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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
Location 1q21.3      Physical location : 153.516.095 - 153.518.282
Synonym name
  • malignant transformation suppression 1
  • S100 calcium binding protein A4 (calcium protein, calvasculin, metastasin, murine placental homolog)
  • calcium placental protein
  • fibroblast-specific protein-1
  • metastasin
  • protein Mts1
  • calvasculin
    • Synonym symbol(s) CAPL, ST1, MTS1, P9KA, PEL98, 18A2, 42A, FSP1, p9Ka, 42A, pEL98
    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)
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    2 - 512 - 101 - 1995 7607566
    3 splicing 564 - 101 - 1995 7607566
    EXPRESSION
    Type ubiquitous
    constitutive of
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
     vessel   highly
    Digestiveintestinelarge intestinecolon  
    Visualeyeanterior segmentcornea  
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialabsorptive excretorydigestive epithelium (mucosa)  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/ImmuneT 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)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein 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
    SystemTypeDisorderPubmed
    cancerreproductiveprostate
    could be used as a biomarker for prostate carcinoma progression and a novel therapeutic or chemopreventive target for prostate carcinoma treatment (suppressor of S100A4)
    cancermetastases 
    potentially valuable molecular target for cancer therapy
    cancermetastases 
    C-terminal region of S100A4 is a possible target for inhibitors of its metastatic action
    ANIMAL & CELL MODELS