Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Protein S100-A9

Gene

S100A9

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

S100A9 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, adhesion, can increase the bactericidal activity of neutrophils by promoting phagocytosis via activation of SYK, PI3K/AKT, and ERK1/2 and can induce degranulation of neutrophils by a MAPK-dependent mechanism. 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. Has transnitrosylase activity; in oxidatively-modified low-densitity lipoprotein (LDL(ox))-induced S-nitrosylation of GAPDH on 'Cys-247' proposed to transfer the NO moiety from NOS2/iNOS to GAPDH via its own S-nitrosylated Cys-3. The iNOS-S100A8/A9 transnitrosylase complex is proposed to also direct selective inflammatory stimulus-dependent S-nitrosylation of multiple targets such as ANXA5, EZR, MSN and VIM by recognizing a [IL]-x-C-x-x-[DE] motif.18 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi20ZincCurated1
Metal bindingi30ZincCurated1
Metal bindingi91ZincCurated1
Metal bindingi95ZincCurated1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Calcium bindingi23 – 361; low affinityAdd BLAST14
Calcium bindingi67 – 782; high affinityCuratedAdd BLAST12

GO - Molecular functioni

  • antioxidant activity Source: UniProtKB-KW
  • arachidonic acid binding Source: UniProtKB
  • calcium ion binding Source: UniProtKB
  • microtubule binding Source: UniProtKB
  • RAGE receptor binding Source: UniProtKB
  • signal transducer activity Source: ProtInc
  • Toll-like receptor 4 binding Source: UniProtKB
  • zinc ion binding Source: UniProtKB

GO - Biological processi

  • actin cytoskeleton reorganization Source: Ensembl
  • activation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
  • apoptotic process Source: UniProtKB-KW
  • astrocyte development Source: Ensembl
  • autophagy Source: UniProtKB
  • cell-cell signaling Source: ProtInc
  • chemokine production Source: UniProtKB
  • cytokine production Source: UniProtKB
  • defense response to bacterium Source: UniProtKB
  • defense response to fungus Source: UniProtKB
  • inflammatory response Source: ProtInc
  • innate immune response Source: UniProtKB-KW
  • leukocyte migration involved in inflammatory response Source: UniProtKB
  • neutrophil aggregation Source: UniProtKB
  • neutrophil chemotaxis Source: UniProtKB
  • peptidyl-cysteine S-trans-nitrosylation Source: UniProtKB
  • positive regulation of blood coagulation Source: Ensembl
  • positive regulation of cell growth Source: UniProtKB
  • positive regulation of inflammatory response Source: UniProtKB
  • positive regulation of intrinsic apoptotic signaling pathway Source: UniProtKB
  • positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
  • positive regulation of peptide secretion Source: Ensembl
  • regulation of cytoskeleton organization Source: UniProtKB
  • regulation of integrin biosynthetic process Source: Ensembl
  • regulation of translation Source: Ensembl
  • sequestering of zinc ion Source: UniProtKB
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

Enzyme and pathway databases

BioCyciZFISH:ENSG00000163220-MONOMER.
ReactomeiR-HSA-5686938. Regulation of TLR by endogenous ligand.
R-HSA-6798695. Neutrophil degranulation.
R-HSA-6799990. Metal sequestration by antimicrobial proteins.

Names & Taxonomyi

Protein namesi
Recommended name:
Protein S100-A9
Alternative name(s):
Calgranulin-B
Calprotectin L1H subunit
Leukocyte L1 complex heavy chain
Migration inhibitory factor-related protein 14
Short name:
MRP-14
Short name:
p14
S100 calcium-binding protein A9
Gene namesi
Name:S100A9
Synonyms:CAGB, CFAG, MRP14
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:10499. S100A9.

Subcellular locationi

GO - Cellular componenti

  • cytoskeleton Source: UniProtKB
  • cytosol Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • extracellular matrix Source: BHF-UCL
  • extracellular region Source: UniProtKB
  • extracellular space Source: UniProtKB
  • nucleus Source: UniProtKB
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Cytoskeleton, Membrane, Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi3C → A: Disrupts interaction with NOS2 and inhibits LDL(ox)-induced GAPDH S-nitrosylation; no effect on interaction with S100A8. 1 Publication1
Mutagenesisi36E → Q: Loss of resistance to bacterial invasion; when associated with Q-78. 1 Publication1
Mutagenesisi63M → A: Loss of antifungal activity. 1 Publication1
Mutagenesisi78E → Q: Loss of resistance to bacterial invasion; when associated with Q-36. 1 Publication1
Mutagenesisi81M → A: No effect on antifungal activity. 1 Publication1
Mutagenesisi83M → A: Loss of antifungal activity. 1 Publication1

Organism-specific databases

DisGeNETi6280.
OpenTargetsiENSG00000163220.
PharmGKBiPA34911.

Polymorphism and mutation databases

BioMutaiS100A9.
DMDMi115444.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00001439972 – 114Protein S100-A9Add BLAST113

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2Blocked amino end (Thr)1
Modified residuei3S-nitrosocysteine; transient1 Publication1
Modified residuei105Pros-methylhistidineBy similarity1
Modified residuei113Phosphothreonine; by MAPK14Combined sources3 Publications1

Post-translational modificationi

Phosphorylated. Phosphorylation inhibits activation of tubulin polymerization.3 Publications
S-nitrosylation of Cys-3 is implicated in LDL(ox)-induced S-nitrosylation of GAPDH at 'Cys-247' through a transnitrosylase mechanism involving a iNOS-S100A8/9 complex (PubMed:25417112).1 Publication

Keywords - PTMi

Methylation, Phosphoprotein, S-nitrosylation

Proteomic databases

EPDiP06702.
MaxQBiP06702.
PaxDbiP06702.
PeptideAtlasiP06702.
PRIDEiP06702.
TopDownProteomicsiP06702.

2D gel databases

OGPiP06702.
SWISS-2DPAGEP06702.
UCD-2DPAGEP06702.

PTM databases

iPTMnetiP06702.
PhosphoSitePlusiP06702.
SwissPalmiP06702.

Expressioni

Tissue specificityi

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.5 Publications

Gene expression databases

BgeeiENSG00000163220.
CleanExiHS_S100A9.
GenevisibleiP06702. HS.

Organism-specific databases

HPAiCAB009441.
HPA004193.

Interactioni

Subunit structurei

Homodimer. Preferentially exists as a heterodimer or heterotetramer with S100A8 known as calprotectin (S100A8/A9). S100A9 interacts with ATP2A2 (By similarity). S100A9 interacts with AGER, and with the heterodimeric complex formed by TLR4 and LY96 in the presence of calcium and/or zinc ions. S100A9 binds quinoline-3-carboxamides in the presence of calcium and/or zinc ions. S100A9 interacts with beta-APP40 (beta-amyloid protein 40) peptide of APP. 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. Calprotectin (S100A8/9) interacts with NCF2/P67PHOX, RAC1, RAC2, CYBA and CYBB. Calprotectin (S100A8/9) interacts with NOS2 to form the iNOS-S100A8/A9 transnitrosylase complex; induced by LDL(ox) (PubMed:25417112).By similarity1 Publication15 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ARRB1P494072EBI-1055001,EBI-743313
ARRB2P321212EBI-1055001,EBI-714559
S100A8P051097EBI-1055001,EBI-355281

GO - Molecular functioni

  • microtubule binding Source: UniProtKB
  • RAGE receptor binding Source: UniProtKB
  • Toll-like receptor 4 binding Source: UniProtKB

Protein-protein interaction databases

BioGridi112188. 96 interactors.
DIPiDIP-1166N.
IntActiP06702. 25 interactors.
MINTiMINT-5002390.
STRINGi9606.ENSP00000357727.

Structurei

Secondary structure

1114
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi7 – 23Combined sources17
Beta strandi25 – 28Combined sources4
Helixi34 – 44Combined sources11
Turni45 – 49Combined sources5
Helixi50 – 53Combined sources4
Helixi56 – 66Combined sources11
Beta strandi71 – 74Combined sources4
Helixi76 – 94Combined sources19
Turni95 – 97Combined sources3
Turni108 – 110Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1IRJX-ray2.10A/B/C/D/E/F/G/H2-114[»]
1XK4X-ray1.80C/D/G/H/K/L2-114[»]
4GGFX-ray1.60C/L/T/V1-114[»]
4XJKX-ray1.76B/D/F/H/J1-114[»]
5I8NNMR-A/B1-114[»]
ProteinModelPortaliP06702.
SMRiP06702.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP06702.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini12 – 47EF-hand 1PROSITE-ProRule annotationAdd BLAST36
Domaini54 – 89EF-hand 2PROSITE-ProRule annotationAdd BLAST36

Sequence similaritiesi

Belongs to the S-100 family.Curated
Contains 2 EF-hand domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiENOG410J1XC. Eukaryota.
ENOG4111C30. LUCA.
GeneTreeiENSGT00760000119034.
HOGENOMiHOG000246968.
HOVERGENiHBG001479.
InParanoidiP06702.
OMAiDHIMEDL.
OrthoDBiEOG091G12NB.
PhylomeDBiP06702.
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.
IPR028475. S100-A9.
IPR001751. S100/CaBP-9k_CS.
IPR013787. S100_Ca-bd_sub.
[Graphical view]
PANTHERiPTHR11639:SF79. PTHR11639:SF79. 1 hit.
PfamiPF01023. S_100. 1 hit.
[Graphical view]
SMARTiSM00054. EFh. 1 hit.
SM01394. S_100. 1 hit.
[Graphical view]
SUPFAMiSSF47473. SSF47473. 1 hit.
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.

P06702-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTCKMSQLER NIETIINTFH QYSVKLGHPD TLNQGEFKEL VRKDLQNFLK
60 70 80 90 100
KENKNEKVIE HIMEDLDTNA DKQLSFEEFI MLMARLTWAS HEKMHEGDEG
110
PGHHHKPGLG EGTP
Length:114
Mass (Da):13,242
Last modified:January 1, 1988 - v1
Checksum:iC3BE19729E14C078
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti6S → H AA sequence (PubMed:8423249).Curated1
Sequence conflicti25K → F AA sequence (PubMed:8423249).Curated1
Sequence conflicti28H → L AA sequence (PubMed:8423249).Curated1

Mass spectrometryi

Molecular mass is 13115 Da from positions 2 - 114. Determined by MALDI. 1 Publication

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01300820H → R.1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X06233 mRNA. Translation: CAA29579.1.
M21064 Genomic DNA. Translation: AAA36326.1.
M26311 mRNA. Translation: AAA68480.1.
AF237581 Genomic DNA. Translation: AAF62536.1.
AF237582 Genomic DNA. Translation: AAF62537.1.
CR542207 mRNA. Translation: CAG47003.1.
CR542224 mRNA. Translation: CAG47020.1.
AL591704 Genomic DNA. Translation: CAI19494.1.
CH471121 Genomic DNA. Translation: EAW53333.1.
CH471121 Genomic DNA. Translation: EAW53334.1.
BC047681 mRNA. Translation: AAH47681.1.
CCDSiCCDS1036.1.
PIRiB31848.
RefSeqiNP_002956.1. NM_002965.3.
UniGeneiHs.112405.

Genome annotation databases

EnsembliENST00000368738; ENSP00000357727; ENSG00000163220.
GeneIDi6280.
KEGGihsa:6280.
UCSCiuc001fbq.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X06233 mRNA. Translation: CAA29579.1.
M21064 Genomic DNA. Translation: AAA36326.1.
M26311 mRNA. Translation: AAA68480.1.
AF237581 Genomic DNA. Translation: AAF62536.1.
AF237582 Genomic DNA. Translation: AAF62537.1.
CR542207 mRNA. Translation: CAG47003.1.
CR542224 mRNA. Translation: CAG47020.1.
AL591704 Genomic DNA. Translation: CAI19494.1.
CH471121 Genomic DNA. Translation: EAW53333.1.
CH471121 Genomic DNA. Translation: EAW53334.1.
BC047681 mRNA. Translation: AAH47681.1.
CCDSiCCDS1036.1.
PIRiB31848.
RefSeqiNP_002956.1. NM_002965.3.
UniGeneiHs.112405.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1IRJX-ray2.10A/B/C/D/E/F/G/H2-114[»]
1XK4X-ray1.80C/D/G/H/K/L2-114[»]
4GGFX-ray1.60C/L/T/V1-114[»]
4XJKX-ray1.76B/D/F/H/J1-114[»]
5I8NNMR-A/B1-114[»]
ProteinModelPortaliP06702.
SMRiP06702.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112188. 96 interactors.
DIPiDIP-1166N.
IntActiP06702. 25 interactors.
MINTiMINT-5002390.
STRINGi9606.ENSP00000357727.

PTM databases

iPTMnetiP06702.
PhosphoSitePlusiP06702.
SwissPalmiP06702.

Polymorphism and mutation databases

BioMutaiS100A9.
DMDMi115444.

2D gel databases

OGPiP06702.
SWISS-2DPAGEP06702.
UCD-2DPAGEP06702.

Proteomic databases

EPDiP06702.
MaxQBiP06702.
PaxDbiP06702.
PeptideAtlasiP06702.
PRIDEiP06702.
TopDownProteomicsiP06702.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000368738; ENSP00000357727; ENSG00000163220.
GeneIDi6280.
KEGGihsa:6280.
UCSCiuc001fbq.3. human.

Organism-specific databases

CTDi6280.
DisGeNETi6280.
GeneCardsiS100A9.
HGNCiHGNC:10499. S100A9.
HPAiCAB009441.
HPA004193.
MIMi123886. gene.
neXtProtiNX_P06702.
OpenTargetsiENSG00000163220.
PharmGKBiPA34911.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410J1XC. Eukaryota.
ENOG4111C30. LUCA.
GeneTreeiENSGT00760000119034.
HOGENOMiHOG000246968.
HOVERGENiHBG001479.
InParanoidiP06702.
OMAiDHIMEDL.
OrthoDBiEOG091G12NB.
PhylomeDBiP06702.
TreeFamiTF332727.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000163220-MONOMER.
ReactomeiR-HSA-5686938. Regulation of TLR by endogenous ligand.
R-HSA-6798695. Neutrophil degranulation.
R-HSA-6799990. Metal sequestration by antimicrobial proteins.

Miscellaneous databases

ChiTaRSiS100A9. human.
EvolutionaryTraceiP06702.
GeneWikiiS100A9.
GenomeRNAii6280.
PROiP06702.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000163220.
CleanExiHS_S100A9.
GenevisibleiP06702. HS.

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.
IPR028475. S100-A9.
IPR001751. S100/CaBP-9k_CS.
IPR013787. S100_Ca-bd_sub.
[Graphical view]
PANTHERiPTHR11639:SF79. PTHR11639:SF79. 1 hit.
PfamiPF01023. S_100. 1 hit.
[Graphical view]
SMARTiSM00054. EFh. 1 hit.
SM01394. S_100. 1 hit.
[Graphical view]
SUPFAMiSSF47473. SSF47473. 1 hit.
PROSITEiPS00018. EF_HAND_1. 1 hit.
PS50222. EF_HAND_2. 1 hit.
PS00303. S100_CABP. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiS10A9_HUMAN
AccessioniPrimary (citable) accession number: P06702
Secondary accession number(s): D3DV36
, Q6FGA1, Q9NYM0, Q9UCJ1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: January 1, 1988
Last modified: November 30, 2016
This is version 192 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.