844401.
VAR_024294
Natural variant6441R → Q: dbSNP rs2498323. Ref.3
VAR_024295

Secondary structure

............................................. 655
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q04756-1 [UniParc].

Last modified June 1, 1994. Version 1.
Checksum: 2CF72F1E1B862ED7

FASTA65570,682
        10         20         30         40         50         60 
MGRWAWVPSP WPPPGLGPFL LLLLLLLLLP RGFQPQPGGN RTESPEPNAT ATPAIPTILV 

        70         80         90        100        110        120 
TSVTSETPAT SAPEAEGPQS GGLPPPPRAV PSSSSPQAQA LTEDGRPCRF PFRYGGRMLH 

       130        140        150        160        170        180 
ACTSEGSAHR KWCATTHNYD RDRAWGYCVE ATPPPGGPAA LDPCASGPCL NGGSCSNTQD 

       190        200        210        220        230        240 
PQSYHCSCPR AFTGKDCGTE KCFDETRYEY LEGGDRWARV RQGHVEQCEC FGGRTWCEGT 

       250        260        270        280        290        300 
RHTACLSSPC LNGGTCHLIV ATGTTVCACP PGFAGRLCNI EPDERCFLGN GTGYRGVAST 

       310        320        330        340        350        360 
SASGLSCLAW NSDLLYQELH VDSVGAAALL GLGPHAYCRN PDNDERPWCY VVKDSALSWE 

       370        380        390        400        410        420 
YCRLEACESL TRVQLSPDLL ATLPEPASPG RQACGRRHKK RTFLRPRIIG GSSSLPGSHP 

       430        440        450        460        470        480 
WLAAIYIGDS FCAGSLVHTC WVVSAAHCFS HSPPRDSVSV VLGQHFFNRT TDVTQTFGIE 

       490        500        510        520        530        540 
KYIPYTLYSV FNPSDHDLVL IRLKKKGDRC ATRSQFVQPI CLPEPGSTFP AGHKCQIAGW 

       550        560        570        580        590        600 
GHLDENVSGY SSSLREALVP LVADHKCSSP EVYGADISPN MLCAGYFDCK SDACQGDSGG 

       610        620        630        640        650 
PLACEKNGVA YLYGIISWGD GCGRLHKPGV YTRVANYVDW INDRIRPPRR LVAPS 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning and sequence analysis of the cDNA for a human serine protease reponsible for activation of hepatocyte growth factor. Structural similarity of the protease precursor to blood coagulation factor XII."
Miyazawa K., Shimomura T., Kitamura A., Kondo J., Morimoto Y., Kitamura N.
J. Biol. Chem. 268:10024-10028(1993) [PubMed: 7683665] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
Tissue: Liver and Serum.
[2]"Structural organization and chromosomal localization of the human hepatocyte growth factor activator gene -- phylogenetic and functional relationship with blood coagulation factor XII, urokinase, and tissue-type plasminogen activator."
Miyazawa K., Wang Y., Minoshima S., Shimizu N., Kitamura N.
Eur. J. Biochem. 258:355-361(1998) [PubMed: 9874200] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed: 15815621] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT LEU-231.
Tissue: Liver.
[6]"Signal peptide prediction based on analysis of experimentally verified cleavage sites."
Zhang Z., Henzel W.J.
Protein Sci. 13:2819-2824(2004) [PubMed: 15340161] [Abstract]
Cited for: PROTEIN SEQUENCE OF 36-50.
[7]"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry."
Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D.
J. Proteome Res. 4:2070-2080(2005) [PubMed: 16335952] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-468, MASS SPECTROMETRY.
Tissue: Plasma.
[8]"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
J. Proteome Res. 8:651-661(2009) [PubMed: 19159218] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-468, MASS SPECTROMETRY.
Tissue: Liver.
[9]"Conformational lability in serine protease active sites: structures of hepatocyte growth factor activator (HGFA) alone and with the inhibitory domain from HGFA inhibitor-1B."
Shia S., Stamos J., Kirchhofer D., Fan B., Wu J., Corpuz R.T., Santell L., Lazarus R.A., Eigenbrot C.
J. Mol. Biol. 346:1335-1349(2005) [PubMed: 15713485] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 373-655 ALONE AND IN COMPLEX WITH INHIBITOR HAI1B, ACTIVE SITE, DISUFIDE BONDS.
[10]"Structural insight into distinct mechanisms of protease inhibition by antibodies."
Wu Y., Eigenbrot C., Liang W.C., Stawicki S., Shia S., Fan B., Ganesan R., Lipari M.T., Kirchhofer D.
Proc. Natl. Acad. Sci. U.S.A. 104:19784-19789(2007) [PubMed: 18077410] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 373-655 IN COMPLEX WITH ANTIBODY, GLYCOSYLATION AT ASN-468, DISUFIDE BONDS.
+Additional computationally mapped references.

Cross-references

Sequence databases

D14012 mRNA. Translation: BAA03113.1.
BC112190 mRNA. Translation: AAI12191.1.
D50030 Genomic DNA. Translation: BAA74450.1.
AL590235 Genomic DNA. Translation: CAM21456.1.
CH471131 Genomic DNA. Translation: EAW82464.1.
BC112192 mRNA. Translation: AAI12193.1.
IPIIPI00029193.
PIRA46688.
RefSeqNP_001519.1.
UniGeneHs.104

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
1YBWX-ray2.70A/B373-655[»]
1YC0X-ray2.60A373-655[»]
2R0KX-ray3.51A373-655[»]
2R0LX-ray2.20A408-655[»]
B373-407[»]
ModBaseSearch...

Protein-protein interaction databases

DIPDIP:6022N.
IntActQ04756. 1 interaction.

Protein family/group databases

MEROPSS01.228.

PTM databases

PhosphoSiteQ04756.

Proteomic databases

PeptideAtlasQ04756.
PRIDEQ04756.

Genome annotation databases

EnsemblENSG00000109758. Homo sapiens. [Contig view]
GeneID3083.
KEGGhsa:3083.

Organism-specific databases

GeneCardsGC04P003413.
H-InvDBHIX0031501.
HGNCHGNC:4894. HGFAC.
HPACAB005215.
MIM604552. gene.
PharmGKBPA29270.
GenAtlasSearch...

Phylogenomic databases

HOGENOMQ04756.
HOVERGENQ04756.
OMAQ04756. CKSDACQ.

Gene expression databases

ArrayExpressQ04756.
BgeeQ04756.
CleanExHS_HGFAC.
GermOnlineENSG00000109758. Homo sapiens.

Family and domain databases

InterProIPR014394. Coagulation_fac_XII_Hep-GF-Act.
IPR006209. EGF.
IPR006210. EGF-like.
IPR013032. EGF-like_reg_CS.
IPR000742. EGF_3.
IPR000083. Fibrnctn1.
IPR000562. FN_type2_col_bd.
IPR000001. Kringle.
IPR018056. Kringle_CS.
IPR018059. Kringle_sub.
IPR018114. Peptidase_S1/S6_AS.
IPR001254. Peptidase_S1_S6.
IPR001314. Peptidase_S1A.
[Graphical view]
Gene3DG3DSA:2.40.20.10. Kringle. 1 hit.
PfamPF00008. EGF. 2 hits.
PF00039. fn1. 1 hit.
PF00040. fn2. 1 hit.
PF00051. Kringle. 1 hit.
PF00089. Trypsin. 1 hit.
[Graphical view]
PIRSFPIRSF001146. Factor_XII_HGFA. 1 hit.
PRINTSPR00722. CHYMOTRYPSIN.
PR00013. FNTYPEII.
PR00018. KRINGLE.
ProDomPD000995. FN_Type_II. 1 hit.
PD000395. Kringle. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTSM00181. EGF. 2 hits.
SM00058. FN1. 1 hit.
SM00059. FN2. 1 hit.
SM00130. KR. 1 hit.
SM00020. Tryp_SPc. 1 hit.
[Graphical view]
PROSITEPS00022. EGF_1. 2 hits.
PS01186. EGF_2. 1 hit.
PS50026. EGF_3. 2 hits.
PS01253. FN1_1. 1 hit.
PS51091. FN1_2. 1 hit.
PS00023. FN2_1. 1 hit.
PS51092. FN2_2. 1 hit.
PS00021. KRINGLE_1. 1 hit.
PS50070. KRINGLE_2. 1 hit.
PS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio12223.
PMAP-CutDBQ04756.
SOURCESearch...

Entry information

Entry nameHGFA_HUMAN
AccessionPrimary (citable) accession number: Q04756
Secondary accession number(s): Q14726, Q2M1W7, Q53X47
Entry history
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: June 16, 2009
This is version 97 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

Peptidase families

Classification of peptidase families and list of entries

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents