7qD3. View the map and BAC clones (data from UCSC genome browser).
Rab38/NM_028238: 3 exons, 61,300bp, Chr7: 80,826,675-80,887,974.
The figure below shows the structure of the Rab38 gene (data from UCSC genome browser).
Search the 5'UTR and 1kb upstream regions (seq1=human RAB38, seq2=mouse Rab38) by CONREAL with 80% Position Weight Matrices (PWMs) threshold (view results here).
Tissue specificity: Mouse Rab38 transcript is detected in melanocytes, melanoma cell lines, lung type II cells, and at varying levels in many tissues including adrenal gland, uterus, testes, kidney, prostate, placenta, and others.
Affymetrix microarray expression pattern in SymAtlas from GNF is shown below.
|Protein||NP_071732 (211aa)||NP_665717 (211aa)||04204 (167aa)||Q86PD0 (222aa)|
|Identities||97% /205aa||98% /208aa||73% /114aa||72% /127aa|
View multiple sequence alignment (PDF file) by ClustalW and GeneDoc.
(1) Domains predicted by SMART:
a) RAB: 10 - 180
(2) Transmembrane domains predicted by SOSUI: none.
(3) Graphic view of InterPro domain structure.
(1) Predicted results by ScanProsite:
a) Protein kinases ATP-binding region signature :
18 - 49: LGVGKTSIIKrYvhqnfsshyratigvd..FALK
b) ATP/GTP-binding site motif A (P-loop) : [occurs frequently]
16 - 23: GdlgvGKT
c) N-myristoylation site : [occurs frequently]
19 - 24: GVgkTS, 43 - 48: GVdfAL.
d) N-glycosylation site : [occurs frequently]
33 - 36: NFSS, 74 - 77: NMTR.
e) Protein kinase C phosphorylation site : [occurs frequently]
159 - 161: SaK, 199 - 201: SpK.
f) Casein kinase II phosphorylation site : [occurs frequently]
159 - 162: SakE.
(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: found KKXX- like motif in the C-terminus: GCAK
d) VAC possible vacuolar targeting motif: found TLPN at 113
e) Actinin-type actin-binding motif: type 1: none; type 2: none
f) Prenylation motif: S-farnesyl cysteine at 208
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 matched entries found, results here.
(2)ModBase predicted comparative 3D structure of Q8QZZ8 from UCSC Genome Sorter.
From left to right: Front, Top, and Side views of predicted protein.
This protein does not exist in the current release of SWISS-2DPAGE.
Computed theoretical MW=23,776Da, pI=7.65 (NP_082514).
(1) Biological process: intracellular protein transport
(2) GTPase activity.
(3) ATP binding; GTP binding
Immunofluorescence staining demonstrated that expressed GST-tagged Rab38 was mainly co-localized with endoplasmic reticulum-resident protein and also partly with intermittent vesicles between the endoplasmic reticulum and the Golgi complex (Osanai, et al (2005)). Rab38 localizes to perinuclear vesicles carrying tyrosinase and tyrosinase-related protein 1 (Wasmeier, et al).
The RAB family of proteins is comprised of small GTP-binding proteins that transition between the cytoplasm and organelle membranes and are believed to regulate vesicle transport. The two-cysteine carboxy terminal motif important for the binding of lipid moieties differs from the consensus sequence found in other RAB proteins and is more like that found in RAS proteins. Varp (VPS9-ankyrin-repeat protein)/Ankrd27 specifically binds two small GTPases, Rab32 and Rab38. A conserved Val residue in the switch II region of Rab32(Val-92) and Rab38(Val-78) is required for Varp binding activity (Tamura, et al (2009); Tamura, et al (2011)).
Rab38 drosophila homolog CG8024/Rab-RP1 interaction information in CuraGen interaction database.
RAB38 is important in the vesicular trafficking that moves TYRP1 from the trans-Golgi network to the end-stage melanosome (Luftus, et al). Rab38 and Rab32 regulate a critical step in the trafficking of melanogenic enzymes, in particular, tyrosinase and TYRP1, from the TGN to melanosomes (Wasmeier, et al).
SNPs deposited in dbSNP.
|Exon 1||56G>T||56G>T||G19V||missense||cht (B6)||Luftus, et al|
The G19V mutation is localized within highly conserved phosphate/Mg2+ domain and is predicted to contact GTP directly in the nucleotide binding pocket (Luftus, et al). Rab38(G19V) is inactive and that the nearly normal pigmentation in cht melanocytes results from functional compensation by the closely related Rab32 (Wasmeier, et al).
Mutation in the Rab38 gene is the cause of recessive chocolate (cht) mutant (Luftus, et al). The cht allele arose spontaneously in the C57BL/6 strain. The strain is described in more detail in JAX Mice database (C57BL/6J-Rab38cht/J). Homozygotes have lighter eyes and skin at birth and brown rather than black hair pigment (nonagouti chocolate (a/a-cht/cht) mice). The end-stage melanosomes of chocolate mice contain less TYRP1 than do wild type mice. The cht/cht melanosomes are similar in morphology to Tyrp1b melanosomes (Luftus, et al). Mutation of both Rab38 and Tyrp1 produced mice with ocular and coat color pigment dilution greater than that seen with either mutation alone (Brooks, et al). Loss of functional Rab38 in the cht mouse causes dramatically reduced numbers of melanosomes in adult RPE, but less severe in skin melanocytes and choroidal melanocytes (Lopes, et al). The chocolate mice do not have extended bleeding times (Davisson, et al) and platelet storage defects (Luftus, et al). Cht lungs exhibited a uniform enlargement of the distal airspaces with mild alveolar destruction as well as a slight increase in lung compliance. Alveolar type II cells were engorged with lamellar bodies of increased size and number. Hydrophobic surfactant constituents (ie, phosphatidylcholine and surfactant protein B) were increased in lung tissues but decreased in alveolar spaces, consistent with a malfunction in lamellar body secretion and the subsequent cellular accumulation of these organelles (Osanai, et al (2008)).
In the rat, two HPS models are known, Fawn-hooded (FH) and Tester Moriyama (TM), non-complementing strains in which HPS-like hypopigmentation and platelet storage pool deficiency result from a mutation of the Ruby (red eyed dilution; R) locus on Chromosome (Chr) 1. FH and TM rats have identical Rab38 M1I mutations (protein-null), occurring on an identical Chr 1 marker allele haplotype, indicating that these two strains derive from a common ancestor. This ancestor appears to have been a sub-strain of the outbred Long Evans (LE) strain, and several modern LE sub-strains carry the Rab38 M1I R mutation on the same Chr 1 marker haplotype (Oiso, et al). Unlike rhe cht mice, FH rat platelets and megakaryocytes lacked dense granules (Ninkovic, et al). In LE rat HPS model, Rab38-deficient type II cells appear to carry abnormality in lung surfactant secretion but not in synthesis or uptake (Osanai, et al (2010)). A Rab38-KO rat was generated by zinc-finger nuclease (ZFN) targeting (Geurts, et al ) .