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Protein

Importin subunit alpha-3

Gene

Kpna4

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.

GO - Molecular functioni

  • nuclear localization sequence binding Source: GO_Central
  • protein transporter activity Source: MGI

GO - Biological processi

  • NLS-bearing protein import into nucleus Source: GO_Central
  • protein import into nucleus Source: MGI
  • response to hydrogen peroxide Source: MGI
Complete GO annotation...

Keywords - Biological processi

Protein transport, Transport

Names & Taxonomyi

Protein namesi
Recommended name:
Importin subunit alpha-3
Alternative name(s):
Importin alpha Q1
Short name:
Qip1
Karyopherin subunit alpha-4
Gene namesi
Name:Kpna4
Synonyms:Qip1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:1100848. Kpna4.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: GO_Central
  • extracellular exosome Source: MGI
  • nuclear pore Source: GO_Central
  • nucleoplasm Source: GO_Central
  • nucleus Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00001207272 – 521Importin subunit alpha-3Add BLAST520

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineBy similarity1
Modified residuei60PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiO35343.
PaxDbiO35343.
PeptideAtlasiO35343.
PRIDEiO35343.

PTM databases

iPTMnetiO35343.
PhosphoSitePlusiO35343.

Expressioni

Tissue specificityi

Detected more or less in all tissues examined (Ehrlich ascites tumor cells, testis, kidney, spleen, liver, heart, lung, thymus, skeletal muscle, cerebellum and brain (without cerebellum)). Multiple-sized transcripts were highly expressed, especially in testis.

Gene expression databases

BgeeiENSMUSG00000027782.
CleanExiMM_KPNA4.
ExpressionAtlasiO35343. baseline and differential.
GenevisibleiO35343. MM.

Interactioni

Subunit structurei

Forms a complex with importin subunit beta-1. Interacts with SNAI1 (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
SF1Q156373EBI-8372758,EBI-744603From a different organism.

Protein-protein interaction databases

BioGridi201009. 6 interactors.
DIPiDIP-62053N.
IntActiO35343. 4 interactors.
MINTiMINT-4098648.
STRINGi10090.ENSMUSP00000029353.

Structurei

3D structure databases

ProteinModelPortaliO35343.
SMRiO35343.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini2 – 58IBBPROSITE-ProRule annotationAdd BLAST57
Repeati66 – 106ARM 1; truncatedAdd BLAST41
Repeati107 – 149ARM 2Add BLAST43
Repeati150 – 194ARM 3Add BLAST45
Repeati195 – 233ARM 4Add BLAST39
Repeati234 – 278ARM 5Add BLAST45
Repeati279 – 318ARM 6Add BLAST40
Repeati319 – 360ARM 7Add BLAST42
Repeati361 – 400ARM 8Add BLAST40
Repeati401 – 443ARM 9Add BLAST43
Repeati447 – 485ARM 10; atypicalAdd BLAST39

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni137 – 229NLS binding site (major)By similarityAdd BLAST93
Regioni306 – 394NLS binding site (minor)By similarityAdd BLAST89

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi43 – 52Nuclear localization signalBy similarity10

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi233 – 236Poly-Pro4

Domaini

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 (By similarity).By similarity
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).By similarity

Sequence similaritiesi

Belongs to the importin alpha family.Curated
Contains 10 ARM repeats.PROSITE-ProRule annotation
Contains 1 IBB domain.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0166. Eukaryota.
COG5064. LUCA.
GeneTreeiENSGT00760000119094.
HOVERGENiHBG001846.
InParanoidiO35343.
PhylomeDBiO35343.
TreeFamiTF101178.

Family and domain databases

Gene3Di1.25.10.10. 1 hit.
InterProiIPR011989. ARM-like.
IPR016024. ARM-type_fold.
IPR032413. Arm_3.
IPR000225. Armadillo.
IPR002652. Importin-a_IBB.
IPR024931. Importing_su_alpha.
[Graphical view]
PfamiPF00514. Arm. 8 hits.
PF16186. Arm_3. 1 hit.
PF01749. IBB. 1 hit.
[Graphical view]
PIRSFiPIRSF005673. Importin_alpha. 1 hit.
SMARTiSM00185. ARM. 8 hits.
[Graphical view]
SUPFAMiSSF48371. SSF48371. 1 hit.
PROSITEiPS50176. ARM_REPEAT. 3 hits.
PS51214. IBB. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

O35343-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MADNEKLDNQ RLKNFKNKGR DLETMRRQRN EVVVELRKNK RDEHLLKRRN
60 70 80 90 100
VPQEDICEDS DIDGDYRVQN TSLEAIVQNA SSDNQGIQLS AVQAARKLLS
110 120 130 140 150
SDRNPPIDDL IKSGILPILV HCLERDDNPS LQFEAAWALT NIASGTSEQT
160 170 180 190 200
QAVVQSNAVP LFLRLLHSPH QNVCEQAVWA LGNIIGDGPQ CRDYVISLGV
210 220 230 240 250
VKPLLSFISP SIPITFLRNV TWVMVNLCRH KDPPPPMETI QEILPALCVL
260 270 280 290 300
IHHTDVNILV DTVWALSYLT DAGNEQIQMV IDSGIVPHLV PLLSHQEVKV
310 320 330 340 350
QTAALRAVGN IVTGTDEQTQ VVLNCDALSH FPALLTHPKE KINKEAVWFL
360 370 380 390 400
SNITAGNQQQ VQAVIDANLV PMIIHLLDKG DFGTQKEAAW AISNLTISGR
410 420 430 440 450
KDQVAYLIQQ NVIPPFCNLL TVKDAQVVQV VLDGLSNILK MAEDQAETIA
460 470 480 490 500
NLIEECGGLE KIEQLQNHEN EDIYKLAYEI IDQFFSSDDI DEDPSLVPES
510 520
VQGGTFGFNS STNVPTEGFQ F
Length:521
Mass (Da):57,923
Last modified:January 1, 1998 - v1
Checksum:iA0578EC9D411E060
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF020771 mRNA. Translation: AAC53371.1.
BC026821 mRNA. Translation: AAH26821.1.
BC052162 mRNA. Translation: AAH52162.1.
CCDSiCCDS17403.1.
RefSeqiNP_032493.1. NM_008467.4.
UniGeneiMm.30601.

Genome annotation databases

EnsembliENSMUST00000194558; ENSMUSP00000141227; ENSMUSG00000027782.
GeneIDi16649.
KEGGimmu:16649.
UCSCiuc008pme.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF020771 mRNA. Translation: AAC53371.1.
BC026821 mRNA. Translation: AAH26821.1.
BC052162 mRNA. Translation: AAH52162.1.
CCDSiCCDS17403.1.
RefSeqiNP_032493.1. NM_008467.4.
UniGeneiMm.30601.

3D structure databases

ProteinModelPortaliO35343.
SMRiO35343.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi201009. 6 interactors.
DIPiDIP-62053N.
IntActiO35343. 4 interactors.
MINTiMINT-4098648.
STRINGi10090.ENSMUSP00000029353.

PTM databases

iPTMnetiO35343.
PhosphoSitePlusiO35343.

Proteomic databases

EPDiO35343.
PaxDbiO35343.
PeptideAtlasiO35343.
PRIDEiO35343.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000194558; ENSMUSP00000141227; ENSMUSG00000027782.
GeneIDi16649.
KEGGimmu:16649.
UCSCiuc008pme.1. mouse.

Organism-specific databases

CTDi3840.
MGIiMGI:1100848. Kpna4.

Phylogenomic databases

eggNOGiKOG0166. Eukaryota.
COG5064. LUCA.
GeneTreeiENSGT00760000119094.
HOVERGENiHBG001846.
InParanoidiO35343.
PhylomeDBiO35343.
TreeFamiTF101178.

Miscellaneous databases

ChiTaRSiKpna4. mouse.
PROiO35343.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000027782.
CleanExiMM_KPNA4.
ExpressionAtlasiO35343. baseline and differential.
GenevisibleiO35343. MM.

Family and domain databases

Gene3Di1.25.10.10. 1 hit.
InterProiIPR011989. ARM-like.
IPR016024. ARM-type_fold.
IPR032413. Arm_3.
IPR000225. Armadillo.
IPR002652. Importin-a_IBB.
IPR024931. Importing_su_alpha.
[Graphical view]
PfamiPF00514. Arm. 8 hits.
PF16186. Arm_3. 1 hit.
PF01749. IBB. 1 hit.
[Graphical view]
PIRSFiPIRSF005673. Importin_alpha. 1 hit.
SMARTiSM00185. ARM. 8 hits.
[Graphical view]
SUPFAMiSSF48371. SSF48371. 1 hit.
PROSITEiPS50176. ARM_REPEAT. 3 hits.
PS51214. IBB. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiIMA3_MOUSE
AccessioniPrimary (citable) accession number: O35343
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: January 1, 1998
Last modified: November 2, 2016
This is version 136 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.