PNPLA8
entrez
50640
canonical
uniprot
Q9NP80
canonical
ensembl
ENSG00000135241
resolver
ensp
ENSP00000257694
resolver
ensp
ENSP00000387789
resolver
ensp
ENSP00000394988
resolver
ensp
ENSP00000402274
resolver
ensp
ENSP00000406779
resolver
ensp
ENSP00000410804
resolver
ensp
ENSP00000594217
resolver
genesymbol
PNPLA8
resolver
genesymbol_syn
IPLA22
resolver
genesymbol_syn
IPLA2G
resolver
hgnc
HGNC:28900
resolver
uniprot
A4D0S1
resolver
uniprot
C9JZI4
resolver
uniprot
O95035
resolver
uniprot
Q8N3I3
resolver
uniprot
Q9H7T5
resolver
uniprot
Q9NR17
resolver
uniprot
Q9NUN2
resolver
uniprot
Q9NZ79
resolver
uniprot_entry
PLPL8_HUMAN
resolver
uniprot_sec
A4D0S1
resolver
uniprot_sec
C9JZI4
resolver
uniprot_sec
O95035
resolver
uniprot_sec
Q8N3I3
resolver
uniprot_sec
Q9H7T5
resolver
uniprot_sec
Q9NR17
resolver
uniprot_sec
Q9NUN2
resolver
uniprot_sec
Q9NZ79
resolver
activity_regulation
ACTIVITY REGULATION: Calcium-independent phospholipase (PubMed:10744668, PubMed:10833412). Inhibited by (E)-6-bromomethylene-3-1-naphthalenyl-2H-tetrahydropyran-2-one (BEL) (PubMed:10744668, PubMed:15908428, PubMed:18171998). The activity toward 1-hexadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine is stimulated by cardiolipin (PubMed:28442572). {ECO:0000269|PubMed:10744668, ECO:0000269|PubMed:10833412, ECO:0000269|PubMed:15908428, ECO:0000269|PubMed:18171998, ECO:0000269|PubMed:28442572}.
uniprot
proteins
amino_acid_sequence
MSINLTVDIYIYLLSNARSVCGKQRSKQLYFLFSPKHYWRISHISLQRGFHTNIIRCKWTKSEAHSCSKHCYSPSNHGLHIGILKLSTSAPKGLTKVNICMSRIKSTLNSVSKAVFGNQNEMISRLAQFKPSSQILRKVSDSGWLKQKNIKQAIKSLKKYSDKSAEKSPFPEEKSHIIDKEEDIGKRSLFHYTSSITTKFGDSFYFLSNHINSYFKRKEKMSQQKENEHFRDKSELEDKKVEEGKLRSPDPGILAYKPGSESVHTVDKPTSPSAIPDVLQVSTKQSIANFLSRPTEGVQALVGGYIGGLVPKLKYDSKSQSEEQEEPAKTDQAVSKDRNAEEKKRLSLQREKIIARVSIDNRTRALVQALRRTTDPKLCITRVEELTFHLLEFPEGKGVAVKERIIPYLLRLRQIKDETLQAAVREILALIGYVDPVKGRGIRILSIDGGGTRGVVALQTLRKLVELTQKPVHQLFDYICGVSTGAILAFMLGLFHMPLDECEELYRKLGSDVFSQNVIVGTVKMSWSHAFYDSQTWENILKDRMGSALMIETARNPTCPKVAAVSTIVNRGITPKAFVFRNYGHFPGINSHYLGGCQYKMWQAIRASSAAPGYFAEYALGNDLHQDGGLLLNNPSALAMHECKCLWPDVPLECIVSLGTGRYESDVRNTVTYTSLKTKLSNVINSATDTEEVHIMLDGLLPPDTYFRFNPVMCENIPLDESRNEKLDQLQLEGLKYIERNEQKMKKVAKILSQEKTTLQKINDWIKLKTDMYEGLPFFSKL
uniprot
proteins
disease_involvement
DISEASE: Mitochondrial myopathy with lactic acidosis (MMLA) [MIM:251950]: An autosomal recessive disorder characterized by progressive muscle weakness, hypotonia, seizures, poor weight gain, lactic acidosis, and elevated serum pyruvate concentration. Some patients manifest growth failure and moderate neural deafness. {ECO:0000269|PubMed:25512002}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
3.1.1.-
uniprot
proteins
ec_number
3.1.1.5
uniprot
proteins
function
FUNCTION: Calcium-independent and membrane-bound phospholipase, that catalyzes the esterolytic cleavage of fatty acids from glycerophospholipids to yield free fatty acids and lysophospholipids, hence regulating membrane physical properties and the release of lipid second messengers and growth factors (PubMed:10744668, PubMed:10833412, PubMed:15695510, PubMed:15908428, PubMed:17213206, PubMed:18171998, PubMed:28442572). Hydrolyzes phosphatidylethanolamine, phosphatidylcholine and probably phosphatidylinositol with a possible preference for the former (PubMed:15695510). Also has a broad substrate specificity in terms of fatty acid moieties, hydrolyzing saturated and mono-unsaturated fatty acids at nearly equal rates from either the sn-1 or sn-2 position in diacyl phosphatidylcholine (PubMed:10744668, PubMed:10833412, PubMed:15695510, PubMed:15908428). However, has a weak activity toward polyunsaturated fatty acids at the sn-2 position, and thereby favors the production of 2-arachidonoyl lysophosphatidylcholine, a key branch point metabolite in eicosanoid signaling (PubMed:15908428). On the other hand, can produce arachidonic acid from the sn-1 position of diacyl phospholipid and from the sn-2 position of arachidonate-containing plasmalogen substrates (PubMed:15908428). Therefore, plays an important role in the mobilization of arachidonic acid in response to cellular stimuli and the generation of lipid second messengers (PubMed:15695510, PubMed:15908428). Can also hydrolyze lysophosphatidylcholine (PubMed:15695510). In the mitochondrial compartment, catalyzes the hydrolysis and release of oxidized aliphatic chains from cardiolipin and integrates mitochondrial bioenergetics and signaling. It is essential for maintaining efficient bioenergetic mitochondrial function through tailoring mitochondrial membrane lipid metabolism and composition (PubMed:28442572). {ECO:0000250|UniProtKB:Q8K1N1, ECO:0000269|PubMed:10744668, ECO:0000269|PubMed:10833412, ECO:0000269|PubMed:15695510, ECO:0000269|PubMed:15908428, ECO:0000269|PubMed:17213206, ECO:0000269|PubMed:18171998, ECO:0000269|PubMed:28442572}.
uniprot
proteins
mass_dalton
88477
uniprot
proteins
pathway_participation
PATHWAY: Phospholipid metabolism. {ECO:0000305|PubMed:15908428}.
uniprot
proteins
pubmed
10744668
uniprot
proteins
pubmed
10833412
uniprot
proteins
pubmed
12690205
uniprot
proteins
pubmed
12853948
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15629460
uniprot
proteins
pubmed
15695510
uniprot
proteins
pubmed
15908428
uniprot
proteins
pubmed
17213206
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
18171998
uniprot
proteins
pubmed
25512002
uniprot
proteins
pubmed
28442572
uniprot
proteins
sequence_length
782
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:Q5XTS1}; Single-pass membrane protein {ECO:0000305|PubMed:10744668, ECO:0000305|PubMed:10833412}. Mitochondrion membrane {ECO:0000305|PubMed:17213206}; Single-pass membrane protein {ECO:0000305|PubMed:10744668, ECO:0000305|PubMed:10833412}. Peroxisome membrane {ECO:0000269|PubMed:15695510}; Single-pass membrane protein {ECO:0000305|PubMed:10744668, ECO:0000305|PubMed:10833412}.
uniprot
proteins
transmembrane_region
TRANSMEM 475..495; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins