UniProt functional annotation for O95166



	UniProt functional annotation for O95166

UniProt code: O95166.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Ubiquitin-like modifier that plays a role in intracellular transport of GABA(A) receptors and its interaction with the cytoskeleton (PubMed:9892355). Involved in autophagy: while LC3s are involved in elongation of the phagophore membrane, the GABARAP/GATE-16 subfamily is essential for a later stage in autophagosome maturation (PubMed:15169837, PubMed:20562859, PubMed:22948227). Through its interaction with the reticulophagy receptor TEX264, participates in the remodeling of subdomains of the endoplasmic reticulum into autophagosomes upon nutrient stress, which then fuse with lysosomes for endoplasmic reticulum turnover (PubMed:31006538). Also required for the local activition of the CUL3(KBTBD6/7) E3 ubiquitin ligase complex, regulating ubiquitination and degradation of TIAM1, a guanyl-nucleotide exchange factor (GEF) that activates RAC1 and downstream signal transduction (PubMed:25684205). Thereby, regulates different biological processes including the organization of the cytoskeleton, cell migration and proliferation (PubMed:25684205). Involved in apoptosis (PubMed:15977068). {ECO:0000269|PubMed:15169837, ECO:0000269|PubMed:15977068, ECO:0000269|PubMed:20562859, ECO:0000269|PubMed:22948227, ECO:0000269|PubMed:25684205, ECO:0000269|PubMed:31006538, ECO:0000269|PubMed:9892355}.

Subunit: Interacts with GPHN and NSF (By similarity). Interacts with ATG3, ATG7, ATG13 (PubMed:11096062, PubMed:11825910, PubMed:12507496, PubMed:23043107). Interacts with alpha- and beta-tubulin (PubMed:9892355, PubMed:11729197). Interacts with GABRG2 (PubMed:9892355, PubMed:11729197). Interacts with RB1CC1 (PubMed:23043107). Interacts with ULK1 (PubMed:11146101, PubMed:23043107). Interacts with CALR (PubMed:19154346). Interacts with DDX47 (PubMed:15977068). Interacts with TP53INP1 and TP53INP2 (PubMed:19056683, PubMed:22421968, PubMed:22470510). Interacts with TBC1D5 and TBC1D25 (PubMed:21383079, PubMed:22354992). Directly interacts with SQSTM1 (PubMed:17580304, PubMed:24668264). Interacts with MAPK15 (PubMed:22948227). Interacts with TECPR2 (PubMed:20562859). Interacts with PCM1 (PubMed:24089205). Interacts with TRIM5 and TRIM21 (PubMed:25127057, PubMed:26347139). Interacts with MEFV (PubMed:26347139). Interacts with KIF21B (By similarity). Interacts with WDFY3; this interaction is required for WDFY3 recruitment to MAP1LC3B-positive p62/SQSTM1 bodies (PubMed:24668264). Interacts with the reticulophagy receptor TEX264 (PubMed:31006538). Interacts with UBA5 (PubMed:26929408). Interacts with FLCN; interaction regulates autophagy (PubMed:25126726). Interacts with KBTBD6 and KBTBD7; the interaction is direct and required for the ubiquitination of TIAM1 (PubMed:25684205). {ECO:0000250|UniProtKB:P60517, ECO:0000269|PubMed:11096062, ECO:0000269|PubMed:11146101, ECO:0000269|PubMed:11729197, ECO:0000269|PubMed:11825910, ECO:0000269|PubMed:12507496, ECO:0000269|PubMed:15977068, ECO:0000269|PubMed:17580304, ECO:0000269|PubMed:19056683, ECO:0000269|PubMed:19154346, ECO:0000269|PubMed:20562859, ECO:0000269|PubMed:21383079, ECO:0000269|PubMed:22354992, ECO:0000269|PubMed:22421968, ECO:0000269|PubMed:22470510, ECO:0000269|PubMed:22948227, ECO:0000269|PubMed:23043107, ECO:0000269|PubMed:24089205, ECO:0000269|PubMed:24668264, ECO:0000269|PubMed:25126726, ECO:0000269|PubMed:25127057, ECO:0000269|PubMed:25684205, ECO:0000269|PubMed:26347139, ECO:0000269|PubMed:26929408, ECO:0000269|PubMed:31006538, ECO:0000269|PubMed:9892355}.

Subcellular location: Endomembrane system {ECO:0000250|UniProtKB:P60517}. Cytoplasm, cytoskeleton {ECO:0000250|UniProtKB:P60517}. Golgi apparatus membrane {ECO:0000250|UniProtKB:P60517}. Cytoplasmic vesicle, autophagosome {ECO:0000269|PubMed:12507496, ECO:0000269|PubMed:15169837, ECO:0000269|PubMed:17580304, ECO:0000269|PubMed:19056683}. Cytoplasmic vesicle {ECO:0000250|UniProtKB:P60517}. Note=Largely associated with intracellular membrane structures including the Golgi apparatus and postsynaptic cisternae. Colocalizes with microtubules (By similarity). Localizes also to discrete punctae along the ciliary axoneme (By similarity). {ECO:0000250|UniProtKB:P60517, ECO:0000250|UniProtKB:Q9DCD6}.

Tissue specificity: Heart, brain, placenta, liver, skeletal muscle, kidney and pancreas. {ECO:0000269|PubMed:11146101, ECO:0000269|PubMed:9892355}.

Ptm: The precursor molecule is cleaved by ATG4B to form the cytosolic form, GABARAP-I (PubMed:15169837). This is activated by APG7L/ATG7, transferred to ATG3 and conjugated to phospholipid to form the membrane-bound form, GABARAP-II (PubMed:15169837). {ECO:0000269|PubMed:15169837}.

Similarity: Belongs to the ATG8 family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Ubiquitin-like modifier that plays a role in intracellular transport of GABA(A) receptors and its interaction with the cytoskeleton (PubMed:9892355). Involved in autophagy: while LC3s are involved in elongation of the phagophore membrane, the GABARAP/GATE-16 subfamily is essential for a later stage in autophagosome maturation (PubMed:15169837, PubMed:20562859, PubMed:22948227). Through its interaction with the reticulophagy receptor TEX264, participates in the remodeling of subdomains of the endoplasmic reticulum into autophagosomes upon nutrient stress, which then fuse with lysosomes for endoplasmic reticulum turnover (PubMed:31006538). Also required for the local activition of the CUL3(KBTBD6/7) E3 ubiquitin ligase complex, regulating ubiquitination and degradation of TIAM1, a guanyl-nucleotide exchange factor (GEF) that activates RAC1 and downstream signal transduction (PubMed:25684205). Thereby, regulates different biological processes including the organization of the cytoskeleton, cell migration and proliferation (PubMed:25684205). Involved in apoptosis (PubMed:15977068). {ECO:0000269\|PubMed:15169837, ECO:0000269\|PubMed:15977068, ECO:0000269\|PubMed:20562859, ECO:0000269\|PubMed:22948227, ECO:0000269\|PubMed:25684205, ECO:0000269\|PubMed:31006538, ECO:0000269\|PubMed:9892355}.


Subunit:		Interacts with GPHN and NSF (By similarity). Interacts with ATG3, ATG7, ATG13 (PubMed:11096062, PubMed:11825910, PubMed:12507496, PubMed:23043107). Interacts with alpha- and beta-tubulin (PubMed:9892355, PubMed:11729197). Interacts with GABRG2 (PubMed:9892355, PubMed:11729197). Interacts with RB1CC1 (PubMed:23043107). Interacts with ULK1 (PubMed:11146101, PubMed:23043107). Interacts with CALR (PubMed:19154346). Interacts with DDX47 (PubMed:15977068). Interacts with TP53INP1 and TP53INP2 (PubMed:19056683, PubMed:22421968, PubMed:22470510). Interacts with TBC1D5 and TBC1D25 (PubMed:21383079, PubMed:22354992). Directly interacts with SQSTM1 (PubMed:17580304, PubMed:24668264). Interacts with MAPK15 (PubMed:22948227). Interacts with TECPR2 (PubMed:20562859). Interacts with PCM1 (PubMed:24089205). Interacts with TRIM5 and TRIM21 (PubMed:25127057, PubMed:26347139). Interacts with MEFV (PubMed:26347139). Interacts with KIF21B (By similarity). Interacts with WDFY3; this interaction is required for WDFY3 recruitment to MAP1LC3B-positive p62/SQSTM1 bodies (PubMed:24668264). Interacts with the reticulophagy receptor TEX264 (PubMed:31006538). Interacts with UBA5 (PubMed:26929408). Interacts with FLCN; interaction regulates autophagy (PubMed:25126726). Interacts with KBTBD6 and KBTBD7; the interaction is direct and required for the ubiquitination of TIAM1 (PubMed:25684205). {ECO:0000250\|UniProtKB:P60517, ECO:0000269\|PubMed:11096062, ECO:0000269\|PubMed:11146101, ECO:0000269\|PubMed:11729197, ECO:0000269\|PubMed:11825910, ECO:0000269\|PubMed:12507496, ECO:0000269\|PubMed:15977068, ECO:0000269\|PubMed:17580304, ECO:0000269\|PubMed:19056683, ECO:0000269\|PubMed:19154346, ECO:0000269\|PubMed:20562859, ECO:0000269\|PubMed:21383079, ECO:0000269\|PubMed:22354992, ECO:0000269\|PubMed:22421968, ECO:0000269\|PubMed:22470510, ECO:0000269\|PubMed:22948227, ECO:0000269\|PubMed:23043107, ECO:0000269\|PubMed:24089205, ECO:0000269\|PubMed:24668264, ECO:0000269\|PubMed:25126726, ECO:0000269\|PubMed:25127057, ECO:0000269\|PubMed:25684205, ECO:0000269\|PubMed:26347139, ECO:0000269\|PubMed:26929408, ECO:0000269\|PubMed:31006538, ECO:0000269\|PubMed:9892355}.
Subcellular location:		Endomembrane system {ECO:0000250\|UniProtKB:P60517}. Cytoplasm, cytoskeleton {ECO:0000250\|UniProtKB:P60517}. Golgi apparatus membrane {ECO:0000250\|UniProtKB:P60517}. Cytoplasmic vesicle, autophagosome {ECO:0000269\|PubMed:12507496, ECO:0000269\|PubMed:15169837, ECO:0000269\|PubMed:17580304, ECO:0000269\|PubMed:19056683}. Cytoplasmic vesicle {ECO:0000250\|UniProtKB:P60517}. Note=Largely associated with intracellular membrane structures including the Golgi apparatus and postsynaptic cisternae. Colocalizes with microtubules (By similarity). Localizes also to discrete punctae along the ciliary axoneme (By similarity). {ECO:0000250\|UniProtKB:P60517, ECO:0000250\|UniProtKB:Q9DCD6}.
Tissue specificity:		Heart, brain, placenta, liver, skeletal muscle, kidney and pancreas. {ECO:0000269\|PubMed:11146101, ECO:0000269\|PubMed:9892355}.
Ptm:		The precursor molecule is cleaved by ATG4B to form the cytosolic form, GABARAP-I (PubMed:15169837). This is activated by APG7L/ATG7, transferred to ATG3 and conjugated to phospholipid to form the membrane-bound form, GABARAP-II (PubMed:15169837). {ECO:0000269\|PubMed:15169837}.
Similarity:		Belongs to the ATG8 family. {ECO:0000305}.