DB code: M00227

RLCP classification	1.13.30000.10 : Hydrolysis
CATH domain	-.-.-.- :
	3.30.70.960 : Alpha-Beta Plaits
	2.60.120.290 : Jelly Rolls
	2.-.-.- :
	2.60.120.290 : Jelly Rolls
	-.-.-.- :
	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.	3.4.21.9
CSA
M-CSA
MACiE

CATH domain	Related DB codes (homologues)
2.40.10.10 : Thrombin, subunit H	M00139 D00214 M00167 D00426 M00133 D00428 D00429 D00430 D00431 D00432 D00433 D00434 D00435 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 M00349 T00074 T00410 T00411
2.60.120.290 : Jelly Rolls	M00139 M00315 M00316 M00317 M00348
3.10.250.10 : Mac-2 Binding Protein	M00349
3.30.70.960 : Alpha-Beta Plaits	M00348

Uniprot Enzyme Name
UniprotKB	Protein name	Synonyms	Contains	RefSeq	MEROPS	Pfam
P98072	Enteropeptidase	EC 3.4.21.9 Enterokinase Serine protease 7	Enteropeptidase non-catalytic heavy chain Enteropeptidase catalytic light chain	NP_776864.1 (Protein) NM_174439.2 (DNA/RNA sequence)	S01.156 (Serine)	PF00431 (CUB) PF00057 (Ldl_recept_a) PF00629 (MAM) PF01390 (SEA) PF00530 (SRCR) PF00089 (Trypsin) [Graphical View]

KEGG enzyme name
enteropeptidase enterokinase

UniprotKB: Accession Number	Entry name	Activity	Subunit	Subcellular location	Cofactor
P98072	ENTK_BOVIN	Activation of trypsinogen by selective cleavage of 6-Lys-\|-Ile-7 bond.	Heterodimer of a catalytic (light) chain and a multidomain (heavy) chain linked by a disulfide bond.	Membrane, Single-pass type II membrane protein (Probable).

KEGG Pathways
Map code	Pathways	E.C.

Compound table
	Substrates		Products	Intermediates
KEGG-id	L00076	C00001	C00298	I00087	I00085	I00086
E.C.
Compound	Trypsinogen	H2O	Trypsin	Peptidyl-tetrahedral intermediate	Acyl-enzyme	Tetrahedral intermediate
Type	peptide/protein	H2O	peptide/protein
ChEBI		15377 15377
PubChem		22247451 962 22247451 962

1ekbB01	Unbound		Unbound	Unbound	Unbound	Intermediate-analogue:ASP-ASP-ASP-LYS (chain C)
1ekbB02	Unbound		Unbound	Unbound	Unbound	Unbound

Reference for Active-site residues
resource	references	E.C.

Active-site residues
PDB	Catalytic residues	Cofactor-binding residues	Modified residues	Main-chain involved in catalysis	Comment

1ekbB01	SER 195			GLY 193;ASP 194;SER 195(mainchain amide)
1ekbB02	HIS 57;ASP 102

References for Catalytic Mechanism
References	Sections	No. of steps in catalysis
[10]	p.364

References
[1]
Resource
Comments
Medline ID
PubMed ID	12810
Journal	Biochim Biophys Acta
Year	1976
Volume	452
Pages	488-96
Authors	Baratti J, Maroux S
Title	On the catalytic and binding sites of porcine enteropeptidase.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID	8051081
Journal	J Biol Chem
Year	1994
Volume	269
Pages	19976-82
Authors	Matsushima M, Ichinose M, Yahagi N, Kakei N, Tsukada S, Miki K, Kurokawa K, Tashiro K, Shiokawa K, Shinomiya K, et al
Title	Structural characterization of porcine enteropeptidase.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID	8052624
Journal	Proc Natl Acad Sci U S A
Year	1994
Volume	91
Pages	7588-92
Authors	Kitamoto Y, Yuan X, Wu Q, McCourt DW, Sadler JE
Title	Enterokinase, the initiator of intestinal digestion, is a mosaic protease composed of a distinctive assortment of domains.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID	8962677
Journal	Biol Chem Hoppe Seyler
Year	1995
Volume	376
Pages	681-4
Authors	Wang ZM, Rubin H, Schechter NM
Title	Production of active recombinant human chymase from a construct containing the enterokinase cleavage site of trypsinogen in place of the native propeptide sequence.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID	9636275
Journal	Biotechnology (N Y)
Year	1995
Volume	13
Pages	982-7
Authors	Collins-Racie LA, McColgan JM, Grant KL, DiBlasio-Smith EA, McCoy JM, LaVallie ER
Title	Production of recombinant bovine enterokinase catalytic subunit in Escherichia coli using the novel secretory fusion partner DsbA.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID	9636316
Journal	Biotechnology (N Y)
Year	1996
Volume	14
Pages	77-81
Authors	Vozza LA, Wittwer L, Higgins DR, Purcell TJ, Bergseid M, Collins-Racie LA, LaVallie ER, Hoeffler JP
Title	Production of a recombinant bovine enterokinase catalytic subunit in the methylotrophic yeast Pichia pastoris.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID	9395456
Journal	J Biol Chem
Year	1997
Volume	272
Pages	31293-300
Authors	Lu D, Yuan X, Zheng X, Sadler JE
Title	Bovine proenteropeptidase is activated by trypsin, and the specificity of enteropeptidase depends on the heavy chain.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID	10094769
Journal	Anal Biochem
Year	1999
Volume	269
Pages	10-6
Authors	Hosfield T, Lu Q
Title	Influence of the amino acid residue downstream of (Asp)4Lys on enterokinase cleavage of a fusion protein.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID	9880538
Journal	J Biol Chem
Year	1999
Volume	274
Pages	1596-605
Authors	Zheng X, Lu D, Sadler JE
Title	Apical sorting of bovine enteropeptidase does not involve detergent-resistant association with sphingolipid-cholesterol rafts.
Related PDB
Related UniProtKB
[10]
Resource
Comments	X-ray crystallography
Medline ID
PubMed ID	10493881
Journal	J Mol Biol
Year	1999
Volume	292
Pages	361-73
Authors	Lu D, Futterer K, Korolev S, Zheng X, Tan K, Waksman G, Sadler JE
Title	Crystal structure of enteropeptidase light chain complexed with an analog of the trypsinogen activation peptide.
Related PDB	1ekb
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID	10656339
Journal	J Biotechnol
Year	2000
Volume	76
Pages	245-51
Authors	Svetina M, Krasevec N, Gaberc-Porekar V, Komel R
Title	Expression of catalytic subunit of bovine enterokinase in the filamentous fungus Aspergillus niger.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID	11719902
Journal	Am J Hum Genet
Year	2002
Volume	70
Pages	20-5
Authors	Holzinger A, Maier EM, Buck C, Mayerhofer PU, Kappler M, Haworth JC, Moroz SP, Hadorn HB, Sadler JE, Roscher AA
Title	Mutations in the proenteropeptidase gene are the molecular cause of congenital enteropeptidase deficiency.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID	11913964
Journal	Arch Biochem Biophys
Year	2002
Volume	400
Pages	1-6
Authors	Song HW, Choi SI, Seong BL
Title	Engineered recombinant enteropeptidase catalytic subunit: effect of N-terminal modification.
Related PDB
Related UniProtKB

Comments
This enzyme belongs to the peptidase family-S1. This protein is composed of a non-catalytic heavy chain, which is a multidomain bound to membrane, and a catalytic light chain. These two chains are linked by a disulfide bond (see [3]). The tertiary strucutre of the catalytic chain has been determined so far. (The chain A in 1ekb is a C-terminal fragment of heavy chain.) However, the homologous domains have been elucidated. Moreover, this enzyme is a member of type II transmembrane serine protease family (see M00348, M00349 in EzCatDB). According to the literature [10], this enzyme has got the catalytic triad, which is a signature of serine proteases; His57, Asp102 and Ser195. Moreover, the Ser195 is bound to the C-terminal of Lys residue, to form a tetrahedral hemiketal intermediate, which showed that Ser195 could function as nucleophile.

Comments

This enzyme belongs to the peptidase family-S1.
This protein is composed of a non-catalytic heavy chain, which is a multidomain bound to membrane, and a catalytic light chain. These two chains are linked by a disulfide bond (see [3]). The tertiary strucutre of the catalytic chain has been determined so far. (The chain A in 1ekb is a C-terminal fragment of heavy chain.) However, the homologous domains have been elucidated. Moreover, this enzyme is a member of type II transmembrane serine protease family (see M00348, M00349 in EzCatDB).
According to the literature [10], this enzyme has got the catalytic triad, which is a signature of serine proteases; His57, Asp102 and Ser195. Moreover, the Ser195 is bound to the C-terminal of Lys residue, to form a tetrahedral hemiketal intermediate, which showed that Ser195 could function as nucleophile.

Created	Updated
2004-03-26	2012-08-06