KPNA2 karyopherin alpha 2 (RAG cohort 1, importin alpha 1) [ Homo sapiens ]

Gene ID: 3838, updated on 13-May-2012

Help top of page

Summary

Official Symbol: KPNA2provided by HGNC
Official Full Name: karyopherin alpha 2 (RAG cohort 1, importin alpha 1)provided by HGNC
Primary source: HGNC:6395
See related: Ensembl:ENSG00000182481; HPRD:02818; MIM:600685
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: QIP2; RCH1; IPOA1; SRP1alpha
Summary: The import of proteins into the nucleus is a process that involves at least 2 steps. The first is an energy-independent docking of the protein to the nuclear envelope and the second is an energy-dependent translocation through the nuclear pore complex. Imported proteins require a nuclear localization sequence (NLS) which generally consists of a short region of basic amino acids or 2 such regions spaced about 10 amino acids apart. Proteins involved in the first step of nuclear import have been identified in different systems. These include the Xenopus protein importin and its yeast homolog, SRP1 (a suppressor of certain temperature-sensitive mutations of RNA polymerase I in Saccharomyces cerevisiae), which bind to the NLS. KPNA2 protein interacts with the NLSs of DNA helicase Q1 and SV40 T antigen and may be involved in the nuclear transport of proteins. KPNA2 also may play a role in V(D)J recombination [provided by RefSeq, Jul 2008]

Help top of page

Genomic context

Location :: 17q24.2

Sequence :: Chromosome: 17; NC_000017.10 (66031848..66042970)

See KPNA2 in Epigenomics, MapViewer

Chromosome 17 - NC_000017.10 Genomic Context describing neighboring genes

Help top of page

Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Help top of page

Bibliography

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

Crystallographic analysis of mammalian importin alpha1 in complex with the hPLSCR4-NLS reveals this minimal NLS binds specifically and exclusively to the minor binding site of importin alpha
Title: A minimal nuclear localization signal (NLS) in human phospholipid scramblase 4 that binds only the minor NLS-binding site of importin alpha1.
findings suggest that the deregulated activity of E2F in cancer cells causes increased activation of the Kpnbeta1 and Kpnalpha2 promoters, leading to elevated levels of these proteins, and ultimately impacting the cancer phenotype.
Title: Overexpression of Kpnβ1 and Kpnα2 importin proteins in cancer derives from deregulated E2F activity.
Overexpression of importin alpha1 is associated with hepatocellular carcinoma.
Title: Importin-α1 as a novel prognostic target for hepatocellular carcinoma.
KPNA2 expression was significantly upregulated in carcinomas of the prostate, especially in metastatic and castration-resistant prostate cancer samples; it is a novel independent prognostic marker for disease progression after radical prostatectomy
Title: KPNA2 expression is an independent adverse predictor of biochemical recurrence after radical prostatectomy.
Taspase1 appears to exploit the nuclear export activity of importin-alpha/nucleophosmin to gain transient access to the cytoplasm required to also cleave its cytoplasmic substrates.
Title: The importin-alpha/nucleophosmin switch controls taspase1 protease function.
KPNA2 expression is a marker for progression of non-muscle-invasive bladder cancer and a prognostic marker in patients undergoing radical cystectomy.
Title: High expression of karyopherin-α2 defines poor prognosis in non-muscle-invasive bladder cancer and in patients with invasive bladder cancer undergoing radical cystectomy.
importin alpha interacted with the zinc finger domain of Snail to compete with the binding of importin beta1 and Snail did not form a ternary complex with importin alpha/importin beta1.
Title: Importin alpha protein acts as a negative regulator for Snail protein nuclear import.
protein levels of KPNA2 in pleural effusion from NSCLC patients were also significantly higher than those from non-lung cancer. Moreover, knockdown of KPNA2 inhibited the migration ability and viability of lung cancer cells
Title: Importin subunit alpha-2 is identified as a potential biomarker for non-small cell lung cancer by integration of the cancer cell secretome and tissue transcriptome.
Overexpression of KPNA2 in patients with epithelial ovarian cancer is positively associated with an epithelial ovarian cancer-specific histologic type and a poor prognosis.
Title: Overexpression of karyopherin-2 in epithelial ovarian cancer and correlation with poor prognosis.
Data reveal the involvement of importin alpha1 in the assembly of RNA granules and its pro-survival role during stress
Title: Identification of importin alpha1 as a novel constituent of RNA stress granules.

Submit: New GeneRIF Correction See all (39)

Help top of page

Phenotypes

Review eQTL and phenotype association data in this region using PheGenI

Help top of page

HIV-1 protein interactions

Protein	Gene	Interaction	Pubs
Vpr	vpr	HIV-1 Vpr interacts with importin-alpha through alphaH1 (residues 17-34) and alphaH2 (residues 46-74); the interaction via alphaH1 is indispensable for the nuclear entry of Vpr, and residues 393-462 of importin-alpha promote entry of Vpr into the nucleus	PubMed
	vpr	HIV-1 Vpr interacts with both karyopherin alpha 1 and alpha 2 to facilitate nuclear import of the HIV-1 preintegration complex, however conflicting reports indicate it may also be imported by other mechanisms independently of karyopherin alpha 1 and 2	PubMed
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

Help top of page

Products	Interactant	Other Gene	Source	Pubs	Description
NP_002257.1	NP_004055.1	CDKN1B	BIND	PubMed	p27 interacts with importin-alpha.
NP_002257.1	AAA02807.1	HSPA4	BIND	PubMed	Hsp70 interacts with karyopherin alpha (K-alpha).
NP_002257.1	NP_005537.3	ITK	BIND	PubMed	Itk interacts with and phosphorylates Rch1-alpha.
NP_002257.1		STAT1	BIND	PubMed	An unspecified isoform of STAT1 interacts with karyopherin alpha (K-alpha).
NP_002257.1	NP_043127.1	SV40gp6	BIND	PubMed	TAg interacts with karyopherin alpha (K-alpha).
NP_002257.1	NP_043127.1	SV40gp6	BIND	PubMed	SV40T interacts with Imp-alpha.
NP_002257.1	NP_006463.2	TXNIP	BIND	PubMed	TXNIP (TBP-2) interacts with KPNA2 (Rch1).
NP_002257.1	AAC03774.1		BIND	PubMed	Importin-alpha interacts with Rep68.
NP_002257.1	AAC03775.1		BIND	PubMed	Importin-alpha interacts with Rep78.
NP_002257.1			BIND	PubMed	Importin-alpha interacts with the ITR-Rep78 complex.
NP_002257.1			BIND	PubMed	Importin-alpha interacts with the ITR-Rep68 complex.
P52292	P41238	APOBEC1	HPRD	PubMed
P52292	P40617	ARL4A	HPRD	PubMed
P52292	Q9Y689	ARL5A	HPRD	PubMed
P52292	P38398	BRCA1	HPRD	PubMed
P52292	P42575	CASP2	HPRD	PubMed
P52292	P32320	CDA	HPRD	PubMed
P52292	Q12873	CHD3	HPRD	PubMed
P52292	O96017	CHEK2	HPRD	PubMed
P52292	Q92793	CREBBP	HPRD	PubMed
P52292	P48729	CSNK1A1	HPRD	PubMed
P52292	Q09472	EP300	HPRD	PubMed
P52292	P11171	EPB41	HPRD	PubMed
P52292	P07305	H1F0	HPRD	PubMed
P52292	P54257	HAP1	HPRD	PubMed
P52292	P34932	HSPA4	HPRD	PubMed
P52292	Q08881	ITK	HPRD	PubMed
P52292	P52292	KPNA2	HPRD	PubMed
P52292	Q14974	KPNB1	HPRD	PubMed
P52292	Q9UJU2	LEF1	HPRD	PubMed
P52292	Q9H213	MAGEH1	HPRD	PubMed
P52292	Q15653	NFKBIB	HPRD	PubMed
P52292	P04150	NR3C1	HPRD	PubMed
P52292	P49790	NUP153	HPRD	PubMed
P52292	Q9UKX7	NUP50	HPRD	PubMed
P52292	Q02548	PAX5	HPRD	PubMed
P52292	PLAG1	PLAG1	HPRD	PubMed
P52292	O94806	PRKD3	HPRD	PubMed
P52292	P06454	PTMA	HPRD	PubMed
P52292	P15918	RAG1	HPRD	PubMed
P52292	Hypothetical protein DKFZp564O0523	RBM48	HPRD	PubMed
P52292	P46063	RECQL	HPRD	PubMed
P52292	Q04206	RELA	HPRD	PubMed
P52292	Q01201	RELB	HPRD	PubMed
P52292	O43148	RNMT	HPRD	PubMed
P52292	O00141	SGK1	HPRD	PubMed
P52292	P11168	SLC2A2	HPRD	PubMed
P52292	P04637	TP53	HPRD	PubMed
P52292	Q9H3M7	TXNIP	HPRD	PubMed
P52292	O95071	UBR5	HPRD	PubMed
BioGRID:110036	BioGRID:106836	APOBEC1	BioGRID	PubMed	Two-hybrid
BioGRID:110036	BioGRID:115428	ARL4A	BioGRID	PubMed	Reconstituted Complex; Two-hybrid
BioGRID:110036	BioGRID:117616	ARL5A	BioGRID	PubMed	Reconstituted Complex
BioGRID:110036	BioGRID:107140	BRCA1	BioGRID	PubMed	Two-hybrid
BioGRID:110036	BioGRID:120548	C20orf20	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110036	BioGRID:107459	CDK9	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110036	BioGRID:123555	CDT1	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110036	BioGRID:107777	CREBBP	BioGRID	PubMed	Biochemical Activity
BioGRID:110036	BioGRID:107821	CSE1L	BioGRID	PubMed	Reconstituted Complex
BioGRID:110036	BioGRID:107836	CSNK1A1	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110036	BioGRID:115906	CTCF	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110036	BioGRID:121123	CTNNBL1	BioGRID	PubMed	Affinity Capture-MS; Affinity Capture-Western
BioGRID:110036	BioGRID:114028	CUL4B	BioGRID	PubMed	Reconstituted Complex
BioGRID:110036	BioGRID:108347	EP300	BioGRID	PubMed	Biochemical Activity
BioGRID:110036	BioGRID:108349	EPB41	BioGRID	PubMed	Reconstituted Complex
BioGRID:110036	BioGRID:116452	GPN1	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110036	BioGRID:109217	GTF2F1	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110036	BioGRID:109318	HDGF	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110036	BioGRID:109428	HNRNPH1	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110036	BioGRID:109314	HTT	BioGRID	PubMed	Two-hybrid
BioGRID:110036	BioGRID:109833	ING1	BioGRID	PubMed	Affinity Capture-MS; Affinity Capture-Western
BioGRID:110036	BioGRID:109907	ITK	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:110036	BioGRID:110035	KPNB1	BioGRID	PubMed	Reconstituted Complex
BioGRID:110036	BioGRID:200952	Kifc5b	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110036	BioGRID:121122	MEPCE	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110036	BioGRID:110438	MLH1	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110036	BioGRID:115001	MORF4L2	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110036	BioGRID:110694	MYC	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110036	BioGRID:201430	Mki67	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110036	BioGRID:115982	NUP50	BioGRID	PubMed	Reconstituted Complex
BioGRID:110036	BioGRID:203509	Nhp2l1	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110036	BioGRID:111340	PLAG1	BioGRID	PubMed	Reconstituted Complex; Two-hybrid
BioGRID:110036	BioGRID:111370	PLRG1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110036	BioGRID:111391	PMS1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110036	BioGRID:111404	PMS2	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110036	BioGRID:118151	PRPF19	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110036	BioGRID:117563	PRPF31	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110036	BioGRID:202032	Pax5	BioGRID	PubMed	Two-hybrid
BioGRID:110036	BioGRID:198967	Pcyt1a	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110036	BioGRID:111832	RAG1	BioGRID	PubMed	Two-hybrid
BioGRID:110036	BioGRID:111897	RECQL	BioGRID	PubMed	Reconstituted Complex; Two-hybrid
BioGRID:110036	BioGRID:111902	RELA	BioGRID	PubMed	Reconstituted Complex
BioGRID:110036	BioGRID:111903	RELB	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110036	BioGRID:202582	Ranbp2	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110036	BioGRID:941018	SAP25	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110036	BioGRID:112344	SGK1	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex; Two-hybrid
BioGRID:110036	BioGRID:116983	SIRT1	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110036	BioGRID:112405	SLC2A2	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex; Two-hybrid
BioGRID:110036	BioGRID:112481	SMARCA4	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110036	BioGRID:112485	SMARCC2	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110036	BioGRID:112486	SMARCD1	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110036	BioGRID:112497	SUMO2	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110036	BioGRID:112872	TERF1	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110036	BioGRID:112873	TERF2	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110036	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110036	BioGRID:276686	spi1	BioGRID	PubMed	Reconstituted Complex
BioGRID:110036	BioGRID:1205541	tat	BioGRID	PubMed	Reconstituted Complex

Function	Evidence Code	Pubs
histone deacetylase binding	IPI Inferred from Physical Interaction more info	PubMed
nuclear localization sequence binding	IDA Inferred from Direct Assay more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein transporter activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
DNA metabolic process	TAS Traceable Author Statement more info	PubMed
G2 phase of mitotic cell cycle	TAS Traceable Author Statement more info	PubMed
M phase specific microtubule process	TAS Traceable Author Statement more info	PubMed
NLS-bearing substrate import into nucleus	IDA Inferred from Direct Assay more info	PubMed
cytokine-mediated signaling pathway	TAS Traceable Author Statement more info
interspecies interaction between organisms	IEA Inferred from Electronic Annotation more info
regulation of DNA recombination	TAS Traceable Author Statement more info	PubMed

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-2

Names: importin subunit alpha-2; pendulin; SRP1-alpha; RAG cohort 1; importin alpha 1; importin alpha 2; importin-alpha-P1; RAG cohort protein 1; karyopherin subunit alpha-2

Help top of page

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_002266.2 → NP_002257.1 importin subunit alpha-2

Status: REVIEWED

Source sequence(s)

AK024833, BC053343, U28386

Consensus CDS

CCDS32713.1

UniProtKB/Swiss-Prot

P52292

UniProtKB/TrEMBL

Q7Z726

Related

ENSP00000332455, ENST00000330459

Conserved Domains (3) summary

cd00020
Location:252 – 364
Blast Score: 252

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:10 – 528
Blast Score: 1245

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

pfam01749
Location:5 – 99
Blast Score: 331

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_000017.10 Reference GRCh37.p5 Primary Assembly

Range

66031848..66042970

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000149.1 Alternate HuRef

Range

61416714..61427908

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Help top of page

Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AC134407.6 (166860..177982)	None
genomic	AC145081.2 (102564..113684)	None
genomic	AJ303086.1	CAC83080.1
genomic	CH471099.1	EAW89040.1
		EAW89041.1
mRNA	AK024833.1	None
mRNA	AK058111.1	None
mRNA	AK291954.1	BAF84643.1
mRNA	BC005978.1	AAH05978.1
mRNA	BC013257.1	None
mRNA	BC034443.1	None
mRNA	BC053343.1	AAH53343.1
mRNA	BC067848.1	AAH67848.1
mRNA	BC146905.1	AAI46906.1
mRNA	BT006665.1	AAP35311.1
mRNA	U09559.1	AAA65700.1
mRNA	U28386.1	AAA69957.1
other-genetic	DQ890599.2	ABM92216.1
other-genetic	DQ893768.2	ABM84694.1

Protein Accession	Links
Protein Accession	GenPept Link	UniProtKB Link
P52292.1	GenPept	UniProtKB/Swiss-Prot:P52292
Q53YE3	GenPept	UniProtKB/TrEMBL:Q53YE3
Q6NVW7	GenPept	UniProtKB/TrEMBL:Q6NVW7
Q7Z726	GenPept	UniProtKB/TrEMBL:Q7Z726