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P05109 (S10A8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 155. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Protein S100-A8
Alternative name(s):
Calgranulin-A
Calprotectin L1L subunit
Cystic fibrosis antigen
Short name=CFAG
Leukocyte L1 complex light chain
Migration inhibitory factor-related protein 8
Short name=MRP-8
Short name=p8
S100 calcium-binding protein A8
Urinary stone protein band A

Cleaved into the following chain:

  1. Protein S100-A8, N-terminally processed
Gene names
Name:S100A8
Synonyms:CAGA, CFAG, MRP8
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length93 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. Can act as a potent amplifier of inflammation in autoimmunity as well as in cancer development and tumor spread. Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 Ref.28 Ref.29 Ref.31 Ref.36 Ref.39 Ref.40

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 By similarity. 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. Ref.17 Ref.18 Ref.20 Ref.22 Ref.23 Ref.24 Ref.29 Ref.39 Ref.42

Subcellular location

Secreted. Cytoplasm. Cytoplasmcytoskeleton. Cell membrane; Peripheral membrane protein. 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. Ref.17 Ref.21 Ref.24 Ref.36 Ref.39

Tissue specificity

Calprotectin (S100A8/9) is predominantly expressed in myeloid cells. Except for inflammatory conditions, the expression is restricted to a specific stage of myeloid differentiation since both proteins are expressed in circulating neutrophils and monocytes but are absent in normal tissue macrophages and lymphocytes. Under chronic inflammatory conditions, such as psoriasis and malignant disorders, also expressed in the epidermis. Found in high concentrations at local sites of inflammation or in the serum of patients with inflammatory diseases such as rheumatoid, cystic fibrosis, inflammatory bowel disease, Crohn's disease, giant cell arteritis, cystic fibrosis, Sjogren's syndrome, systemic lupus erythematosus, and progressive systemic sclerosis. Involved in the formation and deposition of amyloids in the aging prostate known as corpora amylacea inclusions. Strongly up-regulated in many tumors, including gastric, esophageal, colon, pancreatic, bladder, ovarian, thyroid, breast and skin cancers. Ref.17 Ref.21

Miscellaneous

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

Sequence similarities

Belongs to the S-100 family.

Contains 2 EF-hand domains.

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
   PTMS-nitrosylation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processactivation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from direct assay Ref.31. Source: UniProtKB

acute inflammatory response

Inferred from electronic annotation. Source: Ensembl

autophagy

Inferred from direct assay Ref.31. Source: UniProtKB

chemokine production

Traceable author statement Ref.37. Source: UniProtKB

chronic inflammatory response

Inferred from electronic annotation. Source: Ensembl

cytokine production

Traceable author statement Ref.37. Source: UniProtKB

defense response to bacterium

Traceable author statement Ref.37. Source: UniProtKB

defense response to fungus

Traceable author statement Ref.37. Source: UniProtKB

inflammatory response

Traceable author statement Ref.2. Source: ProtInc

innate immune response

Inferred from electronic annotation. Source: UniProtKB-KW

leukocyte migration involved in inflammatory response

Inferred from direct assay Ref.19. Source: UniProtKB

neutrophil aggregation

Inferred from direct assay Ref.19. Source: UniProtKB

neutrophil chemotaxis

Inferred from direct assay Ref.19. Source: UniProtKB

positive regulation of NF-kappaB transcription factor activity

Traceable author statement Ref.37. Source: UniProtKB

positive regulation of cell growth

Traceable author statement Ref.37. Source: UniProtKB

positive regulation of inflammatory response

Inferred from direct assay Ref.19. Source: UniProtKB

positive regulation of intrinsic apoptotic signaling pathway

Inferred from direct assay Ref.31. Source: UniProtKB

regulation of cytoskeleton organization

Traceable author statement Ref.37. Source: UniProtKB

response to ethanol

Inferred from electronic annotation. Source: Ensembl

response to lipopolysaccharide

Inferred from electronic annotation. Source: Ensembl

response to zinc ion

Inferred from electronic annotation. Source: Ensembl

sequestering of zinc ion

Traceable author statement Ref.37. Source: UniProtKB

wound healing

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcytoskeleton

Traceable author statement Ref.37. Source: UniProtKB

cytosol

Traceable author statement Ref.37. Source: UniProtKB

extracellular region

Traceable author statement Ref.37. Source: UniProtKB

extracellular space

Inferred from direct assay PubMed 22664934. Source: UniProt

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867PubMed 19199708. Source: UniProt

plasma membrane

Traceable author statement Ref.37. Source: UniProtKB

   Molecular_functionRAGE receptor binding

Traceable author statement Ref.37. Source: UniProtKB

Toll-like receptor 4 binding

Traceable author statement Ref.37. Source: UniProtKB

arachidonic acid binding

Traceable author statement Ref.37. Source: UniProtKB

calcium ion binding

Traceable author statement Ref.37. Source: UniProtKB

microtubule binding

Traceable author statement Ref.37. Source: UniProtKB

zinc ion binding

Traceable author statement Ref.37. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

S100A9P067023EBI-355281,EBI-1055001

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 9393Protein S100-A8
PRO_0000143993
Initiator methionine11Removed; alternate By similarity
Chain2 – 9392Protein S100-A8, N-terminally processed
PRO_0000421773

Regions

Domain12 – 4736EF-hand 1
Domain46 – 8136EF-hand 2
Calcium binding20 – 33141; low affinity
Calcium binding59 – 70122; high affinity

Sites

Metal binding171Zinc Probable
Metal binding271Zinc Probable
Metal binding831Zinc Probable
Metal binding871Zinc Probable

Amino acid modifications

Modified residue421S-nitrosocysteine Ref.25

Experimental info

Mutagenesis421C → A: Loss of antifungal activity. Ref.28
Sequence conflict80 – 9314VAAHK…ESHKE → WQPTKKAMKKATKSS in CAA68390. Ref.1

Secondary structure

............... 93
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P05109 [UniParc].

Last modified January 1, 1988. Version 1.
Checksum: 78F589140B9CE166

FASTA9310,835
        10         20         30         40         50         60 
MLTELEKALN SIIDVYHKYS LIKGNFHAVY RDDLKKLLET ECPQYIRKKG ADVWFKELDI 

        70         80         90 
NTDGAVNFQE FLILVIKMGV AAHKKSHEES HKE 

« Hide

References

« Hide 'large scale' references
[1]"A clue to the basic defect in cystic fibrosis from cloning the CF antigen gene."
Dorin J.R., Novak M., Hill R.E., Brock D.J.H., Secher D.S., van Heyningen V.
Nature 326:614-617(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Two calcium-binding proteins in infiltrate macrophages of rheumatoid arthritis."
Odink K., Cerletti N., Bruggen J., Clerc R.G., Tarcsay L., Zwaldo G., Gerhards G., Schlegel R., Sorg C.
Nature 330:80-82(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"Cloning and expression of two human genes encoding calcium-binding proteins that are regulated during myeloid differentiation."
Lagasse E., Clerc R.G.
Mol. Cell. Biol. 8:2402-2410(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"The calcium-binding protein MRP-8 is produced by human pulmonary tumor cells."
Schaefer T., Sachse G.E., Gassen H.G.
Biol. Chem. Hoppe-Seyler 372:1-4(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 1-30.
[5]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Tongue.
[6]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[7]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[8]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Skeletal muscle.
[11]"Host-parasite interaction in human onchocerciasis: identification and sequence analysis of a novel human calgranulin."
Marti T., Erttmann K.D., Gallin M.Y.
Biochem. Biophys. Res. Commun. 221:454-458(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 1-19; 24-35 AND 63-89.
[12]"In vitro antimicrobial activity of the human neutrophil cytosolic S-100 protein complex, calprotectin, against Capnocytophaga sputigena."
Miyasaki K.T., Bodeau A.L., Murthy A.R., Lehrer R.I.
J. Dent. Res. 72:517-523(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 1-27.
[13]"Translocation of a small cytosolic calcium-binding protein (MRP-8) to plasma membrane correlates with human neutrophil activation."
Lemarchand P., Vaglio M., Mauel J., Markert M.
J. Biol. Chem. 267:19379-19382(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 1-25.
Tissue: Neutrophil.
[14]"Calprotectin-like protein is related to soluble organic matrix in calcium oxalate urinary stone."
Umekawa T., Kurita T.
Biochem. Mol. Biol. Int. 34:309-313(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 1-20.
[15]"Isolation of an ascitic oncodevelopmental protein exhibiting high sequence homology with calcium-binding protein MRP8."
Nakai M., Ishikawa M., Hamada Y., Sugano S.
Biol. Chem. Hoppe-Seyler 375:789-792(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 1-20.
Tissue: Ascites.
[16]"Microsequences of 145 proteins recorded in the two-dimensional gel protein database of normal human epidermal keratinocytes."
Rasmussen H.H., van Damme J., Puype M., Gesser B., Celis J.E., Vandekerckhove J.
Electrophoresis 13:960-969(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 38-47 AND 50-56.
Tissue: Keratinocyte.
[17]"Myeloid-related protein (MRP) 8 and MRP14, calcium-binding proteins of the S100 family, are secreted by activated monocytes via a novel, tubulin-dependent pathway."
Rammes A., Roth J., Goebeler M., Klempt M., Hartmann M., Sorg C.
J. Biol. Chem. 272:9496-9502(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, SUBUNIT, TISSUE SPECIFICITY.
[18]"The microbial receptor CEACAM3 is linked to the calprotectin complex in granulocytes."
Streichert T., Ebrahimnejad A., Ganzer S., Flayeh R., Wagener C., Bruemmer J.
Biochem. Biophys. Res. Commun. 289:191-197(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CEACAM3.
[19]"Proinflammatory activities of S100: proteins S100A8, S100A9, and S100A8/A9 induce neutrophil chemotaxis and adhesion."
Ryckman C., Vandal K., Rouleau P., Talbot M., Tessier P.A.
J. Immunol. 170:3233-3242(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[20]"MRP8 and MRP14 control microtubule reorganization during transendothelial migration of phagocytes."
Vogl T., Ludwig S., Goebeler M., Strey A., Thorey I.S., Reichelt R., Foell D., Gerke V., Manitz M.P., Nacken W., Werner S., Sorg C., Roth J.
Blood 104:4260-4268(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH TUBULIN.
[21]"Myeloid-related proteins 8 and 14 induce a specific inflammatory response in human microvascular endothelial cells."
Viemann D., Strey A., Janning A., Jurk K., Klimmek K., Vogl T., Hirono K., Ichida F., Foell D., Kehrel B., Gerke V., Sorg C., Roth J.
Blood 105:2955-2962(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[22]"The arachidonic acid-binding protein S100A8/A9 promotes NADPH oxidase activation by interaction with p67phox and Rac-2."
Kerkhoff C., Nacken W., Benedyk M., Dagher M.C., Sopalla C., Doussiere J.
FASEB J. 19:467-469(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH NCF2/P67PHOX; RAC1 AND RAC2.
[23]"Regulation of S100A8/A9 (calprotectin) binding to tumor cells by zinc ion and its implication for apoptosis-inducing activity."
Nakatani Y., Yamazaki M., Chazin W.J., Yui S.
Mediators Inflamm. 2005:280-292(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INHIBITION BY ZINC IONS, SUBUNIT.
[24]"Interaction between S100A8/A9 and annexin A6 is involved in the calcium-induced cell surface exposition of S100A8/A9."
Bode G., Lueken A., Kerkhoff C., Roth J., Ludwig S., Nacken W.
J. Biol. Chem. 283:31776-31784(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, INTERACTION WITH ANXA6.
[25]"S-nitrosylated S100A8: novel anti-inflammatory properties."
Lim S.Y., Raftery M., Cai H., Hsu K., Yan W.X., Hseih H.L., Watts R.N., Richardson D., Thomas S., Perry M., Geczy C.L.
J. Immunol. 181:5627-5636(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: S-NITROSYLATION AT CYS-42.
[26]"Anti-infective protective properties of S100 calgranulins."
Hsu K., Champaiboon C., Guenther B.D., Sorenson B.S., Khammanivong A., Ross K.F., Geczy C.L., Herzberg M.C.
Antiinflamm. Antiallergy Agents Med. Chem. 8:290-305(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[27]"S100A8/A9: a Janus-faced molecule in cancer therapy and tumorgenesis."
Ghavami S., Chitayat S., Hashemi M., Eshraghi M., Chazin W.J., Halayko A.J., Kerkhoff C.
Eur. J. Pharmacol. 625:73-83(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[28]"Substitution of methionine 63 or 83 in S100A9 and cysteine 42 in S100A8 abrogate the antifungal activities of S100A8/A9: potential role for oxidative regulation."
Sroussi H.Y., Koehler G.A., Agabian N., Villines D., Palefsky J.M.
FEMS Immunol. Med. Microbiol. 55:55-61(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF CYS-42.
[29]"Calprotectin S100A9 calcium-binding loops I and II are essential for keratinocyte resistance to bacterial invasion."
Champaiboon C., Sappington K.J., Guenther B.D., Ross K.F., Herzberg M.C.
J. Biol. Chem. 284:7078-7090(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBUNIT.
[30]"The endogenous Toll-like receptor 4 agonist S100A8/S100A9 (calprotectin) as innate amplifier of infection, autoimmunity, and cancer."
Ehrchen J.M., Sunderkoetter C., Foell D., Vogl T., Roth J.
J. Leukoc. Biol. 86:557-566(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[31]"S100A8/A9 induces autophagy and apoptosis via ROS-mediated cross-talk between mitochondria and lysosomes that involves BNIP3."
Ghavami S., Eshragi M., Ande S.R., Chazin W.J., Klonisch T., Halayko A.J., McNeill K.D., Hashemi M., Kerkhoff C., Los M.
Cell Res. 20:314-331(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[32]"S100 Calgranulins in inflammatory arthritis."
Perera C., McNeil H.P., Geczy C.L.
Immunol. Cell Biol. 88:41-49(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[33]"Inflammation-associated S100 proteins: new mechanisms that regulate function."
Goyette J., Geczy C.L.
Amino Acids 41:821-842(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[34]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[35]"S100A8 and S100A9 in cardiovascular biology and disease."
Averill M.M., Kerkhoff C., Bornfeldt K.E.
Arterioscler. Thromb. Vasc. Biol. 32:223-229(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[36]"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.
[37]"Pro-inflammatory S100A8 and S100A9 proteins: self-assembly into multifunctional native and amyloid complexes."
Vogl T., Gharibyan A.L., Morozova-Roche L.A.
Int. J. Mol. Sci. 13:2893-2917(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[38]"S100A8 and S100A9: new insights into their roles in malignancy."
Srikrishna G.
J. Innate Immun. 4:31-40(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[39]"Molecular interface of S100A8 with cytochrome b and NADPH oxidase activation."
Berthier S., Nguyen M.V., Baillet A., Hograindleur M.A., Paclet M.H., Polack B., Morel F.
PLoS ONE 7:E40277-E40277(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH CYBA AND CYBB.
[40]"Constitutive neutrophil apoptosis: regulation by cell concentration via S100 A8/9 and the MEK-ERK pathway."
Atallah M., Krispin A., Trahtemberg U., Ben-Hamron S., Grau A., Verbovetski I., Mevorach D.
PLoS ONE 7:E29333-E29333(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY.
[41]"The structure of human MRP8, a member of the S100 calcium-binding protein family, by MAD phasing at 1.9 A resolution."
Ishikawa K., Nakagawa A., Tanaka I., Suzuki M., Nishihira J.
Acta Crystallogr. D 56:559-566(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS).
[42]"The crystal structure of the human (S100A8/S100A9)2 heterotetramer, calprotectin, illustrates how conformational changes of interacting alpha-helices can determine specific association of two EF-hand proteins."
Korndoerfer I.P., Brueckner F., Skerra A.
J. Mol. Biol. 370:887-898(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) IN COMPLEX WITH S100A9, SUBUNIT, ZINC-BINDING.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Y00278 mRNA. Translation: CAA68390.1.
X06234 mRNA. Translation: CAA29580.1.
M21005 Genomic DNA. Translation: AAA36327.1.
AK291328 mRNA. Translation: BAF84017.1.
CR407674 mRNA. Translation: CAG28602.1.
BT007378 mRNA. Translation: AAP36042.1.
AL591704 Genomic DNA. Translation: CAI19497.1.
CH471121 Genomic DNA. Translation: EAW53330.1.
CH471121 Genomic DNA. Translation: EAW53331.1.
BC005928 mRNA. Translation: AAH05928.1.
PIRBCHUCF. A31848.
RefSeqNP_002955.2. NM_002964.4.
UniGeneHs.416073.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1MR8X-ray1.90A/B1-93[»]
1XK4X-ray1.80A/B/E/F/I/J1-93[»]
4GGFX-ray1.60A/K/S/U1-93[»]
ProteinModelPortalP05109.
SMRP05109. Positions 1-90.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112187. 48 interactions.
DIPDIP-1165N.
IntActP05109. 31 interactions.
MINTMINT-1151603.
STRING9606.ENSP00000357721.

PTM databases

PhosphoSiteP05109.

Polymorphism databases

DMDM115442.

2D gel databases

SWISS-2DPAGEP05109.

Proteomic databases

PaxDbP05109.
PeptideAtlasP05109.
PRIDEP05109.

Protocols and materials databases

DNASU6279.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000368732; ENSP00000357721; ENSG00000143546.
ENST00000368733; ENSP00000357722; ENSG00000143546.
GeneID6279.
KEGGhsa:6279.
UCSCuc001fbs.3. human.

Organism-specific databases

CTD6279.
GeneCardsGC01M153362.
HGNCHGNC:10498. S100A8.
HPACAB002791.
HPA024372.
MIM123885. gene.
neXtProtNX_P05109.
PharmGKBPA34910.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG39611.
HOVERGENHBG001479.
InParanoidP05109.
OMADTWFKEL.
OrthoDBEOG76HQ48.
PhylomeDBP05109.
TreeFamTF332727.

Gene expression databases

BgeeP05109.
CleanExHS_S100A8.
GenevestigatorP05109.

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

ChiTaRSS100A8. human.
EvolutionaryTraceP05109.
GeneWikiS100_calcium_binding_protein_A8.
GenomeRNAi6279.
NextBio24373.
PROP05109.
SOURCESearch...

Entry information

Entry nameS10A8_HUMAN
AccessionPrimary (citable) accession number: P05109
Secondary accession number(s): A8K5L3 expand/collapse secondary AC list , D3DV37, Q5SY70, Q9UC84, Q9UC92, Q9UCJ0, Q9UCM6
Entry history
Integrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: January 1, 1988
Last modified: April 16, 2014
This is version 155 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM