5O33

A structure of the GEF Kalirin DH1 domain in complex with the small GTPase Rac1

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	d5o33a_	Alpha and beta proteins (a/b)	P-loop containing nucleoside triphosphate hydrolases	P-loop containing nucleoside triphosphate hydrolases	G proteins	Rac	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	Ras-like P-loop GTPases	8057406	3002022	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	Ras	e5o33A1	A: a/b three-layered sandwiches	X: P-loop domains-like	H: P-loop domains-related	T: P-loop containing nucleoside triphosphate hydrolases	F: Ras	ECOD (1.6)
B	RhoGEF	e5o33B1	A: alpha bundles	X: DH domain-like	H: DBL homology domain (DH-domain) (From Topology)	T: DBL homology domain (DH-domain)	F: RhoGEF	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	3.40.50.300	Alpha Beta	3-Layer(aba) Sandwich	Rossmann fold	P-loop containing nucleotide triphosphate hydrolases	CATH (4.3.0)
B	1.20.900.10	Mainly Alpha	Up-down Bundle	Dbl Homology Domain	Chain A	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A	PF00071	Ras family (Ras)	Ras family	Includes sub-families Ras, Rab, Rac, Ral, Ran, Rap Ypt1 and more. Shares P-loop motif with GTP_EFTU, arf and myosin_head. See Pfam:PF00009 Pfam:PF00025, Pfam:PF00063. As regards Rab GTPases, these are important regulators of vesicle formation, motil ...	Includes sub-families Ras, Rab, Rac, Ral, Ran, Rap Ypt1 and more. Shares P-loop motif with GTP_EFTU, arf and myosin_head. See Pfam:PF00009 Pfam:PF00025, Pfam:PF00063. As regards Rab GTPases, these are important regulators of vesicle formation, motility and fusion. They share a fold in common with all Ras GTPases: this is a six-stranded beta-sheet surrounded by five alpha-helices [1].	Domain
B	PF00621	RhoGEF domain (RhoGEF)	RhoGEF domain	Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that Pfam:PF00169 domains invariably occur C-terminal to RhoGEF/DH domains.	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A	Ras-related C3 botulinum toxin substrate 1	thioesterase binding protein binding binding enzyme 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 Rho GDP-dissociation inhibitor binding GDP-dissociation inhibitor binding thioesterase binding protein binding binding enzyme 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 Rho GDP-dissociation inhibitor binding GDP-dissociation inhibitor binding guanyl nucleotide binding GTP binding nucleotide binding guanyl ribonucleotide binding purine ribonucleotide binding purine ribonucleoside triphosphate binding nucleoside phosphate binding ion binding organic cyclic compound binding purine nucleotide binding anion binding heterocyclic compound binding carbohydrate derivative binding ribonucleotide binding small molecule binding kinase binding protein kinase binding G protein activity molecular function regulator activity	regulation of biological process regulation of cell motility regulation of cellular process regulation of leukocyte migration biological regulation neutrophil migration granulocyte migration leukocyte migration immune system process regulation of locomotion myeloid leukocyte migration regulation of cell migration cell migration cellular process regulation of biological process regulation of cell motility regulation of cellular process regulation of leukocyte migration biological regulation neutrophil migration granulocyte migration leukocyte migration immune system process regulation of locomotion myeloid leukocyte migration regulation of cell migration cell migration cellular process regulation of immune system process cell motility regulation of neutrophil migration locomotion lamellipodium assembly plasma membrane bounded cell projection organization cell projection organization plasma membrane bounded cell projection assembly cellular component organization cellular component biogenesis cellular component assembly lamellipodium organization cellular component organization or biogenesis cell projection assembly regulation of cell-substrate adhesion positive regulation of cell adhesion regulation of cell adhesion positive regulation of biological process cell-substrate adhesion cell adhesion positive regulation of cell-substrate adhesion positive regulation of cellular process regulation of cellular component size regulation of biological quality regulation of cell size regulation of anatomical structure size substrate adhesion-dependent cell spreading multicellular organismal process negative regulation of biological process cytokine production regulation of cytokine production negative regulation of cellular process regulation of multicellular organismal process negative regulation of macromolecule metabolic process regulation of biosynthetic process negative regulation of metabolic process negative regulation of cytokine production regulation of macromolecule metabolic process gene expression macromolecule biosynthetic process interleukin-23 production regulation of gene expression negative regulation of gene expression biosynthetic process negative regulation of biosynthetic process negative regulation of macromolecule biosynthetic process metabolic process regulation of macromolecule biosynthetic process macromolecule metabolic process regulation of interleukin-23 production negative regulation of multicellular organismal process regulation of metabolic process negative regulation of interleukin-23 production positive regulation of substrate adhesion-dependent cell spreading regulation of substrate adhesion-dependent cell spreading organelle organization actin cytoskeleton organization actin filament-based process cytoskeleton organization cellular response to stimulus cell surface receptor signaling pathway response to stimulus signaling cell surface receptor protein tyrosine kinase signaling pathway cell communication hepatocyte growth factor receptor signaling pathway signal transduction enzyme-linked receptor protein signaling pathway regulation of cellular component organization positive regulation of cellular component organization cell-substrate junction assembly positive regulation of cell-substrate junction organization cell junction assembly regulation of cell-substrate junction organization focal adhesion assembly positive regulation of focal adhesion assembly positive regulation of cellular component biogenesis positive regulation of cell-matrix adhesion regulation of cellular component biogenesis regulation of cell junction assembly positive regulation of cell junction assembly cell junction organization cell-matrix adhesion regulation of cell-matrix adhesion cell-substrate junction organization regulation of focal adhesion assembly regulation of cell-substrate junction assembly regulation of localization import into cell transport negative regulation of transport negative regulation of endocytosis vesicle-mediated transport localization regulation of endocytosis negative regulation of cellular component organization negative regulation of receptor-mediated endocytosis regulation of transport regulation of receptor-mediated endocytosis regulation of vesicle-mediated transport establishment of localization endocytosis receptor-mediated endocytosis Wnt signaling pathway, planar cell polarity pathway non-canonical Wnt signaling pathway Wnt signaling pathway small GTPase-mediated signal transduction Rac protein signal transduction intracellular signal transduction intracellular signaling cassette cell chemotaxis chemotaxis response to external stimulus cellular response to chemical stimulus taxis response to chemical response to stress response to wounding establishment or maintenance of cell polarity ruffle organization positive regulation of organelle organization regulation of cytoskeleton organization regulation of microtubule polymerization or depolymerization microtubule cytoskeleton organization regulation of protein-containing complex assembly positive regulation of protein-containing complex assembly microtubule polymerization or depolymerization positive regulation of protein polymerization protein-containing complex assembly protein polymerization positive regulation of microtubule polymerization or depolymerization protein-containing complex organization positive regulation of cytoskeleton organization regulation of microtubule-based process microtubule polymerization positive regulation of supramolecular fiber organization regulation of organelle organization positive regulation of microtubule polymerization regulation of protein polymerization regulation of microtubule polymerization regulation of supramolecular fiber organization microtubule-based process supramolecular fiber organization regulation of microtubule cytoskeleton organization actin filament organization sphingolipid mediated signaling pathway sphingosine-1-phosphate receptor signaling pathway G protein-coupled receptor signaling pathway negative regulation of locomotion regulation of fibroblast migration fibroblast migration negative regulation of fibroblast migration ameboidal-type cell migration negative regulation of cell motility negative regulation of cell migration positive regulation of locomotion endothelial cell migration positive regulation of cell migration positive regulation of endothelial cell migration positive regulation of cell motility regulation of endothelial cell migration regulation of actin filament-based process regulation of actin filament bundle assembly actin filament bundle organization stress fiber assembly regulation of actin filament organization actomyosin structure organization regulation of stress fiber assembly contractile actin filament bundle assembly regulation of actomyosin structure organization actin filament bundle assembly regulation of actin cytoskeleton organization actin polymerization or depolymerization actin filament polymerization axonogenesis cellular developmental process motor neuron axon guidance plasma membrane bounded cell projection morphogenesis cell development neuron projection development cell morphogenesis neurogenesis multicellular organism development cell projection morphogenesis neuron differentiation neuron projection morphogenesis cell differentiation anatomical structure development system development developmental process axon guidance nervous system development axon development cell morphogenesis involved in neuron differentiation generation of neurons anatomical structure morphogenesis neuron projection guidance neuron development positive regulation of cell communication positive regulation of signal transduction regulation of small GTPase mediated signal transduction regulation of signal transduction Rho protein signal transduction positive regulation of response to stimulus regulation of intracellular signal transduction regulation of signaling positive regulation of intracellular signal transduction regulation of Rho protein signal transduction positive regulation of Rho protein signal transduction regulation of response to stimulus regulation of cell communication positive regulation of small GTPase mediated signal transduction positive regulation of signaling respiratory burst regulation of respiratory burst positive regulation of chemotaxis positive regulation of neutrophil chemotaxis positive regulation of immune system process regulation of leukocyte chemotaxis positive regulation of leukocyte chemotaxis positive regulation of granulocyte chemotaxis regulation of neutrophil chemotaxis regulation of response to external stimulus neutrophil chemotaxis regulation of granulocyte chemotaxis positive regulation of response to external stimulus positive regulation of leukocyte migration positive regulation of neutrophil migration regulation of chemotaxis granulocyte chemotaxis leukocyte chemotaxis regulation of hydrogen peroxide metabolic process reactive oxygen species metabolic process hydrogen peroxide metabolic process regulation of reactive oxygen species metabolic process regulation of nitric oxide biosynthetic process reactive nitrogen species metabolic process nitric oxide metabolic process nitric oxide biosynthetic process regulation of nitric oxide metabolic process regulation of developmental process regulation of cell shape regulation of cell morphogenesis regulation of anatomical structure morphogenesis cortical cytoskeleton organization semaphorin-plexin signaling pathway ruffle assembly positive regulation of phosphorylation regulation of protein modification process regulation of protein phosphorylation positive regulation of protein metabolic process positive regulation of phosphate metabolic process regulation of primary metabolic process positive regulation of metabolic process positive regulation of protein modification process regulation of phosphate metabolic process phosphate-containing compound metabolic process positive regulation of macromolecule metabolic process protein metabolic process positive regulation of protein phosphorylation phosphorus metabolic process protein modification process protein phosphorylation positive regulation of phosphorus metabolic process phosphorylation regulation of protein metabolic process primary metabolic process macromolecule modification regulation of phosphorus metabolic process regulation of phosphorylation defense response inflammatory response cellular localization localization within membrane neuron migration regulation of cell projection organization regulation of cell projection assembly regulation of plasma membrane bounded cell projection assembly regulation of lamellipodium assembly regulation of lamellipodium organization regulation of plasma membrane bounded cell projection organization membrane organization engulfment of apoptotic cell phagocytosis, engulfment membrane invagination phagocytosis apoptotic cell clearance plasma membrane invagination positive regulation of cell projection organization positive regulation of lamellipodium assembly positive regulation of lamellipodium organization positive regulation of plasma membrane bounded cell projection assembly positive regulation of actin filament bundle assembly positive regulation of stress fiber assembly	cell projection cellular anatomical structure cell leading edge plasma membrane bounded cell projection lamellipodium membrane extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle extracellular region organelle extracellular space vesicle cell projection cellular anatomical structure cell leading edge plasma membrane bounded cell projection lamellipodium membrane extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle extracellular region organelle extracellular space vesicle extracellular membrane-bounded organelle intracellular anatomical structure cytoplasm cytosol synapse cell junction glutamatergic synapse Golgi apparatus subcompartment Golgi apparatus organelle subcompartment intracellular membrane-bounded organelle endomembrane system intracellular organelle trans-Golgi network cytoskeleton membraneless organelle intracellular membraneless organelle neuron spine neuron projection dendritic spine somatodendritic compartment postsynapse dendrite dendritic tree anchoring junction focal adhesion cell-substrate junction pigment granule intracellular vesicle melanosome cytoplasmic vesicle cell periphery cell cortex ruffle plasma membrane leading edge membrane ruffle membrane plasma membrane region cell projection membrane protein-containing complex catalytic complex plasma membrane protein complex NADPH oxidase complex membrane protein complex oxidoreductase complex endoplasmic reticulum subcompartment nuclear outer membrane-endoplasmic reticulum membrane network endoplasmic reticulum organelle membrane endoplasmic reticulum membrane cytoplasmic ribonucleoprotein granule supramolecular complex ribonucleoprotein granule endosome membrane endosome recycling endosome cytoplasmic vesicle membrane bounding membrane of organelle recycling endosome membrane vesicle membrane secretory granule secretory vesicle secretory granule membrane ficolin-1-rich granule membrane ficolin-1-rich granule tertiary granule nucleus
B	Kalirin	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 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 cation binding metal ion binding catalytic activity, acting on a protein kinase activity protein kinase activity transferase activity catalytic activity protein serine kinase activity phosphotransferase activity, alcohol group as acceptor transferase activity, transferring phosphorus-containing groups GTPase regulator activity enzyme regulator activity guanyl-nucleotide exchange factor activity nucleoside-triphosphatase regulator activity molecular function regulator activity protein serine/threonine kinase activity histone H2AS1 kinase activity histone modifying activity histone H2A kinase activity histone kinase activity protein binding enzyme binding	behavior multicellular organismal process system process learning learning or memory nervous system process nonassociative learning cognition habituation memory axonogenesis cellular developmental process cell projection organization plasma membrane bounded cell projection morphogenesis behavior multicellular organismal process system process learning learning or memory nervous system process nonassociative learning cognition habituation memory axonogenesis cellular developmental process cell projection organization plasma membrane bounded cell projection morphogenesis cell development neuron projection development cell morphogenesis cellular component organization neurogenesis multicellular organism development cell projection morphogenesis neuron differentiation neuron projection morphogenesis cell differentiation anatomical structure development cellular component organization or biogenesis system development developmental process plasma membrane bounded cell projection organization nervous system development axon development cell morphogenesis involved in neuron differentiation generation of neurons anatomical structure morphogenesis neuron development cellular process protein phosphorylation phosphorylation primary metabolic process macromolecule modification phosphate-containing compound metabolic process metabolic process protein metabolic process macromolecule metabolic process protein modification process phosphorus metabolic process regulation of body fluid levels secretion transport mammary gland development gland development animal organ development biological regulation establishment of localization body fluid secretion localization lactation regulation of biological quality regulation of localization nitrogen compound transport regulation of hormone secretion regulation of cellular process regulation of peptide secretion signaling negative regulation of signaling negative regulation of biological process negative regulation of transport hormone secretion negative regulation of cell communication cell communication negative regulation of peptide secretion peptide secretion secretion by cell regulation of secretion by cell negative regulation of secretion amide transport signal release negative regulation of hormone secretion negative regulation of cellular process negative regulation of secretion by cell regulation of peptide hormone secretion regulation of biological process regulation of signaling growth hormone secretion regulation of transport negative regulation of peptide hormone secretion regulation of hormone levels regulation of growth hormone secretion regulation of peptide transport cell-cell signaling export from cell negative regulation of growth hormone secretion regulation of secretion peptide transport peptide hormone secretion hormone transport regulation of cell communication positive regulation of dendritic spine morphogenesis positive regulation of nervous system development positive regulation of dendritic spine development regulation of cell differentiation regulation of neurogenesis regulation of cell morphogenesis regulation of cell development positive regulation of developmental process regulation of dendrite morphogenesis regulation of synapse structure or activity positive regulation of cell projection organization dendritic spine morphogenesis synapse organization dendritic spine development dendritic spine organization postsynapse organization regulation of cell projection organization positive regulation of cell development regulation of postsynapse organization positive regulation of cell morphogenesis regulation of dendrite development positive regulation of multicellular organismal process regulation of neuron projection development regulation of cellular component organization positive regulation of cellular component organization regulation of developmental process positive regulation of biological process regulation of dendritic spine development regulation of nervous system development dendrite development positive regulation of neuron projection development positive regulation of cell differentiation positive regulation of neurogenesis regulation of multicellular organismal process regulation of anatomical structure morphogenesis positive regulation of cellular process regulation of multicellular organismal development dendrite morphogenesis positive regulation of dendrite morphogenesis regulation of synapse organization cell junction organization regulation of dendritic spine morphogenesis neuron projection organization regulation of plasma membrane bounded cell projection organization multi-multicellular organism process maternal process involved in parturition reproductive process multicellular organismal reproductive process parturition multi-organism reproductive process adult locomotory behavior adult behavior locomotory behavior maternal behavior parental behavior reproductive behavior neuromuscular junction development protein localization cellular localization protein localization to synapse regulation of protein localization regulation of neurotransmitter receptor localization to postsynaptic specialization membrane regulation of protein localization to synapse neurotransmitter receptor localization to postsynaptic specialization membrane cellular macromolecule localization regulation of protein localization to membrane regulation of receptor localization to synapse protein localization to postsynaptic specialization membrane protein localization to cell periphery protein localization to postsynaptic membrane localization within membrane regulation of protein localization to cell periphery protein localization to membrane protein-containing complex localization regulation of postsynaptic membrane neurotransmitter receptor levels regulation of cellular localization macromolecule localization protein localization to organelle protein localization to postsynapse protein localization to cell junction receptor localization to synapse axon guidance neuron projection guidance biological process involved in intraspecies interaction between organisms social behavior cellular response to stimulus response to stimulus signal transduction intracellular signal transduction regulation of modification of postsynaptic actin cytoskeleton regulation of modification of synaptic structure modification of postsynaptic actin cytoskeleton regulation of modification of postsynaptic structure modification of synaptic structure modification of postsynaptic structure	cellular anatomical structure intracellular anatomical structure cytoplasm synapse cell junction glutamatergic synapse intracellular organelle cytoskeleton organelle membraneless organelle intracellular membraneless organelle perinuclear region of cytoplasm somatodendritic compartment cell body cellular anatomical structure intracellular anatomical structure cytoplasm synapse cell junction glutamatergic synapse intracellular organelle cytoskeleton organelle membraneless organelle intracellular membraneless organelle perinuclear region of cytoplasm somatodendritic compartment cell body neuronal cell body presynapse membrane extrinsic component of membrane postsynaptic density postsynapse neuron to neuron synapse postsynaptic specialization asymmetric synapse

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A	IPR003578	Small GTPase Rho	Family
A	IPR027417	P-loop containing nucleoside triphosphate hydrolase	Homologous Superfamily
A	IPR005225	Small GTP-binding domain	Domain
A	IPR001806	Small GTPase	Family
B	IPR001251	CRAL-TRIO lipid binding domain	Domain
B	IPR036179	Immunoglobulin-like domain superfamily	Homologous Superfamily
B	IPR000219	Dbl homology (DH) domain	Domain
B	IPR028570	Kalirin/Triple functional domain protein, SH3 domain 1	Domain
B	IPR036028	SH3-like domain superfamily	Homologous Superfamily
B	IPR000719	Protein kinase domain	Domain
B	IPR003599	Immunoglobulin domain subtype	Domain
B	IPR047053	Kalirin/Triple functional domain protein, SH3 domain 2	Domain
B	IPR001452	SH3 domain	Domain
B	IPR013783	Immunoglobulin-like fold	Homologous Superfamily
B	IPR035899	Dbl homology (DH) domain superfamily	Homologous Superfamily
B	IPR007110	Immunoglobulin-like domain	Domain
B	IPR055251	SOS1/NGEF-like, PH domain	Domain
B	IPR002017	Spectrin repeat	Repeat
B	IPR017441	Protein kinase, ATP binding site	Binding Site
B	IPR001849	Pleckstrin homology domain	Domain
B	IPR003598	Immunoglobulin subtype 2	Domain
B	IPR036865	CRAL-TRIO lipid binding domain superfamily	Homologous Superfamily
B	IPR047054	Kalirin/Triple functional domain protein, pleckstrin homology (PH) domain 1	Domain
B	IPR011993	PH-like domain superfamily	Homologous Superfamily
B	IPR013098	Immunoglobulin I-set	Domain
B	IPR051336	Rho GTPase-activating Guanine Nucleotide Exchange Factors	Family
B	IPR003961	Fibronectin type III	Domain
B	IPR011009	Protein kinase-like domain superfamily	Homologous Superfamily
B	IPR018159	Spectrin/alpha-actinin	Repeat
B	IPR008271	Serine/threonine-protein kinase, active site	Active Site
B	IPR036116	Fibronectin type III superfamily	Homologous Superfamily

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A	Pharos: P63000	dilated cardiomyopathy melanoma Cardiotoxicity cutaneous melanoma congestive heart failure diabetes mellitus liver disease malignant glioma osteosarcoma plasma cell myeloma urinary bladder cancer heart disease hepatocellular carcinoma medulloblastoma ovarian cancer dilated cardiomyopathy melanoma Cardiotoxicity cutaneous melanoma congestive heart failure diabetes mellitus liver disease malignant glioma osteosarcoma plasma cell myeloma urinary bladder cancer heart disease hepatocellular carcinoma medulloblastoma ovarian cancer Sjogren syndrome depressive disorder dilated cardiomyopathy 1A heart failure intellectual disability lymphoplasmacytic lymphoma microcephaly pancreatic intraductal papillary-mucinous neoplasm intellectual disability, autosomal dominant 48