DB code: M00349

RLCP classification 1.13.30000.10 : Hydrolysis
CATH domain -.-.-.- :
3.10.250.10 : Mac-2 Binding Protein
2.40.10.10 : Thrombin, subunit H Catalytic domain
2.40.10.10 : Thrombin, subunit H Catalytic domain
E.C. 3.4.21.106
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
3.10.250.10 : Mac-2 Binding Protein M00227
2.40.10.10 : Thrombin, subunit H M00139 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

Uniprot Enzyme Name
UniprotKB Protein name Synonyms Contains RefSeq MEROPS Pfam
P05981 Serine protease hepsin
EC 3.4.21.106
Transmembrane protease serine 1
Serine protease hepsin non-catalytic chain
Serine protease hepsin catalytic chain
NP_002142.1 (Protein)
NM_002151.2 (DNA/RNA sequence)
NP_892028.1 (Protein)
NM_182983.2 (DNA/RNA sequence)
S01.224 (Serine)
PF09272 (Hepsin-SRCR)
PF00089 (Trypsin)
[Graphical View]

KEGG enzyme name
Hepsin

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P05981 HEPS_HUMAN Cleavage after basic amino-acid residues, with Arg strongly preferred to Lys. Membrane. single-pass type II membrane protein.

KEGG Pathways
Map code Pathways E.C.

Compound table
Substrates Products Intermediates
KEGG-id C00012 C00001 C00012 I00087 I00085 I00086
E.C.
Compound Peptide H2O Peptide Peptidyl-Ser-tetrahedral-intermediate (with previous peptide) Acyl-enzyme(Peptidyl-Ser-acyl group) Peptidyl-Ser-tetrahedral-intermediate
Type peptide/protein H2O peptide/protein
ChEBI 15377
PubChem 22247451
962
1o5eL00 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1o5fL00 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1p57A00 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1z8gA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
3t2nA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
3t2nB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1o5eH01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:132 Unbound Unbound Unbound Unbound
1o5fH01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:CR9 Unbound Unbound Unbound Unbound
1p57B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:CR4 Unbound Unbound Unbound Unbound
1z8gA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Transition-state-analogue:ACE-LYS-GLN-LEU-AR7-0QE(chain L)
3t2nA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
3t2nB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1o5eH02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1o5fH02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1p57B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1z8gA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
3t2nA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
3t2nB03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Literature [5] & Swiss-prot;P05981

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1o5eL00 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1o5fL00 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1p57A00 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1z8gA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
3t2nA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
3t2nB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1o5eH01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 195 GLY 193;SER 195
1o5fH01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 195 GLY 193;SER 195
1p57B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 195 GLY 193;SER 195
1z8gA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 353 GLY 351;SER 353
3t2nA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 353 GLY 351;SER 353 invisible 297-306, 343-350
3t2nB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 353 GLY 351;SER 353 invisible 297-306, 343-350
1o5eH02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 57;ASP 102
1o5fH02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 57;ASP 102
1p57B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 57;ASP 102
1z8gA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 203;ASP 257
3t2nA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 203;ASP 257
3t2nB03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 203;ASP 257

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[4]
Figure 5

References
[1]
Resource
Comments
Medline ID
PubMed ID 7814421
Journal J Biol Chem
Year 1995
Volume 270
Pages 66-72
Authors Kazama Y, Hamamoto T, Foster DC, Kisiel W
Title Hepsin, 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.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 9003440
Journal Biochim Biophys Acta
Year 1997
Volume 1337
Pages 85-95
Authors Zhukov A, Hellman U, Ingelman-Sundberg M
Title Purification and characterization of hepsin from rat liver microsomes.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 9395459
Journal J Biol Chem
Year 1997
Volume 272
Pages 31315-20
Authors Vu TK, Liu RW, Haaksma CJ, Tomasek JJ, Howard EW
Title Identification and cloning of the membrane-associated serine protease, hepsin, from mouse preimplantation embryos.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 12475199
Journal Chem Rev
Year 2002
Volume 102
Pages 4501-24
Authors Hedstrom L
Title Serine protease mechanism and specificity.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 12962630
Journal Structure
Year 2003
Volume 11
Pages 1123-31
Authors Somoza JR, Ho JD, Luong C, Ghate M, Sprengeler PA, Mortara K, Shrader WD, Sperandio D, Chan H, McGrath ME, Katz BA
Title The structure of the extracellular region of human hepsin reveals a serine protease domain and a novel scavenger receptor cysteine-rich (SRCR) domain.
Related PDB 1p57
Related UniProtKB P05981
[6]
Resource
Comments
Medline ID
PubMed ID 15522303
Journal J Mol Biol
Year 2004
Volume 344
Pages 527-47
Authors Katz 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
Title Dissecting and designing inhibitor selectivity determinants at the S1 site using an artificial Ala190 protease (Ala190 uPA).
Related PDB 1o5e 1o5f
Related UniProtKB P05981
[7]
Resource
Comments
Medline ID
PubMed ID 15839837
Journal Biochem J
Year 2005
Volume 390
Pages 125-36
Authors Herter 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
Title Hepatocyte growth factor is a preferred in vitro substrate for human hepsin, a membrane-anchored serine protease implicated in prostate and ovarian cancers.
Related PDB 1z8g
Related UniProtKB P05981
[8]
Resource
Comments
Medline ID
PubMed ID 15792801
Journal FEBS Lett
Year 2005
Volume 579
Pages 1945-50
Authors Kirchhofer D, Peek M, Lipari MT, Billeci K, Fan B, Moran P
Title Hepsin activates pro-hepatocyte growth factor and is inhibited by hepatocyte growth factor activator inhibitor-1B (HAI-1B) and HAI-2.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 16651711
Journal Biol Pharm Bull
Year 2006
Volume 29
Pages 868-74
Authors Kunii D, Shimoji M, Nakama S, Ikebe M, Hachiman T, Sato I, Tamaki A, Yamazaki K, Aniya Y
Title Purification of liver serine protease which activates microsomal glutathione S-transferase: possible involvement of hepsin.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 16908524
Journal J Biol Chem
Year 2006
Volume 281
Pages 30439-46
Authors Moran P, Li W, Fan B, Vij R, Eigenbrot C, Kirchhofer D
Title Pro-urokinase-type plasminogen activator is a substrate for hepsin.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 18784072
Journal J Biol Chem
Year 2008
Volume 283
Pages 30576-84
Authors Tripathi M, Nandana S, Yamashita H, Ganesan R, Kirchhofer D, Quaranta V
Title Laminin-332 is a substrate for hepsin, a protease associated with prostate cancer progression.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 20507279
Journal Biochem J
Year 2010
Volume 428
Pages 325-46
Authors Antalis TM, Buzza MS, Hodge KM, Hooper JD, Netzel-Arnett S
Title The cutting edge: membrane-anchored serine protease activities in the pericellular microenvironment.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 20410586
Journal Biol Pharm Bull
Year 2010
Volume 33
Pages 561-7
Authors Nakama S, Oshiro N, Aniya Y
Title Activation of rat liver microsomal glutathione transferase by hepsin.
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 19911255
Journal Mol Cell Biochem
Year 2010
Volume 337
Pages 259-66
Authors Chen M, Chen LM, Lin CY, Chai KX
Title Hepsin activates prostasin and cleaves the extracellular domain of the epidermal growth factor receptor.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 22132769
Journal Biochem J
Year 2012
Volume 442
Pages 483-94
Authors Koschubs 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
Title Allosteric antibody inhibition of human hepsin protease.
Related PDB 3t2n
Related UniProtKB

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.

Created Updated
2011-02-14 2012-08-06