TRPM8_HUMAN - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: TRPM8_HUMAN
• UniProt AC: Q7Z2W7
• Protein Name: Transient receptor potential cation channel subfamily M member 8
• Gene Name: TRPM8
• Organism: Homo sapiens (Human).
• Sequence Length: 1104
• Subcellular Localization: Cell membrane; Multi-pass membrane protein. Membrane raft. Endoplasmic reticulum membrane. Localizes to membrane rafts but is also located in the cell membrane outside of these regions where channel response to cold is enhanced compared to membrane r
• Protein Description: Receptor-activated non-selective cation channel involved in detection of sensations such as coolness, by being activated by cold temperature below 25 degrees Celsius. Activated by icilin, eucalyptol, menthol, cold and modulation of intracellular pH. Involved in menthol sensation. Permeable for monovalent cations sodium, potassium, and cesium and divalent cation calcium. Temperature sensing is tightly linked to voltage-dependent gating. Activated upon depolarization, changes in temperature resulting in graded shifts of its voltage-dependent activation curves. The chemical agonist menthol functions as a gating modifier, shifting activation curves towards physiological membrane potentials. Temperature sensitivity arises from a tenfold difference in the activation energies associated with voltage-dependent opening and closing. In prostate cancer cells, shows strong inward rectification and high calcium selectivity in contrast to its behavior in normal cells which is characterized by outward rectification and poor cationic selectivity. Plays a role in prostate cancer cell migration. [PubMed: 25559186 Isoform 2 and isoform 3 negatively regulate menthol- and cold-induced channel activity by stabilizing the closed state of the channel.]
• Protein Sequence: MSFRAARLSMRNRRNDTLDSTRTLYSSASRSTDLSYSESDLVNFIQANFKKRECVFFTKDSKATENVCKCGYAQSQHMEGTQINQSEKWNYKKHTKEFPTDAFGDIQFETLGKKGKYIRLSCDTDAEILYELLTQHWHLKTPNLVISVTGGAKNFALKPRMRKIFSRLIYIAQSKGAWILTGGTHYGLMKYIGEVVRDNTISRSSEENIVAIGIAAWGMVSNRDTLIRNCDAEGYFLAQYLMDDFTRDPLYILDNNHTHLLLVDNGCHGHPTVEAKLRNQLEKYISERTIQDSNYGGKIPIVCFAQGGGKETLKAINTSIKNKIPCVVVEGSGQIADVIASLVEVEDALTSSAVKEKLVRFLPRTVSRLPEEETESWIKWLKEILECSHLLTVIKMEEAGDEIVSNAISYALYKAFSTSEQDKDNWNGQLKLLLEWNQLDLANDEIFTNDRRWESADLQEVMFTALIKDRPKFVRLFLENGLNLRKFLTHDVLTELFSNHFSTLVYRNLQIAKNSYNDALLTFVWKLVANFRRGFRKEDRNGRDEMDIELHDVSPITRHPLQALFIWAILQNKKELSKVIWEQTRGCTLAALGASKLLKTLAKVKNDINAAGESEELANEYETRAVELFTECYSSDEDLAEQLLVYSCEAWGGSNCLELAVEATDQHFIAQPGVQNFLSKQWYGEISRDTKNWKIILCLFIIPLVGCGFVSFRKKPVDKHKKLLWYYVAFFTSPFVVFSWNVVFYIAFLLLFAYVLLMDFHSVPHPPELVLYSLVFVLFCDEVRQWYVNGVNYFTDLWNVMDTLGLFYFIAGIVFRLHSSNKSSLYSGRVIFCLDYIIFTLRLIHIFTVSRNLGPKIIMLQRMLIDVFFFLFLFAVWMVAFGVARQGILRQNEQRWRWIFRSVIYEPYLAMFGQVPSDVDGTTYDFAHCTFTGNESKPLCVELDEHNLPRFPEWITIPLVCIYMLSTNILLVNLLVAMFGYTVGTVQENNDQVWKFQRYFLVQEYCSRLNIPFPFIVFAYFYMVVKKCFKCCCKEKNMESSVCCFKNEDNETLAWEGVMKENYLVKINTKANDTSEEMRHRFRQLDTKLNDLKGLLKEIANKIK

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	Phosphorylation	------MSFRAARLS ------CCHHHHHHH	34.44	24719451
9	Phosphorylation	SFRAARLSMRNRRND CHHHHHHHHHHCCCC	15.33	20110357
17	Phosphorylation	MRNRRNDTLDSTRTL HHHCCCCCCHHHHHH	35.69	20110357
503	Phosphorylation	LFSNHFSTLVYRNLQ HHHHCHHHHHHHHHH	21.21	-
506	Phosphorylation	NHFSTLVYRNLQIAK HCHHHHHHHHHHHHH	9.26	-
683	Phosphorylation	NFLSKQWYGEISRDT HHHCHHCCCCCCCCC	11.46	29052541
687	Phosphorylation	KQWYGEISRDTKNWK HHCCCCCCCCCCCCC	21.57	29052541
690	Phosphorylation	YGEISRDTKNWKIIL CCCCCCCCCCCCCEE	25.76	29052541
840	Phosphorylation	CLDYIIFTLRLIHIF HHHHHHHHHHHHHHH	10.68	24719451
850	Phosphorylation	LIHIFTVSRNLGPKI HHHHHHHCCCCCHHH	16.64	-
934	N-linked_Glycosylation	AHCTFTGNESKPLCV EEEEEECCCCCCEEE	47.51	17065148
936	Phosphorylation	CTFTGNESKPLCVEL EEEECCCCCCEEEEE	43.50	24719451
1040	Phosphorylation	CKEKNMESSVCCFKN HCCCCCCCCEEEEEC	19.80	-
1041	Phosphorylation	KEKNMESSVCCFKNE CCCCCCCCEEEEECC	13.08	-
1063	Phosphorylation	EGVMKENYLVKINTK EEEEECCEEEEEECC	17.60	30631047

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
9	S	Phosphorylation	Kinase	PRKACA	P17612	GPS
17	T	Phosphorylation	Kinase	PRKACA	P17612	GPS
1040	S	Phosphorylation	Kinase	PKCB	P05771	PSP
1041	S	Phosphorylation	Kinase	PKCB	P05771	PSP

Functions of PTM Sites

Oops, there are no descriptions of PTM sites of TRPM8_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 TRPM8_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
CHAP1_HUMAN	CHAMP1	physical	22939629
UBP10_HUMAN	USP10	physical	22939629
TXLNA_HUMAN	TXLNA	physical	22939629
ZCH18_HUMAN	ZC3H18	physical	22939629
AKAP5_HUMAN	AKAP5	physical	18701070
TRPM4_HUMAN	TRPM4	physical	28514442
KCJ11_HUMAN	KCNJ11	physical	28514442
STX5_HUMAN	STX5	physical	28514442
PCX3_HUMAN	PCNXL3	physical	28514442
BI1_HUMAN	TMBIM6	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
• D00064: l-Menthol (JP16); Levomenthol; l-Menthol (TN)
• D04849: dl-Menthol (JP16)
• D04918: Menthol (USP); Fisherman's friend lozenges (TN)
• DrugBank
• DB00825: Menthol