STAP2

Summary

STAP2 (signal transducing adaptor family member 2, HGNC:30430) is a protein-coding gene on chromosome 19p13.3, encoding Signal-transducing adaptor protein 2 (Q9UGK3). Substrate of protein kinase PTK6.

This gene encodes the substrate of breast tumor kinase, an Src-type non-receptor tyrosine kinase. The encoded protein possesses domains and several tyrosine phosphorylation sites characteristic of adaptor proteins that mediate the interactions linking proteins involved in signal transduction pathways. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 55620 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 96 total
• MANE Select transcript: NM_001013841

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30430
Approved symbol	STAP2
Name	signal transducing adaptor family member 2
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	STAP-2, BKS
Ensembl gene	ENSG00000178078
Ensembl biotype	protein_coding
OMIM	607881
Entrez	55620

Gene structure

Transcript identifiers

Ensembl transcripts: 42 — 37 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000594605, ENST00000596242, ENST00000597593, ENST00000598443, ENST00000599736, ENST00000600324, ENST00000601179, ENST00000601482, ENST00000601956, ENST00000602007, ENST00000859620, ENST00000859621, ENST00000859622, ENST00000859623, ENST00000859624, ENST00000859625, ENST00000859626, ENST00000859627, ENST00000859628, ENST00000859629, ENST00000859630, ENST00000859631, ENST00000859632, ENST00000859633, ENST00000859634, ENST00000859635, ENST00000859636, ENST00000859637, ENST00000935915, ENST00000935916, ENST00000935917, ENST00000935918, ENST00000935919, ENST00000970040, ENST00000970041, ENST00000970042, ENST00000970043, ENST00000970044, ENST00000970045, ENST00000970046, ENST00000970047, ENST00000970048

RefSeq mRNA: 2 — MANE Select: NM_001013841 NM_001013841, NM_017720

CCDS: CCDS12128, CCDS45926

Canonical transcript exons

ENST00000594605 — 13 exons

Exon	Start	End
ENSE00001253054	4333694	4333816
ENSE00001318694	4332022	4332078
ENSE00001641592	4324455	4324529
ENSE00002980645	4338652	4338827
ENSE00003072382	4324043	4324197
ENSE00003476457	4328675	4328809
ENSE00003494264	4325216	4325308
ENSE00003495347	4327124	4327226
ENSE00003501642	4329961	4330061
ENSE00003547777	4325396	4325545
ENSE00003560920	4333973	4334044
ENSE00003668609	4326942	4327007
ENSE00003677480	4327316	4327385

Expression profiles

Bgee: expression breadth ubiquitous, 215 present calls, max score 98.86.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.5641 / max 92.8727, expressed in 1271 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
178424	6.5361	996
178426	1.0658	483
178425	0.7461	438
178423	0.1631	99
178422	0.0530	21

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	98.86	gold quality
lower esophagus mucosa	UBERON:0035834	98.02	gold quality
ileal mucosa	UBERON:0000331	96.20	gold quality
esophagus mucosa	UBERON:0002469	96.07	gold quality
skin of abdomen	UBERON:0001416	95.66	gold quality
skin of leg	UBERON:0001511	95.50	gold quality
rectum	UBERON:0001052	95.24	gold quality
colonic mucosa	UBERON:0000317	94.67	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.62	gold quality
mucosa of sigmoid colon	UBERON:0004993	94.30	gold quality
zone of skin	UBERON:0000014	94.17	gold quality
pancreatic ductal cell	CL:0002079	93.58	gold quality
right lobe of liver	UBERON:0001114	93.54	gold quality
tongue squamous epithelium	UBERON:0006919	93.45	gold quality
minor salivary gland	UBERON:0001830	93.31	gold quality
gingival epithelium	UBERON:0001949	93.24	gold quality
gingiva	UBERON:0001828	92.87	gold quality
mouth mucosa	UBERON:0003729	92.80	gold quality
duodenum	UBERON:0002114	92.17	gold quality
transverse colon	UBERON:0001157	91.83	gold quality
nasal cavity epithelium	UBERON:0005384	91.41	gold quality
upper arm skin	UBERON:0004263	91.36	silver quality
saliva-secreting gland	UBERON:0001044	91.23	gold quality
squamous epithelium	UBERON:0006914	90.96	gold quality
epithelium of esophagus	UBERON:0001976	90.52	gold quality
esophagus squamous epithelium	UBERON:0006920	90.12	gold quality
small intestine Peyer’s patch	UBERON:0003454	89.83	gold quality
upper leg skin	UBERON:0004262	89.66	gold quality
cervix epithelium	UBERON:0004801	89.65	silver quality
metanephros cortex	UBERON:0010533	89.54	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-8410	yes	14.16
E-GEOD-125970	yes	13.78
E-ANND-3	yes	12.24

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 16)

• These data indicate that STAP-2/BKS negatively controls the FcepsilonRI-mediated calcium mobilization and degranulation by direct modulation of tyrosine phosphorylation of PLC-gamma. (PMID:12810085)
• STAP-2/BKS is a modulator of STAT5-mediated signaling (PMID:15611091)
• STAP-2 associates with FAK and enhances its degradation, proteasome inhibitors block FAK degradation, and STAP-2 recruits an endogenous E3 ubiquitin ligase, Cbl, to FAK. (PMID:17675501)
• These results suggest that STAP-2 acts as an endogenous negative regulator of Epstein-Barr virus LMP1-mediated signaling through TRAF3 and TRADD. (PMID:18573890)
• STAP-2 is phosphorylated at Tyr250 by Brk, and plays an important role in Brk-mediated STAT3 activation. (PMID:19393627)
• These results indicate that Cbl regulates STAP-2 protein levels and Brk/STAP-2-mediated STAT3 activation. (PMID:19401194)
• STAP-2 expression in Jurkat T cells affects migration following stromal cell-derived factor-1alpha (SDF-1alpha) treatment; STAP-2 association with Vav1, the guanine-nucleotide exchanging factor for Rac1, enhances downstream Vav1/Rac1 signaling. (PMID:19933863)
• Interactions of STAP-2 with Brk and STAT3 participate in cell growth of human breast cancer cells. (PMID:20929863)
• Our results demonstrate a critical contribution of STAP-2 in BCR-ABL activity. (PMID:22231445)
• STAP-2 is a novel participant in the regulation of T cell apoptosis after stimulation (PMID:22611243)
• STAP2 is upregulated in uterosacral ligaments in pelvic organ prolapse (PMID:23700042)
• These findings indicate an essential role for STAP2 in the generation of a high-quality memory CD8+ CTLs periphery, and suggest the therapeutic potential of STAP2 in cancer patients. (PMID:28430604)
• The Pyk2/STAP-2 interaction is a novel mechanism to regulate SDF-1alpha-dependent T-cell chemotaxis. (PMID:28478037)
• High STAP2 expression is associated with prostate cancer. (PMID:28986450)
• Signal-transducing adaptor protein-1 and protein-2 in hematopoiesis and diseases. (PMID:34780812)
• STAP-2 facilitates insulin signaling through binding to CAP/c-Cbl and regulates adipocyte differentiation. (PMID:38461189)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	stap2b	ENSDARG00000043281
danio_rerio	stap2a	ENSDARG00000092810
mus_musculus	Stap2	ENSMUSG00000038781
rattus_norvegicus	Stap2	ENSRNOG00000047306

Paralogs (1): STAP1 (ENSG00000035720)

Protein

Protein identifiers

Signal-transducing adaptor protein 2 — Q9UGK3 (reviewed: Q9UGK3)

Alternative names: Breast tumor kinase substrate

All UniProt accessions (5): Q9UGK3, M0QY82, M0QZ60, M0R0J5, M0R2W4

UniProt curated annotations — full annotation on UniProt →

Function. Substrate of protein kinase PTK6. May play a regulatory role in the acute-phase response in systemic inflammation and may modulate STAT3 activity.

Subunit / interactions. Interacts with PTK6 and CSF1R.

Subcellular location. Cytoplasm.

Tissue specificity. Widely expressed.

Post-translational modifications. Phosphorylated on tyrosine. Tyr-250 may be important for interaction with kinases. Phosphorylated by PTK6 at Tyr-250 modulates PTK6-mediated STAT3 activation. Tyr-22 and Tyr-322 appears to be phosphorylated by SRC.

Miscellaneous. Alu insert from position 358 to 403.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UGK3-1	1	yes
Q9UGK3-2	2

RefSeq proteins (2): NP_001013863, NP_060190 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000980	SH2	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR035878	STAP2_SH2	Domain
IPR036860	SH2_dom_sf	Homologous_superfamily
IPR039111	STAP1/STAP2	Family

UniProt features (25 total): strand 6, modified residue 4, mutagenesis site 4, domain 2, helix 2, region of interest 2, chain 1, splice variant 1, sequence variant 1, coiled-coil region 1, compositionally biased region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2EL8	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UGK3-F1	72.25	0.35

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 (4): 322, 22, 250, 310

Mutagenesis-validated functional residues (4):

Position	Phenotype
22	small decrease in tyrosine phosphorylation.
250	loss of tyrosine phosphorylation.
310	decrease in tyrosine phosphorylation.
322	decrease in tyrosine phosphorylation.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-8849474	PTK6 Activates STAT3
R-HSA-9707564	Cytoprotection by HMOX1
R-HSA-162582	Signal Transduction
R-HSA-2262752	Cellular responses to stress
R-HSA-8848021	Signaling by PTK6
R-HSA-8953897	Cellular responses to stimuli
R-HSA-9006927	Signaling by Non-Receptor Tyrosine Kinases
R-HSA-9711123	Cellular response to chemical stress

MSigDB gene sets: 125 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, JAEGER_METASTASIS_DN, GOZGIT_ESR1_TARGETS_DN, chr19p13, GOMF_SIGNALING_ADAPTOR_ACTIVITY, LIM_MAMMARY_STEM_CELL_DN, REACTOME_CELLULAR_RESPONSES_TO_STIMULI, REACTOME_SIGNALING_BY_PTK6, ARID5B_TARGET_GENES, ARNT2_TARGET_GENES, ASH1L_TARGET_GENES, CAVIN1_TARGET_GENES, CENPT_TARGET_GENES, E2F5_TARGET_GENES, FOXE1_TARGET_GENES

GO Biological Process (0):

GO Molecular Function (2): signaling adaptor activity (GO:0035591), protein binding (GO:0005515)

GO Cellular Component (3): cytosol (GO:0005829), plasma membrane (GO:0005886), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Signaling by PTK6	1
Cellular response to chemical stress	1
Cellular responses to stimuli	1
Signaling by Non-Receptor Tyrosine Kinases	1
Signal Transduction	1
Cellular responses to stress	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
protein-macromolecule adaptor activity	1
binding	1
cytoplasm	1
membrane	1
cell periphery	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

400 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
STAP2	PTK6	Q13882	958
STAP2	STAT3	P40763	899
STAP2	CSF1R	P07333	732
STAP2	LEPR	P48357	720
STAP2	STAM	Q92783	669
STAP2	DOCK7	Q96N67	667
STAP2	MYD88	P78397	658
STAP2	D6RGC4	D6RGC4	653
STAP2	MARCHF1	Q8TCQ1	632
STAP2	STAM2	O75886	590
STAP2	INS	P01308	571
STAP2	STAT5B	P51692	565
STAP2	HLA-DPA1	P01905	548
STAP2	STAT5A	P42229	522
STAP2	PLCG1	P19174	499

IntAct

56 interactions, top by confidence:

A	B	Type	Score
STAP2	IKBKB	psi-mi:“MI:0914”(association)	0.620
IKBKB	STAP2	psi-mi:“MI:0915”(physical association)	0.620
STAP2	IKBKB	psi-mi:“MI:0915”(physical association)	0.620
PADI1	STAP2	psi-mi:“MI:0915”(physical association)	0.590
BLK	STAP2	psi-mi:“MI:0915”(physical association)	0.560
YES1	STAP2	psi-mi:“MI:0915”(physical association)	0.560
TXK	STAP2	psi-mi:“MI:0915”(physical association)	0.560
KEAP1	STAP2	psi-mi:“MI:0915”(physical association)	0.560
STAT5A	STAP2	psi-mi:“MI:0915”(physical association)	0.560
STAP2	STAT5A	psi-mi:“MI:0915”(physical association)	0.560
STAP2	STAT5A	psi-mi:“MI:0403”(colocalization)	0.560
EGFR	STAP2	psi-mi:“MI:0915”(physical association)	0.550

BioGRID (32): STAP2 (Two-hybrid), STAP2 (PCA), STAP2 (Affinity Capture-MS), PTK6 (Two-hybrid), STAP2 (Affinity Capture-RNA), STAP2 (Affinity Capture-Western), STAP2 (Two-hybrid), STAP2 (Two-hybrid), STAP2 (Two-hybrid), STAP2 (Two-hybrid), STAP2 (Proximity Label-MS), STAP2 (Affinity Capture-MS), PTK6 (Reconstituted Complex), STAP2 (Co-fractionation), STAP2 (Co-fractionation)

ESM2 similar proteins: A0A8I3NFE2, A0FI79, B1AVH7, B5DFA1, D2H0G5, D7PF45, O00750, O15357, O70143, P29353, P97573, P98083, Q00IB7, Q0IIE2, Q15678, Q16825, Q17R13, Q2I6J0, Q2I6J1, Q2V2M9, Q5JV73, Q5M824, Q5R7W7, Q5U2X5, Q61120, Q62130, Q62136, Q62728, Q62925, Q69Z98, Q6P4S2, Q6P549, Q80TI1, Q8AY68, Q8BMC3, Q8BYW1, Q8IWQ3, Q8K245, Q92529, Q92835

Diamond homologs: Q8R0L1, Q9JM90, Q9UGK3, Q9ULZ2, Q64398, Q86XP1

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
PTK6	“up-regulates activity”	STAP2	phosphorylation
SRC	“up-regulates activity”	STAP2	phosphorylation
PTK6	up-regulates	STAP2	phosphorylation
JAK2	“up-regulates activity”	STAP2	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	71
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1881 predictions. Top by Δscore:

Variant	Effect	Δscore
19:4325395:CCAT:C	donor_gain	1.0000
19:4325455:T:TA	donor_gain	1.0000
19:4327139:AGT:A	donor_gain	1.0000
19:4327227:C:CC	acceptor_gain	1.0000
19:4327315:CCGG:C	donor_gain	1.0000
19:4327382:CGTC:C	acceptor_gain	1.0000
19:4327383:GTC:G	acceptor_gain	1.0000
19:4327383:GTCC:G	acceptor_loss	1.0000
19:4327384:TC:T	acceptor_gain	1.0000
19:4327385:CC:C	acceptor_gain	1.0000
19:4327386:C:CC	acceptor_gain	1.0000
19:4327386:CTGCA:C	acceptor_loss	1.0000
19:4327387:T:C	acceptor_loss	1.0000
19:4327392:C:CT	acceptor_gain	1.0000
19:4327393:A:T	acceptor_gain	1.0000
19:4328670:CGCA:C	donor_loss	1.0000
19:4328673:A:AC	donor_gain	1.0000
19:4328673:A:C	donor_loss	1.0000
19:4328673:AC:A	donor_gain	1.0000
19:4328674:C:CA	donor_gain	1.0000
19:4328674:C:CC	donor_gain	1.0000
19:4328674:C:CG	donor_loss	1.0000
19:4328674:CCCG:C	donor_gain	1.0000
19:4329959:A:AC	donor_gain	1.0000
19:4329960:C:CC	donor_gain	1.0000
19:4330057:CGGAG:C	acceptor_gain	1.0000
19:4332016:TCTTA:T	donor_loss	1.0000
19:4332017:CTTAC:C	donor_loss	1.0000
19:4332018:TTACC:T	donor_loss	1.0000
19:4332019:TACC:T	donor_loss	1.0000

AlphaMissense

2595 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:4332051:A:G	W109R	0.999
19:4332051:A:T	W109R	0.999
19:4328699:A:T	V189D	0.997
19:4328741:A:G	L175P	0.997
19:4332049:C:A	W109C	0.995
19:4332049:C:G	W109C	0.995
19:4328747:C:T	G173E	0.994
19:4328738:A:G	L176P	0.993
19:4328781:C:G	A162P	0.993
19:4327332:A:T	I215N	0.992
19:4332050:C:G	W109S	0.992
19:4333698:A:G	F98S	0.992
19:4327189:A:G	F233S	0.991
19:4328747:C:A	G173V	0.991
19:4332045:C:G	G111R	0.991
19:4327366:A:C	Y204D	0.989
19:4328735:A:G	L177P	0.989
19:4328771:A:G	L165P	0.989
19:4332044:C:T	G111D	0.989
19:4334026:C:G	A41P	0.989
19:4327367:A:C	H203Q	0.988
19:4327367:A:T	H203Q	0.988
19:4328748:C:A	G173W	0.988
19:4328768:A:G	L166P	0.988
19:4334029:A:G	W40R	0.988
19:4334029:A:T	W40R	0.988
19:4338677:A:G	L26P	0.987
19:4328735:A:C	L177R	0.986
19:4328808:A:G	C153R	0.986
19:4334019:A:G	L43P	0.986

dbSNP variants (sampled 300 via entrez): RS1000174572 (19:4330646 CAG>C), RS1000275526 (19:4325280 C>T), RS1000327813 (19:4336512 A>G), RS1000443785 (19:4336765 G>T), RS1000539835 (19:4332032 G>A,T), RS1000611522 (19:4330907 G>T), RS1000777292 (19:4338150 T>A), RS1000799734 (19:4338192 C>A,T), RS1000888050 (19:4326447 C>G,T), RS1000975770 (19:4326685 C>G), RS1001235489 (19:4326147 C>T), RS1001243194 (19:4340381 G>A), RS1001312464 (19:4327993 C>G,T), RS1001461809 (19:4335476 A>G,T), RS1001554206 (19:4329642 C>T)

Disease associations

OMIM: gene MIM:607881 | 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
GCST008529_22	Tea consumption	2.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010091	tea consumption measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	3
Acetaminophen	decreases expression	2
Benzo(a)pyrene	decreases methylation, affects methylation, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
aristolochic acid I	increases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
trichostatin A	increases expression	1
epigallocatechin gallate	increases expression	1
di-n-butylphosphoric acid	affects expression	1
pinostrobin	increases phosphorylation	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
Calcitriol	increases expression, affects cotreatment	1
Carbamazepine	affects expression	1
Diethylhexyl Phthalate	increases expression	1
Doxorubicin	decreases expression	1
Estradiol	decreases expression, affects cotreatment	1
Smoke	decreases expression	1
Testosterone	increases expression, affects cotreatment	1
Tetrachlorodibenzodioxin	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Isotretinoin	decreases expression	1
Cyclosporine	decreases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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