KPNA6 karyopherin subunit alpha 6 [Homo sapiens (human)] - Gene

Summary

Official Symbol: KPNA6provided by HGNC
Official Full Name: karyopherin subunit alpha 6provided by HGNC
Primary source: HGNC:HGNC:6399
See related: Ensembl:ENSG00000025800 MIM:610563; AllianceGenome:HGNC:6399
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: IPOA7
Summary: Nucleocytoplasmic transport, a signal- and energy-dependent process, takes place through nuclear pore complexes embedded in the nuclear envelope. The import of proteins containing a nuclear localization signal (NLS) requires the NLS import receptor, a heterodimer of importin alpha and beta subunits also known as karyopherins. Importin alpha binds the NLS-containing cargo in the cytoplasm and importin beta docks the complex at the cytoplasmic side of the nuclear pore complex. In the presence of nucleoside triphosphates and the small GTP binding protein Ran, the complex moves into the nuclear pore complex and the importin subunits dissociate. Importin alpha enters the nucleoplasm with its passenger protein and importin beta remains at the pore. The protein encoded by this gene is a member of the importin alpha family. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in testis (RPKM 11.5), brain (RPKM 9.1) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 1p35.2

Exon count:: 18

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (32108056..32176563)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (31965999..32034460)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (32573657..32642164)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

KPNA6 is a Cofactor of ANP32A/B in Supporting Influenza Virus Polymerase Activity.
Title: KPNA6 is a Cofactor of ANP32A/B in Supporting Influenza Virus Polymerase Activity.
Structural characterization of human importin alpha 7 in its cargo-free form at 2.5 A resolution.
Title: Structural characterization of human importin alpha 7 in its cargo-free form at 2.5 Å resolution.
HNF1A-MODY Mutations in Nuclear Localization Signal Impair HNF1A-Import Receptor KPNA6 Interactions.
Title: HNF1A-MODY Mutations in Nuclear Localization Signal Impair HNF1A-Import Receptor KPNA6 Interactions.
Development of a pipeline for automated, high-throughput analysis of PSPC1 paraspeckle protein isoforms reveals specific roles for KPNA2, KPNA4 and KPNA6 proteins.
Title: Development of a pipeline for automated, high-throughput analysis of paraspeckle proteins reveals specific roles for importin α proteins.
the data showed that viral infection induced an elevation of the KPNA6 protein level due to an extension of the KPNA6 half-life via viral interference of the ubiquitin-proteasomal degradation of KPNA6. Notably, KPNA6 silencing or knockout dramatically reduced the replication of PRRSV and ZIKV.
Title: Karyopherin Alpha 6 Is Required for Replication of Porcine Reproductive and Respiratory Syndrome Virus and Zika Virus.
a decreased H7N9 influenza A virus polymerase activity when importin-alpha7 was silenced by siRNA, is reported.
Title: H7N9 Influenza A Virus Exhibits Importin-α7-Mediated Replication in the Mammalian Respiratory Tract.
BIG3 may block the KPNAs (KPNA1, KPNA5, and KPNA6) binding region(s) of PHB2.
Title: BIG3 Inhibits the Estrogen-Dependent Nuclear Translocation of PHB2 via Multiple Karyopherin-Alpha Proteins in Breast Cancer Cells.
Bel1 fragment with residues 215-223, which bears the NLS, interacts with KPNA1, KPNA6, and KPNA7.
Title: [Identification of prototype foamy virus Bel1 nuclear localization signal and its corresponding importins].
Importin alpha1 and alpha7 are positive regulators of human-like polymerase activity and pathogenicity beyond their role in nuclear transport.
Title: Human-like PB2 627K influenza virus polymerase activity is regulated by importin-α1 and -α7.
Overexpression of KPNA6 facilitates KEAP1 nuclear import and attenuates NRF2 signaling, whereas knockdown of KPNA6 slows down KEAP1 nuclear import and enhances the NRF2-mediated adaptive response induced by oxidative stress.
Title: KPNA6 (Importin {alpha}7)-mediated nuclear import of Keap1 represses the Nrf2-dependent antioxidant response.

Submit: New GeneRIF Correction See all GeneRIFs (11)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

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 6 (importin alpha 7) (KPNA6), is identified by the in-vitro binding experiments involving cytosolic or nuclear extracts from HeLa cells	PubMed
integrase	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
	gag-pol	Karyopherin alpha binds to a bipartite nuclear localization signal in HIV-1 integrase (amino acids 186-189 and 211-219)	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

A005X47 (e-PCR)
- UniSTS:17923

G20585 (e-PCR)
- UniSTS:17924

SHGC-74534 (e-PCR)
- UniSTS:59406

L18426 (e-PCR)
- UniSTS:34648

RH123949 (e-PCR)
- UniSTS:136085

SHGC-74528 (e-PCR)
- UniSTS:60318

RH66672 (e-PCR)
- UniSTS:57510

G44365 (e-PCR)
- UniSTS:95151

RH67781 (e-PCR)
- UniSTS:72937

KPNA6_1800 (e-PCR)
- UniSTS:280814

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 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_or_within entry of viral genome into host nucleus through nuclear pore complex via importin	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in maternal process involved in female pregnancy	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of cytokine production involved in inflammatory response	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of transcription by RNA polymerase II	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within positive regulation of viral life cycle	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein import into nucleus	ISS Inferred from Sequence or Structural Similarity more info
involved_in transcription by RNA polymerase II	IEA Inferred from Electronic Annotation more info
involved_in viral genome replication	IEA Inferred from Electronic Annotation more info

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 host cell	IEA Inferred from Electronic Annotation more info
located_in membrane	HDA more info	PubMed
is_active_in nucleoplasm	IBA Inferred from Biological aspect of Ancestor 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-7

Names: importin alpha 7 subunit; importin-alpha-S2; karyopherin alpha 6 (importin alpha 7)

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_012316.5 → NP_036448.1 importin subunit alpha-7

See identical proteins and their annotated locations for NP_036448.1

Status: REVIEWED

Source sequence(s)

AL049795, BC020520, BP374991

Consensus CDS

CCDS352.1

UniProtKB/Swiss-Prot

B2RDC7, D3DPP5, O60684, Q5VVU3

UniProtKB/TrEMBL

B4DII5

Related

ENSP00000362728.3, ENST00000373625.8

Conserved Domains (2) summary

COG5064
Location:36 → 525

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

sd00043
Location:254 → 279

ARM; armadillo repeat [structural motif]

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000001.11 Reference GRCh38.p14 Primary Assembly

Range

32108056..32176563

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_024446165.2 → XP_024301933.1 importin subunit alpha-7 isoform X2

UniProtKB/TrEMBL

B4DII5

Conserved Domains (2) summary

COG5064
Location:33 → 522

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

sd00043
Location:251 → 276

ARM; armadillo repeat [structural motif]
XM_024446166.2 → XP_024301934.1 importin subunit alpha-7 isoform X2

UniProtKB/TrEMBL

B4DII5

Conserved Domains (2) summary

COG5064
Location:33 → 522

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

sd00043
Location:251 → 276

ARM; armadillo repeat [structural motif]
XM_047416671.1 → XP_047272627.1 importin subunit alpha-7 isoform X2

UniProtKB/TrEMBL

B4DII5
XM_005270711.4 → XP_005270768.1 importin subunit alpha-7 isoform X1

See identical proteins and their annotated locations for XP_005270768.1

UniProtKB/TrEMBL

B4DWX3

Conserved Domains (2) summary

COG5064
Location:66 → 555

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

sd00043
Location:284 → 309

ARM; armadillo repeat [structural motif]

Alternate T2T-CHM13v2.0

Genomic

NC_060925.1 Alternate T2T-CHM13v2.0

Range

31965999..32034460

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054335737.1 → XP_054191712.1 importin subunit alpha-7 isoform X2

UniProtKB/TrEMBL

B4DII5
XM_054335739.1 → XP_054191714.1 importin subunit alpha-7 isoform X2

UniProtKB/TrEMBL

B4DII5
XM_054335738.1 → XP_054191713.1 importin subunit alpha-7 isoform X2

UniProtKB/TrEMBL

B4DII5
XM_054335736.1 → XP_054191711.1 importin subunit alpha-7 isoform X1

UniProtKB/TrEMBL

B4DWX3