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Protein

Hepatocyte growth factor activator

Gene

HGFAC

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei447Charge relay system1 Publication1
Active sitei497Charge relay system1 Publication1
Active sitei598Charge relay system1 Publication1

GO - Molecular functioni

  • serine-type endopeptidase activity Source: ProtInc
  • serine-type peptidase activity Source: ProtInc

GO - Biological processi

  • proteolysis Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Serine protease

Enzyme and pathway databases

BioCyciZFISH:ENSG00000109758-MONOMER.
ReactomeiR-HSA-6806942. MET Receptor Activation.

Protein family/group databases

MEROPSiS01.228.

Names & Taxonomyi

Protein namesi
Recommended name:
Hepatocyte growth factor activator (EC:3.4.21.-)
Short name:
HGF activator
Short name:
HGFA
Cleaved into the following 2 chains:
Gene namesi
Name:HGFAC
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:4894. HGFAC.

Subcellular locationi

  • Secreted

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

GO - Cellular componenti

  • extracellular region Source: UniProtKB
  • extracellular space Source: InterPro
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi3083.
OpenTargetsiENSG00000109758.
PharmGKBiPA29270.

Chemistry databases

ChEMBLiCHEMBL3351190.

Polymorphism and mutation databases

BioMutaiHGFAC.
DMDMi547643.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 351 PublicationAdd BLAST35
PropeptideiPRO_000002791136 – 372Removed in mature formAdd BLAST337
ChainiPRO_0000027912373 – 407Hepatocyte growth factor activator short chainAdd BLAST35
ChainiPRO_0000027913408 – 655Hepatocyte growth factor activator long chainAdd BLAST248

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi48N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi108 ↔ 133By similarity
Disulfide bondi122 ↔ 148By similarity
Disulfide bondi164 ↔ 175By similarity
Disulfide bondi169 ↔ 186By similarity
Disulfide bondi188 ↔ 197By similarity
Disulfide bondi202 ↔ 230By similarity
Disulfide bondi228 ↔ 237By similarity
Disulfide bondi245 ↔ 256By similarity
Disulfide bondi250 ↔ 267By similarity
Disulfide bondi269 ↔ 278By similarity
Disulfide bondi286 ↔ 367By similarity
Glycosylationi290N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi307 ↔ 349By similarity
Disulfide bondi338 ↔ 362By similarity
Disulfide bondi394 ↔ 521Interchain (between short and long chains)
Disulfide bondi432 ↔ 448
Disulfide bondi440 ↔ 510
Glycosylationi468N-linked (GlcNAc...)3 Publications1
Glycosylationi492N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi535 ↔ 604
Glycosylationi546N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi567 ↔ 583
Disulfide bondi594 ↔ 622

Keywords - PTMi

Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

EPDiQ04756.
MaxQBiQ04756.
PaxDbiQ04756.
PeptideAtlasiQ04756.
PRIDEiQ04756.

PTM databases

iPTMnetiQ04756.
PhosphoSitePlusiQ04756.

Miscellaneous databases

PMAP-CutDBQ04756.

Expressioni

Tissue specificityi

Liver.

Gene expression databases

BgeeiENSG00000109758.
CleanExiHS_HGFAC.
ExpressionAtlasiQ04756. baseline and differential.
GenevisibleiQ04756. HS.

Organism-specific databases

HPAiHPA058279.
HPA059076.

Interactioni

Subunit structurei

Heterodimer of a short chain and a long chain linked by a disulfide bond.2 Publications

Protein-protein interaction databases

BioGridi109331. 6 interactors.
DIPiDIP-6022N.
IntActiQ04756. 3 interactors.
STRINGi9606.ENSP00000372224.

Chemistry databases

BindingDBiQ04756.

Structurei

Secondary structure

1655
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi422 – 427Combined sources6
Beta strandi430 – 438Combined sources9
Beta strandi441 – 444Combined sources4
Helixi446 – 449Combined sources4
Helixi455 – 457Combined sources3
Beta strandi458 – 463Combined sources6
Beta strandi475 – 477Combined sources3
Beta strandi479 – 484Combined sources6
Beta strandi490 – 492Combined sources3
Turni493 – 496Combined sources4
Beta strandi499 – 503Combined sources5
Beta strandi506 – 508Combined sources3
Beta strandi509 – 511Combined sources3
Beta strandi514 – 516Combined sources3
Beta strandi534 – 540Combined sources7
Beta strandi543 – 546Combined sources4
Beta strandi555 – 561Combined sources7
Helixi564 – 567Combined sources4
Turni570 – 573Combined sources4
Helixi574 – 576Combined sources3
Beta strandi581 – 585Combined sources5
Beta strandi587 – 589Combined sources3
Turni595 – 599Combined sources5
Beta strandi601 – 606Combined sources6
Beta strandi609 – 618Combined sources10
Turni621 – 623Combined sources3
Beta strandi625 – 627Combined sources3
Beta strandi629 – 633Combined sources5
Helixi634 – 637Combined sources4
Helixi638 – 645Combined sources8

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
ProteinModelPortaliQ04756.
SMRiQ04756.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ04756.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini103 – 150Fibronectin type-IIPROSITE-ProRule annotationAdd BLAST48
Domaini160 – 198EGF-like 1PROSITE-ProRule annotationAdd BLAST39
Domaini200 – 240Fibronectin type-IPROSITE-ProRule annotationAdd BLAST41
Domaini241 – 279EGF-like 2PROSITE-ProRule annotationAdd BLAST39
Domaini286 – 367KringlePROSITE-ProRule annotationAdd BLAST82
Domaini408 – 646Peptidase S1PROSITE-ProRule annotationAdd BLAST239

Sequence similaritiesi

Belongs to the peptidase S1 family.PROSITE-ProRule annotation
Contains 2 EGF-like domains.PROSITE-ProRule annotation
Contains 1 fibronectin type-I domain.PROSITE-ProRule annotation
Contains 1 fibronectin type-II domain.PROSITE-ProRule annotation
Contains 1 kringle domain.PROSITE-ProRule annotation
Contains 1 peptidase S1 domain.PROSITE-ProRule annotation

Keywords - Domaini

EGF-like domain, Kringle, Repeat, Signal

Phylogenomic databases

eggNOGiKOG1217. Eukaryota.
KOG3627. Eukaryota.
COG5640. LUCA.
GeneTreeiENSGT00760000119133.
HOGENOMiHOG000237314.
HOVERGENiHBG004345.
InParanoidiQ04756.
KOiK09631.
PhylomeDBiQ04756.
TreeFamiTF329901.

Family and domain databases

CDDicd00062. FN2. 1 hit.
cd00190. Tryp_SPc. 1 hit.
Gene3Di2.10.10.10. 1 hit.
InterProiIPR014394. Coagulation_fac_XIIa/HGFA.
IPR013032. EGF-like_CS.
IPR000742. EGF-like_dom.
IPR000083. Fibronectin_type1.
IPR000562. FN_type2_col-bd.
IPR000001. Kringle.
IPR013806. Kringle-like.
IPR018056. Kringle_CS.
IPR009003. Peptidase_S1_PA.
IPR001314. Peptidase_S1A.
IPR001254. Trypsin_dom.
IPR018114. TRYPSIN_HIS.
IPR033116. TRYPSIN_SER.
[Graphical view]
PfamiPF00008. EGF. 1 hit.
PF00039. fn1. 1 hit.
PF00040. fn2. 1 hit.
PF00051. Kringle. 1 hit.
PF00089. Trypsin. 1 hit.
[Graphical view]
PIRSFiPIRSF001146. Factor_XII_HGFA. 1 hit.
PRINTSiPR00722. CHYMOTRYPSIN.
SMARTiSM00181. EGF. 2 hits.
SM00058. FN1. 1 hit.
SM00059. FN2. 1 hit.
SM00130. KR. 1 hit.
SM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMiSSF50494. SSF50494. 1 hit.
SSF57440. SSF57440. 2 hits.
PROSITEiPS00022. 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]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q04756-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGRWAWVPSP WPPPGLGPFL LLLLLLLLLP RGFQPQPGGN RTESPEPNAT
60 70 80 90 100
ATPAIPTILV TSVTSETPAT SAPEAEGPQS GGLPPPPRAV PSSSSPQAQA
110 120 130 140 150
LTEDGRPCRF PFRYGGRMLH ACTSEGSAHR KWCATTHNYD RDRAWGYCVE
160 170 180 190 200
ATPPPGGPAA LDPCASGPCL NGGSCSNTQD PQSYHCSCPR AFTGKDCGTE
210 220 230 240 250
KCFDETRYEY LEGGDRWARV RQGHVEQCEC FGGRTWCEGT RHTACLSSPC
260 270 280 290 300
LNGGTCHLIV ATGTTVCACP PGFAGRLCNI EPDERCFLGN GTGYRGVAST
310 320 330 340 350
SASGLSCLAW NSDLLYQELH VDSVGAAALL GLGPHAYCRN PDNDERPWCY
360 370 380 390 400
VVKDSALSWE YCRLEACESL TRVQLSPDLL ATLPEPASPG RQACGRRHKK
410 420 430 440 450
RTFLRPRIIG GSSSLPGSHP WLAAIYIGDS FCAGSLVHTC WVVSAAHCFS
460 470 480 490 500
HSPPRDSVSV VLGQHFFNRT TDVTQTFGIE KYIPYTLYSV FNPSDHDLVL
510 520 530 540 550
IRLKKKGDRC ATRSQFVQPI CLPEPGSTFP AGHKCQIAGW GHLDENVSGY
560 570 580 590 600
SSSLREALVP LVADHKCSSP EVYGADISPN MLCAGYFDCK SDACQGDSGG
610 620 630 640 650
PLACEKNGVA YLYGIISWGD GCGRLHKPGV YTRVANYVDW INDRIRPPRR

LVAPS
Length:655
Mass (Da):70,682
Last modified:June 1, 1994 - v1
Checksum:i2CF72F1E1B862ED7
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_051851218A → S.Corresponds to variant rs3748034dbSNPEnsembl.1
Natural variantiVAR_033651225V → M.Corresponds to variant rs16844370dbSNPEnsembl.1
Natural variantiVAR_033652231F → L.1 PublicationCorresponds to variant rs1987546dbSNPEnsembl.1
Natural variantiVAR_024294509R → H.Corresponds to variant rs16844401dbSNPEnsembl.1
Natural variantiVAR_024295644R → Q.Corresponds to variant rs2498323dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS3369.1.
PIRiA46688.
RefSeqiNP_001284368.1. NM_001297439.1.
NP_001519.1. NM_001528.3.
UniGeneiHs.104.

Genome annotation databases

EnsembliENST00000382774; ENSP00000372224; ENSG00000109758.
GeneIDi3083.
KEGGihsa:3083.
UCSCiuc003ghc.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS3369.1.
PIRiA46688.
RefSeqiNP_001284368.1. NM_001297439.1.
NP_001519.1. NM_001528.3.
UniGeneiHs.104.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
ProteinModelPortaliQ04756.
SMRiQ04756.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109331. 6 interactors.
DIPiDIP-6022N.
IntActiQ04756. 3 interactors.
STRINGi9606.ENSP00000372224.

Chemistry databases

BindingDBiQ04756.
ChEMBLiCHEMBL3351190.

Protein family/group databases

MEROPSiS01.228.

PTM databases

iPTMnetiQ04756.
PhosphoSitePlusiQ04756.

Polymorphism and mutation databases

BioMutaiHGFAC.
DMDMi547643.

Proteomic databases

EPDiQ04756.
MaxQBiQ04756.
PaxDbiQ04756.
PeptideAtlasiQ04756.
PRIDEiQ04756.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000382774; ENSP00000372224; ENSG00000109758.
GeneIDi3083.
KEGGihsa:3083.
UCSCiuc003ghc.4. human.

Organism-specific databases

CTDi3083.
DisGeNETi3083.
GeneCardsiHGFAC.
HGNCiHGNC:4894. HGFAC.
HPAiHPA058279.
HPA059076.
MIMi604552. gene.
neXtProtiNX_Q04756.
OpenTargetsiENSG00000109758.
PharmGKBiPA29270.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1217. Eukaryota.
KOG3627. Eukaryota.
COG5640. LUCA.
GeneTreeiENSGT00760000119133.
HOGENOMiHOG000237314.
HOVERGENiHBG004345.
InParanoidiQ04756.
KOiK09631.
PhylomeDBiQ04756.
TreeFamiTF329901.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000109758-MONOMER.
ReactomeiR-HSA-6806942. MET Receptor Activation.

Miscellaneous databases

EvolutionaryTraceiQ04756.
GeneWikiiHGFAC.
GenomeRNAii3083.
PMAP-CutDBQ04756.
PROiQ04756.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000109758.
CleanExiHS_HGFAC.
ExpressionAtlasiQ04756. baseline and differential.
GenevisibleiQ04756. HS.

Family and domain databases

CDDicd00062. FN2. 1 hit.
cd00190. Tryp_SPc. 1 hit.
Gene3Di2.10.10.10. 1 hit.
InterProiIPR014394. Coagulation_fac_XIIa/HGFA.
IPR013032. EGF-like_CS.
IPR000742. EGF-like_dom.
IPR000083. Fibronectin_type1.
IPR000562. FN_type2_col-bd.
IPR000001. Kringle.
IPR013806. Kringle-like.
IPR018056. Kringle_CS.
IPR009003. Peptidase_S1_PA.
IPR001314. Peptidase_S1A.
IPR001254. Trypsin_dom.
IPR018114. TRYPSIN_HIS.
IPR033116. TRYPSIN_SER.
[Graphical view]
PfamiPF00008. EGF. 1 hit.
PF00039. fn1. 1 hit.
PF00040. fn2. 1 hit.
PF00051. Kringle. 1 hit.
PF00089. Trypsin. 1 hit.
[Graphical view]
PIRSFiPIRSF001146. Factor_XII_HGFA. 1 hit.
PRINTSiPR00722. CHYMOTRYPSIN.
SMARTiSM00181. EGF. 2 hits.
SM00058. FN1. 1 hit.
SM00059. FN2. 1 hit.
SM00130. KR. 1 hit.
SM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMiSSF50494. SSF50494. 1 hit.
SSF57440. SSF57440. 2 hits.
PROSITEiPS00022. 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]
ProtoNetiSearch...

Entry informationi

Entry nameiHGFA_HUMAN
AccessioniPrimary (citable) accession number: Q04756
Secondary accession number(s): Q14726, Q2M1W7, Q53X47
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: November 30, 2016
This is version 163 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Caution

It is uncertain whether Met-1 is the initiator.Curated

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Peptidase families
    Classification of peptidase families and list of entries
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.