Importin subunit alpha-2 - Homo sapiens (Human)

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Reviewed, UniProtKB/Swiss-Prot P52292 (IMA2_HUMAN)

Last modified January 19, 2010. Version 123. History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein names

Recommended name:
    Importin subunit alpha-2
Alternative name(s):
    Karyopherin subunit alpha-2
    SRP1-alpha
    RAG cohort protein 1

Gene names

Name:	KPNA2
Synonyms:	RCH1, SRP1

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	529 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Function	Functions in nuclear protein import as an adapter protein for nuclear receptor KPNB1. Binds specifically and directly to substrates containing either a simple or bipartite NLS motif. Docking of the importin/substrate complex to the nuclear pore complex (NPC) is mediated by KPNB1 through binding to nucleoporin FxFG repeats and the complex is subsequently translocated through the pore by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to importin-beta and the three components separate and importin-alpha and -beta are re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran from importin. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus. Ref.7
Subunit structure	Forms a complex with importin subunit beta-1. Found in a complex with CSE1L/XPO2, Ran and KPNA2. Interacts with CSE1L/XPO2 and NBN. Interacts with ANP32E By similarity. Interacts with HIV-1 Vpr and PLAG1. Ref.7 Ref.10 Ref.11 Ref.12 Ref.14
Subcellular location	Cytoplasm. Nucleus.
Tissue specificity	Expressed ubiquitously.
Domain	Consists of an N-terminal hydrophilic region, a hydrophobic central region composed of 10 repeats, and a short hydrophilic C-terminus. The N-terminal hydrophilic region contains the importin beta binding domain (IBB domain), which is sufficient for binding importin beta and essential for nuclear protein import. Ref.8 The IBB domain is thought to act as an intrasteric autoregulatory sequence by interacting with the internal autoinhibitory NLS. Binding of KPNB1 probably overlaps the internal NLS and contributes to a high affinity for cytoplasmic NLS-containing cargo substrates. After dissociation of the importin/substrate complex in the nucleus the internal autohibitory NLS contributes to a low affinity for nuclear NLS-containing proteins By similarity. Ref.8 The major and minor NLS binding sites are mainly involved in recognition of simple or bipartite NLS motifs. Structurally located within in a helical surface groove they contain several conserved Trp and Asn residues of the corresponding third helices (H3) of ARM repeats which mainly contribute to binding By similarity. Ref.8
Sequence similarities	Belongs to the importin alpha family. Contains 10 ARM repeats. Contains 1 IBB domain.
Mass spectrometry	Molecular mass is 57861.92 Da from positions 1 - 529. Determined by MALDI. Ref.13

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Ontologies

Keywords
Biological process	Host-virus interaction Protein transport Transport
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Domain	Repeat
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	DNA metabolic process Traceable author statement. Source: ProtInc G2 phase of mitotic cell cycle Traceable author statement. Source: ProtInc M phase specific microtubule process Traceable author statement. Source: ProtInc NLS-bearing substrate import into nucleus Traceable author statement. Source: ProtInc interspecies interaction between organisms Inferred from electronic annotation. Source: UniProtKB-KW regulation of DNA recombination Ref.6 Traceable author statement. Source: ProtInc
Cellular component	cytoplasm Ref.1 Traceable author statement. Source: ProtInc nuclear pore Inferred from electronic annotation. Source: InterPro nucleoplasm Traceable author statement. Source: ProtInc
Molecular function	histone deacetylase binding Inferred from physical interaction. Source: UniProtKB nuclear localization sequence binding Traceable author statement. Source: ProtInc protein transporter activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

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Binary interactions

With	Entry	#Exp.	IntAct	Notes
BRCA1	P38398	1	EBI-349938,EBI-349905

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

Removed Ref.4

Chain

2 – 529

528

Importin subunit alpha-2

PRO_0000120722

Regions

Domain

2 – 60

IBB

Repeat

71 – 111

ARM 1; truncated

Repeat

112 – 151

ARM 2

Repeat

152 – 193

ARM 3

Repeat

200 – 244

ARM 4

Repeat

246 – 282

ARM 5

Repeat

283 – 322

ARM 6

Repeat

325 – 364

ARM 7

Repeat

367 – 409

ARM 8

Repeat

410 – 456

ARM 9

Repeat

457 – 496

ARM 10; atypical

Region

142 – 238

NLS binding site (major) By similarity

Region

315 – 403

NLS binding site (minor) By similarity

Motif

45 – 54

Nuclear localization signal By similarity

Compositional bias

28 – 31

Poly-Arg

Compositional bias

499 – 502

Poly-Glu

Amino acid modifications

Modified residue

N-acetylserine Ref.4

Modified residue

Phosphothreonine Ref.24

Modified residue

Phosphothreonine Ref.24

Modified residue

Phosphoserine Ref.15

Modified residue

Phosphothreonine Ref.19

Modified residue

Phosphoserine Ref.24 Ref.19 Ref.16 Ref.17 Ref.18 Ref.20 Ref.21 Ref.22 Ref.25

Modified residue

490

Phosphoserine Ref.16 Ref.21 Ref.22

Natural variations

Natural variant

165

P → R: dbSNP rs11545989. Ref.2

VAR_013137

Natural variant

430

T → P: dbSNP rs1059538.

VAR_014453

Experimental info

Sequence conflict

157

A → V in AAH05978. Ref.4

Sequence conflict

453

K → N in AAH05978. Ref.4

Secondary structure

529

Helix Strand Turn

Details...

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Sequences

Sequence

Length

Mass (Da)

Tools

P52292-1 [UniParc].

Last modified October 1, 1996. Version 1.
Checksum: B0F94A0475B80EED
Show »

FASTA

529

57,862

        10         20         30         40         50         60 
MSTNENANTP AARLHRFKNK GKDSTEMRRR RIEVNVELRK AKKDDQMLKR RNVSSFPDDA 

        70         80         90        100        110        120 
TSPLQENRNN QGTVNWSVDD IVKGINSSNV ENQLQATQAA RKLLSREKQP PIDNIIRAGL 

       130        140        150        160        170        180 
IPKFVSFLGR TDCSPIQFES AWALTNIASG TSEQTKAVVD GGAIPAFISL LASPHAHISE 

       190        200        210        220        230        240 
QAVWALGNIA GDGSVFRDLV IKYGAVDPLL ALLAVPDMSS LACGYLRNLT WTLSNLCRNK 

       250        260        270        280        290        300 
NPAPPIDAVE QILPTLVRLL HHDDPEVLAD TCWAISYLTD GPNERIGMVV KTGVVPQLVK 

       310        320        330        340        350        360 
LLGASELPIV TPALRAIGNI VTGTDEQTQV VIDAGALAVF PSLLTNPKTN IQKEATWTMS 

       370        380        390        400        410        420 
NITAGRQDQI QQVVNHGLVP FLVSVLSKAD FKTQKEAVWA VTNYTSGGTV EQIVYLVHCG 

       430        440        450        460        470        480 
IIEPLMNLLT AKDTKIILVI LDAISNIFQA AEKLGETEKL SIMIEECGGL DKIEALQNHE 

       490        500        510        520 
NESVYKASLS LIEKYFSVEE EEDQNVVPET TSEGYTFQVQ DGAPGTFNF

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of hSRP1 alpha as a functional receptor for nuclear localization sequences." Weis K., Mattaj I.W., Lamond A.I. Science 268:1049-1053(1995) [PubMed: 7754385] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Genomic structure of karyopherin alpha2 (KPNA2) within a low-copy repeat on chromosome 17q23-q24 and mutation analysis in patients with Russell-Silver syndrome." Doerr S., Schlicker M., Hansmann I. Hum. Genet. 109:479-486(2001) [PubMed: 11735022] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ARG-165.
[3]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Bone marrow and Testis.
[5]	Bienvenut W.V., Boldt K., von Kriegsheim A.F., Kolch W. Submitted (JUL-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-13; 69-101; 107-117; 239-258; 292-315; 354-388 AND 487-494, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT SER-2, MASS SPECTROMETRY. Tissue: Hepatoma.
[6]	"Rch1, a protein that specifically interacts with the RAG-1 recombination-activating protein." Cuomo C.A., Kirch S.A., Gyuris J., Brent R., Oettinger M.A. Proc. Natl. Acad. Sci. U.S.A. 91:6156-6160(1994) [PubMed: 8016130] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 33-529. Tissue: Cervix carcinoma.
[7]	"Mammalian karyopherin alpha 1 beta and alpha 2 beta heterodimers: alpha 1 or alpha 2 subunit binds nuclear localization signal and beta subunit interacts with peptide repeat-containing nucleoporins." Moroianu J., Hijikata M., Blobel G., Radu A. Proc. Natl. Acad. Sci. U.S.A. 92:6532-6536(1995) [PubMed: 7604027] [Abstract] Cited for: FUNCTIONAL SUBSTITUTION OF ALPHA-1 BY ALPHA-2 SUBUNIT.
[8]	"The conserved amino-terminal domain of hSRP1 alpha is essential for nuclear protein import." Weis K., Ryder U., Lamond A.I. EMBO J. 15:1818-1825(1996) [PubMed: 8617227] [Abstract] Cited for: IDENTIFICATION OF IBB DOMAIN.
[9]	"Export of importin-alpha from the nucleus is mediated by a specific nuclear transport factor." Kutay U., Bischoff F.R., Kostka S., Kraft R., Goerlich D. Cell 90:1061-1071(1997) [PubMed: 9323134] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH RAN AND CSE1L.
[10]	"Viral protein R regulates nuclear import of the HIV-1 pre-integration complex." Popov S., Rexach M., Zybarth G., Reiling N., Lee M.A., Ratner L., Lane C.M., Moore M.S., Blobel G., Bukrinsky M. EMBO J. 17:909-917(1998) [PubMed: 9463369] [Abstract] Cited for: INTERACTION WITH HIV-1 VPR.
[11]	"Determination of the functional domain organization of the importin alpha nuclear import factor." Herold A., Truant R., Wiegand H., Cullen B.R. J. Cell Biol. 143:309-318(1998) [PubMed: 9786944] [Abstract] Cited for: INTERACTION WITH XPO2/CSE1L.
[12]	"Identification of a karyopherin alpha 2 recognition site in PLAG1, which functions as a nuclear localization signal." Braem C.V., Kas K., Meyen E., Debiec-Rychter M., Van De Ven W.J.M., Voz M.L. J. Biol. Chem. 277:19673-19678(2002) [PubMed: 11882654] [Abstract] Cited for: INTERACTION WITH PLAG1.
[13]	"Cluster analysis of an extensive human breast cancer cell line protein expression map database." Harris R.A., Yang A., Stein R.C., Lucy K., Brusten L., Herath A., Parekh R., Waterfield M.D., O'Hare M.J., Neville M.A., Page M.J., Zvelebil M.J. Proteomics 2:212-223(2002) [PubMed: 11840567] [Abstract] Cited for: MASS SPECTROMETRY. Tissue: Mammary cancer.
[14]	"Importin KPNA2 is required for proper nuclear localization and multiple functions of NBS1." Tseng S.-F., Chang C.-Y., Wu K.-J., Teng S.-C. J. Biol. Chem. 280:39594-39600(2005) [PubMed: 16188882] [Abstract] Cited for: INTERACTION WITH NBN.
[15]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-24, MASS SPECTROMETRY. Tissue: Epithelium.
[16]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-62 AND SER-490, MASS SPECTROMETRY. Tissue: Epithelium.
[17]	"Phosphoproteome analysis of the human mitotic spindle." Nousiainen M., Sillje H.H.W., Sauer G., Nigg E.A., Koerner R. Proc. Natl. Acad. Sci. U.S.A. 103:5391-5396(2006) [PubMed: 16565220] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-62, MASS SPECTROMETRY. Tissue: Epithelium.
[18]	"Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra." Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D. J. Proteome Res. 6:4150-4162(2007) [PubMed: 17924679] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-62, MASS SPECTROMETRY. Tissue: Epithelium.
[19]	"Evaluation of the low-specificity protease elastase for large-scale phosphoproteome analysis." Wang B., Malik R., Nigg E.A., Korner R. Anal. Chem. 80:9526-9533(2008) [PubMed: 19007248] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-61 AND SER-62, MASS SPECTROMETRY.
[20]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed: 18220336] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-62, MASS SPECTROMETRY.
[21]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-62 AND SER-490, MASS SPECTROMETRY.
[22]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-62 AND SER-490, MASS SPECTROMETRY.
[23]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[24]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-3; THR-9 AND SER-62, MASS SPECTROMETRY.
[25]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-62, MASS SPECTROMETRY. Tissue: T-cell.
[26]	"Structure of importin-beta bound to the IBB domain of importin-alpha." Cingolani G., Petosa C., Weis K., Muller C.W. Nature 399:221-229(1999) [PubMed: 10353244] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 11-54.
+	Additional computationally mapped references.

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Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U28386 mRNA. Translation: AAA69957.1.
AJ303086 Genomic DNA. Translation: CAC83080.1.
CH471099 Genomic DNA. Translation: EAW89041.1.
BC005978 mRNA. Translation: AAH05978.1.
BC146905 mRNA. Translation: AAI46906.1.
U09559 mRNA. Translation: AAA65700.1.

IPI

IPI00002214.

PIR

A56516.

RefSeq

NP_002257.1.

UniGene

Hs.594238

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1EFX	X-ray	3.00	C	204-212	[»]
1QGK	X-ray	2.50	B	11-54	[»]
1QGR	X-ray	2.30	B	28-54	[»]
3FEX	X-ray	3.55	C	70-529	[»]
3FEY	X-ray	2.20	C	70-529	[»]

SMR

P52292. Positions 44-496.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-6205N.

IntAct

P52292. 11 interactions.

STRING

P52292.

PTM databases

PhosphoSite

P52292.

2-D gel databases

SWISS-2DPAGE

P52292.

Proteomic databases

PeptideAtlas

P52292.

PRIDE

P52292.

Genome annotation databases

Ensembl

ENST00000330459; ENSP00000332455; ENSG00000182481; Homo sapiens. [Genome view]

GeneID

3838.

KEGG

hsa:3838.

UCSC

uc002jgk.1. human.

Organism-specific databases

CTD

3838.

GeneCards

GC17M8C0097.
GC17P063463.

H-InvDB

HIX0021306.
HIX0023282.

HGNC

HGNC:6395. KPNA2.

HPA

CAB015460.

MIM

600685. gene.

PharmGKB

PA30186.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG08271.

HOGENOM

HBG590318.

HOVERGEN

P52292.

InParanoid

P52292.

OMA

NIAXSAL.

OrthoDB

EOG9577S4.

PhylomeDB

P52292.

Enzyme and pathway databases

Pathway_Interaction_DB

smad2_3pathway. Regulation of cytoplasmic and nuclear SMAD2/3 signaling.
nfat_3pathway. Role of Calcineurin-dependent NFAT signaling in lymphocytes.

Gene expression databases

ArrayExpress

P52292.

Bgee

P52292.

CleanEx

HS_KPNA2.

Genevestigator

P52292.

GermOnline

ENSG00000182481. Homo sapiens.

Family and domain databases

InterPro

IPR011989. ARM-like.
IPR016024. ARM-type_fold.
IPR000225. Armadillo.
IPR002652. Importin-a-like_IBB-bd_dom.
[Graphical view]

Gene3D

G3DSA:1.25.10.10. ARM-like. 1 hit.
G3DSA:1.20.5.690. Importin-a-like_IBB-bd. 1 hit.

Pfam

PF00514. Arm. 8 hits.
PF01749. IBB. 1 hit.
[Graphical view]

SMART

SM00185. ARM. 8 hits.
[Graphical view]

PROSITE

PS50176. ARM_REPEAT. 5 hits.
PS51214. IBB. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

15087.

SOURCE

Search...

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Entry information

Entry name

IMA2_HUMAN

Accession

Primary (citable) accession number: P52292
Secondary accession number(s): B9EJD6, Q9BRU5

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	January 19, 2010
This is version 123 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

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List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Regions

Amino acid modifications

Natural variations

Experimental info

Secondary structure

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

2-D gel databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents