SMR3B

Summary

SMR3B (submaxillary gland androgen regulated protein 3B, HGNC:17326) is a protein-coding gene on chromosome 4q13.3, encoding Submaxillary gland androgen-regulated protein 3B (P02814). It is a selective cancer dependency (DepMap: 34.6% of cell lines).

Predicted to enable endopeptidase inhibitor activity. Predicted to be involved in cellular response to lipopolysaccharide; negative regulation of peptidase activity; and regulation of sensory perception of pain. Located in extracellular exosome.

Source: NCBI Gene 10879 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 19 total
• Cancer dependency (DepMap): dependent in 34.6% of screened cell lines
• MANE Select transcript: NM_006685

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17326
Approved symbol	SMR3B
Name	submaxillary gland androgen regulated protein 3B
Location	4q13.3
Locus type	gene with protein product
Status	Approved
Aliases	P-B, PRL3
Ensembl gene	ENSG00000171201
Ensembl biotype	protein_coding
OMIM	611593
Entrez	10879

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 retained_intron

ENST00000304915, ENST00000504825, ENST00000508027

RefSeq mRNA: 1 — MANE Select: NM_006685 NM_006685

CCDS: CCDS3540

Canonical transcript exons

ENST00000304915 — 3 exons

Exon	Start	End
ENSE00001138931	70389663	70390244
ENSE00002466810	70384497	70384564
ENSE00002514420	70383131	70383212

Expression profiles

Bgee: expression breadth ubiquitous, 119 present calls, max score 100.00.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1183.5906 / max 1358084.0250, expressed in 44 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
47918	1183.5906	44

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	100.00	gold quality
palpebral conjunctiva	UBERON:0001812	78.85	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	76.39	gold quality
saliva-secreting gland	UBERON:0001044	75.36	gold quality
minor salivary gland	UBERON:0001830	68.83	gold quality
mouth mucosa	UBERON:0003729	65.77	gold quality
diaphragm	UBERON:0001103	65.33	gold quality
adult organism	UBERON:0007023	65.04	gold quality
trachea	UBERON:0003126	64.31	gold quality
nasal cavity mucosa	UBERON:0001826	64.28	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	63.60	gold quality
left testis	UBERON:0004533	59.62	gold quality
right testis	UBERON:0004534	58.89	gold quality
buccal mucosa cell	CL:0002336	57.80	silver quality
testis	UBERON:0000473	57.78	gold quality
mucosa of paranasal sinus	UBERON:0005030	57.09	gold quality
male germ cell	CL:0000015	57.06	gold quality
sperm	CL:0000019	56.86	gold quality
bone marrow cell	CL:0002092	56.77	gold quality
decidua	UBERON:0002450	56.55	gold quality
thymus	UBERON:0002370	55.51	silver quality
tonsil	UBERON:0002372	54.68	gold quality
saphenous vein	UBERON:0007318	54.65	silver quality
caput epididymis	UBERON:0004358	54.52	gold quality
tongue	UBERON:0001723	53.54	gold quality
hair follicle	UBERON:0002073	53.29	gold quality
bone marrow	UBERON:0002371	52.00	gold quality
adenohypophysis	UBERON:0002196	50.15	gold quality
quadriceps femoris	UBERON:0001377	49.54	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	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

miRNA regulators (miRDB)

41 targeting SMR3B, 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-4531	99.99	69.70	3181
HSA-MIR-6755-5P	99.95	65.59	464
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-671-5P	99.52	67.11	1277
HSA-MIR-5007-3P	99.51	68.14	1242
HSA-MIR-12131	99.48	68.72	1673
HSA-MIR-6828-5P	99.31	69.21	1433
HSA-MIR-4263	99.18	69.25	2236
HSA-MIR-5703	99.10	67.09	2053
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-4774-3P	98.90	67.82	737
HSA-MIR-5572	98.55	65.84	970
HSA-MIR-4722-5P	98.46	66.34	1611
HSA-MIR-654-3P	98.38	67.61	905
HSA-MIR-4664-5P	98.17	65.07	1020
HSA-MIR-6870-3P	98.08	65.10	692
HSA-MIR-6819-5P	97.96	66.59	1071

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 34.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 2)

• Androgen regulated protein and pyruvate dehydrogenase kinase 4 in severe erectile dysfunction: A gene expression analysis, and computational study of protein structure. (PMID:34817334)
• Targeted proteomics using parallel reaction monitoring confirms salivary proteins indicative of metastatic triple-negative breast cancer. (PMID:35995384)

Cross-species orthologs

0 orthologs

Protein

Protein identifiers

Submaxillary gland androgen-regulated protein 3B — P02814 (reviewed: P02814)

Alternative names: Proline-rich peptide P-B, Proline-rich protein 3

All UniProt accessions (1): P02814

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted.

Tissue specificity. Secreted into saliva by submaxillary gland. Not expressed in heart, brain, lung, liver, skeletal muscle, Kidney, pancreas or placenta.

Post-translational modifications. P-A and D1A are probably degradation products of P-B.

Similarity. Belongs to the PROL1/PROL3 family.

RefSeq proteins (1): NP_006676* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026288	SMR-like	Family

Pfam: PF15621

UniProt features (7 total): peptide 2, signal peptide 1, chain 1, region of interest 1, compositionally biased region 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P02814-F1	71.50	0.07

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 (1): 23

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 67 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, XU_GH1_AUTOCRINE_TARGETS_UP, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_UP, chr4q13, GOBP_SENSORY_PERCEPTION_OF_PAIN, GOBP_REGULATION_OF_SENSORY_PERCEPTION, GOBP_REGULATION_OF_NERVOUS_SYSTEM_PROCESS, GOBP_REGULATION_OF_SYSTEM_PROCESS, GOBP_SENSORY_PERCEPTION, RASHI_RESPONSE_TO_IONIZING_RADIATION_5, MCCLUNG_COCAIN_REWARD_4WK

GO Biological Process (1): regulation of sensory perception of pain (GO:0051930)

GO Molecular Function (2): endopeptidase inhibitor activity (GO:0004866), protein binding (GO:0005515)

GO Cellular Component (3): obsolete extracellular space (GO:0005615), extracellular exosome (GO:0070062), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
sensory perception of pain	1
regulation of sensory perception	1
endopeptidase activity	1
peptidase inhibitor activity	1
endopeptidase regulator activity	1
binding	1
extracellular vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

442 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SMR3B	STATH	P02808	621
SMR3B	PRB2	P02811	584
SMR3B	SMCO1	Q147U7	576
SMR3B	LCN1	P31025	571
SMR3B	PIP	P12273	552
SMR3B	AMY2A	P04746	520
SMR3B	PRB1	P04280	513
SMR3B	TMEM252	Q8N6L7	507
SMR3B	HTN1	P15515	501
SMR3B	HSPB3	Q12988	498
SMR3B	AMY1B	P04745	480
SMR3B	AMY2B	P19961	478
SMR3B	MUC7	Q8TAX7	478
SMR3B	LYZL1	Q6UWQ5	477
SMR3B	HTN3	P15516	464

IntAct

42 interactions, top by confidence:

A	B	Type	Score
RBBP7	HAT1	psi-mi:“MI:0914”(association)	0.730
KNOP1	RRP8	psi-mi:“MI:0914”(association)	0.640
UBQLN1	SMR3B	psi-mi:“MI:0915”(physical association)	0.560
SMR3B	UBQLN1	psi-mi:“MI:0915”(physical association)	0.560
SMR3B	BCHE	psi-mi:“MI:0915”(physical association)	0.560
SMR3B	HOMER3	psi-mi:“MI:0915”(physical association)	0.560
SMR3B	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
UBTD2	CST4	psi-mi:“MI:0914”(association)	0.530
SNRPF	SNRPGP15	psi-mi:“MI:0914”(association)	0.530
PSG3	MGRN1	psi-mi:“MI:0914”(association)	0.530
SMR3B	MTFP1	psi-mi:“MI:0915”(physical association)	0.400
SMR3B	OXCT2	psi-mi:“MI:0915”(physical association)	0.400
MUC7	SMR3B	psi-mi:“MI:0915”(physical association)	0.370
STK4	ANXA2P2	psi-mi:“MI:0914”(association)	0.350
TNFRSF19	NOP56	psi-mi:“MI:0914”(association)	0.350
SNRPF	GEMIN2	psi-mi:“MI:0914”(association)	0.350
	AP3B1	psi-mi:“MI:0914”(association)	0.350
BRD4	CST1	psi-mi:“MI:0914”(association)	0.350
SAT2	SMR3B	psi-mi:“MI:0914”(association)	0.350
RPS6KA4		psi-mi:“MI:0914”(association)	0.350
AXL		psi-mi:“MI:0914”(association)	0.350
CDKL3		psi-mi:“MI:0914”(association)	0.350
TNFRSF19	PLD2	psi-mi:“MI:0914”(association)	0.350
SMR3B	CRTAP	psi-mi:“MI:0914”(association)	0.350
TIMM10	IGLL5	psi-mi:“MI:0914”(association)	0.350

BioGRID (29): UBQLN1 (Two-hybrid), SMR3B (Affinity Capture-MS), SMR3B (Affinity Capture-MS), SMR3B (Affinity Capture-MS), BCHE (Affinity Capture-MS), SMR3B (Affinity Capture-MS), SMR3B (Affinity Capture-MS), SMR3B (Affinity Capture-MS), SMR3B (Two-hybrid), UBQLN2 (Two-hybrid), SAT2 (Affinity Capture-MS), SMR3B (Affinity Capture-MS), CST1 (Affinity Capture-MS), SMR3B (Affinity Capture-MS), BCHE (Affinity Capture-MS)

ESM2 similar proteins: A2BN31, A6XMY1, G1T168, H2A0N0, O10443, O29590, O30091, O30279, O30280, O77302, P02814, P0AAA9, P0AAB0, P0AAB1, P0DKK8, P0DKK9, P14269, P35986, P41824, P46783, P54912, P56623, P56624, P63325, P63326, P86963, Q05904, Q07254, Q2KS10, Q3T0F4, Q57844, Q57845, Q57H53, Q58166, Q5PK98, Q5UP53, Q64858, Q725P0, Q89707, Q8CVI9

Diamond homologs: P02814, P13432, Q99935, Q99954, O09133, O35979, O35985, Q61900

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	17
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

645 predictions. Top by Δscore:

Variant	Effect	Δscore
4:70383042:G:GT	donor_gain	1.0000
4:70384495:A:AG	acceptor_gain	1.0000
4:70384496:G:GG	acceptor_gain	1.0000
4:70384496:GA:G	acceptor_gain	1.0000
4:70384496:GAGGC:G	acceptor_gain	1.0000
4:70384561:CACAG:C	donor_loss	1.0000
4:70384562:ACAG:A	donor_loss	1.0000
4:70384563:CA:C	donor_gain	1.0000
4:70384563:CAGT:C	donor_loss	1.0000
4:70384564:AGTA:A	donor_loss	1.0000
4:70384565:G:GG	donor_gain	1.0000
4:70384565:GTAA:G	donor_loss	1.0000
4:70384566:TAA:T	donor_loss	1.0000
4:70384567:AA:A	donor_loss	1.0000
4:70384491:TTTCA:T	acceptor_loss	0.9900
4:70384494:CA:C	acceptor_loss	0.9900
4:70384495:A:AC	acceptor_loss	0.9900
4:70384495:AGAG:A	acceptor_gain	0.9900
4:70384496:G:GT	acceptor_loss	0.9900
4:70384496:GAGG:G	acceptor_gain	0.9900
4:70384560:TCACA:T	donor_gain	0.9900
4:70384561:CACA:C	donor_gain	0.9900
4:70384562:ACA:A	donor_gain	0.9900
4:70384568:AGTAT:A	donor_loss	0.9900
4:70383042:G:T	donor_gain	0.9800
4:70384490:C:G	acceptor_gain	0.9800
4:70389661:AGCCT:A	acceptor_gain	0.9800
4:70389662:GCCTG:G	acceptor_gain	0.9800
4:70370173:G:GG	donor_gain	0.9700
4:70383046:T:G	donor_gain	0.9700

AlphaMissense

483 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:70384559:T:C	F17L	0.955
4:70384561:C:A	F17L	0.955
4:70384561:C:G	F17L	0.955
4:70384535:G:C	G9R	0.951
4:70384560:T:C	F17S	0.904
4:70384536:G:A	G9D	0.903
4:70384556:T:C	C16R	0.894
4:70384548:T:A	L13H	0.889
4:70384541:T:A	W11R	0.885
4:70384541:T:C	W11R	0.885
4:70389672:A:C	S22R	0.873
4:70389674:T:A	S22R	0.873
4:70389674:T:G	S22R	0.873
4:70389784:T:C	I59T	0.872
4:70384539:T:A	L10H	0.861
4:70384545:C:A	A12D	0.842
4:70389670:A:T	E21V	0.828
4:70389729:T:C	F41L	0.820
4:70389731:T:A	F41L	0.820
4:70389731:T:G	F41L	0.820
4:70384544:G:C	A12P	0.813
4:70384559:T:A	F17I	0.806
4:70384539:T:C	L10P	0.794
4:70384560:T:G	F17C	0.790
4:70384530:T:C	I7T	0.773
4:70384548:T:G	L13R	0.770
4:70384539:T:G	L10R	0.755
4:70384548:T:C	L13P	0.744
4:70384558:T:G	C16W	0.744
4:70389741:T:C	F45L	0.737

dbSNP variants (sampled 300 via entrez): RS10000799 (4:70383724 T>A), RS10004069 (4:70387268 G>A,C,T), RS10004188 (4:70384940 T>A,C), RS1000518861 (4:70381403 GGGAGGGAA>G), RS1000534114 (4:70387293 T>A), RS1000977767 (4:70381659 T>G), RS10012120 (4:70384999 G>A), RS1001451021 (4:70386288 G>A,C), RS1002247471 (4:70383032 C>G), RS1002486320 (4:70385530 T>A,G), RS1002600143 (4:70382826 G>A), RS10027711 (4:70387905 C>G), RS10031247 (4:70383335 C>T), RS1003222560 (4:70388210 T>C), RS1003231308 (4:70384190 A>C)

Disease associations

OMIM: gene MIM:611593 | 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

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, decreases methylation	1
(+)-JQ1 compound	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Benzo(a)pyrene	affects methylation	1
Fenfluramine	increases expression	1
Lead	affects binding	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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