CPLM-008484

Genbank Nucleotide ID

Importin subunit alpha-1

Protein Synonyms/Alias

Karyopherin subunit alpha-2; RAG cohort protein 1; SRP1-alpha

Homo sapiens (Human)

Position	Peptide	Type	References
22	HRFKNKGKDSTEMRR	acetylation	[1]
83	WSVDDIVKGINSSNV	ubiquitination	[2, 3, 4, 5]
108	RKLLSREKQPPIDNI	ubiquitination	[3, 4, 5, 6]
123	IRAGLIPKFVSFLGR	ubiquitination	[2, 4, 6]
240	LSNLCRNKNPAPPID	ubiquitination	[2, 3, 4, 5, 6, 7, 8, 9, 10, 11]
291	ERIGMVVKTGVVPQL	ubiquitination	[2, 3, 4, 5, 6, 8, 9, 10, 11]
300	GVVPQLVKLLGASEL	ubiquitination	[4, 5, 7, 9]
353	NPKTNIQKEATWTMS	acetylation	[12]
353	NPKTNIQKEATWTMS	ubiquitination	[2, 3, 4, 5, 8, 9, 11]
392	VLSKADFKTQKEAVW	ubiquitination	[3]
459	EKLGETEKLSIMIEE	ubiquitination	[7, 8, 10]
486	HENESVYKASLSLIE	ubiquitination	[2, 3, 5, 10]

[1] Acetylation of importin-alpha nuclear import factors by CBP/p300.
Bannister AJ, Miska EA, Görlich D, Kouzarides T.
Curr Biol. 2000 Apr 20;10(8):467-70. [PMID: 10801418]
[2] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
[3] Systematic and quantitative assessment of the ubiquitin-modified proteome.
Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
[4] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
[5] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
[6] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
[7] Global analysis of lysine ubiquitination by ubiquitin remnant immunoaffinity profiling.
Xu G, Paige JS, Jaffrey SR.
Nat Biotechnol. 2010 Aug;28(8):868-73. [PMID: 20639865]
[8] Global identification of modular cullin-RING ligase substrates.
Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
[9] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572]
[10] Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin.
Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI.
J Proteome Res. 2012 Feb 3;11(2):796-807. [PMID: 22053931]
[11] Integrated proteomic analysis of post-translational modifications by serial enrichment.
Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
[12] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
PLoS One. 2012;7(12):e50545. [PMID: 23236377]

Functional Description

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.

DOMAIN 2 60 IBB.
REPEAT 71 111 ARM 1; truncated.
REPEAT 112 151 ARM 2.
REPEAT 152 193 ARM 3.
REPEAT 200 244 ARM 4.
REPEAT 246 282 ARM 5.
REPEAT 283 322 ARM 6.
REPEAT 325 364 ARM 7.
REPEAT 367 409 ARM 8.
REPEAT 410 456 ARM 9.
REPEAT 457 496 ARM 10; atypical.
REGION 142 238 NLS binding site (major) (By similarity).
REGION 315 403 NLS binding site (minor) (By similarity).
MOTIF 45 54 Nuclear localization signal (By
MOD_RES 2 2 N-acetylserine.
MOD_RES 62 62 Phosphoserine.
MOD_RES 490 490 Phosphoserine.

3D-structure; Acetylation; Complete proteome; Cytoplasm; Direct protein sequencing; Host-virus interaction; Nucleus; Phosphoprotein; Polymorphism; Protein transport; Reference proteome; Repeat; Transport.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0005829; C:cytosol; TAS:Reactome.
GO:0005654; C:nucleoplasm; TAS:Reactome.
GO:0008139; F:nuclear localization sequence binding; IDA:UniProtKB.
GO:0008565; F:protein transporter activity; IEA:InterPro.
GO:0019221; P:cytokine-mediated signaling pathway; TAS:Reactome.
GO:0006259; P:DNA metabolic process; TAS:ProtInc.
GO:0000085; P:G2 phase of mitotic cell cycle; TAS:ProtInc.
GO:0000072; P:M phase specific microtubule process; TAS:ProtInc.
GO:0006607; P:NLS-bearing substrate import into nucleus; IDA:UniProtKB.
GO:0000018; P:regulation of DNA recombination; TAS:ProtInc.
GO:0019048; P:virus-host interaction; IEA:UniProtKB-KW.

IPR011989; ARM-like.
IPR016024; ARM-type_fold.
IPR000225; Armadillo.
IPR002652; Importin-a_IBB.
IPR024931; Importing_su_alpha.

PF00514; Arm
PF01749; IBB

PS50176; ARM_REPEAT
PS51214; IBB