PTTG2

Summary

PTTG2 (pituitary tumor-transforming 2, HGNC:9691) is a protein-coding gene on chromosome 4p14, encoding Securin-2 (Q9NZH5).

Predicted to enable SH3 domain binding activity. Predicted to be involved in homologous chromosome segregation. Predicted to be located in cytoplasm. Predicted to be active in nucleus.

Source: NCBI Gene 10744 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 40 total
• MANE Select transcript: NM_006607

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9691
Approved symbol	PTTG2
Name	pituitary tumor-transforming 2
Location	4p14
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000250254
Ensembl biotype	protein_coding
OMIM	604231
Entrez	10744

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000504686

RefSeq mRNA: 1 — MANE Select: NM_006607 NM_006607

CCDS: CCDS54755

Canonical transcript exons

ENST00000504686 — 1 exons

Exon	Start	End
ENSE00002019979	37960398	37961128

Expression profiles

Bgee: expression breadth ubiquitous, 149 present calls, max score 85.04.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.4351 / max 44.3196, expressed in 1039 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
47311	3.4351	1039

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.04	gold quality
oocyte	CL:0000023	82.50	gold quality
granulocyte	CL:0000094	70.75	gold quality
tibial artery	UBERON:0007610	64.78	gold quality
popliteal artery	UBERON:0002250	64.76	gold quality
monocyte	CL:0000576	64.58	gold quality
leukocyte	CL:0000738	64.52	gold quality
mononuclear cell	CL:0000842	64.35	gold quality
aorta	UBERON:0000947	63.00	gold quality
muscle layer of sigmoid colon	UBERON:0035805	62.85	gold quality
type B pancreatic cell	CL:0000169	61.83	gold quality
hindlimb stylopod muscle	UBERON:0004252	61.34	gold quality
ascending aorta	UBERON:0001496	61.09	gold quality
thoracic aorta	UBERON:0001515	60.96	gold quality
endometrium epithelium	UBERON:0004811	60.52	gold quality
descending thoracic aorta	UBERON:0002345	59.16	gold quality
gastrocnemius	UBERON:0001388	58.86	gold quality
sigmoid colon	UBERON:0001159	58.69	gold quality
lower esophagus muscularis layer	UBERON:0035833	58.50	gold quality
lower esophagus	UBERON:0013473	58.46	gold quality
left coronary artery	UBERON:0001626	58.34	gold quality
mucosa of stomach	UBERON:0001199	58.30	gold quality
heart left ventricle	UBERON:0002084	58.15	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	57.90	gold quality
blood	UBERON:0000178	57.60	gold quality
cardiac ventricle	UBERON:0002082	57.55	gold quality
apex of heart	UBERON:0002098	57.44	gold quality
secondary oocyte	CL:0000655	57.30	gold quality
muscle of leg	UBERON:0001383	56.58	gold quality
decidua	UBERON:0002450	56.55	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.89

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 2)

• Knockdown of PTTG2 results in concomitant downregulation of E-cadherin and elevated vimentin levels, consistent with epithelial-to-mesenchymal transition. (PMID:23470537)
• PTTG2 induces psoriasis by regulating epidermal expression of vimentin and E-cadherin. (PMID:26617803)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	pttg1	ENSDARG00000075421
mus_musculus	Pttg1	ENSMUSG00000020415
rattus_norvegicus	Pttg1	ENSRNOG00000003802

Paralogs (1): PTTG1 (ENSG00000164611)

Protein

Protein identifiers

Securin-2 — Q9NZH5 (reviewed: Q9NZH5)

Alternative names: Pituitary tumor-transforming gene 2 protein

All UniProt accessions (1): Q9NZH5

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Expressed at low levels in the pituitary, liver, spleen, prostate, testis, ovary, small intestine and colon. Also expressed in various pituitary, testicular, liver and ovarian tumors.

Domain organisation. The N-terminal destruction box (D-box) acts as a recognition signal for degradation via the ubiquitin-proteasome pathway.

Similarity. Belongs to the securin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NZH5-1	1	yes
Q9NZH5-2	2

RefSeq proteins (1): NP_006598* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006940	Securin_separation_inhibitor	Family

Pfam: PF04856

UniProt features (6 total): short sequence motif 2, chain 1, region of interest 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NZH5-F1	62.32	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 63 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, GOBP_MEIOTIC_CHROMOSOME_SEGREGATION, RNGTGGGC_UNKNOWN, GOBP_CHROMOSOME_ORGANIZATION, PUJANA_CHEK2_PCC_NETWORK, GOBP_ORGANELLE_FISSION, RYTTCCTG_ETS2_B, GOBP_HOMOLOGOUS_CHROMOSOME_SEGREGATION, GOBP_MEIOTIC_CELL_CYCLE_PROCESS, GOBP_NUCLEAR_CHROMOSOME_SEGREGATION, KEGG_OOCYTE_MEIOSIS, GOBP_MEIOTIC_CELL_CYCLE, NUYTTEN_EZH2_TARGETS_DN, GOBP_CELL_CYCLE_PROCESS, GOMF_PEPTIDASE_REGULATOR_ACTIVITY

GO Biological Process (2): homologous chromosome segregation (GO:0045143), chromosome organization (GO:0051276)

GO Molecular Function (2): SH3 domain binding (GO:0017124), protein binding (GO:0005515)

GO Cellular Component (2): nucleus (GO:0005634), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
meiosis I	1
meiotic chromosome segregation	1
organelle organization	1
protein domain specific binding	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1080 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PTTG2	ESPL1	Q14674	999
PTTG2	CDC20	Q12834	970
PTTG2	BUB1B	O60566	895
PTTG2	CCNB1	P14635	859
PTTG2	CDK1	P06493	859
PTTG2	BUB3	O43684	826
PTTG2	CCNL2	Q96S94	750
PTTG2	CDC14A	Q9UNH5	740
PTTG2	BUB1	O43683	736
PTTG2	SGO1	Q5FBB7	728
PTTG2	PLK1	P53350	693
PTTG2	WEE1	P30291	687
PTTG2	CDC27	P30260	684
PTTG2	INCENP	Q9NQS7	682
PTTG2	RAE1	P78406	677

IntAct

121 interactions, top by confidence:

A	B	Type	Score
PTTG2	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
PTTG2	NHERF4	psi-mi:“MI:0407”(direct interaction)	0.440
PTTG2	GRIP2	psi-mi:“MI:0407”(direct interaction)	0.440
PATJ	PTTG2	psi-mi:“MI:0407”(direct interaction)	0.440
PTTG2	TJP1	psi-mi:“MI:0407”(direct interaction)	0.440
PTTG2	SCRIB	psi-mi:“MI:0407”(direct interaction)	0.440
PARD3	PTTG2	psi-mi:“MI:0407”(direct interaction)	0.440
PTTG2	MPP7	psi-mi:“MI:0407”(direct interaction)	0.440
PTTG2	PTPN3	psi-mi:“MI:0407”(direct interaction)	0.440
PTTG2	PDZD2	psi-mi:“MI:0407”(direct interaction)	0.440
PTTG2	TAX1BP3	psi-mi:“MI:0407”(direct interaction)	0.440
PTTG2	DLG3	psi-mi:“MI:0407”(direct interaction)	0.440
PTTG2	MAST1	psi-mi:“MI:0407”(direct interaction)	0.440
PTTG2	GIPC2	psi-mi:“MI:0407”(direct interaction)	0.440
PTTG2	ARHGAP21	psi-mi:“MI:0407”(direct interaction)	0.440
PTTG2	LIN7C	psi-mi:“MI:0407”(direct interaction)	0.440
PTTG2	HTRA4	psi-mi:“MI:0407”(direct interaction)	0.440
PTTG2	APBA3	psi-mi:“MI:0407”(direct interaction)	0.440
PTTG2	PDZRN4	psi-mi:“MI:0407”(direct interaction)	0.440
PTTG2	DLG4	psi-mi:“MI:0407”(direct interaction)	0.440
PTTG2	PDZD7	psi-mi:“MI:0407”(direct interaction)	0.440
PTTG2	PATJ	psi-mi:“MI:0407”(direct interaction)	0.440
PTTG2	GOPC	psi-mi:“MI:0407”(direct interaction)	0.440
PTTG2	MAGI2	psi-mi:“MI:0407”(direct interaction)	0.440
PTTG2	SNTB1	psi-mi:“MI:0407”(direct interaction)	0.440
PTTG2	WHRN	psi-mi:“MI:0407”(direct interaction)	0.440
PTTG2	MPP2	psi-mi:“MI:0407”(direct interaction)	0.440
PTTG2	MAGI3	psi-mi:“MI:0407”(direct interaction)	0.440
PTTG2	APBA2	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (15): PTTG2 (Reconstituted Complex), PTTG2 (Two-hybrid), PTTG2 (Two-hybrid), PTTG2 (Two-hybrid), PTTG2 (Two-hybrid), PTTG2 (Two-hybrid), PTTG2 (Two-hybrid), PTTG2 (Two-hybrid), PTTG2 (Two-hybrid), PTTG2 (Two-hybrid), PTTG2 (Two-hybrid), PTTG2 (Two-hybrid), PTTG2 (Reconstituted Complex), PTTG2 (Affinity Capture-RNA), APP (Reconstituted Complex)

ESM2 similar proteins: A1YF19, A2T767, B0K035, F1RCE7, F7BHS0, O95997, P0DPK0, P23999, P97613, Q08B36, Q08BD8, Q09HN1, Q0VA20, Q14140, Q2KHM9, Q2QD14, Q2QD15, Q2T9X8, Q2WG80, Q3SZY3, Q3UHI0, Q3V1H1, Q5R7F8, Q5RBY6, Q5RKG1, Q5XG16, Q5ZJU5, Q6A000, Q6AYH4, Q6DF94, Q7SXC6, Q8BHE0, Q8BHZ5, Q8C804, Q8N0Z3, Q8QGU6, Q8R080, Q8WWK9, Q96C57, Q96FF9

Diamond homologs: A1YF19, A2T767, O95997, P97613, Q2QD14, Q2QD15, Q3SZY3, Q9BDP6, Q9CQJ7, Q9NZH4, Q9NZH5

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CDK1	“up-regulates activity”	PTTG2	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 76 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Ras activation upon Ca2+ influx through NMDA receptor	5	58.3×	8e-07
Unblocking of NMDA receptors, glutamate binding and activation	5	55.5×	8e-07
Negative regulation of NMDA receptor-mediated neuronal transmission	5	55.5×	8e-07
Long-term potentiation	5	48.5×	1e-06
Assembly and cell surface presentation of NMDA receptors	9	46.6×	2e-11
Neurexins and neuroligins	10	40.2×	7e-12
Protein-protein interactions at synapses	6	32.5×	8e-07
RHOB GTPase cycle	5	15.8×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	11	87.6×	7e-17
protein localization to synapse	6	63.0×	5e-08
receptor clustering	7	59.9×	4e-09
regulation of postsynaptic membrane neurotransmitter receptor levels	7	47.5×	2e-08
cell-cell adhesion	10	13.9×	2e-07
protein-containing complex assembly	8	12.5×	1e-05
protein localization to plasma membrane	5	7.5×	9e-03
chemical synaptic transmission	7	7.4×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

129 predictions. Top by Δscore:

Variant	Effect	Δscore
4:37960653:G:GG	donor_gain	0.9400
4:37960648:GAAAA:G	donor_gain	0.9100
4:37960711:A:G	donor_gain	0.8700
4:37960657:G:GG	donor_gain	0.8600
4:37960656:A:AG	donor_gain	0.8200
4:37960498:G:GT	donor_gain	0.8000
4:37961003:G:GT	donor_gain	0.7800
4:37960621:GCTT:G	donor_gain	0.7600
4:37960740:T:G	donor_gain	0.7400
4:37960727:T:G	donor_gain	0.6900
4:37960719:G:GT	donor_gain	0.6600
4:37960541:A:G	donor_gain	0.6300
4:37960891:G:GT	donor_gain	0.6200
4:37960610:C:G	donor_gain	0.6000
4:37960757:A:G	donor_gain	0.5900
4:37960915:C:G	donor_gain	0.5900
4:37960565:G:GT	donor_gain	0.5800
4:37960643:C:G	donor_gain	0.5800
4:37960651:AAGTC:A	donor_loss	0.5500
4:37960652:AGT:A	donor_loss	0.5500
4:37960653:G:A	donor_loss	0.5500
4:37960654:T:G	donor_loss	0.5500
4:37960655:CAGT:C	donor_loss	0.5500
4:37960656:A:AT	donor_loss	0.5500
4:37960657:G:T	donor_loss	0.5500
4:37960722:GACT:G	donor_gain	0.5400
4:37960658:T:G	donor_loss	0.5200
4:37960690:C:G	donor_gain	0.5200
4:37960463:A:T	donor_gain	0.4900
4:37960771:G:GT	donor_gain	0.4800

AlphaMissense

1231 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000331421 (4:37961581 C>A), RS1000335488 (4:37961241 A>C,G), RS1000443497 (4:37960981 T>C), RS1000831916 (4:37959269 C>T), RS1001444729 (4:37959557 A>C,G), RS1001655471 (4:37960419 G>A), RS1002561897 (4:37959072 G>T), RS1006240557 (4:37959936 C>G), RS1006741021 (4:37959438 G>T), RS1007428214 (4:37960667 A>G), RS1008479979 (4:37958929 G>A), RS1010030682 (4:37959533 C>A,T), RS1012550008 (4:37958720 G>C,T), RS1013006316 (4:37961296 G>A), RS1014057606 (4:37959600 C>A)

Disease associations

OMIM: gene MIM:604231 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001588_16	Periodontal microbiota	4.000000e-06
GCST007060_7	Response to SSRI (symptom remission)	2.000000e-06
GCST007061_7	Response to antidepressants (symptom remission)	3.000000e-06
GCST009391_1246	Metabolite levels	3.000000e-07

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005658	response to selective serotonin reuptake inhibitor
EFO:0010423	triacylglycerol 54:5 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
propionaldehyde	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	increases expression	1
beta-methylcholine	affects expression	1
CGP 52608	affects binding, increases reaction	1
Air Pollutants	affects expression, increases abundance	1
Arsenic	affects methylation	1
Benzo(a)pyrene	increases methylation	1
Caffeine	decreases phosphorylation	1
Calcitriol	affects cotreatment, decreases expression	1
Ozone	affects expression, increases abundance	1
Testosterone	decreases expression, affects cotreatment	1
Aflatoxin B1	increases methylation	1
Copper Sulfate	decreases expression	1
Particulate Matter	decreases expression	1

Clinical trials (associated diseases)

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