4HAT

Crystal structure of CRM1 inhibitor Leptomycin B in complex with CRM1-Ran-RanBP1

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	d4hata_	Alpha and beta proteins (a/b)	P-loop containing nucleoside triphosphate hydrolases	P-loop containing nucleoside triphosphate hydrolases	G proteins	Ran	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d4hatb_	All beta proteins	PH domain-like barrel	PH domain-like	automated matches	automated matches	yeast (Saccharomyces cerevisiae ) [TaxId: 4932 ],	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	8057412	3002022	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	PH domain-like	8081156	3000134	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	e4hatA2	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)
C	CRM1_C	e4hatC2	A: alpha superhelices	X: Repetitive alpha hairpins	H: ARM repeat (From Topology)	T: ARM repeat	F: CRM1_C	ECOD (1.6)
C	Xpo1	e4hatC3	A: alpha superhelices	X: Repetitive alpha hairpins	H: ARM repeat (From Topology)	T: ARM repeat	F: Xpo1	ECOD (1.6)
B	Ran_BP1	e4hatB3	A: beta barrels	X: PH domain-like	H: PH domain-like (From Topology)	T: PH domain-like	F: Ran_BP1	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	2.30.29.30	Mainly Beta	Roll	PH-domain like	Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB)	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
C	PF08389	Exportin 1-like protein (Xpo1)	Exportin 1-like protein	-	Repeat
C	PF18784	CRM1 / Exportin repeat 2 (CRM1_repeat_2)	CRM1 / Exportin repeat 2	-	Repeat
C	PF18777	Chromosome region maintenance or exportin repeat (CRM1_repeat)	Chromosome region maintenance or exportin repeat	-	Repeat
C	PF18787	CRM1 / Exportin repeat 3 (CRM1_repeat_3)	CRM1 / Exportin repeat 3	-	Repeat
C	PF03810	Importin-beta N-terminal domain (IBN_N)	Importin-beta N-terminal domain	-	Repeat
C	PF08767	CRM1 C terminal (CRM1_C)	CRM1 C terminal	-	Repeat

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A	GTP-binding nuclear protein Ran	cell adhesion molecule binding cadherin binding protein binding binding dynein intermediate chain 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 protein domain specific binding chromatin binding cell adhesion molecule binding cadherin binding protein binding binding dynein intermediate chain 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 protein domain specific binding chromatin binding protein heterodimerization activity protein dimerization activity RNA binding organic cyclic compound binding nucleic acid binding guanyl nucleotide binding GTP binding nucleotide binding guanyl ribonucleotide binding purine ribonucleotide binding purine ribonucleoside triphosphate binding nucleoside phosphate binding ion binding purine nucleotide binding anion binding heterocyclic compound binding carbohydrate derivative binding ribonucleotide binding small molecule binding cation binding magnesium ion binding metal ion binding GDP binding G protein activity molecular function regulator activity importin-alpha family protein binding	protein localization cellular localization establishment of protein localization nitrogen compound transport nucleocytoplasmic transport transport nuclear transport intracellular transport protein export from nucleus establishment of localization localization protein transport establishment of localization in cell cellular macromolecule localization macromolecule localization protein localization cellular localization establishment of protein localization nitrogen compound transport nucleocytoplasmic transport transport nuclear transport intracellular transport protein export from nucleus establishment of localization localization protein transport establishment of localization in cell cellular macromolecule localization macromolecule localization cellular process nuclear export intracellular protein transport viral process cell division protein localization to nucleus import into nucleus establishment of protein localization to organelle protein localization to organelle protein import into nucleus cellular component organization organelle organization actin cytoskeleton organization actin filament-based process cellular component organization or biogenesis cytoskeleton organization regulation of localization regulation of cellular process regulation of protein localization positive regulation of nucleocytoplasmic transport positive regulation of biological process positive regulation of establishment of protein localization regulation of protein localization to nucleus positive regulation of protein transport regulation of protein import into nucleus positive regulation of intracellular transport positive regulation of cellular process regulation of intracellular transport regulation of biological process regulation of transport positive regulation of protein localization to nucleus biological regulation regulation of establishment of protein localization positive regulation of protein import into nucleus regulation of nucleocytoplasmic transport regulation of protein transport positive regulation of transport regulation of cellular localization positive regulation of protein localization regulation of intracellular protein transport positive regulation of intracellular protein transport developmental process spermatid development spermatid differentiation sexual reproduction cellular developmental process spermatogenesis reproductive process multicellular organismal reproductive process cell development cellular process involved in reproduction in multicellular organism developmental process involved in reproduction gamete generation male gamete generation cell differentiation anatomical structure development germ cell development nucleobase-containing compound metabolic process metabolic process primary metabolic process DNA metabolic process macromolecule metabolic process nucleic acid metabolic process nucleoside phosphate metabolic process ribose phosphate metabolic process purine nucleoside triphosphate metabolic process GTP metabolic process carbohydrate derivative metabolic process nucleotide metabolic process purine-containing compound metabolic process purine nucleotide metabolic process ribonucleotide metabolic process organophosphate metabolic process nucleobase-containing small molecule metabolic process purine ribonucleoside triphosphate metabolic process phosphate-containing compound metabolic process small molecule metabolic process nucleoside triphosphate metabolic process purine ribonucleotide metabolic process phosphorus metabolic process ribonucleoside triphosphate metabolic process regulation of protein binding positive regulation of molecular function regulation of molecular function positive regulation of protein binding regulation of binding positive regulation of binding cellular response to stimulus cellular response to mineralocorticoid stimulus response to lipid response to stimulus response to endogenous stimulus cellular response to organic cyclic compound response to mineralocorticoid cellular response to corticosteroid stimulus cellular response to endogenous stimulus response to corticosteroid cellular response to chemical stimulus response to hormone response to chemical response to steroid hormone cellular response to lipid cellular response to steroid hormone stimulus response to organic cyclic compound cellular response to hormone stimulus cell cycle mitotic cell cycle multicellular organismal process head development forebrain development animal organ development brain development nervous system development pallium development multicellular organism development central nervous system development telencephalon development hippocampus development limbic system development system development negative regulation of biological process post-transcriptional regulation of gene expression negative regulation of cellular process RNA localization nucleobase-containing compound transport negative regulation of macromolecule metabolic process regulation of biosynthetic process RNA transport negative regulation of metabolic process nucleic acid transport pre-miRNA export from nucleus regulation of macromolecule metabolic process gene expression macromolecule biosynthetic process regulatory ncRNA-mediated post-transcriptional gene silencing RNA export from nucleus regulatory ncRNA-mediated gene silencing miRNA-mediated post-transcriptional gene silencing regulation of gene expression negative regulation of gene expression establishment of RNA localization biosynthetic process negative regulation of biosynthetic process negative regulation of macromolecule biosynthetic process post-transcriptional gene silencing regulation of macromolecule biosynthetic process regulation of metabolic process establishment of organelle localization ribonucleoprotein complex biogenesis ribosomal subunit export from nucleus protein-containing complex localization cellular component biogenesis ribosome biogenesis ribosomal small subunit export from nucleus organelle localization ribosome localization ribosomal large subunit export from nucleus mitotic nuclear division organelle fission chromosome organization sister chromatid segregation nuclear division mitotic cell cycle process mitotic sister chromatid segregation nuclear chromosome segregation chromosome segregation cell cycle process protein localization to nucleolus microtubule cytoskeleton organization mitotic spindle organization microtubule-based process microtubule cytoskeleton organization involved in mitosis spindle organization RNA import into nucleus snRNA import into nucleus snRNA transport	cellular anatomical structure membrane protein-containing complex nucleocytoplasmic transport complex RNA nuclear export complex membrane-bounded organelle intracellular organelle organelle envelope intracellular anatomical structure organelle nuclear envelope nucleus intracellular membrane-bounded organelle endomembrane system cellular anatomical structure membrane protein-containing complex nucleocytoplasmic transport complex RNA nuclear export complex membrane-bounded organelle intracellular organelle organelle envelope intracellular anatomical structure organelle nuclear envelope nucleus intracellular membrane-bounded organelle endomembrane system extracellular exosome extracellular vesicle extracellular organelle extracellular region extracellular space vesicle extracellular membrane-bounded organelle cytoplasm cytosol cell projection cilium 9+2 motile cilium sperm flagellum motile cilium plasma membrane bounded cell projection nuclear protein-containing complex nuclear pore membraneless organelle intracellular membraneless organelle chromatin chromosome endosome intracellular vesicle recycling endosome cytoplasmic vesicle male germ cell nucleus germ cell nucleus midbody membrane-enclosed lumen nucleolus intracellular organelle lumen organelle lumen nuclear lumen pigment granule melanosome microtubule organizing center cytoskeleton centriole microtubule cytoskeleton nucleoplasm manchette
C	Exportin-1	small GTPase binding protein binding binding enzyme binding GTPase binding RNA binding snRNA binding organic cyclic compound binding nucleic acid binding U1 snRNA binding U6 snRNA binding U4 snRNA binding nucleocytoplasmic carrier activity nuclear export signal receptor activity small GTPase binding protein binding binding enzyme binding GTPase binding RNA binding snRNA binding organic cyclic compound binding nucleic acid binding U1 snRNA binding U6 snRNA binding U4 snRNA binding nucleocytoplasmic carrier activity nuclear export signal receptor activity molecular carrier activity U5 snRNA binding nuclear import signal receptor activity U2 snRNA binding	cellular localization RNA transport nitrogen compound transport nucleocytoplasmic transport transport nuclear transport nucleic acid transport intracellular transport tRNA export from nucleus establishment of localization RNA export from nucleus localization tRNA re-export from nucleus tRNA transport establishment of RNA localization cellular localization RNA transport nitrogen compound transport nucleocytoplasmic transport transport nuclear transport nucleic acid transport intracellular transport tRNA export from nucleus establishment of localization RNA export from nucleus localization tRNA re-export from nucleus tRNA transport establishment of RNA localization establishment of localization in cell macromolecule localization cellular process RNA localization nuclear export nucleobase-containing compound transport establishment of organelle localization ribonucleoprotein complex biogenesis ribosomal subunit export from nucleus protein-containing complex localization cellular component biogenesis ribosome biogenesis ribosomal small subunit export from nucleus organelle localization cellular component organization or biogenesis ribosome localization protein localization establishment of protein localization protein export from nucleus protein transport cellular macromolecule localization intracellular protein transport protein localization to chromosome, centromeric region protein localization to kinetochore protein localization to chromosome protein localization to condensed chromosome protein localization to organelle mRNA transport mRNA export from nucleus gene expression macromolecule biosynthetic process biosynthetic process metabolic process macromolecule metabolic process ribosomal large subunit export from nucleus	cellular anatomical structure intracellular anatomical structure cytoplasm intracellular membraneless organelle chromosome chromosomal region kinetochore intracellular organelle organelle membraneless organelle chromosome, centromeric region condensed chromosome, centromeric region supramolecular complex condensed chromosome cellular anatomical structure intracellular anatomical structure cytoplasm intracellular membraneless organelle chromosome chromosomal region kinetochore intracellular organelle organelle membraneless organelle chromosome, centromeric region condensed chromosome, centromeric region supramolecular complex condensed chromosome microtubule organizing center cytoskeleton spindle pole body microtubule cytoskeleton perinuclear region of cytoplasm membrane-bounded organelle nucleus intracellular membrane-bounded organelle
B	Ran-specific GTPase-activating protein 1	small GTPase binding protein binding binding enzyme binding GTPase binding GTPase regulator activity enzyme regulator activity enzyme activator activity GTPase activator activity molecular function activator activity nucleoside-triphosphatase regulator activity molecular function regulator activity	catabolic process proteolysis involved in protein catabolic process primary metabolic process protein catabolic process macromolecule catabolic process modification-dependent macromolecule catabolic process modification-dependent protein catabolic process proteolysis ubiquitin-dependent protein catabolic process metabolic process cellular process protein metabolic process macromolecule metabolic process protein localization catabolic process proteolysis involved in protein catabolic process primary metabolic process protein catabolic process macromolecule catabolic process modification-dependent macromolecule catabolic process modification-dependent protein catabolic process proteolysis ubiquitin-dependent protein catabolic process metabolic process cellular process protein metabolic process macromolecule metabolic process protein localization establishment of protein localization cellular localization NLS-bearing protein import into nucleus 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 mitotic cell cycle process cell cycle phase transition cell cycle G1/S transition of mitotic cell cycle cell cycle G1/S phase transition mitotic cell cycle mitotic cell cycle phase transition cell cycle process RNA transport nucleic acid transport RNA export from nucleus establishment of RNA localization RNA localization nuclear export nucleobase-containing compound transport	membrane-bounded organelle protein-containing complex intracellular anatomical structure nucleus nuclear protein-containing complex intracellular membrane-bounded organelle endomembrane system intracellular organelle organelle envelope cellular anatomical structure organelle nuclear envelope nuclear pore cytoplasm

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A	IPR027417	P-loop containing nucleoside triphosphate hydrolase	Homologous Superfamily
A	IPR002041	Ran GTPase	Family
A	IPR005225	Small GTP-binding domain	Domain
A	IPR001806	Small GTPase	Family
C	IPR041123	Chromosome region maintenance repeat	Repeat
C	IPR016024	Armadillo-type fold	Homologous Superfamily
C	IPR041235	Exportin-1, repeat 2	Repeat
C	IPR001494	Importin-beta, N-terminal domain	Domain
C	IPR011989	Armadillo-like helical	Homologous Superfamily
C	IPR045065	Exportin-1/5	Family
C	IPR013598	Exportin-1/Importin-beta-like	Domain
C	IPR014877	Exportin-1, C-terminal	Domain
C	IPR040485	Exportin-1, repeat 3	Repeat
B	IPR011993	PH-like domain superfamily	Homologous Superfamily
B	IPR000156	Ran binding domain	Domain
B	IPR045256	Ran-specific GTPase-activating protein 1, Ran-binding domain	Domain
B	IPR045255	Ran binding protein RanBP1-like	Family

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A	Pharos: P62826	keloid carcinoma HIV infectious disease Mammary Neoplasms, Experimental sarcomatoid carcinoma pemphigus undifferentiated carcinoma acute myeloid leukemia mammary neoplasms, animal nasopharyngeal carcinoma plasma cell myeloma amyotrophic lateral sclerosis lymphoplasmacytic lymphoma osteoarthritis ovarian cancer keloid carcinoma HIV infectious disease Mammary Neoplasms, Experimental sarcomatoid carcinoma pemphigus undifferentiated carcinoma acute myeloid leukemia mammary neoplasms, animal nasopharyngeal carcinoma plasma cell myeloma amyotrophic lateral sclerosis lymphoplasmacytic lymphoma osteoarthritis ovarian cancer invasive ductal breast carcinoma myopathy osteoarthritis susceptibility 1

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.