SLURP2

Summary

SLURP2 (secreted LY6/PLAUR domain containing 2, HGNC:25549) is a protein-coding gene on chromosome 8q24.3, encoding Secreted Ly-6/uPAR domain-containing protein 2 (P0DP57). Binds and may modulate the functional properties of nicotinic and muscarinic acetylcholine receptors.

This gene encodes a novel, secreted member of the Ly6/uPAR (LU) superfamily of proteins containing the unique three-finger LU domain. This gene is mainly expressed in epithelial cells, including skin and keratinocytes, and is up-regulated in psoriatic skin lesions, suggesting its involvement in the pathophysiology of psoriasis. Alternatively spliced transcript variants have been found for this gene. Read-through transcription from the neighboring upstream gene (LYNX1) generates naturally-occurring transcripts (LYNX1-SLURP2) that encode a fusion protein comprised of sequence sharing identity with each individual gene product.

Source: NCBI Gene 432355 — RefSeq curated summary.

At a glance

• MANE Select transcript: NM_177458

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25549
Approved symbol	SLURP2
Name	secreted LY6/PLAUR domain containing 2
Location	8q24.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000283992
Ensembl biotype	protein_coding
Entrez	432355

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000317543, ENST00000521396, ENST00000853245

RefSeq mRNA: 2 — MANE Select: NM_177458 NM_001356372, NM_177458

CCDS: CCDS34952

Canonical transcript exons

ENST00000317543 — 3 exons

Exon	Start	End
ENSE00001307579	142769755	142769828
ENSE00003806916	142765036	142765140
ENSE00003807580	142764338	142764741

Expression profiles

Bgee: expression breadth ubiquitous, 116 present calls, max score 99.55.

FANTOM5 (CAGE): breadth broad, TPM avg 2.3690 / max 543.8351, expressed in 191 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
95424	2.3690	191

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	99.55	gold quality
esophagus mucosa	UBERON:0002469	98.92	gold quality
skin of leg	UBERON:0001511	97.81	gold quality
zone of skin	UBERON:0000014	97.12	gold quality
skin of abdomen	UBERON:0001416	96.44	gold quality
esophagus	UBERON:0001043	92.35	gold quality
vagina	UBERON:0000996	91.21	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.69	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	87.17	gold quality
lower esophagus	UBERON:0013473	85.10	gold quality
lower esophagus muscularis layer	UBERON:0035833	85.06	gold quality
muscle layer of sigmoid colon	UBERON:0035805	84.55	gold quality
descending thoracic aorta	UBERON:0002345	84.29	gold quality
mucosa of stomach	UBERON:0001199	83.65	gold quality
thoracic aorta	UBERON:0001515	83.12	gold quality
ascending aorta	UBERON:0001496	82.91	gold quality
popliteal artery	UBERON:0002250	82.80	gold quality
tibial artery	UBERON:0007610	82.77	gold quality
ectocervix	UBERON:0012249	81.39	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	79.91	gold quality
right coronary artery	UBERON:0001625	79.64	gold quality
left coronary artery	UBERON:0001626	77.38	gold quality
uterine cervix	UBERON:0000002	75.59	gold quality
prostate gland	UBERON:0002367	72.98	gold quality
left uterine tube	UBERON:0001303	72.97	gold quality
body of uterus	UBERON:0009853	72.03	gold quality
colon	UBERON:0001155	70.94	gold quality
endocervix	UBERON:0000458	69.06	gold quality
myometrium	UBERON:0001296	68.89	gold quality
urinary bladder	UBERON:0001255	68.33	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	392.69
E-MTAB-10283	yes	145.68
E-ANND-3	yes	10.04

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

14 targeting SLURP2, 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-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-5001-5P	99.05	66.76	1972
HSA-MIR-6846-5P	98.81	65.86	1121
HSA-MIR-6848-5P	98.81	65.49	1126
HSA-MIR-1233-3P	96.81	65.44	573
HSA-MIR-4296	96.35	63.55	1233
HSA-MIR-6796-5P	95.37	66.08	1120

Literature-anchored findings (GeneRIF, showing 2)

• Computer modeling revealed possible SLURP-2 binding to the ‘classical’ orthosteric agonist/antagonist binding sites at alpha7 and alpha3beta2-nAChRs. (PMID:27485575)
• SLURPs inhibit growth of epithelial cancer cells in vitro and merit further investigation as potential agents for anticancer therapy (PMID:29505672)

Cross-species orthologs

0 orthologs

Protein

Protein identifiers

Secreted Ly-6/uPAR domain-containing protein 2 — P0DP57 (reviewed: P0DP57)

Alternative names: Secreted LY6/PLAUR domain-containing protein 2, Secreted Ly-6/uPAR-related protein 2

All UniProt accessions (2): P0DP57, H0YB12

UniProt curated annotations — full annotation on UniProt →

Function. Binds and may modulate the functional properties of nicotinic and muscarinic acetylcholine receptors. May regulate keratinocytes proliferation, differentiation and apoptosis. In vitro moderately inhibits ACh-evoked currents of alpha-3:beta-2-containing nAChRs and strongly these of alpha-4:beta-2-containing nAChRs, modulates alpha-7-containing nAChRs, and inhibits nicotine-induced signaling probably implicating alpha-3:beta-4-containing nAChRs. Proposed to act on alpha-3:beta-2 and alpha-7 nAChRs in an orthosteric, and on mAChRs, such as CHRM1 and CHRM3, in an allosteric manner.

Subunit / interactions. Interacts with CHRNA3, CHRNA4, CHRNA5, CHRNA7, CHRNB2 and CHRNB4. Interacts with CHRM1 and CHRM3 probably in an allosteric manner.

Subcellular location. Secreted.

Tissue specificity. Expressed at highest levels in cervix and esophagus, followed by adult and fetal skin. Expressed at lower levels in brain, lung, stomach, small intestine, colon, rectum, uterus, and thymus. Not detected in spleen nor bone marrow. Up-regulated 3-fold in psoriatic lesional skin. In the epidermis, predominantly produced by keratinocytes of the suprabasal epidermal compartment (at protein level). In attached gingiva, produced at highest levels by basal cells located in the lowermost epithelial layers (at protein level). Detected in serum (at protein level).

Induction. Up-regulation by IL22/interleukin-22 is suppressed by IFNG/Interferon gamma (at protein level).

RefSeq proteins (2): NP_001343301, NP_803253* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR016054	LY6_UPA_recep-like	Domain
IPR045860	Snake_toxin-like_sf	Homologous_superfamily
IPR051110	Ly-6/neurotoxin-like_GPI-ap	Family

Pfam: PF00021

UniProt features (17 total): strand 6, disulfide bond 5, turn 2, signal peptide 1, chain 1, helix 1, domain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2N99	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0DP57-F1	84.49	0.51

Functional residue map

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

Disulfide bonds (5): 25–47, 28–34, 40–68, 72–88, 89–94

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 24 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_CELL_CELL_SIGNALING, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_CELLULAR_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_SYNAPTIC_SIGNALING, GOBP_RESPONSE_TO_ACETYLCHOLINE, GOBP_REGULATION_OF_NEUROTRANSMITTER_RECEPTOR_ACTIVITY, GOMF_SIGNALING_RECEPTOR_BINDING, DURCHDEWALD_SKIN_CARCINOGENESIS_UP, GOCC_SYNAPSE, GOMF_SIGNALING_RECEPTOR_REGULATOR_ACTIVITY, GOMF_SIGNALING_RECEPTOR_INHIBITOR_ACTIVITY, RICKMAN_HEAD_AND_NECK_CANCER_E, GOBP_REGULATION_OF_SIGNALING_RECEPTOR_ACTIVITY

GO Biological Process (2): acetylcholine receptor signaling pathway (GO:0095500), regulation of neurotransmitter receptor activity (GO:0099601)

GO Molecular Function (3): acetylcholine receptor regulator activity (GO:0030548), acetylcholine receptor inhibitor activity (GO:0030550), acetylcholine receptor binding (GO:0033130)

GO Cellular Component (4): obsolete extracellular space (GO:0005615), plasma membrane (GO:0005886), synapse (GO:0045202), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
acetylcholine receptor activity	3
postsynaptic signal transduction	1
cellular response to acetylcholine	1
regulation of signaling receptor activity	1
neurotransmitter receptor activity	1
neurotransmitter receptor regulator activity	1
signaling receptor inhibitor activity	1
acetylcholine receptor regulator activity	1
signaling receptor binding	1
membrane	1
cell periphery	1
cell junction	1
cellular anatomical structure	1

Protein interactions and networks

STRING

78 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLURP2	SLURP1	P55000	688
SLURP2	LYNX1	P0DP58	580
SLURP2	SPACA4	Q8TDM5	447
SLURP2	LYPD6B	Q8NI32	435
SLURP2	LYPD6	Q86Y78	396
SLURP2	AMER1	Q5JTC6	313
SLURP2	LYG2	Q86SG7	258
SLURP2	PLAUR	Q03405	250
SLURP2	LY6G5B	Q8NDX9	249
SLURP2	A0A0B4J1T7	A0A0B4J1T7	246
SLURP2	CHRNA9	Q9UGM1	232
SLURP2	PSCA	O43653	225
SLURP2	LY6G5C	Q5SRR4	222
SLURP2	LY6G6C	O95867	212
SLURP2	MFAP1	P55081	203

IntAct

2 interactions, top by confidence:

A	B	Type	Score
CHRNA7	SLURP2	psi-mi:“MI:0915”(physical association)	0.400

ESM2 similar proteins: A0JNL5, H2LID1, O55006, O55186, O62680, O77541, O95867, O95868, P05533, P0DP57, P0DP59, P0DP61, P0DPQ9, P13987, P27274, P35459, P35460, P35461, P46657, P51447, P55000, P58019, P81827, P81828, P83121, Q14210, Q17RY6, Q28216, Q28785, Q32PB3, Q5R510, Q63317, Q66H42, Q6MG58, Q6UWN5, Q6UXB3, Q7TQN2, Q80ZQ0, Q8BLC3, Q8N2G4

Diamond homologs: P0DP57, P0DP59, P0DP61, Q6UXB3, P0DP62, Q63317, Q9DD23, Q9CWP4, O43653, P55000, Q9Z0K7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

622 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:142764701:C:A	K66N	0.985
8:142764701:C:G	K66N	0.985
8:142765053:C:G	C47S	0.984
8:142765054:A:T	C47S	0.984
8:142764618:C:G	C94S	0.979
8:142764619:A:T	C94S	0.979
8:142764696:C:G	C68S	0.975
8:142764697:A:T	C68S	0.975
8:142765100:G:C	F31L	0.975
8:142765100:G:T	F31L	0.975
8:142765102:A:G	F31L	0.975
8:142764633:C:G	C89S	0.972
8:142764634:A:T	C89S	0.972
8:142764684:C:G	C72S	0.972
8:142764685:A:T	C72S	0.972
8:142765119:C:G	C25S	0.972
8:142765120:A:T	C25S	0.972
8:142765053:C:T	C47Y	0.969
8:142765092:C:G	C34S	0.968
8:142765093:A:T	C34S	0.968
8:142764646:A:G	S85P	0.965
8:142765054:A:G	C47R	0.963
8:142764618:C:T	C94Y	0.962
8:142764633:C:T	C89Y	0.962
8:142765052:A:C	C47W	0.962
8:142765110:C:G	C28S	0.962
8:142765111:A:T	C28S	0.962
8:142764685:A:G	C72R	0.961
8:142765101:A:C	F31C	0.961
8:142764636:C:G	C88S	0.958

dbSNP variants (sampled 300 via entrez): RS1000084537 (8:142768329 AC>A), RS1000154996 (8:142769410 G>T), RS1001063061 (8:142765419 T>G), RS1001255802 (8:142767817 T>G), RS1001430542 (8:142765613 G>C), RS1001735412 (8:142767453 G>A), RS1002105978 (8:142767653 A>C), RS1002126971 (8:142771118 G>A), RS1002469319 (8:142766388 G>A), RS1002669462 (8:142768864 C>A,T), RS1002744389 (8:142768597 C>T), RS1002809091 (8:142763912 G>A), RS1002979971 (8:142764074 G>A), RS1003112923 (8:142771343 C>T), RS1003163789 (8:142771531 G>T)

Disease associations

OMIM: gene `` | 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

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
benzo(e)pyrene	decreases methylation	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Methapyrilene	decreases methylation	1
Smoke	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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