PRB3

Summary

PRB3 (proline rich protein BstNI subfamily 3, HGNC:9339) is a protein-coding gene on chromosome 12p13.2, encoding Basic salivary proline-rich protein 3 (Q04118). Acts as a receptor for the Gram-negative bacterium F.nucleatum.

This gene encodes a member of the heterogeneous family of basic, proline-rich, human salivary glycoproteins. Multiple alleles of this gene exhibiting variations in the length of the tandem repeats have been identified. The reference genome encodes the “Long” allele. The protein isoforms encoded by this gene are recognized as the “first line of oral defense” against the detrimental effects of polyphenols in the diet and pathogen infections. This gene is located in a cluster of closely related salivary proline-rich proteins on chromosome 12.

Source: NCBI Gene 5544 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 66 total — 2 pathogenic
• MANE Select transcript: NM_001394862

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9339
Approved symbol	PRB3
Name	proline rich protein BstNI subfamily 3
Location	12p13.2
Locus type	gene with protein product
Status	Approved
Aliases	PRG
Ensembl gene	ENSG00000197870
Ensembl biotype	protein_coding
OMIM	168840
Entrez	5544

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 retained_intron

ENST00000538488, ENST00000539835

RefSeq mRNA: 2 — MANE Select: NM_001394862 NM_001394862, NM_006249

CCDS: CCDS91655

Canonical transcript exons

ENST00000538488 — 4 exons

Exon	Start	End
ENSE00002237628	11267176	11268148
ENSE00003584900	11268633	11268668
ENSE00003688938	11269606	11269707
ENSE00003744985	11265914	11266029

Expression profiles

Bgee: expression breadth ubiquitous, 108 present calls, max score 97.46.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 83.5765 / max 148479.0902, expressed in 22 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
129618	83.1956	21
129617	0.2628	5
129620	0.0807	3
129619	0.0374	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
olfactory segment of nasal mucosa	UBERON:0005386	97.46	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.37	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	74.89	gold quality
tonsil	UBERON:0002372	71.86	gold quality
bone marrow	UBERON:0002371	62.33	gold quality
bone marrow cell	CL:0002092	55.90	silver quality
sural nerve	UBERON:0015488	53.86	silver quality
saliva-secreting gland	UBERON:0001044	51.44	gold quality
left testis	UBERON:0004533	51.30	gold quality
right testis	UBERON:0004534	50.81	gold quality
skin of leg	UBERON:0001511	50.74	gold quality
testis	UBERON:0000473	50.66	gold quality
zone of skin	UBERON:0000014	50.61	gold quality
rectum	UBERON:0001052	50.50	gold quality
skin of abdomen	UBERON:0001416	50.18	gold quality
urinary bladder	UBERON:0001255	48.29	gold quality
colonic epithelium	UBERON:0000397	48.28	silver quality
adrenal tissue	UBERON:0018303	47.60	gold quality
minor salivary gland	UBERON:0001830	46.87	gold quality
lower esophagus mucosa	UBERON:0035834	46.67	silver quality
endometrium	UBERON:0001295	46.05	gold quality
primary visual cortex	UBERON:0002436	45.34	gold quality
placenta	UBERON:0001987	45.27	gold quality
calcaneal tendon	UBERON:0003701	45.18	silver quality
prostate gland	UBERON:0002367	45.01	gold quality
gall bladder	UBERON:0002110	44.76	gold quality
mucosa of transverse colon	UBERON:0004991	43.69	silver quality
liver	UBERON:0002107	43.31	silver quality
right uterine tube	UBERON:0001302	42.96	silver quality
blood	UBERON:0000178	42.78	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-CURD-114	no	171.18
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

7 targeting PRB3, 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-4778-3P	99.93	70.40	1818
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-15B-3P	97.85	66.68	974
HSA-MIR-5699-3P	97.81	65.00	861
HSA-MIR-6760-3P	96.35	68.31	1001

Literature-anchored findings (GeneRIF, showing 1)

• The results of this study suggested that low levels of PRB3 mRNA may have a role in dopamine-agonist resistance and tumor recurrence of prolactinomas. (PMID:24135847)

Cross-species orthologs

0 orthologs

Paralogs (6): PRR4 (ENSG00000111215), PRB2 (ENSG00000121335), PRH2 (ENSG00000134551), PRB4 (ENSG00000230657), PRH1 (ENSG00000231887), PRB1 (ENSG00000251655)

Protein

Protein identifiers

Basic salivary proline-rich protein 3 — Q04118 (reviewed: Q04118)

Alternative names: Parotid salivary glycoprotein G1, Proline-rich protein G1

All UniProt accessions (1): Q04118

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a receptor for the Gram-negative bacterium F.nucleatum.

Subcellular location. Secreted.

Post-translational modifications. N- and O-glycosylated; contains about 50% carbohydrate. This is composed of highly fucosylated N-linked saccharides, the major structure is a biantennary asialosaccharide containing 2 fucose residues on one antenna and an unsubstituted terminal lactosamine sequence on the other. The Gram-negative bacterium F.nucleatum binds to carbohydrates containing unsubstituted GalBeta1,4GlcNAc residues. N-glycosylation on Asn-87 is prevalent in head and neck cancer patients. Proteolytically cleaved at the tripeptide Xaa-Pro-Gln, where Xaa in the P(3) position is mostly lysine. The endoprotease may be of microbial origin. Besides on the N-terminal of mature PRB3, pyroglutamate formation found on at least Gln-67, Gln-88, Gln-256 and Gln-337.

Polymorphism. The number of repeats is polymorphic and varies among different alleles, at least four alleles (small, medium, large and very large) are known.

RefSeq proteins (2): NP_001381791, NP_006240 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026086	Pro-rich	Family

Pfam: PF15240

UniProt features (56 total): repeat 12, sequence conflict 12, compositionally biased region 11, glycosylation site 10, sequence variant 5, region of interest 2, modified residue 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q04118-F1	47.58	0.00

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 (2): 17, 24

Glycosylation sites (10): 66, 87, 89, 108, 129, 150, 192, 213, 234, 297

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 23 (showing top): GOBP_DEFENSE_RESPONSE_TO_GRAM_NEGATIVE_BACTERIUM, GOBP_DEFENSE_RESPONSE_TO_BACTERIUM, LIU_SOX4_TARGETS_DN, GOBP_RESPONSE_TO_BACTERIUM, YOSHIMURA_MAPK8_TARGETS_UP, SWEET_LUNG_CANCER_KRAS_UP, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, IL21_UP.V1_DN, MIR15B_3P, DURANTE_ADULT_OLFACTORY_NEUROEPITHELIUM_RESPIRATORY_SECRETORY_CELLS, DURANTE_ADULT_OLFACTORY_NEUROEPITHELIUM_RESPIRATORY_EPITHELIAL_CELLS, SCHERER_PBMC_YF_VAX_AGE_18_40YO_4_TO_7DY_DN, SCHERER_PBMC_YF_VAX_AGE_18_40YO_ANYD_DN, TRAVAGLINI_LUNG_SEROUS_CELL, GOBP_BIOLOGICAL_PROCESS_INVOLVED_IN_INTERSPECIES_INTERACTION_BETWEEN_ORGANISMS

GO Biological Process (1): defense response to Gram-negative bacterium (GO:0050829)

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

GO Cellular Component (1): extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
defense response to bacterium	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1352 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRB3	RB1	P06400	809
PRB3	C4BPA	P04003	744
PRB3	ZNF80	P51504	671
PRB3	SFTPA2	P07714	535
PRB3	X6REF7	X6REF7	533
PRB3	SPANXN2	Q5MJ10	478
PRB3	KRTAP10-9	P60411	471
PRB3	STATH	P02808	448
PRB3	MSANTD3	Q96H12	445
PRB3	KRTAP10-3	P60369	432
PRB3	KRTAP10-4	P60372	420
PRB3	KRTAP10-11	P60412	418
PRB3	HTN3	P15516	418
PRB3	MUCL3	Q3MIW9	395
PRB3	KRTAP10-5	P60370	392

IntAct

31 interactions, top by confidence:

A	B	Type	Score
	PRB3	psi-mi:“MI:0915”(physical association)	0.560
PRB3	SGTB	psi-mi:“MI:0915”(physical association)	0.560
PPIF	PRB3	psi-mi:“MI:0915”(physical association)	0.560
GET3	PRB3	psi-mi:“MI:0915”(physical association)	0.560
PRB3	SH3GL1	psi-mi:“MI:0915”(physical association)	0.560
PRB3	TBRG4	psi-mi:“MI:0915”(physical association)	0.560
PRB3	PBX3	psi-mi:“MI:0915”(physical association)	0.560
	PRB3	psi-mi:“MI:0915”(physical association)	0.490
TTK	PRB3	psi-mi:“MI:0915”(physical association)	0.400
NUAK1	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
CLK1	PIGR	psi-mi:“MI:0914”(association)	0.350
CDKL3		psi-mi:“MI:0914”(association)	0.350
ANKK1	DNAJB6	psi-mi:“MI:0914”(association)	0.350
SCYL1	CNOT1	psi-mi:“MI:0914”(association)	0.350
SRPK1	SNRPGP15	psi-mi:“MI:0914”(association)	0.350
PRB3	SGTB	psi-mi:“MI:0915”(physical association)	0.000
PPIF	PRB3	psi-mi:“MI:0915”(physical association)	0.000
GET3	PRB3	psi-mi:“MI:0915”(physical association)	0.000
SH3GL1	PRB3	psi-mi:“MI:0915”(physical association)	0.000
TBRG4	PRB3	psi-mi:“MI:0915”(physical association)	0.000
PBX3	PRB3	psi-mi:“MI:0915”(physical association)	0.000

ESM2 similar proteins: A0A2H4S6M4, A2XT03, C0HM81, C9JFL3, J4WMI6, O31510, O94426, P02810, P04474, P04706, P06600, P06680, P08297, P10163, P10165, P16329, P17816, P19470, P21749, P37705, P50439, P54643, P86960, Q00451, Q00725, Q01642, Q01643, Q01644, Q01645, Q04118, Q0WV37, Q20689, Q25055, Q27270, Q32L04, Q5U1W2, Q61900, Q62266, Q62267, Q63532

Diamond homologs: P02810, P02812, P04280, Q04118, Q16378, P10163

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	37
Likely benign	14
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
13733	NM_001394862.1(PRB3):c.145C>T (p.Arg49Cys)	Pathogenic
13734	NM_001394862.1(PRB3):c.848dup (p.His284fs)	Pathogenic

SpliceAI

365 predictions. Top by Δscore:

Variant	Effect	Δscore
12:11269602:TTA:T	donor_loss	1.0000
12:11269604:A:AG	donor_loss	1.0000
12:11269605:C:CA	donor_loss	1.0000
12:11266168:T:A	donor_gain	0.9900
12:11268629:TTACC:T	donor_loss	0.9900
12:11268632:C:CT	donor_loss	0.9900
12:11269605:CCTT:C	donor_gain	0.9900
12:11268146:TTCC:T	acceptor_loss	0.9800
12:11268147:TCCTG:T	acceptor_loss	0.9800
12:11268148:CCT:C	acceptor_loss	0.9800
12:11268149:C:T	acceptor_loss	0.9800
12:11268150:T:C	acceptor_loss	0.9800
12:11268666:CAT:C	acceptor_gain	0.9800
12:11268667:ATCT:A	acceptor_loss	0.9800
12:11268669:C:A	acceptor_loss	0.9800
12:11268670:T:A	acceptor_loss	0.9800
12:11269604:A:AC	donor_gain	0.9800
12:11269605:C:CC	donor_gain	0.9800
12:11268149:C:CC	acceptor_gain	0.9700
12:11268669:C:CC	acceptor_gain	0.9700
12:11267427:T:TA	donor_gain	0.9600
12:11266026:CTTC:C	acceptor_gain	0.9500
12:11266155:T:TA	donor_gain	0.9500
12:11268206:CGCAG:C	acceptor_gain	0.9500
12:11268144:CTTTC:C	acceptor_gain	0.9400
12:11268145:TTTC:T	acceptor_gain	0.9300
12:11268631:ACCT:A	acceptor_loss	0.9300
12:11266028:TCC:T	acceptor_loss	0.9100
12:11266030:C:CA	acceptor_loss	0.9100
12:11266031:T:A	acceptor_loss	0.9100

AlphaMissense

2155 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000676497 (12:11271223 C>G,T), RS1001192013 (12:11271423 T>C), RS1001340491 (12:11268122 C>T), RS1001922342 (12:11269945 G>A), RS1002604516 (12:11266419 C>T), RS1003603076 (12:11269974 T>C), RS1004435511 (12:11269742 G>A), RS1004588693 (12:11271702 G>A,T), RS1004768466 (12:11271436 A>C), RS1004779434 (12:11271639 A>G), RS1005223435 (12:11268610 A>G), RS1005241010 (12:11268465 G>A,C), RS1005893060 (12:11268741 G>A), RS1006482942 (12:11270285 G>A), RS1006863918 (12:11270055 A>T)

Disease associations

OMIM: gene MIM:168840 | 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

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Estradiol	increases expression, decreases expression	2
CGP 52608	affects binding, increases reaction	1
Resveratrol	affects cotreatment, decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Hydralazine	affects cotreatment, increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Valproic Acid	affects cotreatment, increases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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