S10A9_BOVIN
ID S10A9_BOVIN Reviewed; 156 AA.
AC P28783; Q2NKV0;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2006, sequence version 3.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Protein S100-A9;
DE AltName: Full=BEE22;
DE AltName: Full=Calgranulin-B;
DE AltName: Full=Neutrophil cytosolic 23 kDa protein;
DE Short=p23;
DE AltName: Full=S100 calcium-binding protein A9;
GN Name=S100A9;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Testis;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP PROTEIN SEQUENCE OF 5-126.
RC TISSUE=Esophageal epithelium;
RX PubMed=8505358; DOI=10.1242/jcs.104.2.237;
RA Tang T.K., Hong T.-M., Lin C.-Y., Lai M.-L., Liu C.H.L., Lo H.-J.,
RA Wang M.-E., Chen L.B., Chen W.-T., Ip W., Lin D.C., Lin J.J.-C., Lin S.,
RA Sun T.-T., Wang E., Wang J.L., Wu R., Wu C.-W., Chien S.;
RT "Nuclear proteins of the bovine esophageal epithelium. I. Monoclonal
RT antibody W2 specifically reacts with condensed nuclei of differentiated
RT superficial cells.";
RL J. Cell Sci. 104:237-247(1993).
RN [3]
RP PROTEIN SEQUENCE OF 8-60.
RC TISSUE=Neutrophil;
RX PubMed=1610833; DOI=10.1021/bi00140a028;
RA Dianoux A.-C., Stasia M.-J., Garin J., Gagnon J., Vignais P.V.;
RT "The 23-kilodalton protein, a substrate of protein kinase C, in bovine
RT neutrophil cytosol is a member of the S100 family.";
RL Biochemistry 31:5898-5905(1992).
CC -!- FUNCTION: S100A9 is a calcium- and zinc-binding protein which plays a
CC prominent role in the regulation of inflammatory processes and immune
CC response. It can induce neutrophil chemotaxis, adhesion, can increase
CC the bactericidal activity of neutrophils by promoting phagocytosis via
CC activation of SYK, PI3K/AKT, and ERK1/2 and can induce degranulation of
CC neutrophils by a MAPK-dependent mechanism. Predominantly found as
CC calprotectin (S100A8/A9) which has a wide plethora of intra- and
CC extracellular functions. The intracellular functions include:
CC facilitating leukocyte arachidonic acid trafficking and metabolism,
CC modulation of the tubulin-dependent cytoskeleton during migration of
CC phagocytes and activation of the neutrophilic NADPH-oxidase. Activates
CC NADPH-oxidase by facilitating the enzyme complex assembly at the cell
CC membrane, transferring arachidonic acid, an essential cofactor, to the
CC enzyme complex and S100A8 contributes to the enzyme assembly by
CC directly binding to NCF2/P67PHOX. The extracellular functions involve
CC pro-inflammatory, antimicrobial, oxidant-scavenging and apoptosis-
CC inducing activities. Its pro-inflammatory activity includes recruitment
CC of leukocytes, promotion of cytokine and chemokine production, and
CC regulation of leukocyte adhesion and migration. Acts as an alarmin or a
CC danger associated molecular pattern (DAMP) molecule and stimulates
CC innate immune cells via binding to pattern recognition receptors such
CC as Toll-like receptor 4 (TLR4) and receptor for advanced glycation
CC endproducts (AGER). Binding to TLR4 and AGER activates the MAP-kinase
CC and NF-kappa-B signaling pathways resulting in the amplification of the
CC pro-inflammatory cascade. Has antimicrobial activity towards bacteria
CC and fungi and exerts its antimicrobial activity probably via chelation
CC of Zn(2+) which is essential for microbial growth. Can induce cell
CC death via autophagy and apoptosis and this occurs through the cross-
CC talk of mitochondria and lysosomes via reactive oxygen species (ROS)
CC and the process involves BNIP3. Can regulate neutrophil number and
CC apoptosis by an anti-apoptotic effect; regulates cell survival via
CC ITGAM/ITGB and TLR4 and a signaling mechanism involving MEK-ERK. Its
CC role as an oxidant scavenger has a protective role in preventing
CC exaggerated tissue damage by scavenging oxidants. The iNOS-S100A8/A9
CC transnitrosylase complex is proposed to direct selective inflammatory
CC stimulus-dependent S-nitrosylation of multiple targets such as GAPDH,
CC NXA5, EZR, MSN and VIM by recognizing a [IL]-x-C-x-x-[DE] motif.
CC {ECO:0000250|UniProtKB:P06702}.
CC -!- SUBUNIT: Homodimer. Preferentially exists as a heterodimer or
CC heterotetramer with S100A8 known as calprotectin (S100A8/A9) (By
CC similarity). S100A9 interacts with ATP2A2 (By similarity). S100A9
CC interacts with AGER, and with the heterodimeric complex formed by TLR4
CC and LY96 in the presence of calcium and/or zinc ions. S100A9 binds
CC quinoline-3-carboxamides in the presence of calcium and/or zinc ions.
CC S100A9 interacts with amyloid-beta protein 40. Calprotectin (S100A8/9)
CC interacts with CEACAM3 and tubulin filaments in a calcium-dependent
CC manner. Heterotetrameric calprotectin (S100A8/A9) interacts with ANXA6
CC and associates with tubulin filaments in activated monocytes.
CC Calprotectin (S100A8/9) interacts with NCF2/P67PHOX, RAC1, RAC2, CYBA
CC and CYBB. Calprotectin (S100A8/9) interacts with NOS2 to form the iNOS-
CC S100A8/A9 transnitrosylase complex; induced by LDL(ox) (By similarity).
CC {ECO:0000250|UniProtKB:P06702, ECO:0000250|UniProtKB:P31725}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P06702}.
CC Cytoplasm {ECO:0000250|UniProtKB:P06702}. Cytoplasm, cytoskeleton
CC {ECO:0000250|UniProtKB:P06702}. Cell membrane
CC {ECO:0000250|UniProtKB:P06702}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P06702}. Note=Predominantly localized in the
CC cytoplasm. Upon elevation of the intracellular calcium level,
CC translocated from the cytoplasm to the cytoskeleton and the cell
CC membrane. Upon neutrophil activation or endothelial adhesion of
CC monocytes, is secreted via a microtubule-mediated, alternative pathway.
CC {ECO:0000250|UniProtKB:P06702}.
CC -!- TISSUE SPECIFICITY: Found essentially in phagocytic cells.
CC -!- PTM: Phosphorylated. Phosphorylation inhibits activation of tubulin
CC polymerization. {ECO:0000250|UniProtKB:P06702}.
CC -!- PTM: Methylation at His-106 by METTL9 reduces zinc-binding without
CC affecting heterodimerization with S100A8.
CC {ECO:0000250|UniProtKB:P31725}.
CC -!- SIMILARITY: Belongs to the S-100 family. {ECO:0000305}.
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DR EMBL; BC111626; AAI11627.1; -; mRNA.
DR PIR; B22309; A42628.
DR RefSeq; NP_001039793.1; NM_001046328.2.
DR AlphaFoldDB; P28783; -.
DR SMR; P28783; -.
DR BioGRID; 189176; 1.
DR STRING; 9913.ENSBTAP00000008523; -.
DR PaxDb; P28783; -.
DR PeptideAtlas; P28783; -.
DR PRIDE; P28783; -.
DR GeneID; 532569; -.
DR KEGG; bta:532569; -.
DR CTD; 6280; -.
DR eggNOG; ENOG502SA01; Eukaryota.
DR InParanoid; P28783; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016209; F:antioxidant activity; IEA:UniProtKB-KW.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; ISS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0006914; P:autophagy; ISS:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0002523; P:leukocyte migration involved in inflammatory response; ISS:UniProtKB.
DR GO; GO:0070488; P:neutrophil aggregation; ISS:UniProtKB.
DR GO; GO:0030593; P:neutrophil chemotaxis; ISS:UniProtKB.
DR GO; GO:0050729; P:positive regulation of inflammatory response; ISS:UniProtKB.
DR GO; GO:2001244; P:positive regulation of intrinsic apoptotic signaling pathway; ISS:UniProtKB.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR001751; S100/CaBP7/8-like_CS.
DR InterPro; IPR013787; S100_Ca-bd_sub.
DR Pfam; PF01023; S_100; 1.
DR SMART; SM00054; EFh; 1.
DR SMART; SM01394; S_100; 1.
DR SUPFAM; SSF47473; SSF47473; 1.
DR PROSITE; PS50222; EF_HAND_2; 1.
DR PROSITE; PS00303; S100_CABP; 1.
PE 1: Evidence at protein level;
KW Antimicrobial; Antioxidant; Apoptosis; Autophagy; Calcium; Cell membrane;
KW Chemotaxis; Cytoplasm; Cytoskeleton; Direct protein sequencing; Immunity;
KW Inflammatory response; Innate immunity; Membrane; Metal-binding;
KW Methylation; Phosphoprotein; Reference proteome; Repeat; Secreted; Zinc.
FT CHAIN 1..156
FT /note="Protein S100-A9"
FT /id="PRO_0000143996"
FT DOMAIN 16..51
FT /note="EF-hand 1"
FT /evidence="ECO:0000305"
FT DOMAIN 54..89
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REGION 94..156
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 138..156
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 20
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P06702"
FT BINDING 23
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P06702"
FT BINDING 26
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P06702"
FT BINDING 28
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P06702"
FT BINDING 30
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P06702"
FT BINDING 31
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P06702"
FT BINDING 36
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P06702"
FT BINDING 67
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P06702"
FT BINDING 69
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P06702"
FT BINDING 71
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P06702"
FT BINDING 73
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P06702"
FT BINDING 78
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P06702"
FT BINDING 91
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P06702"
FT BINDING 95
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P06702"
FT MOD_RES 106
FT /note="Pros-methylhistidine"
FT /evidence="ECO:0000250|UniProtKB:P50116"
FT CONFLICT 113..121
FT /note="Missing (in Ref. 1; AAI11627)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 156 AA; 17114 MW; 4FE83C862297BA64 CRC64;
MEDKMSQMES SIETIINIFH QYSVRLGHYD TLIQKEFKQL VQKELPNFLK KQKKNEAAIN
EIMEDLDTNV DKQLSFEEFI MLVARLTVAS HEEMHNTAPP GQGHRHGPGY GKGGSGSCSG
QGSPDQGSHD LGSHGHGHGH SHGGHGHSHG GHGHSH
