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Protein

Importin subunit alpha-5

Gene

KPNA1

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

GO - Molecular functioni

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

Keywordsi

Biological processHost-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 eukaryotic nuclear pore complex (e-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

EuPathDBiHostDB:ENSG00000114030.12
HGNCiHGNC:6394 KPNA1
MIMi600686 gene
neXtProtiNX_P52294

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

DisGeNETi3836
OpenTargetsiENSG00000114030
PharmGKBiPA30185

Polymorphism and mutation databases

BioMutaiKPNA1
DMDMi296439328

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001207191 – 538Importin subunit alpha-5Add BLAST538
Initiator methionineiRemoved; alternateCombined sources
ChainiPRO_00004244912 – 538Importin subunit alpha-5, N-terminally processedAdd BLAST537

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei2N-acetylthreonine; in Importin subunit alpha-5, N-terminally processedCombined sources1
Modified residuei3PhosphothreonineCombined sources1
Modified residuei63PhosphoserineCombined sources1

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
ProteomicsDBi56476

PTM databases

iPTMnetiP52294
PhosphoSitePlusiP52294

Miscellaneous databases

PMAP-CutDBiP52294

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 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 similarity6 Publications
(Microbial infection) Interacts with human cytomegalovirus/HCMV UL84.1 Publication
(Microbial infection) Interacts with HIV-1 Vpr.1 Publication
(Microbial infection) Interacts with ebolavirus protein VP24.1 Publication

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi110034, 127 interactors
ComplexPortaliCPX-1055 Importin complex, KPNA1 variant
CORUMiP52294
DIPiDIP-29296N
ELMiP52294
IntActiP52294, 95 interactors
MINTiP52294
STRINGi9606.ENSP00000343701

Structurei

Secondary structure

1538
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi85 – 92Combined sources8
Helixi96 – 111Combined sources16
Beta strandi112 – 115Combined sources4
Helixi118 – 122Combined sources5
Helixi127 – 135Combined sources9
Helixi141 – 155Combined sources15
Helixi159 – 167Combined sources9
Helixi170 – 177Combined sources8
Helixi183 – 197Combined sources15
Helixi201 – 209Combined sources9
Helixi213 – 219Combined sources7
Helixi226 – 240Combined sources15
Beta strandi243 – 245Combined sources3
Helixi249 – 251Combined sources3
Helixi253 – 255Combined sources3
Helixi256 – 262Combined sources7
Helixi268 – 281Combined sources14
Beta strandi283 – 285Combined sources3
Helixi286 – 294Combined sources9
Turni295 – 297Combined sources3
Helixi298 – 304Combined sources7
Helixi310 – 323Combined sources14
Helixi328 – 335Combined sources8
Turni336 – 338Combined sources3
Helixi339 – 346Combined sources8
Helixi352 – 365Combined sources14
Helixi370 – 378Combined sources9
Helixi381 – 391Combined sources11
Helixi394 – 410Combined sources17
Helixi413 – 422Combined sources10
Helixi425 – 430Combined sources6
Helixi431 – 433Combined sources3
Helixi437 – 460Combined sources24
Beta strandi461 – 463Combined sources3
Helixi468 – 476Combined sources9
Helixi478 – 485Combined sources8
Helixi487 – 504Combined sources18

3D structure databases

ProteinModelPortaliP52294
SMRiP52294
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP52294

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 57IBBPROSITE-ProRule annotationAdd BLAST57
Repeati77 – 117ARM 1; truncatedAdd BLAST41
Repeati118 – 161ARM 2Add BLAST44
Repeati162 – 206ARM 3Add BLAST45
Repeati207 – 245ARM 4Add BLAST39
Repeati246 – 290ARM 5Add BLAST45
Repeati291 – 330ARM 6Add BLAST40
Repeati331 – 372ARM 7Add BLAST42
Repeati373 – 412ARM 8Add BLAST40
Repeati413 – 457ARM 9Add BLAST45
Repeati460 – 504ARM 10; atypicalAdd BLAST45

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni149 – 241NLS binding site (major)By similarityAdd BLAST93
Regioni245 – 437Binding to RAG1Add BLAST193
Regioni318 – 406NLS 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.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
InParanoidiP52294
KOiK15042
OMAiSWLLFVN
OrthoDBiEOG091G095Z
PhylomeDBiP52294
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, 4 hits
PS51214 IBB, 1 hit

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)DescriptionActionsGraphical viewLength
Sequence conflicti142T → S in AAC60648 (PubMed:7831767).Curated1
Sequence conflicti169G → R in AAC60648 (PubMed:7831767).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05000273S → N4 PublicationsCorresponds to variant dbSNP:rs4678193Ensembl.1

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

Similar proteinsi

Entry informationi

Entry nameiIMA5_HUMAN
AccessioniPrimary (citable) accession number: P52294
Secondary accession number(s): D3DN93, Q6IBQ9, Q9BQ56
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: May 18, 2010
Last modified: July 18, 2018
This is version 196 of the entry and version 3 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 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

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