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FLASH GENE

Symbol

S100A4

contributors: mct/pgu - updated : 16-11-2016

HGNC name	S100 calcium binding protein A4
HGNC id	10494

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
SPECIAL FEATURE	arranged in tandem, component of a cluster
STRUCTURE	2.19 kb     3 Exon(s)

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

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

text	alternative splicing occurs within the 5'-untranslated region (UTR) of S100A4 pre-mRNA (PMID: 7607566)

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_002961 2 - 512 NP_002952 - 101 - 1995 7607566 NM_019554 3 splicing 564 NP_062427 - 101 - 1995 7607566

EXPRESSION

Type	ubiquitous

constitutive of

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       highly   vessel       highly Digestive intestine large intestine colon     Visual eye anterior segment cornea

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial absorptive excretory digestive epithelium (mucosa)

cells

System Cell Pubmed Species Stage Rna symbol Lymphoid/Immune T cell

cell lineage
cell lines	breast carcinoma cells, highly
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, with a shorter alternatively spliced variant expressed in infiltrating carcinoma of the breast (two C-terminal lysine residues are required for the enhanced metastasis, invasion and migration abilities)

mono polymer

polymer

HOMOLOGY

interspecies

homolog to murine placental

Homologene

FAMILY

Ca(2+) dependent S100 protein family

CATEGORY

regulatory

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm
	intracellular,nucleus

basic FUNCTION	possessing metastasis-inducing capabilities
	modulating intercellular adhesion
	playing a functional role in regulating endothelial cell growth and tumor metastasis
	playing extracellular roles such as neuritogenic and angiogenic activities
	controlling the invasive potential of prostate carcinoma cells through regulation of MMP9 and this association may contribute to metastasis of prostate carcinoma cells
	playing a role in neuronal plasticity
	having a direct role in metastatic progression, likely due to the modulation of actomyosin cytoskeletal dynamics, which results in increased cellular motility
	calcium-binding protein that can act as a novel cardiac growth and survival factor and may have regenerative effects in injured myocardium
	directly involved in tumor invasion and metastasis via interactions with specific protein targets, including nonmuscle MYH9
	might be involved in the progression and metastasis of human CC, presumably via modulation of the wild-type TP53 protein (Kim 2009)
	can potentiate transcriptional activity of SMAD3 and increase cell invasion ability induced by TGF-beta in cancer cells
	developmentally regulated and playing a functional role in mammary gland development
	nonimmune S100A4+ stromal cells associated with metastatic nodules are important mediators of metastatic colonization
	is likely crucial for cell motility in pancreatic cancer and some downstream genes may play important roles in cell motility
	MTA1-S100A4-MYH9 axis exists in endothelial cells as a novel pathway in promoting tumor vascular formation

CELLULAR PROCESS	cell cycle

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

constituent of epidermal differentiation complex

INTERACTION

DNA

RNA

small molecule	metal binding,
	Ca2+

protein	S100A1 (activation of capability to metastasis)
	PPFIBP1 (target of S100A4)
	associates with METAP2 in a calcium-dependent manner
	direct beta-catenin/TCF target, inducing metastasis and having value for prognosis of metastasis formation in colon cancer patients
	Ca2+-dependent conformational change is required for S100A4 to bind peptide sequences derived from the C-terminal portion of MYH9
	formation of PGLYRP1-S100A4 complex had virtually no effect on the role of S100A4 in the regulation of intracellular Ca2+ metabolism
	can physically and functionally interact with SMAD3 in a Ca2+dependent manner
	with S100A1, S100A2 and S100A6, interacting with MDM2, making the binding to MDM2 a general feature of S100 proteins
	LAMTOR5 is able to up-regulate S100A4 expression in breast cancer cells
	interacts with the Rho-binding domain (RBD) of Rhotekin, thus connecting S100A4 to the Rho pathway, which permit S100A4 to complex with RHOA and switch Rho function from stress fiber formation to membrane ruffling to confer an invasive phenotype
	modulates TP53 function in fibroblasts and thereby mediates myocardial interstitial fibrosis through two distinct mechanisms, cell proliferation and collagen expression
	LRP6 promotes TNBC cell migration and invasion by regulating the expression and function of S100A4 via the WNT/CTNNB1 signaling pathway
	cytoplasmic MTA1, but not nuclear MTA1, was colocalized with S100A4, suggesting bthe involvement of MTA1 in S100A4 stability

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in bile duct adenocarcinoma with invasivenessand in colon carcinoma and liver metastases tumoral     --over   during the progression of prostate cancer tumoral     --over   in Barrett's adenocarcinomas constitutional     --over   in injured myocardium and promotes growth and survival of cardiac myocytes tumoral     --over   in colorectal carcinoma with metastasis tumoral     --over   by hypomethylation in the grade 3 endometrioid tumors, uterine papillary serous carcinoma, and uterine malignant mixed mllerian tumor tumoral     --over   is an inducer of metastasis and indicator of poor prognosis in breast cancer constitutional     --over   of RLN2 and S100A4 might be related to the prediction of metastasis potency and poor prognosis for osteosarcoma patients tumoral     --over   in pancreatic cancer

Susceptibility

Variant & Polymorphism

Candidate gene
Marker	detection of RLN2 and S100A4 might be useful in evaluating the outcome of patients with osteosarcoma
Therapy target
	System Type Disorder Pubmed cancer reproductive prostate could be used as a biomarker for prostate carcinoma progression and a novel therapeutic or chemopreventive target for prostate carcinoma treatment (suppressor of S100A4) cancer metastases   potentially valuable molecular target for cancer therapy cancer metastases   C-terminal region of S100A4 is a possible target for inhibitors of its metastatic action

ANIMAL & CELL MODELS