1Z8G

Crystal structure of the extracellular region of the transmembrane serine protease hepsin with covalently bound preferred substrate.

External Resource: Annotation

Domain Annotation: SCOP/SCOPe Classification
Domain Annotation: SCOP2 Classification
Domain Annotation: ECOD Classification
Domain Annotation: CATH
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations
Protein Modification Annotation

Domain Annotation: SCOP/SCOPe Classification SCOP-e Database Homepage

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
A	d1z8ga1	All beta proteins	Trypsin-like serine proteases	Trypsin-like serine proteases	Eukaryotic proteases	Hepsin, catalytic domain	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
A	d1z8ga2	Alpha and beta proteins (a+b)	SRCR-like	SRCR-like	Hepsin, N-terminal domain	Hepsin, N-terminal domain	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
A	SCOP2 Family	Eukaryotic proteases	8022995	4000286	SCOP2 (2022-06-29)
A	SCOP2 Family	Hepsin, N-terminal domain	8022998	4001629	SCOP2 (2022-06-29)
A	SCOP2 Superfamily	Trypsin-like serine proteases	8035375	3000114	SCOP2 (2022-06-29)
A	SCOP2 Superfamily	SRCR-like	8035378	3001377	SCOP2 (2022-06-29)

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
A	Trypsin_1	e1z8gA1	A: beta barrels	X: cradle loop barrel	H: RIFT-related	T: FMN-binding split barrel 2	F: Trypsin_1	ECOD (1.6)
A	Hepsin-SRCR	e1z8gA2	A: a+b complex topology	X: SRCR-like	H: SRCR-like (From Topology)	T: SRCR-like	F: Hepsin-SRCR	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	3.10.250.10	Alpha Beta	Roll	Mac-2 Binding Protein	SRCR-like domain	CATH (4.3.0)
A	2.40.10.10	Mainly Beta	Beta Barrel	Thrombin, subunit H	Trypsin-like serine proteases	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A	PF09272	Hepsin, SRCR domain (Hepsin-SRCR)	Hepsin, SRCR domain	Members of this family form an extracellular domain of the serine protease hepsin. They are formed primarily by three elements of regular secondary structure: a 12-residue alpha helix, a twisted five-stranded antiparallel beta sheet, and a second, tw ...	Members of this family form an extracellular domain of the serine protease hepsin. They are formed primarily by three elements of regular secondary structure: a 12-residue alpha helix, a twisted five-stranded antiparallel beta sheet, and a second, two-stranded, antiparallel sheet. The two beta-sheets lie at roughly right angles to each other, with the helix nestled between the two, adopting an SRCR fold. The exact function of this domain has not been identified, though it probably may serve to orient the protease domain or place it in the vicinity of its substrate [1].	Domain
A	PF00089	Trypsin (Trypsin)	Trypsin	-	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A	Serine protease hepsin	peptidase activity catalytic activity, acting on a protein hydrolase activity catalytic activity serine-type exopeptidase activity serine hydrolase activity serine-type peptidase activity exopeptidase activity serine-type endopeptidase activity endopeptidase activity	regulation of biological process regulation of growth regulation of cellular process regulation of cellular component organization positive regulation of biological process biological regulation growth positive regulation of cell growth regulation of cell growth cell growth cellular component organization positive regulation of growth cellular process cellular component organization or biogenesis regulation of biological process regulation of growth regulation of cellular process regulation of cellular component organization positive regulation of biological process biological regulation growth positive regulation of cell growth regulation of cell growth cell growth cellular component organization positive regulation of growth cellular process cellular component organization or biogenesis positive regulation of cellular process transport monoatomic ion transmembrane transport potassium ion transmembrane transport inorganic ion transmembrane transport establishment of localization metal ion transport inorganic cation transmembrane transport transmembrane transport monoatomic cation transmembrane transport localization monoatomic ion transport potassium ion transport monoatomic cation transport regulation of protein maturation positive regulation of protein maturation cellular biosynthetic process positive regulation of protein metabolic process positive regulation of cellular metabolic process positive regulation of macromolecule biosynthetic process positive regulation of protein processing protein maturation regulation of primary metabolic process positive regulation of metabolic process positive regulation of plasminogen activation regulation of proteolysis positive regulation of biosynthetic process proteolysis regulation of plasminogen activation positive regulation of macromolecule metabolic process protein metabolic process plasminogen activation zymogen activation regulation of biosynthetic process cellular metabolic process regulation of protein metabolic process primary metabolic process regulation of cellular metabolic process regulation of macromolecule metabolic process gene expression macromolecule biosynthetic process regulation of cellular biosynthetic process regulation of gene expression biosynthetic process positive regulation of gene expression positive regulation of proteolysis regulation of protein processing protein processing metabolic process regulation of macromolecule biosynthetic process macromolecule metabolic process regulation of metabolic process positive regulation of cellular biosynthetic process negative regulation of programmed cell death regulation of apoptotic process negative regulation of biological process regulation of programmed cell death cell death negative regulation of apoptotic process negative regulation of cellular process apoptotic process programmed cell death reflex response to stimulus pilomotor reflex response to external stimulus cellular component disassembly extracellular matrix disassembly basement membrane disassembly extracellular matrix organization extracellular structure organization external encapsulating structure organization basement membrane organization developmental process regulation of developmental process regulation of cell shape cell morphogenesis regulation of cell morphogenesis anatomical structure morphogenesis anatomical structure development regulation of biological quality regulation of anatomical structure morphogenesis regulation of hormone metabolic process organic hydroxy compound metabolic process thyroid hormone generation positive regulation of thyroid hormone generation positive regulation of hormone metabolic process regulation of hormone levels hormone metabolic process cellular modified amino acid metabolic process thyroid hormone metabolic process phenol-containing compound metabolic process regulation of thyroid hormone generation multicellular organismal process detection of external stimulus system process nervous system process detection of mechanical stimulus involved in sensory perception of sound response to mechanical stimulus detection of mechanical stimulus involved in sensory perception sensory perception of mechanical stimulus detection of abiotic stimulus detection of stimulus sensory perception detection of mechanical stimulus response to abiotic stimulus detection of stimulus involved in sensory perception sensory perception of sound regulation of hepatocyte proliferation positive regulation of cell population proliferation gland development liver development multicellular organism development gland morphogenesis animal organ morphogenesis epithelial cell proliferation liver morphogenesis system development cell population proliferation positive regulation of epithelial cell proliferation animal organ development epithelial cell proliferation involved in liver morphogenesis hepatocyte proliferation regulation of cell population proliferation hepaticobiliary system development positive regulation of hepatocyte proliferation regulation of epithelial cell proliferation viral gene expression biological process involved in interspecies interaction between organisms modulation by host of symbiont process viral process biological process involved in interaction with symbiont viral transcription positive regulation by host of viral transcription biological process involved in symbiotic interaction ear morphogenesis embryonic organ morphogenesis ear development sensory organ development embryonic morphogenesis embryo development sensory organ morphogenesis inner ear development cochlea development inner ear morphogenesis cochlea morphogenesis embryonic organ development response to thyroid hormone response to hormone response to endogenous stimulus response to chemical regulation of epithelial to mesenchymal transition cellular developmental process regulation of cell differentiation mesenchyme development cell differentiation negative regulation of cell differentiation regulation of multicellular organismal process negative regulation of developmental process tissue development negative regulation of epithelial to mesenchymal transition epithelial to mesenchymal transition mesenchymal cell differentiation negative regulation of multicellular organismal process negative regulation of cell population proliferation negative regulation of epithelial cell proliferation	membrane cellular anatomical entity cell-cell junction anchoring junction cell junction cell periphery apical part of cell plasma membrane plasma membrane region apical plasma membrane extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle membrane cellular anatomical entity cell-cell junction anchoring junction cell junction cell periphery apical part of cell plasma membrane plasma membrane region apical plasma membrane extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle extracellular region organelle extracellular space vesicle extracellular membrane-bounded organelle cell surface intracellular anatomical structure organelle subcompartment intracellular membrane-bounded organelle endomembrane system endoplasmic reticulum subcompartment intracellular organelle nuclear outer membrane-endoplasmic reticulum membrane network endoplasmic reticulum cytoplasm organelle membrane endoplasmic reticulum membrane somatodendritic compartment cell body neuronal cell body
B [auth L]	ACE-LYS-GLN-LEU-ARG-Chloromethylketone	-	-	-

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A	IPR018114	Serine proteases, trypsin family, histidine active site	Active Site
A	IPR015352	Hepsin, SRCR domain	Domain
A	IPR017448	SRCR-like_dom	Unknown
A	IPR009003	Peptidase S1, PA clan	Homologous Superfamily
A	IPR001314	Peptidase S1A, chymotrypsin family	Family
A	IPR033116	Serine proteases, trypsin family, serine active site	Active Site
A	IPR036772	SRCR-like domain superfamily	Homologous Superfamily
A	IPR001254	Serine proteases, trypsin domain	Domain
A	IPR043504	Peptidase S1, PA clan, chymotrypsin-like fold	Homologous Superfamily

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A	Pharos: P05981	prostate cancer Prostatic Neoplasms breast cancer Crohn disease invasive ductal breast carcinoma malignant pancreatic neoplasm pancreatic ductal adenocarcinoma psoriasis breast carcinoma cystic fibrosis Hodgkins lymphoma nephrosclerosis pancreatic intraductal papillary-mucinous neoplasm breast fibroadenoma familial hyperlipidemia prostate cancer Prostatic Neoplasms breast cancer Crohn disease invasive ductal breast carcinoma malignant pancreatic neoplasm pancreatic ductal adenocarcinoma psoriasis breast carcinoma cystic fibrosis Hodgkins lymphoma nephrosclerosis pancreatic intraductal papillary-mucinous neoplasm breast fibroadenoma familial hyperlipidemia lysosomal lipid storage disorder ovarian cancer

Protein Modification Annotation

Modified Residue(s)
Chain	Residue(s)	Description
B [auth L]	0QE
B [auth L]	ACE	RESID: AA0041 , AA0042 , AA0043 , AA0044 , AA0045 , AA0046 , AA0049 , AA0050 , AA0051 , AA0052 , AA0053 , AA0054 , AA0354 PSI-MOD : N-acetyl-L-alanine MOD:00050 , N-acetyl-L-aspartic acid MOD:00051 , N-acetyl-L-cysteine MOD:00052 , N-acetyl-S-archeol-cysteine MOD:00897 , N-acetyl-L-glutamic acid MOD:00053 , N-acetyl-L-glutamine MOD:00054 , N-acetylglycine MOD:00055 , N-acetyl-L-methionine MOD:00058 , N-acetyl-L-proline MOD:00059 , N-acetyl-L-serine MOD:00060 , N,O-diacetylated L-serine MOD:00648 , N-acetyl-L-threonine MOD:00061 , N-acetyl-L-tyrosine MOD:00062 , N-acetyl-L-valine MOD:00063 , N2-acetyl-L-arginine MOD:00359
B [auth L]	AR7	Parent Component: ARG RESID: AA0041 , AA0042 , AA0043 , AA0044 , AA0045 , AA0046 , AA0049 , AA0050 , AA0051 , AA0052 , AA0053 , AA0054 , AA0354

RCSB PDB Core Operations are funded by the U.S. National Science Foundation (DBI-2321666), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM157729.