SPINK7 (serine peptidase inhibitor, Kazal type 7 (putative))

2007-04-01 Xiying Yu , Shih-Hsin Lu Affiliation

Department of Etiology, Carcinogenesis, Cancer Institute Peking Union, Medical College, Chinese Academy of Medical Sciences Beijing 100021

Identity

HGNC

SPINK7

LOCATION

5q32

LOCUSID

84651

ALIAS

ECG2,ECRG2

DNA/RNA

Diagram of ECRG2 gene. Exons are represented by red boxes. Exons 1 to 4 from 5 to 3 direction.

Description

The ECRG2 gene contains 4 exons and spans about 3540 bp.

Transcription

The full-length of cDNA of ECRG2 gene was revealed 569 bp, the open reading frame (ORF) is 258 bp. The sequence upstream of the exon-1 upon the NT_2023158.1 genomic sequence revealed a typical TATA box contained promotor at 44 bp from the predicted translation start site. The transcription start site is just 6 bp upstream of the 5 end sequence.

Pseudogene

None

Proteins

Note

The N-terminal 1-19 is the single peptide of the protein. The C-terminal 30-85 of the protein contains a typical x(8)-C-x(6)-C-x(7)-C-x(6)-Y-x(3)-C-x(2,3)-C-x(17)-C conserve region, coding a Kazal type serine protease inhibitors (Kazal) domain.

Description

The molecular weight of the encoding protein contained 85 amino acids is about 9.23 kDa. ECRG2 gene contains a typical Kazal serine protease inhibitors conserved domain about 56 amino acids at its C-terminal and three kinase phosphorlation site (protein kinase C, Casein kinase II and Tyrosine kinase).

Expression

ECRG2 gene was expressed in normal tissues, such as esophagus, liver, colon and lung. But it was less expressed in the cancerous tissues, especially low frequency of expression of ECRG2 gene in esophageal cancer but was less expressed in the cancerous tissues, especially low frequency of expression of ECRG2 gene in esophageal cancer.

Localisation

The protein was localized on the cell membrane.

Function

The expression of ECRG2 can inhibit the migratory ability of high metastasic tumor cells.

Homology

The sequence of the ECRG2 gene did not reveal remarkable similarity to the known sequence in the homology analysis with the public database of GenBank while the deduced amino acid sequence showed 97% homology to a tumor associated KAZAL-type serine protease inhibitor peptide (US patent 5851987).

Mutations

Note

None

Implicated in

Entity name

Esophageal cancer

Note

Expression profile of ECRG2 gene in 7 normal esophageal epithelia, 51 esophageal cancer and 33 tumor adjacent tissues were 100%, 21% and 52% respectively. About 79% of ECRG2 gene was no expressed in the esophageal cancer. ECRG2 was highly expressed in the adult normal esophageal tissue, low expressed in the fetal esophageal tissue and completely loss of expression in the esophageal cancer and corresponding adjacent tissues. The results show that the ECRG2 gene may be a specific gene for carcinogenesis of esophagus.
The studies provide more evidences on the role of ECRG2 in the inhibition of tumor cell proliferation, migration and metastasis, and give a straightforward way to block enzymatic activity in extra-cellular matrix to achieve the therapeutic benefit in the tested human cancers.
1. Short tandem repeat polymorphism in a novel esophageal cancer-related gene (ECRG2) implicates susceptibility to esophageal cancer
2. Potential interaction partner for ECRG2 might be involved in regulation of cell proliferation and apoptosis and in various physiological processes.
3. Data suggest that the physical interaction of esophageal cancer related gene 2 (ECRG2) and metallothionein2A (MT2A) may play an important role in the carcinogenesis of esophageal cancer.

Bibliography

Pubmed ID	Last Year	Title	Authors
12646258	2003	ECRG2, a novel candidate of tumor suppressor gene in the esophageal carcinoma, interacts directly with metallothionein 2A and links to apoptosis.	Cui Y et al
12970870	2003	Using yeast two-hybrid system to identify ECRG2 associated proteins and their possible interactions with ECRG2 gene.	Cui YP et al
15857172	2005	Monoclonal antibodies to esophageal cancer-related gene2 protein.	Huang G et al
17352218	2007	Short tandem repeat polymorphisms of exon 4 in Kazal-type gene ECRG2 in pancreatic carcinoma and chronic pancreatitis.	Kaifi JT et al
16324322	2005	[Inhibitory effects of esophageal cancer related gene 2 on proliferation of human esophageal cancer cell EC9706].	Li MN et al
10920976	1998	[Cloning and identification of cDNA fragments related to human esophageal cancer].	Su T et al
14639608	2004	Short tandem repeat polymorphism in a novel esophageal cancer-related gene (ECRG2) implicates susceptibility to esophageal cancer in Chinese population.	Yue CM et al

Other Information

Locus ID:

NCBI: 84651
MIM: 617288
HGNC: 24643
Ensembl: ENSG00000145879

Variants:

dbSNP: 84651
ClinVar: 84651
TCGA: ENSG00000145879
COSMIC: SPINK7

RNA/Proteins

Gene ID	Transcript ID	Uniprot
ENSG00000145879	ENST00000274565	P58062
ENSG00000145879	ENST00000523535	E5RFX6

Expression (GTEx)

100

150

200

250

300

350

400

450

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Protein levels (Protein atlas)

Not detected

Low

Medium

High

References

Pubmed ID	Year	Title	Citations
22315007	2013	MicroRNA-1322 regulates ECRG2 allele specifically and acts as a potential biomarker in patients with esophageal squamous cell carcinoma.	15
26434587	2016	Negative regulation of RNA-binding protein HuR by tumor-suppressor ECRG2.	12
29875205	2018	The antiprotease SPINK7 serves as an inhibitory checkpoint for esophageal epithelial inflammatory responses.	12
12646258	2003	ECRG2, a novel candidate of tumor suppressor gene in the esophageal carcinoma, interacts directly with metallothionein 2A and links to apoptosis.	9
18162463	2008	ECRG2 disruption leads to centrosome amplification and spindle checkpoint defects contributing chromosome instability.	9
17602171	2007	ECRG2 inhibits cancer cell migration, invasion and metastasis through the down-regulation of uPA/plasmin activity.	8
19796867	2010	ECRG2 regulates ECM degradation and uPAR/FPRL1 pathway contributing cell invasion/migration.	7
19717562	2009	ECRG2 regulates cell migration/invasion through urokinase-type plasmin activator receptor (uPAR)/beta1 integrin pathway.	5
21042721	2010	Molecular cloning and characterization of a novel esophageal cancer related gene.	5
28348485	2017	ECRG2 enhances the anti-cancer effects of cisplatin in cisplatin-resistant esophageal cancer cells via upregulation of p53 and downregulation of PCNA.	5

Citation

Xiying Yu ; Shih-Hsin Lu

SPINK7 (serine peptidase inhibitor, Kazal type 7 (putative))

Atlas Genet Cytogenet Oncol Haematol. 2007-04-01

Online version: http://atlasgeneticsoncology.org/gene/40396/spink7