GPX4_HUMAN - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: GPX4_HUMAN
• UniProt AC: P36969
• Protein Name: Phospholipid hydroperoxide glutathione peroxidase
• Gene Name: GPX4 {ECO:0000303|PubMed:9705830, ECO:0000312|HGNC:HGNC:4556}
• Organism: Homo sapiens (Human).
• Sequence Length: 197
• Subcellular Localization: Isoform Mitochondrial: Mitochondrion .; Isoform Cytoplasmic: Cytoplasm .
• Protein Description: Essential antioxidant peroxidase that directly reduces phospholipid hydroperoxide even if they are incorporated in membranes and lipoproteins (By similarity). Can also reduce fatty acid hydroperoxide, cholesterol hydroperoxide and thymine hydroperoxide (By similarity). Plays a key role in protecting cells from oxidative damage by preventing membrane lipid peroxidation (By similarity). Required to prevent cells from ferroptosis, a non-apoptotic cell death resulting from an iron-dependent accumulation of lipid reactive oxygen species. [PubMed: 24439385 The presence of selenocysteine (Sec) versus Cys at the active site is essential for life: it provides resistance to overoxidation and prevents cells against ferroptosis (By similarity The presence of Sec at the active site is also essential for the survival of a specific type of parvalbumin-positive interneurons, thereby preventing against fatal epileptic seizures (By similarity May be required to protect cells from the toxicity of ingested lipid hydroperoxides (By similarity Required for normal sperm development and male fertility (By similarity Essential for maturation and survival of photoreceptor cells (By similarity Plays a role in a primary T-cell response to viral and parasitic infection by protecting T-cells from ferroptosis and by supporting T-cell expansion (By similarity]
• Protein Sequence: MSLGRLCRLLKPALLCGALAAPGLAGTMCASRDDWRCARSMHEFSAKDIDGHMVNLDKYRGFVCIVTNVASQUGKTEVNYTQLVDLHARYAECGLRILAFPCNQFGKQEPGSNEEIKEFAAGYNVKFDMFSKICVNGDDAHPLWKWMKIQPKGKGILGNAIKWNFTKFLIDKNGCVVKRYGPMEEPLVIEKDLPHYF

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
40	Phosphorylation	DDWRCARSMHEFSAK CCHHHHHHHHEECCH	13.13	27251275
47	Acetylation	SMHEFSAKDIDGHMV HHHEECCHHCCCCEE	54.76	19608861
53	Sulfoxidation	AKDIDGHMVNLDKYR CHHCCCCEECHHHCC	2.33	30846556
58	Acetylation	GHMVNLDKYRGFVCI CCEECHHHCCCEEEE	39.76	26822725
107	Acetylation	FPCNQFGKQEPGSNE EEHHHCCCCCCCCHH	53.42	23236377
112	Phosphorylation	FGKQEPGSNEEIKEF CCCCCCCCHHHHHHH	52.35	30622161
135 (in isoform 2)	Ubiquitination	-	11.61	21890473
140 (in isoform 2)	Ubiquitination	-	15.78	21890473
145	Acetylation	DDAHPLWKWMKIQPK CCCCCHHHHCCCCCC	45.13	25038526
148	Acetylation	HPLWKWMKIQPKGKG CCHHHHCCCCCCCCC	36.75	25953088
162	Acetylation	GILGNAIKWNFTKFL CCCCHHHHCCCCEEE	33.40	25953088
162 (in isoform 1)	Ubiquitination	-	33.40	21890473
162	Ubiquitination	GILGNAIKWNFTKFL CCCCHHHHCCCCEEE	33.40	21890473
167 (in isoform 1)	Ubiquitination	-	33.75	21890473
167	Ubiquitination	AIKWNFTKFLIDKNG HHHCCCCEEEECCCC	33.75	21890473
172	Acetylation	FTKFLIDKNGCVVKR CCEEEECCCCCEEEE	48.52	25953088
183	Sulfoxidation	VVKRYGPMEEPLVIE EEEEECCCCCCEEEE	8.71	21406390
191	Acetylation	EEPLVIEKDLPHYF- CCCEEEECCCCCCC-	54.14	25038526

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

Oops, there are no upstream regulatory protein records of GPX4_HUMAN !!

Functions of PTM Sites

Oops, there are no descriptions of PTM sites of GPX4_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 GPX4_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
MK13_HUMAN	MAPK13	physical	21988832
PRDX6_HUMAN	PRDX6	physical	21988832
ALDR_HUMAN	AKR1B1	physical	26344197
ALDOA_HUMAN	ALDOA	physical	26344197
ALDOC_HUMAN	ALDOC	physical	26344197
DUT_HUMAN	DUT	physical	26344197
ENOA_HUMAN	ENO1	physical	26344197
ENOG_HUMAN	ENO2	physical	26344197
ENOB_HUMAN	ENO3	physical	26344197
FKB1A_HUMAN	FKBP1A	physical	26344197
GLRX2_HUMAN	GLRX2	physical	26344197
CH10_HUMAN	HSPE1	physical	26344197
MAOX_HUMAN	ME1	physical	26344197
PIN1_HUMAN	PIN1	physical	26344197
PPIF_HUMAN	PPIF	physical	26344197
PRDX2_HUMAN	PRDX2	physical	26344197
PRDX6_HUMAN	PRDX6	physical	26344197
STIP1_HUMAN	STIP1	physical	26344197

Drug and Disease Associations

• Kegg Disease
• There are no disease associations of PTM sites.
• OMIM Disease
• 250220: Spondylometaphyseal dysplasia, Sedaghatian type (SMDS)
• Kegg Drug
• There are no disease associations of PTM sites.
• DrugBank
• DB00143: Glutathione

Related Literatures of Post-Translational Modification

Acetylation

"Lysine acetylation targets protein complexes and co-regulates majorcellular functions.";
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.,Olsen J.V., Mann M.;
Science 325:834-840(2009).
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-47, AND MASS SPECTROMETRY.
PubMed: 19608861