NAA35

Summary

NAA35 (N-alpha-acetyltransferase 35, NatC auxiliary subunit, HGNC:24340) is a protein-coding gene on chromosome 9q21.33, encoding N-alpha-acetyltransferase 35, NatC auxiliary subunit (Q5VZE5). Auxillary component of the N-terminal acetyltransferase C (NatC) complex which catalyzes acetylation of N-terminal methionine residues. It is a selective cancer dependency (DepMap: 54.5% of cell lines).

Predicted to enable transferase activity. Involved in negative regulation of apoptotic process. Located in cytosol; nucleoplasm; and plasma membrane. Part of NatC complex.

Source: NCBI Gene 60560 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 174 total
• Cancer dependency (DepMap): dependent in 54.5% of screened cell lines
• MANE Select transcript: NM_024635

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24340
Approved symbol	NAA35
Name	N-alpha-acetyltransferase 35, NatC auxiliary subunit
Location	9q21.33
Locus type	gene with protein product
Status	Approved
Aliases	FLJ21613, FLJ22643, bA379P1.1
Ensembl gene	ENSG00000135040
Ensembl biotype	protein_coding
OMIM	619438
Entrez	60560

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 16 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000361671, ENST00000376040, ENST00000416045, ENST00000910060, ENST00000910061, ENST00000910062, ENST00000910063, ENST00000910064, ENST00000910065, ENST00000910066, ENST00000910067, ENST00000910068, ENST00000910069, ENST00000910070, ENST00000935821, ENST00000935822, ENST00000970125

RefSeq mRNA: 3 — MANE Select: NM_024635 NM_001321881, NM_001321882, NM_024635

CCDS: CCDS6673

Canonical transcript exons

ENST00000361671 — 23 exons

Exon	Start	End
ENSE00000637291	86013046	86013144
ENSE00000637292	86018255	86018395
ENSE00000710045	85977363	85977446
ENSE00000710048	85978267	85978381
ENSE00000710180	86020889	86020969
ENSE00000804082	85974967	85975033
ENSE00000804084	85976685	85976735
ENSE00000804086	86013719	86013897
ENSE00000804088	86016539	86016675
ENSE00000917723	85959793	85959867
ENSE00000917724	85962013	85962180
ENSE00000982965	86003585	86003644
ENSE00000982966	86007358	86007464
ENSE00001171803	86009865	86009931
ENSE00001171812	85996399	85996577
ENSE00001171822	85975114	85975157
ENSE00001171831	85958472	85958586
ENSE00001171838	85956360	85956393
ENSE00001219236	86018699	86018821
ENSE00001219245	86017498	86017565
ENSE00001469254	86021901	86025462
ENSE00001841607	85941146	85941273
ENSE00003769847	85942155	85942283

Expression profiles

Bgee: expression breadth ubiquitous, 277 present calls, max score 99.60.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.1371 / max 123.7550, expressed in 1802 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
97187	6.7298	1739
97185	4.7744	1638
97186	1.3753	923
97188	0.2577	100

Top tissues by expression

288 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	99.60	gold quality
oocyte	CL:0000023	98.68	gold quality
nipple	UBERON:0002030	90.50	gold quality
bronchial epithelial cell	CL:0002328	89.74	gold quality
mucosa of sigmoid colon	UBERON:0004993	89.74	gold quality
adrenal tissue	UBERON:0018303	89.12	gold quality
colonic mucosa	UBERON:0000317	88.98	gold quality
calcaneal tendon	UBERON:0003701	88.93	gold quality
pons	UBERON:0000988	88.89	gold quality
corpus callosum	UBERON:0002336	88.78	gold quality
superior vestibular nucleus	UBERON:0007227	88.02	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	87.57	gold quality
inferior vagus X ganglion	UBERON:0005363	87.46	gold quality
tibia	UBERON:0000979	87.36	gold quality
pylorus	UBERON:0001166	87.15	gold quality
postcentral gyrus	UBERON:0002581	86.75	gold quality
parietal lobe	UBERON:0001872	86.58	gold quality
body of tongue	UBERON:0011876	86.58	gold quality
biceps brachii	UBERON:0001507	86.57	gold quality
renal medulla	UBERON:0000362	86.46	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	86.29	gold quality
cortical plate	UBERON:0005343	86.18	gold quality
jejunum	UBERON:0002115	86.12	gold quality
jejunal mucosa	UBERON:0000399	85.94	gold quality
medulla oblongata	UBERON:0001896	85.92	gold quality
subthalamic nucleus	UBERON:0001906	85.82	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.80	gold quality
epithelium of bronchus	UBERON:0002031	85.78	gold quality
cartilage tissue	UBERON:0002418	85.74	gold quality
bronchus	UBERON:0002185	85.63	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-100618	yes	321.99
E-ANND-3	yes	5.31
E-MTAB-4850	no	668.55
E-MTAB-7606	no	244.53

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): STAT1

miRNA regulators (miRDB)

16 targeting NAA35, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-6516-3P	99.65	68.57	1238
HSA-MIR-497-3P	99.61	69.71	1990
HSA-MIR-580-5P	99.28	70.94	1776
HSA-MIR-8070	99.07	69.30	1303
HSA-MIR-382-3P	98.83	67.10	1074
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-4290	98.51	65.17	907
HSA-MIR-1255B-2-3P	97.80	67.04	880
HSA-MIR-1913	97.07	66.20	1417
HSA-MIR-193A-5P	95.70	65.33	613

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 54.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 4)

• Human Naa35 (MAK10) is an auxiliary subunit of the human NatC N-terminal acetyltransferase complex. NatC acetylates hydrophobic Met-starting N-termini, and NatC knockdown induces p53-dependent apoptosis. (PMID:19398576)
• Data demonstrate that chimera GOLM1-MAK10 encodes a secreted fusion protein. Mechanistic studies reveal that GOLM1-MAK10 is likely derived from transcription read-through/splicing rather than being generated from a fusion gene. (PMID:24243830)
• A cytokine QTL at the NAA35-GOLM1 locus markedly modulated interleukin (IL)-6 production in response to multiple pathogens and was associated with susceptibility to candidemia. (PMID:27376574)
• salivary exosomal GOLM1-NAA35 chimeric RNA (seG-NchiRNA) constitutes an effective candidate noninvasive biomarker for the convenient, reliable assessment of therapeutic response, recurrence, and early detection. (PMID:30745298)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	naa35	ENSDARG00000012378
mus_musculus	Naa35	ENSMUSG00000021555
rattus_norvegicus	Naa35	ENSRNOG00000018417
drosophila_melanogaster	Naa35	FBGN0034982
caenorhabditis_elegans		WBGENE00020719

Protein

Protein identifiers

N-alpha-acetyltransferase 35, NatC auxiliary subunit — Q5VZE5 (reviewed: Q5VZE5)

Alternative names: Embryonic growth-associated protein homolog, Protein MAK10 homolog

All UniProt accessions (1): Q5VZE5

UniProt curated annotations — full annotation on UniProt →

Function. Auxillary component of the N-terminal acetyltransferase C (NatC) complex which catalyzes acetylation of N-terminal methionine residues. N-terminal acetylation protects proteins from ubiquitination and degradation by the N-end rule pathway. Involved in regulation of apoptosis and proliferation of smooth muscle cells.

Subunit / interactions. Component of the N-terminal acetyltransferase C (NatC) complex, which is composed of NAA35, NAA38 and NAA30.

Subcellular location. Cytoplasm.

Similarity. Belongs to the MAK10 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q5VZE5-1	1	yes
Q5VZE5-2	2

RefSeq proteins (3): NP_001308810, NP_001308811, NP_078911* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007244	Naa35_N	Family
IPR057982	TPR_NAA35	Domain
IPR057983	NAA35-like_N	Domain

Pfam: PF04112, PF25789

UniProt features (46 total): helix 27, turn 6, strand 5, splice variant 2, sequence conflict 2, chain 1, region of interest 1, compositionally biased region 1, modified residue 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
7RB3	ELECTRON MICROSCOPY	3.1
7MX2	ELECTRON MICROSCOPY	3.64

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5VZE5-F1	89.90	0.75

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 187

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-6811440	Retrograde transport at the Trans-Golgi-Network
R-HSA-199991	Membrane Trafficking
R-HSA-5653656	Vesicle-mediated transport
R-HSA-6811442	Intra-Golgi and retrograde Golgi-to-ER traffic

MSigDB gene sets: 118 (showing top): GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, REACTOME_MEMBRANE_TRAFFICKING, GOBP_MUSCLE_CELL_PROLIFERATION, RODWELL_AGING_KIDNEY_NO_BLOOD_DN, GOCC_TRANSFERASE_COMPLEX, GOCC_N_TERMINAL_PROTEIN_ACETYLTRANSFERASE_COMPLEX, BLALOCK_ALZHEIMERS_DISEASE_DN, chr9q21, WANG_TUMOR_INVASIVENESS_DN, WEST_ADRENOCORTICAL_TUMOR_UP, GOBP_SMOOTH_MUSCLE_CELL_PROLIFERATION, EGR_Q6, REACTOME_VESICLE_MEDIATED_TRANSPORT, REACTOME_RETROGRADE_TRANSPORT_AT_THE_TRANS_GOLGI_NETWORK

GO Biological Process (3): negative regulation of apoptotic process (GO:0043066), smooth muscle cell proliferation (GO:0048659), N-terminal peptidyl-methionine acetylation (GO:0017196)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (5): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), NatC complex (GO:0031417)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Intra-Golgi and retrograde Golgi-to-ER traffic	1
Vesicle-mediated transport	1
Membrane Trafficking	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
muscle cell proliferation	1
N-terminal protein amino acid acetylation	1
peptidyl-methionine modification	1
binding	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
membrane	1
cell periphery	1
N-terminal protein acetyltransferase complex	1

Protein interactions and networks

STRING

1262 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NAA35	NAA30	Q147X3	996
NAA35	NAA38	Q9BRA0	982
NAA35	NAA20	P61599	851
NAA35	NAA25	Q14CX7	839
NAA35	NAA15	Q9BXJ9	774
NAA35	NAA10	P41227	742
NAA35	NAA40	Q86UY6	717
NAA35	NAA50	Q9GZZ1	707
NAA35	NAA60	Q9H7X0	650
NAA35	NAA11	Q9BSU3	624
NAA35	GOLM1	Q8NBJ4	618
NAA35	NAA16	Q6N069	589
NAA35	PAK1IP1	Q9NWT1	510
NAA35	KATNAL1	Q9BW62	459
NAA35	HYPK	Q9NX55	446

IntAct

25 interactions, top by confidence:

A	B	Type	Score
SMNDC1	SF3B1	psi-mi:“MI:0914”(association)	0.790
NAA30	NAA35	psi-mi:“MI:0915”(physical association)	0.740
NAA30	NAA35	psi-mi:“MI:0914”(association)	0.740
NAA35	TRIM7	psi-mi:“MI:0915”(physical association)	0.560
NAA38	NAA35	psi-mi:“MI:0915”(physical association)	0.560
FGL1	DNM1L	psi-mi:“MI:0914”(association)	0.350
ERBB2	PGM3	psi-mi:“MI:0914”(association)	0.350
PSMB10	DDX46	psi-mi:“MI:0914”(association)	0.350
PAGE1	CIBAR1	psi-mi:“MI:0914”(association)	0.350
BTF3	NACAD	psi-mi:“MI:0914”(association)	0.350
NAA38	EIF3H	psi-mi:“MI:0914”(association)	0.350
MMTAG2	HEXIM1	psi-mi:“MI:0914”(association)	0.350
NAA30	HARS2	psi-mi:“MI:0914”(association)	0.350
FAM133A	DNM1L	psi-mi:“MI:0914”(association)	0.350
NAA38	PRORP	psi-mi:“MI:0914”(association)	0.350
NAA30	ATP1A3	psi-mi:“MI:0914”(association)	0.350
CXCR3	RIMOC1	psi-mi:“MI:0914”(association)	0.350
FZD10	PDE2A	psi-mi:“MI:0914”(association)	0.350
NAA30	PAPSS1	psi-mi:“MI:0914”(association)	0.350
NAA30	RPL26	psi-mi:“MI:0403”(colocalization)	0.350
KCNJ2	ELAPOR2	psi-mi:“MI:2364”(proximity)	0.270
NAA35	TRIM7	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (56): NAA35 (Affinity Capture-MS), NAA35 (Co-fractionation), NAA35 (Affinity Capture-MS), NAA35 (Affinity Capture-MS), NAA35 (Affinity Capture-MS), NAA35 (Affinity Capture-MS), NAA35 (Affinity Capture-MS), NAA35 (Affinity Capture-MS), NAA35 (Affinity Capture-MS), NAA35 (Affinity Capture-RNA), NAA35 (Affinity Capture-MS), TRIM7 (Two-hybrid), NAA35 (Affinity Capture-MS), NAA35 (Proximity Label-MS), NAA35 (Affinity Capture-MS)

ESM2 similar proteins: A1A5Q4, A1L3F5, B0I564, B1AY13, O15327, O75934, Q0IIE6, Q28DG8, Q29RL1, Q2IA00, Q4R4D7, Q4R6T7, Q4R708, Q5NVD7, Q5RA60, Q5RAX7, Q5RBT3, Q5U1Z0, Q5VZE5, Q5ZHV2, Q62717, Q6DDI6, Q6DFL5, Q6DKG0, Q6GLR7, Q6PBE2, Q6PE87, Q6PHQ8, Q7SYB2, Q7T322, Q7ZXA8, Q86UW7, Q86VS3, Q8BMG7, Q8BYR5, Q8C9J3, Q8CDG3, Q8CF97, Q8CJF7, Q8IYR0

Diamond homologs: Q4R708, Q5RBT3, Q5VZE5, Q5ZHV2, Q6DKG0, Q6PHQ8, Q7T322, Q9W1A2

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
NAA35	“form complex”	NatC	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

174 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	81
Likely benign	61
Benign	12

Top pathogenic / likely-pathogenic (0)

SpliceAI

3496 predictions. Top by Δscore:

Variant	Effect	Δscore
9:85942153:A:AG	acceptor_gain	1.0000
9:85942154:G:GG	acceptor_gain	1.0000
9:85942281:GAGGT:G	donor_loss	1.0000
9:85942282:AGG:A	donor_loss	1.0000
9:85942283:GGT:G	donor_loss	1.0000
9:85942284:G:GG	donor_gain	1.0000
9:85942284:G:T	donor_loss	1.0000
9:85942285:T:G	donor_loss	1.0000
9:85956358:A:AG	acceptor_gain	1.0000
9:85956359:G:GG	acceptor_gain	1.0000
9:85956391:GCT:G	donor_gain	1.0000
9:85956392:CT:C	donor_gain	1.0000
9:85956393:TGT:T	donor_loss	1.0000
9:85956394:G:GG	donor_gain	1.0000
9:85956394:GTA:G	donor_loss	1.0000
9:85956396:AA:A	donor_loss	1.0000
9:85958464:A:AG	acceptor_gain	1.0000
9:85958465:T:G	acceptor_gain	1.0000
9:85958470:A:AG	acceptor_gain	1.0000
9:85958471:G:GA	acceptor_gain	1.0000
9:85958471:GA:G	acceptor_gain	1.0000
9:85958471:GAT:G	acceptor_gain	1.0000
9:85958471:GATT:G	acceptor_gain	1.0000
9:85958471:GATTT:G	acceptor_gain	1.0000
9:85958583:CAAG:C	donor_loss	1.0000
9:85958584:AAG:A	donor_loss	1.0000
9:85958585:AGGTA:A	donor_loss	1.0000
9:85958586:GGTAG:G	donor_loss	1.0000
9:85958587:G:GG	donor_gain	1.0000
9:85958587:G:T	donor_gain	1.0000

AlphaMissense

4891 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:85956372:G:T	G46V	1.000
9:85956378:T:C	L48P	1.000
9:85958473:T:C	F54L	1.000
9:85958474:T:C	F54S	1.000
9:85958475:T:A	F54L	1.000
9:85958475:T:G	F54L	1.000
9:85958480:T:A	L56H	1.000
9:85958480:T:C	L56P	1.000
9:85958488:G:C	A59P	1.000
9:85958489:C:A	A59D	1.000
9:85958492:T:A	M60K	1.000
9:85958492:T:G	M60R	1.000
9:85958493:G:A	M60I	1.000
9:85958493:G:C	M60I	1.000
9:85958493:G:T	M60I	1.000
9:85958494:T:C	S61P	1.000
9:85958497:G:C	A62P	1.000
9:85958498:C:A	A62D	1.000
9:85958501:T:A	I63N	1.000
9:85958507:T:G	M65R	1.000
9:85958511:G:A	M66I	1.000
9:85958511:G:C	M66I	1.000
9:85958511:G:T	M66I	1.000
9:85958513:A:G	D67G	1.000
9:85958520:G:C	K69N	1.000
9:85958520:G:T	K69N	1.000
9:85958522:T:A	M70K	1.000
9:85958522:T:C	M70T	1.000
9:85958522:T:G	M70R	1.000
9:85958523:G:A	M70I	1.000

dbSNP variants (sampled 300 via entrez): RS1000000904 (9:85953061 A>G), RS1000043012 (9:85988092 T>C), RS1000136120 (9:85988430 A>G), RS1000140533 (9:86006565 C>A,T), RS1000146855 (9:86015579 T>C), RS1000226302 (9:85941106 C>G,T), RS1000259771 (9:85958971 T>C), RS1000276741 (9:86024841 A>G), RS1000379538 (9:86010344 A>G), RS1000380691 (9:85982128 A>G), RS1000406011 (9:85963904 A>C), RS1000423052 (9:85969749 C>T), RS1000430010 (9:85994341 C>T), RS1000440448 (9:85975251 C>T), RS1000464228 (9:85987729 T>C)

Disease associations

OMIM: gene MIM:619438 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST007006_7	Logical memory (delayed recall) in normal cognition	2.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004874	memory performance

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	2
Arsenic	affects methylation, affects cotreatment, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
di-n-butylphosphoric acid	affects expression	1
K 7174	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Benzo(a)pyrene	increases methylation	1
Doxorubicin	decreases expression	1
Hydrogen Peroxide	affects expression	1
Ivermectin	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Vanadates	decreases expression	1
Cyclosporine	increases expression	1
Cadmium Chloride	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_SZ75	HAP1 NAA35 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.