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Protein

Importin subunit alpha-5

Gene

KPNA1

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.

GO - Molecular functioni

  • nuclear localization sequence binding Source: ProtInc
  • protein transporter activity Source: GO_Central

GO - Biological processi

  • apoptotic DNA fragmentation Source: Reactome
  • intracellular transport of virus Source: Reactome
  • modulation by virus of host process Source: Reactome
  • NLS-bearing protein import into nucleus Source: ProtInc
  • regulation of DNA recombination Source: ProtInc
Complete GO annotation...

Keywords - Biological processi

Host-virus interaction, Protein transport, Transport

Enzyme and pathway databases

ReactomeiR-HSA-1169408. ISG15 antiviral mechanism.
R-HSA-162592. Integration of provirus.
R-HSA-168271. Transport of Ribonucleoproteins into the Host Nucleus.
R-HSA-168276. NS1 Mediated Effects on Host Pathways.
R-HSA-180910. Vpr-mediated nuclear import of PICs.
R-HSA-211227. Activation of DNA fragmentation factor.
SignaLinkiP52294.

Protein family/group databases

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

Names & Taxonomyi

Protein namesi
Recommended name:
Importin subunit alpha-5
Alternative name(s):
Karyopherin subunit alpha-1
Nucleoprotein interactor 1
Short name:
NPI-1
RAG cohort protein 2
SRP1-beta
Cleaved into the following chain:
Gene namesi
Name:KPNA1
Synonyms:RCH2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:6394. KPNA1.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: HPA
  • cytosol Source: GO_Central
  • dendrite Source: UniProtKB
  • nuclear pore Source: ProtInc
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA30185.

Polymorphism and mutation databases

BioMutaiKPNA1.
DMDMi296439328.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 538538Importin subunit alpha-5PRO_0000120719Add
BLAST
Initiator methionineiRemoved; alternateCombined sources
Chaini2 – 538537Importin subunit alpha-5, N-terminally processedPRO_0000424491Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionineCombined sources
Modified residuei2 – 21N-acetylthreonine; in Importin subunit alpha-5, N-terminally processedCombined sources
Modified residuei3 – 31PhosphothreonineCombined sources
Modified residuei63 – 631PhosphoserineCombined sources

Post-translational modificationi

Polyubiquitinated in the presence of RAG1 (in vitro).1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP52294.
MaxQBiP52294.
PaxDbiP52294.
PeptideAtlasiP52294.
PRIDEiP52294.

PTM databases

iPTMnetiP52294.
PhosphoSiteiP52294.

Miscellaneous databases

PMAP-CutDBP52294.

Expressioni

Tissue specificityi

Expressed ubiquitously.

Gene expression databases

BgeeiENSG00000114030.
CleanExiHS_KPNA1.
ExpressionAtlasiP52294. baseline and differential.
GenevisibleiP52294. HS.

Organism-specific databases

HPAiHPA053627.
HPA063426.

Interactioni

Subunit structurei

Heterodimer; with KPNB1. Interacts with ANP32E. Interacts with ZIC3 (By similarity). Interacts with NSMF; the interaction occurs in a calcium-independent manner after synaptic NMDA receptor stimulation and is required for nuclear import of NSMF but is competed by CABP1 (By similarity). Interacts with the nucleoprotein of influenza A viruses. Binds to HCMV (human cytomegalovirus) UL84, HIV-1 Vpr and to ebolavirus VP24. Interacts with APEX1 and RAG1. Interacts with CTNNBL1 (via its N-terminal). Interacts with AICDA (via its NLS). Interacts with SNAI1 (via zinc fingers). Interacts with DCAF8.By similarity9 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Q9WMX22EBI-358383,EBI-6863741From a different organism.
ANP32BQ926885EBI-358383,EBI-762428
CLK4Q9HAZ13EBI-358383,EBI-633400
DCAF8Q5TAQ92EBI-358383,EBI-740686
GRM1Q132552EBI-358383,EBI-8527352
NUP50Q9UKX74EBI-358383,EBI-2371082
PB2B4URF72EBI-358383,EBI-6050648From a different organism.
SF1Q156373EBI-358383,EBI-744603
TAF9Q165944EBI-358383,EBI-712521

Protein-protein interaction databases

BioGridi110034. 107 interactions.
DIPiDIP-29296N.
IntActiP52294. 70 interactions.
MINTiMINT-240027.
STRINGi9606.ENSP00000343701.

Structurei

Secondary structure

1
538
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi85 – 928Combined sources
Helixi96 – 11116Combined sources
Beta strandi112 – 1154Combined sources
Helixi118 – 1225Combined sources
Helixi127 – 1359Combined sources
Helixi141 – 15515Combined sources
Helixi159 – 1679Combined sources
Helixi170 – 1778Combined sources
Helixi183 – 19715Combined sources
Helixi201 – 2099Combined sources
Helixi213 – 2197Combined sources
Helixi226 – 24015Combined sources
Beta strandi243 – 2453Combined sources
Helixi249 – 2513Combined sources
Helixi253 – 2553Combined sources
Helixi256 – 2627Combined sources
Helixi268 – 28114Combined sources
Beta strandi283 – 2853Combined sources
Helixi286 – 2949Combined sources
Turni295 – 2973Combined sources
Helixi298 – 3047Combined sources
Helixi310 – 32314Combined sources
Helixi328 – 3358Combined sources
Turni336 – 3383Combined sources
Helixi339 – 3468Combined sources
Helixi352 – 36514Combined sources
Helixi370 – 3789Combined sources
Helixi381 – 39111Combined sources
Helixi394 – 41017Combined sources
Helixi413 – 42210Combined sources
Helixi425 – 4306Combined sources
Helixi431 – 4333Combined sources
Helixi437 – 46024Combined sources
Beta strandi461 – 4633Combined sources
Helixi468 – 4769Combined sources
Helixi478 – 4858Combined sources
Helixi487 – 50418Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2JDQX-ray2.20A/B66-512[»]
3TJ3X-ray2.70A/B66-512[»]
4B18X-ray2.52A66-512[»]
ProteinModelPortaliP52294.
SMRiP52294. Positions 10-509.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP52294.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini1 – 5757IBBPROSITE-ProRule annotationAdd
BLAST
Repeati77 – 11741ARM 1; truncatedAdd
BLAST
Repeati118 – 16144ARM 2Add
BLAST
Repeati162 – 20645ARM 3Add
BLAST
Repeati207 – 24539ARM 4Add
BLAST
Repeati246 – 29045ARM 5Add
BLAST
Repeati291 – 33040ARM 6Add
BLAST
Repeati331 – 37242ARM 7Add
BLAST
Repeati373 – 41240ARM 8Add
BLAST
Repeati413 – 45745ARM 9Add
BLAST
Repeati460 – 50445ARM 10; atypicalAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni149 – 24193NLS binding site (major)By similarityAdd
BLAST
Regioni245 – 437193Binding to RAG1Add
BLAST
Regioni318 – 40689NLS binding site (minor)By similarityAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi42 – 5110Nuclear localization signalBy similarity

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi25 – 284Poly-Arg

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
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.
InParanoidiP52294.
KOiK15042.
OMAiWNCESES.
OrthoDBiEOG091G095Z.
PhylomeDBiP52294.
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. 4 hits.
PS51214. IBB. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

P52294-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTTPGKENFR LKSYKNKSLN PDEMRRRREE EGLQLRKQKR EEQLFKRRNV
60 70 80 90 100
ATAEEETEEE VMSDGGFHEA QISNMEMAPG GVITSDMIEM IFSKSPEQQL
110 120 130 140 150
SATQKFRKLL SKEPNPPIDE VISTPGVVAR FVEFLKRKEN CTLQFESAWV
160 170 180 190 200
LTNIASGNSL QTRIVIQAGA VPIFIELLSS EFEDVQEQAV WALGNIAGDS
210 220 230 240 250
TMCRDYVLDC NILPPLLQLF SKQNRLTMTR NAVWALSNLC RGKSPPPEFA
260 270 280 290 300
KVSPCLNVLS WLLFVSDTDV LADACWALSY LSDGPNDKIQ AVIDAGVCRR
310 320 330 340 350
LVELLMHNDY KVVSPALRAV GNIVTGDDIQ TQVILNCSAL QSLLHLLSSP
360 370 380 390 400
KESIKKEACW TISNITAGNR AQIQTVIDAN IFPALISILQ TAEFRTRKEA
410 420 430 440 450
AWAITNATSG GSAEQIKYLV ELGCIKPLCD LLTVMDSKIV QVALNGLENI
460 470 480 490 500
LRLGEQEAKR NGTGINPYCA LIEEAYGLDK IEFLQSHENQ EIYQKAFDLI
510 520 530
EHYFGTEDED SSIAPQVDLN QQQYIFQQCE APMEGFQL
Length:538
Mass (Da):60,222
Last modified:May 18, 2010 - v3
Checksum:iE8407A3352D6051C
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti142 – 1421T → S in AAC60648 (PubMed:7831767).Curated
Sequence conflicti169 – 1691G → R in AAC60648 (PubMed:7831767).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti73 – 731S → N.4 Publications
Corresponds to variant rs4678193 [ dbSNP | Ensembl ].
VAR_050002

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S75295 mRNA. Translation: AAC60648.1.
BT006959 mRNA. Translation: AAP35605.1.
CR456743 mRNA. Translation: CAG33024.1.
AC083798 Genomic DNA. No translation available.
AC096861 Genomic DNA. No translation available.
CH471052 Genomic DNA. Translation: EAW79482.1.
CH471052 Genomic DNA. Translation: EAW79483.1.
BC002374 mRNA. Translation: AAH02374.1.
BC003009 mRNA. Translation: AAH03009.1.
CCDSiCCDS3013.1.
PIRiI59931.
RefSeqiNP_002255.3. NM_002264.3.
XP_005247494.1. XM_005247437.3.
UniGeneiHs.161008.

Genome annotation databases

EnsembliENST00000344337; ENSP00000343701; ENSG00000114030.
GeneIDi3836.
KEGGihsa:3836.
UCSCiuc003efe.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S75295 mRNA. Translation: AAC60648.1.
BT006959 mRNA. Translation: AAP35605.1.
CR456743 mRNA. Translation: CAG33024.1.
AC083798 Genomic DNA. No translation available.
AC096861 Genomic DNA. No translation available.
CH471052 Genomic DNA. Translation: EAW79482.1.
CH471052 Genomic DNA. Translation: EAW79483.1.
BC002374 mRNA. Translation: AAH02374.1.
BC003009 mRNA. Translation: AAH03009.1.
CCDSiCCDS3013.1.
PIRiI59931.
RefSeqiNP_002255.3. NM_002264.3.
XP_005247494.1. XM_005247437.3.
UniGeneiHs.161008.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2JDQX-ray2.20A/B66-512[»]
3TJ3X-ray2.70A/B66-512[»]
4B18X-ray2.52A66-512[»]
ProteinModelPortaliP52294.
SMRiP52294. Positions 10-509.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110034. 107 interactions.
DIPiDIP-29296N.
IntActiP52294. 70 interactions.
MINTiMINT-240027.
STRINGi9606.ENSP00000343701.

Protein family/group databases

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

PTM databases

iPTMnetiP52294.
PhosphoSiteiP52294.

Polymorphism and mutation databases

BioMutaiKPNA1.
DMDMi296439328.

Proteomic databases

EPDiP52294.
MaxQBiP52294.
PaxDbiP52294.
PeptideAtlasiP52294.
PRIDEiP52294.

Protocols and materials databases

DNASUi3836.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000344337; ENSP00000343701; ENSG00000114030.
GeneIDi3836.
KEGGihsa:3836.
UCSCiuc003efe.3. human.

Organism-specific databases

CTDi3836.
GeneCardsiKPNA1.
HGNCiHGNC:6394. KPNA1.
HPAiHPA053627.
HPA063426.
MIMi600686. gene.
neXtProtiNX_P52294.
PharmGKBiPA30185.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0166. Eukaryota.
COG5064. LUCA.
GeneTreeiENSGT00760000119094.
HOGENOMiHOG000167616.
HOVERGENiHBG001846.
InParanoidiP52294.
KOiK15042.
OMAiWNCESES.
OrthoDBiEOG091G095Z.
PhylomeDBiP52294.
TreeFamiTF354205.

Enzyme and pathway databases

ReactomeiR-HSA-1169408. ISG15 antiviral mechanism.
R-HSA-162592. Integration of provirus.
R-HSA-168271. Transport of Ribonucleoproteins into the Host Nucleus.
R-HSA-168276. NS1 Mediated Effects on Host Pathways.
R-HSA-180910. Vpr-mediated nuclear import of PICs.
R-HSA-211227. Activation of DNA fragmentation factor.
SignaLinkiP52294.

Miscellaneous databases

ChiTaRSiKPNA1. human.
EvolutionaryTraceiP52294.
GeneWikiiKaryopherin_alpha_1.
GenomeRNAii3836.
PMAP-CutDBP52294.
PROiP52294.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000114030.
CleanExiHS_KPNA1.
ExpressionAtlasiP52294. baseline and differential.
GenevisibleiP52294. 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. 4 hits.
PS51214. IBB. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiIMA5_HUMAN
AccessioniPrimary (citable) accession number: P52294
Secondary accession number(s): D3DN93, Q6IBQ9, Q9BQ56
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: May 18, 2010
Last modified: September 7, 2016
This is version 177 of the entry and version 3 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, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: 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.