Ras-related protein Rab-38 (RAB38)






GENOMIC

Mapping

11q14.2 View the map and BAC clones (data from UCSC genome browser).

Structure

(assembly 07/03)
RAB38 (NM_022337): 3 exons, 62,169bp, Chr11: 87,534,584 - 87,596,752.

The figure below shows the structure of the known isoform (data from UCSC genome browser).

Regulatory Element

Search the 5'UTR and 1kb upstream regions (seq1=human SNAPAP, seq2=mouse Snapap) by CONREAL with 80% Position Weight Matrices (PWMs) threshold (view results here).






TRANSCRIPT

RefSeq/ORF

RAB38 (NM_022337), 1,412bp, view ORF and the alignment to genomic.

Expression Pattern

Tissue specificity: Expressed highly in melanocytes. The mRNA and the native protein were expressed in a tissue-specific manner, e.g., in the lung, skin, stomach, liver, and kidney. Freshly isolated rat alveolar type II cells were highly positive for the mRNA signal, but the signal was rapidly lost over time (Osanai, et al).


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

Sequence

RAB38 (NP_071732): 211aa, ExPaSy NiceProt view of Swiss-Prot:P57729.
Synonym: Ras-related protein Rab-38.

Ortholog

Species MouseRatZebrafishFruitfly
GeneView Rab38/chtRab38/R27987CG8024/Rab-RP1
Protein NP_082514 (211aa)NP_665717 (211aa)04204 (167aa)Q86PD0 (222aa)
Identities 97% /205aa96% /203aa73% /114aa72% /127aa

View multiple sequence alignment (PDF file) by ClustalW and GeneDoc.

Domain

(1) Domains predicted by SMART:
a) RAB: 10 - 180

(2) Transmembrane domains predicted by SOSUI: none.

(3) Graphic view of InterPro domain structure.

Motif/Site

(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: none
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

3D Model

(1) ModBase entry found, results here.

(2) ModBase predicted comparative 3D structure of P57729 from UCSC Genome Sorter.
Front Top Side
From left to right: Front, Top, and Side views of predicted protein

2D-PAGE

This protein does not exist in the current release of SWISS-2DPAGE.
Computed theoretical MW=23,712Da, pI=7.65 (NP_071732).






FUNCTION

Ontology

(1) Biological process: intracellular protein transport
(2) GTPase activity.
(3) ATP binding; GTP binding

Location

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). Rab38 localizes to perinuclear vesicles carrying tyrosinase and tyrosinase-related protein 1 (Wasmeier, et al).

Interaction

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.

Pathway

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).






MUTATION

Allele or SNP

Suzuki, et al performed the mutation screening in 25 unidentified OCA patients. No defects were detected.

SNPs deposited in dbSNP.

Distribution

(none)

Effect

(none)






PHENOTYPE

(Animal Models) (see also OMIM:606281)
Mutation in the murine Rab38 gene is the cause of chocolate (cht) mutant (Luftus, et al). Mutation in the rat Rab38 gene is the cause of Ruby (R) mutant (Oiso, et al), a model of HPS-like disorder.






REFERENCE

  1. Loftus SK, Larson DM, Baxter LL, Antonellis A, Chen Y, Wu X, Jiang Y, Bittner M, Hammer JA 3rd, Pavan WJ. Mutation of melanosome protein RAB38 in chocolate mice. Proc Natl Acad Sci U S A 2002; 99: 4471-6. PMID: 11917121
  2. Oiso N, Riddle SR, Serikawa T, Kuramoto T, Spritz RA. The rat Ruby ( R) locus is Rab38: identical mutations in Fawn-hooded and Tester-Moriyama rats derived from an ancestral Long Evans rat sub-strain. Mamm Genome 2004; 15: 307-14. PMID: 15112108
  3. Osanai K, Takahashi K, Nakamura K, Takahashi M, Ishigaki M, Sakuma T, Toga H, Suzuki T, Voelker DR. Expression and characterization of Rab38, a new member of the Rab small G protein family. Biol Chem 2005; 386: 143-53. PMID: 15843158
  4. Suzuki T, Miyamura Y, Inagaki K, Tomita Y. Characterization of the human RAB38 and RAB7 genes: exclusion of new major pathological loci for Japanese OCA. J Dermatol Sci 2003; 32: 131-6. PMID: 12850305
  5. Tamura K, Ohbayashi N, Maruta Y, Kanno E, Itoh T, Fukuda M. Varp is a novel Rab32/38-binding protein that regulates Tyrp1 trafficking in melanocytes. Mol Biol Cell 2009; 20: 2900-8. PMID: 19403694
  6. Tamura K, Ohbayashi N, Ishibashi K, Fukuda M. Structure-function analysis of VPS9-ankyrin-repeat protein (Varp) in the trafficking of tyrosinase-related protein 1 in melanocytes. J Biol Chem 2011; 286: 7507-21. PMID: 21187289
  7. Wasmeier C, Romao M, Plowright L, Bennett DC, Raposo G, Seabra MC. Rab38 and Rab32 control post-Golgi trafficking of melanogenic enzymes. J Cell Biol. 2006; 175: 271-81. PMID: 17043139

EDIT HISTORY:

Created by Wei Li and Johnathan Bourne, 07/23/2004
Updated by Wei Li, 12/28/2006
Updated by Wei Li, 05/29/2011

(Back to Index) (Back to Homepage)