7qB3. View the map and BAC cotig (data from UCSC genome browser).
Isoform a (AF534396): 23 exons, 4,625 bp, chr7:39644540-39679750.
Isoform a (AF534397): 23 exons, 4,601 bp, chr7:39644540-39679750.
Isoform b (AF534398): 21 exons, 4,190 bp, chr7:39644540-39673243.
Isoform c (AF534399): 24 exons, 4,756 bp, chr7:39644540-39679750.
Alternative splicing in kidney(Zhang, et al):
1) AF534397: alternatively spliced; contains shorter exon 2 than AF534396, encodes same isoform (a) because it does not alter the ORF.
2) AF534398: alternatively spliced; lacks of exon 1 and contains partial exon 2 compared with AF534396, utilizes alternative ATG start site to encode isoform (b) (truncated by 165aa at N-terminal isoform a).
3) AF534399: alternatively spliced; contains additional exon between exons 12 and 13 compared with AF534396, encoding isoform (c) (truncated by 600aa at C-terminal isoform a).
The figure shows the comparison of these 4 variants (data from UCSC genome browser).
Search the 5'UTR regions (human and mouse) of isoform (a) by CONREAL with 80% Position Weight Matrices (PWMs) threshold (view results here).
a) Transcript variant 1 (AF534396), 4,625bp, view ORF and the alignment to genomic.
b) Transcript variant 2 (AF534397), 4,601bp, view ORF and the alignment to genomic.
c) Transcript variant 3 (AF534398), 4,190bp, view ORF and the alignment to genomic.
d) Transcript variant 4 (AF534399), 4,756bp, view ORF and the alignment to genomic.
Tissue specificity: widely expressed, with lowest expression in skeletal muscle and spleen (Zhang, et al).
Affymetrix microarray expression pattern in SymAtlas from GNF is shown below.
Isoform a (AAO25958), 1126 aa, ExPaSy NiceProt view of Swiss-Prot: P59438.
Isoform b (AAO25960), 961 aa, ExPaSy NiceProt view of Swiss-Prot: P59438.2.
Isoform c (AAO25961), 526 aa, ExPaSy NiceProt view of Swiss-Prot: P59438.3.
Synonyms: Ruby-eye protein 2; Hermansky-Pudlak syndrome 5 protein homolog.
|Protein||NP_852608 (1129aa)||XP_218589 (903aa)||10114 (1138aa)||Q7M564 (1110aa)||Q8SXI1 (826aa)|
View multiple sequence alignment (PDF file) by ClustalW and GeneDoc.
(1) Domains predicted by SMART(isoform a):
a) low complexity: 429-449
b) low complexity: 775-786
c) low complexity: 989-998
d) low complexity: 1021-1033
(2) Transmembrane domains predicted by SOSUI(isoform a): none.
(3) Graphic view of InterPro domain structure.
(1) Predicted results by ScanProsite(isoform a):
a) N-glycosylation site [pattern] [Warning: pattern with a high probability of occurrence]:
659 - 662 NTSS, 710 - 713 NLSE, 1047 - 1050 NGSL.
b) Tyrosine sulfation site [rule] [Warning: rule with a high probability of occurrence]:
82 - 96 ccshdddYvavatsq, 812 - 826 marsnpaYteleegd.
c) Glycosaminoglycan attachment site [rule] [Warning: rule with a high probability of occurrence]:
686 - 689 SGeG.
d) cAMP- and cGMP-dependent protein kinase phosphorylation site [pattern] [Warning: pattern with a high probability of occurrence]:
124 - 127 RKvT, 434 - 437 RRsS, 458 - 461 RRgS, 551 - 554 RKtT, 690 - 693 RRvS.
e)Tyrosine kinase phosphorylation site [pattern] [Warning: pattern with a high probability of occurrence]:
328 - 336 KdiqDvavY.
e) Amidation site [pattern]:
122 - 125 kGRK, 688 - 691 eGRR.
f) Serine-rich region [profile]:
429 - 476 SacssrrssisshvsfsildsgiyriissrrgsqsdedscslhsqtfS.
(2) Predicted results of subprograms by PSORT II(isoform a):
a) N-terminal signal peptide: none, N-terminal side will be inside.
b) KDEL ER retention motif in the C-terminus: none
c) ER Membrane Retention Signals: none
d) VAC possible vacuolar targeting motif: none
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: none
i) Dileucine motif in the tail: none
(1) ModBase: none.
(2) 3D models of isoform (a) predicted by SPARKS (fold recognition) below. View the models by PDB2MGIF.
This protein does not exist in the current release of SWISS-2DPAGE.
Computed theoretical MW=126,307Da, pI=5.54 (isoform a).
Computed theoretical MW=108,189Da, pI=5.22 (isoform b).
Computed theoretical MW= 59,028Da, pI=5.54 (isoform c).
(1) Biological process: visual perception
(2) May regulate the synthesis and function of lysosomes and of highly specialized organelles, such as melanosomes and platelet dense granules (view diagram of BLOC-2 pathway here).
Zhang, et al reported that HPS5p directly interacts with HPS6p in a complex known as biogenesis of lysosome-related organelles complex-2 (or BLOC2). Gautum, et al found that HPS3p resides in the same protein complex. The native molecular mass of BLOC-2 was estimated to be 340 +/- 64 kDa (view diagram of BLOC-2 complex here). BLOC-2 exists in a soluble pool and associates to membranes as a peripheral membrane protein (Di Pietro, et al).
No interactions found in the CuraGen database by searching its drosophila homolog CG9770.
SNPs deposited in dbSNP.
|Exon 10||997delG||997delG||V333delG||frame-shift |
| ru2d |
|Hirobe, et al|
|Exon 16||2270GdelGinsTT||2270GdelGinsTT||G757delGinsTT||frame-shift |
| ru2J |
|Zhang, et al|
|Exon 18||2698GinsCCGG||2698GinsCCGG||E900insCCGG||frame-shift |
| ru2hz |
|Zhang, et al|
|Exon 18||2601Gins 1kb H2A histone, 2594-2601dup||2601Gins 1kb H2A histone, 2594-2601dup||K867ins 1kb H2A histone||gross insertion||ru2 (B6)||Zhang, et al|
(Numbering of genomic and cDNA sequence is based on the start codon of RefSeq AF534396.)
No differences between the northern blot pattern of tissues of homozygous ru2J and those of wild type mice were observed (Zhang, et al ). The Hps5 protein is missing in Western blots in spleen and lung. The Hps5 protein also exhibits destabilization in Hps3 or Hps6 null mutants (Gautum, et al ). The ru2(d) allele inhibits melanocyte differentiation, and that its impaired differentiation is rescued by excess Tyr (Hirobe, et al ).
Defects in Hps5 are the cause of ruby-eye 2, a mouse model of Hermansky-Pudlak syndrome type 5 (HPS-5, OMIM 607521). Homozygotes have hypopigmented eyes and hair, impaired secretion of lysosomal enzymes by renal proximal tubules and reduced clotting due to a platelet dense granule defect (Novak, et al) (more details in Mouse Locus Catalog #Hps5). The strain is described in more detail in JAX Mice database (B6-Hps5ru2-J/J). Melanosomes of the retinal pigment epithelium (RPE) of the BLOC-2 mutants Hps5/ru and Hps6/ru2 are similar, which are greatly reduced in number and those remaining appear to be degradative forms. Melanosomes of the choroid are smaller, and some are found grouped within distinctive membrane-limited organelles (Zhang, et al). The ru2 and ru mice are completely indistinguishable in appearance. In addition, Hps5/ru2-Hps6/ru doubly homozygous mouse presents a phenotype identical to that of the singly homozygous mutants (Gautum, et al).
The drosophila pigment mutant pink (p) is identified as the homologue of HPS5 (Falcon-Perez, et al).