EMP3

Summary

EMP3 (epithelial membrane protein 3 (MAM blood group), HGNC:3335) is a protein-coding gene on chromosome 19q13.33, encoding Epithelial membrane protein 3 (P54852). Probably involved in cell proliferation and cell-cell interactions.

The protein encoded by this gene belongs to the PMP-22/EMP/MP20 family of proteins. The protein contains four transmembrane domains and two N-linked glycosylation sites. It is thought to be involved in cell proliferation, cell-cell interactions and function as a tumor suppressor. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 2014 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 32 total
• MANE Select transcript: NM_001425

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3335
Approved symbol	EMP3
Name	epithelial membrane protein 3 (MAM blood group)
Location	19q13.33
Locus type	gene with protein product
Status	Approved
Aliases	YMP
Ensembl gene	ENSG00000142227
Ensembl biotype	protein_coding
OMIM	602335
Entrez	2014

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 17 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000270221, ENST00000593437, ENST00000594198, ENST00000596315, ENST00000597057, ENST00000597279, ENST00000597529, ENST00000599255, ENST00000599704, ENST00000850572, ENST00000859923, ENST00000859924, ENST00000859925, ENST00000859926, ENST00000859927, ENST00000859928, ENST00000859929, ENST00000935119, ENST00000964536, ENST00000964537

RefSeq mRNA: 2 — MANE Select: NM_001425 NM_001313905, NM_001425

CCDS: CCDS12715

Canonical transcript exons

ENST00000270221 — 5 exons

Exon	Start	End
ENSE00003006707	48325552	48325610
ENSE00003464671	48329352	48329492
ENSE00003539896	48326830	48326922
ENSE00003590409	48327521	48327623
ENSE00004282157	48330301	48330553

Expression profiles

Bgee: expression breadth ubiquitous, 259 present calls, max score 99.64.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 123.7213 / max 837.9981, expressed in 1807 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
176762	113.4374	1707
176758	2.1167	660
176756	1.7789	819
176763	1.6987	899
176765	1.4821	821
176761	1.4559	564
176759	0.9099	371
176764	0.4619	257
208885	0.3798	182

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	99.64	gold quality
monocyte	CL:0000576	99.51	gold quality
leukocyte	CL:0000738	99.47	gold quality
mononuclear cell	CL:0000842	99.46	gold quality
synovial joint	UBERON:0002217	99.32	gold quality
stromal cell of endometrium	CL:0002255	99.21	gold quality
smooth muscle tissue	UBERON:0001135	98.96	gold quality
endocervix	UBERON:0000458	98.80	gold quality
layer of synovial tissue	UBERON:0007616	98.73	gold quality
body of uterus	UBERON:0009853	98.65	gold quality
right lung	UBERON:0002167	98.58	gold quality
left uterine tube	UBERON:0001303	98.57	gold quality
thoracic aorta	UBERON:0001515	98.53	gold quality
ascending aorta	UBERON:0001496	98.52	gold quality
descending thoracic aorta	UBERON:0002345	98.51	gold quality
blood	UBERON:0000178	98.50	gold quality
upper lobe of left lung	UBERON:0008952	98.50	gold quality
mucosa of stomach	UBERON:0001199	98.48	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.45	gold quality
right coronary artery	UBERON:0001625	98.39	gold quality
left coronary artery	UBERON:0001626	98.35	gold quality
calcaneal tendon	UBERON:0003701	98.34	gold quality
right ovary	UBERON:0002118	98.29	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.25	gold quality
coronary artery	UBERON:0001621	98.21	gold quality
upper lobe of lung	UBERON:0008948	98.17	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.01	gold quality
lower esophagus	UBERON:0013473	97.96	gold quality
bone marrow	UBERON:0002371	97.91	gold quality
aorta	UBERON:0000947	97.86	gold quality

Single-cell (SCXA)

Detected in 25 experiment(s), a significant marker in 22.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	2034.76
E-MTAB-10485	yes	904.11
E-HCAD-4	yes	246.40
E-HCAD-1	yes	94.89
E-HCAD-6	yes	72.29
E-CURD-114	yes	65.90
E-CURD-122	yes	50.07
E-MTAB-8410	yes	41.93
E-GEOD-135922	yes	41.30
E-MTAB-6701	yes	33.18
E-HCAD-10	yes	31.29
E-CURD-88	yes	26.39
E-ANND-3	yes	21.71
E-CURD-112	yes	21.53
E-HCAD-9	yes	21.40

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 28)

• The five genes, and three of the encoded proteins, were shown differentially expressed between a group of keratoconus patients and a reference group using different techniques (PMID:16015083)
• EMP3 overexpression is associated with oligodendroglial tumors (PMID:17187361)
• Oligodendroglial and astrocytic gliomas show EMP3 hypermethylation and aberrant expression. Primary and secondary glioblastomas have distinct genetic profiles and also differ in their epigenetic aberrations. (PMID:17610521)
• Loss of EMP3 is associated with esophageal squamous cell carcinoma. (PMID:18823699)
• Epithelial membrane protein 3 overexpression in breast carcinomas was significantly related to histological grade III , lymph node metastasis , and strong Her-2 expression. (PMID:19270820)
• The promoter methylation and mRNA expressions of EMP3 and PCDH-gamma-A11 are closely related with the malignant development of glioma. (PMID:20388442)
• LOH 19q determines the complete loss of EMP3 function, as the conserved allele is frequently hypermethylated, and this may represent the molecular basis of the higher risk of relapse in this subgroup of grade II oligodendroglioma patients. (PMID:22992787)
• Decreased expression of EMP3 by promoter methylation is associated by lung cancer (PMID:23920144)
• The aim of this study was to investigate the EMP3 promoter hypermethylation status in a series of 229 astrocytic and oligodendroglial tumors and in 16 glioblastoma cell lines. (PMID:24083241)
• EMP3 functions as an oncogene and is regulated by microRNA-765 in primary breast carcinoma. (PMID:26398721)
• The study provided a new insight into EMP3, suggesting that EMP3 enhances malignancy of hepatocellular carcinoma cells (PMID:26472188)
• The studies implicating GAS3 protein family (EMP1, EMP2, EMP3 and PMP22) in cancer pathogenesis as well as probe the structural similarities between the family members were highlighted. (PMID:27279240)
• High EMP3 expression is associated with high grade glioma. (PMID:27527869)
• Independent validation with glioma patients tissue (n = 70) and normal brain tissue (n = 19) found PPIC, EMP3 and CHI3L1 were up-regulated in glioma tissue. Survival value validation showed that the three genes correlated with patient survival by Kaplan-Meir analysis, including grades, age and therapy. (PMID:27801851)
• epithelial membrane protein 3 is a downstream effector of TWIST1/2 in inducing epithelial-to-mesenchymal transition in gastric cancer. Epithelial membrane protein 3 upregulation might be associated with gastric cancer metastasis and is a potential indicator of unfavorable overall survival and progression-free survival in gastric cancer patients (PMID:28718375)
• This study identified and validated a three-gene (EMP3, GSX2 and EMILIN3) prognostic signature in Lower-Grade Gliomas. (PMID:29794476)
• Results found that EMP3 interacts with proteins involved in trafficking and signaling regulation. Its knockdown downregulates mitogenic signaling pathways and reduces cell proliferation and migration of HT-1080 fibrosarcoma cell line. (PMID:30614533)
• Disruption of the tumour-associated EMP3 enhances erythroid proliferation and causes the MAM-negative phenotype. (PMID:32678083)
• EMP3 mediates glioblastoma-associated macrophage infiltration to drive T cell exclusion. (PMID:33964937)
• The Multifunctional Role of EMP3 in the Regulation of Membrane Receptors Associated with IDH-Wild-Type Glioblastoma. (PMID:34067658)
• Establishment of a nomogram with EMP3 for predicting clinical outcomes in patients with glioma: A bi-center study. (PMID:34268874)
• Epithelial membrane protein 3 regulates lung cancer stem cells via the TGFbeta signaling pathway. (PMID:34476496)
• EMP3 negatively modulates breast cancer cell DNA replication, DNA damage repair, and stem-like properties. (PMID:34511602)
• Expression of epithelial membrane protein (EMP) 1, EMP 2, and EMP 3 in thyroid cancer. (PMID:34617578)
• Identification of candidate biomarker EMP3 and its prognostic potential in clear cell renal cell carcinoma. (PMID:34856762)
• Yes, MAM: how the cancer-related EMP3 protein became a regulator of erythropoiesis and the key protein underlying a new blood group system. (PMID:36789459)
• EMP3 sustains oncogenic EGFR/CDK2 signaling by restricting receptor degradation in glioblastoma. (PMID:37936247)
• EMP3 as a prognostic biomarker correlates with EMT in GBM. (PMID:38229014)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	emp3a	ENSDARG00000036428
danio_rerio	emp3b	ENSDARG00000101461
mus_musculus	Emp3	ENSMUSG00000040212
rattus_norvegicus	Emp3	ENSRNOG00000021104

Paralogs (10): LIM2 (ENSG00000105370), NKG7 (ENSG00000105374), PMP22 (ENSG00000109099), GSG1 (ENSG00000111305), EMP1 (ENSG00000134531), CLDND2 (ENSG00000160318), GSG1L (ENSG00000169181), TMEM202 (ENSG00000187806), EMP2 (ENSG00000213853), GSG1L2 (ENSG00000214978)

Protein

Protein identifiers

Epithelial membrane protein 3 — P54852 (reviewed: P54852)

Alternative names: Hematopoietic neural membrane protein 1, Protein YMP

All UniProt accessions (6): P54852, M0QXN1, M0QXS0, M0QZ66, M0R122, M0R1L9

UniProt curated annotations — full annotation on UniProt →

Function. Probably involved in cell proliferation and cell-cell interactions.

Subcellular location. Membrane.

Similarity. Belongs to the PMP-22/EMP/MP20 family.

RefSeq proteins (2): NP_001300834, NP_001416* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003934	EMP_3	Family
IPR004031	PMP22/EMP/MP20/Claudin	Family
IPR004032	PMP22_EMP_MP20	Family
IPR050579	PMP-22/EMP/MP20-like	Family

Pfam: PF00822

UniProt features (9 total): transmembrane region 4, glycosylation site 2, chain 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P54852-F1	90.68	0.62

Functional residue map

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

Glycosylation sites (2): 47, 56

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 347 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_UP, MODULE_52, AP1_01, ZHAN_LATE_DIFFERENTIATION_GENES_UP, GNF2_MSN, PAL_PRMT5_TARGETS_UP, ENK_UV_RESPONSE_KERATINOCYTE_UP, MODULE_45, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, AP4_Q6, MODULE_16, CAGCTG_AP4_Q5, HERNANDEZ_MITOTIC_ARREST_BY_DOCETAXEL_1_UP, GOLDRATH_ANTIGEN_RESPONSE

GO Biological Process (2): apoptotic process (GO:0006915), bleb assembly (GO:0032060)

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

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
plasma membrane bounded cell projection assembly	1
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

759 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EMP3	LIM2	P55344	721
EMP3	PCDHGA11	Q9Y5H2	541
EMP3	TNFRSF12A	Q9NP84	417
EMP3	TMEM61	Q8N0U2	411
EMP3	NT5C1A	Q9BXI3	398
EMP3	MGMT	P16455	394
EMP3	EPOR	P19235	372
EMP3	TMEM47	Q9BQJ4	358
EMP3	TMEM143	Q96AN5	357
EMP3	RNMT	O43148	352
EMP3	AJAP1	Q9UKB5	339
EMP3	LGALS1	P09382	317
EMP3	RAB42	Q8N4Z0	316
EMP3	DYDC1	Q8WWB3	314
EMP3	ATP5MK	Q96IX5	310

IntAct

162 interactions, top by confidence:

A	B	Type	Score
EDA	EMP3	psi-mi:“MI:0915”(physical association)	0.780
EMP3	EDA	psi-mi:“MI:0915”(physical association)	0.780
KLRC1	EMP3	psi-mi:“MI:0915”(physical association)	0.600
EMP3	ELOVL7	psi-mi:“MI:0915”(physical association)	0.560
EMP3	IFNGR2	psi-mi:“MI:0915”(physical association)	0.560
EMP3	KIR3DL3	psi-mi:“MI:0915”(physical association)	0.560
EMP3	CREB3L1	psi-mi:“MI:0915”(physical association)	0.560
EMP3	LYVE1	psi-mi:“MI:0915”(physical association)	0.560
EMP3	TSPAN12	psi-mi:“MI:0915”(physical association)	0.560
EMP3	LDLRAD1	psi-mi:“MI:0915”(physical association)	0.560
EMP3	SMIM3	psi-mi:“MI:0915”(physical association)	0.560
EMP3	PLEKHB2	psi-mi:“MI:0915”(physical association)	0.560
EMP3	GPR61	psi-mi:“MI:0915”(physical association)	0.560
EMP3	SLC30A2	psi-mi:“MI:0915”(physical association)	0.560
OPRM1	EMP3	psi-mi:“MI:0915”(physical association)	0.560
EMP3	MS4A3	psi-mi:“MI:0915”(physical association)	0.560
EMP3	SAR1A	psi-mi:“MI:0915”(physical association)	0.560
EMP3	SLAMF8	psi-mi:“MI:0915”(physical association)	0.560
EMP3	MR1	psi-mi:“MI:0915”(physical association)	0.560
EMP3	TM4SF18	psi-mi:“MI:0915”(physical association)	0.560
EMP3	VSIG1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (70): EMP3 (Two-hybrid), EMP3 (Affinity Capture-MS), EMP3 (Two-hybrid), EMP3 (Two-hybrid), EMP3 (Two-hybrid), EMP3 (Two-hybrid), EMP3 (Two-hybrid), EMP3 (Two-hybrid), EMP3 (Two-hybrid), EMP3 (Two-hybrid), EMP3 (Two-hybrid), EMP3 (Two-hybrid), EMP3 (Two-hybrid), EMP3 (Two-hybrid), EMP3 (Two-hybrid)

ESM2 similar proteins: A5A6N6, D3ZQJ0, F1QIK8, O09117, O35912, O88662, P19075, P47801, P54848, P54849, P54850, P54851, P54852, P56748, Q12999, Q16563, Q2NKU9, Q32KP1, Q3ZBY0, Q4KL25, Q58DR6, Q5PPI7, Q5R9S6, Q5RAI2, Q5RAP8, Q5RCY3, Q5U1V9, Q5XHG6, Q66HH2, Q66IV3, Q6DHB5, Q6GPN9, Q6P742, Q6Y1E2, Q6ZUX7, Q7ZUB3, Q7ZWW7, Q7ZZL8, Q8BGA2, Q8BI08

Diamond homologs: A5A6N6, F1QIK8, O35912, O88662, P16646, P25094, P47801, P54848, P54849, P54850, P54851, P54852, Q01453, Q2NKU9, Q58DR6, Q5RAZ3, Q5RCY3, Q66HH2, Q6WL85, Q9QYW5, Q9TQZ3, P20274, Q2KIY2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	25
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

771 predictions. Top by Δscore:

Variant	Effect	Δscore
19:48327509:T:TA	acceptor_gain	1.0000
19:48327515:T:G	acceptor_gain	1.0000
19:48327606:G:GG	donor_gain	1.0000
19:48329493:G:GG	donor_gain	1.0000
19:48330300:GGC:G	acceptor_gain	1.0000
19:48330300:GGCGT:G	acceptor_gain	1.0000
19:48327514:A:AG	acceptor_gain	0.9900
19:48327519:A:AG	acceptor_gain	0.9900
19:48327520:G:GA	acceptor_gain	0.9900
19:48327520:GT:G	acceptor_gain	0.9900
19:48327520:GTC:G	acceptor_gain	0.9900
19:48327520:GTCC:G	acceptor_gain	0.9900
19:48327520:GTCCT:G	acceptor_gain	0.9900
19:48327619:GAATG:G	donor_gain	0.9900
19:48329348:GCA:G	acceptor_loss	0.9900
19:48329349:CA:C	acceptor_loss	0.9900
19:48329350:A:AC	acceptor_loss	0.9900
19:48329350:A:AG	acceptor_gain	0.9900
19:48329350:AG:A	acceptor_gain	0.9900
19:48329350:AGGCT:A	acceptor_gain	0.9900
19:48329351:G:GG	acceptor_gain	0.9900
19:48329351:GG:G	acceptor_gain	0.9900
19:48329351:GGC:G	acceptor_gain	0.9900
19:48329351:GGCT:G	acceptor_gain	0.9900
19:48329351:GGCTG:G	acceptor_gain	0.9900
19:48329483:C:G	donor_gain	0.9900
19:48329488:CACCA:C	donor_gain	0.9900
19:48329489:ACCA:A	donor_gain	0.9900
19:48329490:CCA:C	donor_gain	0.9900
19:48329491:CA:C	donor_gain	0.9900

AlphaMissense

1050 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:48327526:G:C	W28C	0.998
19:48327526:G:T	W28C	0.998
19:48327562:G:C	W40C	0.998
19:48327562:G:T	W40C	0.998
19:48329492:A:C	S108R	0.998
19:48330302:C:A	S108R	0.998
19:48330302:C:G	S108R	0.998
19:48330432:A:C	S152R	0.998
19:48330434:C:A	S152R	0.998
19:48330434:C:G	S152R	0.998
19:48327569:T:A	C43S	0.997
19:48327570:G:C	C43S	0.997
19:48329420:T:C	F84L	0.997
19:48329422:C:A	F84L	0.997
19:48329422:C:G	F84L	0.997
19:48329459:T:C	F97L	0.997
19:48329461:C:A	F97L	0.997
19:48329461:C:G	F97L	0.997
19:48330392:C:G	C138W	0.997
19:48330435:G:C	G153R	0.997
19:48327524:T:A	W28R	0.996
19:48327524:T:C	W28R	0.996
19:48327560:T:A	W40R	0.996
19:48327560:T:C	W40R	0.996
19:48329460:T:G	F97C	0.996
19:48329472:G:A	G101D	0.996
19:48330318:G:C	G114R	0.996
19:48330436:G:A	G153D	0.996
19:48327529:G:C	W29C	0.995
19:48327529:G:T	W29C	0.995

dbSNP variants (sampled 300 via entrez): RS1000049741 (19:48325625 C>T), RS1000103620 (19:48330695 G>A,T), RS1000622336 (19:48330970 C>G), RS1000910810 (19:48325120 C>A), RS1001354085 (19:48330181 A>C,G), RS1001363270 (19:48324898 C>A,T), RS1001683261 (19:48324241 T>A), RS1002281659 (19:48329466 C>T), RS1002632152 (19:48328693 C>T), RS1002706686 (19:48330391 G>C), RS1003354620 (19:48327243 G>A,T), RS1004299670 (19:48326112 G>A,C,T), RS1004309564 (19:48326310 G>T), RS1004540288 (19:48325219 G>A), RS1004632891 (19:48324795 C>A,T)

Disease associations

OMIM: gene MIM:602335 | 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

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression, increases methylation	4
Cisplatin	affects expression, increases expression, affects response to substance	4
Valproic Acid	affects cotreatment, increases expression, decreases expression	4
Cyclosporine	increases expression	4
(+)-JQ1 compound	decreases expression	3
Tetrachlorodibenzodioxin	affects expression, increases expression	3
Aflatoxin B1	affects expression, increases expression	3
Zoledronic Acid	increases expression, affects cotreatment	2
Methyl Methanesulfonate	decreases expression, increases expression	2
Quercetin	affects cotreatment, increases expression	2
Smoke	increases expression, decreases expression	2
aristolochic acid I	increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	decreases expression	1
salinomycin	decreases expression	1
beta-lapachone	increases expression	1
sulforaphane	decreases expression	1
sodium arsenite	decreases expression	1
ferrous chloride	increases expression	1
avobenzone	increases expression	1
di-n-butylphosphoric acid	affects expression	1
seocalcitol	decreases expression	1
chloropicrin	decreases expression	1
abrine	increases expression	1
jinfukang	increases expression	1
Decitabine	affects expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	decreases 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_D6CJ	HyCyte SH-SY5Y KO-hEMP3	Cancer cell line	Female

Clinical trials (associated diseases)

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