UniProt functional annotation for P63104



	UniProt functional annotation for P63104

UniProt codes: P63104, P29312.

Organism: Homo sapiens (Human).

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

Function: Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. Induces ARHGEF7 activity on RAC1 as well as lamellipodia and membrane ruffle formation (PubMed:16959763). In neurons, regulates spine maturation through the modulation of ARHGEF7 activity (By similarity). {ECO:0000250|UniProtKB:O55043, ECO:0000269|PubMed:14578935, ECO:0000269|PubMed:15071501, ECO:0000269|PubMed:15644438, ECO:0000269|PubMed:16376338, ECO:0000269|PubMed:16959763, ECO:0000269|PubMed:31024343, ECO:0000269|PubMed:9360956}.

Subunit: Interacts with CDK16 and BSPRY (By similarity). Interacts with WEE1 (C-terminal). Interacts with SAMSN1 (By similarity). Interacts with MLF1 (phosphorylated form); the interaction retains it in the cytoplasm (By similarity). Interacts with Thr-phosphorylated ITGB2 (By similarity). Interacts with BCL2L11 (By similarity). Homodimer. Heterodimerizes with YWHAE. Homo- and heterodimerization is inhibited by phosphorylation on Ser-58. Interacts with FOXO4, NOXA1, SSH1 and ARHGEF2. Interacts with Pseudomonas aeruginosa exoS (unphosphorylated form). Interacts with BAX; the interaction occurs in the cytoplasm. Under stress conditions, MAPK8-mediated phosphorylation releases BAX to mitochondria. Interacts with phosphorylated RAF1; the interaction is inhibited when YWHAZ is phosphorylated on Thr-232 (PubMed:31024343). Interacts with BRAF (PubMed:31024343). Interacts with TP53; the interaction enhances p53 transcriptional activity. The Ser-58 phosphorylated form inhibits this interaction and p53 transcriptional activity. Interacts with ABL1 (phosphorylated form); the interaction retains ABL1 in the cytoplasm. Interacts with PKA-phosphorylated AANAT; the interaction modulates AANAT enzymatic activity by increasing affinity for arylalkylamines and acetyl-CoA and protecting the enzyme from dephosphorylation and proteasomal degradation. It may also prevent thiol-dependent inactivation. Interacts with AKT1; the interaction phosphorylates YWHAZ and modulates dimerization. Interacts with GAB2 and TLK2. Interacts with the 'Thr-369' phosphorylated form of DAPK2 (PubMed:26047703). Interacts with PI4KB, TBC1D22A and TBC1D22B (PubMed:23572552). Interacts with ZFP36L1 (via phosphorylated form); this interaction occurs in a p38 MAPK- and AKT-signaling pathways (By similarity). Interacts with SLITRK1 (PubMed:19640509). Interacts with AK5, LDB1, MADD, MARK3, PDE1A and SMARCB1 (PubMed:16959763). Interacts with MEFV (PubMed:27030597). {ECO:0000250|UniProtKB:P63101, ECO:0000250|UniProtKB:Q9ES28, ECO:0000269|PubMed:10455159, ECO:0000269|PubMed:11336675, ECO:0000269|PubMed:11427721, ECO:0000269|PubMed:11956222, ECO:0000269|PubMed:14578935, ECO:0000269|PubMed:14970201, ECO:0000269|PubMed:15071501, ECO:0000269|PubMed:15159416, ECO:0000269|PubMed:15644438, ECO:0000269|PubMed:15660133, ECO:0000269|PubMed:15696159, ECO:0000269|PubMed:16114898, ECO:0000269|PubMed:16246723, ECO:0000269|PubMed:16376338, ECO:0000269|PubMed:16959763, ECO:0000269|PubMed:17235285, ECO:0000269|PubMed:17913709, ECO:0000269|PubMed:19172738, ECO:0000269|PubMed:19640509, ECO:0000269|PubMed:23572552, ECO:0000269|PubMed:26047703, ECO:0000269|PubMed:27030597, ECO:0000269|PubMed:31024343, ECO:0000269|PubMed:9360956}.

Subcellular location: Cytoplasm {ECO:0000269|PubMed:17081065}. Melanosome {ECO:0000269|PubMed:17081065}. Note=Located to stage I to stage IV melanosomes.

Ptm: The delta, brain-specific form differs from the zeta form in being phosphorylated (By similarity). Phosphorylation on Ser-184 by MAPK8; promotes dissociation of BAX and translocation of BAX to mitochondria. Phosphorylation on Thr-232; inhibits binding of RAF1. Phosphorylated on Ser-58 by PKA and protein kinase C delta type catalytic subunit in a sphingosine-dependent fashion. Phosphorylation on Ser-58 by PKA; disrupts homodimerization and heterodimerization with YHAE and TP53. {ECO:0000250, ECO:0000269|PubMed:11956222, ECO:0000269|PubMed:12865427, ECO:0000269|PubMed:15071501, ECO:0000269|PubMed:15696159, ECO:0000269|PubMed:15883165, ECO:0000269|PubMed:16376338, ECO:0000269|PubMed:9360956}.

Similarity: Belongs to the 14-3-3 family. {ECO:0000305}.

Sequence caution: Sequence=AAH51814.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=AAH73141.1; 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:		Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. Induces ARHGEF7 activity on RAC1 as well as lamellipodia and membrane ruffle formation (PubMed:16959763). In neurons, regulates spine maturation through the modulation of ARHGEF7 activity (By similarity). {ECO:0000250\|UniProtKB:O55043, ECO:0000269\|PubMed:14578935, ECO:0000269\|PubMed:15071501, ECO:0000269\|PubMed:15644438, ECO:0000269\|PubMed:16376338, ECO:0000269\|PubMed:16959763, ECO:0000269\|PubMed:31024343, ECO:0000269\|PubMed:9360956}.


Subunit:		Interacts with CDK16 and BSPRY (By similarity). Interacts with WEE1 (C-terminal). Interacts with SAMSN1 (By similarity). Interacts with MLF1 (phosphorylated form); the interaction retains it in the cytoplasm (By similarity). Interacts with Thr-phosphorylated ITGB2 (By similarity). Interacts with BCL2L11 (By similarity). Homodimer. Heterodimerizes with YWHAE. Homo- and heterodimerization is inhibited by phosphorylation on Ser-58. Interacts with FOXO4, NOXA1, SSH1 and ARHGEF2. Interacts with Pseudomonas aeruginosa exoS (unphosphorylated form). Interacts with BAX; the interaction occurs in the cytoplasm. Under stress conditions, MAPK8-mediated phosphorylation releases BAX to mitochondria. Interacts with phosphorylated RAF1; the interaction is inhibited when YWHAZ is phosphorylated on Thr-232 (PubMed:31024343). Interacts with BRAF (PubMed:31024343). Interacts with TP53; the interaction enhances p53 transcriptional activity. The Ser-58 phosphorylated form inhibits this interaction and p53 transcriptional activity. Interacts with ABL1 (phosphorylated form); the interaction retains ABL1 in the cytoplasm. Interacts with PKA-phosphorylated AANAT; the interaction modulates AANAT enzymatic activity by increasing affinity for arylalkylamines and acetyl-CoA and protecting the enzyme from dephosphorylation and proteasomal degradation. It may also prevent thiol-dependent inactivation. Interacts with AKT1; the interaction phosphorylates YWHAZ and modulates dimerization. Interacts with GAB2 and TLK2. Interacts with the 'Thr-369' phosphorylated form of DAPK2 (PubMed:26047703). Interacts with PI4KB, TBC1D22A and TBC1D22B (PubMed:23572552). Interacts with ZFP36L1 (via phosphorylated form); this interaction occurs in a p38 MAPK- and AKT-signaling pathways (By similarity). Interacts with SLITRK1 (PubMed:19640509). Interacts with AK5, LDB1, MADD, MARK3, PDE1A and SMARCB1 (PubMed:16959763). Interacts with MEFV (PubMed:27030597). {ECO:0000250\|UniProtKB:P63101, ECO:0000250\|UniProtKB:Q9ES28, ECO:0000269\|PubMed:10455159, ECO:0000269\|PubMed:11336675, ECO:0000269\|PubMed:11427721, ECO:0000269\|PubMed:11956222, ECO:0000269\|PubMed:14578935, ECO:0000269\|PubMed:14970201, ECO:0000269\|PubMed:15071501, ECO:0000269\|PubMed:15159416, ECO:0000269\|PubMed:15644438, ECO:0000269\|PubMed:15660133, ECO:0000269\|PubMed:15696159, ECO:0000269\|PubMed:16114898, ECO:0000269\|PubMed:16246723, ECO:0000269\|PubMed:16376338, ECO:0000269\|PubMed:16959763, ECO:0000269\|PubMed:17235285, ECO:0000269\|PubMed:17913709, ECO:0000269\|PubMed:19172738, ECO:0000269\|PubMed:19640509, ECO:0000269\|PubMed:23572552, ECO:0000269\|PubMed:26047703, ECO:0000269\|PubMed:27030597, ECO:0000269\|PubMed:31024343, ECO:0000269\|PubMed:9360956}.
Subcellular location:		Cytoplasm {ECO:0000269\|PubMed:17081065}. Melanosome {ECO:0000269\|PubMed:17081065}. Note=Located to stage I to stage IV melanosomes.
Ptm:		The delta, brain-specific form differs from the zeta form in being phosphorylated (By similarity). Phosphorylation on Ser-184 by MAPK8; promotes dissociation of BAX and translocation of BAX to mitochondria. Phosphorylation on Thr-232; inhibits binding of RAF1. Phosphorylated on Ser-58 by PKA and protein kinase C delta type catalytic subunit in a sphingosine-dependent fashion. Phosphorylation on Ser-58 by PKA; disrupts homodimerization and heterodimerization with YHAE and TP53. {ECO:0000250, ECO:0000269\|PubMed:11956222, ECO:0000269\|PubMed:12865427, ECO:0000269\|PubMed:15071501, ECO:0000269\|PubMed:15696159, ECO:0000269\|PubMed:15883165, ECO:0000269\|PubMed:16376338, ECO:0000269\|PubMed:9360956}.
Similarity:		Belongs to the 14-3-3 family. {ECO:0000305}.
Sequence caution:		Sequence=AAH51814.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=AAH73141.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};