USE1

Summary

USE1 (unconventional SNARE in the ER 1, HGNC:30882) is a protein-coding gene on chromosome 19p13.11, encoding Vesicle transport protein USE1 (Q9NZ43). SNARE that may be involved in targeting and fusion of Golgi-derived retrograde transport vesicles with the ER.

Predicted to enable SNAP receptor activity. Predicted to be involved in several processes, including lysosomal transport; protein catabolic process; and retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum. Predicted to act upstream of or within endoplasmic reticulum tubular network organization and regulation of ER to Golgi vesicle-mediated transport. Located in endoplasmic reticulum.

Source: NCBI Gene 55850 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 41 total
• Druggable target: yes
• MANE Select transcript: NM_018467

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30882
Approved symbol	USE1
Name	unconventional SNARE in the ER 1
Location	19p13.11
Locus type	gene with protein product
Status	Approved
Aliases	p31, SLT1, MDS032, D12
Ensembl gene	ENSG00000053501
Ensembl biotype	protein_coding
OMIM	610675
Entrez	55850

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 4 protein_coding, 3 retained_intron, 3 nonsense_mediated_decay

ENST00000263897, ENST00000593597, ENST00000594399, ENST00000594724, ENST00000595101, ENST00000596136, ENST00000600970, ENST00000601592, ENST00000601662, ENST00000850647

RefSeq mRNA: 1 — MANE Select: NM_018467 NM_018467

CCDS: CCDS46011

Canonical transcript exons

ENST00000263897 — 8 exons

Exon	Start	End
ENSE00000777912	17215802	17215851
ENSE00003064519	17215357	17215507
ENSE00003495005	17219213	17219387
ENSE00003541208	17218364	17218391
ENSE00003656291	17215992	17216070
ENSE00003661811	17216169	17216321
ENSE00003686699	17217453	17217462
ENSE00003688379	17219631	17219829

Expression profiles

Bgee: expression breadth ubiquitous, 279 present calls, max score 95.22.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.9503 / max 155.4288, expressed in 1812 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
174464	8.6090	1773
174465	8.3768	1768
174466	3.0553	1165
174467	0.9092	380

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	95.22	gold quality
anterior cingulate cortex	UBERON:0009835	94.96	gold quality
apex of heart	UBERON:0002098	94.94	gold quality
cingulate cortex	UBERON:0003027	94.88	gold quality
prefrontal cortex	UBERON:0000451	94.86	gold quality
amygdala	UBERON:0001876	94.75	gold quality
right frontal lobe	UBERON:0002810	94.06	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	93.85	gold quality
putamen	UBERON:0001874	93.49	gold quality
nucleus accumbens	UBERON:0001882	93.43	gold quality
Brodmann (1909) area 9	UBERON:0013540	93.19	gold quality
caudate nucleus	UBERON:0001873	92.95	gold quality
spinal cord	UBERON:0002240	92.71	gold quality
right adrenal gland cortex	UBERON:0035827	92.60	gold quality
right adrenal gland	UBERON:0001233	92.56	gold quality
gastrocnemius	UBERON:0001388	92.47	gold quality
heart left ventricle	UBERON:0002084	92.31	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	92.23	gold quality
neocortex	UBERON:0001950	92.22	gold quality
left adrenal gland	UBERON:0001234	92.21	gold quality
left adrenal gland cortex	UBERON:0035825	92.20	gold quality
cardiac ventricle	UBERON:0002082	92.11	gold quality
frontal cortex	UBERON:0001870	92.01	gold quality
hindlimb stylopod muscle	UBERON:0004252	91.98	gold quality
muscle of leg	UBERON:0001383	91.88	gold quality
adrenal cortex	UBERON:0001235	91.80	gold quality
body of pancreas	UBERON:0001150	91.71	gold quality
substantia nigra	UBERON:0002038	91.53	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.31	gold quality
telencephalon	UBERON:0001893	91.29	gold quality

Single-cell (SCXA)

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

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

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 6)

• Results together suggest that NAG links between p31 and ZW10-RINT-1 and is involved in Golgi-to-ER transport. (PMID:19369418)
• USE1 is not only the first E2 enzyme but also the first known substrate of FAT10 conjugation, as it was efficiently auto-FAT10ylated in cis but not in trans. (PMID:20975683)
• FAT10 ubiquitination of USE1 leads to its accelerated degradation by the proteasome. (PMID:24528925)
• Grsf1 controls translation of the protein Use1, possibly by positioning the 40S ribosomal subunit and associated translation factors in front of the translation start site. (PMID:25184340)
• this study revealed a novel function of LMO2 involving in the regulatory hierarchy of UBA6-USE1-FAT10ylation pathway by targeting the E1 enzyme UBA6. (PMID:27569286)
• Tumor necrosis factor mediates USE1-independent FAT10ylation under inflammatory conditions. (PMID:37604583)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	use1	ENSDARG00000007250
mus_musculus	Use1	ENSMUSG00000002395
rattus_norvegicus	Use1	ENSRNOG00000016619
drosophila_melanogaster	Use1	FBGN0035965
caenorhabditis_elegans	use-1	WBGENE00022460

Protein

Protein identifiers

Vesicle transport protein USE1 — Q9NZ43 (reviewed: Q9NZ43)

Alternative names: Putative MAPK-activating protein PM26, USE1-like protein, p31

All UniProt accessions (4): Q9NZ43, M0QYT5, M0QZE0, M0QZZ6

UniProt curated annotations — full annotation on UniProt →

Function. SNARE that may be involved in targeting and fusion of Golgi-derived retrograde transport vesicles with the ER.

Subunit / interactions. Component of a SNARE complex consisting of STX18, USE1L, BNIP1/SEC20L and SEC22B. Interacts directly with STX18.

Subcellular location. Endoplasmic reticulum membrane.

Similarity. Belongs to the USE1 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9NZ43-1	1	yes
Q9NZ43-2	2
Q9NZ43-3	3

RefSeq proteins (1): NP_060937* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019150	Vesicle_transport_protein_Use1	Family

Pfam: PF09753

UniProt features (11 total): splice variant 4, topological domain 2, chain 1, sequence conflict 1, transmembrane region 1, coiled-coil region 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NZ43-F1	72.85	0.18

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6811434	COPI-dependent Golgi-to-ER retrograde traffic

MSigDB gene sets: 178 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, GSE45365_NK_CELL_VS_CD11B_DC_UP, GOBP_LYSOSOMAL_TRANSPORT, YAO_HOXA10_TARGETS_VIA_PROGESTERONE_UP, GOBP_MEMBRANE_FUSION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_VACUOLAR_TRANSPORT, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, MOLENAAR_TARGETS_OF_CCND1_AND_CDK4_UP, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, GOBP_ENDOPLASMIC_RETICULUM_TO_GOLGI_VESICLE_MEDIATED_TRANSPORT, KESHELAVA_MULTIPLE_DRUG_RESISTANCE

GO Biological Process (10): retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum (GO:0006890), lysosomal transport (GO:0007041), protein transport (GO:0015031), protein catabolic process (GO:0030163), secretion by cell (GO:0032940), regulation of ER to Golgi vesicle-mediated transport (GO:0060628), endoplasmic reticulum tubular network organization (GO:0071786), endoplasmic reticulum organization (GO:0007029), vesicle-mediated transport (GO:0016192), membrane fusion (GO:0061025)

GO Molecular Function (2): SNAP receptor activity (GO:0005484), protein binding (GO:0005515)

GO Cellular Component (5): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), COPI-coated vesicle (GO:0030137), SNARE complex (GO:0031201), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Golgi-to-ER retrograde transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	2
cytoplasm	2
Golgi vesicle transport	1
vacuolar transport	1
intracellular protein localization	1
establishment of protein localization	1
macromolecule catabolic process	1
protein metabolic process	1
secretion	1
export from cell	1
endoplasmic reticulum to Golgi vesicle-mediated transport	1
regulation of intracellular transport	1
regulation of vesicle-mediated transport	1
endoplasmic reticulum organization	1
organelle organization	1
endomembrane system organization	1
cellular process	1
membrane organization	1
protein-macromolecule adaptor activity	1
membrane fusion	1
fusogenic activity	1
binding	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
Golgi-associated vesicle	1
coated vesicle	1
membrane protein complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

844 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
USE1	STX18	Q9P2W9	931
USE1	SEC22B	O75396	908
USE1	BNIP1	Q12981	858
USE1	VAMP7	P51809	800
USE1	RINT1	Q6NUQ1	689
USE1	ZNF787	Q6DD87	687
USE1	NAPA	P54920	669
USE1	MPZL2	O60487	633
USE1	STX6	O43752	614
USE1	ZW10	O43264	609
USE1	YKT6	O15498	607
USE1	NBAS	A2RRP1	594
USE1	VTI1B	Q9UEU0	584
USE1	STX5	Q13190	550
USE1	GOSR2	O14653	538

IntAct

124 interactions, top by confidence:

A	B	Type	Score
USE1	STX18	psi-mi:“MI:0915”(physical association)	0.850
RINT1	NBAS	psi-mi:“MI:0914”(association)	0.830
STX18	NBAS	psi-mi:“MI:0914”(association)	0.810
NAPA	SNAP23	psi-mi:“MI:0914”(association)	0.780
NBAS	ZW10	psi-mi:“MI:0914”(association)	0.720
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
USE1	NBAS	psi-mi:“MI:0914”(association)	0.640
NBAS	USE1	psi-mi:“MI:0914”(association)	0.640
BNIP1	NBAS	psi-mi:“MI:0914”(association)	0.640
STX7	SNAP23	psi-mi:“MI:0914”(association)	0.640
MEOX2	USE1	psi-mi:“MI:0915”(physical association)	0.560
TRIM27	USE1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (221): USE1 (Two-hybrid), USE1 (Two-hybrid), USE1 (Affinity Capture-MS), BNIP1 (Affinity Capture-MS), NAPA (Affinity Capture-MS), STX18 (Affinity Capture-MS), MGLL (Affinity Capture-MS), SCFD2 (Affinity Capture-MS), ZW10 (Affinity Capture-MS), STX5 (Affinity Capture-MS), NBAS (Affinity Capture-MS), RINT1 (Affinity Capture-MS), TYW5 (Affinity Capture-MS), SCFD1 (Affinity Capture-MS), C19orf25 (Affinity Capture-MS)

ESM2 similar proteins: O08522, O14662, O22151, O49160, O60499, O64791, O73787, O88384, O88630, O88983, O95249, P56962, P58200, Q08851, Q08DB5, Q13190, Q2KIU0, Q2TBU3, Q40554, Q4VBI7, Q5E9Y2, Q5RBL6, Q5REB4, Q62931, Q63635, Q68FW4, Q6DDF4, Q7ZTY7, Q8BVI5, Q8K1E0, Q8VDS8, Q944A9, Q946Y7, Q94KK7, Q9CQ56, Q9D0I4, Q9LMP7, Q9LNH6, Q9LRP1, Q9NZ43

Diamond homologs: Q7ZTY7, Q9CQ56, Q9NZ43, Q9VSU7

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 62 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Intra-Golgi traffic	5	32.4×	1e-05
COPII-mediated vesicle transport	6	24.5×	5e-06
COPI-dependent Golgi-to-ER retrograde traffic	8	22.2×	4e-07
Golgi-to-ER retrograde transport	6	19.9×	1e-05
ER to Golgi Anterograde Transport	5	16.6×	1e-04
Intra-Golgi and retrograde Golgi-to-ER traffic	6	15.7×	4e-05
COPI-mediated anterograde transport	5	13.7×	2e-04
Transport to the Golgi and subsequent modification	5	12.9×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
vesicle fusion	8	96.3×	4e-12
obsolete vesicle docking	6	91.9×	6e-09
retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	7	47.2×	1e-08
endoplasmic reticulum to Golgi vesicle-mediated transport	6	16.3×	1e-04
intracellular protein transport	10	13.0×	3e-07
protein transport	8	7.0×	7e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	35
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

1666 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:17215443:T:C	L13P	0.994
19:17219757:T:C	C242R	0.994
19:17215493:T:A	W30R	0.993
19:17215493:T:C	W30R	0.993
19:17215456:C:G	C17W	0.992
19:17219677:T:C	L215P	0.992
19:17215434:T:C	L10P	0.991
19:17215455:G:A	C17Y	0.991
19:17215815:T:C	L39P	0.991
19:17219338:T:C	L183P	0.991
19:17219380:A:T	D197V	0.991
19:17215446:T:C	L14P	0.990
19:17216042:T:C	L68P	0.990
19:17219379:G:C	D197H	0.990
19:17219688:T:C	S219P	0.990
19:17219766:T:C	F245L	0.990
19:17219768:C:A	F245L	0.990
19:17219768:C:G	F245L	0.990
19:17215495:G:C	W30C	0.989
19:17215495:G:T	W30C	0.989
19:17215496:C:A	R31S	0.989
19:17219380:A:C	D197A	0.989
19:17215454:T:C	C17R	0.988
19:17219655:G:C	A208P	0.987
19:17219643:T:C	S204P	0.986
19:17219358:G:C	A190P	0.985
19:17219695:G:C	R221P	0.985
19:17216038:T:C	F67L	0.982
19:17216040:T:A	F67L	0.982
19:17216040:T:G	F67L	0.982

dbSNP variants (sampled 300 via entrez): RS1000117418 (19:17214210 G>A,T), RS1000782575 (19:17216497 T>C), RS1000887027 (19:17216921 T>G), RS1001826784 (19:17217265 C>T), RS1001887853 (19:17215560 T>C), RS1002440270 (19:17215580 C>A,T), RS1002494369 (19:17215313 G>A,C), RS1002830074 (19:17214042 T>C), RS1002830122 (19:17218552 G>A), RS1004162089 (19:17219835 G>A,C), RS1004411246 (19:17213801 C>G), RS1005837957 (19:17218126 C>A,T), RS1006126123 (19:17216944 C>G), RS1006849955 (19:17217457 C>G,T), RS1008198390 (19:17215080 A>G,T)

Disease associations

OMIM: gene MIM:610675 | 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: yes

ChEMBL targets (1): CHEMBL6066524 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases methylation, affects cotreatment, decreases expression	5
sodium arsenite	affects cotreatment, increases abundance, increases expression	2
Tunicamycin	increases expression	2
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	increases expression	1
zinc chloride	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	increases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
jinfukang	increases expression	1
(+)-JQ1 compound	decreases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Doxorubicin	decreases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Selenium	increases expression	1
Smoke	decreases expression	1
Tretinoin	decreases expression	1
Zinc	increases expression	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	increases expression	1
Thapsigargin	increases expression	1
Lactic Acid	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652782	Binding	Binding affinity to human USE1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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