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S100A10 (S100 calcium binding protein A10)

Written2008-10Patricia A Madureira, David M Waisman
Dalhousie University, Halifax, Nova Scotia, Canada

(Note : for Links provided by Atlas : click)

Identity

Alias_namesANX2LG
CAL1L
S100 calcium-binding protein A10 (annexin II ligand, calpactin I, light polypeptide (p11))
S100 calcium binding protein A10 (annexin II ligand, calpactin I, light polypeptide (p11))
Alias_symbol (synonym)P11
42C
CLP11
HGNC (Hugo) S100A10
LocusID (NCBI) 6281
Atlas_Id 44145
Location 1q21.3  [Link to chromosome band 1q21]
Location_base_pair Starts at 151955386 and ends at 151966714 bp from pter ( according to hg19-Feb_2009)  [Mapping S100A10.png]
Local_order According to NCBI Map Viewer, genes flanking S100A10 in centromere to telomere direction on 1q21 are: THEM4 (1q21) thioesterase superfamily member 4, KRT8P28 (1q21.3) keratin 8 pseudogene 28, S100A10 (1q21) S100 calcium binding protein A10, NBPF18P (1q21.3) neuroblastoma breakpoint family member 18 (pseudogene), S100A11 (1q21) S100 calcium binding protein A11.
Fusion genes
(updated 2016)
ANP32B (9q22.33) / S100A10 (1q21.3)CSF1 (1p13.3) / S100A10 (1q21.3)HDGF (1q23.1) / S100A10 (1q21.3)
MALAT1 (11q13.1) / S100A10 (1q21.3)MCUR1 (6p23) / S100A10 (1q21.3)S100A10 (1q21.3) / AGBL5 (2p23.3)
S100A10 (1q21.3) / CTSZ (20q13.32)THEM4 (1q21.3) / S100A10 (1q21.3)

DNA/RNA

 
Description The S100A10 gene contains two introns, one in the 5 prime untranslated region of the gene and the other in the protein coding region. The second intron separates the codons for two corresponding amino acids which reside in the sequence connecting the two helix-loop-helix (EF-hand) motifs.
Transcription Transcription produces 7 different mRNAs, 6 alternatively spliced variants and 1 unspliced form. The mRNAs differ by truncation of the 5' end, alternative splicing or retention of 2 introns.
Pseudogene No known pseudogenes.

Protein

 
Description S100A10 is a member of the S100 family of Ca2+ binding proteins containing 2 EF-hand calcium-binding motifs (Donato, 2001). In contrast to all other S100 proteins, S100A10 is calcium insensitive because of amino acid replacements in its calcium-binding loops that lock the protein in a permanently active state. S100A10 protein is a dimeric protein composed of two 11-kDa subunits (p11 subunits) (Waisman, 1995). S100A10 is found in most cells bound to its annexin II ligand as the heterotetrameric [(S100A10)2 (annexin II)2] complex, also called annexin A2 tetramer (AIIt), in which a central S100A10 dimer interacts with two annexin A2 chains (Lewit-Bentley et al., 2000).
Expression Ubiquitous expression. S100A10 protein is highly expressed in the brain, heart and lung; moderate expression in the liver, bone marrow, spleen, skeletal muscle, pancreas, prostate and kidney.
Localisation Cell surface membrane, Ion channels, membrane of early endosomes and cytoplasm.
Function S100A10 protein plays a key role in the regulation of plasminogen/ plasmin activity. The carboxyl-terminal lysines of S100A10 bind tPA and plasminogen resulting in the stimulation of tPA-dependent plasmin production (MacLeod et al., 2003). Plasmin binds to S100A10 at a distinct site and the formation of the S100A10-plasmin complex stimulates plasmin auto-proteolysis thereby providing a highly localized transient pulse of plasmin activity at the cell surface (MacLeod et al., 2003; Kwon et al., 2005). The binding of tPA and plasmin to S100A10 also protects against inhibition by their physiological inhibitors, PAI-1 and alpha2-antiplasmin, respectively (Kassam et al., 1998). S100A10 also co-localizes plasminogen with the urokinase-type plasminogen activator/(uPA/uPAR) complex thereby localizing and stimulating uPA-dependent plasmin formation to the surface of cancer cells (Kassam et al., 1998). The loss of S100A10 from the extracellular surface of cancer cells results in a significant loss in plasmin generation. In addition, S100A10 knockdown cells demonstrate a dramatic loss in extracellular matrix degradation and invasiveness as well as reduced metastasis (Zhang et al., 2004; Choi et al., 2003). S100A10 has also been shown to be involved in the intracellular trafficking of a set of plasma membrane ion channels and receptors through direct protein interaction. S100A10 has been shown to bind to and regulate the plasma localization of the tetrodotoxin-resistant sodium channel Nav 1.8 (Okuse et al., 2002). Binding of S100A10 to the two-pore domain potassium channel TWIK-related acid sensitive K-1 (TASK 1) protein is important for TASK translocation to the plasma membrane (Renigunta et al., 2006). S100A10 is also involved in the expression of the transient receptor potential (TRP) channels, TRPV5 and TRPV6 at the cell surface (van de Graaf et al., 2003). S100A10 was also shown to bind and regulate the activity of the acid-sensing ion channel ASIC1a (Donier et al., 2005) and the plasma membrane-resident serotonin 5-HT1B receptor (Svenningsson et al., 2006). Increasing evidence suggests that the AIIt protein plays an important role in linking the micro-domain formation to actin rearrangements, either through direct binding to F-actin or through the recruitment of proteins that modulate the actin cytoskeleton (Hayes et al., 2004; Hayes et al., 2006). The AIIt complex recruits the actin-binding protein AHNAK to the plasma membrane; this protein is involved in the development of the cell membrane cytoarchitecture in polarizing epithelial cells (Benaud et al., 2004; De Seranno et al., 2006).
Homology S100A10 is highly conserved between different species. Human S100A10 has 100% homology to S100A10 from Bos Taurus, Macaca mulatta, Pan troglodytes, Pongo pygmaeus, 98% homology to S100A10 from Canis familiaris, equus caballus, Felis catus, 91% homology to S100A10 from Mus musculus, 88% homology to S100A10 from Rattus norvegicus.

Mutations

Note No mutations have been reported for S100A10 that cause congenital anomalies. A recent study tested for rare variants in p11 by resequencing promoter, exonic and flanking intronic regions in 176 Major Depressive Disorder (MDD) cases and 176 matched controls. These studies also assessed common variation by genotyping eight single nucleotide polymorphisms (SNPs), seven tag SNPs and one found through resequencing, in 641 MDD cases and 650 controls. Resequencing revealed nine novel rare variants, including a missense mutation (Asp60Glu) observed in one case and one control, and four variants that occurred only in cases and not controls. The number of rare variants in cases did not exceed that expected by chance for the length of sequence analyzed, and also was not significantly greater than that observed in controls. Resequencing also identified two known SNPs, one (rs4845720) of which was significantly more frequent in MDD cases than controls in the resequenced sample (3.1% vs. 0.9%, P = 0.03), though not in the larger sample (3% vs. 2%, P = 0.15). None of the tag SNPs showed any evidence of association. In conclusion these results did not support a major role for either common or rare p11 SNPs with MDD (Verma et al., 2007).

Implicated in

Note
  
Entity Various cancers
Note S100A10 has been shown to be over-expressed a number of different cancers, including thyroid neoplasms, anaplastic large cell lymphoma, gastric cancer and renal cell carcinoma.
  
  
Entity Depressive disorders
Note S100A10 knockout mice are viable indicating that S100A10 is not required for normal development. Nevertheless these mice show a depression-like phenotype and reduced responsiveness to serotonin 1B receptor agonists. Moreover, these mice respond less to anti-depressants, suggesting a main role for S100A10 in regulating 5-HT1B receptor function and subsequent depressive disorders (Svenningsson et al., 2006).
  

Bibliography

AHNAK interaction with the annexin 2/S100A10 complex regulates cell membrane cytoarchitecture.
Benaud C, Gentil BJ, Assard N, Court M, Garin J, Delphin C, Baudier J.
J Cell Biol. 2004 Jan 5;164(1):133-44.
PMID 14699089
 
8.p11 regulates extracellular plasmin production and invasiveness of HT1080 fibrosarcoma cells.
Choi KS, Fogg DK, Yoon CS, Waisman DM.
FASEB J. 2003 Feb;17(2):235-46.
PMID 12554702
 
Identification of an AHNAK binding motif specific for the Annexin2/S100A10 tetramer.
De Seranno S, Benaud C, Assard N, Khediri S, Gerke V, Baudier J, Delphin C.
J Biol Chem. 2006 Nov 17;281(46):35030-8.
PMID 16984913
 
S100: a multigenic family of calcium-modulated proteins of the EF-hand type with intracellular and extracellular functional roles.
Donato R.
Int J Biochem Cell Biol. 2001 Jul;33(7):637-68.
PMID 11390274
 
Annexin II light chain p11 promotes functional expression of acid-sensing ion channel ASIC1a.
Donier E, Rugiero F, Okuse K, Wood JN.
J Biol Chem. 2005 Nov 18;280(46):38666-72.
PMID 16169854
 
Annexin-actin interactions.
Hayes MJ, Rescher U, Gerke V, Moss SE.
Traffic. 2004 Aug; 5(8):571-6.
PMID 15260827
 
Regulation of actin dynamics by annexin 2.
Hayes MJ, Shao D, Bailly M, Moss SE.
EMBO J. 2006 May 3; 25(9):1816-26.
PMID 16601677
 
The p11 subunit of the annexin II tetramer plays a key role in the stimulation of t-PA-dependent plasminogen activation.
Kassam G, Le BH, Choi KS, Kang HM, Fitzpatrick SL, Louie P, Waisman DM.
Biochemistry. 1998 Dec 1;37(48):16958-66.
PMID 9836589
 
S100A10, annexin A2, and annexin a2 heterotetramer as candidate plasminogen receptors.
Kwon M, MacLeod TJ, Zhang Y, Waisman DM.
Front Biosci. 2005 Jan 1;10:300-25. (Review)
PMID 15574370
 
S100-annexin complexes: some insights from structural studies.
Lewit-Bentley A, Rety S, Sopkova-de Oliveira Santos J, Gerke V.
Cell Biol Int. 2000;24(11):799-802.
PMID 11067764
 
Phospholipid-associated annexin A2-S100A10 heterotetramer and its subunits: characterization of the interaction with tissue plasminogen activator, plasminogen, and plasmin.
MacLeod TJ, Kwon M, Filipenko NR, Waisman DM.
J Biol Chem. 2003 Jul 11;278(28):25577-84.
PMID 12730231
 
Annexin II light chain regulates sensory neuron-specific sodium channel expression.
Okuse K, Malik-Hall M, Baker MD, Poon WY, Kong H, Chao MV, Wood JN.
Nature. 2002 Jun 6;417(6889):653-6.
PMID 12050667
 
The retention factor p11 confers an endoplasmic reticulum-localization signal to the potassium channel TASK-1.
Renigunta V, Yuan H, Zuzarte M, Rinne S, Koch A, Wischmeyer, E, Schlichthorl G, Gao Y, Karschin A, Jacob R, Schwappach B, Daut J, Preisig-Muller R.
Traffic. 2006 Feb;7(2):168-81.
PMID 16420525
 
Alterations in 5-HT1B receptor function by p11 in depression-like states.
Svenningsson P, Chergui K, Rachleff I, Flajolet M, Zhang X, El Yacoubi M, Vaugeois JM, Nomikos GG, Greengard P.
Science. 2006 Jan 6; 311(5757):77-80.
PMID 16400147
 
Investigating the role of p11 (S100A10) sequence variation in susceptibility to major depression.
Verma R, Cutler DJ, Holmans P, Knowles JA, Crowe RR, Scheftner WA, Weissman MM, DePaulo JR Jr, Levinson DF, Potash JB.
Am J Med Genet B Neuropsychiatr Genet. 2007 Dec 5;144B(8):1079-82.
PMID 17510952
 
Annexin II tetramer: structure and function.
Waisman DM.
Mol Cell Biochem. 1995 Aug-Sep;149-150:301-22. (Review)
PMID 8569746
 
RNA interference-mediated silencing of the S100A10 gene attenuates plasmin generation and invasiveness of Colo 222 colorectal cancer cells.
Zhang L, Fogg DK, Waisman DM.
J Biol Chem. 2004 Jan 16;279(3):2053-62.
PMID 14570893
 
Functional expression of the epithelial Ca(2+) channels (TRPV5 and TRPV6) requires association of the S100A10-annexin 2 complex.
van de Graaf SF, Hoenderop JG, Gkika D, Lamers D, Prenen J, Rescher U, Gerke V, Staub O, Nilius B, Bindels RJ.
EMBO J. 2003 Apr 1; 22(7):1478-87.
PMID 12660155
 

Citation

This paper should be referenced as such :
Madureira, PA ; Waisman, DM
S100A10 (S100 calcium binding protein A10)
Atlas Genet Cytogenet Oncol Haematol. 2009;13(9):657-659.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/S100A10ID44145ch1q21.html


External links

Nomenclature
HGNC (Hugo)S100A10   10487
Cards
AtlasS100A10ID44145ch1q21
Entrez_Gene (NCBI)S100A10  6281  S100 calcium binding protein A10
Aliases42C; ANX2L; ANX2LG; CAL1L; 
CLP11; Ca[1]; GP11; P11; p10
GeneCards (Weizmann)S100A10
Ensembl hg19 (Hinxton)ENSG00000197747 [Gene_View]  chr1:151955386-151966714 [Contig_View]  S100A10 [Vega]
Ensembl hg38 (Hinxton)ENSG00000197747 [Gene_View]  chr1:151955386-151966714 [Contig_View]  S100A10 [Vega]
ICGC DataPortalENSG00000197747
TCGA cBioPortalS100A10
AceView (NCBI)S100A10
Genatlas (Paris)S100A10
WikiGenes6281
SOURCE (Princeton)S100A10
Genetics Home Reference (NIH)S100A10
Genomic and cartography
GoldenPath hg19 (UCSC)S100A10  -     chr1:151955386-151966714 -  1q21   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)S100A10  -     1q21   [Description]    (hg38-Dec_2013)
EnsemblS100A10 - 1q21 [CytoView hg19]  S100A10 - 1q21 [CytoView hg38]
Mapping of homologs : NCBIS100A10 [Mapview hg19]  S100A10 [Mapview hg38]
OMIM114085   
Gene and transcription
Genbank (Entrez)AK291073 BC015973 BC105786 BE378444 BI827113
RefSeq transcript (Entrez)NM_002966
RefSeq genomic (Entrez)NC_000001 NC_018912 NT_004487 NW_004929293
Consensus coding sequences : CCDS (NCBI)S100A10
Cluster EST : UnigeneHs.143873 [ NCBI ]
CGAP (NCI)Hs.143873
Alternative Splicing GalleryENSG00000197747
Gene ExpressionS100A10 [ NCBI-GEO ]   S100A10 [ EBI - ARRAY_EXPRESS ]   S100A10 [ SEEK ]   S100A10 [ MEM ]
Gene Expression Viewer (FireBrowse)S100A10 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)6281
GTEX Portal (Tissue expression)S100A10
Protein : pattern, domain, 3D structure
UniProt/SwissProtP60903   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP60903  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP60903
Splice isoforms : SwissVarP60903
PhosPhoSitePlusP60903
Domaine pattern : Prosite (Expaxy)S100_CABP (PS00303)   
Domains : Interpro (EBI)EF-hand-dom_pair    S100-A10    S100/CaBP-9k_CS    S100_Ca-bd_sub   
Domain families : Pfam (Sanger)S_100 (PF01023)   
Domain families : Pfam (NCBI)pfam01023   
Conserved Domain (NCBI)S100A10
DMDM Disease mutations6281
Blocks (Seattle)S100A10
PDB (SRS)1A4P    1BT6    4DRW    4FTG    4HRE    4HRG    4HRH   
PDB (PDBSum)1A4P    1BT6    4DRW    4FTG    4HRE    4HRG    4HRH   
PDB (IMB)1A4P    1BT6    4DRW    4FTG    4HRE    4HRG    4HRH   
PDB (RSDB)1A4P    1BT6    4DRW    4FTG    4HRE    4HRG    4HRH   
Structural Biology KnowledgeBase1A4P    1BT6    4DRW    4FTG    4HRE    4HRG    4HRH   
SCOP (Structural Classification of Proteins)1A4P    1BT6    4DRW    4FTG    4HRE    4HRG    4HRH   
CATH (Classification of proteins structures)1A4P    1BT6    4DRW    4FTG    4HRE    4HRG    4HRH   
SuperfamilyP60903
Human Protein AtlasENSG00000197747
Peptide AtlasP60903
HPRD00232
IPIIPI00183695   
Protein Interaction databases
DIP (DOE-UCLA)P60903
IntAct (EBI)P60903
FunCoupENSG00000197747
BioGRIDS100A10
STRING (EMBL)S100A10
ZODIACS100A10
Ontologies - Pathways
QuickGOP60903
Ontology : AmiGOmembrane raft assembly  calcium ion binding  protein binding  membrane budding  lipid binding  extrinsic component of plasma membrane  protein homodimerization activity  positive regulation of GTPase activity  ion channel binding  membrane raft  positive regulation of binding  protein heterotetramerization  positive regulation of stress fiber assembly  positive regulation of focal adhesion assembly  extracellular exosome  establishment of protein localization to plasma membrane  positive regulation of substrate adhesion-dependent cell spreading  
Ontology : EGO-EBImembrane raft assembly  calcium ion binding  protein binding  membrane budding  lipid binding  extrinsic component of plasma membrane  protein homodimerization activity  positive regulation of GTPase activity  ion channel binding  membrane raft  positive regulation of binding  protein heterotetramerization  positive regulation of stress fiber assembly  positive regulation of focal adhesion assembly  extracellular exosome  establishment of protein localization to plasma membrane  positive regulation of substrate adhesion-dependent cell spreading  
REACTOMEP60903 [protein]
REACTOME Pathways75205 [pathway]   
NDEx NetworkS100A10
Atlas of Cancer Signalling NetworkS100A10
Wikipedia pathwaysS100A10
Orthology - Evolution
OrthoDB6281
GeneTree (enSembl)ENSG00000197747
Phylogenetic Trees/Animal Genes : TreeFamS100A10
HOVERGENP60903
HOGENOMP60903
Homologs : HomoloGeneS100A10
Homology/Alignments : Family Browser (UCSC)S100A10
Gene fusions - Rearrangements
Fusion : MitelmanCSF1/S100A10 [1p13.3/1q21.3]  [t(1;1)(p13;q21)]  
Fusion : MitelmanHDGF/S100A10 [1q23.1/1q21.3]  [t(1;1)(q21;q23)]  
Fusion : MitelmanMCUR1/S100A10 [6p23/1q21.3]  [t(1;6)(q21;p23)]  
Fusion : MitelmanTHEM4/S100A10 [1q21.3/1q21.3]  [t(1;1)(q21;q21)]  
Fusion: TCGACCDC90A S100A10 1q21.3 BRCA
Fusion: TCGATHEM4 1q21.3 S100A10 1q21.3 BRCA
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerS100A10 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)S100A10
dbVarS100A10
ClinVarS100A10
1000_GenomesS100A10 
Exome Variant ServerS100A10
ExAC (Exome Aggregation Consortium)S100A10 (select the gene name)
Genetic variants : HAPMAP6281
Genomic Variants (DGV)S100A10 [DGVbeta]
DECIPHER (Syndromes)1:151955386-151966714  ENSG00000197747
CONAN: Copy Number AnalysisS100A10 
Mutations
ICGC Data PortalS100A10 
TCGA Data PortalS100A10 
Broad Tumor PortalS100A10
OASIS PortalS100A10 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICS100A10  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDS100A10
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch S100A10
DgiDB (Drug Gene Interaction Database)S100A10
DoCM (Curated mutations)S100A10 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)S100A10 (select a term)
intoGenS100A10
NCG5 (London)S100A10
Cancer3DS100A10(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM114085   
Orphanet
MedgenS100A10
Genetic Testing Registry S100A10
NextProtP60903 [Medical]
TSGene6281
GENETestsS100A10
Huge Navigator S100A10 [HugePedia]
snp3D : Map Gene to Disease6281
BioCentury BCIQS100A10
ClinGenS100A10
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD6281
Chemical/Pharm GKB GenePA34899
Clinical trialS100A10
Miscellaneous
canSAR (ICR)S100A10 (select the gene name)
Probes
Litterature
PubMed99 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineS100A10
EVEXS100A10
GoPubMedS100A10
iHOPS100A10
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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