S10A9_RAT
ID S10A9_RAT Reviewed; 113 AA.
AC P50116; Q761U7;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Protein S100-A9;
DE AltName: Full=Calgranulin-B;
DE AltName: Full=Migration inhibitory factor-related protein 14;
DE Short=MRP-14;
DE Short=p14;
DE AltName: Full=Myeloid-related protein 14;
DE AltName: Full=S100 calcium-binding protein A9;
GN Name=S100a9; Synonyms=Mrp14;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=Lewis/N; TISSUE=Peritoneal cavity;
RX PubMed=8343166; DOI=10.1006/bbrc.1993.1895;
RA Imamichi T., Uchida I., Wahl S.M., McCartney-Francis N.;
RT "Expression and cloning of migration inhibitory factor-related protein
RT (MRP)8 and MRP14 in arthritis-susceptible rats.";
RL Biochem. Biophys. Res. Commun. 194:819-825(1993).
RN [2]
RP PROTEIN SEQUENCE OF 2-57; 62-65 AND 72-113, MASS SPECTROMETRY, ACETYLATION
RP AT ALA-2, AND METHYLATION AT HIS-107.
RC TISSUE=Spleen;
RX PubMed=9570842; DOI=10.1006/abio.1997.2601;
RA Raftery M.J., Geczy C.L.;
RT "Identification of posttranslational modifications and cDNA sequencing
RT errors in the rat S100 proteins MRP8 and 14 using electrospray ionization
RT mass spectrometry.";
RL Anal. Biochem. 258:285-292(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 3-113, PROTEIN SEQUENCE OF 11-25; 38-67;
RP 81-90 AND 94-112, FUNCTION, SUBUNIT, AND TISSUE SPECIFICITY.
RC STRAIN=Wistar; TISSUE=Macrophage, and Peritoneal cavity;
RX PubMed=15153104; DOI=10.1111/j.1432-1033.2004.04129.x;
RA Shibata F., Miyama K., Shinoda F., Mizumoto J., Takano K., Nakagawa H.;
RT "Fibroblast growth-stimulating activity of S100A9 (MRP-14).";
RL Eur. J. Biochem. 271:2137-2143(2004).
RN [4]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=21487906; DOI=10.1007/s10753-011-9330-8;
RA Koike A., Arai S., Yamada S., Nagae A., Saita N., Itoh H., Uemoto S.,
RA Totani M., Ikemoto M.;
RT "Dynamic mobility of immunological cells expressing S100A8 and S100A9 in
RT vivo: a variety of functional roles of the two proteins as regulators in
RT acute inflammatory reaction.";
RL Inflammation 35:409-419(2012).
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 (PubMed:15153104, PubMed:21487906). It can induce neutrophil
CC chemotaxis, adhesion, can increase the bactericidal activity of
CC neutrophils by promoting phagocytosis via activation of SYK, PI3K/AKT,
CC and ERK1/2 and can induce degranulation of neutrophils by a MAPK-
CC dependent mechanism (By similarity). Predominantly found as
CC calprotectin (S100A8/A9) which has a wide plethora of intra- and
CC extracellular functions (By similarity). The intracellular functions
CC include: facilitating leukocyte arachidonic acid trafficking and
CC metabolism, modulation of the tubulin-dependent cytoskeleton during
CC migration of phagocytes and activation of the neutrophilic NADPH-
CC oxidase (By similarity). Activates NADPH-oxidase by facilitating the
CC enzyme complex assembly at the cell membrane, transferring arachidonic
CC acid, an essential cofactor, to the enzyme complex and S100A8
CC contributes to the enzyme assembly by directly binding to NCF2/P67PHOX
CC (By similarity). The extracellular functions involve pro-inflammatory,
CC antimicrobial, oxidant-scavenging and apoptosis-inducing activities
CC (PubMed:21487906). Its pro-inflammatory activity includes recruitment
CC of leukocytes, promotion of cytokine and chemokine production, and
CC regulation of leukocyte adhesion and migration (By similarity). Acts as
CC an alarmin or a danger associated molecular pattern (DAMP) molecule and
CC stimulates innate immune cells via binding to pattern recognition
CC receptors such as Toll-like receptor 4 (TLR4) and receptor for advanced
CC glycation endproducts (AGER) (By similarity). Binding to TLR4 and AGER
CC activates the MAP-kinase and NF-kappa-B signaling pathways resulting in
CC the amplification of the pro-inflammatory cascade (By similarity). Has
CC antimicrobial activity towards bacteria and fungi and exerts its
CC antimicrobial activity probably via chelation of Zn(2+) which is
CC essential for microbial growth (By similarity). Can induce cell death
CC via autophagy and apoptosis and this occurs through the cross-talk of
CC mitochondria and lysosomes via reactive oxygen species (ROS) and the
CC process involves BNIP3 (By similarity). Can regulate neutrophil number
CC and apoptosis by an anti-apoptotic effect; regulates cell survival via
CC ITGAM/ITGB and TLR4 and a signaling mechanism involving MEK-ERK (By
CC similarity). Its role as an oxidant scavenger has a protective role in
CC preventing exaggerated tissue damage by scavenging oxidants (By
CC similarity). The iNOS-S100A8/A9 transnitrosylase complex is proposed to
CC direct selective inflammatory stimulus-dependent S-nitrosylation of
CC multiple targets such as GAPDH, NXA5, EZR, MSN and VIM by recognizing a
CC [IL]-x-C-x-x-[DE] motif (By similarity). {ECO:0000250|UniProtKB:P06702,
CC ECO:0000269|PubMed:15153104, ECO:0000269|PubMed:21487906}.
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:0000269|PubMed:21487906}; Peripheral membrane protein
CC {ECO:0000269|PubMed:21487906}. 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: Highly expressed at sites of inflammation.
CC {ECO:0000269|PubMed:15153104, ECO:0000269|PubMed:8343166}.
CC -!- PTM: Phosphorylated. Phosphorylation inhibits activation of tubulin
CC polymerization. {ECO:0000250|UniProtKB:P06702}.
CC -!- PTM: Methylation at His-107 by METTL9 reduces zinc-binding without
CC affecting heterodimerization with S100A8.
CC {ECO:0000250|UniProtKB:P31725}.
CC -!- MASS SPECTROMETRY: Mass=13069; Mass_error=2; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:9570842};
CC -!- SIMILARITY: Belongs to the S-100 family. {ECO:0000305}.
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DR EMBL; L18948; AAA18214.1; -; mRNA.
DR EMBL; AB118215; BAC82423.1; -; mRNA.
DR PIR; JN0686; JN0686.
DR RefSeq; NP_446039.1; NM_053587.1.
DR AlphaFoldDB; P50116; -.
DR SMR; P50116; -.
DR IntAct; P50116; 1.
DR STRING; 10116.ENSRNOP00000015351; -.
DR iPTMnet; P50116; -.
DR PhosphoSitePlus; P50116; -.
DR PaxDb; P50116; -.
DR PRIDE; P50116; -.
DR GeneID; 94195; -.
DR KEGG; rno:94195; -.
DR UCSC; RGD:620267; rat.
DR CTD; 6280; -.
DR RGD; 620267; S100a9.
DR eggNOG; ENOG502SA01; Eukaryota.
DR HOGENOM; CLU_138624_6_0_1; -.
DR InParanoid; P50116; -.
DR PhylomeDB; P50116; -.
DR TreeFam; TF332727; -.
DR Reactome; R-RNO-5668599; RHO GTPases Activate NADPH Oxidases.
DR Reactome; R-RNO-6798695; Neutrophil degranulation.
DR Reactome; R-RNO-6799990; Metal sequestration by antimicrobial proteins.
DR PRO; PR:P50116; -.
DR Proteomes; UP000002494; Unplaced.
DR Genevisible; P50116; RN.
DR GO; GO:0001533; C:cornified envelope; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0016209; F:antioxidant activity; IEA:UniProtKB-KW.
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:0031532; P:actin cytoskeleton reorganization; ISO:RGD.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; ISS:UniProtKB.
DR GO; GO:0061844; P:antimicrobial humoral immune response mediated by antimicrobial peptide; ISO:RGD.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0014002; P:astrocyte development; ISO:RGD.
DR GO; GO:0035425; P:autocrine signaling; IGI:ARUK-UCL.
DR GO; GO:0006914; P:autophagy; ISS:UniProtKB.
DR GO; GO:0002544; P:chronic inflammatory response; IEP:RGD.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0030595; P:leukocyte chemotaxis; ISO:RGD.
DR GO; GO:0002523; P:leukocyte migration involved in inflammatory response; ISS:UniProtKB.
DR GO; GO:0035821; P:modulation of process of another organism; ISO:RGD.
DR GO; GO:0070488; P:neutrophil aggregation; ISS:UniProtKB.
DR GO; GO:0030593; P:neutrophil chemotaxis; ISS:UniProtKB.
DR GO; GO:0018119; P:peptidyl-cysteine S-nitrosylation; ISO:RGD.
DR GO; GO:0035606; P:peptidyl-cysteine S-trans-nitrosylation; ISO:RGD.
DR GO; GO:0030194; P:positive regulation of blood coagulation; ISO:RGD.
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 GO; GO:0010976; P:positive regulation of neuron projection development; IDA:ParkinsonsUK-UCL.
DR GO; GO:0002793; P:positive regulation of peptide secretion; ISO:RGD.
DR GO; GO:0045113; P:regulation of integrin biosynthetic process; ISO:RGD.
DR GO; GO:0006417; P:regulation of translation; ISO:RGD.
DR GO; GO:0045471; P:response to ethanol; IEP:RGD.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEP:RGD.
DR GO; GO:0010043; P:response to zinc ion; IEP:RGD.
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 Acetylation; Antimicrobial; Antioxidant; Apoptosis; Autophagy; Calcium;
KW Cell membrane; Chemotaxis; Cytoplasm; Cytoskeleton;
KW Direct protein sequencing; Immunity; Inflammatory response;
KW Innate immunity; Membrane; Metal-binding; Methylation; Phosphoprotein;
KW Reference proteome; Repeat; Secreted; Zinc.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:9570842"
FT CHAIN 2..113
FT /note="Protein S100-A9"
FT /id="PRO_0000143999"
FT DOMAIN 13..48
FT /note="EF-hand 1"
FT /evidence="ECO:0000305"
FT DOMAIN 55..90
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 21
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P06702"
FT BINDING 24
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /ligand_note="low affinity"
FT /evidence="ECO:0000250|UniProtKB:P06702"
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:0000250|UniProtKB:P06702"
FT BINDING 31
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P06702"
FT BINDING 32
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /ligand_note="low affinity"
FT /evidence="ECO:0000250|UniProtKB:P06702"
FT BINDING 37
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /ligand_note="low affinity"
FT /evidence="ECO:0000250|UniProtKB:P06702"
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:0000250|UniProtKB:P06702"
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:0000250|UniProtKB:P06702"
FT BINDING 72
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /ligand_note="high affinity"
FT /evidence="ECO:0000250|UniProtKB:P06702"
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:0000250|UniProtKB:P06702"
FT BINDING 79
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /ligand_note="high affinity"
FT /evidence="ECO:0000250|UniProtKB:P06702"
FT BINDING 92
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P06702"
FT BINDING 96
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P06702"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000269|PubMed:9570842"
FT MOD_RES 107
FT /note="Pros-methylhistidine"
FT /evidence="ECO:0000269|PubMed:9570842"
FT CONFLICT 17
FT /note="I -> Q (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 24
FT /note="S -> C (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 106
FT /note="S -> R (in Ref. 1; AAA18214)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 113 AA; 13145 MW; 6C3A0044A7AEC4FA CRC64;
MAAKTGSQLE RSISTIINVF HQYSRKYGHP DTLNKAEFKE MVNKDLPNFL KREKRNENLL
RDIMEDLDTN QDNQLSFEEC MMLMGKLIFA CHEKLHENNP RGHDHSHGKG CGK
