S10A2_HUMAN
ID S10A2_HUMAN Reviewed; 98 AA.
AC P29034; O00266; Q3KRB9; Q5RHS8; Q9BU83;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 05-SEP-2006, sequence version 3.
DT 03-AUG-2022, entry version 190.
DE RecName: Full=Protein S100-A2;
DE AltName: Full=CAN19;
DE AltName: Full=Protein S-100L;
DE AltName: Full=S100 calcium-binding protein A2;
GN Name=S100A2; Synonyms=S100L;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, AND INDUCTION.
RC TISSUE=Mammary epithelium;
RX PubMed=1372446; DOI=10.1073/pnas.89.6.2504;
RA Lee S.W., Tomasetto C., Swisshelm K., Keyomarsi K., Sager R.;
RT "Down-regulation of a member of the S100 gene family in mammary carcinoma
RT cells and reexpression by azadeoxycytidine treatment.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:2504-2508(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], DEVELOPMENTAL STAGE, AND INDUCTION.
RX PubMed=9481475; DOI=10.1016/s0143-4160(97)90063-4;
RA Wicki R., Franz C., Scholl F.A., Heizmann C.W., Schaefer B.W.;
RT "Repression of the candidate tumor suppressor gene S100A2 in breast cancer
RT is mediated by site-specific hypermethylation.";
RL Cell Calcium 22:243-254(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Ovary;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP PROTEIN SEQUENCE OF 37-40 AND 42-49.
RC TISSUE=Keratinocyte;
RX PubMed=1286667; DOI=10.1002/elps.11501301199;
RA Rasmussen H.H., van Damme J., Puype M., Gesser B., Celis J.E.,
RA Vandekerckhove J.;
RT "Microsequences of 145 proteins recorded in the two-dimensional gel protein
RT database of normal human epidermal keratinocytes.";
RL Electrophoresis 13:960-969(1992).
RN [6]
RP INTERACTION WITH FKBP4.
RX PubMed=20188096; DOI=10.1016/j.febslet.2010.02.055;
RA Shimamoto S., Kubota Y., Tokumitsu H., Kobayashi R.;
RT "S100 proteins regulate the interaction of Hsp90 with cyclophilin 40 and
RT FKBP52 through their tetratricopeptide repeats.";
RL FEBS Lett. 584:1119-1125(2010).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [8]
RP FUNCTION IN CALCIUM SIGNALING, AND INTERACTION WITH PPP5C.
RX PubMed=22399290; DOI=10.1074/jbc.m111.329771;
RA Yamaguchi F., Umeda Y., Shimamoto S., Tsuchiya M., Tokumitsu H., Tokuda M.,
RA Kobayashi R.;
RT "S100 proteins modulate protein phosphatase 5 function: a link between CA2+
RT signal transduction and protein dephosphorylation.";
RL J. Biol. Chem. 287:13787-13798(2012).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS), AND SUBUNIT.
RX PubMed=18394645; DOI=10.1016/j.jmb.2008.03.019;
RA Koch M., Diez J., Fritz G.;
RT "Crystal structure of Ca2+ -free S100A2 at 1.6-A resolution.";
RL J. Mol. Biol. 378:933-942(2008).
RN [10]
RP INTERACTION WITH TPPP.
RX PubMed=33831707; DOI=10.1016/j.ceca.2021.102404;
RA Doi S., Fujioka N., Ohtsuka S., Kondo R., Yamamoto M., Denda M., Magari M.,
RA Kanayama N., Hatano N., Morishita R., Hasegawa T., Tokumitsu H.;
RT "Regulation of the tubulin polymerization-promoting protein by Ca2+/S100
RT proteins.";
RL Cell Calcium 96:102404-102404(2021).
CC -!- FUNCTION: May function as calcium sensor and modulator, contributing to
CC cellular calcium signaling. May function by interacting with other
CC proteins, such as TPR-containing proteins, and indirectly play a role
CC in many physiological processes. May also play a role in suppressing
CC tumor cell growth. {ECO:0000269|PubMed:1372446,
CC ECO:0000269|PubMed:22399290}.
CC -!- SUBUNIT: Homodimer. Interacts with FKBP4. Interacts with PPP5C (via TPR
CC repeats); the interaction is calcium-dependent and modulates PPP5C
CC activity. Interacts with TPPP; this interaction inhibits TPPP
CC dimerization (PubMed:33831707). {ECO:0000269|PubMed:18394645,
CC ECO:0000269|PubMed:20188096, ECO:0000269|PubMed:22399290,
CC ECO:0000269|PubMed:33831707}.
CC -!- INTERACTION:
CC P29034; Q3SXY8: ARL13B; NbExp=3; IntAct=EBI-752230, EBI-11343438;
CC P29034; P15311: EZR; NbExp=2; IntAct=EBI-752230, EBI-1056902;
CC P29034; Q5JX71: FAM209A; NbExp=3; IntAct=EBI-752230, EBI-18304435;
CC P29034; Q02790: FKBP4; NbExp=3; IntAct=EBI-752230, EBI-1047444;
CC P29034; P52292: KPNA2; NbExp=5; IntAct=EBI-752230, EBI-349938;
CC P29034; Q00987: MDM2; NbExp=2; IntAct=EBI-752230, EBI-389668;
CC P29034; O15151: MDM4; NbExp=2; IntAct=EBI-752230, EBI-398437;
CC P29034; P35579: MYH9; NbExp=2; IntAct=EBI-752230, EBI-350338;
CC P29034; P23297: S100A1; NbExp=7; IntAct=EBI-752230, EBI-743686;
CC P29034; P29034: S100A2; NbExp=6; IntAct=EBI-752230, EBI-752230;
CC P29034; P33764: S100A3; NbExp=5; IntAct=EBI-752230, EBI-1044747;
CC P29034; P04271: S100B; NbExp=9; IntAct=EBI-752230, EBI-458391;
CC P29034; P04637: TP53; NbExp=4; IntAct=EBI-752230, EBI-366083;
CC P29034; Q8TD43: TRPM4; NbExp=2; IntAct=EBI-752230, EBI-11723041;
CC P29034; P52293: Kpna2; Xeno; NbExp=2; IntAct=EBI-752230, EBI-3043908;
CC P29034; P26882: PPID; Xeno; NbExp=3; IntAct=EBI-752230, EBI-6477155;
CC -!- TISSUE SPECIFICITY: A subset of epithelial cells including normal human
CC mammary epithelial cells and keratinocytes.
CC {ECO:0000269|PubMed:1372446}.
CC -!- DEVELOPMENTAL STAGE: Preferentially expressed in normal human mammary
CC epithelial cells as opposed to tumor-derived ones. The level of S100L
CC was shown to correlate inversely with tumor progression.
CC {ECO:0000269|PubMed:9481475}.
CC -!- INDUCTION: By growth factors in early G1 phase and probably by cell-
CC cycle regulation in S phase. DNA methylation probably plays a direct
CC negative role in suppressing S100L gene expression in tumor cells.
CC {ECO:0000269|PubMed:1372446, ECO:0000269|PubMed:9481475}.
CC -!- MISCELLANEOUS: This protein binds two calcium ions. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the S-100 family. {ECO:0000305}.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-2 is the initiator.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA69033.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/S100A2ID42191ch1q21.html";
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DR EMBL; M87068; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; Y07755; CAA69033.1; ALT_INIT; Genomic_DNA.
DR EMBL; BX470102; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC002829; AAH02829.3; -; mRNA.
DR EMBL; BC105787; AAI05788.1; -; mRNA.
DR CCDS; CCDS1044.1; -.
DR PIR; A41988; A41988.
DR RefSeq; NP_005969.1; NM_005978.3.
DR PDB; 2RGI; X-ray; 1.60 A; A/B=1-98.
DR PDB; 4DUQ; X-ray; 1.30 A; A/B=1-98.
DR PDBsum; 2RGI; -.
DR PDBsum; 4DUQ; -.
DR AlphaFoldDB; P29034; -.
DR BMRB; P29034; -.
DR SMR; P29034; -.
DR BioGRID; 112181; 436.
DR IntAct; P29034; 30.
DR MINT; P29034; -.
DR STRING; 9606.ENSP00000357697; -.
DR DrugBank; DB01373; Calcium.
DR DrugBank; DB09130; Copper.
DR DrugBank; DB00768; Olopatadine.
DR DrugBank; DB01593; Zinc.
DR DrugBank; DB14487; Zinc acetate.
DR DrugBank; DB14533; Zinc chloride.
DR DrugBank; DB14548; Zinc sulfate, unspecified form.
DR iPTMnet; P29034; -.
DR PhosphoSitePlus; P29034; -.
DR BioMuta; S100A2; -.
DR DMDM; 114152869; -.
DR CPTAC; CPTAC-1453; -.
DR EPD; P29034; -.
DR jPOST; P29034; -.
DR MassIVE; P29034; -.
DR MaxQB; P29034; -.
DR PaxDb; P29034; -.
DR PeptideAtlas; P29034; -.
DR PRIDE; P29034; -.
DR ProteomicsDB; 54515; -.
DR Antibodypedia; 34127; 253 antibodies from 30 providers.
DR CPTC; P29034; 3 antibodies.
DR DNASU; 6273; -.
DR Ensembl; ENST00000368708.9; ENSP00000357697.4; ENSG00000196754.13.
DR Ensembl; ENST00000368709.6; ENSP00000357698.2; ENSG00000196754.13.
DR Ensembl; ENST00000368710.6; ENSP00000357699.2; ENSG00000196754.13.
DR Ensembl; ENST00000487430.7; ENSP00000473260.2; ENSG00000196754.13.
DR GeneID; 6273; -.
DR KEGG; hsa:6273; -.
DR MANE-Select; ENST00000368708.9; ENSP00000357697.4; NM_005978.4; NP_005969.2.
DR UCSC; uc001fcb.4; human.
DR CTD; 6273; -.
DR DisGeNET; 6273; -.
DR GeneCards; S100A2; -.
DR HGNC; HGNC:10492; S100A2.
DR HPA; ENSG00000196754; Tissue enhanced (esophagus, urinary bladder).
DR MIM; 176993; gene.
DR neXtProt; NX_P29034; -.
DR OpenTargets; ENSG00000196754; -.
DR PharmGKB; PA34904; -.
DR VEuPathDB; HostDB:ENSG00000196754; -.
DR eggNOG; ENOG502S4AU; Eukaryota.
DR GeneTree; ENSGT00940000163114; -.
DR HOGENOM; CLU_138624_2_0_1; -.
DR InParanoid; P29034; -.
DR OMA; TMMCNDF; -.
DR OrthoDB; 1560865at2759; -.
DR PhylomeDB; P29034; -.
DR TreeFam; TF332727; -.
DR PathwayCommons; P29034; -.
DR SignaLink; P29034; -.
DR BioGRID-ORCS; 6273; 7 hits in 1071 CRISPR screens.
DR ChiTaRS; S100A2; human.
DR EvolutionaryTrace; P29034; -.
DR GeneWiki; S100A2; -.
DR GenomeRNAi; 6273; -.
DR Pharos; P29034; Tbio.
DR PRO; PR:P29034; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P29034; protein.
DR Bgee; ENSG00000196754; Expressed in tongue squamous epithelium and 135 other tissues.
DR ExpressionAtlas; P29034; baseline and differential.
DR Genevisible; P29034; HS.
DR GO; GO:0005509; F:calcium ion binding; IBA:GO_Central.
DR GO; GO:0048306; F:calcium-dependent protein binding; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0046914; F:transition metal ion binding; IEA:InterPro.
DR GO; GO:0043542; P:endothelial cell migration; IMP:UniProtKB.
DR CDD; cd00213; S-100; 1.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR034325; S-100_dom.
DR InterPro; IPR001751; S100/CaBP7/8-like_CS.
DR InterPro; IPR013787; S100_Ca-bd_sub.
DR Pfam; PF01023; S_100; 1.
DR SMART; SM01394; S_100; 1.
DR SUPFAM; SSF47473; SSF47473; 1.
DR PROSITE; PS00018; EF_HAND_1; 1.
DR PROSITE; PS50222; EF_HAND_2; 1.
DR PROSITE; PS00303; S100_CABP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Calcium; Direct protein sequencing; Metal-binding;
KW Reference proteome; Repeat.
FT CHAIN 1..98
FT /note="Protein S100-A2"
FT /id="PRO_0000143971"
FT DOMAIN 13..48
FT /note="EF-hand 1"
FT /evidence="ECO:0000305"
FT DOMAIN 51..86
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 29
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /ligand_note="low affinity"
FT /evidence="ECO:0000305"
FT BINDING 34
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /ligand_note="low affinity"
FT /evidence="ECO:0000305"
FT BINDING 64
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /ligand_note="high affinity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 66
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /ligand_note="high affinity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 68
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /ligand_note="high affinity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 70
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /ligand_note="high affinity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 75
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /ligand_note="high affinity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT CONFLICT 62
FT /note="S -> N (in Ref. 1; M87068)"
FT /evidence="ECO:0000305"
FT HELIX 5..21
FT /evidence="ECO:0007829|PDB:4DUQ"
FT STRAND 23..26
FT /evidence="ECO:0007829|PDB:4DUQ"
FT HELIX 32..42
FT /evidence="ECO:0007829|PDB:4DUQ"
FT HELIX 44..47
FT /evidence="ECO:0007829|PDB:4DUQ"
FT HELIX 53..63
FT /evidence="ECO:0007829|PDB:4DUQ"
FT STRAND 67..71
FT /evidence="ECO:0007829|PDB:4DUQ"
FT HELIX 73..89
FT /evidence="ECO:0007829|PDB:4DUQ"
SQ SEQUENCE 98 AA; 11117 MW; 56D09548450142A9 CRC64;
MMCSSLEQAL AVLVTTFHKY SCQEGDKFKL SKGEMKELLH KELPSFVGEK VDEEGLKKLM
GSLDENSDQQ VDFQEYAVFL ALITVMCNDF FQGCPDRP
