Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P50115 (S10A8_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 111. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Protein S100-A8
Alternative name(s):
Calgranulin-A
Migration inhibitory factor-related protein 8
Short name=MRP-8
Short name=p8
S100 calcium-binding protein A8
Gene names
Name:S100a8
Synonyms:Mrp8
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length89 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

S100A8 is a calcium- and zinc-binding protein which plays a prominent role in the regulation of inflammatory processes and immune response. It can induce neutrophil chemotaxis and adhesion. Predominantly found as calprotectin (S100A8/A9) which has a wide plethora of intra- and extracellular functions. The intracellular functions include: facilitating leukocyte arachidonic acid trafficking and metabolism, modulation of the tubulin-dependent cytoskeleton during migration of phagocytes and activation of the neutrophilic NADPH-oxidase. Activates NADPH-oxidase by facilitating the enzyme complex assembly at the cell membrane, transferring arachidonic acid, an essential cofactor, to the enzyme complex and S100A8 contributes to the enzyme assembly by directly binding to NCF2/P67PHOX. The extracellular functions involve proinfammatory, antimicrobial, oxidant-scavenging and apoptosis-inducing activities. Its proinflammatory activity includes recruitment of leukocytes, promotion of cytokine and chemokine production, and regulation of leukocyte adhesion and migration. Acts as an alarmin or a danger associated molecular pattern (DAMP) molecule and stimulates innate immune cells via binding to pattern recognition receptors such as Toll-like receptor 4 (TLR4) and receptor for advanced glycation endproducts (AGER). Binding to TLR4 and AGER activates the MAP-kinase and NF-kappa-B signaling pathways resulting in the amplification of the proinflammatory cascade. Has antimicrobial activity towards bacteria and fungi and exerts its antimicrobial activity probably via chelation of Zn2+ which is essential for microbial growth. Can induce cell death via autophagy and apoptosis and this occurs through the cross-talk of mitochondria and lysosomes via reactive oxygen species (ROS) and the process involves BNIP3. Can regulate neutrophil number and apoptosis by an anti-apoptotic effect; regulates cell survival via ITGAM/ITGB and TLR4 and a signaling mechanism involving MEK-ERK. Its role as an oxidant scavenger has a protective role in preventing exaggerated tissue damage by scavenging oxidants. Ref.3

Subunit structure

Homodimer. Preferentially exists as a heterodimer or heterotetramer with S100A9 known as calprotectin (S100A8/A9). S100A8 interacts with AGER, ATP2A2 and with the heterodimeric complex formed by TLR4 and LY96. Calprotectin (S100A8/9) interacts with CEACAM3 and tubulin filaments in a calcium-dependent manner. Heterotetrameric calprotectin (S100A8/A9) interacts with ANXA6 and associates with tubulin filaments in activated monocytes. S100A8 and calprotectin (S100A8/9) interact with NCF2/P67PHOX, RAC1 and RAC2. Calprotectin (S100A8/9) interacts with CYBA and CYBB By similarity.

Subcellular location

Secreted By similarity. Cytoplasm. Cytoplasmcytoskeleton By similarity. Cell membrane; Peripheral membrane protein By similarity. Note: Predominantly localized in the cytoplasm. Upon elevation of the intracellular calcium level, translocated from the cytoplasm to the cytoskeleton and the cell membrane. Upon neutrophil activation or endothelial adhesion of monocytes, is secreted via a microtubule-mediated, alternative pathway By similarity. Ref.3

Miscellaneous

Binds two calcium ions per molecule with an affinity similar to that of the S100 proteins By similarity.

Sequence similarities

Belongs to the S-100 family.

Contains 2 EF-hand domains.

Mass spectrometry

Molecular mass is 10149±2 Da from positions 2 - 89. Determined by ESI. Ref.2

Ontologies

Keywords
   Biological processApoptosis
Autophagy
Chemotaxis
Immunity
Inflammatory response
Innate immunity
   Cellular componentCell membrane
Cytoplasm
Cytoskeleton
Membrane
Secreted
   DomainRepeat
   LigandCalcium
Metal-binding
Zinc
   Molecular functionAntimicrobial
Antioxidant
   PTMAcetylation
S-nitrosylation
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processactivation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

acute inflammatory response

Inferred from expression pattern PubMed 15221771. Source: RGD

autophagy

Inferred from sequence or structural similarity. Source: UniProtKB

chronic inflammatory response

Inferred from expression pattern Ref.1. Source: RGD

inflammatory response

Non-traceable author statement Ref.2. Source: RGD

innate immune response

Inferred from electronic annotation. Source: UniProtKB-KW

leukocyte migration involved in inflammatory response

Inferred from sequence or structural similarity. Source: UniProtKB

neutrophil aggregation

Inferred from sequence or structural similarity. Source: UniProtKB

neutrophil chemotaxis

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of inflammatory response

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of intrinsic apoptotic signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

response to ethanol

Inferred from expression pattern PubMed 17207109. Source: RGD

response to lipopolysaccharide

Inferred from expression pattern PubMed 17207109. Source: RGD

response to zinc ion

Inferred from expression pattern PubMed 19111725. Source: RGD

wound healing

Inferred from expression pattern PubMed 15943814. Source: RGD

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytoskeleton

Inferred from electronic annotation. Source: UniProtKB-SubCell

extracellular space

Inferred from direct assay PubMed 15221771. Source: RGD

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionantioxidant activity

Inferred from electronic annotation. Source: UniProtKB-KW

arachidonic acid binding

Inferred from electronic annotation. Source: InterPro

calcium ion binding

Inferred from electronic annotation. Source: InterPro

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.2
Chain2 – 8988Protein S100-A8
PRO_0000143995

Regions

Domain13 – 4836EF-hand 1
Domain46 – 8136EF-hand 2
Calcium binding20 – 33141; low affinity Potential
Calcium binding59 – 70122; high affinity Potential

Sites

Metal binding171Zinc By similarity
Metal binding271Zinc By similarity
Metal binding831Zinc By similarity

Amino acid modifications

Modified residue21N-acetylalanine Ref.2
Modified residue421S-nitrosocysteine By similarity

Experimental info

Sequence conflict731V → A in AAA41637. Ref.1

Sequences

Sequence LengthMass (Da)Tools
P50115 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: 6AC1AFAF3429B01E

FASTA8910,239
        10         20         30         40         50         60 
MATELEKALS NVIEVYHNYS GIKGNHHALY RDDFRKMVTT ECPQFVQNKN TESLFKELDV 

        70         80 
NSDNAINFEE FLVLVIRVGV AAHKDSHKE 

« Hide

References

[1]"Expression and cloning of migration inhibitory factor-related protein (MRP)8 and MRP14 in arthritis-susceptible rats."
Imamichi T., Uchida I., Wahl S.M., McCartney-Francis N.
Biochem. Biophys. Res. Commun. 194:819-825(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: Lewis/N.
Tissue: Peritoneal cavity.
[2]"Identification of posttranslational modifications and cDNA sequencing errors in the rat S100 proteins MRP8 and 14 using electrospray ionization mass spectrometry."
Raftery M.J., Geczy C.L.
Anal. Biochem. 258:285-292(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-89, MASS SPECTROMETRY, ACETYLATION AT ALA-2.
Tissue: Spleen.
[3]"Dynamic mobility of immunological cells expressing S100A8 and S100A9 in vivo: a variety of functional roles of the two proteins as regulators in acute inflammatory reaction."
Koike A., Arai S., Yamada S., Nagae A., Saita N., Itoh H., Uemoto S., Totani M., Ikemoto M.
Inflammation 35:409-419(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L18891 mRNA. Translation: AAA41637.1.
PIRJN0685.
RefSeqNP_446274.2. NM_053822.2.
XP_006232627.1. XM_006232565.1.
UniGeneRn.31839.

3D structure databases

ProteinModelPortalP50115.
SMRP50115. Positions 1-89.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING10116.ENSRNOP00000015473.

Proteomic databases

PaxDbP50115.
PRIDEP50115.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000015473; ENSRNOP00000015473; ENSRNOG00000011557.
GeneID116547.
KEGGrno:116547.

Organism-specific databases

CTD6279.
RGD620265. S100a8.

Phylogenomic databases

eggNOGNOG39611.
GeneTreeENSGT00730000111352.
HOGENOMHOG000246968.
HOVERGENHBG001479.
InParanoidP50115.
OMADTWFKEL.
OrthoDBEOG76HQ48.
PhylomeDBP50115.
TreeFamTF332727.

Gene expression databases

GenevestigatorP50115.

Family and domain databases

Gene3D1.10.238.10. 1 hit.
InterProIPR011992. EF-hand-dom_pair.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
IPR001751. S100/CaBP-9k_CS.
IPR013787. S100_Ca-bd_sub.
IPR028474. S100A8.
[Graphical view]
PANTHERPTHR11639:SF5. PTHR11639:SF5. 1 hit.
PfamPF01023. S_100. 1 hit.
[Graphical view]
PROSITEPS00018. EF_HAND_1. 1 hit.
PS50222. EF_HAND_2. 1 hit.
PS00303. S100_CABP. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio619165.
PROP50115.

Entry information

Entry nameS10A8_RAT
AccessionPrimary (citable) accession number: P50115
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: January 23, 2007
Last modified: April 16, 2014
This is version 111 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families