S100A13 (S100 calcium binding protein A13)

2008-02-01   Carlo Barone , Cinzia Bagalà , Matteo Landriscina 

Catholic University of Sacred Heart, Institute of Internal Medicine, Oncology Unit, Largo A. Gemelli 8, 00168 Roma, Itlaly

Identity

HGNC
LOCATION
1q21.3
LOCUSID
ALIAS
-
FUSION GENES

DNA/RNA

Description

The gene contains five exons and four introns; it is composed of a variable 5 untranslated region, a 296 bp coding sequence, a 3 untranslated region and a polyA tail.

Transcription

The gene has 5 alternatively spliced variants encoding the same protein; the variant 1 represents the longest transcript (951 bp), all the other variants have distinct and shorter 5UTR as compared to variant 1.

Proteins

Atlas Image
Schematic representation of the domains structure of S100A13 monomer.

Description

Small homodimeric protein (98 amino-acids, M.W. 11,47 kDa), with 2 Ca2+-binding EF-hands motifs and a positively charged C-terminal region mediating the interaction with specific target molecules.

Expression

Highly expressed in skeletal muscle, heart, kidney, pancreas, ovary, spleen and small intestine, follicle cells of thyroid; moderate expression in prostate, testis, colon and brain; little expression in thymus, lung, liver and placenta, non detectable expression in leukocytes.

Localisation

Cytosolic

Function

It may function in exocytosis, since it is one of the targets of some antiallergic drugs, such as amlexanox and cromolyn, which inhibit degranulation of mast cells; marker of active angiogenesis in some tumours and endometriosis; released with signal peptide-less proteins such as FGF1 and IL-1alpha upon intracellular stress conditions.

Homology

68% homology with human S100A14 and 50.5% with human S100A5; 86,7% with mouse S100A13.

Implicated in

Entity name
Astrocytic gliomas
Disease
Astrocytic gliomas are the most common primary brain tumours; they include WHO grade IV tumours, such as glioblastomas with its variants and WHO grade III tumours (anaplastic forms of astrocytoma, oligodendroglioma and oligoastrocytoma).
Prognosis
Poor for glioblastoma, relatively better for who grade III tumours.
Cytogenetics
Anaplastic astrocytomas carry gain of chromosome 7 or 7q and deletions on chromosomes 6, 9p, 11p, 19q and 22q. Glioblastomas demonstrate deletions of chromosome 10 and allelic losses on 19q and 13q.
Oncogenesis
Homozigous deletion of CDKN2A, CDKN2B and p14ARF(9p) (9p), negative regulators of cell cycle or amplification of the cyclin-dependent kinase CDK4 are frequent in astrocytoma gr. III and glioblastoma. Glioblastoma and a subset of anaplastic astrocytoma with no abnormality of CDK4 and CDKN2A carries mutation in the retinoblastoma gene (Rb1); p53-pathway is frequently altered and PTEN is mutated in 30-40% of glioblastoma and in astrocytoma with poor prognosis. Astrocytic gliomas generally stain positive for S-100 proteins; S100-A13 is up-regulated in high-grade gliomas and correlated with microvessel density and tumour grading.
Entity name
Endometriosis
Disease
Endometriosis is characterized by the presence and proliferation of functional endometrial glands and stroma outside the uterine cavity. It is a multifactorial genetic disorders. Increasing evidence points to the role of angiogenesis in the disease pathogenesis and many angiogenic factors and cytokines such as VEGF-A, FGF1, endoglin and interleukin-1 alpha are up-regulated in endometriotic lesions. S100A13 is over-expressed in endometriotic specimens, particularly in microvascular endothelia.
Prognosis
It is a chronic and recurrent disease associated with infertility.
Entity name
Lung cancer
Disease
Lung cancer is the most preventable of all the major forms of cancer since at least 75% of all cases worldwide are due to tobacco smoking. It can be classified into two main groups: small cell lung cancer and non-small cell lung cancer. The latter group is a heterogeneous aggregate of at least 3 distinct histologies including epidermoid or squamous carcinoma, adenocarcinoma and large cell carcinoma with the potential for cure with surgical resection when localized. Small cell lung carcinoma has a greater tendency to be disseminated by the time of diagnosis but is much more responsive to chemotherapy and radiation compared to non-small cell lung cancer.
Prognosis
Poor; small cell carcinoma has the most aggressive clinical course with median survival of only 2-4 months without treatment.
Cytogenetics
Loss of heterozigosity in chromosome regions 3p (fragile histidine triad, FHIT, locus), 12p, 13q (Rb1 locus) and 17p (p53 locus).
Oncogenesis
Inactivation of p16 by promoter hypermethylation is more frequent in squamous cell carcinoma compared with adenocarcinoma and is almost never found in small-cell lung cancer; K-ras mutations are documented only in non- small cell lung tumours particularly adenocarcinoma. Overexpression of myc family members and inactivation of p53, pRb and FHIT are found in all histologic types of lung cancer. S100P and S100A2 may be predictors of distant metastasis and poor survival in non-small cell lung tumours since they are overexpressed in tumours that metastatized during the course of the disease; S100A13 expression correlates with a more invasive phenotype in vitro.

Bibliography

Pubmed IDLast YearTitleAuthors
158217782005Endoglin (cd105) and S100A13 as markers of active angiogenesis in endometriosis.Hayrabedyan S et al
157461982005Interleukin 1alpha and tissue-lytic matrix metalloproteinase-1 are elevated in ectopic endometrium of patients with endometriosis.Hudelist G et al
109860542000Differential frequencies of p16(INK4a) promoter hypermethylation, p53 mutation, and K-ras mutation in exfoliative material mark the development of lung cancer in symptomatic chronic smokers.Kersting M et al
113093022001p16(INK4a) and histology-specific methylation of CpG islands by exposure to tobacco smoke in non-small cell lung cancer.Kim DH et al
167732192006S100A13, a new marker of angiogenesis in human astrocytic gliomas.Landriscina M et al
173743622007Crystal structure study on human S100A13 at 2.0 A resolution.Li M et al
127464882003S100A13 mediates the copper-dependent stress-induced release of IL-1alpha from both human U937 and murine NIH 3T3 cells.Mandinova A et al
180614372008Identification of a novel, functional role for S100A13 in invasive lung cancer cell lines.Pierce A et al
146253812003The non-classical export routes: FGF1 and IL-1alpha point the way.Prudovsky I et al
107227102000S100A13. Biochemical characterization and subcellular localization in different cell lines.Ridinger K et al
161127382005Bacterial infection and semen quality.Sanocka-Maciejewska D et al
100514261999Three distinct anti-allergic drugs, amlexanox, cromolyn and tranilast, bind to S100A12 and S100A13 of the S100 protein family.Shishibori T et al
88785581996Characterization of the human and mouse cDNAs coding for S100A13, a new member of the S100 protein family.Wicki R et al
114798912001Molecular genetics of small cell lung carcinoma.Wistuba II et al

Other Information

Locus ID:

NCBI: 6284
MIM: 601989
HGNC: 10490
Ensembl: ENSG00000189171

Variants:

dbSNP: 6284
ClinVar: 6284
TCGA: ENSG00000189171
COSMIC: S100A13

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000189171ENST00000339556Q99584
ENSG00000189171ENST00000392622Q99584
ENSG00000189171ENST00000392623Q99584
ENSG00000189171ENST00000440685Q99584

Expression (GTEx)

0
50
100
150
200
250

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
127464882003S100A13 mediates the copper-dependent stress-induced release of IL-1alpha from both human U937 and murine NIH 3T3 cells.25
150334942004S100 protein translocation in response to extracellular S100 is mediated by receptor for advanced glycation endproducts in human endothelial cells.23
202084802010S100A13 is a new angiogenic marker in human melanoma.16
167732192006S100A13, a new marker of angiogenesis in human astrocytic gliomas.14
247221842014Proteomics analysis of melanoma metastases: association between S100A13 expression and chemotherapy resistance.12
212701232011The IL1alpha-S100A13 heterotetrameric complex structure: a component in the non-classical pathway for interleukin 1alpha secretion.9
158217782005Endoglin (cd105) and S100A13 as markers of active angiogenesis in endometriosis.7
249820312014Interaction of S100A13 with C2 domain of receptor for advanced glycation end products (RAGE).7
126450082003Differential expression of S100 proteins in the developing human hippocampus and temporal cortex.5
173743622007Crystal structure study on human S100A13 at 2.0 A resolution.5

Citation

Carlo Barone ; Cinzia Bagalà ; Matteo Landriscina

S100A13 (S100 calcium binding protein A13)

Atlas Genet Cytogenet Oncol Haematol. 2008-02-01

Online version: http://atlasgeneticsoncology.org/gene/44197/s100a13