TMUB1

Summary

TMUB1 (transmembrane and ubiquitin like domain containing 1, HGNC:21709) is a protein-coding gene on chromosome 7q36.1, encoding Transmembrane and ubiquitin-like domain-containing protein 1 (Q9BVT8). Involved in sterol-regulated ubiquitination and degradation of HMG-CoA reductase HMGCR.

Involved in ERAD pathway. Predicted to be located in several cellular components, including centrosome; postsynaptic membrane; and recycling endosome. Predicted to be active in postsynaptic recycling endosome membrane.

Source: NCBI Gene 83590 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 37 total
• MANE Select transcript: NM_001136044

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21709
Approved symbol	TMUB1
Name	transmembrane and ubiquitin like domain containing 1
Location	7q36.1
Locus type	gene with protein product
Status	Approved
Aliases	SB144, HOPS
Ensembl gene	ENSG00000164897
Ensembl biotype	protein_coding
OMIM	614792
Entrez	83590

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 15 protein_coding

ENST00000297533, ENST00000392818, ENST00000462940, ENST00000476627, ENST00000482202, ENST00000488752, ENST00000492838, ENST00000653405, ENST00000873650, ENST00000873651, ENST00000873652, ENST00000873653, ENST00000873654, ENST00000924882, ENST00000924883

RefSeq mRNA: 2 — MANE Select: NM_001136044 NM_001136044, NM_031434

CCDS: CCDS5920

Canonical transcript exons

ENST00000297533 — 3 exons

Exon	Start	End
ENSE00001088367	151082175	151082593
ENSE00001088369	151083434	151083493
ENSE00001825881	151081085	151081900

Expression profiles

Bgee: expression breadth ubiquitous, 139 present calls, max score 96.33.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.2561 / max 226.8990, expressed in 1809 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
86864	20.2572	1804
86863	1.4343	367
86865	0.5647	320

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	96.33	gold quality
right lobe of liver	UBERON:0001114	95.87	gold quality
lower esophagus mucosa	UBERON:0035834	95.79	gold quality
body of pancreas	UBERON:0001150	95.66	gold quality
thymus	UBERON:0002370	95.27	silver quality
body of stomach	UBERON:0001161	95.04	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.65	gold quality
gastrocnemius	UBERON:0001388	94.57	gold quality
adenohypophysis	UBERON:0002196	94.48	gold quality
fundus of stomach	UBERON:0001160	94.44	gold quality
pituitary gland	UBERON:0000007	94.29	gold quality
apex of heart	UBERON:0002098	94.28	gold quality
granulocyte	CL:0000094	93.81	gold quality
small intestine Peyer’s patch	UBERON:0003454	93.50	gold quality
duodenum	UBERON:0002114	93.44	gold quality
muscle of leg	UBERON:0001383	93.34	gold quality
transverse colon	UBERON:0001157	93.30	gold quality
metanephros cortex	UBERON:0010533	93.28	gold quality
small intestine	UBERON:0002108	93.13	gold quality
liver	UBERON:0002107	93.09	gold quality
right lobe of thyroid gland	UBERON:0001119	93.01	gold quality
left lobe of thyroid gland	UBERON:0001120	92.82	gold quality
lower esophagus	UBERON:0013473	92.80	gold quality
lower esophagus muscularis layer	UBERON:0035833	92.80	gold quality
adult mammalian kidney	UBERON:0000082	92.60	gold quality
muscle layer of sigmoid colon	UBERON:0035805	92.58	gold quality
mucosa of stomach	UBERON:0001199	92.56	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	92.48	gold quality
blood	UBERON:0000178	92.46	gold quality
popliteal artery	UBERON:0002250	92.41	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.24
E-MTAB-6379	no	52.29

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

11 targeting TMUB1, 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-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-6793-3P	97.66	65.78	1084
HSA-MIR-1913	97.07	66.20	1417
HSA-MIR-5587-3P	82.90	60.79	138

Literature-anchored findings (GeneRIF, showing 7)

• a novel ubiquitin-like molecule DULP from human dendritic cells was identified. (PMID:19254477)
• TMUB1 promoted the expression of STAT1, and suppressed the expression of CCND1 in HCC cells. TMUB1 negatively regulates hepatocellular carcinoma proliferation via regulating STAT1. (PMID:31827061)
• The Ins and Outs of HOPS/TMUB1 in biology and pathology. (PMID:32860479)
• TMUB1 Correlated with Immune Infiltration Is a Prognostic Marker for Colorectal Cancer. (PMID:35928927)
• Promoting anti-tumor immunity by targeting TMUB1 to modulate PD-L1 polyubiquitination and glycosylation. (PMID:36376293)
• Inhibition of TMUB1 blocks apoptosis and NF-kappaB pathway-mediated inflammation in recurrent spontaneous abortion. (PMID:37249279)
• TMUB1 expression is associated with the prognosis of colon cancer and immune cell infiltration. (PMID:38025742)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmub1	ENSDARG00000038787
mus_musculus	Tmub1	ENSMUSG00000028958
rattus_norvegicus	Tmub1	ENSRNOG00000013383
caenorhabditis_elegans		WBGENE00015126

Paralogs (1): TMUB2 (ENSG00000168591)

Protein

Protein identifiers

Transmembrane and ubiquitin-like domain-containing protein 1 — Q9BVT8 (reviewed: Q9BVT8)

Alternative names: Dendritic cell-derived ubiquitin-like protein, Hepatocyte odd protein shuttling protein, Ubiquitin-like protein SB144

All UniProt accessions (5): A0A090N8Q3, A0A590UJA9, C9JCW7, C9JE12, Q9BVT8

UniProt curated annotations — full annotation on UniProt →

Function. Involved in sterol-regulated ubiquitination and degradation of HMG-CoA reductase HMGCR. Involved in positive regulation of AMPA-selective glutamate receptor GRIA2 recycling to the cell surface. Acts as a negative regulator of hepatocyte growth during regeneration. May contribute to the regulation of translation during cell-cycle progression. May contribute to the regulation of cell proliferation. May be involved in centrosome assembly. Modulates stabilization and nucleolar localization of tumor suppressor CDKN2A and enhances association between CDKN2A and NPM1.

Subunit / interactions. Interacts with EEF1A1, GRIA2, GRIP1, CAMLG, TUBG1. Interacts with NPM1 and CDKN2A; TMUB1 can enhance interaction between NPM1 and CDKN2A and is proposed to bridge the proteins; proposed to be mediated by iHOPS. Interacts with ERLIN2 and AMFR; TMUB1 promotes the interaction of ERLIN2 with AMFR.

Subcellular location. Membrane. Postsynaptic cell membrane. Recycling endosome. Cytoplasm. Nucleus. Nucleolus Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Nucleolus.

Tissue specificity. Ubiquitously expressed with highest levels in mammary and thyroid glands, bone marrow and spleen; limited expression in cardiac, pancreatic and ovarian tissues.

Post-translational modifications. Processed by regulated intramembrane proteolysis (RIP)in the N-terminus to release iHOPS from membranes.

RefSeq proteins (2): NP_001129516, NP_113622 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000626	Ubiquitin-like_dom	Domain
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily
IPR040352	TMUB1/2	Family

Pfam: PF00240

UniProt features (14 total): modified residue 5, transmembrane region 3, chain 2, region of interest 2, domain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BVT8-F1	67.20	0.04

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 (5): 73, 92, 98, 127, 71

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 78 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOCC_CENTROSOME, GOBP_PROTEASOMAL_PROTEIN_CATABOLIC_PROCESS, GOBP_ERAD_PATHWAY, GOBP_PROTEIN_CATABOLIC_PROCESS, GOCC_POSTSYNAPSE, GOCC_SYNAPSE, GOCC_POSTSYNAPTIC_MEMBRANE, GOBP_PROTEOLYSIS, GOCC_PLASMA_MEMBRANE_REGION, GOCC_NUCLEOLUS, GOCC_RECYCLING_ENDOSOME

GO Biological Process (1): ERAD pathway (GO:0036503)

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

GO Cellular Component (11): nucleolus (GO:0005730), centrosome (GO:0005813), postsynaptic membrane (GO:0045211), recycling endosome (GO:0055037), nucleus (GO:0005634), cytoplasm (GO:0005737), endosome (GO:0005768), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), membrane (GO:0016020), synapse (GO:0045202)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membraneless organelle	2
cellular anatomical structure	2
proteasomal protein catabolic process	1
response to endoplasmic reticulum stress	1
response to chemical	1
binding	1
nuclear lumen	1
centriole	1
microtubule organizing center	1
synaptic membrane	1
postsynapse	1
endosome	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
endomembrane system	1
cytoplasmic vesicle	1
membrane	1
cell periphery	1
cell junction	1

Protein interactions and networks

STRING

814 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMUB1	TMEM259	Q4ZIN3	851
TMUB1	ERLIN2	O94905	747
TMUB1	RNF185	Q96GF1	701
TMUB1	AMFR	P26442	660
TMUB1	ERLIN1	O75477	625
TMUB1	A0A2R8Y422	A0A2R8Y422	576
TMUB1	FAM8A1	Q9UBU6	574
TMUB1	RNF170	Q96K19	557
TMUB1	TMEM126A	Q9H061	546
TMUB1	C6orf120	Q7Z4R8	495
TMUB1	UBE2G2	P56554	461
TMUB1	TMEM53	Q6P2H8	461
TMUB1	TMUB2	Q71RG4	456
TMUB1	UBE2J1	Q9Y385	456
TMUB1	PLEKHM1	Q9Y4G2	446

IntAct

74 interactions, top by confidence:

A	B	Type	Score
ERLIN1	ERLIN2	psi-mi:“MI:0914”(association)	0.740
ERLIN2	TMUB1	psi-mi:“MI:0915”(physical association)	0.660
ERLIN2	TMUB1	psi-mi:“MI:0914”(association)	0.660
TMUB1	ERLIN2	psi-mi:“MI:0915”(physical association)	0.660
TMUB1	ERLIN2	psi-mi:“MI:0914”(association)	0.660
TMUB1	AMFR	psi-mi:“MI:0915”(physical association)	0.560
SGTB	TMUB1	psi-mi:“MI:0915”(physical association)	0.560
GOLM1	TMUB1	psi-mi:“MI:0915”(physical association)	0.560
TMBIM6	TMUB1	psi-mi:“MI:0915”(physical association)	0.560
TMUB1	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
TMUB1	JPH3	psi-mi:“MI:0915”(physical association)	0.560
ADGRG5	KLRG2	psi-mi:“MI:0914”(association)	0.530
RIC3	ATP9A	psi-mi:“MI:0914”(association)	0.530
DUSP3	ERLIN1	psi-mi:“MI:0914”(association)	0.530
ANKH	FAM234B	psi-mi:“MI:0914”(association)	0.530
TMUB1	SYVN1	psi-mi:“MI:0915”(physical association)	0.400
RNF139	TMUB1	psi-mi:“MI:0915”(physical association)	0.400
KISS1R	ERLIN1	psi-mi:“MI:0915”(physical association)	0.400
ERLIN2		psi-mi:“MI:0914”(association)	0.350
CHRNA9	TMEM120B	psi-mi:“MI:0914”(association)	0.350
KCNK16	EMC8	psi-mi:“MI:0914”(association)	0.350
RIC3	ATP9A	psi-mi:“MI:0914”(association)	0.350
TMUB2	ERLIN1	psi-mi:“MI:0914”(association)	0.350
	NBAS	psi-mi:“MI:0914”(association)	0.350

BioGRID (152): TMUB1 (Affinity Capture-MS), TMUB1 (Affinity Capture-MS), TMUB1 (Affinity Capture-MS), TMUB1 (Affinity Capture-MS), TMUB1 (Affinity Capture-MS), TMUB1 (Affinity Capture-MS), TMUB1 (Affinity Capture-MS), TMUB1 (Affinity Capture-MS), TMUB1 (Affinity Capture-MS), TMUB1 (Affinity Capture-MS), TMUB1 (Affinity Capture-MS), TMUB1 (Affinity Capture-MS), TMUB1 (Affinity Capture-MS), TMUB1 (Affinity Capture-MS), TMUB1 (Affinity Capture-MS)

ESM2 similar proteins: A7E3N7, B1AVH7, B5DFA1, D2H0G5, D3ZZN9, E9PY61, E9Q6X9, O75425, O95382, Q0QWG9, Q24JP5, Q3T033, Q3ZBI9, Q53AQ4, Q5TG30, Q60806, Q6F5E8, Q6PGG2, Q6V7V2, Q6ZW31, Q76MJ5, Q7Z465, Q80WF4, Q8BGG6, Q8C0R7, Q8C6B2, Q8CJ00, Q8R2K4, Q8WVB6, Q91WA6, Q922P8, Q924T7, Q969H4, Q96EP0, Q96F46, Q99JU7, Q9BST9, Q9BVT8, Q9BXM7, Q9DBZ9

Diamond homologs: P34256, Q2HJA8, Q3KPV4, Q3V209, Q3ZBI9, Q4FZV7, Q4V9Y1, Q53AQ4, Q6P135, Q71RG4, Q9BVT8, Q9JMG3

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 75 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
Calnexin/calreticulin cycle	5	70.0×	2e-06
N-glycan trimming in the ER and Calnexin/Calreticulin cycle	5	41.5×	1e-05
Defective CFTR causes cystic fibrosis	5	21.5×	2e-04
AMPK-induced ERAD and lysosome mediated degradation of PD-L1(CD274)	5	19.0×	2e-04
ABC-family protein mediated transport	5	11.9×	2e-03
SLC-mediated transmembrane transport	8	9.3×	1e-04
Transport of small molecules	11	5.4×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
ERAD pathway	9	24.7×	4e-08
transmembrane transport	6	15.3×	4e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

37 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

681 predictions. Top by Δscore:

Variant	Effect	Δscore
7:151081901:C:CC	acceptor_gain	1.0000
7:151081902:T:C	acceptor_loss	1.0000
7:151082171:TTA:T	donor_loss	1.0000
7:151082173:A:AC	donor_gain	1.0000
7:151082174:C:CC	donor_gain	1.0000
7:151083432:ACCGC:A	donor_gain	1.0000
7:151083433:CCGCC:C	donor_gain	1.0000
7:151081896:GGGTC:G	acceptor_gain	0.9900
7:151081898:GTC:G	acceptor_gain	0.9900
7:151081899:TC:T	acceptor_gain	0.9900
7:151081900:CC:C	acceptor_gain	0.9900
7:151082170:CTTA:C	donor_gain	0.9900
7:151082173:AC:A	donor_gain	0.9900
7:151082174:CC:C	donor_gain	0.9900
7:151082174:CCT:C	donor_gain	0.9900
7:151082174:CCTT:C	donor_gain	0.9900
7:151082174:CCTTT:C	donor_gain	0.9900
7:151082498:C:CT	acceptor_gain	0.9900
7:151082589:CCGAG:C	acceptor_gain	0.9900
7:151082590:CGAG:C	acceptor_gain	0.9900
7:151082590:CGAGC:C	acceptor_gain	0.9900
7:151082594:C:CC	acceptor_gain	0.9900
7:151083426:GGACT:G	donor_loss	0.9900
7:151083427:GACT:G	donor_loss	0.9900
7:151083428:ACTC:A	donor_loss	0.9900
7:151083429:CTC:C	donor_loss	0.9900
7:151083430:TCA:T	donor_loss	0.9900
7:151083431:CA:C	donor_loss	0.9900
7:151083432:A:AC	donor_gain	0.9900
7:151083432:A:T	donor_loss	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000693573 (7:151080811 G>A), RS1001512726 (7:151080781 G>A,C), RS1002326513 (7:151084183 A>T), RS1002778273 (7:151083886 C>A,T), RS1003410218 (7:151082946 T>G), RS1003777174 (7:151082696 C>T), RS1004651210 (7:151084221 C>T), RS1004810846 (7:151081378 A>G,T), RS1005918073 (7:151084827 C>A,T), RS1006494715 (7:151085034 C>A), RS1006714174 (7:151081140 T>C), RS1007097750 (7:151081454 C>T), RS1008503443 (7:151082238 A>G,T), RS1009507801 (7:151080891 C>G,T), RS1009944318 (7:151085453 G>A,C)

Disease associations

OMIM: gene MIM:614792 | 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
GCST003476_9	Eyebrow thickness	7.000000e-06

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, increases expression	3
aristolochic acid I	increases expression	1
beta-lapachone	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
abrine	decreases expression	1
(+)-JQ1 compound	decreases expression	1
MT19c compound	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	affects methylation	1
Caffeine	affects phosphorylation	1
Gallic Acid	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Copper Sulfate	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2IX	Abcam HeLa TMUB1 KO	Cancer cell line	Female
CVCL_B2IY	Abcam HeLa TMUB1 partial KO	Cancer cell line	Female

Clinical trials (associated diseases)

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