Skip Header

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

UniProtKB - P06702 (S10A9_HUMAN)

(max 400 entries)x

Your basket is currently empty. i

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Protein

Protein S100-A9

Gene

S100A9

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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 proinflammatory, 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
  • Toll-like receptor 4 binding Source: UniProtKB
  • zinc ion binding Source: UniProtKB
View the complete GO annotation on QuickGO ...

GO - Biological processi

  • actin cytoskeleton reorganization Source: Ensembl
  • activation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
  • antimicrobial humoral immune response mediated by antimicrobial peptide Source: UniProtKB
  • antimicrobial humoral response Source: Reactome
  • 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
  • modification of morphology or physiology of other organism Source: UniProtKB
  • neutrophil aggregation Source: UniProtKB
  • neutrophil chemotaxis Source: UniProtKB
  • neutrophil degranulation Source: Reactome
  • 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 neuron projection development Source: ARUK-UCL
  • 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
  • toll-like receptor signaling pathway Source: Reactome
View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionAntimicrobial, Antioxidant
Biological processApoptosis, Autophagy, Chemotaxis, Immunity, Inflammatory response, Innate immunity
LigandCalcium, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-5686938 Regulation of TLR by endogenous ligand
R-HSA-6798695 Neutrophil degranulation
R-HSA-6799990 Metal sequestration by antimicrobial proteins
SIGNORiP06702

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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000163220.10
HGNCiHGNC:10499 S100A9
MIMi123886 gene
neXtProtiNX_P06702

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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
ChainiPRO_00001439971 – 114Protein S100-A9Add BLAST114

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
ProteomicsDBi51910
TopDownProteomicsiP06702

2D gel databases

OGPiP06702
SWISS-2DPAGEiP06702
UCD-2DPAGEiP06702

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 amyloid-beta protein 40. 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

Show more details

GO - Molecular functioni

  • microtubule binding Source: UniProtKB
  • RAGE receptor binding Source: UniProtKB
  • Toll-like receptor 4 binding Source: UniProtKB
View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi112188, 117 interactors
ComplexPortaliCPX-37 Calprotectin heterotetramer
CPX-39 Calprotectin heterodimer
CPX-48 S100A9 complex
CPX-52 iNOS-S100A8/A9 complex
CORUMiP06702
DIPiDIP-1166N
IntActiP06702, 33 interactors
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

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

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiENOG410J1XC Eukaryota
ENOG4111C30 LUCA
GeneTreeiENSGT00910000144230
HOGENOMiHOG000246968
HOVERGENiHBG001479
InParanoidiP06702
KOiK21128
OMAiDHIMEDL
OrthoDBiEOG091G12NB
PhylomeDBiP06702
TreeFamiTF332727

Family and domain databases

InterProiView protein in InterPro
IPR011992 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
PANTHERiPTHR11639:SF79 PTHR11639:SF79, 1 hit
PfamiView protein in Pfam
PF01023 S_100, 1 hit
SMARTiView protein in SMART
SM00054 EFh, 1 hit
SM01394 S_100, 1 hit
SUPFAMiSSF47473 SSF47473, 1 hit
PROSITEiView protein in PROSITE
PS00018 EF_HAND_1, 1 hit
PS50222 EF_HAND_2, 1 hit
PS00303 S100_CABP, 1 hit

Sequencei

Sequence statusi: Complete.

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 → R1 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 No translation available.
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

Similar proteinsi

Entry informationi

Entry nameiS10A9_HUMAN
AccessioniPrimary (citable) accession number: P06702
Secondary accession number(s): D3DV36
, Q6FGA1, Q9NYM0, Q9UCJ1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: January 1, 1988
Last modified: July 18, 2018
This is version 208 of the entry and version 1 of the sequence. See 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

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health