DESI2

Summary

DESI2 (desumoylating isopeptidase 2, HGNC:24264) is a protein-coding gene on chromosome 1q44, encoding Deubiquitinase DESI2 (Q9BSY9). Has deubiquitinating activity towards ‘Lys-48’- and ‘Lys-63’-linked polyubiquitin chains.

Enables deubiquitinase activity and long-chain fatty acyl-CoA hydrolase activity. Predicted to be involved in macromolecule depalmitoylation and proteolysis. Predicted to be located in cytoplasm.

Source: NCBI Gene 51029 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 23 total
• MANE Select transcript: NM_016076

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24264
Approved symbol	DESI2
Name	desumoylating isopeptidase 2
Location	1q44
Locus type	gene with protein product
Status	Approved
Aliases	CGI-146, FLJ21998, PNAS-4, DESI-2
Ensembl gene	ENSG00000121644
Ensembl biotype	protein_coding
OMIM	614638
Entrez	51029

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000263831, ENST00000302550, ENST00000418162, ENST00000484738, ENST00000859653, ENST00000859654, ENST00000930300, ENST00000967560

RefSeq mRNA: 2 — MANE Select: NM_016076 NM_001297746, NM_016076

CCDS: CCDS1626, CCDS73055

Canonical transcript exons

ENST00000302550 — 5 exons

Exon	Start	End
ENSE00000961671	244689249	244689342
ENSE00001303900	244705556	244709033
ENSE00001368207	244686597	244686669
ENSE00001396240	244653126	244653355
ENSE00002183314	244691879	244692020

Expression profiles

Bgee: expression breadth ubiquitous, 296 present calls, max score 96.89.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 28.5984 / max 312.1367, expressed in 1816 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
9480	26.9087	1815
9481	0.8567	582
9479	0.8331	504

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	96.89	gold quality
pericardium	UBERON:0002407	96.82	gold quality
saphenous vein	UBERON:0007318	96.81	gold quality
superior surface of tongue	UBERON:0007371	96.39	gold quality
sperm	CL:0000019	96.34	gold quality
body of tongue	UBERON:0011876	96.26	gold quality
male germ cell	CL:0000015	96.13	gold quality
pharyngeal mucosa	UBERON:0000355	96.05	gold quality
vena cava	UBERON:0004087	96.00	gold quality
tongue	UBERON:0001723	95.62	gold quality
lower lobe of lung	UBERON:0008949	95.35	gold quality
adult organism	UBERON:0007023	95.09	gold quality
nipple	UBERON:0002030	95.04	gold quality
cartilage tissue	UBERON:0002418	94.86	gold quality
cauda epididymis	UBERON:0004360	94.20	gold quality
visceral pleura	UBERON:0002401	92.87	gold quality
mammary duct	UBERON:0001765	92.67	gold quality
blood vessel layer	UBERON:0004797	92.46	gold quality
synovial joint	UBERON:0002217	92.42	gold quality
trachea	UBERON:0003126	92.42	gold quality
cardia of stomach	UBERON:0001162	92.36	gold quality
choroid plexus epithelium	UBERON:0003911	92.35	gold quality
epithelium of nasopharynx	UBERON:0001951	92.32	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	92.22	gold quality
epithelium of mammary gland	UBERON:0003244	92.22	gold quality
pylorus	UBERON:0001166	92.18	gold quality
deltoid	UBERON:0001476	91.76	gold quality
ventricular zone	UBERON:0003053	91.73	gold quality
pleura	UBERON:0000977	91.64	gold quality
skin of hip	UBERON:0001554	91.52	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-10290	no	118.86
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

146 targeting DESI2, 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-3163	100.00	77.23	8605
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-5688	99.96	73.23	4504

Literature-anchored findings (GeneRIF, showing 9)

• overexpression of human PNAS4 induced apoptosis and arrested cell cycle in S phase in A549 human lung adenocarcinoma cells. (PMID:19133312)
• PNAS-4 is not a p53 target, but overexpression of PNAS-4 is correlated to p53 inactivity in colorectal cancer. (PMID:21556770)
• hPNAS-4 inhibits proliferation of ovarian cancer cells by inducing S phase arrest and apoptosis via activation of Cdc25A-Cdk2-Cyclin E/Cyclin A axis and mitochondrial dysfunction-mediated caspase-dependent and -independent apoptotic pathways. (PMID:23322088)
• DESI2 may influence the AKT/mTOR signal in pancreatic cancer. (PMID:25079376)
• findings suggest a novel mechanism by which elevated PNAS-4 first causes DNA-dependent protein kinase-mediated Chk1/2 activation and then results in inhibition of the Cdc25A-CDK2-cyclin E/A pathway (PMID:25918161)
• The PPPDE1 could mediate the ubiquitin chain editing of RPS7, deubiquitinating Lys 48-linked ubiquitination, and finally stabilize RPS7 proteins. (PMID:28483520)
• Combination of DESI2 and endostatin gene therapy in the mouse models significantly improves antitumor efficacy by accumulating DNA lesions, inducing apoptosis and inhibiting angiogenesis. (PMID:30055135)
• DESI2 regulates the proliferation and apoptosis of pancreatic cancer cells through PI3K/AKT/mTOR signaling pathway (PMID:30411297)
• PPPDE1 is a key modulator of p53 protein level and its down stream apoptosis pathway. These results suggested that PPPDE1 is a putative Hepatocellular carcinoma driver gene. (PMID:30426280)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	desi2	ENSDARG00000004460
mus_musculus	Desi2	ENSMUSG00000026502
rattus_norvegicus	Desi2	ENSRNOG00000004524
drosophila_melanogaster	CG7222	FBGN0033551

Paralogs (1): DESI1 (ENSG00000100418)

Protein

Protein identifiers

Deubiquitinase DESI2 — Q9BSY9 (reviewed: Q9BSY9)

Alternative names: Desumoylating isopeptidase 2, PPPDE peptidase domain-containing protein 1, Palmitoyl protein thioesterase DESI2, Protein FAM152A, S-depalmitoylase DESI2

All UniProt accessions (2): B1APK7, Q9BSY9

UniProt curated annotations — full annotation on UniProt →

Function. Has deubiquitinating activity towards ‘Lys-48’- and ‘Lys-63’-linked polyubiquitin chains. Deubiquitinates ‘Lys-48’-linked polyubiquitination of RPS7 leading to its stabilization. Exhibits palmitoyl protein thioesterase (S-depalmitoylation) activity towards synthetic substrates 4-methylumbelliferyl-6-S-palmitoyl-beta-D-glucopyranoside and S-depalmitoylation probe 5 (DPP-5).

Subunit / interactions. Interacts with RPS7.

Subcellular location. Cytoplasm.

Activity regulation. Palmostatin B inhibits its palmitoyl protein thioesterase activity.

Similarity. Belongs to the DeSI family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BSY9-1	1	yes
Q9BSY9-2	2

RefSeq proteins (2): NP_001284675, NP_057160* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008580	PPPDE_dom	Domain
IPR042266	PPPDE_sf	Homologous_superfamily

Pfam: PF05903

Catalyzed reactions (Rhea), 1 shown:

• S-hexadecanoyl-L-cysteinyl-[protein] + H2O = L-cysteinyl-[protein] + hexadecanoate + H(+) (RHEA:19233)

UniProt features (9 total): active site 2, chain 1, domain 1, region of interest 1, compositionally biased region 1, splice variant 1, mutagenesis site 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BSY9-F1	86.26	0.55

Functional residue map

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

Catalytic / active sites (2): 30; 108

Mutagenesis-validated functional residues (1):

Position	Phenotype
108	loss of deubiquitination activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 198 (showing top): BORCZUK_MALIGNANT_MESOTHELIOMA_UP, GOBP_MACROMOLECULE_DEACYLATION, CACCAGC_MIR138, PUJANA_CHEK2_PCC_NETWORK, BLALOCK_ALZHEIMERS_DISEASE_UP, GOMF_CYSTEINE_TYPE_PEPTIDASE_ACTIVITY, TGTTTAC_MIR30A5P_MIR30C_MIR30D_MIR30B_MIR30E5P, SENESE_HDAC1_TARGETS_UP, VANTVEER_BREAST_CANCER_ESR1_DN, ACEVEDO_LIVER_CANCER_UP, TGCCTTA_MIR124A, chr1q44, IVANOVA_HEMATOPOIESIS_INTERMEDIATE_PROGENITOR, NAKAMURA_METASTASIS, GOBP_PROTEOLYSIS

GO Biological Process (2): proteolysis (GO:0006508), macromolecule depalmitoylation (GO:0098734)

GO Molecular Function (9): cysteine-type deubiquitinase activity (GO:0004843), palmitoyl-(protein) hydrolase activity (GO:0008474), long-chain fatty acyl-CoA hydrolase activity (GO:0052816), K63-linked deubiquitinase activity (GO:0061578), deubiquitinase activity (GO:0101005), K48-linked deubiquitinase activity (GO:1990380), protein binding (GO:0005515), peptidase activity (GO:0008233), hydrolase activity (GO:0016787)

GO Cellular Component (1): cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
deubiquitinase activity	3
catalytic activity, acting on a protein	2
protein metabolic process	1
macromolecule deacylation	1
cysteine-type peptidase activity	1
thiolester hydrolase activity	1
palmitoyl hydrolase activity	1
fatty acyl-CoA hydrolase activity	1
ubiquitin-like protein peptidase activity	1
binding	1
hydrolase activity	1
catalytic activity	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

564 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DESI2	USPL1	Q5W0Q7	772
DESI2	SENP5	Q96HI0	667
DESI2	SENP1	Q9P0U3	637
DESI2	SENP3	Q9H4L4	581
DESI2	SENP6	Q9GZR1	579
DESI2	SENP7	Q9BQF6	578
DESI2	SUMO1	P55856	576
DESI2	SAE1	Q9UBE0	558
DESI2	SUMO2	P55855	541
DESI2	UBA2	Q9UBT2	480
DESI2	SPMIP3	Q5SVJ3	476
DESI2	TIMM29	Q9BSF4	458
DESI2	UBE2I	P50550	446
DESI2	IFFO2	Q5TF58	437
DESI2	SENP8	Q96LD8	428

IntAct

36 interactions, top by confidence:

A	B	Type	Score
CDRT15P3	NFKBIE	psi-mi:“MI:0914”(association)	0.620
SPART	DESI2	psi-mi:“MI:0915”(physical association)	0.560
COQ8A	DESI2	psi-mi:“MI:0915”(physical association)	0.560
PLIN2	DESI2	psi-mi:“MI:0915”(physical association)	0.560
DESI2	MYG1	psi-mi:“MI:0915”(physical association)	0.560
DESI2	SEMA3G	psi-mi:“MI:0915”(physical association)	0.560
DESI2	THAP7	psi-mi:“MI:0915”(physical association)	0.560
DESI2	SH3GLB1	psi-mi:“MI:0915”(physical association)	0.560
PBX3	DESI2	psi-mi:“MI:0915”(physical association)	0.560
ARFIP1	DESI2	psi-mi:“MI:0915”(physical association)	0.560
BNIP2	DESI2	psi-mi:“MI:0915”(physical association)	0.560
DESI2	NFU1	psi-mi:“MI:0915”(physical association)	0.560
DESI2	BMPR1A	psi-mi:“MI:0914”(association)	0.350
COQ8A	DESI2	psi-mi:“MI:0915”(physical association)	0.000
MYG1	DESI2	psi-mi:“MI:0915”(physical association)	0.000
THAP7	DESI2	psi-mi:“MI:0915”(physical association)	0.000
SH3GLB1	DESI2	psi-mi:“MI:0915”(physical association)	0.000
ARFIP1	DESI2	psi-mi:“MI:0915”(physical association)	0.000
BNIP2	DESI2	psi-mi:“MI:0915”(physical association)	0.000
PLIN2	DESI2	psi-mi:“MI:0915”(physical association)	0.000
SEMA3G	DESI2	psi-mi:“MI:0915”(physical association)	0.000
PBX3	DESI2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (23): DESI2 (Two-hybrid), DESI2 (Two-hybrid), SPG20 (Two-hybrid), C12orf10 (Two-hybrid), BNIP2 (Two-hybrid), PLIN2 (Two-hybrid), ADCK3 (Two-hybrid), ARFIP1 (Two-hybrid), PBX3 (Two-hybrid), NFU1 (Two-hybrid), THAP7 (Two-hybrid), DESI2 (Proximity Label-MS), DESI2 (Proximity Label-MS), DESI2 (Proximity Label-MS), DESI2 (Proximity Label-MS)

ESM2 similar proteins: A2YQ56, A3QRX8, A6NHC0, O08529, O14815, O35350, O35920, P00789, P07384, P17569, P17655, P20807, P35750, P36776, P39866, P93648, P93655, P97571, Q07009, Q07093, Q11002, Q27970, Q27971, Q4KM30, Q59HJ6, Q5NVS7, Q5PQ09, Q5R456, Q5XIT6, Q5ZIV7, Q641Z6, Q69UZ3, Q6DC39, Q6GLM5, Q6ICB0, Q78EJ9, Q8CGK3, Q8X1T0, Q91VA3, Q92178

Diamond homologs: A3QRX8, H2KZK4, Q5PQ09, Q5R456, Q5XIT6, Q5ZIV7, Q6DC39, Q6GLM5, Q8X1T0, Q93VG8, Q9BSY9, Q9D291, Q4KM30, Q6ICB0, Q9CQT7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	16
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1214 predictions. Top by Δscore:

Variant	Effect	Δscore
1:244686591:TCTCA:T	acceptor_loss	1.0000
1:244686592:CTCAG:C	acceptor_loss	1.0000
1:244686593:TCAG:T	acceptor_loss	1.0000
1:244686595:A:AG	acceptor_gain	1.0000
1:244686595:AGTA:A	acceptor_loss	1.0000
1:244686596:G:GA	acceptor_gain	1.0000
1:244686596:GT:G	acceptor_gain	1.0000
1:244686596:GTA:G	acceptor_gain	1.0000
1:244686596:GTAT:G	acceptor_gain	1.0000
1:244686596:GTATT:G	acceptor_gain	1.0000
1:244686666:AGAGG:A	donor_loss	1.0000
1:244686667:GAG:G	donor_gain	1.0000
1:244686668:AGGT:A	donor_loss	1.0000
1:244686669:GGTA:G	donor_loss	1.0000
1:244686670:G:GG	donor_gain	1.0000
1:244686671:T:A	donor_loss	1.0000
1:244689243:TTTCA:T	acceptor_loss	1.0000
1:244689244:TTCAG:T	acceptor_loss	1.0000
1:244689245:TCAGA:T	acceptor_loss	1.0000
1:244689246:CA:C	acceptor_loss	1.0000
1:244689247:A:AG	acceptor_gain	1.0000
1:244689247:AG:A	acceptor_loss	1.0000
1:244689248:G:GC	acceptor_loss	1.0000
1:244689248:G:GG	acceptor_gain	1.0000
1:244689248:GA:G	acceptor_gain	1.0000
1:244689338:TTTAA:T	donor_gain	1.0000
1:244689339:T:G	donor_gain	1.0000
1:244689339:TTAA:T	donor_loss	1.0000
1:244689340:TAAG:T	donor_loss	1.0000
1:244689341:AAG:A	donor_loss	1.0000

AlphaMissense

1263 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:244686628:G:A	G25E	1.000
1:244686634:G:A	G27E	1.000
1:244686642:C:A	H30N	1.000
1:244686642:C:G	H30D	1.000
1:244686644:T:A	H30Q	1.000
1:244686644:T:G	H30Q	1.000
1:244686645:T:C	S31P	1.000
1:244686649:G:A	G32E	1.000
1:244689255:C:A	A41D	1.000
1:244689257:T:G	Y42D	1.000
1:244689261:G:A	G43D	1.000
1:244689264:G:A	G44D	1.000
1:244689266:C:G	H45D	1.000
1:244689267:A:G	H45R	1.000
1:244689268:T:A	H45Q	1.000
1:244689268:T:G	H45Q	1.000
1:244689284:G:A	G51R	1.000
1:244689284:G:C	G51R	1.000
1:244689285:G:A	G51E	1.000
1:244689285:G:T	G51V	1.000
1:244689288:T:A	I52K	1.000
1:244689290:T:C	F53L	1.000
1:244689292:T:A	F53L	1.000
1:244689292:T:G	F53L	1.000
1:244689332:T:C	F67L	1.000
1:244689334:T:A	F67L	1.000
1:244689334:T:G	F67L	1.000
1:244691895:G:T	G76W	1.000
1:244691961:G:C	G98R	1.000
1:244691961:G:T	G98C	1.000

dbSNP variants (sampled 300 via entrez): RS1000043606 (1:244685710 C>A), RS1000069120 (1:244687316 GT>G,GTT), RS1000274823 (1:244706842 C>A,T), RS1000284934 (1:244707044 C>A), RS1000294023 (1:244680567 C>T), RS1000303745 (1:244681742 A>G), RS1000373163 (1:244674029 C>G), RS1000409028 (1:244674182 A>T), RS1000513209 (1:244663419 G>A), RS1000588170 (1:244663277 C>T), RS1000633781 (1:244708632 G>A), RS1000701490 (1:244668055 G>T), RS1000715229 (1:244698425 G>A,T), RS1000745066 (1:244675701 A>G,T), RS1000796572 (1:244657751 C>T)

Disease associations

OMIM: gene MIM:614638 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

35 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression	2
sodium arsenite	decreases expression, increases expression	2
Arsenic Trioxide	increases expression	2
Acetaminophen	increases expression	2
Silicon Dioxide	decreases expression	2
Tretinoin	decreases expression	2
Valproic Acid	decreases expression, decreases methylation	2
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
salinomycin	decreases expression	1
cobaltous chloride	decreases expression	1
coumarin	increases phosphorylation	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases reaction, increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Irinotecan	decreases expression	1
Sunitinib	increases expression	1
Vorinostat	affects cotreatment, decreases expression	1
Vehicle Emissions	decreases reaction, increases expression	1
Benzene	increases expression	1
Coumestrol	increases expression	1
Diethylstilbestrol	decreases expression	1
Ketoconazole	decreases expression	1
Selenium	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Cyclosporine	increases expression	1

Clinical trials (associated diseases)

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