Search Results

Overview

Uniprot IDQ8NEN9
Protein NamePDZ domain-containing protein 8
Gene NamePDZD8
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
930 EASKSVNKTTGLTRH

Function

Lipid transfer and molecular tethering protein, which plays a key role in the formation of membrane contact sites between the endoplasmic reticulum and other organelles, such as late endosomes/lysosomes and mitochondria (PubMed:29097544, PubMed:31636202, PubMed:31818884, PubMed:32686675, PubMed:33912962, PubMed:40246839, PubMed:40839735, PubMed:41512824). Faciliates the exchange of lipids at membrane contact sites between the endoplasmic reticulum and organelles by mediating the transport of lipids, such as ceramide, cholesterol and phosphatidylserine (PubMed:33912962, PubMed:40839735). Also acts as a molecular glue by undergoing liquid-liquid phase separation, forming condensates that mediate stable adhesion between endoplasmic reticulum and surrounding organelles, connecting two distinct membrane-bound vesicles coupled together (PubMed:41512824). Connects the endoplasmic reticulum to late endosomes/lysosomes, facilitating the exchange of lipids, which is crucial for membrane remodeling and processes, such as neurite outgrowth (PubMed:31636202, PubMed:32686675, PubMed:33912962). PDZD8-dependent endoplasmic reticulum-mitochondria membrane tethering is essential for endoplasmic reticulum-mitochondria Ca(2+) transfer (PubMed:29097544, PubMed:31818884, PubMed:40246839). In neurons, involved in the regulation of dendritic Ca(2+) dynamics by regulating mitochondrial Ca(2+) uptake in neurons (PubMed:29097544). Mediates lysosomal vacuolation, a process during which lysosomes abnormally enlarge into large membrane-bound sacs in response to stress such as osmotic stress: acts by mediating bulk lipid transfer from the endoplasmic reticulum to lysosomes, leading to vacuole formation (PubMed:40839735). Plays an indirect role in the regulation of cell morphology and cytoskeletal organization (PubMed:21834987). May indirectly inhibit herpes simplex virus 1 infection at an early stage (PubMed:21549406)

Protein Sequence

10 MGLLLMILAS 20 AVLGSFLTLL 30 AQFFLLYRRQ 40 PEPPADEAAR 50 AGEGFRYIKP 60 VPGLLLREYL 70 YGGGRDEEPS 80 GAAPEGGATP 90 TAAPETPAPP 100 TRETCYFLNA 110 TILFLFRELR 120 DTALTRRWVT 130 KKIKVEFEEL 140 LQTKTAGRLL 150 EGLSLRDVFL 160 GETVPFIKTI 170 RLVRPVVPSA 180 TGEPDGPEGE 190 ALPAACPEEL 200 AFEAEVEYNG 210 GFHLAIDVDL 220 VFGKSAYLFV 230 KLSRVVGRLR 240 LVFTRVPFTH 250 WFFSFVEDPL 260 IDFEVRSQFE 270 GRPMPQLTSI 280 IVNQLKKIIK 290 RKHTLPNYKI 300 RFKPFFPYQT 310 LQGFEEDEEH 320 IHIQQWALTE 330 GRLKVTLLEC 340 SRLLIFGSYD 350 REANVHCTLE 360 LSSSVWEEKQ 370 RSSIKTVELI 380 KGNLQSVGLT 390 LRLVQSTDGY 400 AGHVIIETVA 410 PNSPAAIADL 420 QRGDRLIAIG 430 GVKITSTLQV 440 LKLIKQAGDR 450 VLVYYERPVG 460 QSNQGAVLQD 470 NFGQLEENFL 480 SSSCQSGYEE 490 EAAGLTVDTE 500 SRELDSEFED 510 LASDVRAQNE 520 FKDEAQSLSH 530 SPKRVPTTLS 540 IKPLGAISPV 550 LNRKLAVGSH 560 PLPPKIQSKD 570 GNKPPPLKTS 580 EITDPAQVSK 590 PTQGSAFKPP 600 VPPRPQAKVP 610 LPSADAPNQA 620 EPDVLVEKPE 630 KVVPPPLVDK 640 SAEKQAKNVD 650 AIDDAAAPKQ 660 FLAKQEVAKD 670 VTSETSCPTK 680 DSSDDRQTWE 690 SSEILYRNKL 700 GKWTRTRASC 710 LFDIEACHRY 720 LNIALWCRDP 730 FKLGGLICLG 740 HVSLKLEDVA 750 LGCLATSNTE 760 YLSKLRLEAP 770 SPKAIVTRTA 780 LRNLSMQKGF 790 NDKFCYGDIT 800 IHFKYLKEGE 810 SDHHVVTNVE 820 KEKEPHLVEE 830 VSVLPKEEQF 840 VGQMGLTENK 850 HSFQDTQFQN 860 PTWCDYCKKK 870 VWTKAASQCM 880 FCAYVCHKKC 890 QEKCLAETSV 900 CGATDRRIDR 910 TLKNLRLEGQ 920 ETLLGLPPRV 930 DAEASKSVNK 940 TTGLTRHIIN 950 TSSRLLNLRQ 960 VSKTRLSEPG 970 TDLVEPSPKH 980 TPNTSDNEGS 990 DTEVCGPNSP 1000 SKRGNSTGIK 1010 LVRKEGGLDD 1020 SVFIAVKEIG 1030 RDLYRGLPTE 1040 ERIQKLEFML 1050 DKLQNEIDQE 1060 LEHNNSLVRE 1070 EKETTDTRKK 1080 SLLSAALAKS 1090 GERLQALTLL 1100 MIHYRAGIED 1110 IETLESLSLD 1120 QHSKKISKYT 1130 DDTEEDLDNE 1140 ISQLIDSQPF 1150 SSISDDLFGP SESV

Gene Ontology

Classification GO ID Description
Cellular Component GO:0005789 endoplasmic reticulum membrane
Cellular Component GO:0016020 membrane
Cellular Component GO:0044233 mitochondria-associated endoplasmic reticulum membrane contact site
Cellular Component GO:0005739 mitochondrion
Molecular Function GO:0008289 lipid binding
Molecular Function GO:0008270 zinc ion binding
Biological Process GO:0006869 lipid transport
Biological Process GO:0051560 mitochondrial calcium ion homeostasis
Biological Process GO:1990456 mitochondrion-endoplasmic reticulum membrane tethering

Reference

[1] He J, Lai T, Zhou Z, Yang H, Lei Z et al.. Multiomics profiling reveals the involvement of protein lactylation in nonhomologous end joining pathway conferring radioresistance in lung adenocarcinoma cell.. Sci Rep 15(1):24651. 2025 Jul 9. PMID: 40634431.