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Protein

Importin subunit alpha-6

Gene

KPNA5

Organism
Homo sapiens (Human)
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. 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

Complete GO annotation...

Keywords - Biological processi

Protein transport, Transport

Enzyme and pathway databases

BioCyciZFISH:G66-30800-MONOMER.
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 nuclear pore complex (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

HGNCiHGNC:6398. KPNA5.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

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.

PTM databases

iPTMnetiO15131.
PhosphoSitePlusiO15131.
SwissPalmiO15131.

Expressioni

Tissue specificityi

Testis.

Gene expression databases

BgeeiENSG00000196911.
CleanExiHS_KPNA5.
ExpressionAtlasiO15131. baseline and differential.
GenevisibleiO15131. HS.

Organism-specific databases

HPAiCAB026464.
HPA054037.

Interactioni

Subunit structurei

Forms a complex with importin subunit beta-1.

Binary interactionsi

WithEntry#Exp.IntActNotes
ANP32BQ926883EBI-540602,EBI-762428
CDKN1BP465276EBI-540602,EBI-519280
NUP50Q9UKX73EBI-540602,EBI-2371082
SPOPLQ6IQ163EBI-540602,EBI-2822161

Protein-protein interaction databases

BioGridi110039. 25 interactors.
DIPiDIP-33405N.
IntActiO15131. 13 interactors.
MINTiMINT-2860255.
STRINGi9606.ENSP00000348704.

Structurei

Secondary structure

1536
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi339 – 344Combined sources6
Helixi350 – 364Combined sources15
Helixi368 – 376Combined sources9
Helixi380 – 389Combined sources10
Helixi392 – 408Combined sources17
Helixi411 – 420Combined sources10
Helixi423 – 428Combined sources6
Helixi429 – 431Combined sources3
Helixi435 – 457Combined sources23
Helixi465 – 472Combined sources8
Helixi475 – 482Combined sources8
Helixi488 – 501Combined sources14

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...

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
Contains 10 ARM repeats.PROSITE-ProRule annotation
Contains 1 IBB domain.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0166. Eukaryota.
COG5064. LUCA.
HOGENOMiHOG000167616.
HOVERGENiHBG001846.
InParanoidiO15131.
OrthoDBiEOG091G095Z.
PhylomeDBiO15131.
TreeFamiTF354205.

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. 2 hits.
PS51214. IBB. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

Sequence cautioni

The sequence AAH47409 differs from that shown. Reason: Erroneous initiation.Curated
The sequence CAI20500 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. Translation: CAI20500.1. Different initiation.
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

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. Translation: CAI20500.1. Different initiation.
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. 25 interactors.
DIPiDIP-33405N.
IntActiO15131. 13 interactors.
MINTiMINT-2860255.
STRINGi9606.ENSP00000348704.

Protein family/group databases

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

PTM databases

iPTMnetiO15131.
PhosphoSitePlusiO15131.
SwissPalmiO15131.

Polymorphism and mutation databases

BioMutaiKPNA5.

Proteomic databases

EPDiO15131.
MaxQBiO15131.
PaxDbiO15131.
PeptideAtlasiO15131.
PRIDEiO15131.

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.
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

BioCyciZFISH:G66-30800-MONOMER.
ReactomeiR-HSA-1169408. ISG15 antiviral mechanism.
R-HSA-168276. NS1 Mediated Effects on Host Pathways.
SignaLinkiO15131.

Miscellaneous databases

ChiTaRSiKPNA5. human.
GeneWikiiKPNA5.
GenomeRNAii3841.
PROiO15131.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000196911.
CleanExiHS_KPNA5.
ExpressionAtlasiO15131. baseline and differential.
GenevisibleiO15131. HS.

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. 2 hits.
PS51214. IBB. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiIMA6_HUMAN
AccessioniPrimary (citable) accession number: O15131
Secondary accession number(s): B2RAI5, Q86X23
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: June 16, 2009
Last modified: November 30, 2016
This is version 157 of the entry and version 2 of the sequence. [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. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  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. 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.