SDCBP2

Summary

SDCBP2 (syndecan binding protein 2, HGNC:15756) is a protein-coding gene on chromosome 20p13, encoding Syntenin-2 (Q9H190). Binds phosphatidylinositol 4,5-bisphosphate (PIP2).

The protein encoded by this gene contains two class II PDZ domains. PDZ domains facilitate protein-protein interactions by binding to the cytoplasmic C-terminus of transmembrane proteins, and PDZ-containing proteins mediate cell signaling and the organization of protein complexes. The encoded protein binds to phosphatidylinositol 4, 5-bisphosphate (PIP2) and plays a role in nuclear PIP2 organization and cell division. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. Read-through transcription also exists between this gene and the upstream FKBP1A (FK506 binding protein 1A, 12kDa) gene, as represented in GeneID:100528031.

Source: NCBI Gene 27111 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• MANE Select transcript: NM_080489

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15756
Approved symbol	SDCBP2
Name	syndecan binding protein 2
Location	20p13
Locus type	gene with protein product
Status	Approved
Aliases	ST-2, SITAC18
Ensembl gene	ENSG00000125775
Ensembl biotype	protein_coding
OMIM	617358
Entrez	27111

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 13 protein_coding, 2 retained_intron

ENST00000339987, ENST00000360779, ENST00000381808, ENST00000381812, ENST00000467129, ENST00000615838, ENST00000877945, ENST00000877946, ENST00000877947, ENST00000877948, ENST00000941674, ENST00000941675, ENST00000941676, ENST00000941677, ENST00000941678

RefSeq mRNA: 3 — MANE Select: NM_080489 NM_001199784, NM_015685, NM_080489

CCDS: CCDS13013, CCDS42848

Canonical transcript exons

ENST00000360779 — 9 exons

Exon	Start	End
ENSE00000655223	1310800	1310891
ENSE00000655224	1312337	1312508
ENSE00000655225	1312587	1312762
ENSE00001607200	1313340	1313498
ENSE00001798694	1319590	1319659
ENSE00001804580	1318318	1318418
ENSE00002265604	1320363	1320435
ENSE00003622390	1309909	1310495
ENSE00003739967	1329085	1329139

Expression profiles

Bgee: expression breadth ubiquitous, 202 present calls, max score 99.52.

FANTOM5 (CAGE): breadth broad, TPM avg 2.9915 / max 287.5440, expressed in 548 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
186003	1.0641	205
186004	0.7514	226
186002	0.5683	185
186000	0.4536	104
186001	0.1541	72

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	99.52	gold quality
lower esophagus mucosa	UBERON:0035834	99.31	gold quality
mucosa of transverse colon	UBERON:0004991	98.93	gold quality
colonic mucosa	UBERON:0000317	98.03	gold quality
jejunal mucosa	UBERON:0000399	98.03	gold quality
mucosa of sigmoid colon	UBERON:0004993	97.79	gold quality
esophagus mucosa	UBERON:0002469	97.32	gold quality
pancreatic ductal cell	CL:0002079	96.97	gold quality
rectum	UBERON:0001052	96.20	gold quality
nasal cavity epithelium	UBERON:0005384	96.04	gold quality
gall bladder	UBERON:0002110	95.94	gold quality
esophagus squamous epithelium	UBERON:0006920	95.83	gold quality
skin of leg	UBERON:0001511	95.75	gold quality
duodenum	UBERON:0002114	95.66	gold quality
skin of abdomen	UBERON:0001416	95.53	gold quality
zone of skin	UBERON:0000014	93.60	gold quality
epithelial cell of pancreas	CL:0000083	93.17	silver quality
oral cavity	UBERON:0000167	93.07	gold quality
transverse colon	UBERON:0001157	92.84	gold quality
upper arm skin	UBERON:0004263	92.43	silver quality
small intestine Peyer’s patch	UBERON:0003454	92.34	gold quality
amniotic fluid	UBERON:0000173	92.19	gold quality
small intestine	UBERON:0002108	91.67	gold quality
mucosa of stomach	UBERON:0001199	90.48	gold quality
body of stomach	UBERON:0001161	89.54	gold quality
palpebral conjunctiva	UBERON:0001812	89.10	gold quality
gingiva	UBERON:0001828	89.09	gold quality
anterior cingulate cortex	UBERON:0009835	88.86	gold quality
mouth mucosa	UBERON:0003729	88.72	gold quality
nucleus accumbens	UBERON:0001882	88.58	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	928.74
E-CURD-114	yes	45.39
E-MTAB-8410	yes	24.10
E-GEOD-125970	yes	23.57
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

27 targeting SDCBP2, 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-511-3P	99.99	68.85	1467
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-4762-5P	99.57	68.54	1424
HSA-MIR-549A-3P	99.54	68.17	825
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-6809-5P	99.13	68.45	1223
HSA-MIR-4504	99.10	69.14	1328
HSA-MIR-4695-5P	99.06	64.87	1151
HSA-MIR-625-5P	99.02	68.64	2031
HSA-MIR-4451	98.82	68.17	1455
HSA-MIR-935	98.82	69.36	1072
HSA-MIR-4763-5P	98.75	63.89	854
HSA-MIR-26B-3P	98.71	67.49	1102
HSA-MIR-12125	98.59	67.54	1044
HSA-MIR-2117	98.48	67.97	1307
HSA-MIR-6792-5P	98.39	68.16	1330
HSA-MIR-338-3P	98.14	67.38	1137
HSA-MIR-4275	97.96	68.42	1549
HSA-MIR-4665-5P	97.91	67.69	1536
HSA-MIR-4294	97.86	65.72	1110
HSA-MIR-6782-3P	97.60	67.75	931
HSA-MIR-2467-5P	97.36	67.71	991
HSA-MIR-34A-3P	96.80	67.70	805
HSA-MIR-6823-5P	96.26	65.69	919
HSA-MIR-4754	88.00	62.03	37

Literature-anchored findings (GeneRIF, showing 2)

• These results identified syntenin-2 as the first PDZ domain protein controlled by HPV8 and HPV16 at the mRNA level. (PMID:22623796)
• Targeting SDCBP2 in acute myeloid leukemia. (PMID:37714445)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	sdcbp2	ENSDARG00000012513
danio_rerio	sdcbp	ENSDARG00000030097
mus_musculus	Sdcbp2	ENSMUSG00000027456
rattus_norvegicus	Sdcbp2	ENSRNOG00000009528
drosophila_melanogaster	X11Lbeta	FBGN0052677
caenorhabditis_elegans	lin-10	WBGENE00002999

Paralogs (4): APBA3 (ENSG00000011132), APBA2 (ENSG00000034053), APBA1 (ENSG00000107282), SDCBP (ENSG00000137575)

Protein

Protein identifiers

Syntenin-2 — Q9H190 (reviewed: Q9H190)

Alternative names: Similar to TACIP18, Syndecan-binding protein 2

All UniProt accessions (1): Q9H190

UniProt curated annotations — full annotation on UniProt →

Function. Binds phosphatidylinositol 4,5-bisphosphate (PIP2). May play a role in the organization of nuclear PIP2, cell division and cell survival.

Subunit / interactions. Monomer and homodimer. Interacts with SDCBP. Interacts with TM4SF1.

Subcellular location. Cytoplasm. Nucleus. Nucleolus. Nucleoplasm. Cell membrane. Nucleus speckle.

Tissue specificity. Preferentially expressed in cells of the digestive tract. Low expression in skeletal muscle and kidney. Detected in differentiated keratinocytes of normal and malignant epithelium. In healthy skin, expression is localized in suprabasal epidermal layers.

Domain organisation. Binds phosphatidylinositol 4,5-bisphosphate (PIP2) via its two PDZ domains. These domains target SDCBP2 to the plasma membranes and nucleoli, two PIP2-rich regions.

Induction. Down-regulated by HPV8 E6 papillomavirus (HPV) oncoprotein (at protein level).

Isoforms (2)

UniProt ID	Names	Canonical?
Q9H190-1	1, Alpha	yes
Q9H190-3	3, Beta

RefSeq proteins (3): NP_001186713, NP_056500, NP_536737* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001478	PDZ	Domain
IPR036034	PDZ_sf	Homologous_superfamily
IPR051230	APP-Binding	Family

Pfam: PF00595

UniProt features (13 total): mutagenesis site 4, sequence variant 4, domain 2, chain 1, sequence conflict 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H190-F1	81.86	0.57

Functional residue map

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

Mutagenesis-validated functional residues (4):

Position	Phenotype
197	abolishes phosphatidylinositol 4,5-bisphosphate binding and targeting to plasma membrane, speckles and nucleoli; when as
244	abolishes phosphatidylinositol 4,5-bisphosphate binding and targeting to plasma membrane, speckles and nucleoli; when as
113	abolishes phosphatidylinositol 4,5-bisphosphate binding and targeting to plasma membrane, speckles and nucleoli; when as
167	abolishes phosphatidylinositol 4,5-bisphosphate binding and targeting to plasma membrane, speckles and nucleoli; when as

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 136 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_UP, MARTINEZ_RB1_TARGETS_UP, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, CYTAGCAAY_UNKNOWN, WHN_B, MARTINEZ_RB1_AND_TP53_TARGETS_UP, AR_01, AR_Q2, GOCC_NUCLEAR_SPECK, GOCC_NUCLEAR_BODY, GOCC_RIBONUCLEOPROTEIN_GRANULE, RFX1_01, GOCC_NUCLEOLUS, GOMF_PROTEIN_HETERODIMERIZATION_ACTIVITY, GOMF_PROTEIN_DIMERIZATION_ACTIVITY

GO Biological Process (4): nervous system development (GO:0007399), cell population proliferation (GO:0008283), intracellular signal transduction (GO:0035556), intracellular transport (GO:0046907)

GO Molecular Function (6): phosphatidylinositol-4,5-bisphosphate binding (GO:0005546), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), protein heterodimerization activity (GO:0046982), protein binding (GO:0005515), lipid binding (GO:0008289)

GO Cellular Component (10): nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), cytosol (GO:0005829), plasma membrane (GO:0005886), nuclear speck (GO:0016607), extracellular exosome (GO:0070062), nucleus (GO:0005634), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
intracellular anatomical structure	3
protein dimerization activity	2
binding	2
nuclear lumen	2
cytoplasm	2
intracellular membrane-bounded organelle	2
system development	1
cellular process	1
signal transduction	1
transport	1
cellular localization	1
establishment of localization in cell	1
phosphatidylinositol phosphate binding	1
phosphatidylinositol bisphosphate binding	1
protein binding	1
identical protein binding	1
intracellular membraneless organelle	1
endomembrane system	1
membrane	1
cell periphery	1
nuclear ribonucleoprotein granule	1
extracellular vesicle	1

Protein interactions and networks

STRING

946 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SDCBP2	CD63	P08962	992
SDCBP2	SDC1	P18827	922
SDCBP2	CD9	P21926	786
SDCBP2	CD81	P18582	781
SDCBP2	PDCD6IP	Q8WUM4	775
SDCBP2	TSG101	Q99816	771
SDCBP2	B4E171	B4E171	721
SDCBP2	CD6	P30203	717
SDCBP2	UNC93B1	Q9H1C4	712
SDCBP2	DDR1	Q08345	660
SDCBP2	ANXA2	P07355	622
SDCBP2	SDC4	P31431	610
SDCBP2	RAB5A	P20339	604
SDCBP2	SLC6A5	Q9Y345	587
SDCBP2	FLOT1	O75955	571

IntAct

344 interactions, top by confidence:

A	B	Type	Score
SDCBP2	FAM133A	psi-mi:“MI:0915”(physical association)	0.840
FAM133A	SDCBP2	psi-mi:“MI:0915”(physical association)	0.840
SDCBP2	CT45A3	psi-mi:“MI:0915”(physical association)	0.830
SDCBP2	ZCCHC17	psi-mi:“MI:0915”(physical association)	0.830
ZCCHC17	SDCBP2	psi-mi:“MI:0915”(physical association)	0.830
CT45A3	SDCBP2	psi-mi:“MI:0915”(physical association)	0.830
LGALS2	SDCBP2	psi-mi:“MI:0915”(physical association)	0.780
ZRSR2	SDCBP2	psi-mi:“MI:0915”(physical association)	0.780
EIF1AD	SDCBP2	psi-mi:“MI:0915”(physical association)	0.780
PRPF38A	SDCBP2	psi-mi:“MI:0915”(physical association)	0.780
SDCBP2	YTHDC1	psi-mi:“MI:0915”(physical association)	0.780
SDCBP2	LYAR	psi-mi:“MI:0915”(physical association)	0.780
SDCBP2	PRR13	psi-mi:“MI:0915”(physical association)	0.780
SDCBP2	EIF1AD	psi-mi:“MI:0915”(physical association)	0.780
YTHDC1	SDCBP2	psi-mi:“MI:0915”(physical association)	0.780
LYAR	SDCBP2	psi-mi:“MI:0915”(physical association)	0.780
PRR13	SDCBP2	psi-mi:“MI:0915”(physical association)	0.780
SDCBP2	LGALS2	psi-mi:“MI:0915”(physical association)	0.780
SDCBP2	ZRSR2	psi-mi:“MI:0915”(physical association)	0.780

BioGRID (106): SDCBP2 (Two-hybrid), SDCBP2 (Two-hybrid), SDCBP2 (Two-hybrid), SDCBP2 (Two-hybrid), SDCBP2 (Two-hybrid), SDCBP2 (Two-hybrid), SDCBP2 (Two-hybrid), SDCBP2 (Two-hybrid), SDCBP2 (Two-hybrid), SDCBP2 (Two-hybrid), SDCBP2 (Two-hybrid), ZCCHC17 (Two-hybrid), ZNF581 (Two-hybrid), PRR13 (Two-hybrid), ZCCHC10 (Two-hybrid)

ESM2 similar proteins: A0A0G2K2P5, A7MBL8, A8E0R9, A8KBF6, B2RYD2, O00560, O08874, O08992, O88382, O94806, O97758, P0C7A6, P39447, P70175, P97879, Q07157, Q15700, Q16513, Q28C55, Q4KLN0, Q5E9E1, Q5PYH6, Q5PYH7, Q5VZK9, Q62936, Q63622, Q6DEZ7, Q6EDY6, Q6P0D7, Q6R005, Q7ZY29, Q86UL8, Q8BPM2, Q8BVD5, Q8BWW9, Q8IVH8, Q8K1Y2, Q8QFR2, Q91XM9, Q924I2

Diamond homologs: O00560, O08992, P70175, Q09506, Q4KLN0, Q5PYH7, Q5ZM14, Q62936, Q92796, Q99JZ0, Q9H190, Q9JI92, Q9PL97, B2RUJ5, O14907, O17583, O35430, O70248, P31016, P78352, Q02410, Q4H4B6, Q5PYH5, Q62108, Q9DBG9, A4D2P6, A5PKA5, A7UA95, A8MUH7, B7WN72, D3YZU1, D3ZFD0, G5EDM4, O08774, O14745, O14910, O14924, O15085, O60307, O88382

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
TM4SF1	“up-regulates activity”	SDCBP2	relocalization

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

1622 predictions. Top by Δscore:

Variant	Effect	Δscore
20:1310798:A:AC	donor_gain	1.0000
20:1310799:C:CC	donor_gain	1.0000
20:1310801:TTTTG:T	donor_gain	1.0000
20:1310888:TGTC:T	acceptor_gain	1.0000
20:1310890:TC:T	acceptor_gain	1.0000
20:1310891:CC:C	acceptor_gain	1.0000
20:1310891:CCTA:C	acceptor_loss	1.0000
20:1310892:C:CC	acceptor_gain	1.0000
20:1310892:C:CG	acceptor_loss	1.0000
20:1310893:T:G	acceptor_loss	1.0000
20:1312336:C:CG	donor_loss	1.0000
20:1312415:C:CA	donor_gain	1.0000
20:1312505:CGGC:C	acceptor_gain	1.0000
20:1312715:C:CT	acceptor_gain	1.0000
20:1312715:C:T	acceptor_gain	1.0000
20:1313336:CTACC:C	donor_loss	1.0000
20:1313338:ACCTG:A	donor_loss	1.0000
20:1313339:C:G	donor_loss	1.0000
20:1313495:CTGT:C	acceptor_gain	1.0000
20:1318414:CAAAA:C	acceptor_gain	1.0000
20:1310887:TTGTC:T	acceptor_gain	0.9900
20:1310889:GTC:G	acceptor_gain	0.9900
20:1312506:GGCC:G	acceptor_loss	0.9900
20:1312509:C:CA	acceptor_loss	0.9900
20:1312509:C:CC	acceptor_gain	0.9900
20:1312510:T:G	acceptor_loss	0.9900
20:1312582:CTCA:C	donor_loss	0.9900
20:1312583:TCA:T	donor_loss	0.9900
20:1312584:CAC:C	donor_loss	0.9900
20:1312586:C:CT	donor_loss	0.9900

AlphaMissense

1897 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:1312703:A:C	F148L	0.993
20:1312703:A:T	F148L	0.993
20:1312705:A:G	F148L	0.993
20:1312754:A:C	F131L	0.989
20:1312754:A:T	F131L	0.989
20:1312756:A:G	F131L	0.989
20:1312593:C:G	R185P	0.986
20:1312743:A:T	V135D	0.984
20:1312596:A:T	V184D	0.983
20:1312698:T:G	D150A	0.983
20:1312497:C:G	R191P	0.981
20:1312701:C:A	G149V	0.981
20:1313385:C:A	K113N	0.981
20:1313385:C:G	K113N	0.981
20:1312698:T:A	D150V	0.980
20:1312701:C:T	G149E	0.980
20:1312587:C:G	R187T	0.977
20:1312508:C:A	R187S	0.976
20:1312508:C:G	R187S	0.976
20:1312587:C:A	R187M	0.976
20:1312707:C:G	R147P	0.976
20:1312350:A:T	V240D	0.975
20:1312699:C:G	D150H	0.975
20:1312752:A:T	V132E	0.975
20:1312698:T:C	D150G	0.974
20:1312689:A:G	L153P	0.973
20:1312352:A:C	N239K	0.972
20:1312352:A:T	N239K	0.972
20:1312725:G:T	A141E	0.972
20:1312755:A:G	F131S	0.972

dbSNP variants (sampled 300 via entrez): RS1000097636 (20:1329149 C>T), RS1000138257 (20:1321607 C>A,T), RS1000186542 (20:1322007 T>A,C), RS1000322904 (20:1322321 G>C), RS1000468038 (20:1321890 C>G), RS1000485224 (20:1316407 T>C), RS1000524088 (20:1323419 G>A,C), RS1000552648 (20:1328833 C>T), RS1000658152 (20:1323652 C>T), RS1000787900 (20:1329990 T>C,G), RS1000790896 (20:1316090 A>C), RS1000861549 (20:1329620 T>C), RS1000931320 (20:1312151 G>T), RS1001070863 (20:1323355 A>G), RS1001153702 (20:1312034 G>A)

Disease associations

OMIM: gene MIM:617358 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST008058_144	Estimated glomerular filtration rate	9.000000e-15
GCST009391_228	Metabolite levels	8.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010491	glycocholate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression	3
Tobacco Smoke Pollution	increases expression, affects expression, decreases methylation	3
sodium arsenite	decreases methylation, increases expression	2
Air Pollutants	increases abundance, increases expression	2
Valproic Acid	affects expression, increases methylation	2
Cadmium Chloride	decreases expression, increases expression	2
Particulate Matter	increases abundance, increases expression, affects cotreatment, affects expression	2
aristolochic acid I	increases expression	1
GSK-J4	increases expression	1
sotorasib	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
lead acetate	increases expression	1
O,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphate	affects expression, affects response to substance	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	increases expression	1
beta-lapachone	increases expression	1
manganese chloride	decreases expression	1
cupric chloride	increases expression	1
CGP 52608	affects binding, increases reaction	1
corosolic acid	increases expression	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
licochalcone B	increases expression	1
NSC 689534	increases expression	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Zoledronic Acid	increases expression	1
Acetaldehyde	increases expression	1
Ethanol	affects cotreatment, affects expression, increases abundance	1

Clinical trials (associated diseases)

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