SGTA

Summary

SGTA (small glutamine rich tetratricopeptide repeat co-chaperone alpha, HGNC:10819) is a protein-coding gene on chromosome 19p13.3, encoding Small glutamine-rich tetratricopeptide repeat-containing protein alpha (O43765). Co-chaperone that binds misfolded and hydrophobic patches-containing client proteins in the cytosol.

This gene encodes a protein which is capable of interacting with the major nonstructural protein of parvovirus H-1 and 70-kDa heat shock cognate protein; however, its function is not known. Since this transcript is expressed ubiquitously in various tissues, this protein may serve a housekeeping function.

Source: NCBI Gene 6449 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 41 total
• Druggable target: yes
• MANE Select transcript: NM_003021

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10819
Approved symbol	SGTA
Name	small glutamine rich tetratricopeptide repeat co-chaperone alpha
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	UBP, SGT1, Vpu, hSGT, alphaSGT
Ensembl gene	ENSG00000104969
Ensembl biotype	protein_coding
OMIM	603419
Entrez	6449

Gene structure

Transcript identifiers

Ensembl transcripts: 40 — 29 protein_coding, 6 retained_intron, 4 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000221566, ENST00000586711, ENST00000587866, ENST00000589251, ENST00000591984, ENST00000676611, ENST00000676943, ENST00000676984, ENST00000677149, ENST00000677513, ENST00000677562, ENST00000677731, ENST00000677754, ENST00000678109, ENST00000678577, ENST00000678595, ENST00000679132, ENST00000679138, ENST00000897082, ENST00000897083, ENST00000897084, ENST00000897085, ENST00000897086, ENST00000897087, ENST00000927730, ENST00000927731, ENST00000927732, ENST00000927733, ENST00000927734, ENST00000927735, ENST00000927736, ENST00000927737, ENST00000927738, ENST00000927739, ENST00000927740, ENST00000927741, ENST00000952638, ENST00000952639, ENST00000952640, ENST00000952641

RefSeq mRNA: 1 — MANE Select: NM_003021 NM_003021

CCDS: CCDS12094

Canonical transcript exons

ENST00000221566 — 12 exons

Exon	Start	End
ENSE00000663945	2767580	2767686
ENSE00000663947	2767136	2767220
ENSE00000663948	2765186	2765285
ENSE00000663949	2763653	2763757
ENSE00000663950	2762506	2762644
ENSE00000663951	2761460	2761522
ENSE00000663952	2759257	2759294
ENSE00000859577	2768969	2769091
ENSE00000859580	2754715	2755933
ENSE00001357938	2783233	2783273
ENSE00003466617	2757693	2757782
ENSE00003584241	2757337	2757457

Expression profiles

Bgee: expression breadth ubiquitous, 237 present calls, max score 97.18.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 48.0002 / max 206.3944, expressed in 1816 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
178207	34.7671	1811
178208	11.9200	1792
178209	1.3131	859

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	97.18	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.77	gold quality
lower esophagus mucosa	UBERON:0035834	96.25	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.93	gold quality
gastrocnemius	UBERON:0001388	95.92	gold quality
right frontal lobe	UBERON:0002810	95.86	gold quality
middle frontal gyrus	UBERON:0002702	95.85	gold quality
right atrium auricular region	UBERON:0006631	95.74	gold quality
paraflocculus	UBERON:0005351	95.49	gold quality
spinal cord	UBERON:0002240	95.45	gold quality
muscle of leg	UBERON:0001383	95.20	gold quality
cingulate cortex	UBERON:0003027	95.09	gold quality
adenohypophysis	UBERON:0002196	95.07	gold quality
anterior cingulate cortex	UBERON:0009835	95.04	gold quality
amygdala	UBERON:0001876	95.03	gold quality
heart left ventricle	UBERON:0002084	94.87	gold quality
frontal pole	UBERON:0002795	94.73	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.72	gold quality
cardiac atrium	UBERON:0002081	94.70	gold quality
cortical plate	UBERON:0005343	94.61	gold quality
cardiac ventricle	UBERON:0002082	94.57	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.48	gold quality
cerebellar hemisphere	UBERON:0002245	94.47	gold quality
lower esophagus	UBERON:0013473	94.47	gold quality
cerebellar cortex	UBERON:0002129	94.42	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.23	gold quality
mucosa of transverse colon	UBERON:0004991	94.20	gold quality
left testis	UBERON:0004533	94.16	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.16	gold quality
nucleus accumbens	UBERON:0001882	94.13	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.08

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

42 targeting SGTA, 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-7110-3P	100.00	73.18	2486
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-4320	99.75	65.80	793
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-4687-3P	99.48	66.41	968
HSA-MIR-657	99.48	66.02	848
HSA-MIR-5580-5P	99.38	66.96	1139
HSA-MIR-3692-5P	99.29	67.04	1421
HSA-MIR-149-5P	99.25	67.16	1315
HSA-MIR-328-5P	99.08	64.65	1000
HSA-MIR-6868-5P	99.06	65.69	1284
HSA-MIR-6846-5P	98.81	65.86	1121
HSA-MIR-6848-5P	98.81	65.49	1126
HSA-MIR-3938	98.72	66.07	834
HSA-MIR-6804-5P	98.39	65.77	1084
HSA-MIR-4436B-3P	98.25	65.26	1494
HSA-MIR-6735-5P	98.24	65.36	1488
HSA-MIR-7843-5P	98.12	65.26	1421
HSA-MIR-637	97.91	64.05	1517
HSA-MIR-4632-5P	97.82	65.38	1470

Literature-anchored findings (GeneRIF, showing 37)

• small glutamine-rich protein/viral protein U-binding protein (SGT/UBP) is a cochaperone that negatively regulates Hsp70. (PMID:12482202)
• interaction with the ubiquitin-dependent endocytosis motif of the growth hormone receptor (PMID:12735788)
• Complete backbone assignments of the 121 residues of hSGT were determined and deposited in BMRB 5709. (PMID:12815268)
• SGTA (or hSGT) is essential for cell division. Knock down experiments show that cells with reduced levels of SGTA arrest in mitosis and die while undergoing cell division. (PMID:14729056)
• SGT is a new pro-apoptotic factor (PMID:15710426)
• CSP modulates G protein function by preferentially targeting the inactive GDP-bound form of G alpha(s) and promoting GDP/GTP exchange; the guanine nucleotide exchange activity of full-length CSP is regulated by Hsc70-SGT (PMID:15972823)
• the sub-cellular localization of SGT was closely associated with Hsp90beta and apoptosis (PMID:16580629)
• Interaction of hSGT with Hsc70, Hsp70 or Bag-6/Bat-3/Scythe was demonstrated in prometaphase, thereby suggesting a possible role for complexes containing hSGT and distinct (co)-chaperones during mitosis. (PMID:16777091)
• SGTA acts as a rheostat of androgen receptor signaling in prostate cancer (PMID:17942943)
• For SNP rs1640262, homozygotes for minor allele were protected against PCOS. Haplotype 1 (G-A-T) associated with increased risk of PCOS. In PCOS, haplotype 2 (A-G-C) associated with increased insulin resistance, resulting in increased insulin secretion. (PMID:18332089)
• The recombinant human small glutamine-rich tetratricopeptide-repeat protein SGT has been purified and crystallized and preliminary analysis of the tetratricopeptide-repeat (TPR) domain is reported. (PMID:18607086)
• The TPR domain of SGT can bind Vpu and reduce the amount of HIV-1 virus p24, which is the viral capsid, secreted from cells transfected with the HIV-1 proviral construct. (PMID:18759457)
• Homodimerizaion of SGTA is dependent on the structural integrity of amino acids 1-80, and a core evolutionary conserved peptide within this region (amino acids 21-40) necessary for an effect of SGTA on the activity of the androgen receptor. (PMID:22693264)
• findings show that the HERV-K(HML-2) Rec protein binds to hSGT and interferes with its role as a negative regulator of the androgen receptor (AR), resulting in enhanced AR activity (PMID:22733359)
• A BAG6/SGTA cycle operates during protein maturation and quality control in the cytosol. (PMID:23129660)
• Structures of the Sgt2/SGTA dimerization domain with the Get5/UBL4A UBL domain reveal an interaction that forms a conserved dynamic interface. (PMID:23142665)
• SGTA recognizes a noncanonical ubiquitin-like domain in the Bag6-Ubl4A-Trc35 complex to promote endoplasmic reticulum-associated degradation. (PMID:23246001)
• SGTA is present in human ovaries and has the potential to modulate androgen receptor signalling, but it may not be differentially expressed in polycystic ovary syndrome. (PMID:23433514)
• showed a significant increase in the AR:SGTA ratio in cancerous lesions compared to patient-matched benign prostatic hyperplasia tissue (PMID:23740762)
• SGTA depletion decreased cyclin A and cyclin B levels. (PMID:23839012)
• High Small glutamine-rich tetratricopeptide repeat-containing protein alpha expression is associated with non-small-cell lung cancer tumorigenesis. (PMID:23857189)
• High expression of SGTA in esophageal squamous cell carcinoma correlates with proliferation and poor prognosis. (PMID:23939810)
• Univariate analysis showed that the low SGTB expression was associated with poor prognosis (P<0.001) (PMID:24195513)
• Our data suggest a role for SGTA at distinct steps in the chaperone-dependent modulation of androgen, glucocorticoid, and progesterone receptor activity. (PMID:24753260)
• A role of SGTA in Non-Hodgkin’s lymphoma (NHL) cell proliferation, adhesion and drug resistance, and it may pave the way for a novel therapeutic approach for cell adhesion-mediated drug resistance in NHL. (PMID:24974147)
• SGTA overexpression may be involved in the pathogenesis of breast cancer which might serve as a future target for novel treatment in breast cancer. (PMID:25027991)
• data suggest that SGTA regulates the cellular fate of a range of hydrophobic polypeptides should they become exposed to the cytosol. (PMID:25179605)
• Data show that molecular chaperone BAG6_ubiquitin-like domain (UBL) and ubiquitin-like 4A UBL4A_UBL compete for the same binding site on N-terminal dimerisation domain of SGTA protein (SGTA_NT). (PMID:25415308)
• the binding of SGTA to Rpn13 enables specific polypeptides to escape proteasomal degradation and/or selectively modulates substrate degradation. (PMID:26169395)
• Coimmunoprecipitation studies indicated that non-glycosylated tetherin is stabilized through the formation of a ternary SGTA/Vpu/tetherin complex. Although the results do not provide support for a physiological function of SGTA in HIV-1 replication, they demonstrate that SGTA overexpression regulates tetherin expression and stability, thus providing insights into the function of SGTA in endoplasmic reticulum translocation (PMID:27103333)
• evidence that the interaction can mediate the association of Rpn13 and SGTA in a cellular context. (PMID:27827410)
• study demonstrates a critical role of Hsc70 in SV40 endoplasmic reticulum-to-cytosol penetration and reveal how SGTA controls Hsc70 to impact this process (PMID:28356524)
• the results provide novel insights into the structural complexity of SGTA and provide a new basis for mechanistic studies of substrate binding and release at the C-terminal region. (PMID:29996828)
• The SGTA is a co-chaperone that, in collaboration with the complex of BAG6, facilitates the biogenesis and quality control of hydrophobic proteins, protecting them from the aqueous cytosolic environment. (PMID:30635083)
• SGTA associates with nascent membrane protein precursors. (PMID:32216016)
• SGTA associates with intracellular aggregates in neurodegenerative diseases. (PMID:33757575)
• USP5 enhances SGTA mediated protein quality control. (PMID:35895711)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	sgta	ENSDARG00000019941
mus_musculus	Sgta	ENSMUSG00000004937
rattus_norvegicus	Sgta	ENSRNOG00000019891
drosophila_melanogaster	unc-45	FBGN0288846
caenorhabditis_elegans		WBGENE00006781

Paralogs (18): RPAP3 (ENSG00000005175), TOMM34 (ENSG00000025772), ST13 (ENSG00000100380), STUB1 (ENSG00000103266), SPAG1 (ENSG00000104450), TTC1 (ENSG00000113312), TTC31 (ENSG00000115282), UNC45A (ENSG00000140553), UNC45B (ENSG00000141161), SPATA16 (ENSG00000144962), TTC12 (ENSG00000149292), TOMM70 (ENSG00000154174), SUGT1 (ENSG00000165416), STIP1 (ENSG00000168439), TTC32 (ENSG00000183891), SGTB (ENSG00000197860), TTC4 (ENSG00000243725), DNAAF4 (ENSG00000256061)

Protein

Protein identifiers

Small glutamine-rich tetratricopeptide repeat-containing protein alpha — O43765 (reviewed: O43765)

Alternative names: Alpha-SGT, Vpu-binding protein

All UniProt accessions (9): A0A7I2V2U2, A0A7I2V4T9, A0A7I2V588, A0A7I2V5Z3, A0A7I2V697, A0A7I2YQY5, O43765, K7EMD6, K7ERW5

UniProt curated annotations — full annotation on UniProt →

Function. Co-chaperone that binds misfolded and hydrophobic patches-containing client proteins in the cytosol. Mediates their targeting to the endoplasmic reticulum but also regulates their sorting to the proteasome when targeting fails. Functions in tail-anchored/type II transmembrane proteins membrane insertion constituting with ASNA1 and the BAG6 complex a targeting module. Functions upstream of the BAG6 complex and ASNA1, binding more rapidly the transmembrane domain of newly synthesized proteins. It is also involved in the regulation of the endoplasmic reticulum-associated misfolded protein catabolic process via its interaction with BAG6: collaborates with the BAG6 complex to maintain hydrophobic substrates in non-ubiquitinated states. Competes with RNF126 for interaction with BAG6, preventing the ubiquitination of client proteins associated with the BAG6 complex. Binds directly to HSC70 and HSP70 and regulates their ATPase activity. (Microbial infection) In case of infection by polyomavirus, involved in the virus endoplasmic reticulum membrane penetration and infection via interaction with DNAJB12, DNAJB14 and HSPA8/Hsc70.

Subunit / interactions. Homodimer. Homooligomer. Interacts with DNAJC5 and DNAJC5B. Interacts (via TPR repeats) with HSP90AA1. Interacts (via Gln-rich region) with SLC2A1. Interacts with HSP90AB1. Interacts (via TPR repeats) with HSPA8/Hsc70; the interaction is direct. Interacts with BAG6 (via ubiquitin-like domain); interaction prevents interaction between BAG6 and RNF126. Forms a multiprotein complex, at least composed of DNAJB12, DNAJB14, HSPA8/Hsc70 and SGTA; interaction with DNAJB14 and HSPA8/Hsc70 is direct. (Microbial infection) Interacts with Vpu and Gag from HIV-1. (Microbial infection) Interacts with SARS-CoV accessory protein 7a.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Ubiquitous.

Domain organisation. The second tetratricopeptide repeat (TPR 2) mediates the interaction with SARS-CoV accessory protein 7a.

Similarity. Belongs to the SGT family.

RefSeq proteins (1): NP_003012* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR019734	TPR_rpt	Repeat
IPR032374	SGTA_dimer	Domain
IPR047150	SGT	Family

Pfam: PF00515, PF13181, PF16546

UniProt features (26 total): helix 11, modified residue 7, repeat 3, region of interest 2, chain 1, mutagenesis site 1, compositionally biased region 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
4GOF	X-RAY DIFFRACTION	1.35
4GOD	X-RAY DIFFRACTION	1.4
4GOE	X-RAY DIFFRACTION	1.45
2VYI	X-RAY DIFFRACTION	2.4
4CPG	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43765-F1	81.86	0.54

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 (7): 137, 301, 303, 305, 77, 81, 84

Mutagenesis-validated functional residues (1):

Position	Phenotype
38	reduces tail-anchored proteins transfer.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-9609523	Insertion of tail-anchored proteins into the endoplasmic reticulum membrane
R-HSA-9609507	Protein localization

MSigDB gene sets: 144 (showing top): GOBP_NEGATIVE_REGULATION_OF_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_NEGATIVE_REGULATION_OF_PROTEOLYSIS, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_PROTEIN_TARGETING, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ENDOPLASMIC_RETICULUM, MORF_HDAC2, DARWICHE_PAPILLOMA_PROGRESSION_RISK, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_PROTEIN_TARGETING_TO_MEMBRANE, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CATABOLIC_PROCESS

GO Biological Process (7): post-translational protein targeting to endoplasmic reticulum membrane (GO:0006620), ERAD pathway (GO:0036503), tail-anchored membrane protein insertion into ER membrane (GO:0071816), negative regulation of ERAD pathway (GO:1904293), positive regulation of ERAD pathway (GO:1904294), negative regulation of ubiquitin-dependent protein catabolic process (GO:2000059), positive regulation of ubiquitin-dependent protein catabolic process (GO:2000060)

GO Molecular Function (4): identical protein binding (GO:0042802), molecular adaptor activity (GO:0060090), BAT3 complex binding (GO:1904288), protein binding (GO:0005515)

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), membrane (GO:0016020), TRC complex (GO:0072380)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Protein localization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
ERAD pathway	2
regulation of ERAD pathway	2
ubiquitin-dependent protein catabolic process	2
regulation of ubiquitin-dependent protein catabolic process	2
binding	2
protein targeting to membrane	1
protein targeting to ER	1
proteasomal protein catabolic process	1
response to endoplasmic reticulum stress	1
response to chemical	1
protein insertion into ER membrane	1
negative regulation of proteasomal protein catabolic process	1
negative regulation of response to endoplasmic reticulum stress	1
positive regulation of proteasomal protein catabolic process	1
positive regulation of response to endoplasmic reticulum stress	1
negative regulation of protein catabolic process	1
positive regulation of protein catabolic process	1
protein binding	1
molecular_function	1
protein-containing complex binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
ER membrane insertion complex	1

Protein interactions and networks

STRING

2469 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SGTA	UBL4A	P11441	995
SGTA	HSPA8	P11142	994
SGTA	GET4	Q7L5D6	994
SGTA	HSPH1	Q92598	985
SGTA	HSPA4	P34932	962
SGTA	BAG2	O95816	921
SGTA	GET3	O43681	912
SGTA	BAG6	P46379	890
SGTA	HSP90AA1	P07900	865
SGTA	DNAJC5	Q9H3Z4	819
SGTA	HSP90AB1	P08238	809
SGTA	GET1	O00258	780
SGTA	ADRM1	Q16186	741
SGTA	DNAJB14	Q8TBM8	735
SGTA	DNAJB12	Q9NXW2	724

IntAct

927 interactions, top by confidence:

A	B	Type	Score
EFEMP1	SGTA	psi-mi:“MI:0915”(physical association)	0.930
SGTA	EFEMP1	psi-mi:“MI:0915”(physical association)	0.930
SGCA	SGTA	psi-mi:“MI:0915”(physical association)	0.900
SGTA	SGCA	psi-mi:“MI:0915”(physical association)	0.900
SPP1	SGTA	psi-mi:“MI:0915”(physical association)	0.830
SGTA	F11R	psi-mi:“MI:0915”(physical association)	0.830
SGTA	SPP1	psi-mi:“MI:0915”(physical association)	0.830
COL1A2	SGTA	psi-mi:“MI:0915”(physical association)	0.810
BAG6	SGTA	psi-mi:“MI:0915”(physical association)	0.800
SGTA	BAG6	psi-mi:“MI:0915”(physical association)	0.800
KASH5	SGTA	psi-mi:“MI:0915”(physical association)	0.790
SGTA	KASH5	psi-mi:“MI:0915”(physical association)	0.790
SGTA	EFEMP2	psi-mi:“MI:0915”(physical association)	0.780
SGTA	ZG16	psi-mi:“MI:0915”(physical association)	0.780
RPN1	SGTA	psi-mi:“MI:0915”(physical association)	0.780
SGTA	SRGN	psi-mi:“MI:0915”(physical association)	0.780
GRN	SGTA	psi-mi:“MI:0915”(physical association)	0.780
NME3	SGTA	psi-mi:“MI:0915”(physical association)	0.780
SGTA	NAXD	psi-mi:“MI:0915”(physical association)	0.780
SGTA	SPPL2A	psi-mi:“MI:0915”(physical association)	0.780
ERP27	SGTA	psi-mi:“MI:0915”(physical association)	0.780
SGTA	SYT11	psi-mi:“MI:0915”(physical association)	0.780
SYT4	SGTA	psi-mi:“MI:0915”(physical association)	0.780
EFEMP2	SGTA	psi-mi:“MI:0915”(physical association)	0.780

BioGRID (516): SGTA (Affinity Capture-Western), SGTA (Affinity Capture-Western), SGTA (Two-hybrid), SGTA (Two-hybrid), SGTA (Two-hybrid), SGTA (Two-hybrid), SGTA (Two-hybrid), SGTA (Two-hybrid), SGTA (Two-hybrid), SGTA (Two-hybrid), SGTA (Two-hybrid), SGTA (Two-hybrid), SGTA (Two-hybrid), SGTA (Two-hybrid), SGTA (Two-hybrid)

ESM2 similar proteins: A0JPP7, A1L5A6, A4QNE0, O35815, O43765, O70593, O95453, P50502, P50503, P54252, P69341, Q05B58, Q0P5I8, Q13033, Q16186, Q2KIK0, Q32LM2, Q3TDN2, Q5R812, Q5RBU4, Q5RC51, Q5RCR8, Q5RF31, Q5SRX1, Q5ZHS3, Q5ZLF0, Q6GLK9, Q6NRL4, Q6ZVM7, Q75Q39, Q7L5D6, Q80W98, Q8BJU0, Q8NFI4, Q8R1T1, Q8VD33, Q8VDG3, Q8WTU0, Q8WUX9, Q95JI3

Diamond homologs: C9K7C5, F4IXE4, O13797, O16259, O43765, O70593, P0CT30, P25638, P34723, Q07617, Q1RQJ1, Q32LM2, Q5U2X2, Q6NU95, Q6Z4I3, Q80ZX8, Q84JR9, Q84K11, Q86VQ3, Q8BJU0, Q8ILC1, Q96EQ0, Q9LVH5, Q9MAH1, Q9SIN1, A0A3L6DPG1, A4K2V0, A6HD62, A6ZRW3, A8BFN4, B0BN85, D3ZSP7, F4KCL7, F8RP11, O14217, O35814, O48802, O54981, O88196, O94826

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
UBL4A	“up-regulates activity”	SGTA	binding
SGTA	“up-regulates activity”	BAG6	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	18
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

2145 predictions. Top by Δscore:

Variant	Effect	Δscore
19:2757335:A:AC	donor_gain	1.0000
19:2757336:C:CC	donor_gain	1.0000
19:2757336:CG:C	donor_gain	1.0000
19:2757336:CGCAG:C	donor_gain	1.0000
19:2757340:G:C	donor_gain	1.0000
19:2757455:CCC:C	acceptor_gain	1.0000
19:2757456:CC:C	acceptor_gain	1.0000
19:2757456:CCC:C	acceptor_gain	1.0000
19:2757456:CCCT:C	acceptor_loss	1.0000
19:2757457:CC:C	acceptor_gain	1.0000
19:2757458:C:A	acceptor_loss	1.0000
19:2757458:C:CC	acceptor_gain	1.0000
19:2757459:T:C	acceptor_loss	1.0000
19:2757661:T:TA	donor_gain	1.0000
19:2757692:CG:C	donor_gain	1.0000
19:2757779:CATG:C	acceptor_gain	1.0000
19:2757781:TG:T	acceptor_gain	1.0000
19:2759255:A:AC	donor_gain	1.0000
19:2759256:C:CC	donor_gain	1.0000
19:2759256:CAG:C	donor_gain	1.0000
19:2761459:CCATG:C	donor_gain	1.0000
19:2761518:CCCGT:C	acceptor_gain	1.0000
19:2761519:CCGT:C	acceptor_gain	1.0000
19:2761519:CCGTC:C	acceptor_gain	1.0000
19:2761520:CGT:C	acceptor_gain	1.0000
19:2761520:CGTC:C	acceptor_gain	1.0000
19:2761523:C:CC	acceptor_gain	1.0000
19:2762504:A:AC	donor_gain	1.0000
19:2762505:C:CT	donor_gain	1.0000
19:2762505:CG:C	donor_gain	1.0000

AlphaMissense

2078 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:2757443:G:T	A281D	1.000
19:2763670:C:A	K160N	1.000
19:2763670:C:G	K160N	1.000
19:2765285:C:T	G98E	1.000
19:2767136:C:G	G98R	1.000
19:2767136:C:T	G98R	1.000
19:2759293:G:T	A234D	0.999
19:2762610:C:G	A178P	0.999
19:2762642:A:G	L167P	0.999
19:2763653:C:T	G166D	0.999
19:2763654:C:G	G166R	0.999
19:2763658:C:A	R164S	0.999
19:2763658:C:G	R164S	0.999
19:2763659:C:A	R164M	0.999
19:2763659:C:G	R164T	0.999
19:2763662:C:T	G163D	0.999
19:2763672:T:C	K160E	0.999
19:2763749:G:T	A134D	0.999
19:2763755:G:T	A132D	0.999
19:2763757:T:A	R131S	0.999
19:2763757:T:G	R131S	0.999
19:2765188:G:C	N130K	0.999
19:2765188:G:T	N130K	0.999
19:2765249:G:T	A110D	0.999
19:2765285:C:A	G98V	0.999
19:2767143:T:A	K95N	0.999
19:2767143:T:G	K95N	0.999
19:2767671:A:G	L39P	0.999
19:2757401:A:G	L295P	0.998
19:2757446:A:G	F280S	0.998

dbSNP variants (sampled 300 via entrez): RS1000078349 (19:2769687 T>C), RS1000135778 (19:2776035 C>G), RS1000139430 (19:2783182 C>G), RS1000218494 (19:2758889 C>A,T), RS1000261457 (19:2780579 T>A), RS1000511534 (19:2758971 G>A,T), RS1000608552 (19:2767321 G>A,T), RS1000688878 (19:2777089 C>T), RS1000788551 (19:2771799 C>A,T), RS1000801960 (19:2767412 G>A,T), RS1000812266 (19:2781873 G>A), RS1000813761 (19:2754713 CAG>C), RS1000855607 (19:2763191 G>A), RS1000909712 (19:2772010 G>A), RS1001079662 (19:2755626 G>A)

Disease associations

OMIM: gene MIM:603419 | 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
GCST012490_489	Femur bone mineral density x serum urate levels interaction	2.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066222 (SINGLE PROTEIN)

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

ChEMBL bioactivities

3 potent at pChembl≥5 of 4 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.00	IC50	100	nM	CHEMBL5561795
5.70	IC50	2000	nM	CHEMBL5558181
5.22	IC50	6000	nM	CHEMBL5558644

PubChem BioAssay actives

3 with measured affinity, of 5 total; 3 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N,N’-bis(3-carbamoyl-6-ethyl-4,5,6,7-tetrahydro-1-benzothiophen-2-yl)pentanediamide	2084029: Inhibition of GST-tagged human SGTA expressed in Escherichia coli BL21 (DE3) using NH2-EDASRMEEVD-COOH peptide as substrate preincubated for 15 mins followed by substrate addition measured after 15 mins by Alpha Screen assay	ic50	0.1000	uM
N,N’-bis(3-carbamoyl-4,5-dimethylthiophen-2-yl)pentanediamide	2084029: Inhibition of GST-tagged human SGTA expressed in Escherichia coli BL21 (DE3) using NH2-EDASRMEEVD-COOH peptide as substrate preincubated for 15 mins followed by substrate addition measured after 15 mins by Alpha Screen assay	ic50	2.0000	uM
methyl 2-[[2-[[5,6-bis(furan-2-yl)-1,2,4-triazin-3-yl]sulfanyl]acetyl]amino]-4,5-dimethylthiophene-3-carboxylate	2084029: Inhibition of GST-tagged human SGTA expressed in Escherichia coli BL21 (DE3) using NH2-EDASRMEEVD-COOH peptide as substrate preincubated for 15 mins followed by substrate addition measured after 15 mins by Alpha Screen assay	ic50	6.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression	2
sodium arsenite	increases expression, affects binding, increases reaction	2
Acetaminophen	decreases expression	2
Doxorubicin	decreases expression, affects expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
glycidyl methacrylate	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression, affects localization, increases expression	1
decabromobiphenyl ether	increases expression	1
tetrabromobisphenol A	decreases expression	1
perfluorooctanoic acid	increases expression	1
manganese chloride	increases abundance, decreases expression	1
benzo(e)pyrene	increases methylation	1
nickel sulfate	increases expression	1
pinosylvin	increases expression	1
di-n-butylphosphoric acid	affects expression	1
corosolic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	decreases expression	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Ethanol	affects cotreatment, increases abundance, increases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5524502	Binding	Inhibition of GST-tagged human SGTA expressed in Escherichia coli BL21 (DE3) using NH2-EDASRMEEVD-COOH peptide as substrate preincubated for 15 mins followed by substrate addition measured after 15 mins by Alpha Screen assay	Structure-based discovery of small molecule inhibitors of FKBP51-Hsp90 protein-protein interaction. — Eur J Med Chem

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B3GW	Abcam HEK293T SGTA KO	Transformed cell line	Female

Clinical trials (associated diseases)

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