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P50115

- S10A8_RAT

UniProt

P50115 - S10A8_RAT

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Protein
Protein S100-A8
Gene
S100a8, Mrp8
Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi17 – 171Zinc By similarity
Metal bindingi27 – 271Zinc By similarity
Metal bindingi83 – 831Zinc By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Calcium bindingi20 – 33141; low affinity Reviewed prediction
Add
BLAST
Calcium bindingi59 – 70122; high affinity Reviewed prediction
Add
BLAST

GO - Molecular functioni

  1. antioxidant activity Source: UniProtKB-KW
  2. arachidonic acid binding Source: InterPro
  3. calcium ion binding Source: InterPro
  4. zinc ion binding Source: InterPro
Complete GO annotation...

GO - Biological processi

  1. activation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
  2. acute inflammatory response Source: RGD
  3. autophagy Source: UniProtKB
  4. chronic inflammatory response Source: RGD
  5. inflammatory response Source: RGD
  6. innate immune response Source: UniProtKB-KW
  7. leukocyte migration involved in inflammatory response Source: UniProtKB
  8. neutrophil aggregation Source: UniProtKB
  9. neutrophil chemotaxis Source: UniProtKB
  10. positive regulation of inflammatory response Source: UniProtKB
  11. positive regulation of intrinsic apoptotic signaling pathway Source: UniProtKB
  12. response to ethanol Source: RGD
  13. response to lipopolysaccharide Source: RGD
  14. response to zinc ion Source: RGD
  15. wound healing Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Antimicrobial, Antioxidant

Keywords - Biological processi

Apoptosis, Autophagy, Chemotaxis, Immunity, Inflammatory response, Innate immunity

Keywords - Ligandi

Calcium, Metal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:S100a8
Synonyms:Mrp8
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Chromosome 2

Organism-specific databases

RGDi620265. S100a8.

Subcellular locationi

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.1 Publication

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB-SubCell
  2. cytoskeleton Source: UniProtKB-SubCell
  3. extracellular space Source: RGD
  4. plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Cytoskeleton, Membrane, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed1 Publication
Chaini2 – 8988Protein S100-A8
PRO_0000143995Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanine1 Publication
Modified residuei42 – 421S-nitrosocysteine By similarity

Keywords - PTMi

Acetylation, S-nitrosylation

Proteomic databases

PaxDbiP50115.
PRIDEiP50115.

Expressioni

Gene expression databases

GenevestigatoriP50115.

Interactioni

Subunit structurei

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.

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000015473.

Structurei

3D structure databases

ProteinModelPortaliP50115.
SMRiP50115. Positions 1-89.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini13 – 4836EF-hand 1
Add
BLAST
Domaini46 – 8136EF-hand 2
Add
BLAST

Sequence similaritiesi

Belongs to the S-100 family.
Contains 2 EF-hand domains.

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiNOG39611.
GeneTreeiENSGT00730000111352.
HOGENOMiHOG000246968.
HOVERGENiHBG001479.
InParanoidiP50115.
OMAiWNENALE.
OrthoDBiEOG76HQ48.
PhylomeDBiP50115.
TreeFamiTF332727.

Family and domain databases

Gene3Di1.10.238.10. 1 hit.
InterProiIPR011992. 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]
PANTHERiPTHR11639:SF5. PTHR11639:SF5. 1 hit.
PfamiPF01023. S_100. 1 hit.
[Graphical view]
PROSITEiPS00018. EF_HAND_1. 1 hit.
PS50222. EF_HAND_2. 1 hit.
PS00303. S100_CABP. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P50115-1 [UniParc]FASTAAdd to Basket

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MATELEKALS NVIEVYHNYS GIKGNHHALY RDDFRKMVTT ECPQFVQNKN   50
TESLFKELDV NSDNAINFEE FLVLVIRVGV AAHKDSHKE 89
Length:89
Mass (Da):10,239
Last modified:January 23, 2007 - v3
Checksum:i6AC1AFAF3429B01E
GO

Mass spectrometryi

Molecular mass is 10149±2 Da from positions 2 - 89. Determined by ESI. 1 Publication

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti73 – 731V → A in AAA41637. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
L18891 mRNA. Translation: AAA41637.1.
PIRiJN0685.
RefSeqiNP_446274.2. NM_053822.2.
XP_006232627.1. XM_006232565.1.
UniGeneiRn.31839.

Genome annotation databases

EnsembliENSRNOT00000015473; ENSRNOP00000015473; ENSRNOG00000011557.
GeneIDi116547.
KEGGirno:116547.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
L18891 mRNA. Translation: AAA41637.1 .
PIRi JN0685.
RefSeqi NP_446274.2. NM_053822.2.
XP_006232627.1. XM_006232565.1.
UniGenei Rn.31839.

3D structure databases

ProteinModelPortali P50115.
SMRi P50115. Positions 1-89.
ModBasei Search...

Protein-protein interaction databases

STRINGi 10116.ENSRNOP00000015473.

Proteomic databases

PaxDbi P50115.
PRIDEi P50115.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSRNOT00000015473 ; ENSRNOP00000015473 ; ENSRNOG00000011557 .
GeneIDi 116547.
KEGGi rno:116547.

Organism-specific databases

CTDi 6279.
RGDi 620265. S100a8.

Phylogenomic databases

eggNOGi NOG39611.
GeneTreei ENSGT00730000111352.
HOGENOMi HOG000246968.
HOVERGENi HBG001479.
InParanoidi P50115.
OMAi WNENALE.
OrthoDBi EOG76HQ48.
PhylomeDBi P50115.
TreeFami TF332727.

Miscellaneous databases

NextBioi 619165.
PROi P50115.

Gene expression databases

Genevestigatori P50115.

Family and domain databases

Gene3Di 1.10.238.10. 1 hit.
InterProi IPR011992. 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 ]
PANTHERi PTHR11639:SF5. PTHR11639:SF5. 1 hit.
Pfami PF01023. S_100. 1 hit.
[Graphical view ]
PROSITEi PS00018. EF_HAND_1. 1 hit.
PS50222. EF_HAND_2. 1 hit.
PS00303. S100_CABP. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  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.

Entry informationi

Entry nameiS10A8_RAT
AccessioniPrimary (citable) accession number: P50115
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: January 23, 2007
Last modified: May 14, 2014
This is version 112 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

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

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi