UniProt functional annotation for Q8TDY2



	UniProt functional annotation for Q8TDY2

UniProt code: Q8TDY2.

Organism: Homo sapiens (Human).

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

Function: Involved in autophagy (PubMed:21775823). Regulates early events but also late events of autophagosome formation through direct interaction with Atg16L1 (PubMed:23392225). Required for the formation of the autophagosome-like double-membrane structure that surrounds the Salmonella-containing vacuole (SCV) during S.typhimurium infection and subsequent xenophagy (By similarity). Involved in repair of DNA damage caused by ionizing radiation, which subsequently improves cell survival by decreasing apoptosis (By similarity). Inhibits PTK2/FAK1 and PTK2B/PYK2 kinase activity, affecting their downstream signaling pathways (PubMed:10769033, PubMed:12221124). Plays a role as a modulator of TGF-beta-signaling by restricting substrate specificity of RNF111 (By similarity). Functions as a DNA-binding transcription factor (PubMed:12095676). Is a potent regulator of the RB1 pathway through induction of RB1 expression (PubMed:14533007). Plays a crucial role in muscular differentiation (PubMed:12163359). Plays an indispensable role in fetal hematopoiesis and in the regulation of neuronal homeostasis (By similarity). {ECO:0000250|UniProtKB:Q9ESK9, ECO:0000269|PubMed:10769033, ECO:0000269|PubMed:12095676, ECO:0000269|PubMed:12163359, ECO:0000269|PubMed:12221124, ECO:0000269|PubMed:14533007, ECO:0000269|PubMed:21775823, ECO:0000269|PubMed:23392225}.

Subunit: Part of a complex consisting of ATG13/KIAA0652, ULK1 and RB1CC1 (PubMed:19597335, PubMed:19211835). This complex associates with ATG101 (PubMed:19597335, PubMed:19211835). Interacts with PTK2/FAK1 and PTK2B/PYK2 (PubMed:10769033, PubMed:12221124). Interacts with GABARAP and GABARAPL1 (PubMed:23043107). Interacts with ATG16L1; the interaction is required for ULK1 complex-dependent autophagy (PubMed:24954904, PubMed:23262492, PubMed:23392225, PubMed:28890335). Interacts with RNF111, SKI and SMAD7 (By similarity). Interacts with COP1 in the cytoplasm of proliferating cells in response to UV stimulation (PubMed:23289756). Interacts with TP53 (PubMed:21775823). Interacts with C9orf72 (PubMed:27334615). Interacts with WDR45B (PubMed:28561066). Interacts with ATG13; this interaction is increased in the absence of TMEM39A (PubMed:31806350). Interacts with WIPI2 (PubMed:28890335). {ECO:0000250|UniProtKB:Q9ESK9, ECO:0000269|PubMed:10769033, ECO:0000269|PubMed:12221124, ECO:0000269|PubMed:19211835, ECO:0000269|PubMed:19597335, ECO:0000269|PubMed:21775823, ECO:0000269|PubMed:23043107, ECO:0000269|PubMed:23262492, ECO:0000269|PubMed:23289756, ECO:0000269|PubMed:23392225, ECO:0000269|PubMed:24954904, ECO:0000269|PubMed:27334615, ECO:0000269|PubMed:28561066, ECO:0000269|PubMed:28890335, ECO:0000269|PubMed:31806350}.

Subcellular location: Nucleus {ECO:0000269|PubMed:11850849}. Cytoplasm {ECO:0000269|PubMed:10769033}. Cytoplasm, cytosol {ECO:0000250|UniProtKB:Q9ESK9}. Preautophagosomal structure {ECO:0000269|PubMed:28561066}. Lysosome {ECO:0000269|PubMed:28561066}. Note=Under starvation conditions, is localized to puncate structures primarily representing the isolation membrane that sequesters a portion of the cytoplasm resulting in the formation of an autophagosome. {ECO:0000269|PubMed:28561066, ECO:0000269|PubMed:28890335}.

Tissue specificity: Expression levels correlated closely with those of RB1 in cancer cell lines as well as in various normal human tissues. Abundantly expressed in human musculoskeletal and cultured osteosarcoma cells. {ECO:0000269|PubMed:11850849, ECO:0000269|PubMed:12163359}.

Developmental stage: Expression was difficult to detect in immature proliferating chondroblasts or myogenic cells in embryos, but became obvious and prominent concomitantly with the maturation of osteocytes, chondrocytes, and skeletal muscle cells. Expression in these musculoskeletal cells increased with RB1 expression, which is linked to the terminal differentiation of many tissues and cells. The introduction of the wild-type protein decreased the formation of macroscopic colonies in a cell growth assay. {ECO:0000269|PubMed:12163359}.

Miscellaneous: Probably involved in the tumorigenesis of breast cancer. RB1CC1 is frequently mutated in breast cancer and shows characteristics of a classical tumor suppressor gene.

Similarity: Belongs to the ATG17 family. {ECO:0000305}.

Sequence caution: Sequence=BAA13194.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={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:		Involved in autophagy (PubMed:21775823). Regulates early events but also late events of autophagosome formation through direct interaction with Atg16L1 (PubMed:23392225). Required for the formation of the autophagosome-like double-membrane structure that surrounds the Salmonella-containing vacuole (SCV) during S.typhimurium infection and subsequent xenophagy (By similarity). Involved in repair of DNA damage caused by ionizing radiation, which subsequently improves cell survival by decreasing apoptosis (By similarity). Inhibits PTK2/FAK1 and PTK2B/PYK2 kinase activity, affecting their downstream signaling pathways (PubMed:10769033, PubMed:12221124). Plays a role as a modulator of TGF-beta-signaling by restricting substrate specificity of RNF111 (By similarity). Functions as a DNA-binding transcription factor (PubMed:12095676). Is a potent regulator of the RB1 pathway through induction of RB1 expression (PubMed:14533007). Plays a crucial role in muscular differentiation (PubMed:12163359). Plays an indispensable role in fetal hematopoiesis and in the regulation of neuronal homeostasis (By similarity). {ECO:0000250\|UniProtKB:Q9ESK9, ECO:0000269\|PubMed:10769033, ECO:0000269\|PubMed:12095676, ECO:0000269\|PubMed:12163359, ECO:0000269\|PubMed:12221124, ECO:0000269\|PubMed:14533007, ECO:0000269\|PubMed:21775823, ECO:0000269\|PubMed:23392225}.


Subunit:		Part of a complex consisting of ATG13/KIAA0652, ULK1 and RB1CC1 (PubMed:19597335, PubMed:19211835). This complex associates with ATG101 (PubMed:19597335, PubMed:19211835). Interacts with PTK2/FAK1 and PTK2B/PYK2 (PubMed:10769033, PubMed:12221124). Interacts with GABARAP and GABARAPL1 (PubMed:23043107). Interacts with ATG16L1; the interaction is required for ULK1 complex-dependent autophagy (PubMed:24954904, PubMed:23262492, PubMed:23392225, PubMed:28890335). Interacts with RNF111, SKI and SMAD7 (By similarity). Interacts with COP1 in the cytoplasm of proliferating cells in response to UV stimulation (PubMed:23289756). Interacts with TP53 (PubMed:21775823). Interacts with C9orf72 (PubMed:27334615). Interacts with WDR45B (PubMed:28561066). Interacts with ATG13; this interaction is increased in the absence of TMEM39A (PubMed:31806350). Interacts with WIPI2 (PubMed:28890335). {ECO:0000250\|UniProtKB:Q9ESK9, ECO:0000269\|PubMed:10769033, ECO:0000269\|PubMed:12221124, ECO:0000269\|PubMed:19211835, ECO:0000269\|PubMed:19597335, ECO:0000269\|PubMed:21775823, ECO:0000269\|PubMed:23043107, ECO:0000269\|PubMed:23262492, ECO:0000269\|PubMed:23289756, ECO:0000269\|PubMed:23392225, ECO:0000269\|PubMed:24954904, ECO:0000269\|PubMed:27334615, ECO:0000269\|PubMed:28561066, ECO:0000269\|PubMed:28890335, ECO:0000269\|PubMed:31806350}.
Subcellular location:		Nucleus {ECO:0000269\|PubMed:11850849}. Cytoplasm {ECO:0000269\|PubMed:10769033}. Cytoplasm, cytosol {ECO:0000250\|UniProtKB:Q9ESK9}. Preautophagosomal structure {ECO:0000269\|PubMed:28561066}. Lysosome {ECO:0000269\|PubMed:28561066}. Note=Under starvation conditions, is localized to puncate structures primarily representing the isolation membrane that sequesters a portion of the cytoplasm resulting in the formation of an autophagosome. {ECO:0000269\|PubMed:28561066, ECO:0000269\|PubMed:28890335}.
Tissue specificity:		Expression levels correlated closely with those of RB1 in cancer cell lines as well as in various normal human tissues. Abundantly expressed in human musculoskeletal and cultured osteosarcoma cells. {ECO:0000269\|PubMed:11850849, ECO:0000269\|PubMed:12163359}.
Developmental stage:		Expression was difficult to detect in immature proliferating chondroblasts or myogenic cells in embryos, but became obvious and prominent concomitantly with the maturation of osteocytes, chondrocytes, and skeletal muscle cells. Expression in these musculoskeletal cells increased with RB1 expression, which is linked to the terminal differentiation of many tissues and cells. The introduction of the wild-type protein decreased the formation of macroscopic colonies in a cell growth assay. {ECO:0000269\|PubMed:12163359}.
Miscellaneous:		Probably involved in the tumorigenesis of breast cancer. RB1CC1 is frequently mutated in breast cancer and shows characteristics of a classical tumor suppressor gene.
Similarity:		Belongs to the ATG17 family. {ECO:0000305}.
Sequence caution:		Sequence=BAA13194.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};