P52294 (IMA1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Importin subunit alpha-1

Alternative name(s):
Karyopherin subunit alpha-1
Nucleoprotein interactor 1
Short name=NPI-1
RAG cohort protein 2
SRP1-beta

Gene names

Name:	KPNA1
Synonyms:	RCH2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	538 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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.
Subunit structure	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). Ref.7 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.17 Ref.19
Subcellular location	Cytoplasm. Nucleus.
Tissue specificity	Expressed ubiquitously.
Domain	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. Ref.9 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. Ref.9 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. Ref.9
Post-translational modification	Polyubiquitinated in the presence of RAG1 (in vitro).
Sequence similarities	Belongs to the importin alpha family. Contains 10 ARM repeats. Contains 1 IBB domain.

Ontologies

Keywords
Biological process	Host-virus interaction Protein transport Transport
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Domain	Repeat
PTM	Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	NLS-bearing substrate import into nucleus Traceable author statement PubMed 7754385. Source: ProtInc apoptotic DNA fragmentation Traceable author statement. Source: Reactome cytokine-mediated signaling pathway Traceable author statement. Source: Reactome positive regulation of protein import into nucleus Inferred from sequence or structural similarity. Source: UniProtKB regulation of DNA recombination Traceable author statement Ref.7. Source: ProtInc viral infectious cycle Traceable author statement. Source: Reactome virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytosol Traceable author statement. Source: Reactome dendrite Inferred from sequence or structural similarity. Source: UniProtKB nuclear pore Traceable author statement Ref.7. Source: ProtInc nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	nuclear localization sequence binding Traceable author statement PubMed 7754385. Source: ProtInc protein transporter activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 538

538

Importin subunit alpha-1

PRO_0000120719

Regions

Domain

1 – 57

57

IBB

Repeat

77 – 117

41

ARM 1; truncated

Repeat

118 – 161

44

ARM 2

Repeat

162 – 206

45

ARM 3

Repeat

207 – 245

39

ARM 4

Repeat

246 – 290

45

ARM 5

Repeat

291 – 330

40

ARM 6

Repeat

331 – 372

42

ARM 7

Repeat

373 – 412

40

ARM 8

Repeat

413 – 457

45

ARM 9

Repeat

460 – 504

45

ARM 10; atypical

Region

149 – 241

93

NLS binding site (major) By similarity

Region

245 – 437

193

Binding to RAG1

Region

318 – 406

89

NLS binding site (minor) By similarity

Motif

42 – 51

10

Nuclear localization signal By similarity

Compositional bias

25 – 28

4

Poly-Arg

Amino acid modifications

Modified residue

3

1

Phosphothreonine By similarity

Natural variations

Natural variant

73

1

S → N. Ref.2 Ref.3 Ref.5 Ref.6
Corresponds to variant rs4678193 [ dbSNP | Ensembl ].

VAR_050002

Experimental info

Sequence conflict

142

1

T → S in AAC60648. Ref.1

Sequence conflict

169

1

G → R in AAC60648. Ref.1

Secondary structure

1

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538

Helix Strand Turn

Details...

Helix

85 – 92

8

Helix

96 – 111

16

Beta strand

112 – 115

4

Helix

118 – 122

5

Helix

127 – 135

9

Helix

141 – 155

15

Helix

159 – 167

9

Helix

170 – 177

8

Helix

183 – 197

15

Helix

201 – 209

9

Helix

213 – 219

7

Helix

226 – 240

15

Beta strand

243 – 245

3

Helix

249 – 251

3

Helix

253 – 255

3

Helix

256 – 262

7

Helix

268 – 281

14

Beta strand

283 – 285

3

Helix

286 – 294

9

Turn

295 – 297

3

Helix

298 – 304

7

Helix

310 – 323

14

Helix

328 – 335

8

Turn

336 – 338

3

Helix

339 – 346

8

Helix

352 – 365

14

Helix

370 – 378

9

Helix

381 – 391

11

Helix

394 – 410

17

Helix

413 – 422

10

Helix

425 – 430

6

Helix

431 – 433

3

Helix

437 – 460

24

Beta strand

461 – 463

3

Helix

468 – 476

9

Helix

478 – 485

8

Helix

487 – 504

18

Sequences

	Sequence		Length	Mass (Da)
	P52294 [UniParc]. Last modified May 18, 2010. Version 3. Checksum: E8407A3352D6051C	FASTA	538	60,222
	10 20 30 40 50 60 MTTPGKENFR LKSYKNKSLN PDEMRRRREE EGLQLRKQKR EEQLFKRRNV ATAEEETEEE 70 80 90 100 110 120 VMSDGGFHEA QISNMEMAPG GVITSDMIEM IFSKSPEQQL SATQKFRKLL SKEPNPPIDE 130 140 150 160 170 180 VISTPGVVAR FVEFLKRKEN CTLQFESAWV LTNIASGNSL QTRIVIQAGA VPIFIELLSS 190 200 210 220 230 240 EFEDVQEQAV WALGNIAGDS TMCRDYVLDC NILPPLLQLF SKQNRLTMTR NAVWALSNLC 250 260 270 280 290 300 RGKSPPPEFA KVSPCLNVLS WLLFVSDTDV LADACWALSY LSDGPNDKIQ AVIDAGVCRR 310 320 330 340 350 360 LVELLMHNDY KVVSPALRAV GNIVTGDDIQ TQVILNCSAL QSLLHLLSSP KESIKKEACW 370 380 390 400 410 420 TISNITAGNR AQIQTVIDAN IFPALISILQ TAEFRTRKEA AWAITNATSG GSAEQIKYLV 430 440 450 460 470 480 ELGCIKPLCD LLTVMDSKIV QVALNGLENI LRLGEQEAKR NGTGINPYCA LIEEAYGLDK 490 500 510 520 530 IEFLQSHENQ EIYQKAFDLI EHYFGTEDED SSIAPQVDLN QQQYIFQQCE APMEGFQL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"NPI-1, the human homolog of SRP-1, interacts with influenza virus nucleoprotein." O'Neill R.E., Palese P. Virology 206:116-125(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ASN-73.
[3]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ASN-73.
[4]	"The DNA sequence, annotation and analysis of human chromosome 3." Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A. Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT ASN-73.
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ASN-73. Tissue: Lung.
[7]	"RAG-1 interacts with the repeated amino acid motif of the human homologue of the yeast protein SRP1." Cortes P., Ye Z.-S., Baltimore D. Proc. Natl. Acad. Sci. U.S.A. 91:7633-7637(1994) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RAG1.
[8]	"Previously identified protein of uncertain function is karyopherin alpha and together with karyopherin beta docks import substrate at nuclear pore complexes." Moroianu J., Blobel G., Radu A. Proc. Natl. Acad. Sci. U.S.A. 92:2008-2011(1995) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION.
[9]	"The binding site of karyopherin alpha for karyopherin beta overlaps with a nuclear localization sequence." Moroianu J., Blobel G., Radu A. Proc. Natl. Acad. Sci. U.S.A. 93:6572-6576(1996) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 481-495, DOMAINS IBB.
[10]	"Mammalian karyopherin alpha 1 beta and alpha 2 beta heterodimers: alpha 1 or alpha 2 subunit binds nuclear localization signal and beta subunit interacts with peptide repeat-containing nucleoporins." Moroianu J., Hijikata M., Blobel G., Radu A. Proc. Natl. Acad. Sci. U.S.A. 92:6532-6536(1995) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCALIZATION, SUBUNIT.
[11]	"Viral protein R regulates nuclear import of the HIV-1 pre-integration complex." Popov S., Rexach M., Zybarth G., Reiling N., Lee M.A., Ratner L., Lane C.M., Moore M.S., Blobel G., Bukrinsky M. EMBO J. 17:909-917(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HIV-1 VPR.
[12]	"A nonconventional nuclear localization signal within the UL84 protein of human cytomegalovirus mediates nuclear import via the importin alpha/beta pathway." Lischka P., Sorg G., Kann M., Winkler M., Stamminger T. J. Virol. 77:3734-3748(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HCMV UL84.
[13]	"Analysis of nuclear transport signals in the human apurinic/apyrimidinic endonuclease (APE1/Ref1)." Jackson E.B., Theriot C.A., Chattopadhyay R., Mitra S., Izumi T. Nucleic Acids Res. 33:3303-3312(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH APEX1.
[14]	"Ebola virus VP24 binds karyopherin alpha-1 and blocks STAT1 nuclear accumulation." Reid S.P., Leung L.W., Hartman A.L., Martinez O., Shaw M.L., Carbonnelle C., Volchkov V.E., Nichol S.T., Basler C.F. J. Virol. 80:5156-5167(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH EBOLAVIRUS VP24.
[15]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[16]	"Karyopherin alpha 1 is a putative substrate of the RAG1 ubiquitin ligase." Simkus C., Makiya M., Jones J.M. Mol. Immunol. 46:1319-1325(2009) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION.
[17]	"Importin alpha protein acts as a negative regulator for Snail protein nuclear import." Sekimoto T., Miyamoto Y., Arai S., Yoneda Y. J. Biol. Chem. 286:15126-15131(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SNAI1.
[18]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[19]	"CTNNBL1 is a novel nuclear localization sequence-binding protein that recognizes RNA-splicing factors CDC5L and Prp31." Ganesh K., Adam S., Taylor B., Simpson P., Rada C., Neuberger M. J. Biol. Chem. 286:17091-17102(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CTNNBL1 AND AICDA.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00303292.

PIR

I59931.

RefSeq

NP_002255.3. NM_002264.3.

UniGene

Hs.161008.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2JDQ	X-ray	2.20	A/B	66-512	[»]
3TJ3	X-ray	2.70	A/B	66-512	[»]

ProteinModelPortal

P52294.

SMR

P52294. Positions 10-509.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29296N.

IntAct

P52294. 19 interactions.

MINT

MINT-240027.

STRING

9606.ENSP00000343701.

PTM databases

PhosphoSite

P52294.

Polymorphism databases

DMDM

296439328.

Proteomic databases

PaxDb

P52294.

PRIDE

P52294.

Protocols and materials databases

DNASU

3836.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000344337; ENSP00000343701; ENSG00000114030.

GeneID

3836.

KEGG

hsa:3836.

UCSC

uc003efb.1. human.

Organism-specific databases

CTD

3836.

GeneCards

GC03M122140.

HGNC

HGNC:6394. KPNA1.

HPA

HPA053627.

MIM

600686. gene.

neXtProt

NX_P52294.

PharmGKB

PA30185.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5064.

HOGENOM

HOG000167616.

HOVERGEN

HBG001846.

InParanoid

P52294.

KO

K15042.

OMA

ETEPNPP.

OrthoDB

EOG4QNMVZ.

PhylomeDB

P52294.

Enzyme and pathway databases

Pathway_Interaction_DB

pi3kciaktpathway. Class I PI3K signaling events mediated by Akt.

Reactome

REACT_116125. Disease.
REACT_578. Apoptosis.
REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P52294.

Bgee

P52294.

CleanEx

HS_KPNA1.

Genevestigator

P52294.

GermOnline

ENSG00000114030. Homo sapiens.

Family and domain databases

Gene3D

1.25.10.10. 1 hit.

InterPro

IPR011989. ARM-like.
IPR016024. ARM-type_fold.
IPR000225. Armadillo.
IPR002652. Importin-a_IBB.
IPR024931. Importing_su_alpha.
[Graphical view]

Pfam

PF00514. Arm. 8 hits.
PF01749. IBB. 1 hit.
[Graphical view]

PIRSF

PIRSF005673. Importin_alpha. 1 hit.

SMART

SM00185. ARM. 8 hits.
[Graphical view]

SUPFAM

SSF48371. ARM-type_fold. 1 hit.

PROSITE

PS50176. ARM_REPEAT. 4 hits.
PS51214. IBB. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P52294.

GenomeRNAi

3836.

NextBio

15079.

PMAP-CutDB

P52294.

SOURCE

Search...

Entry information

Entry name

IMA1_HUMAN

Accession

Primary (citable) accession number: P52294
Secondary accession number(s): D3DN93, Q6IBQ9, Q9BQ56

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	May 18, 2010
Last modified:	May 1, 2013
This is version 140 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.