S10A8_RAT
ID S10A8_RAT Reviewed; 89 AA.
AC P50115;
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-A8;
DE AltName: Full=Calgranulin-A;
DE AltName: Full=Migration inhibitory factor-related protein 8;
DE Short=MRP-8;
DE Short=p8;
DE AltName: Full=S100 calcium-binding protein A8;
GN Name=S100a8; Synonyms=Mrp8;
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].
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 2-89, MASS SPECTROMETRY, AND ACETYLATION AT ALA-2.
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 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: S100A8 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 and adhesion.
CC Predominantly found as calprotectin (S100A8/A9) which has a wide
CC plethora of intra- and extracellular functions. The intracellular
CC functions include: facilitating leukocyte arachidonic acid trafficking
CC and metabolism, modulation of the tubulin-dependent cytoskeleton during
CC migration of phagocytes and activation of the neutrophilic NADPH-
CC oxidase. Activates NADPH-oxidase by facilitating the enzyme complex
CC assembly at the cell membrane, transferring arachidonic acid, an
CC essential cofactor, to the enzyme complex and S100A8 contributes to the
CC enzyme assembly by directly binding to NCF2/P67PHOX. The extracellular
CC functions involve pro-inflammatory, antimicrobial, oxidant-scavenging
CC and apoptosis-inducing activities. Its pro-inflammatory activity
CC includes recruitment of leukocytes, promotion of cytokine and chemokine
CC production, and regulation of leukocyte adhesion and migration. 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). Binding to TLR4 and AGER activates the
CC MAP-kinase and NF-kappa-B signaling pathways resulting in the
CC amplification of the pro-inflammatory cascade. Has antimicrobial
CC activity towards bacteria and fungi and exerts its antimicrobial
CC activity probably via chelation of Zn(2+) which is essential for
CC microbial growth. Can induce cell death via autophagy and apoptosis and
CC this occurs through the cross-talk of mitochondria and lysosomes via
CC reactive oxygen species (ROS) and the process involves BNIP3. Can
CC regulate neutrophil number and apoptosis by an anti-apoptotic effect;
CC regulates cell survival via ITGAM/ITGB and TLR4 and a signaling
CC mechanism involving MEK-ERK. Its role as an oxidant scavenger has a
CC protective role in preventing exaggerated tissue damage by scavenging
CC oxidants. The iNOS-S100A8/A9 transnitrosylase complex is proposed to
CC direct selective inflammatory stimulus-dependent S-nitrosylation of
CC multiple targets such as GAPDH, ANXA5, EZR, MSN and VIM by recognizing
CC a [IL]-x-C-x-x-[DE] motif; S100A8 seems to contribute to S-
CC nitrosylation site selectivity (By similarity).
CC {ECO:0000250|UniProtKB:P05109, ECO:0000269|PubMed:21487906}.
CC -!- SUBUNIT: Homodimer. Preferentially exists as a heterodimer or
CC heterotetramer with S100A9 known as calprotectin (S100A8/A9). S100A8
CC interacts with AGER, ATP2A2 and with the heterodimeric complex formed
CC by TLR4 and LY96. Calprotectin (S100A8/9) interacts with CEACAM3 and
CC tubulin filaments in a calcium-dependent manner. Heterotetrameric
CC calprotectin (S100A8/A9) interacts with ANXA6 and associates with
CC tubulin filaments in activated monocytes. S100A8 and calprotectin
CC (S100A8/9) interact with NCF2/P67PHOX, RAC1 and RAC2. Calprotectin
CC (S100A8/9) interacts with CYBA and CYBB (By similarity). Calprotectin
CC (S100A8/9) interacts with NOS2 to form the iNOS-S100A8/A9
CC transnitrosylase complex (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:P05109}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}. Cytoplasm
CC {ECO:0000269|PubMed:21487906}. Cytoplasm, cytoskeleton {ECO:0000250}.
CC Cell membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}.
CC Note=Predominantly localized in the cytoplasm. Upon elevation of the
CC intracellular calcium level, translocated from the cytoplasm to the
CC cytoskeleton and the cell membrane. Upon neutrophil activation or
CC endothelial adhesion of monocytes, is secreted via a microtubule-
CC mediated, alternative pathway (By similarity). {ECO:0000250}.
CC -!- MASS SPECTROMETRY: Mass=10149; Mass_error=2; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:9570842};
CC -!- MISCELLANEOUS: Binds two calcium ions per molecule with an affinity
CC similar to that of the S100 proteins. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the S-100 family. {ECO:0000305}.
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DR EMBL; L18891; AAA41637.1; -; mRNA.
DR PIR; JN0685; JN0685.
DR RefSeq; NP_446274.2; NM_053822.2.
DR RefSeq; XP_006232627.1; XM_006232565.3.
DR AlphaFoldDB; P50115; -.
DR SMR; P50115; -.
DR STRING; 10116.ENSRNOP00000015473; -.
DR iPTMnet; P50115; -.
DR PaxDb; P50115; -.
DR PRIDE; P50115; -.
DR Ensembl; ENSRNOT00000015473; ENSRNOP00000015473; ENSRNOG00000011557.
DR GeneID; 116547; -.
DR KEGG; rno:116547; -.
DR CTD; 6279; -.
DR RGD; 620265; S100a8.
DR eggNOG; ENOG502SA01; Eukaryota.
DR GeneTree; ENSGT00910000144329; -.
DR HOGENOM; CLU_138624_6_0_1; -.
DR InParanoid; P50115; -.
DR OMA; YHKYSLE; -.
DR OrthoDB; 1613717at2759; -.
DR PhylomeDB; P50115; -.
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:P50115; -.
DR Proteomes; UP000002494; Chromosome 2.
DR Bgee; ENSRNOG00000011557; Expressed in thymus and 17 other tissues.
DR Genevisible; P50115; RN.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0045111; C:intermediate filament cytoskeleton; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016209; F:antioxidant activity; IEA:UniProtKB-KW.
DR GO; GO:0050544; F:arachidonic acid binding; IEA:InterPro.
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:0008017; F:microtubule binding; IEA:InterPro.
DR GO; GO:0050786; F:RAGE receptor binding; IEA:InterPro.
DR GO; GO:0035662; F:Toll-like receptor 4 binding; IEA:InterPro.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; ISS:UniProtKB.
DR GO; GO:0002526; P:acute inflammatory response; IEP: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:0006954; P:inflammatory response; NAS:RGD.
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:0018119; P:peptidyl-cysteine S-nitrosylation; 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:0002793; P:positive regulation of peptide secretion; 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 GO; GO:0042060; P:wound healing; IEP:RGD.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR001751; S100/CaBP7/8-like_CS.
DR InterPro; IPR013787; S100_Ca-bd_sub.
DR InterPro; IPR028474; S100A8.
DR PANTHER; PTHR11639:SF5; PTHR11639:SF5; 1.
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 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; Reference proteome; Repeat;
KW S-nitrosylation; Secreted; Zinc.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:9570842"
FT CHAIN 2..89
FT /note="Protein S100-A8"
FT /id="PRO_0000143995"
FT DOMAIN 13..48
FT /note="EF-hand 1"
FT /evidence="ECO:0000305"
FT DOMAIN 46..81
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 17
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 27
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
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 59
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 61
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 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 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 83
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000269|PubMed:9570842"
FT MOD_RES 42
FT /note="S-nitrosocysteine"
FT /evidence="ECO:0000250|UniProtKB:P05109"
FT CONFLICT 73
FT /note="V -> A (in Ref. 1; AAA41637)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 89 AA; 10239 MW; 6AC1AFAF3429B01E CRC64;
MATELEKALS NVIEVYHNYS GIKGNHHALY RDDFRKMVTT ECPQFVQNKN TESLFKELDV
NSDNAINFEE FLVLVIRVGV AAHKDSHKE
