TCAM2_HUMAN - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: TCAM2_HUMAN
• UniProt AC: Q86XR7
• Protein Name: TIR domain-containing adapter molecule 2
• Gene Name: TICAM2
• Organism: Homo sapiens (Human).
• Sequence Length: 235
• Subcellular Localization: Isoform 1: Cytoplasm. Golgi apparatus. Cell membrane. Endoplasmic reticulum. Early endosome membrane. Late endosome membrane. Localized to the plasma membrane as a result of myristoylation. Phosphorylation on Ser-16 leads to its depletion from the me
• Protein Description: Functions as sorting adapter in LPS-TLR4 signaling to regulate the MYD88-independent pathway during the innate immune response to LPS. Physically bridges TLR4 and TICAM1 and functionally transmits LPS-TRL4 signal to TICAM1; signaling is proposed to occur in early endosomes after endocytosis of TLR4. May also be involved in IL1-triggered NF-kappa-B activation, functioning upstream of IRAK1, IRAK2, TRAF6, and IKBKB; however, reports are controversial. Involved in IL-18 signaling and is proposed to function as a sorting adaptor for MYD88 in IL-18 signaling during adaptive immune response.; Isoform 2: Proposed to inhibit LPS-TLR4 signaling at the late endosome by interaction with isoform 1 thereby disrupting the association of isoform 1 with TICAM1. May be involved in TLR4 degradation in late endosomes..
• Protein Sequence: MGIGKSKINSCPLSLSWGKRHSVDTSPGYHESDSKKSEDLSLCNVAEHSNTTEGPTGKQEGAQSVEEMFEEEAEEEVFLKFVILHAEDDTDEALRVQNLLQDDFGIKPGIIFAEMPCGRQHLQNLDDAVNGSAWTILLLTENFLRDTWCNFQFYTSLMNSVNRQHKYNSVIPMRPLNNPLPRERTPFALQTINALEEESRGFPTQVERIFQESVYKTQQTIWKETRNMVQRQFIA

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
2	Myristoylation	------MGIGKSKIN ------CCCCCCCCC	37.04	16603631
2	N-myristoyl glycine	------MGIGKSKIN ------CCCCCCCCC	37.04	-
14	Phosphorylation	KINSCPLSLSWGKRH CCCCCCCCCCCCCCC	12.90	-
16	Phosphorylation	NSCPLSLSWGKRHSV CCCCCCCCCCCCCCC	30.33	14519765
22	Phosphorylation	LSWGKRHSVDTSPGY CCCCCCCCCCCCCCC	26.22	26657352
25	Phosphorylation	GKRHSVDTSPGYHES CCCCCCCCCCCCCCC	34.37	26699800
26	Phosphorylation	KRHSVDTSPGYHESD CCCCCCCCCCCCCCC	16.32	26699800
29	Phosphorylation	SVDTSPGYHESDSKK CCCCCCCCCCCCCCC	13.05	23312004
32	Phosphorylation	TSPGYHESDSKKSED CCCCCCCCCCCCCCC	33.59	29449344
34	Phosphorylation	PGYHESDSKKSEDLS CCCCCCCCCCCCCCC	51.79	29449344
35	Acetylation	GYHESDSKKSEDLSL CCCCCCCCCCCCCCC	66.37	20167786
36	Acetylation	YHESDSKKSEDLSLC CCCCCCCCCCCCCCC	64.13	20167786
37	Phosphorylation	HESDSKKSEDLSLCN CCCCCCCCCCCCCCC	39.83	29449344
83 (in isoform 2)	Ubiquitination	-	2.34	-
87 (in isoform 2)	Ubiquitination	-	45.75	-
91 (in isoform 2)	Ubiquitination	-	46.28	-
167	Phosphorylation	SVNRQHKYNSVIPMR HHHCHHCCCCCCCCC	15.56	25825441
204 (in isoform 2)	Acetylation	-	42.88	-
205 (in isoform 2)	Acetylation	-	35.00	-
213	Phosphorylation	VERIFQESVYKTQQT HHHHHHHHHHHHHHH	21.69	22210691
217	Phosphorylation	FQESVYKTQQTIWKE HHHHHHHHHHHHHHH	14.28	22210691
336	Phosphorylation	------------------------------------------------------------------------------------------------------------ ------------------------------------------------------------------------------------------------------------		25825441

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

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
16	S	Phosphorylation	Kinase	PKCE	Q02156	PSP

Functions of PTM Sites

Oops, there are no descriptions of PTM sites of TCAM2_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 TCAM2_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
TLR4_HUMAN	TLR4	physical	21903422
TRAF6_HUMAN	TRAF6	physical	12721283
TRAF6_HUMAN	TRAF6	physical	24812060

Drug and Disease Associations

• Kegg Disease
• There are no disease associations of PTM sites.
• 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.
• There are no disease associations of PTM sites.
• DrugBank
• There are no disease associations of PTM sites.

Related Literatures of Post-Translational Modification

Myristoylation

"The myristoylation of TRIF-related adaptor molecule is essential forToll-like receptor 4 signal transduction.";
Rowe D.C., McGettrick A.F., Latz E., Monks B.G., Gay N.J.,Yamamoto M., Akira S., O'Neill L.A., Fitzgerald K.A., Golenbock D.T.;
Proc. Natl. Acad. Sci. U.S.A. 103:6299-6304(2006).
Cited for: FUNCTION, SUBCELLULAR LOCATION, MYRISTOYLATION AT GLY-2, ANDMUTAGENESIS OF GLY-2.
PubMed: 16603631

Phosphorylation

"Trif-related adapter molecule is phosphorylated by PKCepsilon duringToll-like receptor 4 signaling.";
McGettrick A.F., Brint E.K., Palsson-McDermott E.M., Rowe D.C.,Golenbock D.T., Gay N.J., Fitzgerald K.A., O'Neill L.A.J.;
Proc. Natl. Acad. Sci. U.S.A. 103:9196-9201(2006).
Cited for: FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-16, ANDMUTAGENESIS OF SER-6; SER-10; SER-14 AND SER-16.
PubMed: 16757566