19p13.3. View the map and BAC contig (data from UCSC genome browser).
AP3D1/NM_003938: 30 exons, 50,567bp, Chr19: 2,051,988-2,102,554.
The figure below shows the structure of the AP3D1 gene (data from UCSC genome browser).
Search the 5'UTR and 1kb upstream regions (human and mouse) by CONREAL with 80% Position Weight Matrices (PWMs) threshold (view results here).
Tissue specificity: Present in all adult tissues examined with the highest levels in skeletal muscle, heart, pancreas and testis.
BMR: Bone marrow; SPL: Spleen; TMS: Thymus; BRN: Brain; SPC: Spinal cord; HRT: Heart; MSL: Skeletal muscle; LVR; Liver; PNC: Pancreas; PST: Prostate; KDN: Kidney; LNG: Lung. (data from GeneCards )
|Protein||NP_031486 (1199aa)||XP_234908 (1204aa)||17714 (966aa)||NP_494570 (1251aa)||NP_524785 (1034aa)|
View multiple sequence alignment (PDF file) by ClustalW and GeneDoc.
(1) Domains predicted by SMART:
a) low complexity: 460 - 472, 535 - 548, 659 - 677, 838 - 893.
b) coiled coil: 722 - 756.
(2) Transmembrane domains predicted by SOSUI:
1 transmembrane helix, 272-294.
(3) Pfam domains: PF01602 - Adaptin N terminal region.
(4) CDD conserved domain: KOG1059, vesicle coat complex AP-3, delta subunit (Intracellular trafficking, secretion, and vesicular transport).
(5) Graphic view of InterPro domain structure.
(1) Predicted results by ScanProsite:
a) Lysine-rich region profile : [occurs frequently]
828 - 893: score=20.975
b) Tyrosine kinase phosphorylation site : [occurs frequently]
29 - 35: Ked.Eak.Y, 359 - 365: Ral.Dll.Y
c) Amidation site : [occurs frequently]
255 - 258: lGKK, 752 - 755: kGKR, 886 - 889: kGKK.
d) N-glycosylation site : [occurs frequently]
296 - 299: NHSA, 955 - 958: NRSS.
e) cAMP- and cGMP-dependent protein kinase phosphorylation site : [occurs frequently]
755 - 758: RRhS, 866 - 869: KKkS, 888 - 891: KKkS.
f) Tyrosine sulfation site : [occurs frequently]
385 - 399: dkaegttYrdelltk, 717 - 731: glpmsdqYvkleeer, 792 - 806: dkdpndpYraldidl.
(2) Predicted results of subprograms by PSORT II:
a) N-terminal signal peptide: none
b) KDEL ER retention motif in the C-terminus: none
c) ER Membrane Retention Signals: none
d) VAC possible vacuolar targeting motif: found KLPI at 815
e) Actinin-type actin-binding motif: type 1: none; type 2: none
f) Prenylation motif: none
g) memYQRL transport motif from cell surface to Golgi: none
h) Tyrosines in the tail: too long of a tail
i) Dileucine motif in the tail: found LL at 1118.
(1) ModBase: 1 match found, results here.
(2) ModBase predicted comparative 3D structures on O14617 (data from UCSC Gene Sorter). (from left to right: Front, Top, Side view)
This protein does not exist in the current release of SWISS-2DPAGE.
Computed theoretical MW=128,637Da, pI=8.87 (NP_003929).
a) Biological process: intracellular protein transport, vesicle-mediated transport (overview of trafficking pathway here).
b) Biological process: eye pigment biosynthesis.
c) Component of Golgi apparatus.
Component of the coat surrounding the cytoplasmic face of coated vesicles located at the Golgi complex.
AP3D1 is a subunit of the AP3 adaptor-like complex, which is not associated with clathrin. The AP-3 complex is a heterotetramer composed of two large adaptins (delta/AP3D1 and beta3A/AP3B2 or beta3B/AP3B1), a medium adaptin (mu3A/AP3M1 or mu3B/AP3M2) and a small adaptin (sigma3A/AP3S1 or sigma3B/AP3S2). AP-3, has been identified that interacts with dileucine motifs and mediates endosomal/lysosomal transport in yeast, drosophila, and mammals. In addition, the AP3M1 subunit interacts with tyrosinase for lysosomal targeting (Honing, et al). AP-3 complex interacts with CD1 antigen presenting molecules.
Association of AP-3 with membranes in vitro was enhanced by GTPgammaS and inhibited by brefeldin A (BFA), an inhibitor of ARF1 guanine nucleotide exchange. In addition, recombinant myristoylated ARF1 promoted association of AP-3 with membranes. The membrane recruitment of AP-3 is promoted by ARF1-GTP (Ooi, et al (1998)).
6 proteins are shown to be associated with APL5 in Yeast GRID.
Ap3d drosophila homolog CG10986 interaction information in CuraGen interaction database.
The AP3D1 subunit is implicated in intracellular biogenesis and trafficking of pigment granules and possibly platelet dense granules and neurotransmitter vesicles. AP-3 complex is associated with the Golgi region as well as more peripheral structures. It facilitates the budding of vesicles from the Golgi membrane and appears to be involved in the sorting of a subset of transmembrane proteins targeted to lysosomes and lysosome-related organelles. In yeast, AP-3 sorts the vacuolar membrane enzymes, alkaline phosphatase and Vamp3p, a vacuolar t-SNARE (Odorizzi, et al). Faundez, et al found that the AP-3 complex is involved in synaptic vesicle formation in neuronal cells. Likewise, Sugita, et al concluded that there is an AP-3 dependent pathway for antigen presentation by CD1B (human) or CD1d (mice) molecules. The mechanism of AP-3 dependent pathway is distinct from that dependent on HPS1 (Feng, et al) (view diagram of BLOC-3 and AP-3 pathway here).
Mutations in the Ap3d gene are the cause of mocha (mh) mutants (Katheti, et al (1998; 2003)), a mouse model of Hermansky-Pudlak syndrome (OMIM 607246). Ooi, et al (1997) showed that the garnet mutation in drosophila, which causes reduced pigmentation of the eyes and other tissues, results from a mutation in the fly AP3D1 homolog gene.