EzCatDB: M00349
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DB codeM00349
RLCP classification1.13.30000.10 : Hydrolysis
CATH domainDomain 1-.-.-.-
Domain 23.10.250.10 : Mac-2 Binding Protein
Domain 32.40.10.10 : Thrombin, subunit HCatalytic domain
Domain 42.40.10.10 : Thrombin, subunit HCatalytic domain
E.C.3.4.21.106

CATH domainRelated DB codes (homologues)
2.40.10.10 : Thrombin, subunit HM00139,D00214,M00167,D00426,M00133,D00428,D00429,D00430,D00431,D00432,D00433,D00434,D00435,M00227,M00209,D00194,D00197,D00211,D00212,D00216,M00212,D00224,D00497,M00217,M00216,D00528,D00848,D00850,D00851,D00852,D00855,M00152,M00155,M00157,M00181,M00315,M00316,M00317,M00348,T00074,T00410,T00411
3.10.250.10 : Mac-2 Binding ProteinM00227

Enzyme Name
UniProtKBKEGG

P05981
Protein nameSerine protease hepsinHepsin
SynonymsEC 3.4.21.106
Transmembrane protease serine 1
ContainsSerine protease hepsin non-catalytic chain
Serine protease hepsin catalytic chain
RefSeqNP_002142.1 (Protein)
NM_002151.2 (DNA/RNA sequence)
NP_892028.1 (Protein)
NM_182983.2 (DNA/RNA sequence)
MEROPSS01.224 (Serine)
PfamPF09272 (Hepsin-SRCR)
PF00089 (Trypsin)
[Graphical view]


UniProtKB:Accession NumberP05981
Entry nameHEPS_HUMAN
ActivityCleavage after basic amino-acid residues, with Arg strongly preferred to Lys.
Subunit
Subcellular locationMembrane. single-pass type II membrane protein.
Cofactor

Compound table: links to PDB-related databases & PoSSuM

SubstratesProductsintermediates
KEGG-idC00012C00001C00012I00087I00085I00086
CompoundPeptideH2OPeptidePeptidyl-Ser-tetrahedral-intermediate (with previous peptide)Acyl-enzyme(Peptidyl-Ser-acyl group)Peptidyl-Ser-tetrahedral-intermediate
Typepeptide/proteinH2Opeptide/protein


ChEBI
15377




PubChem
962
22247451




              
1o5eL00Unbound UnboundUnboundUnboundUnbound
1o5fL00Unbound UnboundUnboundUnboundUnbound
1p57A00Unbound UnboundUnboundUnboundUnbound
1z8gA01Unbound UnboundUnboundUnboundUnbound
3t2nA01Unbound UnboundUnboundUnboundUnbound
3t2nB01Unbound UnboundUnboundUnboundUnbound
1o5eH01Analogue:132 UnboundUnboundUnboundUnbound
1o5fH01Analogue:CR9 UnboundUnboundUnboundUnbound
1p57B01Analogue:CR4 UnboundUnboundUnboundUnbound
1z8gA02Unbound UnboundUnboundUnboundTransition-state-analogue:ACE-LYS-GLN-LEU-AR7-0QE(chain L)
3t2nA02Unbound  UnboundUnboundUnbound
3t2nB02Unbound  UnboundUnboundUnbound
1o5eH02Unbound UnboundUnboundUnboundUnbound
1o5fH02Unbound UnboundUnboundUnboundUnbound
1p57B02Unbound UnboundUnboundUnboundUnbound
1z8gA03Unbound UnboundUnboundUnboundUnbound
3t2nA03Unbound  UnboundUnboundUnbound
3t2nB03Unbound  UnboundUnboundUnbound

Active-site residues
resource
Literature [5] & Swiss-prot;P05981
pdbCatalytic residuesMain-chain involved in catalysiscomment
           
1o5eL00 
 
 
1o5fL00 
 
 
1p57A00 
 
 
1z8gA01 
 
 
3t2nA01 
 
 
3t2nB01 
 
 
1o5eH01SER 195
GLY 193;SER 195
 
1o5fH01SER 195
GLY 193;SER 195
 
1p57B01SER 195
GLY 193;SER 195
 
1z8gA02SER 353
GLY 351;SER 353
 
3t2nA02SER 353
GLY 351;SER 353
invisible 297-306, 343-350
3t2nB02SER 353
GLY 351;SER 353
invisible 297-306, 343-350
1o5eH02HIS  57;ASP 102
 
 
1o5fH02HIS  57;ASP 102
 
 
1p57B02HIS  57;ASP 102
 
 
1z8gA03HIS 203;ASP 257
 
 
3t2nA03HIS 203;ASP 257
 
 
3t2nB03HIS 203;ASP 257
 
 

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[4]Figure 5

references
[1]
PubMed ID7814421
JournalJ Biol Chem
Year1995
Volume270
Pages66-72
AuthorsKazama Y, Hamamoto T, Foster DC, Kisiel W
TitleHepsin, a putative membrane-associated serine protease, activates human factor VII and initiates a pathway of blood coagulation on the cell surface leading to thrombin formation.
[2]
PubMed ID9003440
JournalBiochim Biophys Acta
Year1997
Volume1337
Pages85-95
AuthorsZhukov A, Hellman U, Ingelman-Sundberg M
TitlePurification and characterization of hepsin from rat liver microsomes.
[3]
PubMed ID9395459
JournalJ Biol Chem
Year1997
Volume272
Pages31315-20
AuthorsVu TK, Liu RW, Haaksma CJ, Tomasek JJ, Howard EW
TitleIdentification and cloning of the membrane-associated serine protease, hepsin, from mouse preimplantation embryos.
[4]
PubMed ID12475199
JournalChem Rev
Year2002
Volume102
Pages4501-24
AuthorsHedstrom L
TitleSerine protease mechanism and specificity.
[5]
PubMed ID12962630
JournalStructure
Year2003
Volume11
Pages1123-31
AuthorsSomoza JR, Ho JD, Luong C, Ghate M, Sprengeler PA, Mortara K, Shrader WD, Sperandio D, Chan H, McGrath ME, Katz BA
TitleThe structure of the extracellular region of human hepsin reveals a serine protease domain and a novel scavenger receptor cysteine-rich (SRCR) domain.
Related PDB1p57
Related UniProtKBP05981
[6]
PubMed ID15522303
JournalJ Mol Biol
Year2004
Volume344
Pages527-47
AuthorsKatz BA, Luong C, Ho JD, Somoza JR, Gjerstad E, Tang J, Williams SR, Verner E, Mackman RL, Young WB, Sprengeler PA, Chan H, Mortara K, Janc JW, McGrath ME
TitleDissecting and designing inhibitor selectivity determinants at the S1 site using an artificial Ala190 protease (Ala190 uPA).
Related PDB1o5e,1o5f
Related UniProtKBP05981
[7]
PubMed ID15839837
JournalBiochem J
Year2005
Volume390
Pages125-36
AuthorsHerter S, Piper DE, Aaron W, Gabriele T, Cutler G, Cao P, Bhatt AS, Choe Y, Craik CS, Walker N, Meininger D, Hoey T, Austin RJ
TitleHepatocyte growth factor is a preferred in vitro substrate for human hepsin, a membrane-anchored serine protease implicated in prostate and ovarian cancers.
Related PDB1z8g
Related UniProtKBP05981
[8]
PubMed ID15792801
JournalFEBS Lett
Year2005
Volume579
Pages1945-50
AuthorsKirchhofer D, Peek M, Lipari MT, Billeci K, Fan B, Moran P
TitleHepsin activates pro-hepatocyte growth factor and is inhibited by hepatocyte growth factor activator inhibitor-1B (HAI-1B) and HAI-2.
[9]
PubMed ID16651711
JournalBiol Pharm Bull
Year2006
Volume29
Pages868-74
AuthorsKunii D, Shimoji M, Nakama S, Ikebe M, Hachiman T, Sato I, Tamaki A, Yamazaki K, Aniya Y
TitlePurification of liver serine protease which activates microsomal glutathione S-transferase: possible involvement of hepsin.
[10]
PubMed ID16908524
JournalJ Biol Chem
Year2006
Volume281
Pages30439-46
AuthorsMoran P, Li W, Fan B, Vij R, Eigenbrot C, Kirchhofer D
TitlePro-urokinase-type plasminogen activator is a substrate for hepsin.
[11]
PubMed ID18784072
JournalJ Biol Chem
Year2008
Volume283
Pages30576-84
AuthorsTripathi M, Nandana S, Yamashita H, Ganesan R, Kirchhofer D, Quaranta V
TitleLaminin-332 is a substrate for hepsin, a protease associated with prostate cancer progression.
[12]
PubMed ID20507279
JournalBiochem J
Year2010
Volume428
Pages325-46
AuthorsAntalis TM, Buzza MS, Hodge KM, Hooper JD, Netzel-Arnett S
TitleThe cutting edge: membrane-anchored serine protease activities in the pericellular microenvironment.
[13]
PubMed ID20410586
JournalBiol Pharm Bull
Year2010
Volume33
Pages561-7
AuthorsNakama S, Oshiro N, Aniya Y
TitleActivation of rat liver microsomal glutathione transferase by hepsin.
[14]
PubMed ID19911255
JournalMol Cell Biochem
Year2010
Volume337
Pages259-66
AuthorsChen M, Chen LM, Lin CY, Chai KX
TitleHepsin activates prostasin and cleaves the extracellular domain of the epidermal growth factor receptor.
[15]
PubMed ID22132769
JournalBiochem J
Year2012
Volume442
Pages483-94
AuthorsKoschubs T, Dengl S, Durr H, Kaluza K, Georges G, Hartl C, Jennewein S, Lanzendorfer M, Auer J, Stern A, Huang KS, Packman K, Gubler U, Kostrewa D, Ries S, Hansen S, Kohnert U, Cramer P, Mundigl O
TitleAllosteric antibody inhibition of human hepsin protease.
Related PDB3t2n

comments
This enzyme belongs to peptidase family-S1. Moreover, this enzyme is a member of type II transmembrane serine protease family, which inculdes matriptase and enteropeptidase (M00348 and M00227 in EzCatDB) (see [12]).
Since this enzyme has got the same catalytic site as trypsin, it must catalyze the trypsin-like reaction.

createdupdated
2011-02-142012-08-06


Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
Supported by the commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI) (October 2012 - )
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