TPST2

Summary

TPST2 (tyrosylprotein sulfotransferase 2, HGNC:12021) is a protein-coding gene on chromosome 22q12.1, encoding Protein-tyrosine sulfotransferase 2 (O60704). Catalyzes the O-sulfation of tyrosine residues within acidic motifs of polypeptides, using 3’-phosphoadenylyl sulfate (PAPS) as cosubstrate.

The protein encoded by this gene catalyzes the O-sulfation of tyrosine residues within acidic regions of proteins. The encoded protein is a type II integral membrane protein found in the Golgi body. Alternative splicing produces multiple transcript variants encoding distinct isoforms.

Source: NCBI Gene 8459 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 61 total
• GTEx eGene: eQTL in 22 tissues, sQTL in 12 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.96 (unconstrained)
• MANE Select transcript: NM_003595
• Notable: 61 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12021
Approved symbol	TPST2
Name	tyrosylprotein sulfotransferase 2
Location	22q12.1
Locus type	gene with protein product
Status	Approved
Aliases	TANGO13B
Ensembl gene	ENSG00000128294
Ensembl biotype	protein_coding
OMIM	603126
Entrez	8459

Gene structure

Transcript identifiers

Ensembl transcripts: 70 — 59 protein_coding, 11 nonsense_mediated_decay

MANE Select: ENST00000338754

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 3, TSL 3: 1, TSL 4: 2, TSL 5: 2

ENST00000338754, ENST00000398110, ENST00000403880, ENST00000440953, ENST00000442495, ENST00000445720, ENST00000450022, ENST00000453117, ENST00000454778, ENST00000910410, ENST00000910411, ENST00000910412, ENST00000910413, ENST00000910414, ENST00000910415, ENST00000910416, ENST00000910417, ENST00000910418, ENST00000910419, ENST00000910420, ENST00000910421, ENST00000910422, ENST00000910423, ENST00000910424, ENST00000910425, ENST00000910426, ENST00000910427, ENST00000910428, ENST00000910429, ENST00000910430, ENST00000910431, ENST00000910432, ENST00000910433, ENST00000910434, ENST00000910435, ENST00000910436, ENST00000921142, ENST00000921143, ENST00000921144, ENST00000921145, ENST00000921146, ENST00000921147, ENST00000921148, ENST00000921149, ENST00000921150, ENST00000921151, ENST00000921152, ENST00000940994, ENST00000940995, ENST00000940996, ENST00000940997, ENST00000940998, ENST00000940999, ENST00000941000, ENST00000941001, ENST00000941002, ENST00000941003, ENST00000981313, ENST00000981315, ENST00000981316, ENST00001032900, ENST00001032901, ENST00001032902, ENST00001032904, ENST00001032905, ENST00001032906, ENST00001032907, ENST00001071123, ENST00001106103, ENST00001132011

RefSeq mRNA: 4 — MANE Select: NM_003595 NM_001008566, NM_001362922, NM_001362923, NM_003595

CCDS: CCDS13839

Canonical transcript exons

ENST00000338754 — 7 exons

Exon	Start	End
ENSE00001351932	26544604	26544675
ENSE00001643123	26536288	26536486
ENSE00001670168	26528214	26528262
ENSE00001744184	26532695	26532745
ENSE00001823353	26590053	26590132
ENSE00002197957	26540789	26541718
ENSE00002607234	26521996	26526267

Expression profiles

Bgee: expression breadth ubiquitous, 259 present calls, max score 99.10.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.7173 / max 855.0409, expressed in 1805 samples.

Highest expression (Bgee): body of pancreas, buccal mucosa cell, corpus epididymis, granulocyte, blood.

Genetic regulation across tissues (GTEx eQTL / sQTL)

TPST2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 22 tissues and its splicing (sQTL) in 12 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 34 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Artery Tibial	eqtl	3.3e-27	+0.44	22:26588507:T:C
Esophagus Mucosa	eqtl	2.9e-20	+0.29	22:26523190:A:AAAAC
Testis	eqtl	7.4e-19	+0.32	22:26558834:C:T
Cells Cultured fibroblasts	eqtl	7.5e-12	+0.23	22:26525759:A:G
Skin Sun Exposed Lower leg	eqtl	2.9e-11	+0.19	22:26561318:C:A
Skin Not Sun Exposed Suprapubic	eqtl	3.9e-11	+0.25	22:26575190:T:G
Pancreas	eqtl	1.1e-07	+0.17	22:26558834:C:T
Artery Coronary	eqtl	1.3e-07	+0.42	22:26588507:T:C
Nerve Tibial	sqtl	4.1e-07	-0.51	22:26529339:C:T
Heart Atrial Appendage	eqtl	5.6e-07	+0.22	22:26580404:C:T
Nerve Tibial	eqtl	5.0e-06	-0.14	22:26527450:C:G
Lung	sqtl	6.4e-06	-0.65	22:26534581:C:A
Skin Sun Exposed Lower leg	sqtl	2.3e-05	-0.69	22:26537287:G:A
Artery Aorta	eqtl	3.0e-05	+0.19	22:26585075:A:G
Adrenal Gland	eqtl	8.5e-04	-0.20	22:26429808:C:T
Lung	eqtl	1.1e-03	-0.14	22:26527450:C:G
Muscle Skeletal	eqtl	1.4e-03	+0.10	22:26523190:A:AAAAC
Stomach	eqtl	1.5e-03	-0.21	22:26527545:C:G
Brain Cortex	eqtl	2.5e-03	+0.50	22:26972913:T:TG
Pituitary	eqtl	2.9e-03	-0.25	22:26527941:T:C

FANTOM5 promoters

4 alternative TSS:

Promoter ID	TPM avg	Samples expressed
193431	20.1304	1805
193429	0.3507	24
193428	0.1404	6
193430	0.0959	19

Top tissues by expression

showing 100 of 283 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	99.10	gold quality
buccal mucosa cell	CL:0002336	97.16	gold quality
corpus epididymis	UBERON:0004359	97.11	gold quality
granulocyte	CL:0000094	96.39	gold quality
blood	UBERON:0000178	95.41	gold quality
right lung	UBERON:0002167	94.98	gold quality
right lobe of liver	UBERON:0001114	93.94	gold quality
leukocyte	CL:0000738	93.84	gold quality
endothelial cell	CL:0000115	93.74	gold quality
monocyte	CL:0000576	93.74	gold quality
mononuclear cell	CL:0000842	93.72	gold quality
liver	UBERON:0002107	92.90	gold quality
pancreas	UBERON:0001264	92.52	gold quality
upper lobe of left lung	UBERON:0008952	92.46	gold quality
upper lobe of lung	UBERON:0008948	92.21	gold quality
left lobe of thyroid gland	UBERON:0001120	90.84	gold quality
thyroid gland	UBERON:0002046	90.83	gold quality
right adrenal gland	UBERON:0001233	90.55	gold quality
right adrenal gland cortex	UBERON:0035827	90.49	gold quality
right lobe of thyroid gland	UBERON:0001119	90.48	gold quality
periodontal ligament	UBERON:0008266	90.14	gold quality
left adrenal gland	UBERON:0001234	90.07	gold quality
seminal vesicle	UBERON:0000998	89.95	gold quality
spleen	UBERON:0002106	89.93	gold quality
stromal cell of endometrium	CL:0002255	89.86	gold quality
gastrocnemius	UBERON:0001388	89.76	gold quality
hindlimb stylopod muscle	UBERON:0004252	89.57	gold quality
left adrenal gland cortex	UBERON:0035825	89.49	gold quality
placenta	UBERON:0001987	89.37	gold quality
visceral pleura	UBERON:0002401	89.26	gold quality
lung	UBERON:0002048	89.10	gold quality
bone marrow cell	CL:0002092	89.05	gold quality
muscle of leg	UBERON:0001383	88.77	gold quality
adrenal cortex	UBERON:0001235	88.38	gold quality
apex of heart	UBERON:0002098	88.13	gold quality
adipose tissue	UBERON:0001013	87.94	gold quality
adrenal gland	UBERON:0002369	87.89	gold quality
right coronary artery	UBERON:0001625	87.79	gold quality
adipose tissue of abdominal region	UBERON:0007808	87.76	gold quality
omental fat pad	UBERON:0010414	87.67	gold quality
peritoneum	UBERON:0002358	87.60	gold quality
heart left ventricle	UBERON:0002084	87.54	gold quality
bone marrow	UBERON:0002371	87.49	gold quality
adult organism	UBERON:0007023	87.48	gold quality
connective tissue	UBERON:0002384	87.41	gold quality
trabecular bone tissue	UBERON:0002483	87.09	gold quality
cardiac ventricle	UBERON:0002082	87.08	gold quality
right atrium auricular region	UBERON:0006631	86.96	gold quality
lower lobe of lung	UBERON:0008949	86.78	gold quality
subcutaneous adipose tissue	UBERON:0002190	86.50	gold quality
endocervix	UBERON:0000458	86.49	gold quality
tibia	UBERON:0000979	86.21	gold quality
left uterine tube	UBERON:0001303	86.08	gold quality
adult mammalian kidney	UBERON:0000082	85.94	gold quality
ectocervix	UBERON:0012249	85.78	gold quality
endometrium	UBERON:0001295	85.72	gold quality
amniotic fluid	UBERON:0000173	85.64	gold quality
body of uterus	UBERON:0009853	85.54	gold quality
heart	UBERON:0000948	85.53	gold quality
left coronary artery	UBERON:0001626	85.50	gold quality
vagina	UBERON:0000996	85.42	gold quality
prefrontal cortex	UBERON:0000451	85.38	gold quality
esophagus mucosa	UBERON:0002469	85.16	gold quality
coronary artery	UBERON:0001621	84.94	gold quality
cardiac atrium	UBERON:0002081	84.93	gold quality
metanephros cortex	UBERON:0010533	84.91	gold quality
lymph node	UBERON:0000029	84.90	gold quality
right testis	UBERON:0004534	84.77	gold quality
skin of abdomen	UBERON:0001416	84.58	gold quality
muscle organ	UBERON:0001630	84.54	gold quality
pleura	UBERON:0000977	84.23	gold quality
uterus	UBERON:0000995	84.08	gold quality
left testis	UBERON:0004533	83.93	gold quality
middle temporal gyrus	UBERON:0002771	83.88	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.62	gold quality
multicellular organism	UBERON:0000468	83.61	gold quality
material anatomical entity	UBERON:0000465	83.59	gold quality
right frontal lobe	UBERON:0002810	83.53	gold quality
anatomical system	UBERON:0000467	83.48	gold quality
caput epididymis	UBERON:0004358	83.46	gold quality
skin of leg	UBERON:0001511	83.40	gold quality
testis	UBERON:0000473	83.39	gold quality
thoracic aorta	UBERON:0001515	83.38	gold quality
nephron tubule	UBERON:0001231	83.37	gold quality
lower esophagus mucosa	UBERON:0035834	83.37	gold quality
female reproductive system	UBERON:0000474	83.27	gold quality
cortex of kidney	UBERON:0001225	83.27	gold quality
ascending aorta	UBERON:0001496	83.27	gold quality
tibial nerve	UBERON:0001323	83.23	gold quality
descending thoracic aorta	UBERON:0002345	83.22	gold quality
kidney	UBERON:0002113	83.18	gold quality
metanephros	UBERON:0000081	83.16	gold quality
primary visual cortex	UBERON:0002436	83.00	gold quality
zone of skin	UBERON:0000014	82.85	gold quality
myometrium	UBERON:0001296	82.85	gold quality
esophagus	UBERON:0001043	82.83	gold quality
gall bladder	UBERON:0002110	82.82	gold quality
cingulate cortex	UBERON:0003027	82.81	gold quality
sural nerve	UBERON:0015488	82.81	gold quality
vermiform appendix	UBERON:0001154	82.73	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	40.49
E-CURD-112	yes	35.41
E-GEOD-81547	yes	22.69
E-MTAB-5061	yes	20.12
E-HCAD-10	yes	16.51
E-MTAB-9067	yes	12.53
E-HCAD-1	yes	5.36
E-MTAB-6386	no	1564.35
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Pancreas	tissue	306.9	high
Epididymis	tissue	105.4	high
Liver	tissue	46.9	medium
Placenta	tissue	39.4	high
Thyroid gland	tissue	36.4	medium
Choroid plexus	tissue	35.7
Postcentral gyrus	tissue	29.4
Hippocampal formation	tissue	26.0
Skeletal muscle	tissue	25.4	medium
Spleen	tissue	22.2	not detected
Hippocampus	tissue	22.0	medium
Corpus callosum	tissue	21.9
Bone marrow	tissue	21.9	low
Frontal cortex	tissue	21.8
Locus coeruleus	tissue	21.8
Adipose tissue	tissue	21.7	medium
Lung	tissue	21.5	medium
Tongue	tissue	21.0
Spinal cord	tissue	20.8
Caudate putamen	tissue	20.8
Putamen	tissue	19.4
Basal ganglia	tissue	18.8	medium
Lymph node	tissue	17.8	medium
Nucleus accumbens	tissue	17.5
Seminal vesicle	tissue	16.8	high
Vagina	tissue	16.6	not detected
Cerebral cortex	tissue	16.0	medium
Urinary bladder	tissue	16.0	medium
Kidney	tissue	16.0	medium
Occipital cortex	tissue	16.0
Tonsil	tissue	15.9	medium
Adrenal gland	tissue	15.8	medium
Somatosensory cortex	tissue	15.7
Medulla oblongata	tissue	15.6
Heart muscle	tissue	15.5	low
Olfactory bulb	tissue	15.5
Cervix	tissue	15.4	not detected
Substantia nigra	tissue	15.4
Thalamus	tissue	15.1
Septum	tissue	15.1
Ventral forebrain	tissue	15.0
Superior colliculi	tissue	14.9
Amygdala	tissue	14.8
Periaqueductal gray	tissue	14.8
Appendix	tissue	14.8	low
Temporal cortex	tissue	14.5
Midbrain	tissue	14.3
Entorhinal cortex	tissue	14.2
Skin 1	tissue	14.1	not detected
Retrosplenial cortex	tissue	14.1
Hypothalamus	tissue	13.6
Retrosplenial and cingulate cortex	tissue	13.5
Motor cortex	tissue	13.4
Fallopian tube	tissue	13.2	not detected
Duodenum	tissue	13.1	not detected
Prefrontal cortex	tissue	13.0
Endometrium 1	tissue	12.9	high
Testis	tissue	12.7	high
Insular cortex	tissue	12.4
Small intestine	tissue	11.8	low

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Posterior thalamic nucleus (51.3), Medial dorsal thalamic nucleus (39.0), Habenula (36.6), Temporo-occipital transitional zone (34.7), Orbitofrontal gyrus, anterior (34.6).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting TPST2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 37 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-4452	99.50	68.45	1493
HSA-MIR-942-5P	99.41	68.40	1977
HSA-MIR-183-3P	99.41	69.41	1598
HSA-MIR-302A-5P	99.39	68.21	1913
HSA-MIR-520A-5P	99.35	66.72	1632
HSA-MIR-525-5P	99.35	66.85	1615
HSA-MIR-5582-5P	99.27	71.42	1879
HSA-MIR-3973	99.20	69.19	1990
HSA-MIR-4272	98.76	68.74	1810
HSA-MIR-198	98.70	67.32	920
HSA-MIR-496	98.66	69.80	931
HSA-MIR-6780A-3P	98.42	67.49	1518
HSA-MIR-6831-5P	98.26	67.20	990
HSA-MIR-6072	98.00	66.47	804
HSA-MIR-376A-5P	97.70	65.61	863
HSA-MIR-3927-3P	97.68	66.76	892
HSA-MIR-6783-5P	97.67	67.21	1528
HSA-MIR-4436B-5P	96.71	68.37	1346

Functional genomics

gnomAD constraint: pLI 0.000456, LOEUF 0.957, missense Z 1.01 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000338754 — one region, missense o/e 0.85.

Literature-anchored findings (GeneRIF, showing 8)

• Shear stress-dependent upregulation of TPST2 in human endothelium is mediated by a tyrosine kinase-dependent pathway (PMID:12056800)
• Tyrosine sulfation of CCR5 N-terminal peptide follows a discrete pattern and temporal sequence (PMID:12169668)
• The kinetic parameters of tyrosylprotein sulfotransferase-1 and -2, catalyzing tyrosine sulfation of CCR8 peptides, were determined using liquid chromatography electrospray ionisation mass spectrometry. (PMID:18672380)
• The p.R153H variant was found in a family with hereditary pancreatitis; however, it did not segregate with the disease. (PMID:20460947)
• the first crystal structure of the human tyrosylprotein sulfotransferase isoform 2 complexed with a substrate peptide (C4P5Y3) derived from complement C4 and 3’-phosphoadenosine-5’-phosphate at 1.9 A resolution, is reported. (PMID:23481380)
• Using a quantum mechanics protocol of alanine scanning, the study identified unequivocally the role of the amino acids involved in the TPST-2 catalytic mechanism. (PMID:26108987)
• Genetic variations in the host dependency factors ALCAM and TPST2 impact HIV-1 disease progression. (PMID:32287057)
• Sulfation of a FLAG tag mediated by SLC35B2 and TPST2 affects antibody recognition. (PMID:33951064)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	tpst2	ENSDARG00000099155
mus_musculus	Tpst2	ENSMUSG00000029344
rattus_norvegicus	Tpst2	ENSRNOG00000000664
drosophila_melanogaster	Tpst	FBGN0086674
caenorhabditis_elegans		WBGENE00013737
caenorhabditis_elegans		WBGENE00018365

Paralogs (1): TPST1 (ENSG00000169902)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1309516) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 13 distinct phenotype terms.

Mouse phenotype (MP)	Records
small seminiferous tubules	1
abnormal body weight	1
postnatal growth retardation	1
male infertility	1
abnormal postnatal growth/weight/body size	1
abnormal seminiferous tubule morphology	1
decreased activity of thyroid gland	1
abnormal growth hormone level	1
abnormal adenohypophysis morphology	1
decreased testis weight	1
azoospermia	1
decreased circulating thyroxine level	1
enlarged adenohypophysis	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Macaca fascicularis	Q4R863	99.2%	Diamond
Bos taurus	Q3SYY2	94.4%	Diamond
Caenorhabditis briggsae	A8XLL3	90.7%	Diamond
Gallus gallus	Q5ZJI0	83.4%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
MIR548J	ncRNA	100313914
TFIP11-DT	ncRNA	100507599
CRYBA4	protein-coding	1413
CRYBB1	protein-coding	1414
MIATNB	ncRNA	102724827
MIAT	ncRNA	440823
TFIP11	protein-coding	24144
SRRD	protein-coding	402055
ASPHD2	protein-coding	57168
HPS4	protein-coding	89781

Protein

Protein identifiers

Protein-tyrosine sulfotransferase 2 — O60704 (reviewed: O60704)

Alternative names: Tyrosylprotein sulfotransferase 2

All UniProt accessions (7): B1AHJ5, B1AHJ6, B1AHJ7, B1AHJ8, B1AHJ9, B1AHK0, O60704

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the O-sulfation of tyrosine residues within acidic motifs of polypeptides, using 3’-phosphoadenylyl sulfate (PAPS) as cosubstrate.

Subunit / interactions. Homodimer. Can also form heterodimers with TPST1.

Subcellular location. Golgi apparatus membrane.

Tissue specificity. Widely expressed.

Post-translational modifications. N-glycosylated.

Miscellaneous. Substrate peptides must be flexible in order to adopt an L-shaped conformation in the deep binding cleft.

Similarity. Belongs to the protein sulfotransferase family.

RefSeq proteins (4): NP_001008566, NP_001349851, NP_001349852, NP_003586* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026634	TPST-like	Family
IPR027417	P-loop_NTPase	Homologous_superfamily

Pfam: PF13469

Enzyme classification (BRENDA)

• EC 2.8.2.20 — protein-tyrosine sulfotransferase (BRENDA: 19 organisms, 159 substrates, 69 inhibitors, 77 Km, 8 kcat entries)

Substrate kinetics (BRENDA)

36 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
3’-PHOSPHOADENYLYL SULFATE	0.0021–0.59	9
EAY	—	7
3’-PHOSPHOADENYLYLSULFATE	0.0003–0.02	4
VTDYYYPDI	0.0193–120	4
BENZYL-GLU-TYR	1.223–1.297	2
EEFHTDYIYTQDVK	0.071–0.457	2
P-SELECTIN GLYCOPROTEIN LIGAND-1	0.011–0.053	2
PEPTIDE HIR-(57-65)	0.24–0.41	2
PEPTIDE Y+1 TYROSINE	0.002–0.0044	2
PSGL-1	0.0097–0.0269	2
STATHERIN	0.04	2
TYR-TYR-TYR	0.0175–0.022	2
VTDSYYSYPDI	17–21	2
[Y+3 PEPTIDE]-L-TYROSINE	0.0018–0.0019	2
ATEFEFLDYDFL	0.0315	1

Catalyzed reactions (Rhea)

• L-tyrosyl-[protein] + 3’-phosphoadenylyl sulfate = O-sulfo-L-tyrosine-[protein] + adenosine 3’,5’-bisphosphate + H(+) (RHEA:16801)

UniProt features (56 total): helix 16, strand 9, binding site 7, mutagenesis site 7, sequence conflict 3, topological domain 2, site 2, glycosylation site 2, disulfide bond 2, turn 2, chain 1, transmembrane region 1, region of interest 1, active site 1

Structure

Experimental structures (PDB)

5 structures by resolution:

PDB	Title	Method	Resolution (Å)
9WWE	Crystal structure of human tyrosylprotein sulfotransferase 2 (TPST2) in cation-bound state	X-RAY DIFFRACTION	1.75
3AP1	Crystal structure of human tyrosylprotein sulfotransferase-2 complexed with PAP and C4 …	X-RAY DIFFRACTION	1.9
9WWF	Crystal structure of human tyrosylprotein sulfotransferase 2 (TPST2) in Mn2+-bound state	X-RAY DIFFRACTION	2
3AP2	Crystal structure of human tyrosylprotein sulfotransferase-2 complexed with PAP,C4 …	X-RAY DIFFRACTION	2.4
3AP3	Crystal structure of human tyrosylprotein sulfotransferase-2 complexed with PAP	X-RAY DIFFRACTION	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60704-F1	91.18	0.79

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Metabolic proteins, Predicted intracellular proteins

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH enhanced

Functional residue map

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

Catalytic / active sites (3)

Position	Role
158	transition state stabilizer
285	transition state stabilizer
99	proton donor/acceptor

Ligand- & substrate-binding residues (7)

Position	Role
238	3’-phosphoadenylyl sulfate
285–294	3’-phosphoadenylyl sulfate
300	3’-phosphoadenylyl sulfate
78–82	3’-phosphoadenylyl sulfate
183	3’-phosphoadenylyl sulfate
191	3’-phosphoadenylyl sulfate
195	3’-phosphoadenylyl sulfate

Disulfide bonds (2)

Type	Positions
Disulfide bond	96–156, 225–233

Glycosylation sites (2)

Type	Positions
N-linked (glcnac…) asparagine	343, 368

Mutagenesis-validated functional residues (7)

Position	Phenotype
78	strongly reduced enzymatic activity.
99	loss of sulfotransferase activity.
101	prevents dimerization and strongly decreases enzyme activity.
113	prevents dimerization and decreases enzyme activity.
158	nearly complete loss of enzymatic activity.
198	slightly decreased sulfotransferase activity.
285	abolishes sulfotransferase activity.

Function

Pathways and Gene Ontology

Reactome pathways

3 curated (TAS) of 13; 4 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

13 pathways:

ID	Pathway	Evidence
R-HSA-9674519	Defective F8 sulfation at Y1699 ⚕	curated
R-HSA-156584	Cytosolic sulfonation of small molecules	curated
R-HSA-163841	Gamma carboxylation, hypusinylation, hydroxylation, and arylsulfatase activation	curated
R-HSA-9662001	Defective factor VIII causes hemophilia A ⚕	—
R-HSA-1643685	Disease ⚕	—
R-HSA-9671793	Diseases of hemostasis ⚕	—
R-HSA-211859	Biological oxidations	—
R-HSA-9942503	Differentiation of naive CD4+ T cells to T helper 1 cells (Th1 cells)	electronic
R-HSA-1430728	Metabolism	—
R-HSA-392499	Metabolism of proteins	—
R-HSA-156580	Phase II - Conjugation of compounds	—
R-HSA-597592	Post-translational protein modification	—
R-HSA-9651496		—

MSigDB gene sets: 250 (showing top): GOBP_SINGLE_FERTILIZATION, GOBP_NEGATIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, REACTOME_BIOLOGICAL_OXIDATIONS, GOBP_MEMBRANE_FUSION, GOBP_PLASMA_MEMBRANE_ORGANIZATION, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_SULFATION, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GTGCCTT_MIR506, GOCC_TRANS_GOLGI_NETWORK, ONKEN_UVEAL_MELANOMA_UP, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_DN, ROZANOV_MMP14_TARGETS_UP

GO Biological Process (2): peptidyl-tyrosine sulfation (GO:0006478), 3’-phosphoadenosine 5’-phosphosulfate metabolic process (GO:0050427)

GO Molecular Function (3): protein-tyrosine sulfotransferase activity (GO:0008476), protein homodimerization activity (GO:0042803), transferase activity (GO:0016740)

GO Cellular Component (5): Golgi membrane (GO:0000139), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), Golgi lumen (GO:0005796), trans-Golgi network (GO:0005802)

Reactome top-level categories

9 top-level categories:

Category	Pathways
Phase II - Conjugation of compounds	1
Post-translational protein modification	1
Defective factor VIII causes hemophilia A	1
Differentiation of T cells	1
Biological oxidations	1
Metabolism	1
Metabolism of proteins	1
Defects of Coagulation cascade	1
Disease	1

GO top-level categories

17 GO namespaces:

Category	Terms
Golgi apparatus	2
cytoplasm	2
endomembrane system	2
intracellular membrane-bounded organelle	2
protein sulfation	1
sulfur compound metabolic process	1
purine ribonucleotide metabolic process	1
purine ribonucleoside bisphosphate metabolic process	1
oxoacid metabolic process	1
sulfotransferase activity	1
catalytic activity, acting on a protein	1
identical protein binding	1
protein dimerization activity	1
catalytic activity	1
bounding membrane of organelle	1
intracellular organelle lumen	1
Golgi apparatus subcompartment	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 4 of 10 annotations. The rest are phylogenetic / computational / electronic (IEA).

4 experimentally-supported GO terms:

GO term	NS	Evidence
peptidyl-tyrosine sulfation	BP	direct assay
endoplasmic reticulum	CC	direct assay
protein homodimerization activity	MF	physical interaction
protein-tyrosine sulfotransferase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 764 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TPST2	SLC35B2	Q8TB61	744
TPST2	SELPLG	Q14242	595
TPST2	PDILT	Q8N807	562
TPST2	PAPSS1	O43252	531
TPST2	SELP	P16109	497
TPST2	ADAM2	P78326	478
TPST2	SRRD	Q9UH36	450
TPST2	RNASE10	Q5GAN6	449
TPST2	GALNT8	Q9NY28	446
TPST2	ALCAM	Q13740	445
TPST2	CALR3	Q96L12	435
TPST2	CST8	O60676	411
TPST2	CCR5	P51681	405
TPST2	GGA1	Q9UJY5	394
TPST2	SLC35B3	Q9H1N7	392

IntAct

Human interaction partners of TPST2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

6 partners by confidence:

Partner	Interaction type	MIscore	Records
CHRND	association	0.530	1
TCTN2	association	0.530	1
TPST1	association	0.530	1
NDC80	association	0.350	2
GPC1	association	0.350	1
LARP4	association	0.350	1

BioGRID (140 interactions; top human partners by supporting records): HTR3C (Affinity Capture-MS; 3 records), PTCH1 (Affinity Capture-MS; 3 records), SLC39A4 (Affinity Capture-MS; 3 records), ATP2A3 (Affinity Capture-MS; 2 records), CHRNA3 (Affinity Capture-MS; 2 records), CHRND (Affinity Capture-MS; 2 records), CSGALNACT2 (Affinity Capture-MS; 2 records), GOLPH3 (Affinity Capture-MS; 2 records), GOLPH3L (Affinity Capture-MS; 2 records), HTR3A (Affinity Capture-MS; 2 records), SCARB2 (Affinity Capture-Western; 2 records), SLC39A9 (Affinity Capture-MS; 2 records), TCTN2 (Affinity Capture-MS; 2 records), ADPGK (Affinity Capture-MS), ATP12A (Affinity Capture-MS)

Disease & clinical

Genetic variants

Variant evidence for TPST2: 61 ClinVar records (0 pathogenic / likely pathogenic); 5 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	52
Likely benign	0
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 34 predictions of 1,190):

Position(s)	Effect	Δscore	Sites
22:26526156	donor_gain	1.0000
22:26528212–26528213	donor_loss	1.0000	4
22:26536286–26536287	donor_loss	1.0000	4
22:26528213	donor_loss	0.9900
22:26528263–26528264	acceptor_loss	0.9900	6
22:26532693–26532694	donor_loss	0.9900	6
22:26536287	donor_loss	0.9900
22:26536487–26536488	acceptor_loss	0.9900	6
22:26590051–26590052	donor_loss	0.9900	4
22:26526150	donor_gain	0.9800

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

4 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	unfavorable	3.71e-06
Kidney Renal Papillary Cell Carcinoma (TCGA)	unfavorable	6.68e-06
Pancreatic Adenocarcinoma (validation)	unfavorable	0.000109
Uterine Corpus Endometrial Carcinoma (TCGA)	favorable	0.000815

Disease associations

OMIM: gene MIM:603126 | disease phenotypes:

GWAS associations

5 associations:

Study	Trait	p-value
GCST006585_1043	Blood protein levels	7e-9
GCST009391_107	Metabolite levels	2e-6
GCST005025_13	Anti-saccade response	4e-6
GCST005025_24	Anti-saccade response	4e-6
GCST009391_1463	Metabolite levels	9e-6

EFO canonical traits (from GWAS)

3 canonical traits:

EFO ID	Trait name
EFO:0006874	antisaccade response measurement
EFO:0010355	diacylglycerol 36:2 measurement
EFO:0010414	triacylglycerol 52:2 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3178 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

3 measured of 5 human assays (5 total across all organisms); most potent 3 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
6,8-Dichloro-4-oxo-4H-chromene-3-carbaldehyde O-{5-[1-(3,5-dibromo-4-hydroxy-phenyl)-meth-(E)-ylideneaminooxy]-pentyl}-oxime	IC50	30000 nM
6,8-Dichloro-4-oxo-4H-chromene-3-carbaldehyde O-{5-[1-(5-bromo-2-hydroxy-3-nitro-phenyl)-meth-(E)-ylideneaminooxy]-pentyl}-oxime	IC50	40000 nM
3,5-Dibromo-4-hydroxy-benzaldehyde O-methyl-oxime	IC50	425000 nM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression	2
Benzo(a)pyrene	affects methylation, decreases expression	2
Valproic Acid	increases expression	2
aristolochic acid I	increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
PCI 5002	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Zoledronic Acid	decreases expression	1
Acetaminophen	increases expression	1
Diuron	decreases expression	1
Fluorouracil	affects response to substance	1
Quercetin	decreases expression	1
Smoke	decreases expression	1
Tamoxifen	affects expression	1
Testosterone	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	increases expression	1
Zinc	affects cotreatment, increases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	decreases expression	1
tert-Butylhydroperoxide	increases expression	1

ChEMBL screening assays

5 unique, capped per target: 5 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL811422	Binding	Inhibitory activity of compound was determined against human tyrosylprotein sulfotransferase-2 (hTPST-2) using [35S]PAPS radioligand	Tyrosylprotein sulfotransferase inhibitors generated by combinatorial target-guided ligand assembly. — *Bioorg Med Chem Lett*

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for TPST2 across ~30M SureChEMBL compounds — explore on Sugi Predict.