S10A8_HUMAN - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: S10A8_HUMAN
• UniProt AC: P05109
• Protein Name: Protein S100-A8
• Gene Name: S100A8
• Organism: Homo sapiens (Human).
• Sequence Length: 93
• 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: 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 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. The iNOS-S100A8/A9 transnitrosylase complex directs selective inflammatory stimulus-dependent S-nitrosylation of GAPDH and probably multiple targets such as ANXA5, EZR, MSN and VIM by recognizing a [IL]-x-C-x-x-[DE] motif; S100A8 seems to contribute to S-nitrosylation site selectivity..
• Protein Sequence: MLTELEKALNSIIDVYHKYSLIKGNFHAVYRDDLKKLLETECPQYIRKKGADVWFKELDINTDGAVNFQEFLILVIKMGVAAHKKSHEESHKE

Overview of Protein Modification Sites with Functional and Structural Information

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
3	Phosphorylation	-----MLTELEKALN -----CCHHHHHHHH	36.91	-
11	Phosphorylation	ELEKALNSIIDVYHK HHHHHHHHHHHHHHH	23.05	28450419
16	Phosphorylation	LNSIIDVYHKYSLIK HHHHHHHHHHHHHHC	6.72	-
18	Acetylation	SIIDVYHKYSLIKGN HHHHHHHHHHHHCCC	20.88	25038526
20	Phosphorylation	IDVYHKYSLIKGNFH HHHHHHHHHHCCCEE	28.55	24719451
30	Phosphorylation	KGNFHAVYRDDLKKL CCCEEEEEHHHHHHH	14.76	-
40	Phosphorylation	DLKKLLETECPQYIR HHHHHHHCCCHHHHH	42.74	20068231
42	S-nitrosocysteine	KKLLETECPQYIRKK HHHHHCCCHHHHHHH	3.12	-
42	S-nitrosylation	KKLLETECPQYIRKK HHHHHCCCHHHHHHH	3.12	18832721
45	Phosphorylation	LETECPQYIRKKGAD HHCCCHHHHHHHCCC	6.45	21253578
84	Acetylation	KMGVAAHKKSHEESH HHHHHHHHHHHHHHH	51.77	7664305
86	Phosphorylation	GVAAHKKSHEESHKE HHHHHHHHHHHHHCC	40.72	-
90	Phosphorylation	HKKSHEESHKE---- HHHHHHHHHCC----	36.55	-

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Oops, there are no upstream regulatory protein records of S10A8_HUMAN !!

Functions of PTM Sites

Oops, there are no descriptions of PTM sites of S10A8_HUMAN !!

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Oops, there are no SNP-PTM records of S10A8_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
ERG28_HUMAN	C14orf1	physical	16169070
ANM1_HUMAN	PRMT1	physical	16169070
RRP5_HUMAN	PDCD11	physical	16169070
PPIA_HUMAN	PPIA	physical	16169070
SCG1_HUMAN	CHGB	physical	16169070
GDF9_HUMAN	GDF9	physical	16169070
IGS21_HUMAN	IGSF21	physical	16169070
P53_HUMAN	TP53	physical	16169070
TBA1A_MOUSE	Tuba1a	physical	16169070
LRIF1_HUMAN	LRIF1	physical	16169070
U119A_HUMAN	UNC119	physical	16169070
S10A8_HUMAN	S100A8	physical	10771424
A4_HUMAN	APP	physical	21832049
CDC53_YEAST	CDC53	genetic	23483999
UBC3_YEAST	CDC34	genetic	23483999
IMA1_YEAST	SRP1	genetic	23483999
COPB2_YEAST	SEC27	genetic	23483999
BECN1_HUMAN	BECN1	physical	21971985
S10A8_HUMAN	S100A8	physical	23483999
NCF2_HUMAN	NCF2	physical	15642721
S10A9_HUMAN	S100A9	physical	15331440
SMTL2_HUMAN	SMTNL2	physical	28514442
DPH6_HUMAN	DPH6	physical	28514442
EFHD1_HUMAN	EFHD1	physical	28514442

Drug and Disease Associations

• 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.