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Protein

Importin subunit alpha-3

Gene

KPNA4

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. In vitro, mediates the nuclear import of human cytomegalovirus UL84 by recognizing a non-classical NLS. 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

ReactomeiR-HSA-1169408. ISG15 antiviral mechanism.
R-HSA-168276. NS1 Mediated Effects on Host Pathways.
SignaLinkiO00629.
SIGNORiO00629.

Protein family/group databases

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

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:6397. KPNA4.

Subcellular locationi

GO - Cellular componenti

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

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA30188.

Polymorphism and mutation databases

BioMutaiKPNA4.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedCombined sources
Chaini2 – 521520Importin subunit alpha-3PRO_0000120726Add
BLAST

Amino acid modifications

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

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiO00629.
MaxQBiO00629.
PaxDbiO00629.
PeptideAtlasiO00629.
PRIDEiO00629.
TopDownProteomicsiO00629.

PTM databases

iPTMnetiO00629.
PhosphoSiteiO00629.

Miscellaneous databases

PMAP-CutDBO00629.

Expressioni

Tissue specificityi

Highly expressed in testis, ovary, small intestine, heart, skeletal muscle, lung and pancreas, but barely detectable in kidney, thymus, colon and peripheral blood leukocytes.

Gene expression databases

BgeeiENSG00000186432.
CleanExiHS_KPNA4.
ExpressionAtlasiO00629. baseline and differential.
GenevisibleiO00629. HS.

Organism-specific databases

HPAiCAB034336.
HPA043154.
HPA045500.

Interactioni

Subunit structurei

Forms a complex with importin subunit beta-1. Interacts with SNAI1. Interacts with human adenovirus 5 E1A protein; this interaction allows E1A import into the host nucleus (PubMed:23864635).3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CYHR1Q6ZMK13EBI-396343,EBI-3908824
gag-polP045854EBI-396343,EBI-9872653From a different organism.
HNRNPCP079103EBI-396343,EBI-357966
MAT2BQ9NZL93EBI-396343,EBI-10317491
NUP50Q9UKX73EBI-396343,EBI-2371082
PLAAQ9Y2633EBI-396343,EBI-1994037
RECQLP460632EBI-396343,EBI-2823728

Protein-protein interaction databases

BioGridi110038. 83 interactions.
DIPiDIP-32982N.
IntActiO00629. 46 interactions.
MINTiMINT-5003750.
STRINGi9606.ENSP00000334373.

Structurei

Secondary structure

1
521
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi73 – 797Combined sources
Helixi85 – 9814Combined sources
Beta strandi100 – 1045Combined sources
Helixi107 – 1126Combined sources
Helixi115 – 1228Combined sources
Helixi129 – 14315Combined sources
Helixi147 – 1548Combined sources
Turni155 – 1573Combined sources
Helixi159 – 1657Combined sources
Helixi171 – 18515Combined sources
Helixi189 – 1979Combined sources
Helixi201 – 2066Combined sources
Helixi214 – 22815Combined sources
Helixi237 – 25014Combined sources
Helixi256 – 27116Combined sources
Helixi274 – 28310Combined sources
Helixi286 – 2894Combined sources
Helixi290 – 2945Combined sources
Helixi298 – 31114Combined sources
Helixi316 – 3238Combined sources
Turni324 – 3263Combined sources
Helixi327 – 3304Combined sources
Helixi332 – 3354Combined sources
Helixi340 – 35314Combined sources
Helixi358 – 3669Combined sources
Helixi370 – 37910Combined sources
Helixi382 – 39817Combined sources
Helixi401 – 4099Combined sources
Helixi413 – 4175Combined sources
Helixi418 – 4214Combined sources
Helixi425 – 44117Combined sources
Helixi446 – 45510Combined sources
Helixi458 – 4636Combined sources
Helixi471 – 48414Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4UAEX-ray2.70A68-487[»]
ProteinModelPortaliO00629.
SMRiO00629. 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.
GeneTreeiENSGT00760000119094.
HOGENOMiHOG000167616.
HOVERGENiHBG001846.
InParanoidiO00629.
OMAiTMRRQRT.
OrthoDBiEOG091G095Z.
PhylomeDBiO00629.
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.

O00629-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MADNEKLDNQ RLKNFKNKGR DLETMRRQRN EVVVELRKNK RDEHLLKRRN
60 70 80 90 100
VPHEDICEDS 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 MAEDEAETIG
460 470 480 490 500
NLIEECGGLE KIEQLQNHEN EDIYKLAYEI IDQFFSSDDI DEDPSLVPEA
510 520
IQGGTFGFNS SANVPTEGFQ F
Length:521
Mass (Da):57,887
Last modified:July 1, 1997 - v1
Checksum:iD98BC45002C9F57E
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti241 – 2411Q → T in CAA73025 (PubMed:9395085).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB002533 mRNA. Translation: BAA19546.1.
AK291041 mRNA. Translation: BAF83730.1.
CH471052 Genomic DNA. Translation: EAW78632.1.
CH471052 Genomic DNA. Translation: EAW78633.1.
U93240 mRNA. Translation: AAC25605.1.
Y12393 mRNA. Translation: CAA73025.1.
BC028691 mRNA. Translation: AAH28691.1.
BC034493 mRNA. Translation: AAH34493.1.
CCDSiCCDS3191.1.
PIRiJC5505.
RefSeqiNP_002259.1. NM_002268.4.
UniGeneiHs.467866.

Genome annotation databases

EnsembliENST00000334256; ENSP00000334373; ENSG00000186432.
GeneIDi3840.
KEGGihsa:3840.
UCSCiuc003fdn.3. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB002533 mRNA. Translation: BAA19546.1.
AK291041 mRNA. Translation: BAF83730.1.
CH471052 Genomic DNA. Translation: EAW78632.1.
CH471052 Genomic DNA. Translation: EAW78633.1.
U93240 mRNA. Translation: AAC25605.1.
Y12393 mRNA. Translation: CAA73025.1.
BC028691 mRNA. Translation: AAH28691.1.
BC034493 mRNA. Translation: AAH34493.1.
CCDSiCCDS3191.1.
PIRiJC5505.
RefSeqiNP_002259.1. NM_002268.4.
UniGeneiHs.467866.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4UAEX-ray2.70A68-487[»]
ProteinModelPortaliO00629.
SMRiO00629. Positions 11-51, 71-487.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110038. 83 interactions.
DIPiDIP-32982N.
IntActiO00629. 46 interactions.
MINTiMINT-5003750.
STRINGi9606.ENSP00000334373.

Protein family/group databases

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

PTM databases

iPTMnetiO00629.
PhosphoSiteiO00629.

Polymorphism and mutation databases

BioMutaiKPNA4.

Proteomic databases

EPDiO00629.
MaxQBiO00629.
PaxDbiO00629.
PeptideAtlasiO00629.
PRIDEiO00629.
TopDownProteomicsiO00629.

Protocols and materials databases

DNASUi3840.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000334256; ENSP00000334373; ENSG00000186432.
GeneIDi3840.
KEGGihsa:3840.
UCSCiuc003fdn.3. human.

Organism-specific databases

CTDi3840.
GeneCardsiKPNA4.
HGNCiHGNC:6397. KPNA4.
HPAiCAB034336.
HPA043154.
HPA045500.
MIMi602970. gene.
neXtProtiNX_O00629.
PharmGKBiPA30188.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0166. Eukaryota.
COG5064. LUCA.
GeneTreeiENSGT00760000119094.
HOGENOMiHOG000167616.
HOVERGENiHBG001846.
InParanoidiO00629.
OMAiTMRRQRT.
OrthoDBiEOG091G095Z.
PhylomeDBiO00629.
TreeFamiTF101178.

Enzyme and pathway databases

ReactomeiR-HSA-1169408. ISG15 antiviral mechanism.
R-HSA-168276. NS1 Mediated Effects on Host Pathways.
SignaLinkiO00629.
SIGNORiO00629.

Miscellaneous databases

ChiTaRSiKPNA4. human.
GeneWikiiKPNA4.
GenomeRNAii3840.
PMAP-CutDBO00629.
PROiO00629.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000186432.
CleanExiHS_KPNA4.
ExpressionAtlasiO00629. baseline and differential.
GenevisibleiO00629. 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. 3 hits.
PS51214. IBB. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiIMA3_HUMAN
AccessioniPrimary (citable) accession number: O00629
Secondary accession number(s): A8K4S6, D3DNM2, O00190
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: July 1, 1997
Last modified: September 7, 2016
This is version 164 of the entry and version 1 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

Caution

Was termed importin alpha-3.1 Publication

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. 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.