4PX3

Human GKRP bound to AMG-3295 and Sorbitol-6-phosphate

External Resource: Annotation

Domain Annotation: ECOD Classification
Domain Annotation: CATH
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
B	murQ_2nd,murQ_1st	e4px3B3	A: alpha arrays	X: RuvA-C	H: C-terminal lid domain of glucokinase regulatory protein (From Topology)	T: C-terminal lid domain of glucokinase regulatory protein	F: murQ_2nd,murQ_1st	ECOD (1.6)
B	PRK12570	e4px3B2	A: a/b three-layered sandwiches	X: Flavodoxin-like	H: Ribosomal protein S2/SIS domain (From Topology)	T: Ribosomal protein S2/SIS domain	F: PRK12570	ECOD (1.6)
B	murQ_1st	e4px3B1	A: a/b three-layered sandwiches	X: Flavodoxin-like	H: Ribosomal protein S2/SIS domain (From Topology)	T: Ribosomal protein S2/SIS domain	F: murQ_1st	ECOD (1.6)
A	murQ_2nd	e4px3A1	A: alpha arrays	X: RuvA-C	H: C-terminal lid domain of glucokinase regulatory protein (From Topology)	T: C-terminal lid domain of glucokinase regulatory protein	F: murQ_2nd	ECOD (1.6)
A	PRK12570	e4px3A2	A: a/b three-layered sandwiches	X: Flavodoxin-like	H: Ribosomal protein S2/SIS domain (From Topology)	T: Ribosomal protein S2/SIS domain	F: PRK12570	ECOD (1.6)
A	murQ_1st	e4px3A3	A: a/b three-layered sandwiches	X: Flavodoxin-like	H: Ribosomal protein S2/SIS domain (From Topology)	T: Ribosomal protein S2/SIS domain	F: murQ_1st	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
B	3.40.50.10490	Alpha Beta	3-Layer(aba) Sandwich	Rossmann fold	Glucose-6-phosphate isomerase like protein	CATH (4.3.0)
A	3.40.50.10490	Alpha Beta	3-Layer(aba) Sandwich	Rossmann fold	Glucose-6-phosphate isomerase like protein	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B	PF22198	Glucokinase regulatory protein, second SIS domain (GKRP_SIS_2)	Glucokinase regulatory protein, second SIS domain	Glucokinase regulatory protein (GKRP) binds glucokinase (GK) mainly through hydrophobic interactions, functioning as an allosteric switch in blood glucose control by the liver [1]. GKRP is trilobal in shape, consisting of two topologically identical ...	Glucokinase regulatory protein (GKRP) binds glucokinase (GK) mainly through hydrophobic interactions, functioning as an allosteric switch in blood glucose control by the liver [1]. GKRP is trilobal in shape, consisting of two topologically identical sugar isomerase (SIS) domains capped by an alpha-helical lid domain (Pfam:PF20741). This entry represents the second SIS domain from GKRP [1].	Domain
A, B	PF22645	Glucokinase regulatory protein N-terminal SIS domain (GKRP_SIS_N)	Glucokinase regulatory protein N-terminal SIS domain	This domain is found N-terminal in glucokinase regulatory protein (GKRP) and related proteins. GKRP regulates glucokinase and it is activated by fructose 6-phosphate and inactivated by fructose 1-phosphate. It consists of two topologically identical ...	This domain is found N-terminal in glucokinase regulatory protein (GKRP) and related proteins. GKRP regulates glucokinase and it is activated by fructose 6-phosphate and inactivated by fructose 1-phosphate. It consists of two topologically identical SIS domains and and alpha-helical lid domain [1-4].	Domain
A, B	PF20741	C-terminal lid domain of glucokinase regulatory protein (GKRP-like_C)	C-terminal lid domain of glucokinase regulatory protein	This domain is found at the C terminus of Glucokinase regulatory protein (GKRP) from animals and N-acetylmuramic acid 6-phosphate etherase (MurQ) from bacteria. GKRP binds Glucokinase (GK) mainly through hydrophobic interactions, functioning as an al ...	This domain is found at the C terminus of Glucokinase regulatory protein (GKRP) from animals and N-acetylmuramic acid 6-phosphate etherase (MurQ) from bacteria. GKRP binds Glucokinase (GK) mainly through hydrophobic interactions, functioning as an allosteric switch in blood glucose control by the liver [1]. GKRP is trilobal in shape, consisting of two topologically identical sugar isomerase (SIS) domains (Pfam:PF01380 and Pfam:PF13580) capped by an alpha helical C-terminal domain (this entry). The Lid domain consists of a bundle of seven alpha helices with a core that shows a UBA-like fold [2]. MurQ, which also shows a SIS domain, plays a key role in the peptidoglycane recycling pathway. Its crystal structure shows each monomer have an alpha-beta-alpha sandwich fold commonly found in regulatory proteins controlling the expression of genes involved in the synthesis of phosphosugars. The C-terminal domain of this protein (this entry) is comprised of five alpha helices [4].	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B	Glucokinase regulatory protein	binding carbohydrate binding ion binding anion binding carbohydrate derivative binding fructose-6-phosphate binding small molecule binding enzyme regulator activity molecular function inhibitor activity molecular function regulator activity enzyme inhibitor activity molecular sensor activity glucose sensor activity kinase inhibitor activity binding carbohydrate binding ion binding anion binding carbohydrate derivative binding fructose-6-phosphate binding small molecule binding enzyme regulator activity molecular function inhibitor activity molecular function regulator activity enzyme inhibitor activity molecular sensor activity glucose sensor activity kinase inhibitor activity kinase regulator activity protein binding enzyme binding	chemical homeostasis homeostatic process triglyceride homeostasis acylglycerol homeostasis lipid homeostasis small molecule metabolic process metabolic process cellular process urate metabolic process purine-containing compound metabolic process protein localization establishment of protein localization cellular localization nitrogen compound transport chemical homeostasis homeostatic process triglyceride homeostasis acylglycerol homeostasis lipid homeostasis small molecule metabolic process metabolic process cellular process urate metabolic process purine-containing compound metabolic process protein localization establishment of protein localization cellular localization nitrogen compound transport nucleocytoplasmic transport transport nuclear transport intracellular transport protein localization to nucleus establishment of localization localization import into nucleus establishment of protein localization to organelle protein transport cellular macromolecule localization macromolecule localization protein localization to organelle establishment of localization in cell protein import into nucleus intracellular protein transport response to hexose response to monosaccharide response to carbohydrate response to stimulus response to chemical response to oxygen-containing compound response to fructose response to glucose monosaccharide metabolic process regulation of cellular process regulation of catalytic activity negative regulation of biological process negative regulation of glucokinase activity negative regulation of phosphate metabolic process negative regulation of catalytic activity regulation of transferase activity regulation of primary metabolic process negative regulation of hexokinase activity negative regulation of kinase activity negative regulation of transferase activity regulation of small molecule metabolic process regulation of phosphate metabolic process regulation of glucokinase activity phosphate-containing compound metabolic process negative regulation of cellular process phosphorus metabolic process regulation of carbohydrate metabolic process regulation of glucose metabolic process negative regulation of carbohydrate metabolic process carbohydrate metabolic process regulation of biological process phosphorylation negative regulation of metabolic process biological regulation negative regulation of molecular function primary metabolic process hexose metabolic process regulation of molecular function regulation of kinase activity regulation of hexokinase activity negative regulation of phosphorus metabolic process regulation of phosphorylation regulation of phosphorus metabolic process negative regulation of phosphorylation regulation of metabolic process glucose metabolic process carbohydrate derivative metabolic process glucose homeostasis carbohydrate homeostasis	membrane-bounded organelle intracellular organelle cellular anatomical structure intracellular anatomical structure mitochondrion organelle cytoplasm intracellular membrane-bounded organelle cytosol nucleus membrane-enclosed lumen intracellular organelle lumen nucleoplasm organelle lumen membrane-bounded organelle intracellular organelle cellular anatomical structure intracellular anatomical structure mitochondrion organelle cytoplasm intracellular membrane-bounded organelle cytosol nucleus membrane-enclosed lumen intracellular organelle lumen nucleoplasm organelle lumen nuclear lumen

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B	IPR054017	Glucokinase regulatory protein, second SIS domain	Domain
A, B	IPR046348	SIS domain superfamily	Homologous Superfamily
A, B	IPR005486	Glucokinase regulatory protein, conserved site	Conserved Site
A, B	IPR040190	N-acetylmuramic acid 6-phosphate etherase/glucokinase regulatory protein	Family
A, B	IPR001347	SIS domain	Domain

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B	Pharos: Q14397	Crohn disease hypertriglyceridemia non-alcoholic fatty liver disease metabolic syndrome X type 2 diabetes mellitus gout maturity-onset diabetes of the young nephrolithiasis Diabetes Mellitus, Non-Insulin-Dependent metabolic disease gallbladder disease inflammatory bowel disease

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.