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FLASH GENE

Symbol

S100A6

contributors: mct/npt - updated : 24-12-2012

HGNC name	S100 calcium binding protein A6
HGNC id	10496

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
SPECIAL FEATURE	component of a cluster
STRUCTURE	1.64 kb     3 Exon(s)    1 Copie(s)

Genomic sequence alignment details
10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter (TATA box)
	cytosine-phosphate-guanine/HTF
	Binding site   transcription factor
text structure	a basic promoter, including a TATA homology, GC boxes, and an enhancer-like sequence, essential for transcription spanning 167 bp upstream of transcription initiation, in cardiac myocytes, cardiac derived fibroblasts, and aortic smooth muscle cells
	an NF-kB-binding site at position -460/-451 points to the potential role of inflammatory processes in activation of the gene
	transcriptional regulation of the promoter is complex and involves common and cell-specific positive and negative upstream regulatory elements

MAPPING

cloned

Y

linked

N

status

confirmed

Map

see EDC@

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_014624 3 - 683 NP_055439 10.5 90 - 2007 18753141

EXPRESSION

Type	ubiquitous

expressed in

(based on citations)

organ(s)

System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart       lowly Digestive intestine large intestine colon   lowly   stomach       lowly Endocrine pancreas       lowly Lymphoid/Immune lymph node       lowly Nervous brain       lowly Reproductive female system ovary     lowly Respiratory lung       lowly Urinary kidney       lowly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective dense tendon     Muscular smooth     lowly

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	two calcium binding domains with an EF-hand motif
	one S100 specific N-terminus
	one classical C-terminus
	ICaBP type calcium binding domain

HOMOLOGY

Homologene

FAMILY

S100 family of EF-hand, calcium-binding proteins

CATEGORY

signaling cytokine , receptor

SUBCELLULAR LOCALIZATION	extracellular
	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,nuclear envelope,ext
text	in primary human endothelial cells, S100A6 was present in both the nucleus and the cytoplasm

basic FUNCTION	may be playing a role in stimulation of Ca2+-dependent insulin release,stimulation of prolactin secretion and exocytosis
	growth-regulated gene inducible by growth factors, having a functional role in tumor necrosis factor-alpha-induced myocyte apoptosis
	linked with cell cycle progression, cytoskeleton rearrangement, exocytosis, and cell survival
	may be involved in cell proliferation, cytoskeletal dynamics and tumorigenesis
	regulates a spectrum of growth and differentiation properties in cardiac muscle, in keeping with its role in cell cycle progression in proliferating cell lineages
	involvement of this protein in intra- and extra-cellular signalling pathways in the umbilical cord
	small EF-hand calcium- and zinc-binding protein involved in the regulation of cell proliferation and cytoskeletal dynamics
	has an important role in regulating endothelial commitment to, and progression through, the cell cycle

CELLULAR PROCESS	cell cycle

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

component of the pro-survival pathway activated by TNF- alpha and provides a homeostatic mechanism to limit TNF-alpha-induced myocyte apoptosis by interfering with TP53 phosphorylation

a component

constituent of epidermal differentiation complex

INTERACTION

DNA

RNA

small molecule	metal binding,
	Ca2+

protein	increase in intracellular concentration of Ca(2+), transduced by S100A6, is necessary for nuclear translocation of the SUGT1 protein
	with S100A2, S100A4 and S100A1, interacting with MDM2, making the binding to MDM2 a general feature of S100 proteins
	S100A6-SUGT1 dephosphorylation promotes its nuclear translocation, most likely due to disruption of the SUGT1-HSP90AA1 complex
	S100A1, S100A2, S100A6, and S100B proteins specifically interact with PPP5C-tetratricopeptide repeat (TPR) domain

cell & other

REGULATION

activated by

TNFalpha- signaling via NF-kB

induced by

tumor necrosis factor-alpha via an NF-kB-dependent mechanism, serving a role in homeostasis to limit tumor necrosis factor-alpha-induced apoptosis by regulating TP53 phosphorylation

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in primary colorectal adenocarcinomas with liver metastases tumoral     --over   in osteosarcoma cells loss of its expression correlates with a metastatic phenotype constitutional     --over   overexpressed in neurodegenerative disorders and a proposed marker for Amyotrophic Lateral Sclerosis (ALS) constitutional       gain of function upregulation of astrocytic S100A6 in response to extracellular glutamate may be involved in neuronal damage under pathophysiological conditions

Susceptibility

Variant & Polymorphism

Candidate gene
Marker	proposed marker for Amyotrophic Lateral Sclerosis (ALS)
Therapy target
	System Type Disorder Pubmed cancer digestive liver with SPP1, may be promising diagnostic markers and therapeutic targets for hepatocellular carcinoma

ANIMAL & CELL MODELS