RAB38_HUMAN
ID RAB38_HUMAN Reviewed; 211 AA.
AC P57729; Q53XK7;
DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2001, sequence version 1.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=Ras-related protein Rab-38;
DE AltName: Full=Melanoma antigen NY-MEL-1;
GN Name=RAB38;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10910072;
RA Jaeger D., Stockert E., Jaeger E., Guere A.O., Scanlan M.J., Knuth A.,
RA Old L.J., Chen Y.-T.;
RT "Serological cloning of a melanocyte rab guanosine 5'-triphosphate-binding
RT protein and a chromosome condensation protein from a melanoma complementary
RT DNA library.";
RL Cancer Res. 60:3584-3591(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG SeattleSNPs variation discovery resource;
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RC TISSUE=Melanoma;
RX PubMed=12643545; DOI=10.1021/pr025562r;
RA Basrur V., Yang F., Kushimoto T., Higashimoto Y., Yasumoto K., Valencia J.,
RA Muller J., Vieira W.D., Watabe H., Shabanowitz J., Hearing V.J., Hunt D.F.,
RA Appella E.;
RT "Proteomic analysis of early melanosomes: identification of novel
RT melanosomal proteins.";
RL J. Proteome Res. 2:69-79(2003).
RN [6]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RC TISSUE=Melanoma;
RX PubMed=17081065; DOI=10.1021/pr060363j;
RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H., Mangini N.J.,
RA Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R., Yamagishi S.,
RA Shabanowitz J., Hearing V.J., Wu C., Appella E., Hunt D.F.;
RT "Proteomic and bioinformatic characterization of the biogenesis and
RT function of melanosomes.";
RL J. Proteome Res. 5:3135-3144(2006).
RN [7]
RP ISOPRENYLATION AT CYS-208.
RX PubMed=17114793; DOI=10.1074/jbc.m605557200;
RA Leung K.F., Baron R., Ali B.R., Magee A.I., Seabra M.C.;
RT "Rab GTPases containing a CAAX motif are processed post-geranylgeranylation
RT by proteolysis and methylation.";
RL J. Biol. Chem. 282:1487-1497(2007).
RN [8]
RP INTERACTION WITH ANKRD27.
RX PubMed=19403694; DOI=10.1091/mbc.e08-12-1161;
RA Tamura K., Ohbayashi N., Maruta Y., Kanno E., Itoh T., Fukuda M.;
RT "Varp is a novel Rab32/38-binding protein that regulates Tyrp1 trafficking
RT in melanocytes.";
RL Mol. Biol. Cell 20:2900-2908(2009).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [10]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=21255211; DOI=10.1111/j.1600-0854.2011.01165.x;
RA Seto S., Tsujimura K., Koide Y.;
RT "Rab GTPases regulating phagosome maturation are differentially recruited
RT to mycobacterial phagosomes.";
RL Traffic 12:407-420(2011).
RN [11]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=23084991; DOI=10.1016/j.cub.2012.09.020;
RA Gerondopoulos A., Langemeyer L., Liang J.R., Linford A., Barr F.A.;
RT "BLOC-3 mutated in Hermansky-Pudlak syndrome is a Rab32/38 guanine
RT nucleotide exchange factor.";
RL Curr. Biol. 22:2135-2139(2012).
RN [12]
RP VARIANT [LARGE SCALE ANALYSIS] THR-111.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: May be involved in melanosomal transport and docking.
CC Involved in the proper sorting of TYRP1. Involved in peripheral
CC melanosomal distribution of TYRP1 in melanocytes; the function, which
CC probably is implicating vesicle-trafficking, includes cooperation with
CC ANKRD27 and VAMP7 (By similarity). Plays a role in the maturation of
CC phagosomes that engulf pathogens, such as S.aureus and M.tuberculosis
CC (PubMed:21255211). Plays an important role in the control of melanin
CC production and melanosome biogenesis (PubMed:23084991). In concert with
CC RAB32, regulates the proper trafficking of melanogenic enzymes TYR,
CC TYRP1 and DCT/TYRP2 to melanosomes in melanocytes (By similarity).
CC {ECO:0000250|UniProtKB:Q8QZZ8, ECO:0000269|PubMed:21255211,
CC ECO:0000269|PubMed:23084991}.
CC -!- ACTIVITY REGULATION: Regulated by a guanine nucleotide-exchange factor
CC (GEF) and a GTPase-activating protein (GAP) and alternates between an
CC inactive GDP-bound and an active GTP-bound form. The BLOC-3 complex
CC composed of HPS1 and HPS4 acts as its GEF, promotes the exchange of GDP
CC to GTP, converting it from an inactive GDP-bound form into an active
CC GTP-bound form. SGSM2 acts as its GAP and inactivates it by stimulating
CC its GTPase activity. {ECO:0000250|UniProtKB:Q8QZZ8}.
CC -!- SUBUNIT: Interacts with ANKRD27 (PubMed:19403694).
CC {ECO:0000269|PubMed:19403694}.
CC -!- INTERACTION:
CC P57729; P01023: A2M; NbExp=3; IntAct=EBI-6552718, EBI-640741;
CC P57729; P50570-2: DNM2; NbExp=3; IntAct=EBI-6552718, EBI-10968534;
CC P57729; P14136: GFAP; NbExp=3; IntAct=EBI-6552718, EBI-744302;
CC P57729; Q8WXH2: JPH3; NbExp=3; IntAct=EBI-6552718, EBI-1055254;
CC P57729; Q5S007: LRRK2; NbExp=4; IntAct=EBI-6552718, EBI-5323863;
CC P57729; P51608: MECP2; NbExp=3; IntAct=EBI-6552718, EBI-1189067;
CC P57729; P19404: NDUFV2; NbExp=3; IntAct=EBI-6552718, EBI-713665;
CC P57729; Q16637: SMN2; NbExp=3; IntAct=EBI-6552718, EBI-395421;
CC P57729; O14656-2: TOR1A; NbExp=3; IntAct=EBI-6552718, EBI-25847109;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Lipid-anchor
CC {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Melanosome
CC {ECO:0000269|PubMed:12643545}. Cytoplasmic vesicle, phagosome
CC {ECO:0000269|PubMed:21255211}. Cytoplasmic vesicle, phagosome membrane
CC {ECO:0000305}; Lipid-anchor {ECO:0000305}; Cytoplasmic side
CC {ECO:0000305}. Melanosome membrane {ECO:0000269|PubMed:23084991}.
CC Note=Recruited to phagosomes containing S.aureus or M.tuberculosis
CC (PubMed:21255211). The BLOC-3 complex, a heterodimer of HPS1 and HPS4
CC promotes its membrane localization (PubMed:23084991).
CC {ECO:0000269|PubMed:21255211, ECO:0000269|PubMed:23084991}.
CC -!- TISSUE SPECIFICITY: Expressed in melanocytes.
CC -!- PTM: Although at least one in vitro system can process and methylate
CC the prenylated C-terminal, in an in vitro system that normally express
CC Rab-38 and in vivo the prenylated C-terminal is not proteolytically
CC processed and not methylated. {ECO:0000269|PubMed:17114793}.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Rab family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/rab38/";
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DR EMBL; AF235022; AAG30731.1; -; mRNA.
DR EMBL; BT009842; AAP88844.1; -; mRNA.
DR EMBL; DQ178619; ABA03166.1; -; Genomic_DNA.
DR EMBL; BC015808; AAH15808.1; -; mRNA.
DR CCDS; CCDS8281.1; -.
DR RefSeq; NP_071732.1; NM_022337.2.
DR PDB; 6HDU; X-ray; 1.79 A; A/B/C/D=1-181.
DR PDB; 6S5H; X-ray; 2.00 A; A=1-207.
DR PDBsum; 6HDU; -.
DR PDBsum; 6S5H; -.
DR AlphaFoldDB; P57729; -.
DR SMR; P57729; -.
DR BioGRID; 117198; 32.
DR DIP; DIP-60520N; -.
DR IntAct; P57729; 14.
DR STRING; 9606.ENSP00000243662; -.
DR iPTMnet; P57729; -.
DR PhosphoSitePlus; P57729; -.
DR SwissPalm; P57729; -.
DR BioMuta; RAB38; -.
DR DMDM; 12230516; -.
DR EPD; P57729; -.
DR jPOST; P57729; -.
DR MassIVE; P57729; -.
DR MaxQB; P57729; -.
DR PaxDb; P57729; -.
DR PeptideAtlas; P57729; -.
DR PRIDE; P57729; -.
DR ProteomicsDB; 57021; -.
DR Antibodypedia; 31470; 223 antibodies from 31 providers.
DR DNASU; 23682; -.
DR Ensembl; ENST00000243662.11; ENSP00000243662.5; ENSG00000123892.12.
DR GeneID; 23682; -.
DR KEGG; hsa:23682; -.
DR MANE-Select; ENST00000243662.11; ENSP00000243662.5; NM_022337.3; NP_071732.1.
DR UCSC; uc001pcj.3; human.
DR CTD; 23682; -.
DR DisGeNET; 23682; -.
DR GeneCards; RAB38; -.
DR HGNC; HGNC:9776; RAB38.
DR HPA; ENSG00000123892; Tissue enhanced (esophagus, skin).
DR MIM; 606281; gene.
DR neXtProt; NX_P57729; -.
DR OpenTargets; ENSG00000123892; -.
DR PharmGKB; PA34129; -.
DR VEuPathDB; HostDB:ENSG00000123892; -.
DR eggNOG; KOG4423; Eukaryota.
DR GeneTree; ENSGT00940000157301; -.
DR HOGENOM; CLU_041217_10_6_1; -.
DR InParanoid; P57729; -.
DR OMA; NIHIDDA; -.
DR OrthoDB; 1240760at2759; -.
DR PhylomeDB; P57729; -.
DR TreeFam; TF324491; -.
DR PathwayCommons; P57729; -.
DR Reactome; R-HSA-8873719; RAB geranylgeranylation.
DR Reactome; R-HSA-8876198; RAB GEFs exchange GTP for GDP on RABs.
DR SignaLink; P57729; -.
DR SIGNOR; P57729; -.
DR BioGRID-ORCS; 23682; 7 hits in 1066 CRISPR screens.
DR ChiTaRS; RAB38; human.
DR GeneWiki; RAB38; -.
DR GenomeRNAi; 23682; -.
DR Pharos; P57729; Tbio.
DR PRO; PR:P57729; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; P57729; protein.
DR Bgee; ENSG00000123892; Expressed in gingival epithelium and 121 other tissues.
DR ExpressionAtlas; P57729; baseline and differential.
DR Genevisible; P57729; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005769; C:early endosome; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:Ensembl.
DR GO; GO:0005764; C:lysosome; IDA:ParkinsonsUK-UCL.
DR GO; GO:0042470; C:melanosome; IDA:ParkinsonsUK-UCL.
DR GO; GO:0033162; C:melanosome membrane; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:ParkinsonsUK-UCL.
DR GO; GO:0044233; C:mitochondria-associated endoplasmic reticulum membrane; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005739; C:mitochondrion; IDA:ParkinsonsUK-UCL.
DR GO; GO:0045335; C:phagocytic vesicle; IDA:UniProtKB.
DR GO; GO:0030670; C:phagocytic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005802; C:trans-Golgi network; IBA:GO_Central.
DR GO; GO:0035650; F:AP-1 adaptor complex binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0035651; F:AP-3 adaptor complex binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0036461; F:BLOC-2 complex binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0005525; F:GTP binding; NAS:UniProtKB.
DR GO; GO:0030742; F:GTP-dependent protein binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0003924; F:GTPase activity; IBA:GO_Central.
DR GO; GO:0035646; P:endosome to melanosome transport; IMP:ParkinsonsUK-UCL.
DR GO; GO:0006886; P:intracellular protein transport; IBA:GO_Central.
DR GO; GO:1903232; P:melanosome assembly; IDA:UniProtKB.
DR GO; GO:0032438; P:melanosome organization; IBA:GO_Central.
DR GO; GO:0007005; P:mitochondrion organization; IMP:ParkinsonsUK-UCL.
DR GO; GO:0090383; P:phagosome acidification; IMP:UniProtKB.
DR GO; GO:0060155; P:platelet dense granule organization; IEA:Ensembl.
DR GO; GO:2001247; P:positive regulation of phosphatidylcholine biosynthetic process; IEA:Ensembl.
DR GO; GO:0072657; P:protein localization to membrane; IMP:ParkinsonsUK-UCL.
DR GO; GO:0015031; P:protein transport; NAS:UniProtKB.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; NAS:UniProtKB.
DR GO; GO:0016192; P:vesicle-mediated transport; IEA:InterPro.
DR CDD; cd04107; Rab32_Rab38; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR030697; Rab29/Rab38/Rab32.
DR InterPro; IPR005225; Small_GTP-bd_dom.
DR InterPro; IPR001806; Small_GTPase.
DR Pfam; PF00071; Ras; 1.
DR SMART; SM00174; RHO; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00231; small_GTP; 1.
DR PROSITE; PS51419; RAB; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Cytoplasmic vesicle; GTP-binding; Lipoprotein;
KW Membrane; Nucleotide-binding; Palmitate; Prenylation; Protein transport;
KW Reference proteome; Transport.
FT CHAIN 1..211
FT /note="Ras-related protein Rab-38"
FT /id="PRO_0000121251"
FT MOTIF 38..46
FT /note="Effector region"
FT /evidence="ECO:0000250"
FT BINDING 16..23
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 65..69
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 127..130
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT SITE 208
FT /note="Not methylated"
FT LIPID 205
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000255"
FT LIPID 208
FT /note="S-geranylgeranyl cysteine"
FT /evidence="ECO:0000305|PubMed:17114793"
FT VARIANT 111
FT /note="K -> T (in a colorectal cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036415"
FT STRAND 6..17
FT /evidence="ECO:0007829|PDB:6HDU"
FT HELIX 22..31
FT /evidence="ECO:0007829|PDB:6HDU"
FT STRAND 43..54
FT /evidence="ECO:0007829|PDB:6HDU"
FT STRAND 57..66
FT /evidence="ECO:0007829|PDB:6HDU"
FT HELIX 68..72
FT /evidence="ECO:0007829|PDB:6HDU"
FT HELIX 76..80
FT /evidence="ECO:0007829|PDB:6HDU"
FT STRAND 85..91
FT /evidence="ECO:0007829|PDB:6HDU"
FT HELIX 95..111
FT /evidence="ECO:0007829|PDB:6HDU"
FT STRAND 121..127
FT /evidence="ECO:0007829|PDB:6HDU"
FT HELIX 143..150
FT /evidence="ECO:0007829|PDB:6HDU"
FT STRAND 153..157
FT /evidence="ECO:0007829|PDB:6HDU"
FT TURN 160..163
FT /evidence="ECO:0007829|PDB:6HDU"
FT HELIX 166..179
FT /evidence="ECO:0007829|PDB:6HDU"
SQ SEQUENCE 211 AA; 23712 MW; 0D16B42A1B237539 CRC64;
MQAPHKEHLY KLLVIGDLGV GKTSIIKRYV HQNFSSHYRA TIGVDFALKV LHWDPETVVR
LQLWDIAGQE RFGNMTRVYY REAMGAFIVF DVTRPATFEA VAKWKNDLDS KLSLPNGKPV
SVVLLANKCD QGKDVLMNNG LKMDQFCKEH GFVGWFETSA KENINIDEAS RCLVKHILAN
ECDLMESIEP DVVKPHLTST KVASCSGCAK S
