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Protein

Importin subunit alpha-6

Gene

KPNA5

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. Mediates nuclear import of STAT1 homodimers and STAT1/STAT2 heterodimers by recognizing non-classical NLSs of STAT1 and STAT2 through ARM repeats 8-9. Recognizes influenza A virus nucleoprotein through ARM repeat 7-9 In vitro, mediates the nuclear import of human cytomegalovirus UL84 by recognizing a non-classical NLS.

GO - Molecular functioni

GO - Biological processi

Keywordsi

Biological processHost-virus interaction, Protein transport, Transport

Enzyme and pathway databases

ReactomeiR-HSA-1169408 ISG15 antiviral mechanism
R-HSA-168276 NS1 Mediated Effects on Host Pathways
SignaLinkiO15131

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-6
Alternative name(s):
Karyopherin subunit alpha-5
Gene namesi
Name:KPNA5
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

EuPathDBiHostDB:ENSG00000196911.9
HGNCiHGNC:6398 KPNA5
MIMi604545 gene
neXtProtiNX_O15131

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

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA30189

Polymorphism and mutation databases

BioMutaiKPNA5

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001207281 – 536Importin subunit alpha-6Add BLAST536

Proteomic databases

EPDiO15131
MaxQBiO15131
PaxDbiO15131
PeptideAtlasiO15131
PRIDEiO15131
ProteomicsDBi48467

PTM databases

iPTMnetiO15131
PhosphoSitePlusiO15131
SwissPalmiO15131

Expressioni

Tissue specificityi

Testis.

Gene expression databases

BgeeiENSG00000196911 Expressed in 212 organ(s), highest expression level in neocortex
CleanExiHS_KPNA5
ExpressionAtlasiO15131 baseline and differential
GenevisibleiO15131 HS

Organism-specific databases

HPAiCAB026464
HPA054037

Interactioni

Subunit structurei

Forms a complex with importin subunit beta-1.
(Microbial infection) Interacts with ebolavirus protein VP24.1 Publication

Binary interactionsi

Protein-protein interaction databases

BioGridi110039, 34 interactors
ComplexPortaliCPX-1063 Importin complex, KPNA5 variant
DIPiDIP-33405N
ELMiO15131
IntActiO15131, 19 interactors
MINTiO15131
STRINGi9606.ENSP00000348704

Structurei

Secondary structure

1536
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO15131
SMRiO15131
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini2 – 57IBBPROSITE-ProRule annotationAdd BLAST56
Repeati73 – 115ARM 1; truncatedAdd BLAST43
Repeati116 – 159ARM 2Add BLAST44
Repeati160 – 204ARM 3Add BLAST45
Repeati205 – 243ARM 4Add BLAST39
Repeati244 – 288ARM 5Add BLAST45
Repeati289 – 328ARM 6Add BLAST40
Repeati329 – 370ARM 7Add BLAST42
Repeati371 – 410ARM 8Add BLAST40
Repeati411 – 453ARM 9Add BLAST43
Repeati457 – 502ARM 10; atypicalAdd BLAST46

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni147 – 239NLS binding site (major)By similarityAdd BLAST93
Regioni316 – 404NLS binding site (minor)By similarityAdd BLAST89

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi42 – 51Nuclear localization signalBy similarity10

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi25 – 28Poly-Arg4

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
HOGENOMiHOG000167616
HOVERGENiHBG001846
InParanoidiO15131
OrthoDBiEOG091G095Z
PhylomeDBiO15131
TreeFamiTF354205

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, 2 hits
PS51214 IBB, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

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

O15131-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MASPGKDNYR MKSYKNKALN PQEMRRRREE EGIQLRKQKR EEQLFKRRNV
60 70 80 90 100
YLPRNDESML ESPIQDPDIS STVPIPEEEV VTTDMVQMIF SNNADQQLTA
110 120 130 140 150
TQKFRKLLSK EPNPPIDQVI QKPGVVQRFV KFLERNENCT LQFEAAWALT
160 170 180 190 200
NIASGTFLHT KVVIETGAVP IFIKLLNSEH EDVQEQAVWA LGNIAGDNAE
210 220 230 240 250
CRDFVLNCEI LPPLLELLTN SNRLTTTRNA VWALSNLCRG KNPPPNFSKV
260 270 280 290 300
SPCLNVLSRL LFSSDPDVLA DVCWALSYLS DGPNDKIQAV IDSGVCRRLV
310 320 330 340 350
ELLMHNDYKV VSPALRAVGN IVTGDDIQTQ VILNCSALPC LLHLLSSPKE
360 370 380 390 400
SIRKEACWTV SNITAGNRAQ IQAVIDANIF PVLIEILQKA EFRTRKEAAW
410 420 430 440 450
AITNATSGGT PEQIRYLVAL GCIKPLCDLL TVMDSKIVQV ALNGLENILR
460 470 480 490 500
LGEQESKQNG IGINPYCALI EEAYGLDKIE FLQSHENQEI YQKAFDLIEH
510 520 530
YFGVEEDDPS IVPQVDENQQ QFIFQQQEAP MDGFQL
Length:536
Mass (Da):60,349
Last modified:June 16, 2009 - v2
Checksum:i757D4C56D0E5661F
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q5TD90Q5TD90_HUMAN
Importin subunit alpha-6
KPNA5
142Annotation score:

Sequence cautioni

The sequence AAH47409 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti67P → S in AAC51868 (PubMed:9395085).Curated1
Sequence conflicti79E → G in AAC51868 (PubMed:9395085).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03624545F → L in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_036246316R → S in a breast cancer sample; somatic mutation. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF005361 mRNA Translation: AAC51868.1
AK314206 mRNA Translation: BAG36882.1
AL132795 Genomic DNA No translation available.
CH471051 Genomic DNA Translation: EAW48216.1
BC047409 mRNA Translation: AAH47409.1 Different initiation.
RefSeqiNP_002260.2, NM_002269.2
XP_016866328.1, XM_017010839.1
XP_016866329.1, XM_017010840.1
UniGeneiHs.182971

Genome annotation databases

EnsembliENST00000356348; ENSP00000348704; ENSG00000196911
ENST00000368564; ENSP00000357552; ENSG00000196911
GeneIDi3841
KEGGihsa:3841
UCSCiuc003pxh.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF005361 mRNA Translation: AAC51868.1
AK314206 mRNA Translation: BAG36882.1
AL132795 Genomic DNA No translation available.
CH471051 Genomic DNA Translation: EAW48216.1
BC047409 mRNA Translation: AAH47409.1 Different initiation.
RefSeqiNP_002260.2, NM_002269.2
XP_016866328.1, XM_017010839.1
XP_016866329.1, XM_017010840.1
UniGeneiHs.182971

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4U2XX-ray3.15D/E/F329-503[»]
ProteinModelPortaliO15131
SMRiO15131
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110039, 34 interactors
ComplexPortaliCPX-1063 Importin complex, KPNA5 variant
DIPiDIP-33405N
ELMiO15131
IntActiO15131, 19 interactors
MINTiO15131
STRINGi9606.ENSP00000348704

Protein family/group databases

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

PTM databases

iPTMnetiO15131
PhosphoSitePlusiO15131
SwissPalmiO15131

Polymorphism and mutation databases

BioMutaiKPNA5

Proteomic databases

EPDiO15131
MaxQBiO15131
PaxDbiO15131
PeptideAtlasiO15131
PRIDEiO15131
ProteomicsDBi48467

Protocols and materials databases

DNASUi3841
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000356348; ENSP00000348704; ENSG00000196911
ENST00000368564; ENSP00000357552; ENSG00000196911
GeneIDi3841
KEGGihsa:3841
UCSCiuc003pxh.4 human

Organism-specific databases

CTDi3841
EuPathDBiHostDB:ENSG00000196911.9
GeneCardsiKPNA5
HGNCiHGNC:6398 KPNA5
HPAiCAB026464
HPA054037
MIMi604545 gene
neXtProtiNX_O15131
PharmGKBiPA30189
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0166 Eukaryota
COG5064 LUCA
HOGENOMiHOG000167616
HOVERGENiHBG001846
InParanoidiO15131
OrthoDBiEOG091G095Z
PhylomeDBiO15131
TreeFamiTF354205

Enzyme and pathway databases

ReactomeiR-HSA-1169408 ISG15 antiviral mechanism
R-HSA-168276 NS1 Mediated Effects on Host Pathways
SignaLinkiO15131

Miscellaneous databases

ChiTaRSiKPNA5 human
GeneWikiiKPNA5
GenomeRNAii3841
PROiPR:O15131
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000196911 Expressed in 212 organ(s), highest expression level in neocortex
CleanExiHS_KPNA5
ExpressionAtlasiO15131 baseline and differential
GenevisibleiO15131 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, 2 hits
PS51214 IBB, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiIMA6_HUMAN
AccessioniPrimary (citable) accession number: O15131
Secondary accession number(s): B2RAI5, Q86X23
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: June 16, 2009
Last modified: November 7, 2018
This is version 171 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

3D-structure, 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
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