P52293 (IMA2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Importin subunit alpha-2

Alternative name(s):
Importin alpha P1
Karyopherin subunit alpha-2
Pendulin
Pore targeting complex 58 kDa subunit
Short name=PTAC58
RAG cohort protein 1
SRP1-alpha

Gene names

Name:	Kpna2
Synonyms:	Rch1

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

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

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.
Subunit structure	Heterodimer; with KPNB1 By similarity. Component of a complex containing CSE1L, RAN and KPNA2. Interacts directly with CSE1L. Interacts with PLAG1. Interacts with APEX1 (via N-terminus). Interacts with ARL4A, CTNNBL1 and NBN By similarity. Interacts with ANP32E. Interacts with SNAI1 (via zinc fingers). Interacts with SNAI2 (via zinc fingers) By similarity. Ref.5
Subcellular location	Cytoplasm By similarity. Nucleus By similarity.
Tissue specificity	Slightly detected in brain but not in cerebellum and skeletal muscle, highly expressed in testis and spleen.
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. 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. 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.
Sequence similarities	Belongs to the importin alpha family. Contains 10 ARM repeats. Contains 1 IBB domain.

Ontologies

Keywords
Biological process	Protein transport Transport
Cellular component	Cytoplasm Nucleus
Domain	Repeat
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	protein import into nucleus Inferred from electronic annotation. Source: InterPro
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	protein transporter activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed By similarity

Chain

2 – 529

528

Importin subunit alpha-2

PRO_0000120723

Regions

Domain

2 – 60

59

IBB

Repeat

71 – 111

41

ARM 1; truncated

Repeat

112 – 151

40

ARM 2

Repeat

152 – 193

42

ARM 3

Repeat

200 – 244

45

ARM 4

Repeat

246 – 282

37

ARM 5

Repeat

283 – 322

40

ARM 6

Repeat

325 – 364

40

ARM 7

Repeat

367 – 409

43

ARM 8

Repeat

410 – 456

47

ARM 9

Repeat

457 – 496

40

ARM 10; atypical

Region

142 – 238

97

NLS binding site (major)

Region

315 – 403

89

NLS binding site (minor)

Motif

45 – 54

10

Nuclear localization signal Ref.6 Ref.7

Compositional bias

28 – 31

4

Poly-Arg

Compositional bias

499 – 502

4

Poly-Glu

Amino acid modifications

Modified residue

2

1

N-acetylserine By similarity

Modified residue

62

1

Phosphoserine By similarity

Experimental info

Sequence conflict

242

1

P → S in AAA85281. Ref.2

Sequence conflict

418

1

H → P in AAA85281. Ref.2

Sequence conflict

420

1

G → R in AAA85281. Ref.2

Secondary structure

1

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529

Helix Strand Turn

Details...

Helix

71 – 73

3

Helix

78 – 85

8

Beta strand

86 – 88

3

Helix

90 – 104

15

Beta strand

106 – 108

3

Helix

112 – 117

6

Helix

120 – 127

8

Helix

131 – 133

3

Helix

134 – 148

15

Helix

152 – 160

9

Helix

163 – 170

8

Helix

176 – 190

15

Helix

194 – 202

9

Helix

206 – 212

7

Helix

218 – 220

3

Helix

223 – 237

15

Helix

246 – 259

14

Helix

265 – 278

14

Beta strand

280 – 282

3

Helix

283 – 290

8

Turn

291 – 293

3

Helix

295 – 302

8

Helix

307 – 320

14

Helix

325 – 333

9

Helix

336 – 339

4

Helix

340 – 343

4

Helix

349 – 362

14

Helix

367 – 375

9

Helix

378 – 387

10

Helix

391 – 407

17

Helix

410 – 418

9

Helix

422 – 427

6

Helix

428 – 430

3

Helix

434 – 452

19

Turn

453 – 455

3

Helix

457 – 466

10

Helix

469 – 475

7

Helix

476 – 478

3

Beta strand

479 – 481

3

Helix

482 – 495

14

Sequences

	Sequence		Length	Mass (Da)
	P52293 [UniParc]. Last modified November 1, 1997. Version 2. Checksum: 19E64AA3E9C3C7B5	FASTA	529	57,928
	10 20 30 40 50 60 MSTNENANLP AARLNRFKNK GKDSTEMRRR RIEVNVELRK AKKDEQMLKR RNVSSFPDDA 70 80 90 100 110 120 TSPLQENRNN QGTVNWSVED IVKGINSNNL ESQLQATQAA RKLLSREKQP PIDNIIRAGL 130 140 150 160 170 180 IPKFVSFLGK TDCSPIQFES AWALTNIASG TSEQTKAVVD GGAIPAFISL LASPHAHISE 190 200 210 220 230 240 QAVWALGNIA GDGSAFRDLV IKHGAIDPLL ALLAVPDLST LACGYLRNLT WTLSNLCRNK 250 260 270 280 290 300 NPAPPLDAVE QILPTLVRLL HHNDPEVLAD SCWAISYLTD GPNERIEMVV KKGVVPQLVK 310 320 330 340 350 360 LLGATELPIV TPALRAIGNI VTGTDEQTQK VIDAGALAVF PSLLTNPKTN IQKEATWTMS 370 380 390 400 410 420 NITAGRQDQI QQVVNHGLVP FLVGVLSKAD FKTQKEAAWA ITNYTSGGTV EQIVYLVHCG 430 440 450 460 470 480 IIEPLMNLLS AKDTKIIQVI LDAISNIFQA AEKLGETEKL SIMIEECGGL DKIEALQRHE 490 500 510 520 NESVYKASLN LIEKYFSVEE EEDQNVVPET TSEGFAFQVQ DGAPGTFNF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"In vivo evidence for involvement of a 58 kDa component of nuclear pore-targeting complex in nuclear protein import." Imamoto N., Shimamoto T., Takao T., Tachibana T., Kose S., Matsubae M., Sekimoto T., Shimonishi Y., Yoneda Y. EMBO J. 14:3617-3626(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Yeast Srp1, a nuclear protein related to Drosophila and mouse pendulin, is required for normal migration, division, and integrity of nuclei during mitosis." Kuessel P., Frasch M. Mol. Gen. Genet. 248:351-363(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Embryo.
[3]	"The nuclear localization signal of lymphoid enhancer factor-1 is recognized by two differentially expressed Srp1-nuclear localization sequence receptor proteins." Prieve M.G., Guttridge K.L., Waterman M.L. J. Biol. Chem. 271:7654-7658(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	"Characterization of the nuclear transport of a novel leucine-rich acidic nuclear protein-like protein." Matsubae M., Kurihara T., Tachibana T., Imamoto N., Yoneda Y. FEBS Lett. 468:171-175(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ANP32E.
[6]	"Structural basis of recognition of monopartite and bipartite nuclear localization sequences by mammalian importin-alpha." Fontes M.R., Teh T., Kobe B. J. Mol. Biol. 297:1183-1194(2000) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 72-497, NUCLEAR LOCALIZATION SIGNAL RECOGNITION.
[7]	"Autoinhibition by an internal nuclear localization signal revealed by the crystal structure of mammalian importin alpha." Kobe B. Nat. Struct. Biol. 6:388-397(1999) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 44-496, NUCLEAR LOCALIZATION SIGNAL, AUTOINHIBITION.
[8]	"Biophysical characterization of interactions involving importin-alpha during nuclear import." Catimel B., Teh T., Fontes M.R., Jennings I.G., Jans D.A., Howlett G.J., Nice E.C., Kobe B. J. Biol. Chem. 276:34189-34198(2001) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 47-54, AUTOINHIBITION.
[9]	"Nup50/Npap60 function in nuclear protein import complex disassembly and importin recycling." Matsuura Y., Stewart M. EMBO J. 24:3681-3689(2005) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 75-498 IN COMPLEX WITH NUP50.
[10]	"Importin alpha protein acts as a negative regulator for Snail protein nuclear import." Sekimoto T., Miyamoto Y., Arai S., Yoneda Y. J. Biol. Chem. 286:15126-15131(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTS WITH SNAI1.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

D55720 mRNA. Translation: BAA09536.1.
U12270 mRNA. Translation: AAA85281.1.
U34229 mRNA. Translation: AAC52451.1.
BC003274 mRNA. Translation: AAH03274.1.
BC006720 mRNA. Translation: AAH06720.1.

IPI

IPI00124973.

PIR

S57345.
S57873.
S62116.

RefSeq

NP_034785.1. NM_010655.3.

UniGene

Mm.12508.
Mm.391577.
Mm.423000.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1EJL	X-ray	2.80	I	70-529	[»]
1EJY	X-ray	2.90	I	70-529	[»]
1IAL	X-ray	2.50	A	44-496	[»]
1IQ1	X-ray	2.80	A/B	44-54	[»]
			C	70-529	[»]
1PJM	X-ray	2.50	B	70-529	[»]
1PJN	X-ray	2.50	B	70-529	[»]
1Q1S	X-ray	2.30	C	70-529	[»]
1Q1T	X-ray	2.50	C	70-529	[»]
1Y2A	X-ray	2.20	C	70-497	[»]
2C1M	X-ray	2.20	A	75-498	[»]
2YNR	X-ray	2.30	A	72-496	[»]
3BTR	X-ray	2.60	C	70-496	[»]
3KND	X-ray	2.15	A	70-529	[»]
3L3Q	X-ray	2.30	A	71-497	[»]
3OQS	X-ray	2.00	A	70-529	[»]
3Q5U	X-ray	2.50	A	70-529	[»]
3RZ9	X-ray	2.29	A	70-529	[»]
3RZX	X-ray	2.61	A	70-529	[»]
3TPM	X-ray	2.10	A	75-496	[»]
3TPO	X-ray	2.10	A	1-529	[»]
3UKW	X-ray	2.10	B	70-529	[»]
3UKX	X-ray	2.20	B	70-529	[»]
3UKY	X-ray	2.35	B	70-529	[»]
3UKZ	X-ray	2.30	B	70-529	[»]
3UL0	X-ray	2.00	B	70-529	[»]
3UL1	X-ray	1.90	B	70-529	[»]
3UVU	X-ray	2.38	A	70-529	[»]
3VE6	X-ray	2.83	A	71-496	[»]
4BA3	X-ray	2.10	A	70-529	[»]
4HTV	X-ray	3.00	A	70-528	[»]

ProteinModelPortal

P52293.

SMR

P52293. Positions 11-497.

ModBase

Search...

Protein-protein interaction databases

IntAct

P52293. 1 interaction.

PTM databases

PhosphoSite

P52293.

Proteomic databases

PaxDb

P52293.

PRIDE

P52293.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000018506; ENSMUSP00000018506; ENSMUSG00000018362.
ENSMUST00000086423; ENSMUSP00000137310; ENSMUSG00000066878.
ENSMUST00000091289; ENSMUSP00000137080; ENSMUSG00000069083.

GeneID

16647.

KEGG

mmu:16647.

Organism-specific databases

CTD

3838.

MGI

MGI:103561. Kpna2.

Phylogenomic databases

eggNOG

COG5064.

HOGENOM

HOG000167616.

HOVERGEN

HBG001846.

InParanoid

P52293.

KO

K15043.

OMA

LMIEECG.

OrthoDB

EOG4JWVDH.

Gene expression databases

ArrayExpress

P52293.

Bgee

P52293.

CleanEx

MM_KPNA2.

Genevestigator

P52293.

GermOnline

ENSMUSG00000018362. Mus musculus.
ENSMUSG00000066878. Mus musculus.
ENSMUSG00000069083. Mus musculus.

Family and domain databases

Gene3D

1.25.10.10. 1 hit.

InterPro

IPR011989. ARM-like.
IPR016024. ARM-type_fold.
IPR000225. Armadillo.
IPR002652. Importin-a_IBB.
IPR024931. Importing_su_alpha.
[Graphical view]

Pfam

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

PIRSF

PIRSF005673. Importin_alpha. 1 hit.

SMART

SM00185. ARM. 8 hits.
[Graphical view]

SUPFAM

SSF48371. ARM-type_fold. 1 hit.

PROSITE

PS50176. ARM_REPEAT. 6 hits.
PS51214. IBB. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P52293.

NextBio

290325.

SOURCE

Search...

Entry information

Entry name

IMA2_MOUSE

Accession

Primary (citable) accession number: P52293
Secondary accession number(s): Q64292

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	November 1, 1997
Last modified:	May 1, 2013
This is version 130 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program