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Protein

Importin subunit alpha-1

Gene

KPNA2

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.

GO - Molecular functioni

  • histone deacetylase binding Source: BHF-UCL
  • nuclear import signal receptor activity Source: InterPro
  • nuclear localization sequence binding Source: UniProtKB
  • protein transporter activity Source: GO_Central
  • RNA binding Source: UniProtKB

GO - Biological processi

  • DNA metabolic process Source: ProtInc
  • modulation by virus of host process Source: Reactome
  • NLS-bearing protein import into nucleus Source: UniProtKB
  • regulation of DNA recombination Source: ProtInc

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
R-HSA-5693548 Sensing of DNA Double Strand Breaks
R-HSA-9018519 Estrogen-dependent gene expression
SignaLinkiP52292
SIGNORiP52292

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-1
Alternative name(s):
Karyopherin subunit alpha-2
RAG cohort protein 1
SRP1-alpha
Gene namesi
Name:KPNA2
Synonyms:RCH1, SRP1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000182481.8
HGNCiHGNC:6395 KPNA2
MIMi600685 gene
neXtProtiNX_P52292

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

DisGeNETi3838
OpenTargetsiENSG00000182481
PharmGKBiPA30186

Chemistry databases

ChEMBLiCHEMBL1741187

Polymorphism and mutation databases

BioMutaiKPNA2
DMDMi1708480

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources1 Publication
ChainiPRO_00001207222 – 529Importin subunit alpha-1Add BLAST528

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineCombined sources1 Publication1
Modified residuei62PhosphoserineCombined sources1
Modified residuei490PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP52292
MaxQBiP52292
PaxDbiP52292
PeptideAtlasiP52292
PRIDEiP52292

2D gel databases

SWISS-2DPAGEiP52292

PTM databases

iPTMnetiP52292
PhosphoSitePlusiP52292
SwissPalmiP52292

Expressioni

Tissue specificityi

Expressed ubiquitously.

Gene expression databases

BgeeiENSG00000182481
CleanExiHS_KPNA2
ExpressionAtlasiP52292 baseline and differential
GenevisibleiP52292 HS

Organism-specific databases

HPAiCAB015460
HPA041270

Interactioni

Subunit structurei

Heterodimer; with KPNB1. Interacts with ANP32E (By similarity). Component of a complex containing CSE1L, RAN and KPNA2. Interacts directly with CSE1L. Interacts with HIV-1 Vpr and PLAG1. Interacts with APEX1 (via N-terminus). Interacts with FRG1 (via N-terminus). Interacts with ARL4A, CTNNBL1 and NBN. Interacts with SNAI1 (via zinc fingers) and SNAI2 (via zinc fingers).By similarity12 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • histone deacetylase binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi110036, 201 interactors
CORUMiP52292
DIPiDIP-6205N
IntActiP52292, 134 interactors
MINTiP52292
STRINGi9606.ENSP00000332455

Chemistry databases

BindingDBiP52292

Structurei

Secondary structure

1529
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi14 – 16Combined sources3
Turni18 – 21Combined sources4
Helixi30 – 48Combined sources19
Helixi74 – 85Combined sources12
Helixi90 – 104Combined sources15
Beta strandi106 – 108Combined sources3
Helixi112 – 117Combined sources6
Helixi121 – 128Combined sources8
Helixi134 – 148Combined sources15
Helixi152 – 160Combined sources9
Helixi163 – 170Combined sources8
Helixi176 – 190Combined sources15
Helixi194 – 202Combined sources9
Helixi206 – 213Combined sources8
Beta strandi214 – 216Combined sources3
Helixi218 – 220Combined sources3
Helixi223 – 236Combined sources14
Helixi246 – 259Combined sources14
Helixi265 – 278Combined sources14
Helixi283 – 290Combined sources8
Turni291 – 293Combined sources3
Helixi295 – 302Combined sources8
Helixi307 – 320Combined sources14
Helixi325 – 333Combined sources9
Helixi336 – 339Combined sources4
Helixi340 – 344Combined sources5
Helixi349 – 362Combined sources14
Helixi367 – 375Combined sources9
Helixi379 – 388Combined sources10
Helixi391 – 407Combined sources17
Helixi410 – 418Combined sources9
Helixi422 – 427Combined sources6
Helixi428 – 430Combined sources3
Helixi434 – 454Combined sources21
Helixi457 – 466Combined sources10
Helixi469 – 475Combined sources7
Helixi476 – 478Combined sources3
Helixi479 – 481Combined sources3
Helixi482 – 495Combined sources14

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1EFXX-ray3.00C204-212[»]
1QGKX-ray2.50B11-54[»]
1QGRX-ray2.30B28-54[»]
3FEXX-ray3.55C70-529[»]
3FEYX-ray2.20C70-529[»]
3WPTX-ray2.63A/B75-497[»]
4E4VX-ray2.53A/B70-529[»]
4WV6X-ray1.75A60-529[»]
5H43X-ray2.30A70-497[»]
ProteinModelPortaliP52292
SMRiP52292
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP52292

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini2 – 60IBBPROSITE-ProRule annotationAdd BLAST59
Repeati71 – 111ARM 1; truncatedAdd BLAST41
Repeati112 – 151ARM 2Add BLAST40
Repeati152 – 193ARM 3Add BLAST42
Repeati200 – 244ARM 4Add BLAST45
Repeati246 – 282ARM 5Add BLAST37
Repeati283 – 322ARM 6Add BLAST40
Repeati325 – 364ARM 7Add BLAST40
Repeati367 – 409ARM 8Add BLAST43
Repeati410 – 456ARM 9Add BLAST47
Repeati457 – 496ARM 10; atypicalAdd BLAST40

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni142 – 238NLS binding site (major)By similarityAdd BLAST97
Regioni315 – 403NLS binding site (minor)By similarityAdd BLAST89

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi45 – 54Nuclear localization signalBy similarity10

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi28 – 31Poly-Arg4
Compositional biasi499 – 502Poly-Glu4

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.1 Publication
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
InParanoidiP52292
KOiK15043
OMAiDQTRCVI
OrthoDBiEOG091G095Z
PhylomeDBiP52292
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, 5 hits
PS51214 IBB, 1 hit

Sequencei

Sequence statusi: Complete.

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

P52292-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSTNENANTP AARLHRFKNK GKDSTEMRRR RIEVNVELRK AKKDDQMLKR
60 70 80 90 100
RNVSSFPDDA TSPLQENRNN QGTVNWSVDD IVKGINSSNV ENQLQATQAA
110 120 130 140 150
RKLLSREKQP PIDNIIRAGL IPKFVSFLGR TDCSPIQFES AWALTNIASG
160 170 180 190 200
TSEQTKAVVD GGAIPAFISL LASPHAHISE QAVWALGNIA GDGSVFRDLV
210 220 230 240 250
IKYGAVDPLL ALLAVPDMSS LACGYLRNLT WTLSNLCRNK NPAPPIDAVE
260 270 280 290 300
QILPTLVRLL HHDDPEVLAD TCWAISYLTD GPNERIGMVV KTGVVPQLVK
310 320 330 340 350
LLGASELPIV TPALRAIGNI VTGTDEQTQV VIDAGALAVF PSLLTNPKTN
360 370 380 390 400
IQKEATWTMS NITAGRQDQI QQVVNHGLVP FLVSVLSKAD FKTQKEAVWA
410 420 430 440 450
VTNYTSGGTV EQIVYLVHCG IIEPLMNLLT AKDTKIILVI LDAISNIFQA
460 470 480 490 500
AEKLGETEKL SIMIEECGGL DKIEALQNHE NESVYKASLS LIEKYFSVEE
510 520
EEDQNVVPET TSEGYTFQVQ DGAPGTFNF
Length:529
Mass (Da):57,862
Last modified:October 1, 1996 - v1
Checksum:iB0F94A0475B80EED
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti182A → D in AAH67848 (PubMed:15489334).Curated1

Mass spectrometryi

Molecular mass is 57861.92 Da from positions 1 - 529. Determined by MALDI. 1 Publication

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_067625157A → V2 PublicationsCorresponds to variant dbSNP:rs17850032Ensembl.1
Natural variantiVAR_013137165P → R2 PublicationsCorresponds to variant dbSNP:rs11545989Ensembl.1
Natural variantiVAR_067626365G → S. Corresponds to variant dbSNP:rs1059558Ensembl.1
Natural variantiVAR_067627453K → N2 PublicationsCorresponds to variant dbSNP:rs17850031Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U28386 mRNA Translation: AAA69957.1
AJ303086 Genomic DNA Translation: CAC83080.1
BT006665 mRNA Translation: AAP35311.1
CH471099 Genomic DNA Translation: EAW89041.1
BC005978 mRNA Translation: AAH05978.1
BC067848 mRNA Translation: AAH67848.1
BC146905 mRNA Translation: AAI46906.1
U09559 mRNA Translation: AAA65700.1
CCDSiCCDS32713.1
PIRiA56516
RefSeqiNP_001307540.1, NM_001320611.1
NP_002257.1, NM_002266.3
UniGeneiHs.594238

Genome annotation databases

EnsembliENST00000330459; ENSP00000332455; ENSG00000182481
ENST00000537025; ENSP00000438483; ENSG00000182481
GeneIDi3838
KEGGihsa:3838
UCSCiuc002jgk.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiIMA1_HUMAN
AccessioniPrimary (citable) accession number: P52292
Secondary accession number(s): B9EJD6
, Q53YE3, Q6NVW7, Q9BRU5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: May 23, 2018
This is version 212 of the entry and version 1 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, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: 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

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