PTMA

Summary

PTMA (prothymosin alpha, HGNC:9623) is a protein-coding gene on chromosome 2q37.1, encoding Prothymosin alpha (P06454). Prothymosin alpha may mediate immune function by conferring resistance to certain opportunistic infections. It is a selective cancer dependency (DepMap: 54.9% of cell lines).

Enables DNA-binding transcription factor binding activity; calcium ion binding activity; and histone binding activity. Involved in negative regulation of apoptotic process. Located in cytosol and nucleoplasm.

Source: NCBI Gene 5757 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 21 total
• GTEx eGene: eQTL in 11 tissues, sQTL in 44 (q < 0.05)
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types (inferred from mutation patterns)
• Cancer dependency (DepMap): dependent in 54.9% of screened cell lines
• Constraint (gnomAD): pLI 0.93 (loss-of-function intolerant), LOEUF 0.55 (moderately constrained)
• MANE Select transcript: NM_002823
• Interaction hub: 1,828 STRING partners (top 9% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9623
Approved symbol	PTMA
Name	prothymosin alpha
Location	2q37.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000187514
Ensembl biotype	protein_coding
OMIM	188390
Entrez	5757

Gene structure

Transcript identifiers

Ensembl transcripts: 70 — 58 protein_coding, 8 nonsense_mediated_decay, 3 retained_intron, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000409115

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

ENST00000409115, ENST00000341369, ENST00000409321, ENST00000409683, ENST00000410064, ENST00000412128, ENST00000440384, ENST00000448874, ENST00000466801, ENST00000467816, ENST00000468027, ENST00000481928, ENST00000858026, ENST00000858027, ENST00000928473, ENST00000928474, ENST00000928475, ENST00000928476, ENST00000928477, ENST00000928478, ENST00000928479, ENST00000928480, ENST00000928481, ENST00000928482, ENST00000928483, ENST00000928484, ENST00000928485, ENST00000928486, ENST00000928487, ENST00000928488, ENST00000928489, ENST00000928490, ENST00000928491, ENST00000928492, ENST00000928493, ENST00000928494, ENST00000928495, ENST00000928496, ENST00000941372, ENST00000941373, ENST00000941374, ENST00000941375, ENST00001007257, ENST00001007258, ENST00001033664, ENST00001033665, ENST00001033667, ENST00001033668, ENST00001033669, ENST00001033671, ENST00001076449, ENST00001076451, ENST00001076459, ENST00001076465, ENST00001076471, ENST00001076474, ENST00001076480, ENST00001076481, ENST00001076482, ENST00001076483, ENST00001076484, ENST00001076491, ENST00001092493, ENST00001092494, ENST00001092495, ENST00001092496, ENST00001092497, ENST00001092498, ENST00001092499, ENST00001122241

RefSeq mRNA: 2 — MANE Select: NM_002823 NM_001099285, NM_002823

CCDS: CCDS42833, CCDS46541

Canonical transcript exons

ENST00000409115 — 5 exons

Exon	Start	End
ENSE00001873409	231708525	231708751
ENSE00001879102	231712804	231713551
ENSE00003475971	231711348	231711419
ENSE00003520861	231711890	231711983
ENSE00003550625	231712443	231712516

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 36.3152 / max 292.7918, expressed in 1815 samples.

Highest expression (Bgee): calcaneal tendon, monocyte, leukocyte, corpus callosum, ganglionic eminence.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PTMA is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 11 tissues and its splicing (sQTL) in 44 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 55 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Skin Sun Exposed Lower leg	sqtl	1.1e-59	+2.62	2:231695407:G:A
Adipose Visceral Omentum	sqtl	1.1e-52	-2.92	2:231695407:G:A
Artery Tibial	sqtl	3.1e-47	-2.35	2:231706513:G:C
Skin Not Sun Exposed Suprapubic	sqtl	9.0e-44	-2.53	2:231698214:C:A
Testis	sqtl	1.5e-36	+3.52	2:231689885:A:G
Cells Cultured fibroblasts	sqtl	8.0e-36	-2.01	2:231711859:G:A
Cells EBV-transformed lymphocytes	sqtl	4.1e-35	-2.44	2:231708644:C:T
Thyroid	sqtl	7.8e-31	-2.44	2:231706513:G:C
Adipose Subcutaneous	sqtl	2.3e-29	-2.12	2:231706513:G:C
Nerve Tibial	sqtl	3.1e-28	-2.29	2:231710893:C:T
Lung	sqtl	5.5e-27	-2.22	2:231706513:G:C
Esophagus Muscularis	sqtl	5.5e-26	-2.48	2:231706513:G:C
Esophagus Mucosa	sqtl	1.3e-25	-2.35	2:231706513:G:C
Colon Sigmoid	sqtl	2.3e-24	-2.54	2:231706513:G:C
Breast Mammary Tissue	sqtl	5.0e-23	-2.19	2:231706513:G:C
Colon Transverse	sqtl	1.4e-22	-2.33	2:231706513:G:C
Artery Aorta	sqtl	3.5e-18	-2.42	2:231706513:G:C
Stomach	sqtl	8.7e-17	-2.40	2:231706513:G:C
Esophagus Gastroesophageal Junction	sqtl	1.6e-16	-2.26	2:231706513:G:C
Muscle Skeletal	sqtl	1.6e-15	+1.55	2:231722036:C:A

FANTOM5 promoters

showing 10 of 11 alternative TSS:

Promoter ID	TPM avg	Samples expressed
25929	15.0057	1785
25930	13.9353	1780
25933	3.1071	817
25928	1.6353	1066
25924	0.8259	379
25926	0.7069	324
25931	0.6490	240
25925	0.1874	87
25932	0.1672	57
25927	0.0716	20

Top tissues by expression

showing 100 of 134 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	99.88	gold quality
monocyte	CL:0000576	99.87	gold quality
leukocyte	CL:0000738	99.86	gold quality
corpus callosum	UBERON:0002336	99.84	gold quality
ganglionic eminence	UBERON:0004023	99.83	gold quality
endometrium	UBERON:0001295	99.82	gold quality
popliteal artery	UBERON:0002250	99.81	gold quality
tibial artery	UBERON:0007610	99.81	gold quality
thyroid gland	UBERON:0002046	99.80	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.80	gold quality
endocervix	UBERON:0000458	99.79	gold quality
left lobe of thyroid gland	UBERON:0001120	99.79	gold quality
metanephros cortex	UBERON:0010533	99.79	gold quality
left uterine tube	UBERON:0001303	99.78	gold quality
skin of abdomen	UBERON:0001416	99.78	gold quality
ascending aorta	UBERON:0001496	99.78	gold quality
thoracic aorta	UBERON:0001515	99.78	gold quality
right lung	UBERON:0002167	99.78	gold quality
ventricular zone	UBERON:0003053	99.78	gold quality
colonic epithelium	UBERON:0000397	99.77	gold quality
vermiform appendix	UBERON:0001154	99.77	gold quality
right uterine tube	UBERON:0001302	99.77	gold quality
descending thoracic aorta	UBERON:0002345	99.77	gold quality
cortical plate	UBERON:0005343	99.77	gold quality
omental fat pad	UBERON:0010414	99.77	gold quality
uterine cervix	UBERON:0000002	99.76	gold quality
zone of skin	UBERON:0000014	99.76	gold quality
adipose tissue	UBERON:0001013	99.76	gold quality
right lobe of thyroid gland	UBERON:0001119	99.76	gold quality
tibial nerve	UBERON:0001323	99.76	gold quality
fallopian tube	UBERON:0003889	99.76	gold quality
body of uterus	UBERON:0009853	99.76	gold quality
ectocervix	UBERON:0012249	99.76	gold quality
left coronary artery	UBERON:0001626	99.75	gold quality
lung	UBERON:0002048	99.75	gold quality
subcutaneous adipose tissue	UBERON:0002190	99.75	gold quality
upper lobe of left lung	UBERON:0008952	99.75	gold quality
lymph node	UBERON:0000029	99.74	gold quality
rectum	UBERON:0001052	99.74	gold quality
transverse colon	UBERON:0001157	99.74	gold quality
skin of leg	UBERON:0001511	99.74	gold quality
right coronary artery	UBERON:0001625	99.74	gold quality
Ammon’s horn	UBERON:0001954	99.74	gold quality
substantia nigra	UBERON:0002038	99.74	gold quality
mucosa of transverse colon	UBERON:0004991	99.74	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.74	gold quality
granulocyte	CL:0000094	99.73	gold quality
intestine	UBERON:0000160	99.73	gold quality
colon	UBERON:0001155	99.73	gold quality
putamen	UBERON:0001874	99.73	gold quality
left ovary	UBERON:0002119	99.73	gold quality
thoracic mammary gland	UBERON:0005200	99.73	gold quality
ovary	UBERON:0000992	99.72	gold quality
myometrium	UBERON:0001296	99.72	gold quality
caudate nucleus	UBERON:0001873	99.72	gold quality
right ovary	UBERON:0002118	99.72	gold quality
small intestine Peyer’s patch	UBERON:0003454	99.72	gold quality
smooth muscle tissue	UBERON:0001135	99.71	gold quality
placenta	UBERON:0001987	99.71	gold quality
small intestine	UBERON:0002108	99.71	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.71	gold quality
vagina	UBERON:0000996	99.70	gold quality
body of stomach	UBERON:0001161	99.70	gold quality
kidney	UBERON:0002113	99.70	gold quality
cortex of kidney	UBERON:0001225	99.69	gold quality
urinary bladder	UBERON:0001255	99.69	gold quality
spleen	UBERON:0002106	99.69	gold quality
prostate gland	UBERON:0002367	99.69	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.69	gold quality
stomach	UBERON:0000945	99.68	gold quality
esophagus	UBERON:0001043	99.68	gold quality
temporal lobe	UBERON:0001871	99.68	gold quality
amygdala	UBERON:0001876	99.68	gold quality
hypothalamus	UBERON:0001898	99.68	gold quality
bone marrow	UBERON:0002371	99.68	gold quality
primary visual cortex	UBERON:0002436	99.68	gold quality
esophagus mucosa	UBERON:0002469	99.68	gold quality
adult mammalian kidney	UBERON:0000082	99.67	gold quality
lower esophagus	UBERON:0013473	99.67	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.67	gold quality
fundus of stomach	UBERON:0001160	99.66	gold quality
Brodmann (1909) area 9	UBERON:0013540	99.66	gold quality
gall bladder	UBERON:0002110	99.65	gold quality
body of pancreas	UBERON:0001150	99.64	gold quality
mucosa of stomach	UBERON:0001199	99.64	gold quality
minor salivary gland	UBERON:0001830	99.64	gold quality
saliva-secreting gland	UBERON:0001044	99.62	gold quality
tonsil	UBERON:0002372	99.62	gold quality
lower esophagus mucosa	UBERON:0035834	99.62	gold quality
stromal cell of endometrium	CL:0002255	99.61	gold quality
brain	UBERON:0000955	99.61	gold quality
nucleus accumbens	UBERON:0001882	99.61	gold quality
adenohypophysis	UBERON:0002196	99.61	gold quality
pancreas	UBERON:0001264	99.59	gold quality
duodenum	UBERON:0002114	99.59	gold quality
multicellular organism	UBERON:0000468	99.58	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	99.58	gold quality
bone marrow cell	CL:0002092	99.57	gold quality
pituitary gland	UBERON:0000007	99.57	gold quality
cerebral cortex	UBERON:0000956	99.57	gold quality

Single-cell (SCXA)

Detected in 53 experiment(s), a significant marker in 15.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	18802.26
E-HCAD-4	yes	18605.61
E-MTAB-10042	yes	11069.70
E-HCAD-31	yes	8422.62
E-CURD-88	yes	7917.69
E-CURD-122	yes	7888.03
E-MTAB-10553	yes	7246.89
E-HCAD-9	yes	6089.41
E-MTAB-9067	yes	4737.23
E-MTAB-9801	yes	4093.45
E-HCAD-25	yes	3475.61
E-HCAD-35	yes	2184.31
E-MTAB-5061	yes	1756.87
E-GEOD-134144	yes	52.19
E-GEOD-137537	yes	30.79

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 78 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Bone marrow	tissue	2190.5	medium
Thymus	tissue	1918.1
Tonsil	tissue	1426.1	medium
Lymph node	tissue	1304.2	medium
Corpus callosum	tissue	1086.3
Appendix	tissue	970.3	medium
Vagina	tissue	969.4	medium
Ovary	tissue	961.9	not detected
Colon	tissue	949.0	medium
Rectum	tissue	925.1	medium
Skin 1	tissue	876.3	medium
Endometrium 1	tissue	843.5	medium
Stomach 1	tissue	823.5	medium
Thyroid gland	tissue	786.9	medium
Spleen	tissue	786.4	medium
Urinary bladder	tissue	767.2	medium
Small intestine	tissue	748.8	high
Spinal cord	tissue	739.2
Cervix	tissue	734.0	high
Breast	tissue	722.1	medium
Adipose tissue	tissue	720.9	medium
Substantia nigra	tissue	693.7
Fallopian tube	tissue	677.7	high
Medulla oblongata	tissue	677.5
Esophagus	tissue	676.5	medium
Duodenum	tissue	661.4	high
Epididymis	tissue	659.3	medium
Superior colliculi	tissue	654.8
Smooth muscle	tissue	653.3	low
Midbrain	tissue	652.2
Placenta	tissue	646.5	medium
Putamen	tissue	627.7
Postcentral gyrus	tissue	621.2
Nucleus accumbens	tissue	611.5
Pons	tissue	597.4
Lung	tissue	590.1	medium
Periaqueductal gray	tissue	584.2
Pancreas	tissue	583.8	medium
Seminal vesicle	tissue	569.9	medium
Thalamus	tissue	559.1
Hippocampus	tissue	544.0	medium
Hypothalamus	tissue	538.3
Gallbladder	tissue	530.2	high
Locus coeruleus	tissue	522.2
Ventral pallidum	tissue	516.4
Septum	tissue	516.0
Liver	tissue	514.8	medium
Kidney	tissue	501.3	medium
Salivary gland	tissue	499.4	low
Hippocampal formation	tissue	480.1
Prostate	tissue	453.4	medium
Parathyroid gland	tissue	452.4	medium
Adrenal gland	tissue	425.5	high
Retina	tissue	405.1
Basal ganglia	tissue	391.7	medium
Pituitary gland	tissue	379.7
Olfactory bulb	tissue	378.5
Amygdala	tissue	360.5
Choroid plexus	tissue	356.9
Cerebral cortex	tissue	305.9	high

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Blood vessel (1538.2), Temporal white matter (1365.1), Area striata (white matter) (1181.3), Parieto-temporal junction (white matter) (1175.7), Globus pallidus, internus (1124.7).

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

4 targets:

Target	Regulation
CDKN1A	Unknown
IDO1	Activation
IDO2	Activation
TLR9	Repression

Upstream regulators (CollecTRI, top): ESR1, MAX, MYC, RBPJ, SP1, TP53

miRNA regulators (miRDB)

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

showing 30 of 46 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-545-3P	99.95	70.74	2783
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-548AV-5P	99.60	70.84	2107
HSA-MIR-548K	99.60	70.84	2107
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-891B	99.59	69.81	1083
HSA-MIR-5571-5P	99.49	66.99	1764
HSA-MIR-8054	99.48	70.81	2084
HSA-MIR-377-3P	99.37	70.18	1905
HSA-MIR-6128	99.33	67.83	1581
HSA-MIR-6878-3P	99.24	64.23	920
HSA-MIR-3940-5P	99.14	65.26	493

Functional genomics

gnomAD constraint: pLI 0.933, LOEUF 0.554, missense Z 0.23 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000409115 — one region, missense o/e 0.87. DepMap (CRISPR cell-line fitness): dependent in 54.9% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): OCI-AML2 (-1.57), AML-193 (-1.541), COLO 201 (-1.371), COLO-678 (-1.363), DB (-1.328), LP-1 (-1.28), SUP-M2 (-1.243), YAPC (-1.226), MHH-NB-11 (-1.214), OCI-My7 (-1.183), KE-97 (-1.166), U343 (-1.157), IMR-32 (-1.155), HCC-78 (-1.145), Raji (-1.141).

Literature-anchored findings (GeneRIF, showing 40)

• induces unravelling of metaphase chromosomes in vitro (PMID:11528108)
• we demonstrate the existence of three binding partners (31, 29, and 19 kDa) for ProTalpha in the membrane of PHA-activated lymphoblasts. These surface molecules possess the expected affinity and specificity for a ProTalpha receptor (PMID:11727831)
• prothymosin alpha is capable of forming regular elongated fibrils (PMID:12062405)
• regulatory roles of oncoprotein ProT and tumor suppressor PHAP in apoptosis (PMID:12522243)
• study suggests involvement of prothymosin a, in the formation, maintenance, or functioning of the mitotic spindle (PMID:15325071)
• PTMA associates with SET and is involved in chromatin decondensation. (PMID:15556635)
• Prothymosin alpha functions as intranuclear dissociator of the Nrf2-Keap1 complex. (PMID:15657435)
• PTMA expression is intimately involved in the differentiation and progression of human prostate cancers, and could be a target for therapy and diagnostic purposes. (PMID:16353248)
• Antiapoptotic response of cells requires expression of both p8 and ProTalpha. (PMID:16478804)
• the anti-apoptotic effect previously attributed separately to p8 and prothymosin alpha is in fact borne by the p8/ProTalpha complex, the two proteins being individually inactive (PMID:16628001)
• Marked differences in the expression of PTMA and Tim10 were observed during the differentiation of human primary skeletal muscle cells. (PMID:16669873)
• suppression of viral replication by ProTalpha is not HIV LTR specific (PMID:16940531)
• interaction of ProTalpha with core histones in the nucleus may be related to structural modification of histones H3 & H4, & hence to chromatin activity, raising the possibility that other proteins in the nuclear complex may play a role in this process. (PMID:17012289)
• Decreased ERbeta and increased ProTalpha expression in advanced gastric adenocarcinoma indicated that ERbeta may play an anti-proliferation role which is opposed to the role of ProTalpha in gastric epithelium. (PMID:17046193)
• although prothymosin-alpha is overexpressed in gastric adenocarcinoma, it is not associated with alterations in survival (PMID:17188166)
• PTMA may be a novel marker for predicting the effectiveness of radiotherapy in clinical cases. (PMID:17876542)
• Basis on site-specific information obtained here, as well as results from previous studies, we propose that the conformational and dynamic changes upon zinc binding may act as an entropic switch that greatly facilitates the binding to other proteins (PMID:17929838)
• ProTalpha and Nrf2 compete for interaction with Keap1, therefore ProTalpha is able to liberate Nrf2 from complex with Keap1 and hence contribute to Nrf2-dependent transcription. (PMID:18240569)
• Influence of prothymosin alpha and its mutants on activity of the p53 tumor suppressor (PMID:18856068)
• immune response stimulation by ProTalpha is in principle exerted via its bioactive C-terminal decapaptide, which can acquire a sequence-specific beta-sheet conformation and induce DC maturation. (PMID:18976813)
• Prothymosin alpha amino acid residues 4-14, 31-43, 84-87, and 106-110 strongly and specifically bind to apoptotic protease activating factor 1 (Apaf-1) in the regulation of the mitochondrial cell death pathway. (PMID:20121050)
• Data suggest that prothymosin alpha immunostaining may be helpful in predicting pituitary tumor recurrence. (PMID:20430720)
• A study on the relationship between prothymosin alpha kinase(ProTalphaK) activity and pyruvate kinase isoforms confirmed that the M2 isoform is the enzyme responsible for ProTalphaK activity in proliferating cells. (PMID:20977946)
• Nuclear PTMA may serve as prognostic marker in head and neck squamous cell carcinoma to determine the subset of patients that are likely to show recurrence of the disease. (PMID:21573209)
• These results are consistent with the model that ProTa may enhance p53 transcription activity by displacement of histone H1 from p53-H1 repressive complex. (PMID:21954601)
• The PTMA is one of miR-1 target genes which involve in miR-1 inducing apoptosis. (PMID:22059741)
• The prothymosin alpha is one of miR-1 target genes which involve in miR-1 inducing apoptosis (PMID:22059741)
• when added to cultured cells expressing mHtt, the purified recombinant ProTalpha protein not only entered the cells but it also significantly suppressed the mHtt-caused cytotoxicity. (PMID:22110140)
• Findings suggest that the binding of prothymosin alpha (ProTalpha) and Neh2 to Keap1 occurs synergistically via preformed structural elements. (PMID:22125611)
• The decrease of ProTalpha mRNA during differentiation was not accompanied by changes in the methylation status (PMID:22463375)
• Data suggest that plasma thymosin-alpha1 (TA1) and prothymosin-alpha (PTMA) level may be a biomarker for differentiating between renal cell carcinoma (RCC) and urothelial carcinoma. (PMID:22609059)
• ProTalpha is crucial for the interaction with the Kelch domain, while the flanking residues play relatively minor roles in the affinity of binding. (PMID:23318954)
• Western blot analysis of protein extracts from sperm head fractions confirms that the peptide is specifically associated with the inner acrosomal membrane fraction. (PMID:23359453)
• These results demonstrate the clinical relevance of prothymosin alpha in regulating acetylation events during the pathogenesis of emphysema. (PMID:23695700)
• PTalpha offers cardioprotection against ischemic injury by an Akt-dependent mechanism. (PMID:23857453)
• phosphorylation of ProTalpha is required for its antiapoptotic activity, but it does not affect its nuclear import (PMID:23859021)
• prothymosin-alpha expression is a determinant of disease progression in superficial bladder cancer (PMID:24733561)
• disease-free survival and overall survival rates were significantly lower among colorectal cancer patients with PTMA- and TP53-positive tumors (PMID:25197357)
• Data suggest that KEAP1 (kelch-like ECH-associated protein 1) mutations (as those observed in lung cancer patients) affect conformation/folding/stability of KEAP1 and binding affinity for ligands PTMA and NRF2 (nuclear factor erythroid 2-like 2). (PMID:25582950)
• PTMA is a potential novel therapeutic target for type 2 diabetes (PMID:26348351)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:ch211-222l21.1	ENSDARG00000076532
mus_musculus	Ptma	ENSMUSG00000026238
rattus_norvegicus		ENSRNOG00000072334

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:97803) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 31 distinct phenotype terms.

Mouse phenotype (MP)	Records
emphysema	2
postnatal lethality, complete penetrance	2
decreased body weight	1
persistence of hyaloid vascular system	1
cornea opacity	1
increased anxiety-related response	1
decreased locomotor activity	1
abnormal eating behavior	1
reduced long-term potentiation	1
postnatal growth retardation	1
abnormal learning/memory/conditioning	1
abnormal passive avoidance behavior	1
abnormal excitatory postsynaptic potential	1
increased liver weight	1
kidney cyst	1
increased kidney weight	1
renal fibrosis	1
kidney epithelium hyperplasia	1
decreased body temperature	1
increased blood urea nitrogen level	1
pulmonary fibrosis	1
slow postnatal weight gain	1
polycystic kidney	1
impaired cued conditioning behavior	1
decreased birth weight	1

+6 more (showing top 25).

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
Pongo abelii	Q5R790	98.2%	Diamond
Bos taurus	P01252	97.3%	Diamond
Xenopus laevis	Q5U274	95.5%	Diamond
Pelophylax lessonae	Q90ZK2	83.7%	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
MIR1471	ncRNA	100302126
MIR1244-1	ncRNA	100302285
PDE6D	protein-coding	5147
COPS7B	protein-coding	64708
TEX44	protein-coding	165100

Protein

Protein identifiers

Prothymosin alpha — P06454 (reviewed: P06454)

All UniProt accessions (8): B8ZZA1, B8ZZQ6, B8ZZW7, P06454, F8WCE8, H7C031, H7C2N1, Q53S24

UniProt curated annotations — full annotation on UniProt →

Function. Prothymosin alpha may mediate immune function by conferring resistance to certain opportunistic infections.

Subunit / interactions. Interacts with NUPR1; regulates apoptotic process.

Subcellular location. Nucleus.

Post-translational modifications. Covalently linked to a small RNA of about 20 nucleotides.

Similarity. Belongs to the pro/parathymosin family.

Isoforms (2)

UniProt ID	Names	Canonical?
P06454-1	1	yes
P06454-2	2

RefSeq proteins (2): NP_001092755, NP_002814* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004931	Pro/parathymosin	Family

Pfam: PF03247

UniProt features (25 total): modified residue 13, compositionally biased region 3, chain 2, helix 2, initiator methionine 1, cross-link 1, splice variant 1, peptide 1, region of interest 1

Structure

Experimental structures (PDB)

2 structures by resolution:

PDB	Title	Method	Resolution (Å)
2L9I	NMR structure of thymosin alpha-1	SOLUTION NMR
2MNQ	1H, 13C, and 15N Chemical Shift Assignments for Thymosin alpha 1	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P06454-F1	58.32	0.00

Human Protein Atlas

Protein class: Predicted intracellular proteins, Plasma proteins, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm; cytosol

Antibody reliability (HPA): IH approved · IF enhanced

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 (14)

Type	Positions
Phosphoserine	2, 9, 10
Phosphothreonine	8, 13, 14, 102, 107
N6-acetyllysine	15, 103
N6-succinyllysine	15
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo2)	103
N-acetylmethionine	1
N-acetylserine	2

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 313 (showing top): RNGTGGGC_UNKNOWN, E2F_Q4_01, YAGI_AML_WITH_INV_16_TRANSLOCATION, TGCGCANK_UNKNOWN, MODULE_151, GCM_NPM1, MORF_UBE2I, CAIRO_PML_TARGETS_BOUND_BY_MYC_UP, HSIAO_HOUSEKEEPING_GENES, USF_C, YY1_Q6, MODULE_503, SREBP1_02, PUJANA_CHEK2_PCC_NETWORK, CDP_01

GO Biological Process (4): chromatin organization (GO:0006325), DNA-templated transcription (GO:0006351), negative regulation of apoptotic process (GO:0043066), positive regulation of transcription by RNA polymerase II (GO:0045944)

GO Molecular Function (5): calcium ion binding (GO:0005509), histone binding (GO:0042393), DNA-binding transcription factor binding (GO:0140297), histone chaperone activity (GO:0140713), protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829)

GO top-level categories

19 GO namespaces:

Category	Terms
cellular anatomical structure	2
cellular component organization	1
gene expression	1
RNA biosynthetic process	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
metal ion binding	1
protein binding	1
transcription factor binding	1
histone binding	1
protein carrier activity	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 7 of 12 annotations. The rest are phylogenetic / computational / electronic (IEA).

7 experimentally-supported GO terms:

GO term	NS	Evidence
negative regulation of apoptotic process	BP	mutant phenotype
cytosol	CC	direct assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay
DNA-binding transcription factor binding	MF	physical interaction
calcium ion binding	MF	experiment
histone binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 1,828 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PTMA	F5GXR3	F5GXR3	973
PTMA	ANP32A	P39687	767
PTMA	H1-0	P07305	722
PTMA	SLC6A7	Q99884	717
PTMA	CASP9	P55211	608
PTMA	TMSB4X	P01253	578
PTMA	CASP3	P42574	567
PTMA	TMPO	P08918	533
PTMA	PPP2CA	P05323	510
PTMA	TAAR1	Q96RJ0	492
PTMA	SET	Q01105	470
PTMA	RPL6	Q02878	468
PTMA	DEK	P35659	427
PTMA	IFNA13	P01562	421
PTMA	HSBP1	O75506	420

IntAct

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

14 partners by confidence:

Partner	Interaction type	MIscore	Records
NUPR1	physical association	0.670	7
SET	physical association	0.510	3
TERF2IP	physical association	0.510	2
M	physical association	0.400	1
GSK3A	physical association	0.370	1
TERF1	physical association	0.370	1
TERF2	physical association	0.370	1
APTX	association	0.350	1
ARID3A	association	0.350	1
SRP14	association	0.350	1
TDRD3	association	0.350	1
MEF2A	proximity	0.270	1
JUN	physical association	0.000	1
PHB1	physical association	0.000	1

BioGRID (254 interactions; top human partners by supporting records): KEAP1 (Two-hybrid; 7 records), EP300 (Affinity Capture-Western; 4 records), ACTB (Affinity Capture-MS; 3 records), HNRNPA1 (Affinity Capture-MS; 3 records), SET (Co-fractionation; 3 records), ACTC1 (Affinity Capture-MS; 2 records), ANP32B (Affinity Capture-MS; 2 records), CCNF (Proximity Label-MS; 2 records), CREBBP (Affinity Capture-Western; 2 records), ELAVL1 (Affinity Capture-RNA; 2 records), HNRNPA2B1 (Affinity Capture-MS; 2 records), KRAS (Synthetic Lethality; 2 records), PDIA4 (Affinity Capture-MS; 2 records), PHB2 (Two-hybrid; 2 records), PSMA1 (Co-fractionation; 2 records)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
PTMA	down-regulates	CASP9	binding

Protein complexes (CORUM) (7)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

7 complexes by size:

Complex	Subunits	Members
★ ACTB-ANP32A-C1QBP-PSMA1-PTMA-PSMA1 complex	6	C1QBP, PSMA1, PTMA, SLC25A3, ACTB, ANP32A
★ ProTalpha C5 complex	5	ANP32A, C1QBP, PSMA1, PTMA, SLC25A3
ANP32A-ANP32B-PSMA3-PTMA-SLC25A5 complex	5	ANP32A, ANP32B, PSMA3, PTMA, SLC25A5
ProTalpha C2 complex	4	ACTB, MARCKSL1, PTMA, SET
ProTalpha C8 complex	4	PTMA, RAB11A, ANP32A, ANP32B
ProTalpha C7 complex	3	ANP32A, ANP32B, PTMA
ProTalpha C9 complex	2	SET, PTMA

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 1 cancer types — MGCT.

intOGen’s role is a computational inference from cohort mutation patterns and may diverge from the gene’s curated/literature role; read it alongside the evidence above.

Genetic variants

Variant evidence for PTMA: 21 ClinVar records (0 pathogenic / likely pathogenic); 8 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	12
Likely benign	0
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 24 predictions of 573):

Position(s)	Effect	Δscore	Sites
2:231711347	acceptor_loss	1.0000	2
2:231711421	donor_loss	1.0000
2:231711984–231711985	donor_loss	1.0000	5
2:231712442	acceptor_loss	1.0000
2:231712517	donor_loss	1.0000
2:231708752–231708753	donor_loss	0.9900	5
2:231711343	acceptor_gain	0.9900
2:231711346–231711347	acceptor_loss	0.9900	3
2:231711420–231711421	donor_loss	0.9900	4
2:231711880	acceptor_gain	0.9900

AlphaMissense

142 missense substitutions predicted likely pathogenic (of 743 scored), across 55 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
G37	6	0.874	0.936
K106	6	0.848	0.921
K104	6	0.793	0.921
K103	6	0.776	0.905
K89	6	0.769	0.867
D7	6	0.646	0.803
G30	5	0.819	0.871
G45	5	0.720	0.882
A92	4	0.760	0.860
N44	4	0.750	0.852
D111	4	0.723	0.791
S9	3	0.796	0.796
K18	3	0.785	0.857
K15	3	0.731	0.769
N29	3	0.716	0.758
G88	3	0.708	0.830
K21	3	0.701	0.737
R90	3	0.701	0.799
N36	3	0.699	0.745
K20	3	0.685	0.723

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

3 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	2.49e-05
Liver Hepatocellular Carcinoma (validation)	unfavorable	3.07e-05
Pancreatic Adenocarcinoma (TCGA)	unfavorable	0.000853

Disease associations

OMIM: gene MIM:188390 | disease phenotypes:

GWAS associations

8 associations:

Study	Trait	p-value
GCST90002388_418	Lymphocyte count	6e-19
GCST90002407_282	White blood cell count	2e-18
GCST004627_178	Lymphocyte count	6e-13
GCST90002394_493	Monocyte percentage of white cells	7e-12
GCST90002398_461	Neutrophil count	8e-12
GCST004610_129	White blood cell count	3e-9
GCST001959_1	Eating disorders (purging via substances)	7e-7
GCST000175_45	Height	1e-6

EFO canonical traits (from GWAS)

3 canonical traits:

EFO ID	Trait name
EFO:0004587	lymphocyte count
EFO:0007989	monocyte percentage of leukocytes
EFO:0004833	neutrophil count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066338 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (2 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, affects cotreatment, increases expression, affects expression	3
Particulate Matter	decreases expression, increases abundance, increases expression	3
bisphenol F	increases expression, affects cotreatment	2
sodium arsenite	decreases expression, increases expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Copper	affects binding, decreases expression	2
Cadmium Chloride	decreases expression, decreases methylation, increases expression	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	affects phosphorylation	1
testosterone enanthate	affects expression	1
uranyl acetate	affects expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
tetrabromobisphenol A	increases expression, increases response to substance	1
zinc chromate	decreases expression, increases abundance	1
nickel sulfate	decreases expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
CGP 52608	affects binding, increases reaction	1
chloropicrin	increases expression	1
K 7174	decreases expression	1
vandetanib	decreases 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	decreases expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
bisphenol S	affects cotreatment, decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652193	Binding	Binding affinity to human PTMA incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — *ChemMedChem*

Clinical trials (associated diseases)

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

Predicted chemistry — Sugi Predict

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