5UKK

Human GRK2 in complex with human G-beta-gamma subunits and CCG211998 (14ak)

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	d5ukka1	All alpha proteins	Regulator of G-protein signaling, RGS	Regulator of G-protein signaling, RGS	automated matches	automated matches	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
A	d5ukka3	All beta proteins	PH domain-like barrel	PH domain-like	automated matches	automated matches	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
A	d5ukka2	Alpha and beta proteins (a+b)	Protein kinase-like (PK-like)	Protein kinase-like (PK-like)	Protein kinases, catalytic subunit	automated matches	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
C [auth G]	d5ukkg_	All alpha proteins	Non-globular all-alpha subunits of globular proteins	Transducin (heterotrimeric G protein), gamma chain	Transducin (heterotrimeric G protein), gamma chain	Transducin (heterotrimeric G protein), gamma chain	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d5ukkb_	All beta proteins	7-bladed beta-propeller	WD40 repeat-like	WD40-repeat	beta1-subunit of the signal-transducing G protein heterotrimer	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	PH domain-like	8042573	3000134	SCOP2B (2022-06-29)
C [auth G]	SCOP2B Superfamily	Transducin (heterotrimeric G protein), gamma chain	8070798	3001771	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	PH	e5ukkA2	A: beta barrels	X: PH domain-like	H: PH domain-like (From Topology)	T: PH domain-like	F: PH	ECOD (1.6)
A	RGS	e5ukkA3	A: alpha bundles	X: Regulator of G-protein signaling, RGS (From Topology)	H: Regulator of G-protein signaling, RGS (From Topology)	T: Regulator of G-protein signaling, RGS	F: RGS	ECOD (1.6)
A	Pkinase_Tyr	e5ukkA1	A: a+b complex topology	X: Protein kinase/SAICAR synthase/ATP-grasp (From Homology)	H: Protein kinase/SAICAR synthase/ATP-grasp	T: Protein kinase	F: Pkinase_Tyr	ECOD (1.6)
C [auth G]	G-gamma	e5ukkG1	A: extended segments	X: Transducin (heterotrimeric G protein), gamma chain (From Topology)	H: Transducin (heterotrimeric G protein), gamma chain (From Topology)	T: Transducin (heterotrimeric G protein), gamma chain	F: G-gamma	ECOD (1.6)
B	ANAPC4_WD40_3	e5ukkB1	A: beta duplicates or obligate multimers	X: beta-propeller-like	H: beta-propeller	T: 7-bladed	F: ANAPC4_WD40_3	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	1.10.287.1270	Mainly Alpha	Orthogonal Bundle	Helix Hairpins		CATH (4.3.0)
A	1.10.167.10	Mainly Alpha	Orthogonal Bundle	Regulator of G-protein Signalling 4	domain 2	CATH (4.3.0)
A	3.30.200.20	Alpha Beta	2-Layer Sandwich	Phosphorylase Kinase	domain 1	CATH (4.3.0)
A	1.10.510.10	Mainly Alpha	Orthogonal Bundle	Transferase(Phosphotransferase)	domain 1	CATH (4.3.0)
A	2.30.29.30	Mainly Beta	Roll	PH-domain like	Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB)	CATH (4.3.0)
C [auth G]	4.10.260.10	Few Secondary Structures	Irregular	G Protein Gi Gamma 2	Transducin (heterotrimeric G protein), gamma chain	CATH (4.3.0)
B	2.130.10.10	Mainly Beta	7 Propeller	Methylamine Dehydrogenase	Chain H	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A	PF00615	Regulator of G protein signaling domain (RGS)	Regulator of G protein signaling domain	RGS family members are GTPase-activating proteins for heterotrimeric G-protein alpha-subunits.	Domain
A	PF00069	Protein kinase domain (Pkinase)	Protein kinase domain	-	Domain
A	PF00169	PH domain (PH)	PH domain	PH stands for pleckstrin homology.	Domain
C [auth G]	PF00631	GGL domain (G-gamma)	GGL domain	G-protein gamma like domains (GGL) are found in the gamma subunit of the heterotrimeric G protein complex and in regulators of G protein signaling (RGS) proteins [1]. It is also found fused to an inactive Galpha in the Dictyostelium protein gbqA [2] ...	G-protein gamma like domains (GGL) are found in the gamma subunit of the heterotrimeric G protein complex and in regulators of G protein signaling (RGS) proteins [1]. It is also found fused to an inactive Galpha in the Dictyostelium protein gbqA [2]. G-gamma likely shares a common origin with the helical N-terminal unit of G-beta [2]. All organisms that posses a G-beta possess a G-gamma [2].	Domain
B	PF00400	WD domain, G-beta repeat (WD40)	WD domain, G-beta repeat	-	Repeat

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A	Beta-adrenergic receptor kinase 1	catalytic activity, acting on a protein beta-adrenergic receptor kinase activity kinase activity protein kinase activity transferase activity catalytic activity phosphotransferase activity, alcohol group as acceptor transferase activity, transferring phosphorus-containing groups Edg-2 lysophosphatidic acid receptor binding protein binding binding signaling receptor binding endothelial differentiation G protein-coupled receptor binding G protein-coupled receptor binding catalytic activity, acting on a protein beta-adrenergic receptor kinase activity kinase activity protein kinase activity transferase activity catalytic activity phosphotransferase activity, alcohol group as acceptor transferase activity, transferring phosphorus-containing groups Edg-2 lysophosphatidic acid receptor binding protein binding binding signaling receptor binding endothelial differentiation G protein-coupled receptor binding G protein-coupled receptor binding adenyl ribonucleotide binding nucleotide binding purine ribonucleotide binding purine ribonucleoside triphosphate binding nucleoside phosphate binding ion binding purine nucleotide binding organic cyclic compound binding anion binding adenyl nucleotide binding ATP binding heterocyclic compound binding carbohydrate derivative binding ribonucleotide binding small molecule binding adrenergic receptor binding alpha-2A adrenergic receptor binding protein serine/threonine kinase activity G protein-coupled receptor kinase activity	developmental process heart development multicellular organism development multicellular organismal process anatomical structure development animal organ development circulatory system development system development system process regulation of biological process regulation of system process biological regulation negative regulation of biological process muscle contraction developmental process heart development multicellular organism development multicellular organismal process anatomical structure development animal organ development circulatory system development system development system process regulation of biological process regulation of system process biological regulation negative regulation of biological process muscle contraction muscle system process regulation of muscle system process striated muscle contraction negative regulation of muscle contraction regulation of striated muscle contraction regulation of muscle contraction regulation of multicellular organismal process negative regulation of multicellular organismal process negative regulation of striated muscle contraction heart process regulation of heart contraction circulatory system process regulation of blood circulation regulation of biological quality heart contraction regulation of the force of heart contraction blood circulation localization import into cell receptor internalization transport cellular process receptor-mediated endocytosis endocytosis establishment of localization vesicle-mediated transport biological process involved in interspecies interaction between organisms symbiont entry into host cell viral process symbiont entry into host viral life cycle biological process involved in interaction with host biological process involved in symbiotic interaction viral genome replication cellular response to stimulus negative adaptation of signaling pathway regulation of cellular process response to stimulus negative regulation of signaling signaling desensitization of G protein-coupled receptor signaling pathway regulation of signal transduction negative regulation of G protein-coupled receptor signaling pathway negative regulation of cell communication cell communication negative regulation of cellular process signal transduction regulation of G protein-coupled receptor signaling pathway regulation of signaling negative regulation of response to stimulus negative regulation of signal transduction regulation of response to stimulus adaptation of signaling pathway regulation of cell communication G protein-coupled receptor signaling pathway monoamine transport regulation of localization nitrogen compound transport regulation of catecholamine secretion positive regulation of biological process organic hydroxy compound transport positive regulation of secretion by cell positive regulation of amine transport secretion by cell regulation of secretion by cell catecholamine transport positive regulation of secretion positive regulation of cellular process secretion regulation of transport positive regulation of catecholamine secretion export from cell regulation of secretion catecholamine secretion amine transport positive regulation of transport regulation of amine transport negative regulation of blood circulation negative regulation of heart contraction negative regulation of the force of heart contraction by chemical signal regulation of the force of heart contraction by chemical signal cardiac muscle contraction protein phosphorylation phosphorylation primary metabolic process peptidyl-serine modification peptidyl-serine phosphorylation macromolecule modification peptidyl-amino acid modification phosphate-containing compound metabolic process metabolic process protein metabolic process macromolecule metabolic process protein modification process phosphorus metabolic process tachykinin receptor signaling pathway negative regulation of relaxation of smooth muscle relaxation of smooth muscle negative regulation of relaxation of muscle relaxation of muscle regulation of relaxation of smooth muscle regulation of relaxation of muscle cellular response to nitrogen compound synaptic signaling cellular response to acetylcholine response to oxygen-containing compound cell-cell signaling response to nitrogen compound acetylcholine receptor signaling pathway postsynaptic signal transduction cellular response to oxygen-containing compound cellular response to chemical stimulus G protein-coupled acetylcholine receptor signaling pathway response to chemical response to acetylcholine	membrane-bounded organelle cell projection cellular anatomical structure organelle cilium plasma membrane bounded cell projection membrane intracellular anatomical structure cytoplasm cytosol cell periphery plasma membrane presynapse synapse membrane-bounded organelle cell projection cellular anatomical structure organelle cilium plasma membrane bounded cell projection membrane intracellular anatomical structure cytoplasm cytosol cell periphery plasma membrane presynapse synapse cell junction postsynapse
C [auth G]	Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2	protein binding binding G-protein beta-subunit binding	fibroblast proliferation cell population proliferation cellular process cellular response to nitrogen compound cellular response to stimulus response to dopamine regulation of cellular process response to stimulus signaling cellular response to dopamine response to monoamine cell communication response to catecholamine adenylate cyclase-activating dopamine receptor signaling pathway fibroblast proliferation cell population proliferation cellular process cellular response to nitrogen compound cellular response to stimulus response to dopamine regulation of cellular process response to stimulus signaling cellular response to dopamine response to monoamine cell communication response to catecholamine adenylate cyclase-activating dopamine receptor signaling pathway cellular response to catecholamine stimulus signal transduction response to organic cyclic compound regulation of biological process G protein-coupled dopamine receptor signaling pathway cellular response to organic cyclic compound biological regulation response to oxygen-containing compound response to nitrogen compound adenylate cyclase-activating G protein-coupled receptor signaling pathway cellular response to oxygen-containing compound cellular response to chemical stimulus cellular response to monoamine stimulus response to chemical adenylate cyclase-modulating G protein-coupled receptor signaling pathway G protein-coupled receptor signaling pathway response to ketone response to prostaglandin response to lipid response to endogenous stimulus response to alcohol cellular response to prostaglandin stimulus cellular response to endogenous stimulus cellular response to prostaglandin E stimulus cellular response to alcohol response to hormone cellular response to lipid response to prostaglandin E cellular response to ketone cellular response to hormone stimulus	cellular anatomical structure membrane protein-containing complex extrinsic component of plasma membrane catalytic complex plasma membrane protein complex cytoplasmic side of membrane plasma membrane membrane protein complex heterotrimeric G-protein complex side of membrane cell periphery cytoplasmic side of plasma membrane GTPase complex cellular anatomical structure membrane protein-containing complex extrinsic component of plasma membrane catalytic complex plasma membrane protein complex cytoplasmic side of membrane plasma membrane membrane protein complex heterotrimeric G-protein complex side of membrane cell periphery cytoplasmic side of plasma membrane GTPase complex extrinsic component of membrane extrinsic component of cytoplasmic side of plasma membrane extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle extracellular region organelle extracellular space vesicle extracellular membrane-bounded organelle
B	Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	protein binding binding enzyme binding GTPase binding protein-containing complex binding pyrophosphatase activity GTPase activity ribonucleoside triphosphate phosphatase activity hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides hydrolase activity hydrolase activity, acting on acid anhydrides catalytic activity signaling receptor complex adaptor activity protein-macromolecule adaptor activity protein binding binding enzyme binding GTPase binding protein-containing complex binding pyrophosphatase activity GTPase activity ribonucleoside triphosphate phosphatase activity hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides hydrolase activity hydrolase activity, acting on acid anhydrides catalytic activity signaling receptor complex adaptor activity protein-macromolecule adaptor activity molecular adaptor activity signaling adaptor activity	multicellular organismal process system process sensory perception of chemical stimulus sensory perception nervous system process sensory perception of taste developmental process sensory organ development eye development animal organ development retina development in camera-type eye visual system development multicellular organism development camera-type eye development multicellular organismal process system process sensory perception of chemical stimulus sensory perception nervous system process sensory perception of taste developmental process sensory organ development eye development animal organ development retina development in camera-type eye visual system development multicellular organism development camera-type eye development anatomical structure development sensory system development system development cell population proliferation cellular process cellular response to stimulus regulation of biological process regulation of cellular process response to stimulus signaling biological regulation signal transduction cell communication response to ketone response to prostaglandin response to lipid response to endogenous stimulus response to alcohol cellular response to prostaglandin stimulus response to oxygen-containing compound cellular response to oxygen-containing compound cellular response to endogenous stimulus cellular response to prostaglandin E stimulus cellular response to chemical stimulus cellular response to alcohol response to hormone response to chemical cellular response to lipid response to prostaglandin E cellular response to ketone cellular response to hormone stimulus small GTPase-mediated signal transduction Ras protein signal transduction intracellular signal transduction intracellular signaling cassette phospholipase C-activating G protein-coupled receptor signaling pathway G protein-coupled receptor signaling pathway cellular response to nitrogen compound response to dopamine cellular response to dopamine response to monoamine response to catecholamine adenylate cyclase-activating dopamine receptor signaling pathway cellular response to catecholamine stimulus response to organic cyclic compound G protein-coupled dopamine receptor signaling pathway cellular response to organic cyclic compound response to nitrogen compound adenylate cyclase-activating G protein-coupled receptor signaling pathway cellular response to monoamine stimulus adenylate cyclase-modulating G protein-coupled receptor signaling pathway synaptic signaling cellular response to acetylcholine cell-cell signaling acetylcholine receptor signaling pathway postsynaptic signal transduction G protein-coupled acetylcholine receptor signaling pathway response to acetylcholine	cellular anatomical structure membrane protein-containing complex extrinsic component of plasma membrane catalytic complex plasma membrane protein complex cytoplasmic side of membrane plasma membrane membrane protein complex heterotrimeric G-protein complex side of membrane cell periphery cytoplasmic side of plasma membrane GTPase complex cellular anatomical structure membrane protein-containing complex extrinsic component of plasma membrane catalytic complex plasma membrane protein complex cytoplasmic side of membrane plasma membrane membrane protein complex heterotrimeric G-protein complex side of membrane cell periphery cytoplasmic side of plasma membrane GTPase complex extrinsic component of membrane extrinsic component of cytoplasmic side of plasma membrane extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle extracellular region organelle extracellular space vesicle extracellular membrane-bounded organelle non-motile cilium 9+0 non-motile cilium cilium neuron projection photoreceptor disc membrane photoreceptor outer segment plasma membrane bounded cell projection cell projection photoreceptor cell cilium organelle membrane intracellular anatomical structure cytoplasm cytosol vacuolar membrane lytic vacuole vacuole intracellular membrane-bounded organelle intracellular organelle lytic vacuole membrane bounding membrane of organelle lysosomal membrane lysosome synapse cell junction

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A	IPR016137	RGS domain	Domain
A	IPR017441	Protein kinase, ATP binding site	Binding Site
A	IPR001849	Pleckstrin homology domain	Domain
A	IPR036305	RGS domain superfamily	Homologous Superfamily
A	IPR000719	Protein kinase domain	Domain
A	IPR011993	PH-like domain superfamily	Homologous Superfamily
A	IPR000961	AGC-kinase, C-terminal	Domain
A	IPR044926	RGS, subdomain 2	Homologous Superfamily
A	IPR011009	Protein kinase-like domain superfamily	Homologous Superfamily
A	IPR000239	GPCR kinase	Family
A	IPR008271	Serine/threonine-protein kinase, active site	Active Site
C [auth G]	IPR015898	G-protein gamma-like domain	Domain
C [auth G]	IPR001770	G-protein, gamma subunit	Family
C [auth G]	IPR036284	G-protein gamma-like domain superfamily	Homologous Superfamily
B	IPR019775	WD40 repeat, conserved site	Conserved Site
B	IPR015943	WD40/YVTN repeat-like-containing domain superfamily	Homologous Superfamily
B	IPR016346	Guanine nucleotide-binding protein, beta subunit	Family
B	IPR036322	WD40-repeat-containing domain superfamily	Homologous Superfamily
B	IPR001632	G-protein, beta subunit	Domain
B	IPR001680	WD40 repeat	Repeat
B	IPR020472	G-protein beta WD-40 repeat	Repeat

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A	Pharos: P25098	allergic contact dermatitis Cardiomegaly cardiovascular disease congenital abnormality hypertensive disorder congestive heart failure rheumatoid arthritis cardiomyopathy prostate carcinoma subependymal giant cell astrocytoma diabetes mellitus osteosarcoma psoriasis chronic obstructive pulmonary disease heart failure allergic contact dermatitis Cardiomegaly cardiovascular disease congenital abnormality hypertensive disorder congestive heart failure rheumatoid arthritis cardiomyopathy prostate carcinoma subependymal giant cell astrocytoma diabetes mellitus osteosarcoma psoriasis chronic obstructive pulmonary disease heart failure large cell medulloblastoma ovarian cancer colorectal adenocarcinoma depressive disorder
C [auth G]	Pharos: P59768	pancreatic intraductal papillary-mucinous neoplasm pilocytic astrocytoma sarcoidosis ulcerative colitis adrenal cortex carcinoma breast carcinoma Duchenne muscular dystrophy glioblastoma large cell medulloblastoma medulloblastoma ovarian cancer pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia pituitary cancer Sjogren syndrome X-linked mixed deafness with perilymphatic gusher pancreatic intraductal papillary-mucinous neoplasm pilocytic astrocytoma sarcoidosis ulcerative colitis adrenal cortex carcinoma breast carcinoma Duchenne muscular dystrophy glioblastoma large cell medulloblastoma medulloblastoma ovarian cancer pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia pituitary cancer Sjogren syndrome X-linked mixed deafness with perilymphatic gusher astrocytic tumor Crohn disease ductal breast carcinoma in situ interstitial cystitis lung carcinoma non-small cell lung carcinoma pancreatic intraductal papillary-mucinous carcinoma Pick disease primitive neuroectodermal tumor thoracic aortic aneurysm atypical teratoid rhabdoid tumor cystic fibrosis Emery-Dreifuss muscular dystrophy invasive ductal breast carcinoma malignant ependymoma osteosarcoma
B	Pharos: P62873	intellectual disability, autosomal dominant 42 melancholia intellectual disability endogenous depression medulloblastoma myopathy ovarian cancer Precursor Cell Lymphoblastic Leukemia Lymphoma Sjogren syndrome anxiety disorder chronic kidney disease juvenile dermatomyositis lung adenocarcinoma neurotic disorder pancreatic ductal adenocarcinoma intellectual disability, autosomal dominant 42 melancholia intellectual disability endogenous depression medulloblastoma myopathy ovarian cancer Precursor Cell Lymphoblastic Leukemia Lymphoma Sjogren syndrome anxiety disorder chronic kidney disease juvenile dermatomyositis lung adenocarcinoma neurotic disorder pancreatic ductal adenocarcinoma subependymal giant cell astrocytoma breast cancer Duchenne muscular dystrophy leukemia, acute lymphocytic, susceptibility to, 1 malignant pancreatic neoplasm myelodysplastic syndrome osteosarcoma plasma cell myeloma rheumatoid arthritis swine influenza childhood acute lymphoblastic leukemia depressive disorder