3T2N

Human hepsin protease in complex with the Fab fragment of an inhibitory antibody

External Resource: Annotation

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

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

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
C [auth H]	d3t2nh_	All beta proteins	Immunoglobulin-like beta-sandwich	Immunoglobulin	automated matches	automated matches	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
D [auth I]	d3t2ni_	All beta proteins	Immunoglobulin-like beta-sandwich	Immunoglobulin	automated matches	automated matches	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
E [auth L]	d3t2nl2	All beta proteins	Immunoglobulin-like beta-sandwich	Immunoglobulin	C1 set domains (antibody constant domain-like)	automated matches	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
E [auth L]	d3t2nl1	All beta proteins	Immunoglobulin-like beta-sandwich	Immunoglobulin	automated matches	automated matches	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
F [auth M]	d3t2nm2	All beta proteins	Immunoglobulin-like beta-sandwich	Immunoglobulin	C1 set domains (antibody constant domain-like)	automated matches	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
F [auth M]	d3t2nm1	All beta proteins	Immunoglobulin-like beta-sandwich	Immunoglobulin	automated matches	automated matches	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	SCOP2B Superfamily	SRCR-like	8035378	3001377	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	Trypsin-like serine proteases	8035375	3000114	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	SRCR-like	8035378	3001377	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	Trypsin-like serine proteases	8035375	3000114	SCOP2B (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	e3t2nA3	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	e3t2nA2	A: a+b complex topology	X: SRCR-like	H: SRCR-like (From Topology)	T: SRCR-like	F: Hepsin-SRCR	ECOD (1.6)
B	Trypsin_1	e3t2nB2	A: beta barrels	X: cradle loop barrel	H: RIFT-related	T: FMN-binding split barrel 2	F: Trypsin_1	ECOD (1.6)
B	Hepsin-SRCR	e3t2nB1	A: a+b complex topology	X: SRCR-like	H: SRCR-like (From Topology)	T: SRCR-like	F: Hepsin-SRCR	ECOD (1.6)
C [auth H]	V-set_8	e3t2nH1	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: V-set_8	ECOD (1.6)
C [auth H]	C1-set_1	e3t2nH2	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: C1-set_1	ECOD (1.6)
D [auth I]	V-set_8	e3t2nI1	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: V-set_8	ECOD (1.6)
D [auth I]	C1-set_1	e3t2nI2	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: C1-set_1	ECOD (1.6)
E [auth L]	C1-set	e3t2nL2	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: C1-set	ECOD (1.6)
E [auth L]	V-set_3	e3t2nL1	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: V-set_3	ECOD (1.6)
F [auth M]	C1-set	e3t2nM2	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: C1-set	ECOD (1.6)
F [auth M]	V-set_3	e3t2nM1	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: V-set_3	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)
B	3.10.250.10	Alpha Beta	Roll	Mac-2 Binding Protein	SRCR-like domain	CATH (4.3.0)
B	2.40.10.10	Mainly Beta	Beta Barrel	Thrombin, subunit H	Trypsin-like serine proteases	CATH (4.3.0)
C [auth H]	2.60.40.10	Mainly Beta	Sandwich	Immunoglobulin-like	Immunoglobulins	CATH (4.3.0)
D [auth I]	2.60.40.10	Mainly Beta	Sandwich	Immunoglobulin-like	Immunoglobulins	CATH (4.3.0)
E [auth L]	2.60.40.10	Mainly Beta	Sandwich	Immunoglobulin-like	Immunoglobulins	CATH (4.3.0)
F [auth M]	2.60.40.10	Mainly Beta	Sandwich	Immunoglobulin-like	Immunoglobulins	CATH (4.3.0)

IMGT Antibody Annotation IMGT Database Homepage

Chain	Protein Name	Description	Organism Name	Gene Allele Name(s)	Domain Name(s)	Receptor Type	Receptor Description	Provenance Source
C [auth H], D [auth I]	protease	VH-CH1	Homo sapiens (human)	IGHV7-4-102, IGHJ401, IGHJ402, IGHJ403, IGHG101, IGHG102, IGHG1*04	V-DOMAIN VH, C-DOMAIN CH1	IG	FAB-GAMMA-1_KAPPA	IMGT (202415-0)
E [auth L], F [auth M]	protease	L-LAMBDA	Homo sapiens (human)	IGLV7-4301, IGLJ601, IGLC201, IGLC202, IGLC3*04	V-DOMAIN V-LAMBDA, C-DOMAIN C-LAMBDA	IG	FAB-GAMMA-1_KAPPA	IMGT (202415-0)

SAbDab Antibody Annotation SAbDab Database Homepage

Chain	Chain Class	Chain Subclass	Chain Type	Antigen Name(s)	Provenance Source
C [auth H], D [auth I]	Heavy Chain	IGHV7	-	serine protease hepsin	SAbDab (2024-04-19)
E [auth L], F [auth M]	Light Chain	IGLV7	Lambda	serine protease hepsin	SAbDab (2024-04-19)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B	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

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B	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 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 proteolysis organic substance biosynthetic process positive regulation of macromolecule metabolic process plasminogen activation zymogen activation cellular metabolic process regulation of protein metabolic process primary metabolic process regulation of cellular metabolic process regulation of gene expression biosynthetic process positive regulation of proteolysis regulation of protein processing protein processing metabolic process regulation of macromolecule biosynthetic process macromolecule metabolic process regulation of metabolic process cellular biosynthetic process positive regulation of protein metabolic process positive regulation of cellular metabolic process organic substance metabolic process positive regulation of biosynthetic process regulation of plasminogen activation protein metabolic process regulation of biosynthetic process organonitrogen compound metabolic process regulation of macromolecule metabolic process gene expression macromolecule biosynthetic process regulation of cellular biosynthetic process positive regulation of gene expression 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 organic cyclic compound 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 organic substance response to thyroid hormone response to hormone response to chemical response to endogenous stimulus 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
C [auth H], D [auth I]	Antibody, Fab fragment, Heavy Chain	-	-	-
E [auth L], F [auth M]	Antibody, Fab fragment, Light Chain	-	-	-

InterPro: Protein Family Classification InterPro Database Homepage

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

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B	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

RCSB PDB Core Operations are funded by the National Science Foundation (DBI-1832184), 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 R01GM133198.