1GMN

CRYSTAL STRUCTURES OF NK1-HEPARIN COMPLEXES REVEAL THE BASIS FOR NK1 ACTIVITY AND ENABLE ENGINEERING OF POTENT AGONISTS OF THE MET RECEPTOR

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

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

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
A	d1gmna1	Small proteins	Hairpin loop containing domain-like	Hairpin loop containing domain-like	Hairpin loop containing domain	Hepatocyte growth factor	HUMAN (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
A	d1gmna2	Small proteins	Kringle-like	Kringle-like	Kringle modules	NK1 fragment of hepatocyte growth factor	HUMAN (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d1gmnb1	Small proteins	Hairpin loop containing domain-like	Hairpin loop containing domain-like	Hairpin loop containing domain	Hepatocyte growth factor	HUMAN (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d1gmnb2	Small proteins	Kringle-like	Kringle-like	Kringle modules	NK1 fragment of hepatocyte growth factor	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	Hairpin loop containing domain-like	8036022	3000707	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	Kringle-like	8036023	3000761	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	Kringle-like	8036023	3000761	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	Kringle	e1gmnA1	A: few secondary structure elements	X: Kringle-like (From Topology)	H: Kringle-like (From Topology)	T: Kringle-like	F: Kringle	ECOD (1.6)
A	PAN_1	e1gmnA2	A: few secondary structure elements	X: Hairpin loop containing domain-like (From Topology)	H: Hairpin loop containing domain-like (From Topology)	T: Hairpin loop containing domain-like	F: PAN_1	ECOD (1.6)
B	Kringle	e1gmnB1	A: few secondary structure elements	X: Kringle-like (From Topology)	H: Kringle-like (From Topology)	T: Kringle-like	F: Kringle	ECOD (1.6)
B	PAN_1	e1gmnB2	A: few secondary structure elements	X: Hairpin loop containing domain-like (From Topology)	H: Hairpin loop containing domain-like (From Topology)	T: Hairpin loop containing domain-like	F: PAN_1	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	3.50.4.10	Alpha Beta	3-Layer(bba) Sandwich	Hepatocyte Growth Factor	Hepatocyte Growth Factor	CATH (4.3.0)
A	2.40.20.10	Mainly Beta	Beta Barrel	Plasminogen Kringle 4	Plasminogen Kringle 4	CATH (4.3.0)
B	3.50.4.10	Alpha Beta	3-Layer(bba) Sandwich	Hepatocyte Growth Factor	Hepatocyte Growth Factor	CATH (4.3.0)
B	2.40.20.10	Mainly Beta	Beta Barrel	Plasminogen Kringle 4	Plasminogen Kringle 4	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B	PF00051	Kringle domain (Kringle)	Kringle domain	Kringle domains have been found in plasminogen, hepatocyte growth factors, prothrombin, and apolipoprotein A. Structure is disulfide-rich, nearly all-beta.	Domain
A, B	PF00024	PAN domain (PAN_1)	PAN domain	The PAN domain [1] contains a conserved core of three disulphide bridges. In some members of the family there is an additional fourth disulphide bridge the links the N and C termini of the domain. The domain is found in diverse proteins, in some the ...	The PAN domain [1] contains a conserved core of three disulphide bridges. In some members of the family there is an additional fourth disulphide bridge the links the N and C termini of the domain. The domain is found in diverse proteins, in some they mediate protein-protein interactions, in others they mediate protein-carbohydrate interactions.	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B	HEPATOCYTE GROWTH FACTOR	protein binding binding signaling receptor binding molecular function activator activity molecular function regulator activity signaling receptor regulator activity growth factor activity receptor ligand activity signaling receptor activator activity chemoattractant activity identical protein binding	developmental process multicellular organism development multicellular organismal process hepaticobiliary system development gland development animal organ development anatomical structure development liver development system development cellular process cell cycle mitotic cell cycle myoblast proliferation cell population proliferation developmental process multicellular organism development multicellular organismal process hepaticobiliary system development gland development animal organ development anatomical structure development liver development system development cellular process cell cycle mitotic cell cycle myoblast proliferation cell population proliferation interleukin-6 production regulation of cellular process cellular biosynthetic process negative regulation of biological process negative regulation of cellular metabolic process regulation of interleukin-6 production regulation of cytokine production cytokine production negative regulation of cellular process regulation of multicellular organismal process negative regulation of macromolecule metabolic process regulation of biosynthetic process regulation of biological process cellular metabolic process negative regulation of metabolic process biological regulation regulation of cellular metabolic process negative regulation of cytokine production regulation of macromolecule metabolic process gene expression macromolecule biosynthetic process negative regulation of cellular biosynthetic process regulation of cellular biosynthetic process regulation of gene expression negative regulation of interleukin-6 production negative regulation of gene expression biosynthetic process negative regulation of biosynthetic process negative regulation of macromolecule biosynthetic process regulation of macromolecule biosynthetic process metabolic process macromolecule metabolic process negative regulation of multicellular organismal process regulation of metabolic process negative regulation of programmed cell death regulation of apoptotic process regulation of programmed cell death cell death negative regulation of apoptotic process apoptotic process programmed cell death cellular response to stimulus extrinsic apoptotic signaling pathway via death domain receptors response to stimulus signaling negative regulation of signaling regulation of signal transduction extrinsic apoptotic signaling pathway negative regulation of cell communication cell communication negative regulation of extrinsic apoptotic signaling pathway negative regulation of apoptotic signaling pathway signal transduction regulation of signaling cell surface receptor signaling pathway negative regulation of response to stimulus negative regulation of extrinsic apoptotic signaling pathway via death domain receptors negative regulation of signal transduction regulation of extrinsic apoptotic signaling pathway apoptotic signaling pathway regulation of response to stimulus regulation of extrinsic apoptotic signaling pathway via death domain receptors regulation of cell communication regulation of apoptotic signaling pathway regulation of hydrogen peroxide-mediated programmed cell death programmed cell death in response to reactive oxygen species cellular response to oxidative stress cellular response to chemical stress negative regulation of hydrogen peroxide-mediated programmed cell death cellular response to reactive oxygen species hydrogen peroxide-mediated programmed cell death cellular response to stress response to stress response to oxygen-containing compound cellular response to oxygen-containing compound response to reactive oxygen species response to oxidative stress cellular response to chemical stimulus response to chemical regulation of defense response regulation of response to external stimulus negative regulation of inflammatory response defense response response to external stimulus regulation of inflammatory response negative regulation of response to external stimulus regulation of response to stress negative regulation of defense response inflammatory response regulation of protein modification process regulation of protein phosphorylation negative regulation of phosphate metabolic process regulation of peptidyl-serine phosphorylation peptidyl-serine modification regulation of primary metabolic process peptidyl-serine phosphorylation regulation of phosphate metabolic process phosphate-containing compound metabolic process negative regulation of protein modification process peptidyl-amino acid modification protein metabolic process protein modification process phosphorus metabolic process negative regulation of protein metabolic process negative regulation of peptidyl-serine phosphorylation protein phosphorylation phosphorylation regulation of protein metabolic process primary metabolic process negative regulation of protein phosphorylation macromolecule modification negative regulation of phosphorus metabolic process regulation of phosphorylation regulation of phosphorus metabolic process negative regulation of phosphorylation positive regulation of cell communication regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction positive regulation of signal transduction positive regulation of biological process intracellular signal transduction positive regulation of response to stimulus regulation of intracellular signal transduction intracellular signaling cassette positive regulation of cellular process positive regulation of intracellular signal transduction positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction phosphatidylinositol 3-kinase/protein kinase B signal transduction positive regulation of signaling cell surface receptor protein tyrosine kinase signaling pathway hepatocyte growth factor receptor signaling pathway enzyme-linked receptor protein signaling pathway regulation of cellular component organization apoptotic mitochondrial changes regulation of release of cytochrome c from mitochondria cellular component organization negative regulation of release of cytochrome c from mitochondria cellular component organization or biogenesis mitochondrion organization negative regulation of cellular component organization regulation of organelle organization organelle organization release of cytochrome c from mitochondria negative regulation of organelle organization regulation of mitochondrion organization positive regulation of MAPK cascade regulation of MAPK cascade MAPK cascade mesenchymal-epithelial cell signaling regulation of developmental process branching involved in salivary gland morphogenesis gland morphogenesis salivary gland morphogenesis regulation of branching involved in salivary gland morphogenesis regulation of morphogenesis of an epithelium animal organ morphogenesis regulation of anatomical structure morphogenesis regulation of morphogenesis of a branching structure epithelium development regulation of animal organ morphogenesis morphogenesis of an epithelium salivary gland development cell-cell signaling tissue development regulation of branching involved in salivary gland morphogenesis by mesenchymal-epithelial signaling tissue morphogenesis anatomical structure morphogenesis morphogenesis of a branching structure exocrine system development morphogenesis of a branching epithelium cell chemotaxis chemotaxis taxis cell migration cell motility locomotion cell morphogenesis epithelial cell proliferation cellular developmental process cell differentiation mesenchyme development mesenchymal cell differentiation epithelial to mesenchymal transition p38MAPK cascade regulation of p38MAPK cascade regulation of osteoblast differentiation regulation of cell differentiation osteoblast differentiation positive regulation of developmental process positive regulation of osteoblast differentiation ossification positive regulation of cell differentiation positive regulation of locomotion regulation of cell motility positive regulation of cell migration regulation of locomotion positive regulation of cell motility regulation of cell migration interleukin-10 production positive regulation of cellular metabolic process positive regulation of macromolecule biosynthetic process positive regulation of metabolic process positive regulation of biosynthetic process positive regulation of macromolecule metabolic process regulation of interleukin-10 production positive regulation of interleukin-10 production positive regulation of gene expression positive regulation of multicellular organismal process positive regulation of cytokine production positive regulation of cellular biosynthetic process negative regulation of cellular catabolic process negative regulation of catabolic process catabolic process autophagy regulation of catabolic process regulation of autophagy cellular catabolic process negative regulation of autophagy regulation of cellular catabolic process process utilizing autophagic mechanism regulation of DNA biosynthetic process nucleobase-containing compound metabolic process nucleic acid biosynthetic process regulation of nucleobase-containing compound metabolic process positive regulation of nucleobase-containing compound metabolic process positive regulation of DNA biosynthetic process DNA metabolic process nucleobase-containing compound biosynthetic process nucleic acid metabolic process positive regulation of DNA metabolic process DNA biosynthetic process regulation of DNA metabolic process positive regulation of phosphorylation positive regulation of protein metabolic process positive regulation of phosphate metabolic process positive regulation of protein modification process positive regulation of protein phosphorylation positive regulation of phosphorus metabolic process cellular response to endogenous stimulus response to hepatocyte growth factor cellular response to growth factor stimulus cellular response to hepatocyte growth factor stimulus response to endogenous stimulus response to growth factor positive regulation of DNA-templated transcription RNA metabolic process RNA biosynthetic process DNA-templated transcription regulation of RNA metabolic process transcription by RNA polymerase II regulation of RNA biosynthetic process regulation of transcription by RNA polymerase II positive regulation of transcription by RNA polymerase II positive regulation of RNA metabolic process positive regulation of RNA biosynthetic process regulation of DNA-templated transcription muscle cell proliferation skeletal muscle cell proliferation striated muscle cell proliferation	membrane cellular anatomical entity extracellular region membrane-bounded organelle vesicle lumen intracellular anatomical structure intracellular vesicle membrane-enclosed lumen cytoplasmic vesicle lumen intracellular membrane-bounded organelle secretory granule lumen endomembrane system intracellular organelle lumen intracellular organelle membrane cellular anatomical entity extracellular region membrane-bounded organelle vesicle lumen intracellular anatomical structure intracellular vesicle membrane-enclosed lumen cytoplasmic vesicle lumen intracellular membrane-bounded organelle secretory granule lumen endomembrane system intracellular organelle lumen intracellular organelle cytoplasmic vesicle organelle lumen organelle secretory granule secretory vesicle cytoplasm platelet alpha granule vesicle platelet alpha granule lumen extracellular space

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B	IPR018056	Kringle, conserved site	Conserved Site
A, B	IPR003609	PAN/Apple domain	Domain
A, B	IPR013806	Kringle-like fold	Homologous Superfamily
A, B	IPR038178	Kringle superfamily	Homologous Superfamily
A, B	IPR009003	Peptidase S1, PA clan	Homologous Superfamily
A, B	IPR050759	Serine proteases and regulators with kringle domains	Family
A, B	IPR001314	Peptidase S1A, chymotrypsin family	Family
A, B	IPR027284	Hepatocyte growth factor	Family
A, B	IPR024174	Hepatocyte growth factor/Macrophage stimulatory protein	Family
A, B	IPR001254	Serine proteases, trypsin domain	Domain
A, B	IPR043504	Peptidase S1, PA clan, chymotrypsin-like fold	Homologous Superfamily
A, B	IPR000001	Kringle	Domain

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B	Pharos: P14210	autosomal recessive nonsyndromic deafness 39 pilocytic astrocytoma squamous cell carcinoma nonsyndromic genetic deafness pancreatitis subependymal giant cell astrocytoma neuroblastoma Barrett esophagus acute myeloid leukemia cardiomyopathy juvenile pilocytic astrocytoma liver cancer Copper-Overload Cirrhosis protoplasmic astrocytoma diabetic autonomic neuropathy autosomal recessive nonsyndromic deafness 39 pilocytic astrocytoma squamous cell carcinoma nonsyndromic genetic deafness pancreatitis subependymal giant cell astrocytoma neuroblastoma Barrett esophagus acute myeloid leukemia cardiomyopathy juvenile pilocytic astrocytoma liver cancer Copper-Overload Cirrhosis protoplasmic astrocytoma diabetic autonomic neuropathy diabetic neuropathy vascular disease pulmonary fibrosis malignant mesothelioma acute liver failure diabetic polyneuropathy fibrillary astrocytoma anaplastic astrocytoma gemistocytic astrocytoma childhood cerebral astrocytoma cirrhosis of liver Parkinson disease polyomavirus infectious disease pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia liver disease deafness, autosomal recessive lung cancer malignant glioma medulloblastoma myocardial ischemia adrenal cortex carcinoma gastric carcinoma astrocytoma (excluding glioblastoma) hepatocellular carcinoma idiopathic interstitial pneumonia ovarian cancer cancer invasive ductal breast carcinoma cerebral astrocytoma keratoconus pancreatic intraductal papillary-mucinous carcinoma coronary artery disease liver neoplasm plasma cell myeloma lung disease rheumatoid arthritis tuberculosis hepatitis oligodendroglioma interstitial cystitis ischemia reperfusion injury large cell medulloblastoma pancreatic intraductal papillary-mucinous neoplasm malignant ependymoma MALT lymphoma Sjogren syndrome diffuse astrocytoma adrenal cortex adenoma astrocytic tumor thrombotic disease non-small cell lung carcinoma ulcerative colitis osteosarcoma breast cancer

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.