UniProt functional annotation for P27448



	UniProt functional annotation for P27448

UniProt code: P27448.

Organism: Homo sapiens (Human).

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

Function: Serine/threonine-protein kinase (PubMed:23666762). Involved in the specific phosphorylation of microtubule-associated proteins for MAP2 and MAP4. Phosphorylates the microtubule-associated protein MAPT/TAU (PubMed:23666762). Phosphorylates CDC25C on 'Ser-216'. Regulates localization and activity of some histone deacetylases by mediating phosphorylation of HDAC7, promoting subsequent interaction between HDAC7 and 14-3-3 and export from the nucleus (PubMed:16980613). Negatively regulates the Hippo signaling pathway and antagonizes the phosphorylation of LATS1. Cooperates with DLG5 to inhibit the kinase activity of STK3/MST2 toward LATS1 (PubMed:28087714). {ECO:0000269|PubMed:16980613, ECO:0000269|PubMed:23666762, ECO:0000269|PubMed:28087714}.

Catalytic activity: Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl- [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA- COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;

Catalytic activity: Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L- threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.1;

Activity regulation: Activated by phosphorylation on Thr-211. Inhibited by phosphorylation on Thr-564. {ECO:0000269|PubMed:14976552}.

Subunit: Interacts with MAPT/TAU (PubMed:23666762). Interacts with DLG5 (via coiled-coil domain). Interacts with STK3/MST2 and STK4/MST1 in the presence of DLG5 (PubMed:28087714). Interacts with YWHAB, YWHAG, YWHAQ and YWHAZ (PubMed:16959763). {ECO:0000269|PubMed:16959763, ECO:0000269|PubMed:23666762, ECO:0000269|PubMed:28087714}.

Subcellular location: Cell membrane {ECO:0000269|PubMed:21145462}; Peripheral membrane protein {ECO:0000269|PubMed:21145462}. Cell projection, dendrite {ECO:0000269|PubMed:23666762}. Cytoplasm {ECO:0000269|PubMed:23666762}.

Tissue specificity: Ubiquitous.

Ptm: Phosphorylated at Thr-211 by STK11/LKB1 in complex with STE20- related adapter-alpha (STRADA) pseudo kinase and CAB39. Phosphorylation at Thr-564 by PRKCZ/aPKC inhibits the kinase activity. {ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:15084291}.

Disease: Visual impairment and progressive phthisis bulbi (VIPB) [MIM:618283]: An autosomal recessive, progressive disease characterized by poor vision at birth and development of bilateral phthisis bulbi by adulthood. {ECO:0000269|PubMed:29771303}. Note=The disease may be caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily. {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:		Serine/threonine-protein kinase (PubMed:23666762). Involved in the specific phosphorylation of microtubule-associated proteins for MAP2 and MAP4. Phosphorylates the microtubule-associated protein MAPT/TAU (PubMed:23666762). Phosphorylates CDC25C on 'Ser-216'. Regulates localization and activity of some histone deacetylases by mediating phosphorylation of HDAC7, promoting subsequent interaction between HDAC7 and 14-3-3 and export from the nucleus (PubMed:16980613). Negatively regulates the Hippo signaling pathway and antagonizes the phosphorylation of LATS1. Cooperates with DLG5 to inhibit the kinase activity of STK3/MST2 toward LATS1 (PubMed:28087714). {ECO:0000269\|PubMed:16980613, ECO:0000269\|PubMed:23666762, ECO:0000269\|PubMed:28087714}.


Catalytic activity:		Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl- [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA- COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
Catalytic activity:		Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L- threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.1;
Activity regulation:		Activated by phosphorylation on Thr-211. Inhibited by phosphorylation on Thr-564. {ECO:0000269\|PubMed:14976552}.
Subunit:		Interacts with MAPT/TAU (PubMed:23666762). Interacts with DLG5 (via coiled-coil domain). Interacts with STK3/MST2 and STK4/MST1 in the presence of DLG5 (PubMed:28087714). Interacts with YWHAB, YWHAG, YWHAQ and YWHAZ (PubMed:16959763). {ECO:0000269\|PubMed:16959763, ECO:0000269\|PubMed:23666762, ECO:0000269\|PubMed:28087714}.
Subcellular location:		Cell membrane {ECO:0000269\|PubMed:21145462}; Peripheral membrane protein {ECO:0000269\|PubMed:21145462}. Cell projection, dendrite {ECO:0000269\|PubMed:23666762}. Cytoplasm {ECO:0000269\|PubMed:23666762}.
Tissue specificity:		Ubiquitous.
Ptm:		Phosphorylated at Thr-211 by STK11/LKB1 in complex with STE20- related adapter-alpha (STRADA) pseudo kinase and CAB39. Phosphorylation at Thr-564 by PRKCZ/aPKC inhibits the kinase activity. {ECO:0000269\|PubMed:14976552, ECO:0000269\|PubMed:15084291}.
Disease:		Visual impairment and progressive phthisis bulbi (VIPB) [MIM:618283]: An autosomal recessive, progressive disease characterized by poor vision at birth and development of bilateral phthisis bulbi by adulthood. {ECO:0000269\|PubMed:29771303}. Note=The disease may be caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily. {ECO:0000305}.