P05109 (S10A8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	93 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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, transfering 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. Cytoplasm › cytoskeleton. 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 process	Apoptosis Autophagy Chemotaxis Immunity Inflammatory response Innate immunity
Cellular component	Cell membrane Cytoplasm Cytoskeleton Membrane Secreted
Domain	Repeat
Ligand	Calcium Metal-binding Zinc
Molecular function	Antimicrobial
PTM	S-nitrosylation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	activation 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: Compara 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: Compara defense response to bacterium Traceable author statement Ref.37. Source: UniProtKB defense response to fungus Traceable author statement Ref.37. Source: UniProtKB induction of apoptosis Inferred from direct assay Ref.31. Source: UniProtKB 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 regulation of cytoskeleton organization Traceable author statement Ref.37. Source: UniProtKB response to ethanol Inferred from electronic annotation. Source: Compara response to lipopolysaccharide Inferred from electronic annotation. Source: Compara response to zinc ion Inferred from electronic annotation. Source: Compara sequestering of zinc ion Traceable author statement Ref.37. Source: UniProtKB wound healing Inferred from electronic annotation. Source: Compara
Cellular_component	cytoskeleton 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 electronic annotation. Source: Compara plasma membrane Traceable author statement Ref.37. Source: UniProtKB
Molecular_function	RAGE 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
S100A9	P06702	3	EBI-355281,EBI-1055001

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 93

93

Protein S100-A8

PRO_0000143993

Initiator methionine

1

1

Removed; alternate By similarity

Chain

2 – 93

92

Protein S100-A8, N-terminally processed

PRO_0000421773

Regions

Domain

12 – 47

36

EF-hand 1

Domain

46 – 81

36

EF-hand 2

Calcium binding

20 – 33

14

1; low affinity

Calcium binding

59 – 70

12

2; high affinity

Sites

Metal binding

17

1

Zinc Probable

Metal binding

27

1

Zinc Probable

Metal binding

83

1

Zinc Probable

Metal binding

87

1

Zinc Probable

Amino acid modifications

Modified residue

42

1

S-nitrosocysteine Ref.25

Experimental info

Mutagenesis

42

1

C → A: Loss of antifungal activity. Ref.28

Sequence conflict

80 – 93

14

VAAHK…ESHKE → WQPTKKAMKKATKSS in CAA68390. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

93

Helix Strand Turn

Details...

Helix

4 – 20

17

Beta strand

22 – 24

3

Helix

31 – 41

11

Helix

44 – 47

4

Helix

51 – 58

8

Beta strand

63 – 66

4

Helix

68 – 86

19

Sequences

	Sequence		Length	Mass (Da)
	P05109 [UniParc]. Last modified January 1, 1988. Version 1. Checksum: 78F589140B9CE166	FASTA	93	10,835
	10 20 30 40 50 60 MLTELEKALN SIIDVYHKYS LIKGNFHAVY RDDLKKLLET ECPQYIRKKG ADVWFKELDI 70 80 90 NTDGAVNFQE FLILVIKMGV AAHKKSHEES HKE

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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, 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.

IPI

IPI00007047.

PIR

BCHUCF. A31848.

RefSeq

NP_002955.2. NM_002964.4.

UniGene

Hs.416073.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1MR8	X-ray	1.90	A/B	1-93	[»]
1XK4	X-ray	1.80	A/B/E/F/I/J	1-93	[»]
4GGF	X-ray	1.60	A/K/S/U	1-93	[»]

ProteinModelPortal

P05109.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-1165N.

IntAct

P05109. 26 interactions.

MINT

MINT-1151603.

STRING

9606.ENSP00000357721.

PTM databases

PhosphoSite

P05109.

Polymorphism databases

DMDM

115442.

2D gel databases

SWISS-2DPAGE

P05109.

Proteomic databases

PaxDb

P05109.

PeptideAtlas

P05109.

PRIDE

P05109.

Protocols and materials databases

DNASU

6279.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000368732; ENSP00000357721; ENSG00000143546.
ENST00000368733; ENSP00000357722; ENSG00000143546.

GeneID

6279.

KEGG

hsa:6279.

UCSC

uc001fbs.3. human.

Organism-specific databases

CTD

6279.

GeneCards

GC01M153362.

HGNC

HGNC:10498. S100A8.

HPA

CAB002791.
HPA024372.

MIM

123885. gene.

neXtProt

NX_P05109.

PharmGKB

PA34910.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG39611.

HOVERGEN

HBG001479.

InParanoid

P05109.

OMA

KDADTWF.

OrthoDB

EOG4V9TS7.

PhylomeDB

P05109.

Gene expression databases

Bgee

P05109.

CleanEx

HS_S100A8.

Genevestigator

P05109.

GermOnline

ENSG00000143546. Homo sapiens.

Family and domain databases

Gene3D

1.10.238.10. 1 hit.

InterPro

IPR011992. EF-hand-like_dom.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
IPR001751. S100/CaBP-9k_CS.
IPR013787. S100_Ca-bd_sub.
[Graphical view]

Pfam

PF01023. S_100. 1 hit.
[Graphical view]

PROSITE

PS00018. EF_HAND_1. 1 hit.
PS50222. EF_HAND_2. 1 hit.
PS00303. S100_CABP. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

S100A8. human.

EvolutionaryTrace

P05109.

GenomeRNAi

6279.

NextBio

24373.

SOURCE

Search...

Entry information

Entry name

S10A8_HUMAN

Accession

Primary (citable) accession number: P05109
Secondary accession number(s): A8K5L3 , D3DV37, Q5SY70, Q9UC84, Q9UC92, Q9UCJ0, Q9UCM6

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 13, 1987
Last sequence update:	January 1, 1988
Last modified:	May 1, 2013
This is version 145 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.