S10A4_MOUSE
ID S10A4_MOUSE Reviewed; 101 AA.
AC P07091; P20066;
DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1988, sequence version 1.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=Protein S100-A4;
DE AltName: Full=Metastasin;
DE AltName: Full=Metastatic cell protein;
DE AltName: Full=PEL98;
DE AltName: Full=Placental calcium-binding protein;
DE AltName: Full=Protein 18A2;
DE AltName: Full=Protein Mts1;
DE AltName: Full=S100 calcium-binding protein A4;
GN Name=S100a4; Synonyms=Capl, Mts1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ;
RX PubMed=3628004; DOI=10.1093/nar/15.16.6677;
RA Jackson-Grusby L.L., Swiergiel J., Linzer D.I.H.;
RT "A growth-related mRNA in cultured mouse cells encodes a placental calcium
RT binding protein.";
RL Nucleic Acids Res. 15:6677-6690(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ;
RX PubMed=3162911; DOI=10.1093/oxfordjournals.jbchem.a122237;
RA Goto K., Endo H., Fujiyoshi T.;
RT "Cloning of the sequences expressed abundantly in established cell lines:
RT identification of a cDNA clone highly homologous to S-100, a calcium
RT binding protein.";
RL J. Biochem. 103:48-53(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2550322; DOI=10.1101/gad.3.7.1086;
RA Ebralidze A., Tulchinsky E., Grigorian M., Afanasyeva A., Senin V.,
RA Revazova E., Lukanidin E.;
RT "Isolation and characterization of a gene specifically expressed in
RT different metastatic cells and whose deduced gene product has a high degree
RT of homology to a Ca2+-binding protein family.";
RL Genes Dev. 3:1086-1093(1989).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Liver;
RX PubMed=2332170; DOI=10.1016/0378-1119(90)90305-b;
RA Tulchinsky E.M., Grigorian M.S., Ebralidze A.K., Milshina N.I.,
RA Lukanidin E.M.;
RT "Structure of gene mts1, transcribed in metastatic mouse tumor cells.";
RL Gene 87:219-223(1990).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-54.
RX PubMed=8423998;
RA Tulchinsky E., Kramerov D., Ford H.L., Reshetnyak E., Lukanidin E.,
RA Zain S.;
RT "Characterization of a positive regulatory element in the mts1 gene.";
RL Oncogene 8:79-86(1993).
RN [6]
RP FUNCTION, INTERACTION WITH MYH9, AND SUBCELLULAR LOCATION.
RX PubMed=8051043; DOI=10.1016/s0021-9258(17)32072-0;
RA Kriajevska M.V., Cardenas M.N., Grigorian M.S., Ambartsumian N.S.,
RA Georgiev G.P., Lukanidin E.M.;
RT "Non-muscle myosin heavy chain as a possible target for protein encoded by
RT metastasis-related mts-1 gene.";
RL J. Biol. Chem. 269:19679-19682(1994).
RN [7]
RP PROTEIN SEQUENCE OF 2-18 AND 41-48, CLEAVAGE OF INITIATOR METHIONINE,
RP ACETYLATION AT ALA-2, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Embryonic fibroblast;
RA Sumpton D.P., Sandilands E., Frame M.C., Bienvenut W.V.;
RL Submitted (MAR-2008) to UniProtKB.
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=20519440; DOI=10.1091/mbc.e09-07-0609;
RA Li Z.H., Dulyaninova N.G., House R.P., Almo S.C., Bresnick A.R.;
RT "S100A4 regulates macrophage chemotaxis.";
RL Mol. Biol. Cell 21:2598-2610(2010).
RN [9]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=20103644; DOI=10.1158/0008-5472.can-09-3220;
RA Grum-Schwensen B., Klingelhoefer J., Grigorian M., Almholt K.,
RA Nielsen B.S., Lukanidin E., Ambartsumian N.;
RT "Lung metastasis fails in MMTV-PyMT oncomice lacking S100A4 due to a T-cell
RT deficiency in primary tumors.";
RL Cancer Res. 70:936-947(2010).
CC -!- FUNCTION: Calcium-binding protein that plays a role in various cellular
CC processes including motility, angiogenesis, cell differentiation,
CC apoptosis, and autophagy (PubMed:20519440). Increases cell motility and
CC invasiveness by interacting with non-muscle myosin heavy chain (NMMHC)
CC IIA/MYH9 (PubMed:8051043). Mechanistically, promotes filament
CC depolymerization and increases the amount of soluble myosin-IIA,
CC resulting in the formation of stable protrusions facilitating
CC chemotaxis (PubMed:8051043). Modulates also the pro-apoptotic function
CC of TP53 by binding to its C-terminal transactivation domain within the
CC nucleus and reducing its protein levels (By similarity). Within the
CC extracellular space, stimulates cytokine production including
CC granulocyte colony-stimulating factor and CCL24 from T-lymphocytes
CC (PubMed:20103644). In addition, stimulates T-lymphocyte chemotaxis by
CC acting as a chemoattractant complex with PGLYRP1 that promotes
CC lymphocyte migration via CCR5 and CXCR3 receptors (By similarity).
CC {ECO:0000250|UniProtKB:P26447, ECO:0000269|PubMed:20103644,
CC ECO:0000269|PubMed:20519440, ECO:0000269|PubMed:8051043}.
CC -!- SUBUNIT: Homodimer. Interacts with PPFIBP1 in a calcium-dependent mode.
CC Interacts with PGLYRP1; this complex acts as a chemoattractant that
CC promotes lymphocyte movement. Interacts with MYH9; this interaction
CC increases cell motility. Interacts with Annexin 2/ANXA2. Interacts with
CC TP53; this interaction promotes TP53 degradation. Interacts with CCR5
CC and CXCR3. Interacts with FCGR3A; this interaction inhibits PKC-
CC dependent phosphorylation of FCGR3A. {ECO:0000250|UniProtKB:P26447}.
CC -!- INTERACTION:
CC P07091; P56565: S100a1; NbExp=6; IntAct=EBI-1544173, EBI-1544186;
CC P07091; P07091: S100a4; NbExp=4; IntAct=EBI-1544173, EBI-1544173;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P26447}. Nucleus
CC {ECO:0000250|UniProtKB:P26447}. Cytoplasm {ECO:0000269|PubMed:8051043}.
CC -!- TISSUE SPECIFICITY: Specifically expressed in different metastatic
CC cells.
CC -!- INDUCTION: The mRNA coding for this protein increases in abundance
CC after serum stimulation of quiescent mouse fibroblasts.
CC -!- DISRUPTION PHENOTYPE: Deletion mice are fertile, grow normally and
CC exhibit no overt abnormalities; however loss of S100A4 results in
CC impaired recruitment of macrophages to sites of inflammation in vivo
CC (PubMed:20519440). Mice also show decreased metastatic burden in lungs
CC of PyMT-induced mammary tumors which is associated with reduced vessel
CC density (PubMed:20103644). {ECO:0000269|PubMed:20103644,
CC ECO:0000269|PubMed:20519440}.
CC -!- SIMILARITY: Belongs to the S-100 family. {ECO:0000305}.
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DR EMBL; X05835; CAA29282.1; -; mRNA.
DR EMBL; D00208; BAA00148.1; -; mRNA.
DR EMBL; X16190; CAA34316.1; -; mRNA.
DR EMBL; M36578; AAA39749.1; -; Genomic_DNA.
DR EMBL; M36579; AAA39750.1; -; Genomic_DNA.
DR EMBL; X16094; CAA34224.1; -; Genomic_DNA.
DR CCDS; CCDS17538.1; -.
DR PIR; S06207; S06207.
DR RefSeq; NP_035441.1; NM_011311.2.
DR RefSeq; XP_006501240.1; XM_006501177.3.
DR RefSeq; XP_006501241.1; XM_006501178.2.
DR AlphaFoldDB; P07091; -.
DR BMRB; P07091; -.
DR SMR; P07091; -.
DR BioGRID; 203053; 4.
DR IntAct; P07091; 3.
DR STRING; 10090.ENSMUSP00000001046; -.
DR iPTMnet; P07091; -.
DR PhosphoSitePlus; P07091; -.
DR SwissPalm; P07091; -.
DR EPD; P07091; -.
DR jPOST; P07091; -.
DR PaxDb; P07091; -.
DR PeptideAtlas; P07091; -.
DR PRIDE; P07091; -.
DR ProteomicsDB; 255433; -.
DR Antibodypedia; 1551; 892 antibodies from 45 providers.
DR DNASU; 20198; -.
DR Ensembl; ENSMUST00000001046; ENSMUSP00000001046; ENSMUSG00000001020.
DR GeneID; 20198; -.
DR KEGG; mmu:20198; -.
DR UCSC; uc008qcz.2; mouse.
DR CTD; 6275; -.
DR MGI; MGI:1330282; S100a4.
DR VEuPathDB; HostDB:ENSMUSG00000001020; -.
DR eggNOG; ENOG502S4AU; Eukaryota.
DR GeneTree; ENSGT00940000161276; -.
DR InParanoid; P07091; -.
DR OMA; QDLPDKM; -.
DR OrthoDB; 1560865at2759; -.
DR TreeFam; TF332727; -.
DR BioGRID-ORCS; 20198; 1 hit in 73 CRISPR screens.
DR ChiTaRS; S100a4; mouse.
DR PRO; PR:P07091; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; P07091; protein.
DR Bgee; ENSMUSG00000001020; Expressed in lip and 78 other tissues.
DR ExpressionAtlas; P07091; baseline and differential.
DR Genevisible; P07091; MM.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0043005; C:neuron projection; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0003779; F:actin binding; ISO:MGI.
DR GO; GO:0005509; F:calcium ion binding; IDA:MGI.
DR GO; GO:0048306; F:calcium-dependent protein binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0050786; F:RAGE receptor binding; ISO:MGI.
DR GO; GO:0046914; F:transition metal ion binding; IEA:InterPro.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; ISO:MGI.
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; IPR028496; S100-A4.
DR InterPro; IPR001751; S100/CaBP7/8-like_CS.
DR InterPro; IPR013787; S100_Ca-bd_sub.
DR PANTHER; PTHR11639:SF51; PTHR11639:SF51; 1.
DR Pfam; PF01023; S_100; 1.
DR SMART; SM00054; EFh; 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 Acetylation; Calcium; Cytoplasm; Direct protein sequencing; Metal-binding;
KW Nucleus; Reference proteome; Repeat; Secreted.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.7"
FT CHAIN 2..101
FT /note="Protein S100-A4"
FT /id="PRO_0000143978"
FT DOMAIN 12..47
FT /note="EF-hand 1"
FT /evidence="ECO:0000305"
FT DOMAIN 50..85
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
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:0000305"
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:0000305"
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|PROSITE-ProRule:PRU00448"
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|PROSITE-ProRule:PRU00448"
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|PROSITE-ProRule:PRU00448"
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|PROSITE-ProRule:PRU00448"
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|PROSITE-ProRule:PRU00448"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000269|Ref.7"
FT MOD_RES 35
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P26447"
FT CONFLICT 47
FT /note="G -> GVSGSXFNGQ (in Ref. 5; CAA34224)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 101 AA; 11721 MW; 2302254B67A4C873 CRC64;
MARPLEEALD VIVSTFHKYS GKEGDKFKLN KTELKELLTR ELPSFLGKRT DEAAFQKVMS
NLDSNRDNEV DFQEYCVFLS CIAMMCNEFF EGCPDKEPRK K
