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FLASH GENE

Symbol

KPNB1

contributors: mct/npt - updated : 28-12-2016

HGNC name	karyopherin (importin) beta 1
HGNC id	6400

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	17q21.32      Physical location : 45.727.274 - 45.761.004
Synonym name	importin 90
	nuclear factor p97
	importin beta-1 subunit
Synonym symbol(s)	NTF97, IMB1, MGC2155, MGC2156, MGC2157, Impnb, IPO1, IPOB, Kap beta1

DNA

TYPE	functioning gene
STRUCTURE	33.73 kb     22 Exon(s)

10 Kb 5' upstream gene genomic sequence study

motif

repetitive sequence   ALU   long interspersed repetitive elements

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_002265 22 - 4205 NP_002256 97 876 - 2015 26319354 NM_001276453 20 - 3951 NP_001263382 - 731 - 2015 26319354

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol blood / hematopoietic spleen       highly Cardiovascular heart       highly Digestive liver       highly Endocrine pancreas       highly Nervous brain       highly Reproductive male system prostate     highly Respiratory lung       highly Urinary kidney       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / Hematopoietic bone marrow       Epithelial secretory glandular endocrine   Epithelial secretory glandular exocrine   Muscular striatum skeletal

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	an importin N-terminal domain
	eight HEAT repeats, forming a rod-like helical structure, functioning as protein-protein interaction surface and involved in intracellular processus
	a central region (harboring nucleoporin-binding sites) that regulates microtubule dynamic functions and interaction with kinetochores
	C-terminal region (which binds importin-alpha) inhibits mitotic spindle pole formation

mono polymer

heteromer , dimer

HOMOLOGY

interspecies	ortholog to murine Kpnb1
	homolog to drosophila Fs(2)Ket
	homolog to C.elegans imb-1

Homologene

FAMILY

importin beta family

CATEGORY

receptor nuclear , transport carrier

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus,nucleoplasm
	intracellular,nuclear envelope,pore

basic FUNCTION	docking the complex at the cytoplasmic side of the nuclear pore complex
	binds cargo molecules either directly or via two types of adapter molecules, importin alpha, for import of proteins with a classical nuclear localization signal (NLS), or snurportin 1, for import of m3G-capped U snRNPs (Paraskeva 1999)
	involved in nucleo-cytoplasmic trafficking and critical for protein and RNA subcellular localization
	serving as a receptor for nuclear localization signals containing proteins (Van der Watt 2009)
	regulating nucleocytoplasmic transport velocities and therefore potentially the speed of cargo traffic across the nuclear envelope (Yang 2006)
	main vector for interphase nuclear protein import and plays roles after nuclear envelope breakdown
	regulates multiple aspects of mitosis via distinct domains that interact with different classes of proteins in human cells
	having functions at kinetochores exerted via RANBP2 and opposed by XPO1
	localized translation of KPNB1 mRNA enables separation of cytoplasmic and nuclear transport functions of importins and is required for efficient retrograde signaling in injured axons
	major nuclear import receptor, playing an integral role in importing transcription factors, cell signaling proteins, cell cycle proteins, and so forth, into the nucleus, thus playing a crucial role in maintaining normal cell homeostasis
	involved in nuclear-cytoplasmic trafficking and is crucial for protein and RNA subcellular localization
	is one of the soluble nuclear transport receptors, reported to act as an important role in the occurrence and development of tumor, such as cervical cancer, head and neck and lung cancer
	is required for timely nuclear import of PER1/CRY1 in the negative feedback regulation of the circadian clock
	transports nuclear factor RELA from the cytoplasm to the nucleus to increase pro-inflammatory genes expression
	may play a key role in the inflammation process of rheumatoid arthritis via STAT3 signal transduction pathway
	nuclear transport receptors KPNB1 and XPO1 play essential roles in localising the RANBP2-SUMO-RANGAP1 complex away from, or at kinetochores, respectively

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

cellular trafficking transport

text	nucleocytoplasmic transport, nuclear import of ribosomal proteins

PATHWAY

metabolism

signaling

signal transduction

a component	component of the NLS import receptor which is a heterodimer of importin alpha and beta subunits
	forms a high-molecular-weight complex with both AHCTF1 and the NUP107-160 complex in cytosol

INTERACTION

DNA

RNA

small molecule	metal binding,
	Zn2+

protein	binding to RAN importin alpha
	binding specifically to the GTPbound form of RAN
	critical function of RANBP2 is to capture recycling RANGTP-KPNB1 complexes at cytoplasmic fibrils to allow for adequate classical nuclear localization signal-mediated cargo import
	TP53BP1 is imported to the nucleus through the NUP153-KPNB1 interplay
	interacts through its central region with NUP358/RANBP2, which in turn binds SUMO-conjugated RANGAP1 in nuclear pores
	nuclear import of RELA mainly relies on the canonical KPNA2/KPNB1 pathway
	EI24 can bind specifically to KPNA2/KPNB1 to impede their normal role in nuclear import, shedding new light on the cellular functions of EI24 and its tumor suppressor role
	SNAI1 C2H2-type zinc-finger (ZF) domain functions both as a nuclear localization signal which binds to KPNB1 directly and as a DNA-binding domain
	mediates the translocation of NFKB1 into the nuclei of myeloma cells, thereby regulating proliferation and blocking apoptosis
	KPNB1 and NUP153 interact at the nuclear pore complex (NPC) nuclear face to form a Ran-regulated mesh that modulates NPC permeability
	allosteric coupling between a structured domain of a channel nucleoporin (NUP58) and its neighboring disordered domain in interaction with another channel nucleoporin (NUP54) and a transport factor (KPNB1)
	nuclear translocation of IGFBP3 by KPNB1 is a prerequisite for IGFBP3-induced apoptosis
	KPNB1 interacts mainly with PER proteins and directs PER1/CRY1 nuclear transport in a circadian fashion

cell & other

REGULATION

Other

intracellular calcium levels can regulate KPNB1/KPNA-dependent nuclear import

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in cervical cancer and are critical for cancer cell survival and proliferation (van der Watt 2009) tumoral       gain of function in hepatocellular carcinoma (HCC) tissue samples and increasing HCC cells growth and the KPNB1 expression was associated with poor survival tumoral     --over   in cervical cancer, critical for cervical cancer cell survival and proliferation

Susceptibility

Variant & Polymorphism

Candidate gene
Marker	promising candidate as both biomarker in cancer
Therapy target
	System Type Disorder Pubmed cancer digestive liver therapeutic target for HCC cancer     potential anticancer therapeutic target cancer hemopathy   target for myeloma therapies cancer reproductive uterus blocking KPNB1 has potential as an anticancer therapeutic approach

ANIMAL & CELL MODELS