RABL3_HUMAN
ID RABL3_HUMAN Reviewed; 236 AA.
AC Q5HYI8; Q8WUD3;
DT 04-DEC-2007, integrated into UniProtKB/Swiss-Prot.
DT 15-FEB-2005, sequence version 1.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=Rab-like protein 3;
GN Name=RABL3;
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 [LARGE SCALE MRNA].
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Bone marrow, Fetal skin, and Heart;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
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 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 [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [8]
RP FUNCTION, INTERACTION WITH RAP1GDS1, INVOLVEMENT IN PNCA5, VARIANTS PNCA5
RP 36-SER--ASP-236 DEL AND GLN-184, AND CHARACTERIZATION OF VARIANT PNCA5
RP 36-SER--ASP-236 DEL.
RX PubMed=31406347; DOI=10.1038/s41588-019-0475-y;
RA Nissim S., Leshchiner I., Mancias J.D., Greenblatt M.B., Maertens O.,
RA Cassa C.A., Rosenfeld J.A., Cox A.G., Hedgepeth J., Wucherpfennig J.I.,
RA Kim A.J., Henderson J.E., Gonyo P., Brandt A., Lorimer E., Unger B.,
RA Prokop J.W., Heidel J.R., Wang X.X., Ukaegbu C.I., Jennings B.C.,
RA Paulo J.A., Gableske S., Fierke C.A., Getz G., Sunyaev S.R.,
RA Wade Harper J., Cichowski K., Kimmelman A.C., Houvras Y., Syngal S.,
RA Williams C., Goessling W.;
RT "Mutations in RABL3 alter KRAS prenylation and are associated with
RT hereditary pancreatic cancer.";
RL Nat. Genet. 51:1308-1314(2019).
CC -!- FUNCTION: Required for KRAS signaling regulation and modulation of cell
CC proliferation (PubMed:31406347). Regulator of KRAS prenylation, and
CC probably prenylation of other small GTPases (PubMed:31406347). Required
CC for lymphocyte development and function (By similarity). Not required
CC for myeloid cell development (By similarity).
CC {ECO:0000250|UniProtKB:Q9D4V7, ECO:0000269|PubMed:31406347}.
CC -!- SUBUNIT: Homodimer (By similarity). Interacts with GPR89; the
CC interaction stabilizes GPR89 (By similarity). Interacts with RAP1GDS1
CC (PubMed:31406347). {ECO:0000250|UniProtKB:Q9D4V7,
CC ECO:0000269|PubMed:31406347}.
CC -!- DISEASE: Pancreatic cancer 5 (PNCA5) [MIM:618680]: A malignant neoplasm
CC of the pancreas. Tumors can arise from both the exocrine and endocrine
CC portions of the pancreas, but 95% of them develop from the exocrine
CC portion, including the ductal epithelium, acinar cells, connective
CC tissue, and lymphatic tissue. {ECO:0000269|PubMed:31406347}.
CC Note=Disease susceptibility is associated with variants affecting the
CC gene represented in this entry. RABL3 variants have been found in
CC families with a history of pancreatic ductal adenocarcinoma and
CC multiple other occurrences of cancer, including melanoma, breast
CC cancer, prostate cancer, and colon cancer.
CC {ECO:0000269|PubMed:31406347}.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Rab family.
CC {ECO:0000305}.
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DR EMBL; AK293085; BAF85774.1; -; mRNA.
DR EMBL; BX647664; CAI46059.1; -; mRNA.
DR EMBL; BX647593; CAI46064.1; -; mRNA.
DR EMBL; BX647559; CAI46095.1; -; mRNA.
DR EMBL; CH471052; EAW79521.1; -; Genomic_DNA.
DR EMBL; BC020832; AAH20832.1; -; mRNA.
DR CCDS; CCDS3001.1; -.
DR RefSeq; NP_776186.2; NM_173825.3.
DR AlphaFoldDB; Q5HYI8; -.
DR SMR; Q5HYI8; -.
DR BioGRID; 130066; 198.
DR IntAct; Q5HYI8; 50.
DR MINT; Q5HYI8; -.
DR STRING; 9606.ENSP00000273375; -.
DR ChEMBL; CHEMBL4105853; -.
DR iPTMnet; Q5HYI8; -.
DR PhosphoSitePlus; Q5HYI8; -.
DR SwissPalm; Q5HYI8; -.
DR BioMuta; RABL3; -.
DR DMDM; 74762186; -.
DR EPD; Q5HYI8; -.
DR jPOST; Q5HYI8; -.
DR MassIVE; Q5HYI8; -.
DR MaxQB; Q5HYI8; -.
DR PaxDb; Q5HYI8; -.
DR PeptideAtlas; Q5HYI8; -.
DR PRIDE; Q5HYI8; -.
DR ProteomicsDB; 62938; -.
DR TopDownProteomics; Q5HYI8; -.
DR Antibodypedia; 32810; 45 antibodies from 20 providers.
DR DNASU; 285282; -.
DR Ensembl; ENST00000273375.8; ENSP00000273375.4; ENSG00000144840.10.
DR GeneID; 285282; -.
DR KEGG; hsa:285282; -.
DR MANE-Select; ENST00000273375.8; ENSP00000273375.4; NM_173825.5; NP_776186.2.
DR UCSC; uc003edx.3; human.
DR CTD; 285282; -.
DR DisGeNET; 285282; -.
DR GeneCards; RABL3; -.
DR HGNC; HGNC:18072; RABL3.
DR HPA; ENSG00000144840; Low tissue specificity.
DR MalaCards; RABL3; -.
DR MIM; 618542; gene.
DR MIM; 618680; phenotype.
DR neXtProt; NX_Q5HYI8; -.
DR OpenTargets; ENSG00000144840; -.
DR Orphanet; 1333; Familial pancreatic carcinoma.
DR PharmGKB; PA34161; -.
DR VEuPathDB; HostDB:ENSG00000144840; -.
DR eggNOG; ENOG502QT3S; Eukaryota.
DR GeneTree; ENSGT00390000007467; -.
DR HOGENOM; CLU_084875_1_0_1; -.
DR InParanoid; Q5HYI8; -.
DR OMA; EEIWLNC; -.
DR OrthoDB; 1269342at2759; -.
DR PhylomeDB; Q5HYI8; -.
DR TreeFam; TF320841; -.
DR PathwayCommons; Q5HYI8; -.
DR SignaLink; Q5HYI8; -.
DR BioGRID-ORCS; 285282; 33 hits in 1078 CRISPR screens.
DR GenomeRNAi; 285282; -.
DR Pharos; Q5HYI8; Tbio.
DR PRO; PR:Q5HYI8; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q5HYI8; protein.
DR Bgee; ENSG00000144840; Expressed in adrenal tissue and 197 other tissues.
DR ExpressionAtlas; Q5HYI8; baseline and differential.
DR Genevisible; Q5HYI8; HS.
DR GO; GO:0005525; F:GTP binding; ISS:UniProtKB.
DR GO; GO:0003924; F:GTPase activity; IBA:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0030183; P:B cell differentiation; ISS:UniProtKB.
DR GO; GO:0006886; P:intracellular protein transport; IBA:GO_Central.
DR GO; GO:0001779; P:natural killer cell differentiation; ISS:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; ISS:UniProtKB.
DR GO; GO:1903059; P:regulation of protein lipidation; IMP:UniProtKB.
DR GO; GO:0046578; P:regulation of Ras protein signal transduction; IMP:UniProtKB.
DR GO; GO:0033077; P:T cell differentiation in thymus; ISS:UniProtKB.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR027417; P-loop_NTPase.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS51419; RAB; 1.
PE 1: Evidence at protein level;
KW Disease variant; GTP-binding; Nucleotide-binding; Reference proteome.
FT CHAIN 1..236
FT /note="Rab-like protein 3"
FT /id="PRO_0000312166"
FT REGION 1..236
FT /note="Small GTPase-like"
FT BINDING 16..21
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q9D4V7"
FT BINDING 148..150
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q9D4V7"
FT BINDING 179..180
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q9D4V7"
FT VARIANT 36..236
FT /note="Missing (in PNCA5; associated with disease
FT susceptibility; increased KRAS signaling and cell
FT proliferation; increased interaction with RAP1GDS1;
FT increased KRAS prenylation)"
FT /evidence="ECO:0000269|PubMed:31406347"
FT /id="VAR_083453"
FT VARIANT 184
FT /note="R -> Q (in PNCA5; associated with disease
FT susceptibility; dbSNP:rs61756477)"
FT /evidence="ECO:0000269|PubMed:31406347"
FT /id="VAR_083454"
FT CONFLICT 60
FT /note="Y -> C (in Ref. 4; AAH20832)"
FT /evidence="ECO:0000305"
FT CONFLICT 163
FT /note="R -> T (in Ref. 4; AAH20832)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 236 AA; 26423 MW; B80898B1293C88C6 CRC64;
MASLDRVKVL VLGDSGVGKS SLVHLLCQNQ VLGNPSWTVG CSVDVRVHDY KEGTPEEKTY
YIELWDVGGS VGSASSVKST RAVFYNSVNG IIFVHDLTNK KSSQNLRRWS LEALNRDLVP
TGVLVTNGDY DQEQFADNQI PLLVIGTKLD QIHETKRHEV LTRTAFLAED FNPEEINLDC
TNPRYLAAGS SNAVKLSRFF DKVIEKRYFL REGNQIPGFP DRKRFGAGTL KSLHYD
