KPNA4 karyopherin subunit alpha 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: KPNA4provided by HGNC
Official Full Name: karyopherin subunit alpha 4provided by HGNC
Primary source: HGNC:HGNC:6397
See related: Ensembl:ENSG00000186432 MIM:602970; AllianceGenome:HGNC:6397
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: QIP1; SRP3; IPOA3
Summary: The nuclear import of karyophilic proteins is directed by short amino acid sequences termed nuclear localization signals (NLSs). Karyopherins, or importins, are cytoplasmic proteins that recognize NLSs and dock NLS-containing proteins to the nuclear pore complex. The protein encoded by this gene shares the sequence similarity with Xenopus importin-alpha and Saccharomyces cerevisiae Srp1. This protein is found to interact with the NLSs of DNA helicase Q1 and SV40 T antigen. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in heart (RPKM 11.7), esophagus (RPKM 9.8) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 3q25.33

Exon count:: 17

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	3	NC_000003.12 (160495007..160565571, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	3	NC_060927.1 (163269616..163340186, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	3	NC_000003.11 (160212795..160283359, complement)

Chromosome 3 - NC_000003.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Circular RNA hsa_circ_0008003 promotes the progression of non-small-cell lung cancer by sponging miR-548I and regulating KPNA4 expression.
Title: Circular RNA hsa_circ_0008003 promotes the progression of non-small-cell lung cancer by sponging miR-548I and regulating KPNA4 expression.
Human importin alpha3 and its N-terminal truncated form, without the importin-beta-binding domain, are oligomeric species with a low conformational stability in solution.
Title: Human importin α3 and its N-terminal truncated form, without the importin-β-binding domain, are oligomeric species with a low conformational stability in solution.
Ginsenoside Rg3 inhibits osteosarcoma progression by reducing circ_0003074 expression in a miR-516b-5p/KPNA4-dependent manner.
Title: Ginsenoside Rg3 inhibits osteosarcoma progression by reducing circ_0003074 expression in a miR-516b-5p/KPNA4-dependent manner.
The nuclear localization sequence of the epigenetic factor RYBP binds to human importin alpha3.
Title: The nuclear localization sequence of the epigenetic factor RYBP binds to human importin α3.
Value of KPNA4 as a diagnostic and prognostic biomarker for hepatocellular carcinoma.
Title: Value of KPNA4 as a diagnostic and prognostic biomarker for hepatocellular carcinoma.
LINC00467 facilitates osteosarcoma progression by sponging miR217 to regulate KPNA4 expression.
Title: LINC00467 facilitates osteosarcoma progression by sponging miR‑217 to regulate KPNA4 expression.
A Phosphorylation-Induced Switch in the Nuclear Localization Sequence of the Intrinsically Disordered NUPR1 Hampers Binding to Importin.
Title: A Phosphorylation-Induced Switch in the Nuclear Localization Sequence of the Intrinsically Disordered NUPR1 Hampers Binding to Importin.
KPNA4 is involved in cataract formation via the nuclear import of p53.
Title: KPNA4 is involved in cataract formation via the nuclear import of p53.
KPNA4 regulated by miR-548b-3p promotes the malignant phenotypes of papillary thyroid cancer.
Title: KPNA4 regulated by miR-548b-3p promotes the malignant phenotypes of papillary thyroid cancer.
STAT3-induced upregulation of circCCDC66 facilitates the progression of non-small cell lung cancer by targeting miR-33a-5p/KPNA4 axis.
Title: STAT3-induced upregulation of circCCDC66 facilitates the progression of non-small cell lung cancer by targeting miR-33a-5p/KPNA4 axis.

Submit: New GeneRIF Correction See all GeneRIFs (27)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Genome-Wide Association Study of Primary Dentition Pit-and-Fissure and Smooth Surface Caries. EBI GWAS Catalog EBI GWAS CatalogPubMed EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Rev	rev	HIV-1 Rev interacting protein, karyopherin alpha 4 (KPNA4), is identified by the in-vitro binding experiments involving cytosolic or nuclear extracts from HeLa cells	PubMed
Vpr	vpr	Full-length Vpr interacts with QIP1 through its binding to the C-terminal domain (residues 392-537) of QIP1	PubMed
integrase	gag-pol	HIV-1 Integrase (IN) double mutant KK215/219AA and RK263/264AA severely impairs its binding to importin 3 alpha. W179A/N183A and W348A/N352A mutations in the major and the minor NLS binding grooves of Imp alpha3 significantly reduce its binding to IN	PubMed
	gag-pol	HIV-1 IN interacts with importin alpha by the BiFC assay and amino acids 161-173 in IN are required for the interaction with importin alpha	PubMed
	gag-pol	A region encompassing amino acids 251-270 in the C-terminal domain of HIV-1 IN is required for importin alpha3 binding and for nuclear localization	PubMed
	gag-pol	HIV-1 Rev disrupts both IN-TNPO3 and IN-importin alpha complexes	PubMed
	gag-pol	Some reports indicate a possible role for the interactions between karyopherin alpha and beta with HIV-1 integrase in the nuclear import of HIV-1 preintegration complexes (PIC), while other reports indicate integrase is not involved in PIC nuclear import	PubMed
	gag-pol	Karyopherin alpha binds to a bipartite nuclear localization signal in HIV-1 integrase (amino acids 186-189 and 211-219)	PubMed
	gag-pol	Karyopherin alpha and beta are reported to interact with HIV-1 integrase (IN) to facilitate nuclear import of IN, however a conflicting report indicates nuclear accumulation of IN does not involve karyopherin alpha, beta 1, or beta 2 mediated pathways	PubMed
matrix	gag	Nuclear import of HIV-1 preintegration complexes by karyopherin alpha is governed by phosphorylation of HIV-1 Matrix on tyrosine and serine, however the exact role of phosphorylation of the C-terminal tyrosine of Matrix has been debated	PubMed
	gag	HIV-1 Matrix increases intracellular ATP content, an effect hypothesized to support the ATP-dependent nuclear import of HIV-1 preintegration complexes by karyopherin alpha	PubMed
	gag	HIV-1 Vpr increases the affinity of karyopherin alpha to the HIV-1 Matrix nuclear localization signal, thereby mediating the nuclear import of HIV-1 preintegration complexes	PubMed
	gag	Hsp70 stimulates the binding of HIV-1 matrix to karyopherin alpha	PubMed
	gag	The role of HIV-1 Matrix during nuclear import of the HIV-1 preintegration complex has been controversial, however recent understanding indicates HIV-1 Matrix and Vpr proteins act in concert to facilitate nuclear import by binding to karyopherin alpha	PubMed
	gag	HIV-1 Matrix contains two nuclear localization signals (NLS) spanning amino acids 24-33 and 110-114 that are recognized by karyopherin alpha and mediate the nuclear import of HIV-1 preintegration complexes	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

GDB:434012 (e-PCR)
- UniSTS:157204

D6S1216E (e-PCR)
- UniSTS:78367

STS-N58827 (e-PCR)
- UniSTS:9766

D8S2279 (e-PCR)
- UniSTS:473907

STS-N58827 (e-PCR)
- UniSTS:11325

WIAF-1631 (e-PCR)
- UniSTS:19006

GDB:314949 (e-PCR)
- UniSTS:156503

D10S16 (e-PCR)
- UniSTS:155756

D15S1477 (e-PCR)
- UniSTS:474482

D1S1425 (e-PCR)
- UniSTS:149621

GDB:451532 (e-PCR)
- UniSTS:157306

Kpna4 (e-PCR), detects polymorphism
- UniSTS:507011

HSC0TF112 (e-PCR)
- UniSTS:76455

RH46490 (e-PCR)
- UniSTS:76979

KPNA4_907.2 (e-PCR)
- UniSTS:462307

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables nuclear import signal receptor activity	IBA Inferred from Biological aspect of Ancestor more info
enables nuclear import signal receptor activity	IDA Inferred from Direct Assay more info	PubMed
enables nuclear localization sequence binding	IBA Inferred from Biological aspect of Ancestor more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in NLS-bearing protein import into nucleus	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_positive_effect dopamine secretion	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_positive_effect gene expression	IDA Inferred from Direct Assay more info	PubMed
involved_in protein import into nucleus	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
part_of NLS-dependent protein nuclear import complex	IPI Inferred from Physical Interaction more info	PubMed
located_in cytosol	NAS Non-traceable Author Statement more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
located_in nuclear membrane	IDA Inferred from Direct Assay more info
part_of nuclear pore	IDA Inferred from Direct Assay more info	PubMed
is_active_in nucleoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleoplasm	NAS Non-traceable Author Statement more info	PubMed
located_in nucleoplasm	TAS Traceable Author Statement more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: importin subunit alpha-3

Names: importin alpha Q1; importin subunit alpha-4; karyopherin alpha 4 (importin alpha 3)

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_002268.5 → NP_002259.1 importin subunit alpha-3

See identical proteins and their annotated locations for NP_002259.1

Status: REVIEWED

Source sequence(s)

AC078868, BC034493

Consensus CDS

CCDS3191.1

UniProtKB/Swiss-Prot

A8K4S6, D3DNM2, O00190, O00629

UniProtKB/TrEMBL

A0A7I2V340

Related

ENSP00000334373.4, ENST00000334256.9

Conserved Domains (2) summary

COG5064
Location:11 → 513

SRP1; Karyopherin (importin) alpha [Intracellular trafficking and secretion]

sd00043
Location:279 → 311

ARM; armadillo repeat [structural motif]