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Overview

Uniprot ID	O00505
Protein Name	Importin subunit alpha-4
Gene Name	KPNA3
Organism	Homo sapiens

Kla Sites from experimental identification

Position	Flanking peptide
47	KRDEHLLKKRNVPQE

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. Recognizes NLSs of influenza A virus nucleoprotein probably through ARM repeats 7-9

Protein Sequence

10 MAENPSLENH 20 RIKSFKNKGR 30 DVETMRRHRN 40 EVTVELRKNK 50 RDEHLLKKRN 60 VPQEESLEDS 70 DVDADFKAQN 80 VTLEAILQNA 90 TSDNPVVQLS 100 AVQAARKLLS 110 SDRNPPIDDL 120 IKSGILPILV 130 KCLERDDNPS 140 LQFEAAWALT 150 NIASGTSAQT 160 QAVVQSNAVP 170 LFLRLLRSPH 180 QNVCEQAVWA 190 LGNIIGDGPQ 200 CRDYVISLGV 210 VKPLLSFISP 220 SIPITFLRNV 230 TWVIVNLCRN 240 KDPPPPMETV 250 QEILPALCVL 260 IYHTDINILV 270 DTVWALSYLT 280 DGGNEQIQMV 290 IDSGVVPFLV 300 PLLSHQEVKV 310 QTAALRAVGN 320 IVTGTDEQTQ 330 VVLNCDVLSH 340 FPNLLSHPKE 350 KINKEAVWFL 360 SNITAGNQQQ 370 VQAVIDAGLI 380 PMIIHQLAKG 390 DFGTQKEAAW 400 AISNLTISGR 410 KDQVEYLVQQ 420 NVIPPFCNLL 430 SVKDSQVVQV 440 VLDGLKNILI 450 MAGDEASTIA 460 EIIEECGGLE 470 KIEVLQQHEN 480 EDIYKLAFEI 490 IDQYFSGDDI 500 DEDPCLIPEA 510 TQGGTYNFDP 520 TANLQTKEFN F

Gene Ontology

Classification	GO ID	Description
Cellular Component	GO:0005829	cytosol
Cellular Component	GO:0043657	host cell
Cellular Component	GO:0042564	NLS-dependent protein nuclear import complex
Cellular Component	GO:0005643	nuclear pore
Cellular Component	GO:0005654	nucleoplasm
Cellular Component	GO:0005634	nucleus
Molecular Function	GO:0061608	nuclear import signal receptor activity
Molecular Function	GO:0008139	nuclear localization sequence binding
Biological Process	GO:0006607	NLS-bearing protein import into nucleus
Biological Process	GO:0065003	protein-containing complex assembly
Biological Process	GO:0046718	symbiont entry into host cell
Biological Process	GO:0075732	viral penetration into host nucleus

Reference

[1] Yang D, Yin J, Shan L, Yi X, Zhang W et al.. Identification of lysine-lactylated substrates in gastric cancer cells.. iScience 25(7):104630. 2022 Jul 15. PMID: 35800753.

[2] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.

[3] Yang YH, Wang QC, Kong J, Yang JT, Liu JF. Global profiling of lysine lactylation in human lungs.. Proteomics 23(15):e2200437. 2023 Aug. PMID: 37170646.

[4] Shi CM, Wang QC, Li XL, Yang YH, Tang XY et al.. Global Profiling of Protein Lactylation in Human Hippocampi.. Proteomics Clin Appl 19(2):e202400061. 2025 Mar. PMID: 39610256.

[5] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.