Overview
| Uniprot ID | Q9NP80 |
|---|
| Protein Name | Calcium-independent phospholipase A2-gamma |
|---|
| Gene Name | PNPLA8 |
|---|
| Organism | Homo sapiens |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 463 |
VALQTLRKLVELTQK |
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)
Protein Sequence
10
MSINLTVDIY
20
IYLLSNARSV
30
CGKQRSKQLY
40
FLFSPKHYWR
50
ISHISLQRGF
60
HTNIIRCKWT
70
KSEAHSCSKH
80
CYSPSNHGLH
90
IGILKLSTSA
100
PKGLTKVNIC
110
MSRIKSTLNS
120
VSKAVFGNQN
130
EMISRLAQFK
140
PSSQILRKVS
150
DSGWLKQKNI
160
KQAIKSLKKY
170
SDKSAEKSPF
180
PEEKSHIIDK
190
EEDIGKRSLF
200
HYTSSITTKF
210
GDSFYFLSNH
220
INSYFKRKEK
230
MSQQKENEHF
240
RDKSELEDKK
250
VEEGKLRSPD
260
PGILAYKPGS
270
ESVHTVDKPT
280
SPSAIPDVLQ
290
VSTKQSIANF
300
LSRPTEGVQA
310
LVGGYIGGLV
320
PKLKYDSKSQ
330
SEEQEEPAKT
340
DQAVSKDRNA
350
EEKKRLSLQR
360
EKIIARVSID
370
NRTRALVQAL
380
RRTTDPKLCI
390
TRVEELTFHL
400
LEFPEGKGVA
410
VKERIIPYLL
420
RLRQIKDETL
430
QAAVREILAL
440
IGYVDPVKGR
450
GIRILSIDGG
460
GTRGVVALQT
470
LRKLVELTQK
480
PVHQLFDYIC
490
GVSTGAILAF
500
MLGLFHMPLD
510
ECEELYRKLG
520
SDVFSQNVIV
530
GTVKMSWSHA
540
FYDSQTWENI
550
LKDRMGSALM
560
IETARNPTCP
570
KVAAVSTIVN
580
RGITPKAFVF
590
RNYGHFPGIN
600
SHYLGGCQYK
610
MWQAIRASSA
620
APGYFAEYAL
630
GNDLHQDGGL
640
LLNNPSALAM
650
HECKCLWPDV
660
PLECIVSLGT
670
GRYESDVRNT
680
VTYTSLKTKL
690
SNVINSATDT
700
EEVHIMLDGL
710
LPPDTYFRFN
720
PVMCENIPLD
730
ESRNEKLDQL
740
QLEGLKYIER
750
NEQKMKKVAK
760
ILSQEKTTLQ
770
KINDWIKLKT
780
DMYEGLPFFS
KL
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0005789 |
endoplasmic reticulum membrane |
| Cellular Component |
GO:0016020 |
membrane |
| Cellular Component |
GO:0031966 |
mitochondrial membrane |
| Cellular Component |
GO:0005739 |
mitochondrion |
| Cellular Component |
GO:0005778 |
peroxisomal membrane |
| Cellular Component |
GO:0005777 |
peroxisome |
| Molecular Function |
GO:0004623 |
A2-type glycerophospholipase activity |
| Molecular Function |
GO:0005524 |
ATP binding |
| Molecular Function |
GO:0008970 |
glycerophospholipid phospholipase A1 activity |
| Molecular Function |
GO:0004622 |
phosphatidylcholine lysophospholipase A1 activity |
| Biological Process |
GO:0019369 |
arachidonate metabolic process |
| Biological Process |
GO:0050482 |
arachidonate secretion |
| Biological Process |
GO:0032048 |
cardiolipin metabolic process |
| Biological Process |
GO:0006631 |
fatty acid metabolic process |
| Biological Process |
GO:0035556 |
intracellular signal transduction |
| Biological Process |
GO:0043651 |
linoleic acid metabolic process |
| Biological Process |
GO:0055088 |
lipid homeostasis |
| Biological Process |
GO:0034638 |
phosphatidylcholine catabolic process |
| Biological Process |
GO:0046338 |
phosphatidylethanolamine catabolic process |
| Biological Process |
GO:0001516 |
prostaglandin biosynthetic process |
| Biological Process |
GO:1900407 |
regulation of cellular response to oxidative stress |
| Biological Process |
GO:0070328 |
triglyceride homeostasis |
Reference
[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.