Description: Homo sapiens tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta polypeptide (YWHAZ), transcript variant 6, mRNA. RefSeq Summary (NM_001135702): This gene product belongs to the 14-3-3 family of proteins which mediate signal transduction by binding to phosphoserine-containing proteins. This highly conserved protein family is found in both plants and mammals, and this protein is 99% identical to the mouse, rat and sheep orthologs. The encoded protein interacts with IRS1 protein, suggesting a role in regulating insulin sensitivity. Several transcript variants that differ in the 5' UTR but that encode the same protein have been identified for this gene. [provided by RefSeq, Oct 2008]. Transcript (Including UTRs) Position: hg19 chr8:101,930,804-101,962,799 Size: 31,996 Total Exon Count: 6 Strand: - Coding Region Position: hg19 chr8:101,932,921-101,961,117 Size: 28,197 Coding Exon Count: 5
ID:1433Z_HUMAN DESCRIPTION: RecName: Full=14-3-3 protein zeta/delta; AltName: Full=Protein kinase C inhibitor protein 1; Short=KCIP-1; 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. 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 hetero-dimerization 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. 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. INTERACTION: Q29495:AANAT (xeno); NbExp=3; IntAct=EBI-347088, EBI-446413; P00519:ABL1; NbExp=2; IntAct=EBI-347088, EBI-375543; Q9P0K1-3:ADAM22; NbExp=3; IntAct=EBI-347088, EBI-1567267; O00257-3:CBX4; NbExp=2; IntAct=EBI-347088, EBI-4392727; P23528:CFL1; NbExp=2; IntAct=EBI-347088, EBI-352733; P00533:EGFR; NbExp=4; IntAct=EBI-347088, EBI-297353; P30793:GCH1; NbExp=4; IntAct=EBI-347088, EBI-958183; Q99683:MAP3K5; NbExp=2; IntAct=EBI-347088, EBI-476263; Q7KZI7:MARK2; NbExp=3; IntAct=EBI-347088, EBI-516560; P27448:MARK3; NbExp=6; IntAct=EBI-347088, EBI-707595; Q9NYL2:MLTK; NbExp=4; IntAct=EBI-347088, EBI-602273; Q8TEW0:PARD3; NbExp=3; IntAct=EBI-347088, EBI-81968; P04049:RAF1; NbExp=3; IntAct=EBI-347088, EBI-365996; P57059:SIK1; NbExp=4; IntAct=EBI-347088, EBI-1181640; Q9Y2K2:SIK3; NbExp=5; IntAct=EBI-347088, EBI-1181460; O00506:STK25; NbExp=2; IntAct=EBI-347088, EBI-618295; P36897:TGFBR1; NbExp=4; IntAct=EBI-347088, EBI-1027557; P84198:VIM (xeno); NbExp=5; IntAct=EBI-347088, EBI-457639; SUBCELLULAR LOCATION: Cytoplasm. Melanosome. 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 Ser-58 by PKA; disrupts homodimerization and heterodimerization with YHAE and TP53. This phosphorylation appears to be activated by sphingosine. Phosphorylation on Thr-232; inhibits binding of RAF1. SIMILARITY: Belongs to the 14-3-3 family. CAUTION: Was originally (PubMed:1577711) thought to have phospholipase A2 activity. SEQUENCE CAUTION: Sequence=AAH51814.1; Type=Erroneous initiation; Sequence=AAH73141.1; Type=Erroneous initiation;
Amyotrophic Lateral Sclerosis Simon Cronin et al. Human molecular genetics 2008, A genome-wide association study of sporadic ALS in a homogenous Irish population., Human molecular genetics.
[PubMed 18057069]
Attention deficit hyperactivity disorder and conduct disorder Anney ,et al. 2008, Conduct disorder and ADHD: Evaluation of conduct problems as a categorical and quantitative trait in the international multicentre ADHD genetics study, American journal of medical genetics. Part B, Neuropsychiatric genetics 2008 147B- 8 : 1369-78.
[PubMed 18951430]
Echocardiography Ramachandran S Vasan et al. BMC medical genetics 2007, Genome-wide association of echocardiographic dimensions, brachial artery endothelial function and treadmill exercise responses in the Framingham Heart Study., BMC medical genetics.
[PubMed 17903301]
In hypothesis-generating GWAS of echocardiography, ETT and BA vascular function in a moderate-sized community-based sample, we identified several SNPs that are candidates for replication attempts and we provide a web-based GWAS resource for the research community.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P63104
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.