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P52293 (IMA1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 140. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Importin subunit alpha-1
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
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length529 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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 processProtein transport
Transport
   Cellular componentCytoplasm
Nucleus
   DomainRepeat
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processprotein import into nucleus

Inferred from electronic annotation. Source: InterPro

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionprotein binding

Inferred from physical interaction PubMed 12941609. Source: UniProtKB

protein transporter activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

P030703EBI-3043908,EBI-617698From a different organism.
IfngP015805EBI-3043908,EBI-7892102
S100A2P290342EBI-3043908,EBI-752230From a different organism.
TNPO1Q3SYU73EBI-3043908,EBI-8469003From a different organism.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 529528Importin subunit alpha-1
PRO_0000120723

Regions

Domain2 – 6059IBB
Repeat71 – 11141ARM 1; truncated
Repeat112 – 15140ARM 2
Repeat152 – 19342ARM 3
Repeat200 – 24445ARM 4
Repeat246 – 28237ARM 5
Repeat283 – 32240ARM 6
Repeat325 – 36440ARM 7
Repeat367 – 40943ARM 8
Repeat410 – 45647ARM 9
Repeat457 – 49640ARM 10; atypical
Region142 – 23897NLS binding site (major)
Region315 – 40389NLS binding site (minor)
Motif45 – 5410Nuclear localization signal Ref.6 Ref.7
Compositional bias28 – 314Poly-Arg
Compositional bias499 – 5024Poly-Glu

Amino acid modifications

Modified residue21N-acetylserine By similarity
Modified residue621Phosphoserine By similarity

Experimental info

Sequence conflict2421P → S in AAA85281. Ref.2
Sequence conflict4181H → P in AAA85281. Ref.2
Sequence conflict4201G → R in AAA85281. Ref.2

Secondary structure

...................................................................... 529
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P52293 [UniParc].

Last modified November 1, 1997. Version 2.
Checksum: 19E64AA3E9C3C7B5

FASTA52957,928
        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 

« Hide

References

« Hide '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.
CCDSCCDS25565.1.
PIRS57345.
S57873.
S62116.
RefSeqNP_034785.1. NM_010655.3.
UniGeneMm.12508.
Mm.391577.
Mm.423000.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1EJLX-ray2.80I70-529[»]
1EJYX-ray2.90I70-529[»]
1IALX-ray2.50A44-496[»]
1IQ1X-ray2.80A/B44-54[»]
C70-529[»]
1PJMX-ray2.50B70-529[»]
1PJNX-ray2.50B70-529[»]
1Q1SX-ray2.30C70-529[»]
1Q1TX-ray2.50C70-529[»]
1Y2AX-ray2.20C70-497[»]
2C1MX-ray2.20A75-498[»]
2YNRX-ray2.30A72-496[»]
3BTRX-ray2.60C70-496[»]
3KNDX-ray2.15A70-529[»]
3L3QX-ray2.30A71-497[»]
3OQSX-ray2.00A70-529[»]
3Q5UX-ray2.50A70-529[»]
3RZ9X-ray2.29A70-529[»]
3RZXX-ray2.61A70-529[»]
3TPMX-ray2.10A75-496[»]
3TPOX-ray2.10A1-529[»]
3UKWX-ray2.10B70-529[»]
3UKXX-ray2.20B70-529[»]
3UKYX-ray2.35B70-529[»]
3UKZX-ray2.30B70-529[»]
3UL0X-ray2.00B70-529[»]
3UL1X-ray1.90B70-529[»]
3UVUX-ray2.38A70-529[»]
3VE6X-ray2.83A71-496[»]
3ZINX-ray2.00A72-496[»]
3ZIOX-ray2.10A72-496[»]
3ZIPX-ray2.40A72-497[»]
3ZIQX-ray2.10A72-497[»]
3ZIRX-ray2.30A72-497[»]
4BA3X-ray2.10A70-529[»]
4HTVX-ray3.00A70-528[»]
4MZ5X-ray2.10E70-528[»]
4MZ6X-ray1.88E70-528[»]
4OIHX-ray2.10A70-529[»]
ProteinModelPortalP52293.
SMRP52293. Positions 11-497.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid201007. 12 interactions.
IntActP52293. 9 interactions.

PTM databases

PhosphoSiteP52293.

Proteomic databases

MaxQBP52293.
PaxDbP52293.
PRIDEP52293.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000018506; ENSMUSP00000018506; ENSMUSG00000018362.
ENSMUST00000086423; ENSMUSP00000137310; ENSMUSG00000066878.
ENSMUST00000091289; ENSMUSP00000137080; ENSMUSG00000069083.
GeneID16647.
KEGGmmu:16647.
UCSCuc007lzz.1. mouse.

Organism-specific databases

CTD3838.
MGIMGI:103561. Kpna2.

Phylogenomic databases

eggNOGCOG5064.
HOGENOMHOG000167616.
HOVERGENHBG001846.
InParanoidP52293.
KOK15043.
OMANETEKLC.
OrthoDBEOG7VHSWV.
PhylomeDBP52293.
TreeFamTF101178.

Gene expression databases

BgeeP52293.
CleanExMM_KPNA2.
GenevestigatorP52293.

Family and domain databases

Gene3D1.25.10.10. 1 hit.
InterProIPR011989. ARM-like.
IPR016024. ARM-type_fold.
IPR000225. Armadillo.
IPR002652. Importin-a_IBB.
IPR024931. Importing_su_alpha.
[Graphical view]
PfamPF00514. Arm. 8 hits.
PF01749. IBB. 1 hit.
[Graphical view]
PIRSFPIRSF005673. Importin_alpha. 1 hit.
SMARTSM00185. ARM. 8 hits.
[Graphical view]
SUPFAMSSF48371. SSF48371. 1 hit.
PROSITEPS50176. ARM_REPEAT. 6 hits.
PS51214. IBB. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP52293.
NextBio290325.
PROP52293.
SOURCESearch...

Entry information

Entry nameIMA1_MOUSE
AccessionPrimary (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: July 9, 2014
This is version 140 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot