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Overview

Uniprot ID	Q13564
Protein Name	NEDD8-activating enzyme E1 regulatory subunit
Gene Name	NAE1
Organism	Homo sapiens

Kla Sites from experimental identification

Position	Flanking peptide
341	ADSGKYIKLQNVYRE
6	**MAQLGKLLKEQKY
9	AQLGKLLKEQKYDRQ

Function

Regulatory subunit of the dimeric UBA3-NAE1 E1 enzyme. E1 activates NEDD8 by first adenylating its C-terminal glycine residue with ATP, thereafter linking this residue to the side chain of the catalytic cysteine, yielding a NEDD8-UBA3 thioester and free AMP. E1 finally transfers NEDD8 to the catalytic cysteine of UBE2M. Necessary for cell cycle progression through the S-M checkpoint. Overexpression of NAE1 causes apoptosis through deregulation of NEDD8 conjugation. The covalent attachment of NEDD8 to target proteins is known as 'neddylation' and the process is involved in the regulation of cell growth, viability and development

Protein Sequence

10 MAQLGKLLKE 20 QKYDRQLRLW 30 GDHGQEALES 40 AHVCLINATA 50 TGTEILKNLV 60 LPGIGSFTII 70 DGNQVSGEDA 80 GNNFFLQRSS 90 IGKNRAEAAM 100 EFLQELNSDV 110 SGSFVEESPE 120 NLLDNDPSFF 130 CRFTVVVATQ 140 LPESTSLRLA 150 DVLWNSQIPL 160 LICRTYGLVG 170 YMRIIIKEHP 180 VIESHPDNAL 190 EDLRLDKPFP 200 ELREHFQSYD 210 LDHMEKKDHS 220 HTPWIVIIAK 230 YLAQWYSETN 240 GRIPKTYKEK 250 EDFRDLIRQG 260 ILKNENGAPE 270 DEENFEEAIK 280 NVNTALNTTQ 290 IPSSIEDIFN 300 DDRCINITKQ 310 TPSFWILARA 320 LKEFVAKEGQ 330 GNLPVRGTIP 340 DMIADSGKYI 350 KLQNVYREKA 360 KKDAAAVGNH 370 VAKLLQSIGQ 380 APESISEKEL 390 KLLCSNSAFL 400 RVVRCRSLAE 410 EYGLDTINKD 420 EIISSMDNPD 430 NEIVLYLMLR 440 AVDRFHKQQG 450 RYPGVSNYQV 460 EEDIGKLKSC 470 LTGFLQEYGL 480 SVMVKDDYVH 490 EFCRYGAAEP 500 HTIAAFLGGA 510 AAQEVIKIIT 520 KQFVIFNNTY 530 IYSGMSQTSA TFQL

Gene Ontology

Classification	GO ID	Description
Cellular Component	GO:0005737	cytoplasm
Cellular Component	GO:0005829	cytosol
Cellular Component	GO:0098978	glutamatergic synapse
Cellular Component	GO:0005886	plasma membrane
Cellular Component	GO:0032991	protein-containing complex
Molecular Function	GO:0019781	NEDD8 activating enzyme activity
Molecular Function	GO:0046982	protein heterodimerization activity
Molecular Function	GO:0031625	ubiquitin protein ligase binding
Biological Process	GO:0033314	mitotic DNA replication checkpoint signaling
Biological Process	GO:0051402	neuron apoptotic process
Biological Process	GO:0045116	protein neddylation
Biological Process	GO:0042981	regulation of apoptotic process
Biological Process	GO:0043523	regulation of neuron apoptotic process
Biological Process	GO:0150052	regulation of postsynapse assembly
Biological Process	GO:0007165	signal transduction

Reference

[1] Lin Y, Chen M, Wang D, Yu Y, Chen R et al.. Multi-Proteomic Analysis Reveals the Effect of Protein Lactylation on Matrix and Cholesterol Metabolism in Tendinopathy.. J Proteome Res 22(6):1712-1722. 2023 Jun 2. PMID: 37159428.

[2] Guo X, Ren X, Yan C, Huang H. Quantitative Proteomics Reveals the Role of Lysine Lactylation in Lenalidomide-Resistance in Multiple Myeloma Cells.. ACS Chem Biol 20(7):1728-1738. 2025 Jul 18. PMID: 40590393.

[3] 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.