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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

  • protein transporter activity Source: MGI

GO - Biological processi

  • 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

  • cytoplasm Source: UniProtKB-SubCell
  • extracellular exosome Source: MGI
  • nucleus Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedBy similarity
Chaini2 – 521520Importin subunit alpha-3PRO_0000120727Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanineBy similarity
Modified residuei60 – 601PhosphoserineCombined sources

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiO35343.
PaxDbiO35343.
PRIDEiO35343.

PTM databases

iPTMnetiO35343.
PhosphoSiteiO35343.

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

BgeeiO35343.
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. 4 interactions.
IntActiO35343. 4 interactions.
MINTiMINT-4098648.
STRINGi10090.ENSMUSP00000029353.

Structurei

3D structure databases

ProteinModelPortaliO35343.
SMRiO35343. Positions 11-51, 71-487.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini2 – 5857IBBPROSITE-ProRule annotationAdd
BLAST
Repeati66 – 10641ARM 1; truncatedAdd
BLAST
Repeati107 – 14943ARM 2Add
BLAST
Repeati150 – 19445ARM 3Add
BLAST
Repeati195 – 23339ARM 4Add
BLAST
Repeati234 – 27845ARM 5Add
BLAST
Repeati279 – 31840ARM 6Add
BLAST
Repeati319 – 36042ARM 7Add
BLAST
Repeati361 – 40040ARM 8Add
BLAST
Repeati401 – 44343ARM 9Add
BLAST
Repeati447 – 48539ARM 10; atypicalAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni137 – 22993NLS binding site (major)By similarityAdd
BLAST
Regioni306 – 39489NLS binding site (minor)By similarityAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi43 – 5210Nuclear localization signalBy similarity

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi233 – 2364Poly-Pro

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.
HOVERGENiHBG001846.
InParanoidiO35343.
OrthoDBiEOG7VHSWV.
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. Positions 11-51, 71-487.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi201009. 4 interactions.
IntActiO35343. 4 interactions.
MINTiMINT-4098648.
STRINGi10090.ENSMUSP00000029353.

PTM databases

iPTMnetiO35343.
PhosphoSiteiO35343.

Proteomic databases

EPDiO35343.
PaxDbiO35343.
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.
HOVERGENiHBG001846.
InParanoidiO35343.
OrthoDBiEOG7VHSWV.
PhylomeDBiO35343.
TreeFamiTF101178.

Miscellaneous databases

ChiTaRSiKpna4. mouse.
NextBioi290333.
PROiO35343.
SOURCEiSearch...

Gene expression databases

BgeeiO35343.
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...

Publicationsi

« Hide 'large scale' publications
  1. "Identification of novel homologues of mouse importin alpha, the alpha subunit of the nuclear pore-targeting complex, and their tissue-specific expression."
    Tsuji L., Takumi T., Imamoto N., Yoneda Y.
    FEBS Lett. 416:30-34(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "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].
    Strain: FVB/N.
    Tissue: Limb and Mammary gland.
  3. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-60, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  4. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-60, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas, Spleen and Testis.

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: May 11, 2016
This is version 131 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.