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Overview

Uniprot IDQ96QK1
Protein NameVacuolar protein sorting-associated protein 35
Gene NameVPS35
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
419 ILTVLKLKHFHPLFE
659 QCALAASKLLKKPDQ

Function

Acts as a component of the retromer cargo-selective complex (CSC). The CSC is believed to be the core functional component of retromer or respective retromer complex variants acting to prevent missorting of selected transmembrane cargo proteins into the lysosomal degradation pathway. The recruitment of the CSC to the endosomal membrane involves RAB7A and SNX3. The CSC seems to associate with the cytoplasmic domain of cargo proteins predominantly via VPS35; however, these interactions seem to be of low affinity and retromer SNX proteins may also contribute to cargo selectivity thus questioning the classical function of the CSC. The SNX-BAR retromer mediates retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN) and is involved in endosome-to-plasma membrane transport for cargo protein recycling. The SNX3-retromer mediates the retrograde endosome-to-TGN transport of WLS distinct from the SNX-BAR retromer pathway (PubMed:30213940). The SNX27-retromer is believed to be involved in endosome-to-plasma membrane trafficking and recycling of a broad spectrum of cargo proteins. The CSC seems to act as recruitment hub for other proteins, such as the WASH complex and TBC1D5 (Probable). Required for retrograde transport of lysosomal enzyme receptor IGF2R and SLC11A2. Required to regulate transcytosis of the polymeric immunoglobulin receptor (pIgR-pIgA) (PubMed:15078903, PubMed:15247922, PubMed:20164305). Required for endosomal localization of WASHC2C (PubMed:22070227, PubMed:28892079). Mediates the association of the CSC with the WASH complex via WASHC2 (PubMed:22070227, PubMed:24819384, PubMed:24980502). Required for the endosomal localization of TBC1D5 (PubMed:20923837)

Protein Sequence

10 MPTTQQSPQD 20 EQEKLLDEAI 30 QAVKVQSFQM 40 KRCLDKNKLM 50 DALKHASNML 60 GELRTSMLSP 70 KSYYELYMAI 80 SDELHYLEVY 90 LTDEFAKGRK 100 VADLYELVQY 110 AGNIIPRLYL 120 LITVGVVYVK 130 SFPQSRKDIL 140 KDLVEMCRGV 150 QHPLRGLFLR 160 NYLLQCTRNI 170 LPDEGEPTDE 180 ETTGDISDSM 190 DFVLLNFAEM 200 NKLWVRMQHQ 210 GHSRDREKRE 220 RERQELRILV 230 GTNLVRLSQL 240 EGVNVERYKQ 250 IVLTGILEQV 260 VNCRDALAQE 270 YLMECIIQVF 280 PDEFHLQTLN 290 PFLRACAELH 300 QNVNVKNIII 310 ALIDRLALFA 320 HREDGPGIPA 330 DIKLFDIFSQ 340 QVATVIQSRQ 350 DMPSEDVVSL 360 QVSLINLAMK 370 CYPDRVDYVD 380 KVLETTVEIF 390 NKLNLEHIAT 400 SSAVSKELTR 410 LLKIPVDTYN 420 NILTVLKLKH 430 FHPLFEYFDY 440 ESRKSMSCYV 450 LSNVLDYNTE 460 IVSQDQVDSI 470 MNLVSTLIQD 480 QPDQPVEDPD 490 PEDFADEQSL 500 VGRFIHLLRS 510 EDPDQQYLIL 520 NTARKHFGAG 530 GNQRIRFTLP 540 PLVFAAYQLA 550 FRYKENSKVD 560 DKWEKKCQKI 570 FSFAHQTISA 580 LIKAELAELP 590 LRLFLQGALA 600 AGEIGFENHE 610 TVAYEFMSQA 620 FSLYEDEISD 630 SKAQLAAITL 640 IIGTFERMKC 650 FSEENHEPLR 660 TQCALAASKL 670 LKKPDQGRAV 680 STCAHLFWSG 690 RNTDKNGEEL 700 HGGKRVMECL 710 KKALKIANQC 720 MDPSLQVQLF 730 IEILNRYIYF 740 YEKENDAVTI 750 QVLNQLIQKI 760 REDLPNLESS 770 EETEQINKHF 780 HNTLEHLRLR 790 RESPESEGPI YEGLIL

Gene Ontology

Classification GO ID Description
Cellular Component GO:0005829 cytosol
Biological Process GO:0090141 positive regulation of mitochondrial fission
Biological Process GO:0045732 positive regulation of protein catabolic process
Biological Process GO:1904377 positive regulation of protein localization to cell periphery
Biological Process GO:0061357 positive regulation of Wnt protein secretion
Biological Process GO:0031648 protein destabilization
Biological Process GO:0036010 protein localization to endosome
Biological Process GO:1902950 regulation of dendritic spine maintenance
Biological Process GO:0016241 regulation of macroautophagy
Biological Process GO:0010821 regulation of mitochondrion organization
Biological Process GO:0150052 regulation of postsynapse assembly
Biological Process GO:1905606 regulation of presynapse assembly
Biological Process GO:0051246 regulation of protein metabolic process
Biological Process GO:0031647 regulation of protein stability
Biological Process GO:0090128 regulation of synapse maturation
Biological Process GO:2000331 regulation of terminal button organization
Biological Process GO:0042147 retrograde transport, endosome to Golgi
Biological Process GO:0045056 transcytosis
Biological Process GO:0050882 voluntary musculoskeletal movement
Biological Process GO:0016055 Wnt signaling pathway
Cellular Component GO:0098691 dopaminergic synapse
Cellular Component GO:0005769 early endosome
Cellular Component GO:0005768 endosome
Cellular Component GO:0010008 endosome membrane
Cellular Component GO:0070062 extracellular exosome
Cellular Component GO:0098978 glutamatergic synapse
Cellular Component GO:0005770 late endosome
Cellular Component GO:0005765 lysosomal membrane
Cellular Component GO:0099073 mitochondrion-derived vesicle
Cellular Component GO:0043005 neuron projection
Cellular Component GO:0043025 neuronal cell body
Cellular Component GO:0048471 perinuclear region of cytoplasm
Cellular Component GO:0014069 postsynaptic density
Cellular Component GO:0098793 presynapse
Cellular Component GO:0030904 retromer complex
Cellular Component GO:0030906 retromer, cargo-selective complex
Cellular Component GO:0097422 tubular endosome
Molecular Function GO:0031748 D1 dopamine receptor binding
Biological Process GO:0032456 endocytic recycling
Biological Process GO:0006886 intracellular protein transport
Biological Process GO:0007040 lysosome organization
Biological Process GO:0043653 mitochondrial fragmentation involved in apoptotic process
Biological Process GO:0099074 mitochondrion to lysosome vesicle-mediated transport
Biological Process GO:0050804 modulation of chemical synaptic transmission
Biological Process GO:0010629 negative regulation of gene expression
Biological Process GO:0050728 negative regulation of inflammatory response
Biological Process GO:1902823 negative regulation of late endosome to lysosome transport
Biological Process GO:1905166 negative regulation of lysosomal protein catabolic process
Biological Process GO:0032463 negative regulation of protein homooligomerization
Biological Process GO:1903828 negative regulation of protein localization
Biological Process GO:0099639 neurotransmitter receptor transport, endosome to plasma membrane
Biological Process GO:0098887 neurotransmitter receptor transport, endosome to postsynaptic membrane
Biological Process GO:0090263 positive regulation of canonical Wnt signaling pathway
Biological Process GO:1903181 positive regulation of dopamine biosynthetic process
Biological Process GO:0060161 positive regulation of dopamine receptor signaling pathway
Biological Process GO:0010628 positive regulation of gene expression
Biological Process GO:0090326 positive regulation of locomotion involved in locomotory behavior

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.

[2] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.