ZG16B

Summary

ZG16B (zymogen granule protein 16B, HGNC:30456) is a protein-coding gene on chromosome 16p13.3, encoding Pancreatic adenocarcinoma up-regulated factor (Q96DA0). Functions as a lectin that binds to selective commensal dental plaque bacteria, such as Streptococcus vestibularis.

Predicted to enable carbohydrate binding activity. Involved in cell migration. Located in apicolateral plasma membrane; cytoplasm; and extracellular region.

Source: NCBI Gene 124220 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 49 total
• MANE Select transcript: NM_145252

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30456
Approved symbol	ZG16B
Name	zymogen granule protein 16B
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	HRPE773, PRO1567, JCLN2
Ensembl gene	ENSG00000162078
Ensembl biotype	protein_coding
OMIM	620477
Entrez	124220

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding, 2 retained_intron

ENST00000382280, ENST00000570670, ENST00000571723, ENST00000572863, ENST00000573019, ENST00000576423, ENST00000902257

RefSeq mRNA: 1 — MANE Select: NM_145252 NM_145252

CCDS: CCDS10479

Canonical transcript exons

ENST00000382280 — 4 exons

Exon	Start	End
ENSE00001062488	2830694	2830796
ENSE00001062489	2831796	2832276
ENSE00001526902	2830303	2830328
ENSE00001602239	2830415	2830493

Expression profiles

Bgee: expression breadth ubiquitous, 126 present calls, max score 99.95.

FANTOM5 (CAGE): breadth broad, TPM avg 38.4556 / max 34901.6700, expressed in 553 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
152311	35.6324	128
152308	2.2976	461
152309	0.4409	226
152310	0.0846	20

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
olfactory segment of nasal mucosa	UBERON:0005386	99.95	gold quality
saliva-secreting gland	UBERON:0001044	97.57	gold quality
minor salivary gland	UBERON:0001830	97.34	gold quality
gall bladder	UBERON:0002110	95.49	gold quality
prostate gland	UBERON:0002367	94.14	gold quality
rectum	UBERON:0001052	91.32	gold quality
skin of abdomen	UBERON:0001416	90.50	gold quality
adrenal tissue	UBERON:0018303	89.93	gold quality
zone of skin	UBERON:0000014	88.98	gold quality
skin of leg	UBERON:0001511	87.99	gold quality
mucosa of transverse colon	UBERON:0004991	87.49	gold quality
tonsil	UBERON:0002372	86.71	gold quality
duodenum	UBERON:0002114	86.43	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.98	silver quality
monocyte	CL:0000576	79.87	gold quality
body of stomach	UBERON:0001161	79.43	gold quality
leukocyte	CL:0000738	79.42	gold quality
transverse colon	UBERON:0001157	78.94	gold quality
vagina	UBERON:0000996	78.13	gold quality
stomach	UBERON:0000945	77.93	gold quality
placenta	UBERON:0001987	77.92	gold quality
vermiform appendix	UBERON:0001154	77.18	gold quality
granulocyte	CL:0000094	76.31	gold quality
thoracic mammary gland	UBERON:0005200	75.01	gold quality
small intestine Peyer’s patch	UBERON:0003454	74.95	gold quality
small intestine	UBERON:0002108	74.93	gold quality
mucosa of stomach	UBERON:0001199	74.17	gold quality
urinary bladder	UBERON:0001255	72.94	gold quality
bone marrow	UBERON:0002371	72.40	gold quality
intestine	UBERON:0000160	71.74	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-1	yes	13.17
E-GEOD-125970	no	7.16
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

4 targeting ZG16B, 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-3158-5P	99.65	67.51	1763
HSA-MIR-508-5P	99.41	64.25	1248
HSA-MIR-935	98.82	69.36	1072
HSA-MIR-3165	96.18	66.22	473

Literature-anchored findings (GeneRIF, showing 22)

• Bioinformatic analysis identified a putative human CSP-1/Dcpp ortholog, HRPE773, expressed predominantly in human salivary tissue, that shows 31% amino acid identity and 45% amino acid similarity to the mouse Dcpp query sequence. (PMID:16954406)
• pancreatic adenocarcinoma up-regulated factor was secreted into the culture medium of pancreatic adenocarcinoma up-regulated factor-overexpressing Chinese hamster ovary cells, had an apparent molecular mass of approximately 25 kDa, and was N-glycosylated (PMID:19302292)
• Findings indicate that PAUF enhances the metastatic potential of pancreatic cancer cells, at least in part, by upregulating CXCR4 expression. (PMID:19784070)
• PAUF is a mammalian lectin normally found in plant lectins. PAUF induces extracellular signal-regulated kinase phosphorylation and activates the IKK-b-mediated TPL2/MEK/ERK signaling pathway through TLR2. (PMID:20802527)
• Data demonstrate that the host salivary protein CSP-1 (HRPE773 GenBank AAQ89380.1) binds to S. mutans cells and may influence the initial colonization of this pathogenic bacterium onto the tooth surface. (PMID:20858015)
• the sugar-binding site and the adjacent basic patch of ZG16p and ZG16b cooperatively form a functional glycosaminoglycan-binding site. (PMID:21110947)
• PAUF can up-regulate and stabilize beta-catenin via a novel pattern of phosphorylation, thereby contributing to the rapid proliferation of pancreatic cancer cells. (PMID:21196815)
• PAUF-mediated FAK activation plays an important role in pancreatic cancer progression. (PMID:21464589)
• activation of SIRT1 inhibited the proliferation of pancreatic cancer -PAUF cells by down-regulation of cyclin-D1, a target molecule of beta-catenin. (PMID:22640743)
• new possibilities for PAUF’s role in the pathogenesis of angiogenesis-dependent diseases (PMID:22907431)
• PAUF-siRNA inhibited the proliferation of colorectal cancer cells, promoted their apoptosis and induced G0/G1 cell cycle arrest. At the same time, PAUF-siRNA inhibited the invasion, adhesion and migration of the tumor cells. (PMID:23677445)
• PAUF rs12373A>C polymorphisms are associated with colorectal cancer. (PMID:25079514)
• constitutive suppression of PAUF sensitized Bxpc3 pancreatic cancer cells to oncolytic parvovirus H-1 infection (PMID:25727013)
• PAUF mediated dendritic cell activation and immune stimulation are dependent on TLR4 (PMID:26336989)
• High PAUF expression is associated with resistance to gemcitabine in pancreatic cancer. (PMID:26684804)
• we conclude that the PAUF is a powerful and multifunctional promoter of tumor growth through increase and functional activation of myeloid-derived suppressor cells (PMID:27322081)
• Our results suggest that PAUF has tumour-promoting functions in oral squamous cell carcinoma (PMID:27706833)
• Mouse DCPP1 is a multifunctional promoter of tumor growth through functional activation of pancreatic cancer cells, suggesting it to be an ortholog of human PAUF. (PMID:28988106)
• PAUF/ZG16B promotes colorectal cancer progression through alterations of the mitotic functions and the Wnt/beta-catenin pathway. (PMID:31095674)
• Pancreatic cancer induces muscle wasting by promoting the release of pancreatic adenocarcinoma upregulated factor. (PMID:33731895)
• PAUF Induces Migration of Human Pancreatic Cancer Cells Exclusively via the TLR4/MyD88/NF-kappaB Signaling Pathway. (PMID:36232715)
• Human oral lectin ZG16B acts as a cell wall polysaccharide probe to decode host-microbe interactions with oral commensals. (PMID:37216558)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
mus_musculus	Sbpl	ENSMUSG00000024125

Protein

Protein identifiers

Pancreatic adenocarcinoma up-regulated factor — Q96DA0 (reviewed: Q96DA0)

Alternative names: Zymogen granule protein 16 homolog B

All UniProt accessions (4): A0A0C4DGN4, Q96DA0, I3L1H9, I3L3X0

UniProt curated annotations — full annotation on UniProt →

Function. Functions as a lectin that binds to selective commensal dental plaque bacteria, such as Streptococcus vestibularis. Contributes to maintain homeostasis in the oral microbiome by capturing commensal microbes and regulating their growth using a mucin-assisted clearance mechanism. Plays an important role in pancreatic tumor progression and metastasis. Promotes pancreatic cancer cells migration and invasion through the TLR4/MyD88/NF-kappaB signaling pathway, without the involvement of the TLR4/TRIF pathway.

Subunit / interactions. Interacts with MUC7; this interaction enhances the capture of commensal bacteria and promotes their removal via the mucin-assisted clearance pathway. Found in a complex with the salivary mucin MUC7 and with Streptococcus vestibularis.

Subcellular location. Secreted. Cytoplasm. Cell membrane. Apicolateral cell membrane.

Tissue specificity. Highly expressed in pancreatic cancer tissues (at protein levels). Also expressed in the placenta and colon and ovarian cancer tumors. Highly expressed in salivary glands, in submandibular and sublingual glands.

Post-translational modifications. N-glycosylated.

Similarity. Belongs to the jacalin lectin family.

RefSeq proteins (1): NP_660295* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001229	Jacalin-like_lectin_dom	Domain
IPR036404	Jacalin-like_lectin_dom_sf	Homologous_superfamily
IPR052321	PolyBind_ProtTraffic	Family

Pfam: PF01419

UniProt features (15 total): strand 10, signal peptide 1, chain 1, domain 1, glycosylation site 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3AQG	X-RAY DIFFRACTION	2.75

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96DA0-F1	87.91	0.76

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 (1): 161

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 61 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_DN, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOZGIT_ESR1_TARGETS_DN, GOBP_POSITIVE_REGULATION_OF_VASCULATURE_DEVELOPMENT, ROZANOV_MMP14_TARGETS_UP, GOBP_BLOOD_VESSEL_MORPHOGENESIS, GOCC_APICOLATERAL_PLASMA_MEMBRANE, GOBP_POSITIVE_REGULATION_OF_VASCULAR_PERMEABILITY, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_DN, GOBP_POSITIVE_REGULATION_OF_DEVELOPMENTAL_PROCESS, HAN_SATB1_TARGETS_DN, GOBP_DEFENSE_RESPONSE_TO_BACTERIUM, GOBP_REGULATION_OF_VASCULAR_PERMEABILITY, GOBP_CIRCULATORY_SYSTEM_DEVELOPMENT, GOBP_VASCULAR_PROCESS_IN_CIRCULATORY_SYSTEM

GO Biological Process (3): cell migration (GO:0016477), positive regulation of vascular permeability (GO:0043117), positive regulation of angiogenesis (GO:0045766)

GO Molecular Function (2): carbohydrate binding (GO:0030246), protein binding (GO:0005515)

GO Cellular Component (7): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), plasma membrane (GO:0005886), apicolateral plasma membrane (GO:0016327), extracellular exosome (GO:0070062), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
binding	2
cell motility	1
regulation of vascular permeability	1
angiogenesis	1
regulation of angiogenesis	1
positive regulation of vasculature development	1
intracellular anatomical structure	1
membrane	1
cell periphery	1
plasma membrane region	1
extracellular vesicle	1

Protein interactions and networks

STRING

456 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZG16B	PRR27	Q6MZM9	540
ZG16B	S100PBP	Q96BU1	517
ZG16B	PRR4	Q16378	477
ZG16B	LACRT	Q9GZZ8	448
ZG16B	LCN1	P31025	443
ZG16B	ZBTB42	B2RXF5	419
ZG16B	BPIFB2	Q8N4F0	415
ZG16B	BPIFA1	Q9NP55	415
ZG16B	ANKEF1	Q9NU02	398
ZG16B	GTPBP10	A4D1E9	390
ZG16B	SCGB1D1	O95968	383
ZG16B	SCGB2A1	O75556	380
ZG16B	STATH	P02808	374
ZG16B	LPO	P22079	367
ZG16B	PIP	P12273	367

IntAct

199 interactions, top by confidence:

A	B	Type	Score
SMARCE1	ARID1A	psi-mi:“MI:0914”(association)	0.840
STIP1	CCDC117	psi-mi:“MI:0914”(association)	0.770
SNAPC1	SNAPC5	psi-mi:“MI:0914”(association)	0.740
TADA3	TADA2A	psi-mi:“MI:0914”(association)	0.740
COMMD1	VPS26C	psi-mi:“MI:0914”(association)	0.730
SGTA	ZG16B	psi-mi:“MI:0915”(physical association)	0.720
ZG16B	SGTA	psi-mi:“MI:0915”(physical association)	0.720
SNW1	AQR	psi-mi:“MI:0914”(association)	0.650
NSL1	NDC80	psi-mi:“MI:0914”(association)	0.640
GPX7	GAK	psi-mi:“MI:0914”(association)	0.640
FKBP5	IKBKB	psi-mi:“MI:0914”(association)	0.640
KLHL22	METTL15	psi-mi:“MI:0914”(association)	0.640
CXCR4	TLR2	psi-mi:“MI:0914”(association)	0.590
TLR2	CXCR4	psi-mi:“MI:0914”(association)	0.590
TLR2	ZG16B	psi-mi:“MI:0915”(physical association)	0.580
ZG16B	PNMA1	psi-mi:“MI:0915”(physical association)	0.560
UBQLN1	ZG16B	psi-mi:“MI:0915”(physical association)	0.560
PNMA1	ZG16B	psi-mi:“MI:0915”(physical association)	0.560
ZG16B	UBQLN1	psi-mi:“MI:0915”(physical association)	0.560
ZG16B	SERTAD3	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (189): ZG16B (Two-hybrid), ZG16B (Two-hybrid), ZG16B (Two-hybrid), ZG16B (Affinity Capture-MS), ZG16B (Affinity Capture-MS), ZG16B (Affinity Capture-MS), ZG16B (Affinity Capture-MS), ZG16B (Affinity Capture-MS), ZG16B (Affinity Capture-MS), ZG16B (Affinity Capture-MS), ZG16B (Affinity Capture-MS), ZG16B (Affinity Capture-MS), ZG16B (Affinity Capture-MS), ZG16B (Affinity Capture-MS), ZG16B (Affinity Capture-MS)

ESM2 similar proteins: A0A172M485, A2WPN7, C0HK14, C0HM44, D9UBG0, D9UBI3, F4HQX1, F4I837, F4I9R6, F4IB94, F4IB95, H3JUC3, O04313, O04314, O80735, O80736, O80737, O80948, O80950, P15501, P18670, P18674, P82859, P82953, P93114, P93193, Q0JMY8, Q0WMR0, Q5U9T2, Q5XF82, Q84X07, Q8CJD3, Q8GWI7, Q8K0C5, Q96DA0, Q9FFW6, Q9FFW7, Q9FGC4, Q9FGC5, Q9FNM2

Diamond homologs: O60844, P08723, P15501, Q8CJD3, Q8K0C5, Q96DA0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	40
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

361 predictions. Top by Δscore:

Variant	Effect	Δscore
16:2830328:GG:G	donor_loss	1.0000
16:2830329:GTA:G	donor_loss	1.0000
16:2830490:GGGA:G	donor_gain	1.0000
16:2830491:GGAG:G	donor_gain	1.0000
16:2830494:G:GG	donor_gain	1.0000
16:2830692:A:AG	acceptor_gain	1.0000
16:2830693:G:GG	acceptor_gain	1.0000
16:2830693:GAGAT:G	acceptor_gain	1.0000
16:2831795:GT:G	acceptor_gain	1.0000
16:2830324:GCGAG:G	donor_gain	0.9900
16:2830326:GAG:G	donor_gain	0.9900
16:2830329:G:GG	donor_gain	0.9900
16:2830330:T:G	donor_loss	0.9900
16:2830491:GGA:G	donor_gain	0.9900
16:2830492:GA:G	donor_gain	0.9900
16:2830492:GAG:G	donor_gain	0.9900
16:2830675:G:A	acceptor_gain	0.9900
16:2830689:TTCA:T	acceptor_loss	0.9900
16:2830692:AGAGA:A	acceptor_loss	0.9900
16:2830693:GA:G	acceptor_gain	0.9900
16:2830693:GAGA:G	acceptor_gain	0.9900
16:2830792:AAAAG:A	donor_gain	0.9900
16:2830793:AAAGG:A	donor_loss	0.9900
16:2830796:GGTG:G	donor_loss	0.9900
16:2830797:G:GG	donor_gain	0.9900
16:2830798:T:A	donor_loss	0.9900
16:2831794:A:AG	acceptor_gain	0.9900
16:2831795:G:GG	acceptor_gain	0.9900
16:2831795:GTGT:G	acceptor_gain	0.9900
16:2831795:GTGTC:G	acceptor_gain	0.9900

AlphaMissense

1335 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:2832081:G:C	W183C	0.999
16:2832081:G:T	W183C	0.999
16:2831823:G:C	W97C	0.998
16:2831823:G:T	W97C	0.998
16:2832079:T:A	W183R	0.998
16:2832079:T:C	W183R	0.998
16:2831821:T:A	W97R	0.997
16:2831821:T:C	W97R	0.997
16:2830766:G:C	R78P	0.996
16:2830723:T:C	F64L	0.995
16:2830725:C:A	F64L	0.995
16:2830725:C:G	F64L	0.995
16:2831798:T:A	V89D	0.995
16:2831882:A:T	E117V	0.993
16:2832074:T:C	F181S	0.992
16:2832055:G:C	G175R	0.991
16:2832080:G:C	W183S	0.991
16:2831969:G:A	G146E	0.990
16:2832038:G:A	G169D	0.990
16:2831801:A:C	Q90P	0.989
16:2832059:T:C	I176T	0.989
16:2831917:T:C	F129L	0.988
16:2831919:C:A	F129L	0.988
16:2831919:C:G	F129L	0.988
16:2832073:T:C	F181L	0.988
16:2832075:T:A	F181L	0.988
16:2832075:T:G	F181L	0.988
16:2830759:G:T	G76W	0.987
16:2831837:G:A	G102E	0.987
16:2831908:T:C	F126L	0.987

dbSNP variants (sampled 300 via entrez): RS1000410125 (16:2830418 C>G), RS1000879846 (16:2830655 A>C), RS1002781287 (16:2831142 A>G), RS1003121970 (16:2831938 T>C), RS1003352052 (16:2828774 G>T), RS1003447052 (16:2828925 C>A), RS1004063856 (16:2830329 G>A,C,T), RS1004996040 (16:2830166 C>T), RS1005731709 (16:2831390 G>A,T), RS1006316790 (16:2828376 G>A), RS1006368629 (16:2831604 G>A), RS1006671300 (16:2832408 G>A), RS1007413878 (16:2828646 G>A), RS1007485372 (16:2831353 G>C), RS1008146184 (16:2829480 G>A,T)

Disease associations

OMIM: gene MIM:620477 | 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
GCST006585_2769	Blood protein levels	1.000000e-08

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, increases methylation	3
Nickel	decreases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
methyleugenol	increases expression	1
potassium persulfate	increases expression	1
sodium arsenite	increases expression	1
3,4,5,3’,4’-pentachlorobiphenyl	decreases expression	1
nickel sulfate	increases expression	1
monomethylarsonous acid	decreases expression	1
nutlin 3	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Azathioprine	increases expression	1
Camptothecin	increases expression	1
Coumestrol	decreases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Estradiol	affects cotreatment, decreases expression	1
Quercetin	increases expression	1
Silicon Dioxide	decreases expression	1
Valproic Acid	increases methylation	1
Cyclosporine	increases expression	1
Aflatoxin B1	increases expression	1
Copper Sulfate	increases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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