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Protein

Importin subunit alpha-4

Gene

KPNA3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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. In vitro, mediates the nuclear import of human cytomegalovirus UL84 by recognizing a non-classical NLS. Recognizes NLSs of influenza A virus nucleoprotein probably through ARM repeats 7-9.

Caution

Was termed importin alpha-4.1 Publication

GO - Molecular functioni

GO - Biological processi

Keywordsi

Biological processHost-virus interaction, Protein transport, Transport, Viral penetration into host nucleus, Virus entry into host cell

Enzyme and pathway databases

ReactomeiR-HSA-1169408 ISG15 antiviral mechanism
R-HSA-168276 NS1 Mediated Effects on Host Pathways
SignaLinkiO00505
SIGNORiO00505

Protein family/group databases

TCDBi1.I.1.1.3 the eukaryotic nuclear pore complex (e-npc) family

Names & Taxonomyi

Protein namesi
Recommended name:
Importin subunit alpha-4
Alternative name(s):
Importin alpha Q2
Short name:
Qip2
Karyopherin subunit alpha-3
SRP1-gamma
Gene namesi
Name:KPNA3
Synonyms:QIP2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 13

Organism-specific databases

EuPathDBiHostDB:ENSG00000102753.9
HGNCiHGNC:6396 KPNA3
MIMi601892 gene
neXtProtiNX_O00505

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi3839
OpenTargetsiENSG00000102753
PharmGKBiPA30187

Polymorphism and mutation databases

BioMutaiKPNA3

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00001207242 – 521Importin subunit alpha-4Add BLAST520

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei56PhosphoserineCombined sources1
Modified residuei60PhosphoserineCombined sources1
Modified residuei484PhosphotyrosineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiO00505
MaxQBiO00505
PaxDbiO00505
PeptideAtlasiO00505
PRIDEiO00505
ProteomicsDBi47946

PTM databases

iPTMnetiO00505
PhosphoSitePlusiO00505

Expressioni

Tissue specificityi

Ubiquitous. Highest levels in heart and skeletal muscle.

Gene expression databases

BgeeiENSG00000102753 Expressed in 238 organ(s), highest expression level in biceps brachii
CleanExiHS_KPNA3
ExpressionAtlasiO00505 baseline and differential
GenevisibleiO00505 HS

Organism-specific databases

HPAiHPA046852

Interactioni

Subunit structurei

Forms a complex with importin subunit beta-1. Interacts with NCBP2/CBP20 and NCBP3 (PubMed:26382858).1 Publication
(Microbial infection) Interacts with HIV-1 integrase; this interaction might play a role in nuclear import of HIV pre-integration complex.1 Publication
(Microbial infection) Interacts with influenza virus nucleoprotein; this interaction might play a role in nuclear import of viral genome.1 Publication

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi110037, 89 interactors
ComplexPortaliCPX-1057 Importin complex, KPNA3 variant
CORUMiO00505
DIPiDIP-27586N
IntActiO00505, 90 interactors
MINTiO00505
STRINGi9606.ENSP00000261667

Structurei

3D structure databases

ProteinModelPortaliO00505
SMRiO00505
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

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

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0166 Eukaryota
COG5064 LUCA
GeneTreeiENSGT00760000119094
HOGENOMiHOG000167616
HOVERGENiHBG001846
InParanoidiO00505
OMAiHRNEVTI
OrthoDBiEOG091G095Z
PhylomeDBiO00505
TreeFamiTF101178

Family and domain databases

Gene3Di1.20.5.690, 1 hit
1.25.10.10, 1 hit
InterProiView protein in InterPro
IPR011989 ARM-like
IPR016024 ARM-type_fold
IPR032413 Arm_3
IPR000225 Armadillo
IPR002652 Importin-a_IBB
IPR036975 Importin-a_IBB_sf
IPR024931 Importing_su_alpha
PfamiView protein in Pfam
PF00514 Arm, 8 hits
PF16186 Arm_3, 1 hit
PF01749 IBB, 1 hit
PIRSFiPIRSF005673 Importin_alpha, 1 hit
SMARTiView protein in SMART
SM00185 ARM, 8 hits
SUPFAMiSSF48371 SSF48371, 1 hit
PROSITEiView protein in PROSITE
PS50176 ARM_REPEAT, 3 hits
PS51214 IBB, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

O00505-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MAENPSLENH RIKSFKNKGR DVETMRRHRN EVTVELRKNK RDEHLLKKRN
60 70 80 90 100
VPQEESLEDS DVDADFKAQN VTLEAILQNA TSDNPVVQLS AVQAARKLLS
110 120 130 140 150
SDRNPPIDDL IKSGILPILV KCLERDDNPS LQFEAAWALT NIASGTSAQT
160 170 180 190 200
QAVVQSNAVP LFLRLLRSPH QNVCEQAVWA LGNIIGDGPQ CRDYVISLGV
210 220 230 240 250
VKPLLSFISP SIPITFLRNV TWVIVNLCRN KDPPPPMETV QEILPALCVL
260 270 280 290 300
IYHTDINILV DTVWALSYLT DGGNEQIQMV IDSGVVPFLV PLLSHQEVKV
310 320 330 340 350
QTAALRAVGN IVTGTDEQTQ VVLNCDVLSH FPNLLSHPKE KINKEAVWFL
360 370 380 390 400
SNITAGNQQQ VQAVIDAGLI PMIIHQLAKG DFGTQKEAAW AISNLTISGR
410 420 430 440 450
KDQVEYLVQQ NVIPPFCNLL SVKDSQVVQV VLDGLKNILI MAGDEASTIA
460 470 480 490 500
EIIEECGGLE KIEVLQQHEN EDIYKLAFEI IDQYFSGDDI DEDPCLIPEA
510 520
TQGGTYNFDP TANLQTKEFN F
Length:521
Mass (Da):57,811
Last modified:January 23, 2002 - v2
Checksum:iC4FF132C3F346B7F
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H0Y4S9H0Y4S9_HUMAN
Importin subunit alpha-4
KPNA3
91Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti34V → M in CAA73026 (PubMed:9395085).Curated1
Sequence conflicti103R → Q in BAA20378 (PubMed:9154134).Curated1
Sequence conflicti152 – 153AV → DI in AAH35090 (PubMed:15489334).Curated2
Sequence conflicti154V → G in AAB87693 (PubMed:9435235).Curated1
Sequence conflicti236P → T in AAB87693 (PubMed:9435235).Curated1
Sequence conflicti237M → L in CAA73026 (PubMed:9395085).Curated1
Sequence conflicti256I → V in CAA73026 (PubMed:9395085).Curated1
Sequence conflicti259L → V in CAA73026 (PubMed:9395085).Curated1
Sequence conflicti332P → Q in AAH35090 (PubMed:15489334).Curated1
Sequence conflicti411N → D in AAH35090 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_014454291P → S. Corresponds to variant dbSNP:rs1043015Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D89618 mRNA Translation: BAA20378.1
Y12394 mRNA Translation: CAA73026.1
AF034756 mRNA Translation: AAB87693.1
AF005263 mRNA Translation: AAQ13404.1
AK290528 mRNA Translation: BAF83217.1
AK291000 mRNA Translation: BAF83689.1
AL136301 Genomic DNA No translation available.
AL135901 Genomic DNA No translation available.
CH471075 Genomic DNA Translation: EAX08837.1
BC017355 mRNA Translation: AAH17355.1
BC024202 mRNA Translation: AAH24202.1
BC035090 mRNA Translation: AAH35090.1
CCDSiCCDS9421.1
RefSeqiNP_002258.2, NM_002267.3
UniGeneiHs.527919

Genome annotation databases

EnsembliENST00000261667; ENSP00000261667; ENSG00000102753
GeneIDi3839
KEGGihsa:3839
UCSCiuc001vdj.2 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D89618 mRNA Translation: BAA20378.1
Y12394 mRNA Translation: CAA73026.1
AF034756 mRNA Translation: AAB87693.1
AF005263 mRNA Translation: AAQ13404.1
AK290528 mRNA Translation: BAF83217.1
AK291000 mRNA Translation: BAF83689.1
AL136301 Genomic DNA No translation available.
AL135901 Genomic DNA No translation available.
CH471075 Genomic DNA Translation: EAX08837.1
BC017355 mRNA Translation: AAH17355.1
BC024202 mRNA Translation: AAH24202.1
BC035090 mRNA Translation: AAH35090.1
CCDSiCCDS9421.1
RefSeqiNP_002258.2, NM_002267.3
UniGeneiHs.527919

3D structure databases

ProteinModelPortaliO00505
SMRiO00505
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110037, 89 interactors
ComplexPortaliCPX-1057 Importin complex, KPNA3 variant
CORUMiO00505
DIPiDIP-27586N
IntActiO00505, 90 interactors
MINTiO00505
STRINGi9606.ENSP00000261667

Protein family/group databases

TCDBi1.I.1.1.3 the eukaryotic nuclear pore complex (e-npc) family

PTM databases

iPTMnetiO00505
PhosphoSitePlusiO00505

Polymorphism and mutation databases

BioMutaiKPNA3

Proteomic databases

EPDiO00505
MaxQBiO00505
PaxDbiO00505
PeptideAtlasiO00505
PRIDEiO00505
ProteomicsDBi47946

Protocols and materials databases

DNASUi3839
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000261667; ENSP00000261667; ENSG00000102753
GeneIDi3839
KEGGihsa:3839
UCSCiuc001vdj.2 human

Organism-specific databases

CTDi3839
DisGeNETi3839
EuPathDBiHostDB:ENSG00000102753.9
GeneCardsiKPNA3
HGNCiHGNC:6396 KPNA3
HPAiHPA046852
MIMi601892 gene
neXtProtiNX_O00505
OpenTargetsiENSG00000102753
PharmGKBiPA30187
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0166 Eukaryota
COG5064 LUCA
GeneTreeiENSGT00760000119094
HOGENOMiHOG000167616
HOVERGENiHBG001846
InParanoidiO00505
OMAiHRNEVTI
OrthoDBiEOG091G095Z
PhylomeDBiO00505
TreeFamiTF101178

Enzyme and pathway databases

ReactomeiR-HSA-1169408 ISG15 antiviral mechanism
R-HSA-168276 NS1 Mediated Effects on Host Pathways
SignaLinkiO00505
SIGNORiO00505

Miscellaneous databases

ChiTaRSiKPNA3 human
GeneWikiiKPNA3
GenomeRNAii3839
PROiPR:O00505
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000102753 Expressed in 238 organ(s), highest expression level in biceps brachii
CleanExiHS_KPNA3
ExpressionAtlasiO00505 baseline and differential
GenevisibleiO00505 HS

Family and domain databases

Gene3Di1.20.5.690, 1 hit
1.25.10.10, 1 hit
InterProiView protein in InterPro
IPR011989 ARM-like
IPR016024 ARM-type_fold
IPR032413 Arm_3
IPR000225 Armadillo
IPR002652 Importin-a_IBB
IPR036975 Importin-a_IBB_sf
IPR024931 Importing_su_alpha
PfamiView protein in Pfam
PF00514 Arm, 8 hits
PF16186 Arm_3, 1 hit
PF01749 IBB, 1 hit
PIRSFiPIRSF005673 Importin_alpha, 1 hit
SMARTiView protein in SMART
SM00185 ARM, 8 hits
SUPFAMiSSF48371 SSF48371, 1 hit
PROSITEiView protein in PROSITE
PS50176 ARM_REPEAT, 3 hits
PS51214 IBB, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiIMA4_HUMAN
AccessioniPrimary (citable) accession number: O00505
Secondary accession number(s): O00191
, O43195, Q5JVM9, Q8IYQ9, Q96AA7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: January 23, 2002
Last modified: November 7, 2018
This is version 191 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human chromosome 13
    Human chromosome 13: entries, gene names and cross-references to MIM
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Main funding by: National Institutes of Health

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