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Q04756 (HGFA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 143. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Hepatocyte growth factor activator

Short name=HGF activator
Short name=HGFA
EC=3.4.21.-
Gene names
Name:HGFAC
OrganismHomo sapiens (Human) [Reference proteome]
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.

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 Ref.9
Active site4971Charge relay system Ref.9
Active site5981Charge relay system Ref.9

Amino acid modifications

Glycosylation481N-linked (GlcNAc...) Potential
Glycosylation2901N-linked (GlcNAc...) Potential
Glycosylation4681N-linked (GlcNAc...) Ref.7 Ref.8 Ref.10
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) Ref.9 Ref.10
Disulfide bond432 ↔ 448 Ref.9 Ref.10
Disulfide bond440 ↔ 510 Ref.9 Ref.10
Disulfide bond535 ↔ 604 Ref.9 Ref.10
Disulfide bond567 ↔ 583 Ref.9 Ref.10
Disulfide bond594 ↔ 622 Ref.9 Ref.10

Natural variations

Natural variant2181A → S.
Corresponds to variant rs3748034 [ dbSNP | Ensembl ].
VAR_051851
Natural variant2251V → M.
Corresponds to variant rs16844370 [ dbSNP | Ensembl ].
VAR_033651
Natural variant2311F → L. Ref.5
Corresponds to variant rs1987546 [ dbSNP | Ensembl ].
VAR_033652
Natural variant5091R → H.
Corresponds to variant rs16844401 [ dbSNP | Ensembl ].
VAR_024294
Natural variant6441R → Q.
Corresponds to variant rs2498323 [ dbSNP | Ensembl ].
VAR_024295

Secondary structure

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

Details...

Sequences

Sequence LengthMass (Da)Tools
Q04756 [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 responsible 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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]Mural R.J., Istrail S., Sutton G.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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-468.
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] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-468.
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] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 373-655 ALONE AND IN COMPLEX WITH INHIBITOR HAI1B, ACTIVE SITE, DISULFIDE 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] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 373-655 IN COMPLEX WITH ANTIBODY, GLYCOSYLATION AT ASN-468, DISULFIDE BONDS.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS3369.1.
PIRA46688.
RefSeqNP_001519.1. NM_001528.2.
UniGeneHs.104.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1YBWX-ray2.70A/B373-655[»]
1YC0X-ray2.60A373-655[»]
2R0KX-ray3.51A373-655[»]
2R0LX-ray2.20A408-655[»]
B373-407[»]
2WUBX-ray2.90A/C408-655[»]
B/D373-407[»]
2WUCX-ray2.70A408-654[»]
B373-407[»]
3K2UX-ray2.35A408-655[»]
B373-407[»]
ProteinModelPortalQ04756.
SMRQ04756. Positions 92-646.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-6022N.
IntActQ04756. 1 interaction.
STRING9606.ENSP00000372224.

Protein family/group databases

MEROPSS01.228.

PTM databases

PhosphoSiteQ04756.

Polymorphism databases

DMDM547643.

Proteomic databases

MaxQBQ04756.
PaxDbQ04756.
PeptideAtlasQ04756.
PRIDEQ04756.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000382774; ENSP00000372224; ENSG00000109758.
GeneID3083.
KEGGhsa:3083.
UCSCuc003ghc.3. human.

Organism-specific databases

CTD3083.
GeneCardsGC04P003443.
HGNCHGNC:4894. HGFAC.
HPAHPA058279.
HPA059076.
MIM604552. gene.
neXtProtNX_Q04756.
PharmGKBPA29270.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5640.
HOGENOMHOG000237314.
HOVERGENHBG004345.
InParanoidQ04756.
KOK09631.
OrthoDBEOG75B84T.
PhylomeDBQ04756.
TreeFamTF329901.

Gene expression databases

ArrayExpressQ04756.
BgeeQ04756.
CleanExHS_HGFAC.
GenevestigatorQ04756.

Family and domain databases

Gene3D2.10.10.10. 1 hit.
2.40.20.10. 1 hit.
InterProIPR014394. Coagulation_fac_XIIa/HGFA.
IPR000742. EG-like_dom.
IPR013032. EGF-like_CS.
IPR000083. Fibronectin_type1.
IPR000562. FN_type2_col-bd.
IPR000001. Kringle.
IPR013806. Kringle-like.
IPR018056. Kringle_CS.
IPR001254. Peptidase_S1.
IPR018114. Peptidase_S1_AS.
IPR001314. Peptidase_S1A.
IPR009003. Trypsin-like_Pept_dom.
[Graphical view]
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.
SMARTSM00181. EGF. 2 hits.
SM00058. FN1. 1 hit.
SM00059. FN2. 1 hit.
SM00130. KR. 1 hit.
SM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMSSF50494. SSF50494. 1 hit.
SSF57440. SSF57440. 2 hits.
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

EvolutionaryTraceQ04756.
GeneWikiHGFAC.
GenomeRNAi3083.
NextBio12223.
PMAP-CutDBQ04756.
PROQ04756.
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: July 9, 2014
This is version 143 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 4

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