S10A3_HUMAN
ID S10A3_HUMAN Reviewed; 101 AA.
AC P33764; D3DV51; Q6FGE4;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1994, sequence version 1.
DT 03-AUG-2022, entry version 193.
DE RecName: Full=Protein S100-A3;
DE AltName: Full=Protein S-100E;
DE AltName: Full=S100 calcium-binding protein A3;
GN Name=S100A3; Synonyms=S100E;
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 [GENOMIC DNA / MRNA].
RX PubMed=8341667; DOI=10.1073/pnas.90.14.6547;
RA Engelkamp D., Schaefer B.W., Mattei M.-G., Erne P., Heizmann C.W.;
RT "Six S100 genes are clustered on human chromosome 1q21: identification of
RT two genes coding for the two previously unreported calcium-binding proteins
RT S100D and S100E.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:6547-6551(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P.,
RA Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y.,
RA LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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 [7]
RP CHARACTERIZATION.
RX PubMed=9920417; DOI=10.1016/s0167-4889(98)00138-4;
RA Fritz G., Heizmann C.W., Kroneck P.M.H.;
RT "Probing the structure of the human Ca2+- and Zn2+-binding protein S100A3:
RT spectroscopic investigations of its transition metal ion complexes, and
RT three-dimensional structural model.";
RL Biochim. Biophys. Acta 1448:264-276(1998).
RN [8]
RP CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, AND TISSUE
RP SPECIFICITY.
RX PubMed=12470658; DOI=10.1016/s0006-291x(02)02744-4;
RA Kizawa K., Troxler H., Kleinert P., Inoue T., Toyoda M., Morohashi M.,
RA Heizmann C.W.;
RT "Characterization of the cysteine-rich calcium-binding S100A3 protein from
RT human hair cuticles.";
RL Biochem. Biophys. Res. Commun. 299:857-862(2002).
RN [9]
RP FUNCTION, SUBUNIT, CITRULLINATION AT ARG-51, AND SUBCELLULAR LOCATION.
RX PubMed=18083705; DOI=10.1074/jbc.m709357200;
RA Kizawa K., Takahara H., Troxler H., Kleinert P., Mochida U., Heizmann C.W.;
RT "Specific citrullination causes assembly of a globular S100A3 homotetramer:
RT a putative Ca2+ modulator matures human hair cuticle.";
RL J. Biol. Chem. 283:5004-5013(2008).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS).
RX PubMed=12136135; DOI=10.1107/s0907444902008430;
RA Mittl P.R., Fritz G., Sargent D.F., Richmond T.J., Heizmann C.W.,
RA Grutter M.G.;
RT "Metal-free MIRAS phasing: structure of apo-S100A3.";
RL Acta Crystallogr. D 58:1255-1261(2002).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS), DISULFIDE BONDS, ZINC-BINDING
RP SITES, AND MUTAGENESIS OF CYS-30; CYS-68; CYS-81 AND CYS-99.
RX PubMed=21377473; DOI=10.1016/j.jmb.2011.02.055;
RA Unno M., Kawasaki T., Takahara H., Heizmann C.W., Kizawa K.;
RT "Refined crystal structures of human Ca(2+)/Zn(2+)-binding S100A3 protein
RT characterized by two disulfide bridges.";
RL J. Mol. Biol. 408:477-490(2011).
CC -!- FUNCTION: Binds both calcium and zinc. May be involved in calcium-
CC dependent cuticle cell differentiation, hair shaft and hair cuticular
CC barrier formation. {ECO:0000269|PubMed:18083705}.
CC -!- SUBUNIT: Homodimer and homotetramer for the citrullinated form.
CC {ECO:0000269|PubMed:18083705}.
CC -!- INTERACTION:
CC P33764; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-1044747, EBI-739832;
CC P33764; P23297: S100A1; NbExp=3; IntAct=EBI-1044747, EBI-743686;
CC P33764; P60903: S100A10; NbExp=3; IntAct=EBI-1044747, EBI-717048;
CC P33764; P29034: S100A2; NbExp=5; IntAct=EBI-1044747, EBI-752230;
CC P33764; Q8WXG8: S100Z; NbExp=3; IntAct=EBI-1044747, EBI-12198403;
CC P33764; P04637: TP53; NbExp=2; IntAct=EBI-1044747, EBI-366083;
CC P33764; Q8TD43: TRPM4; NbExp=2; IntAct=EBI-1044747, EBI-11723041;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:18083705}.
CC -!- TISSUE SPECIFICITY: Skin specific, specifically expressed at the inner
CC endocuticle of hair fibers. {ECO:0000269|PubMed:12470658}.
CC -!- PTM: More than half of the arginine residues undergo citrullination by
CC PAD1 and PAD2. Arg-51 is specifically citrullinated by PAD3 and
CC promotes tetramerization. {ECO:0000269|PubMed:18083705}.
CC -!- SIMILARITY: Belongs to the S-100 family. {ECO:0000305}.
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DR EMBL; Z18948; CAA79471.1; -; mRNA.
DR EMBL; Z18950; CAA79473.1; -; Genomic_DNA.
DR EMBL; BT006955; AAP35601.1; -; mRNA.
DR EMBL; CR542163; CAG46960.1; -; mRNA.
DR EMBL; CR542185; CAG46982.1; -; mRNA.
DR EMBL; BX470102; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471121; EAW53306.1; -; Genomic_DNA.
DR EMBL; CH471121; EAW53307.1; -; Genomic_DNA.
DR EMBL; BC012893; AAH12893.1; -; mRNA.
DR CCDS; CCDS1043.1; -.
DR PIR; C48219; C48219.
DR PIR; S70326; S70326.
DR RefSeq; NP_002951.1; NM_002960.1.
DR PDB; 1KSO; X-ray; 1.70 A; A/B=1-101.
DR PDB; 3NSI; X-ray; 2.15 A; A/B=1-101.
DR PDB; 3NSK; X-ray; 1.55 A; A/B=1-101.
DR PDB; 3NSL; X-ray; 1.50 A; A/B/C/D/E/F=2-101.
DR PDB; 3NSO; X-ray; 1.45 A; A/B=1-101.
DR PDBsum; 1KSO; -.
DR PDBsum; 3NSI; -.
DR PDBsum; 3NSK; -.
DR PDBsum; 3NSL; -.
DR PDBsum; 3NSO; -.
DR AlphaFoldDB; P33764; -.
DR SMR; P33764; -.
DR BioGRID; 112182; 74.
DR IntAct; P33764; 23.
DR STRING; 9606.ENSP00000357702; -.
DR iPTMnet; P33764; -.
DR BioMuta; S100A3; -.
DR DMDM; 464729; -.
DR EPD; P33764; -.
DR jPOST; P33764; -.
DR MassIVE; P33764; -.
DR MaxQB; P33764; -.
DR PaxDb; P33764; -.
DR PeptideAtlas; P33764; -.
DR PRIDE; P33764; -.
DR ProteomicsDB; 54924; -.
DR Antibodypedia; 20380; 238 antibodies from 31 providers.
DR DNASU; 6274; -.
DR Ensembl; ENST00000368712.1; ENSP00000357701.1; ENSG00000188015.10.
DR Ensembl; ENST00000368713.8; ENSP00000357702.3; ENSG00000188015.10.
DR GeneID; 6274; -.
DR KEGG; hsa:6274; -.
DR MANE-Select; ENST00000368713.8; ENSP00000357702.3; NM_002960.2; NP_002951.1.
DR UCSC; uc001fca.2; human.
DR CTD; 6274; -.
DR DisGeNET; 6274; -.
DR GeneCards; S100A3; -.
DR HGNC; HGNC:10493; S100A3.
DR HPA; ENSG00000188015; Tissue enhanced (skin).
DR MIM; 176992; gene.
DR neXtProt; NX_P33764; -.
DR OpenTargets; ENSG00000188015; -.
DR PharmGKB; PA34905; -.
DR VEuPathDB; HostDB:ENSG00000188015; -.
DR eggNOG; ENOG502SSQB; Eukaryota.
DR GeneTree; ENSGT00940000161959; -.
DR HOGENOM; CLU_138624_2_0_1; -.
DR InParanoid; P33764; -.
DR OMA; CVYCHEY; -.
DR OrthoDB; 1513264at2759; -.
DR PhylomeDB; P33764; -.
DR TreeFam; TF332727; -.
DR PathwayCommons; P33764; -.
DR SignaLink; P33764; -.
DR BioGRID-ORCS; 6274; 11 hits in 1064 CRISPR screens.
DR ChiTaRS; S100A3; human.
DR EvolutionaryTrace; P33764; -.
DR GeneWiki; S100A3; -.
DR GenomeRNAi; 6274; -.
DR Pharos; P33764; Tbio.
DR PRO; PR:P33764; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P33764; protein.
DR Bgee; ENSG00000188015; Expressed in lower esophagus mucosa and 108 other tissues.
DR Genevisible; P33764; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
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:0008270; F:zinc ion binding; IEA:InterPro.
DR CDD; cd00213; S-100; 1.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR034325; S-100_dom.
DR InterPro; IPR001751; S100/CaBP7/8-like_CS.
DR InterPro; IPR013787; S100_Ca-bd_sub.
DR InterPro; IPR028488; S100A3.
DR PANTHER; PTHR11639:SF12; PTHR11639:SF12; 1.
DR Pfam; PF01023; S_100; 1.
DR SMART; SM01394; S_100; 1.
DR SUPFAM; SSF47473; SSF47473; 1.
DR PROSITE; PS00303; S100_CABP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Calcium; Citrullination; Cytoplasm;
KW Disulfide bond; Metal-binding; Reference proteome; Repeat; Zinc.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:12470658"
FT CHAIN 2..101
FT /note="Protein S100-A3"
FT /id="PRO_0000143972"
FT DOMAIN 12..47
FT /note="EF-hand 1"
FT DOMAIN 50..85
FT /note="EF-hand 2"
FT BINDING 28
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /ligand_note="low affinity"
FT /evidence="ECO:0000255"
FT BINDING 33
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /ligand_note="low affinity"
FT /evidence="ECO:0000255"
FT BINDING 63
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /ligand_note="high affinity"
FT /evidence="ECO:0000255"
FT BINDING 65
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /ligand_note="high affinity"
FT /evidence="ECO:0000255"
FT BINDING 67
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /ligand_note="high affinity"
FT /evidence="ECO:0000255"
FT BINDING 69
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /ligand_note="high affinity"
FT /evidence="ECO:0000255"
FT BINDING 74
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /ligand_note="high affinity"
FT /evidence="ECO:0000255"
FT BINDING 83
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT BINDING 86
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT BINDING 87
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT BINDING 93
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000269|PubMed:12470658"
FT MOD_RES 51
FT /note="Citrulline; by PAD3"
FT /evidence="ECO:0000269|PubMed:18083705"
FT DISULFID 30..68
FT /evidence="ECO:0000269|PubMed:21377473"
FT DISULFID 81..99
FT /evidence="ECO:0000269|PubMed:21377473"
FT VARIANT 3
FT /note="R -> K (in dbSNP:rs36022742)"
FT /id="VAR_061047"
FT MUTAGEN 30
FT /note="C->A: Abolishes calcium binding; when associated
FT with Ala-68."
FT /evidence="ECO:0000269|PubMed:21377473"
FT MUTAGEN 68
FT /note="C->A: Abolishes calcium binding; when associated
FT with Ala-30."
FT /evidence="ECO:0000269|PubMed:21377473"
FT MUTAGEN 81
FT /note="C->A: Increases affinity for calcium; when
FT associated with Ala-99."
FT /evidence="ECO:0000269|PubMed:21377473"
FT MUTAGEN 99
FT /note="C->A: Increases affinity for calcium; when
FT associated with Ala-81."
FT /evidence="ECO:0000269|PubMed:21377473"
FT HELIX 4..20
FT /evidence="ECO:0007829|PDB:3NSO"
FT STRAND 22..24
FT /evidence="ECO:0007829|PDB:1KSO"
FT STRAND 28..30
FT /evidence="ECO:0007829|PDB:3NSL"
FT HELIX 31..41
FT /evidence="ECO:0007829|PDB:3NSO"
FT TURN 42..44
FT /evidence="ECO:0007829|PDB:3NSO"
FT TURN 49..51
FT /evidence="ECO:0007829|PDB:3NSK"
FT HELIX 52..64
FT /evidence="ECO:0007829|PDB:3NSO"
FT TURN 65..67
FT /evidence="ECO:0007829|PDB:3NSL"
FT STRAND 68..71
FT /evidence="ECO:0007829|PDB:3NSL"
FT HELIX 72..86
FT /evidence="ECO:0007829|PDB:3NSO"
FT HELIX 88..90
FT /evidence="ECO:0007829|PDB:3NSO"
SQ SEQUENCE 101 AA; 11713 MW; ABCAF4B7E5F2E0A1 CRC64;
MARPLEQAVA AIVCTFQEYA GRCGDKYKLC QAELKELLQK ELATWTPTEF RECDYNKFMS
VLDTNKDCEV DFVEYVRSLA CLCLYCHEYF KDCPSEPPCS Q
