KPNA4 karyopherin alpha 4 (importin alpha 3) [Homo sapiens] - Gene

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Summary

Official Symbol: KPNA4provided by HGNC
Official Full Name: karyopherin alpha 4 (importin alpha 3)provided by HGNC
Primary source: HGNC:6397
See related: Ensembl:ENSG00000186432; HPRD:04275; MIM:602970; Vega:OTTHUMG00000159033
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; FLJ31113; MGC12217; MGC26703
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]

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Genomic context

Location :: 3q25.33

Sequence :: Chromosome: 3; NC_000003.11 (160212783..160283376, complement)

See KPNA4 in Epigenomics, MapViewer

Chromosome 3 - NC_000003.11 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

Impalpha3 is an HIV integrase-interacting cofactor and is required for efficient HIV-1 nuclear import and replication.
Title: Importin alpha3 interacts with HIV-1 integrase and contributes to HIV-1 nuclear import and replication.
The papillomavirus E2 proteins preferentially interacted with alpha importins 3 and 5, and showed very weak or no interaction with the other three widely expressed alpha importins (alpha1, alpha 4, and alpha 7).
Title: Common importin alpha specificity for papillomavirus E2 proteins.
stress-induced accumulation of non-ubiquitinated p53 in the cytoplasm promotes interaction with importin-alpha3 and rapid import
Title: Stress-mediated nuclear stabilization of p53 is regulated by ubiquitination and importin-alpha3 binding.
Expression of importin alpha3, a protein involved in p50/p65 nuclear import, was decreased in cells overexpressing PHB.
Title: Prohibitin inhibits tumor necrosis factor alpha-induced nuclear factor-kappa B nuclear translocation via the novel mechanism of decreasing importin alpha3 expression.
Daxx interacts selectively with importin alpha3 through its NLS1 and NLS2 sequences. Conversely, importin alpha3 utilizes two NLS-binding sites for Daxx interaction, suggesting that it mediates nuclear import of Daxx.
Title: Daxx contains two nuclear localization signals and interacts with importin alpha3.
Our results indicate that the nuclear import of RHA is mediated by the importin-alpha3/importin-beta-dependent pathway and suggest that the specificity for importin may regulate the functions of cargo proteins.
Title: The nuclear import of RNA helicase A is mediated by importin-alpha3.

Submit: New GeneRIF Correction

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Phenotypes

Review eQTL and phenotype association data in this region using PheGenI

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HIV-1 protein interactions

Protein	Gene	Interaction	Pubs
integrase	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	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 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

Go to the HIV-1, Human Protein Interaction Database

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Products	Interactant	Other Gene	Source	Pubs	Description
NP_002259.1	NP_004604.2	TGM2	BIND	PubMed	tTG interacts with importin-alpha3.
O00629	P46063	RECQL	HPRD	PubMed
O00629	P21980	TGM2	HPRD	PubMed
BioGRID:110038	BioGRID:106902	ARRB2	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110038	BioGRID:107461	CDKN1B	BioGRID	PubMed	Reconstituted Complex
BioGRID:110038	BioGRID:107821	CSE1L	BioGRID	PubMed	Reconstituted Complex
BioGRID:110038	BioGRID:115906	CTCF	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110038	BioGRID:114028	CUL4B	BioGRID	PubMed	Reconstituted Complex
BioGRID:110038	BioGRID:114602	EXO1	BioGRID	PubMed	Reconstituted Complex
BioGRID:110038	BioGRID:109272	H3F3A	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110038	BioGRID:110035	KPNB1	BioGRID	PubMed	Reconstituted Complex
BioGRID:110038	BioGRID:110694	MYC	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110038	BioGRID:201430	Mki67	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110038	BioGRID:111817	RAC1	BioGRID	PubMed	Two-hybrid
BioGRID:110038	BioGRID:107529	RCC1	BioGRID	PubMed	Reconstituted Complex
BioGRID:110038	BioGRID:111897	RECQL	BioGRID	PubMed	Reconstituted Complex; Two-hybrid
BioGRID:110038	BioGRID:202582	Ranbp2	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110038	BioGRID:112910	TGM2	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110038	BioGRID:113010	TP53	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:110038	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS

Function	Evidence Code	Pubs
binding	IEA Inferred from Electronic Annotation more info
protein transporter activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
NLS-bearing substrate import into nucleus	TAS Traceable Author Statement more info	PubMed
cytokine-mediated signaling pathway	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
cytoplasm	IEA Inferred from Electronic Annotation more info
cytosol	TAS Traceable Author Statement more info
nucleoplasm	TAS Traceable Author Statement more info
nucleus	IEA Inferred from Electronic Annotation more info

General protein information

Preferred Names: importin subunit alpha-4

Names: importin subunit alpha-4; importin alpha Q1; karyopherin subunit alpha-4

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NCBI Reference Sequences (RefSeq)

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_002268.4 → NP_002259.1 importin subunit alpha-4

Status: REVIEWED

Source sequence(s)

AC078868, BC034493

Consensus CDS

CCDS3191.1

UniProtKB/Swiss-Prot

O00629

Related

ENSP00000334373, OTTHUMP00000213880, ENST00000334256, OTTHUMT00000352960

Conserved Domains (3) summary

cd00020
Location:108 – 229
Blast Score: 261

ARM; Armadillo/beta-catenin-like repeats. An approximately 40 amino acid long tandemly repeated sequence motif first identified in the Drosophila segment polarity gene armadillo; these repeats were also found in the mammalian armadillo homolog beta-catenin, ...

COG5064
Location:7 – 513
Blast Score: 1219

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

pfam01749
Location:3 – 94
Blast Score: 296

IBB; Importin beta binding domain

RefSeqs of Annotated Genomes: Build 37.3

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000003.11 Reference GRCh37.p5 Primary Assembly

Range

160212783..160283376, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000135.1 Alternate HuRef

Range

157611349..157681994, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AC078868.14 (8822..79414)	None
genomic	CH471052.2	EAW78631.1
		EAW78632.1
		EAW78633.1
mRNA	AB002533.2	BAA19546.1
mRNA	AF038199.1	None
mRNA	AK021602.1	None
mRNA	AK055675.1	None
mRNA	AK129841.1	None
mRNA	AK291041.1	BAF83730.1
mRNA	BC007458.1	AAH07458.1
mRNA	BC016754.1	AAH16754.1
mRNA	BC028691.2	AAH28691.1
mRNA	BC034493.2	AAH34493.1
mRNA	BC052814.1	None
mRNA	U93240.1	AAC25605.1
mRNA	Y12393.1	CAA73025.1
other-genetic	DQ890866.2	ABM81792.1
other-genetic	DQ894021.2	ABM84947.1

Protein Accession	Links
Protein Accession	GenPept Link	UniProtKB Link
O00629.1	GenPept	UniProtKB/Swiss-Prot:O00629
Q96IJ5	GenPept	UniProtKB/TrEMBL:Q96IJ5
Q96KW7	GenPept	UniProtKB/TrEMBL:Q96KW7