| UniProt ID | S10A9_HUMAN | |
|---|---|---|
| UniProt AC | P06702 | |
| Protein Name | Protein S100-A9 | |
| Gene Name | S100A9 | |
| Organism | Homo sapiens (Human). | |
| Sequence Length | 114 | |
| Subcellular Localization |
Secreted. Cytoplasm. Cytoplasm, cytoskeleton. Cell membrane Peripheral membrane protein. Predominantly localized in the cytoplasm. Upon elevation of the intracellular calcium level, translocated from the cytoplasm to the cytoskeleton and the cell me |
|
| Protein Description | 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 Zn(2+) 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.. | |
| Protein Sequence | MTCKMSQLERNIETIINTFHQYSVKLGHPDTLNQGEFKELVRKDLQNFLKKENKNEKVIEHIMEDLDTNADKQLSFEEFIMLMARLTWASHEKMHEGDEGPGHHHKPGLGEGTP | |
| Overview of Protein Modification Sites with Functional and Structural Information | ||
|
|
||
* ASA = Accessible Surface Area
| Locations | Modification | Substrate Peptides & Secondary Structure |
ASA (%) | Reference | Orthologous Protein Cluster |
|---|---|---|---|---|---|
| 2 | Blocked amino end (Thr) | ------MTCKMSQLE ------CCCCHHHHH | 22.34 | - | |
| 2 | Blocked amino end | ------MTCKMSQLE ------CCCCHHHHH | 22.34 | - | |
| 2 | Phosphorylation | ------MTCKMSQLE ------CCCCHHHHH | 22.34 | 23532336 | |
| 3 | S-nitrosocysteine | -----MTCKMSQLER -----CCCCHHHHHH | 3.17 | - | |
| 3 | Glutathionylation | -----MTCKMSQLER -----CCCCHHHHHH | 3.17 | 20223829 | |
| 3 | S-nitrosylation | -----MTCKMSQLER -----CCCCHHHHHH | 3.17 | 25417112 | |
| 4 | Ubiquitination | ----MTCKMSQLERN ----CCCCHHHHHHH | 32.21 | 29901268 | |
| 6 | Phosphorylation | --MTCKMSQLERNIE --CCCCHHHHHHHHH | 19.67 | 23532336 | |
| 18 | Phosphorylation | NIETIINTFHQYSVK HHHHHHHHHHHHHHH | 16.46 | 28450419 | |
| 22 | Phosphorylation | IINTFHQYSVKLGHP HHHHHHHHHHHCCCC | 13.58 | 28450419 | |
| 23 | Phosphorylation | INTFHQYSVKLGHPD HHHHHHHHHHCCCCC | 13.25 | 26434552 | |
| 25 | Ubiquitination | TFHQYSVKLGHPDTL HHHHHHHHCCCCCCC | 42.69 | 16196087 | |
| 31 | Phosphorylation | VKLGHPDTLNQGEFK HHCCCCCCCCHHHHH | 31.87 | 23312004 | |
| 38 | Acetylation | TLNQGEFKELVRKDL CCCHHHHHHHHHHHH | 45.92 | 7935057 | |
| 38 | Ubiquitination | TLNQGEFKELVRKDL CCCHHHHHHHHHHHH | 45.92 | 29901268 | |
| 57 | Ubiquitination | KKENKNEKVIEHIME HHCCCCHHHHHHHHH | 58.88 | 29901268 | |
| 63 | Sulfoxidation | EKVIEHIMEDLDTNA HHHHHHHHHHCCCCH | 3.37 | 17138858 | |
| 68 | Phosphorylation | HIMEDLDTNADKQLS HHHHHCCCCHHHCCC | 39.33 | 22499768 | |
| 72 | Ubiquitination | DLDTNADKQLSFEEF HCCCCHHHCCCHHHH | 51.21 | 16196087 | |
| 75 | Phosphorylation | TNADKQLSFEEFIML CCHHHCCCHHHHHHH | 28.28 | 20068231 | |
| 81 | Sulfoxidation | LSFEEFIMLMARLTW CCHHHHHHHHHHHHH | 2.25 | 30380834 | |
| 83 | Sulfoxidation | FEEFIMLMARLTWAS HHHHHHHHHHHHHHH | 0.83 | 17138858 | |
| 105 | Methylation | DEGPGHHHKPGLGEG CCCCCCCCCCCCCCC | 32.12 | - | |
| 113 | Phosphorylation | KPGLGEGTP------ CCCCCCCCC------ | 22.86 | 2478889 |
| Modified Location | Modified Residue | Modification | Type of Upstream Proteins | Gene Name of Upstream Proteins | UniProt AC of Upstream Proteins | Sources |
|---|---|---|---|---|---|---|
| 113 | T | Phosphorylation | Kinase | P38A | Q16539 | PSP |
* Distance = the distance between SAP position and PTM sites.
| Modified Location | Modification | Variant Position (Distance <= 10) |
Residue Change | SAP | Related Disease | Reference |
|---|---|---|---|---|---|---|
Oops, there are no SNP-PTM records of S10A9_HUMAN !! | ||||||
| Kegg Disease | ||||||
|---|---|---|---|---|---|---|
| There are no disease associations of PTM sites. | ||||||
| OMIM Disease | ||||||
| There are no disease associations of PTM sites. | ||||||
| Kegg Drug | ||||||
| There are no disease associations of PTM sites. | ||||||
| DrugBank | ||||||
| There are no disease associations of PTM sites. | ||||||
loading...
| Phosphorylation | |
| Reference | PubMed |
| "Large-scale proteomics analysis of the human kinome."; Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,Mann M., Daub H.; Mol. Cell. Proteomics 8:1751-1764(2009). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-113, AND MASSSPECTROMETRY. | |
| "Phosphorylation analysis of primary human T lymphocytes usingsequential IMAC and titanium oxide enrichment."; Carrascal M., Ovelleiro D., Casas V., Gay M., Abian J.; J. Proteome Res. 7:5167-5176(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-113, AND MASSSPECTROMETRY. | |
| "Large-scale phosphoproteome analysis of human liver tissue byenrichment and fractionation of phosphopeptides with strong anionexchange chromatography."; Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D.,Zou H., Gu J.; Proteomics 8:1346-1361(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-113, AND MASSSPECTROMETRY. | |
| "Ionomycin-regulated phosphorylation of the myeloid calcium-bindingprotein p14."; Edgeworth J., Freemont P., Hogg N.; Nature 342:189-192(1989). Cited for: PROTEIN SEQUENCE OF 84-114, AND PHOSPHORYLATION AT THR-113. | |
