O70405 · ULK1_MOUSE
- ProteinSerine/threonine-protein kinase ULK1
- GeneUlk1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids1051 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Serine/threonine-protein kinase involved in autophagy in response to starvation (PubMed:10624947, PubMed:19258318, PubMed:21205641, PubMed:21258367, PubMed:21460634, PubMed:25040165, PubMed:25723488).
Acts upstream of phosphatidylinositol 3-kinase PIK3C3 to regulate the formation of autophagophores, the precursors of autophagosomes (PubMed:10624947, PubMed:19258318, PubMed:21205641, PubMed:21258367, PubMed:21460634, PubMed:25040165).
Part of regulatory feedback loops in autophagy: acts both as a downstream effector and negative regulator of mammalian target of rapamycin complex 1 (mTORC1) via interaction with RPTOR (PubMed:21205641, PubMed:21258367).
Activated via phosphorylation by AMPK and also acts as a regulator of AMPK by mediating phosphorylation of AMPK subunits PRKAA1, PRKAB2 and PRKAG1, leading to negatively regulate AMPK activity (PubMed:21460634).
May phosphorylate ATG13/KIAA0652 and RPTOR; however such data need additional evidences (PubMed:19258318).
Plays a role early in neuronal differentiation and is required for granule cell axon formation (By similarity).
Also phosphorylates SESN2 and SQSTM1 to regulate autophagy (PubMed:25040165, PubMed:25723488).
Phosphorylates FLCN, promoting autophagy (By similarity).
Phosphorylates AMBRA1 in response to autophagy induction, releasing AMBRA1 from the cytoskeletal docking site to induce autophagosome nucleation (By similarity).
Phosphorylates ATG4B, leading to inhibit autophagy by decreasing both proteolytic activation and delipidation activities of ATG4B (By similarity).
Acts upstream of phosphatidylinositol 3-kinase PIK3C3 to regulate the formation of autophagophores, the precursors of autophagosomes (PubMed:10624947, PubMed:19258318, PubMed:21205641, PubMed:21258367, PubMed:21460634, PubMed:25040165).
Part of regulatory feedback loops in autophagy: acts both as a downstream effector and negative regulator of mammalian target of rapamycin complex 1 (mTORC1) via interaction with RPTOR (PubMed:21205641, PubMed:21258367).
Activated via phosphorylation by AMPK and also acts as a regulator of AMPK by mediating phosphorylation of AMPK subunits PRKAA1, PRKAB2 and PRKAG1, leading to negatively regulate AMPK activity (PubMed:21460634).
May phosphorylate ATG13/KIAA0652 and RPTOR; however such data need additional evidences (PubMed:19258318).
Plays a role early in neuronal differentiation and is required for granule cell axon formation (By similarity).
Also phosphorylates SESN2 and SQSTM1 to regulate autophagy (PubMed:25040165, PubMed:25723488).
Phosphorylates FLCN, promoting autophagy (By similarity).
Phosphorylates AMBRA1 in response to autophagy induction, releasing AMBRA1 from the cytoskeletal docking site to induce autophagosome nucleation (By similarity).
Phosphorylates ATG4B, leading to inhibit autophagy by decreasing both proteolytic activation and delipidation activities of ATG4B (By similarity).
Catalytic activity
- ATP + L-seryl-[protein] = ADP + H+ + O-phospho-L-seryl-[protein]
Activity regulation
Acetylation by KAT5/TIP60 stimulates the protein kinase activity (PubMed:22539723).
The protein kinase activity is activated by unanchored 'Lys-63'-linked polyubiquitin chains: unanchored 'Lys-63'-linked polyubiquitin chains are catalyzed by TRIM32 in an AMBRA1-dependent manner (By similarity).
The protein kinase activity is activated by unanchored 'Lys-63'-linked polyubiquitin chains: unanchored 'Lys-63'-linked polyubiquitin chains are catalyzed by TRIM32 in an AMBRA1-dependent manner (By similarity).
Features
Showing features for binding site, active site.
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameSerine/threonine-protein kinase ULK1
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionO70405
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
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.
Keywords
- Cellular component
Phenotypes & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 46 | Abolished serine/threonine-protein kinase activity. | ||||
Sequence: K → I | ||||||
Mutagenesis | 46 | Loss of kinase activity and autophosphorylation. | ||||
Sequence: K → R | ||||||
Mutagenesis | 162 | In K2R; abolished acetylation by KAT5/TIP60 and decreased kinase activity; when associated with R-606. | ||||
Sequence: K → R | ||||||
Mutagenesis | 317 | Impairs phosphorylation by AMPK and ability to promote autophagy; when associated with A-777. | ||||
Sequence: S → A | ||||||
Mutagenesis | 494 | Does not affect phosphorylation by AMPK in vitro. | ||||
Sequence: S → A | ||||||
Mutagenesis | 555 | Does not affect phosphorylation by AMPK in vitro. | ||||
Sequence: S → A | ||||||
Mutagenesis | 574 | Does not affect phosphorylation by AMPK in vitro. | ||||
Sequence: T → A | ||||||
Mutagenesis | 606 | In K2R; abolished acetylation by KAT5/TIP60 and decreased kinase activity; when associated with R-162. | ||||
Sequence: K → R | ||||||
Mutagenesis | 622 | Does not affect phosphorylation by AMPK in vitro. | ||||
Sequence: S → A | ||||||
Mutagenesis | 624 | Does not affect phosphorylation by AMPK in vitro. | ||||
Sequence: T → A | ||||||
Mutagenesis | 693 | Does not affect phosphorylation by AMPK in vitro. | ||||
Sequence: S → A | ||||||
Mutagenesis | 757 | Impairs interaction with AMPK and subsequent phosphorylation by AMPK. | ||||
Sequence: S → A or D | ||||||
Mutagenesis | 777 | Impairs phosphorylation by AMPK and ability to promote autophagy; when associated with A-317. | ||||
Sequence: S → A | ||||||
Mutagenesis | 811 | Does not affect phosphorylation by AMPK in vitro. | ||||
Sequence: S → A |
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000086781 | 1-1051 | Serine/threonine-protein kinase ULK1 | |||
Sequence: MEPGRGGVETVGKFEFSRKDLIGHGAFAVVFKGRHREKHDLEVAVKCINKKNLAKSQTLLGKEIKILKELKHENIVALYDFQEMANSVYLVMEYCNGGDLADYLHTMRTLSEDTVRLFLQQIAGAMRLLHSKGIIHRDLKPQNILLSNPGGRRANPSNIRVKIADFGFARYLQSNMMAATLCGSPMYMAPEVIMSQHYDGKADLWSIGTIVYQCLTGKAPFQASSPQDLRLFYEKNKTLVPAIPRETSAPLRQLLLALLQRNHKDRMDFDEFFHHPFLDASTPIKKSPPVPVPSYPSSGSGSSSSSSSASHLASPPSLGEMPQLQKTLTSPADAAGFLQGSRDSGGSSKDSCDTDDFVMVPAQFPGDLVAEAASAKPPPDSLLCSGSSLVASAGLESHGRTPSPSPTCSSSPSPSGRPGPFSSNRYGASVPIPVPTQVHNYQRIEQNLQSPTQQQTARSSAIRRSGSTTPLGFGRASPSPPSHTDGAMLARKLSLGGGRPYTPSPQVGTIPERPSWSRVPSPQGADVRVGRSPRPGSSVPEHSPRTTGLGCRLHSAPNLSDFHVVRPKLPKPPTDPLGATFSPPQTSAPQPCPGLQSCRPLRGSPKLPDFLQRSPLPPILGSPTKAGPSFDFPKTPSSQNLLTLLARQGVVMTPPRNRTLPDLSEASPFHGQQLGSGLRPAEDTRGPFGRSFSTSRITDLLLKAAFGTQASDSGSTDSLQEKPMEIAPSAGFGGTLHPGARGGGASSPAPVVFTVGSPPSGATPPQSTRTRMFSVGSSSSLGSTGSSSARHLVPGACGEAPELSAPGHCCSLADPLAANLEGAVTFEAPDLPEETLMEQEHTETLHSLRFTLAFAQQVLEIAALKGSASEAAGGPEYQLQESVVADQISQLSREWGFAEQLVLYLKVAELLSSGLQTAIDQIRAGKLCLSSTVKQVVRRLNELYKASVVSCQGLSLRLQRFFLDKQRLLDGIHGVTAERLILSHAVQMVQSAALDEMFQHREGCVPRYHKALLLLEGLQHTLTDQADIENIAKCKLCIERRLSALLSGVYA | ||||||
Modified residue | 162 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 317 | Phosphoserine; by AMPK | ||||
Sequence: S | ||||||
Modified residue | 403 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 450 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 456 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 467 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 477 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 479 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 521 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 555 | Phosphoserine; by AMPK | ||||
Sequence: S | ||||||
Modified residue | 574 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 606 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 635 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 637 | Phosphoserine; by AMPK | ||||
Sequence: S | ||||||
Modified residue | 638 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 757 | Phosphoserine; by MTOR | ||||
Sequence: S | ||||||
Modified residue | 774 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 777 | Phosphoserine; by AMPK | ||||
Sequence: S |
Post-translational modification
Autophosphorylated. Phosphorylated under nutrient-rich conditions; dephosphorylated during starvation or following treatment with rapamycin. In response to nutrient limitation, phosphorylated and activated by AMPK, leading to activate autophagy. Under nutrient sufficiency, phosphorylated by MTOR/mTOR, disrupting the interaction with AMPK and preventing activation of ULK1.
Ubiquitinated via 'Lys-63'-linkage by a complex composed of AMBRA1 and TRAF6 following autophagy induction, promoting ULK1 stability and kinase activity. Deubiquitinated by USP20; leading to ULK1 stability and autophagy initiation.
Acetylated by KAT5/TIP60 under autophagy induction, promoting protein kinase activity.
Keywords
- PTM
Proteomic databases
PTM databases
Interaction
Subunit
Interacts with GABARAP and GABARAPL2 (By similarity).
Interacts (via C-terminus) with ATG13 (PubMed:19258318).
Part of a complex consisting of ATG13, ATG101, ULK1 and RB1CC1 (PubMed:19258318).
Associates with the mammalian target of rapamycin complex 1 (mTORC1) through an interaction with RPTOR; the association depends on nutrient conditions and is reduced during starvation (By similarity).
Interacts with FEZ1; SCOC interferes with FEZ1-binding (By similarity).
Interacts with TBC1D14 (By similarity).
Interacts (phosphorylated form) with TRIM5 (By similarity).
When phosphorylated at Ser-317, interacts with MEFV and BECN1 simultaneously. Interacts with TRIM21 and IRF3, in the presence of TRIM21 (By similarity).
Interacts with SESN2 (PubMed:25040165).
Interacts with SQSTM1 (PubMed:25040165).
Interacts with C9orf72 (By similarity).
Interacts with WDR45 (By similarity).
Interacts with ATG13; this interaction is increased in the absence of TMEM39A (By similarity).
Interacts with WIPI2 (By similarity).
Interacts with ATP2A2 (By similarity).
Interacts with AMBRA1 (By similarity).
Interacts with Irgm1; promoting the coassembly of ULK1 and BECN1 (By similarity).
Interacts (via C-terminus) with ATG13 (PubMed:19258318).
Part of a complex consisting of ATG13, ATG101, ULK1 and RB1CC1 (PubMed:19258318).
Associates with the mammalian target of rapamycin complex 1 (mTORC1) through an interaction with RPTOR; the association depends on nutrient conditions and is reduced during starvation (By similarity).
Interacts with FEZ1; SCOC interferes with FEZ1-binding (By similarity).
Interacts with TBC1D14 (By similarity).
Interacts (phosphorylated form) with TRIM5 (By similarity).
When phosphorylated at Ser-317, interacts with MEFV and BECN1 simultaneously. Interacts with TRIM21 and IRF3, in the presence of TRIM21 (By similarity).
Interacts with SESN2 (PubMed:25040165).
Interacts with SQSTM1 (PubMed:25040165).
Interacts with C9orf72 (By similarity).
Interacts with WDR45 (By similarity).
Interacts with ATG13; this interaction is increased in the absence of TMEM39A (By similarity).
Interacts with WIPI2 (By similarity).
Interacts with ATP2A2 (By similarity).
Interacts with AMBRA1 (By similarity).
Interacts with Irgm1; promoting the coassembly of ULK1 and BECN1 (By similarity).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | O70405 | Fundc1 Q9DB70 | 2 | EBI-8390771, EBI-10106464 | |
XENO | O70405 | FUNDC1 Q8IVP5 | 3 | EBI-8390771, EBI-3059266 | |
BINARY | O70405 | Htt P42859 | 4 | EBI-8390771, EBI-5327353 | |
BINARY | O70405 | Mtor Q9JLN9 | 3 | EBI-8390771, EBI-1571628 | |
XENO | O70405 | SESN2 P58004 | 5 | EBI-8390771, EBI-3939642 | |
XENO | O70405 | SQSTM1 Q13501 | 2 | EBI-8390771, EBI-307104 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 16-278 | Protein kinase | ||||
Sequence: FSRKDLIGHGAFAVVFKGRHREKHDLEVAVKCINKKNLAKSQTLLGKEIKILKELKHENIVALYDFQEMANSVYLVMEYCNGGDLADYLHTMRTLSEDTVRLFLQQIAGAMRLLHSKGIIHRDLKPQNILLSNPGGRRANPSNIRVKIADFGFARYLQSNMMAATLCGSPMYMAPEVIMSQHYDGKADLWSIGTIVYQCLTGKAPFQASSPQDLRLFYEKNKTLVPAIPRETSAPLRQLLLALLQRNHKDRMDFDEFFHHPFL | ||||||
Region | 283-323 | Disordered | ||||
Sequence: PIKKSPPVPVPSYPSSGSGSSSSSSSASHLASPPSLGEMPQ | ||||||
Region | 287-416 | Interaction with GABARAP and GABARAPL2 | ||||
Sequence: SPPVPVPSYPSSGSGSSSSSSSASHLASPPSLGEMPQLQKTLTSPADAAGFLQGSRDSGGSSKDSCDTDDFVMVPAQFPGDLVAEAASAKPPPDSLLCSGSSLVASAGLESHGRTPSPSPTCSSSPSPSG | ||||||
Compositional bias | 296-323 | Polar residues | ||||
Sequence: PSSGSGSSSSSSSASHLASPPSLGEMPQ | ||||||
Region | 335-358 | Disordered | ||||
Sequence: AGFLQGSRDSGGSSKDSCDTDDFV | ||||||
Region | 394-554 | Disordered | ||||
Sequence: GLESHGRTPSPSPTCSSSPSPSGRPGPFSSNRYGASVPIPVPTQVHNYQRIEQNLQSPTQQQTARSSAIRRSGSTTPLGFGRASPSPPSHTDGAMLARKLSLGGGRPYTPSPQVGTIPERPSWSRVPSPQGADVRVGRSPRPGSSVPEHSPRTTGLGCRLH | ||||||
Compositional bias | 435-475 | Polar residues | ||||
Sequence: PTQVHNYQRIEQNLQSPTQQQTARSSAIRRSGSTTPLGFGR | ||||||
Region | 661-686 | Disordered | ||||
Sequence: PDLSEASPFHGQQLGSGLRPAEDTRG | ||||||
Region | 727-787 | Disordered | ||||
Sequence: APSAGFGGTLHPGARGGGASSPAPVVFTVGSPPSGATPPQSTRTRMFSVGSSSSLGSTGSS | ||||||
Compositional bias | 759-787 | Polar residues | ||||
Sequence: PSGATPPQSTRTRMFSVGSSSSLGSTGSS | ||||||
Region | 829-1051 | C-terminal domain; mediates interaction with SESN2 | ||||
Sequence: PDLPEETLMEQEHTETLHSLRFTLAFAQQVLEIAALKGSASEAAGGPEYQLQESVVADQISQLSREWGFAEQLVLYLKVAELLSSGLQTAIDQIRAGKLCLSSTVKQVVRRLNELYKASVVSCQGLSLRLQRFFLDKQRLLDGIHGVTAERLILSHAVQMVQSAALDEMFQHREGCVPRYHKALLLLEGLQHTLTDQADIENIAKCKLCIERRLSALLSGVYA |
Sequence similarities
Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. APG1/unc-51/ULK1 subfamily.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length1,051
- Mass (Da)112,463
- Last updated1998-08-01 v1
- Checksum99B021985FB4E8A0
Computationally mapped potential isoform sequences
There are 4 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A0R4J0B3 | A0A0R4J0B3_MOUSE | Ulk1 | 1051 | ||
Q6PB82 | Q6PB82_MOUSE | Ulk1 | 1057 | ||
A0A0G2JFU2 | A0A0G2JFU2_MOUSE | Ulk1 | 86 | ||
A0A0G2JG09 | A0A0G2JG09_MOUSE | Ulk1 | 84 |
Features
Showing features for compositional bias, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 296-323 | Polar residues | ||||
Sequence: PSSGSGSSSSSSSASHLASPPSLGEMPQ | ||||||
Compositional bias | 435-475 | Polar residues | ||||
Sequence: PTQVHNYQRIEQNLQSPTQQQTARSSAIRRSGSTTPLGFGR | ||||||
Sequence conflict | 469 | in Ref. 3; AAH57121 | ||||
Sequence: T → S | ||||||
Compositional bias | 759-787 | Polar residues | ||||
Sequence: PSGATPPQSTRTRMFSVGSSSSLGSTGSS |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF053756 EMBL· GenBank· DDBJ | AAC40118.1 EMBL· GenBank· DDBJ | mRNA | ||
AF072370 EMBL· GenBank· DDBJ | AAF23317.1 EMBL· GenBank· DDBJ | mRNA | ||
BC057121 EMBL· GenBank· DDBJ | AAH57121.1 EMBL· GenBank· DDBJ | mRNA |