RAE2_HUMAN
ID RAE2_HUMAN Reviewed; 656 AA.
AC P26374; B2RAB9; Q17RE0; Q9H1Y4;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2004, sequence version 2.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=Rab proteins geranylgeranyltransferase component A 2;
DE AltName: Full=Choroideremia-like protein;
DE AltName: Full=Rab escort protein 2;
DE Short=REP-2;
GN Name=CHML; Synonyms=REP2;
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].
RC TISSUE=Brain;
RX PubMed=1301160; DOI=10.1093/hmg/1.2.71;
RA Cremers F.P.M., Molloy C.M., van de Pol D.J.R., van den Hurk J.A.J.M.,
RA Bach I., Geurts van Kessel A.H.M., Ropers H.-H.;
RT "An autosomal homologue of the choroideremia gene colocalizes with the
RT Usher syndrome type II locus on the distal part of chromosome 1q.";
RL Hum. Mol. Genet. 1:71-75(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=12242008; DOI=10.1016/s0378-1119(02)00799-0;
RA Kasper G., Taudien S., Staub E., Mennerich D., Rieder M., Hinzmann B.,
RA Dahl E., Schwidetzky U., Rosenthal A., Rump A.;
RT "Different structural organization of the encephalopsin gene in man and
RT mouse.";
RL Gene 295:27-32(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Hippocampus;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [7]
RP FUNCTION, AND SUBUNIT.
RX PubMed=8294464; DOI=10.1016/s0021-9258(17)42142-9;
RA Cremers F.P.M., Armstrong S.A., Seabra M.C., Brown M.S., Goldstein J.L.;
RT "REP-2, a Rab escort protein encoded by the choroideremia-like gene.";
RL J. Biol. Chem. 269:2111-2117(1994).
RN [8]
RP FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, SUBUNIT, AND SUBCELLULAR
RP LOCATION.
RX PubMed=12356470; DOI=10.1016/s1046-5928(02)00506-5;
RA Sidorovitch V., Niculae A., Kan N., Ceacareanu A.C., Alexandrov K.;
RT "Expression of mammalian Rab Escort protein-1 and -2 in yeast Saccharomyces
RT cerevisiae.";
RL Protein Expr. Purif. 26:50-58(2002).
RN [9]
RP FUNCTION, INTERACTION WITH RAB1A; RAB7A AND RAB27A, AND SUBUNIT.
RX PubMed=15186776; DOI=10.1016/j.cell.2004.05.017;
RA Rak A., Pylypenko O., Niculae A., Pyatkov K., Goody R.S., Alexandrov K.;
RT "Structure of the Rab7:REP-1 complex: insights into the mechanism of Rab
RT prenylation and choroideremia disease.";
RL Cell 117:749-760(2004).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [11]
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 [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-649, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND INTERACTION WITH RAB8A.
RX PubMed=26824392; DOI=10.7554/elife.12813;
RA Steger M., Tonelli F., Ito G., Davies P., Trost M., Vetter M., Wachter S.,
RA Lorentzen E., Duddy G., Wilson S., Baptista M.A., Fiske B.K., Fell M.J.,
RA Morrow J.A., Reith A.D., Alessi D.R., Mann M.;
RT "Phosphoproteomics reveals that Parkinson's disease kinase LRRK2 regulates
RT a subset of Rab GTPases.";
RL Elife 5:0-0(2016).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND INTERACTION WITH RAB3A; RAB3B;
RP RAB3C; RAB3D; RAB5B; RAB5C; RAB8A; RAB8B; RAB10; RAB12; RAB35 AND RAB43.
RX PubMed=29125462; DOI=10.7554/elife.31012;
RA Steger M., Diez F., Dhekne H.S., Lis P., Nirujogi R.S., Karayel O.,
RA Tonelli F., Martinez T.N., Lorentzen E., Pfeffer S.R., Alessi D.R.,
RA Mann M.;
RT "Systematic proteomic analysis of LRRK2-mediated Rab GTPase phosphorylation
RT establishes a connection to ciliogenesis.";
RL Elife 6:0-0(2017).
CC -!- FUNCTION: Substrate-binding subunit (component A) of the Rab
CC geranylgeranyltransferase (GGTase) complex. Binds unprenylated Rab
CC proteins and presents the substrate peptide to the catalytic component
CC B. The component A is thought to be regenerated by transferring its
CC prenylated Rab back to the donor membrane. Less effective than CHM in
CC supporting prenylation of Rab3 family. {ECO:0000269|PubMed:12356470,
CC ECO:0000269|PubMed:15186776, ECO:0000269|PubMed:8294464}.
CC -!- SUBUNIT: Monomer (PubMed:8294464). Heterotrimer composed of RABGGTA,
CC RABGGTB and CHML; within this trimer, RABGGTA and RABGGTB form the
CC catalytic component B, while CHML (component A) mediates Rab protein
CC binding (PubMed:12356470). Interacts with RAB1A, RAB7A and RAB27A, but
CC has much lower affinity for RAB1A, RAB7A and RAB27A than CHM
CC (PubMed:15186776). Interacts with the non-phosphorylated forms of
CC RAB3A, RAB3B, RAB3C, RAB3D, RAB5B, RAB5C, RAB8A, RAB8B, RAB10, RAB12,
CC RAB35, and RAB43 (PubMed:26824392, PubMed:29125462).
CC {ECO:0000269|PubMed:12356470, ECO:0000269|PubMed:15186776,
CC ECO:0000269|PubMed:26824392, ECO:0000269|PubMed:29125462,
CC ECO:0000269|PubMed:8294464}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:12356470}.
CC -!- MISCELLANEOUS: Substitutes for REP-1 thereby preventing widespread
CC tissue abnormalities in patients with choroideremia who lack REP-1.
CC -!- SIMILARITY: Belongs to the Rab GDI family. {ECO:0000305}.
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DR EMBL; X64728; CAA45979.1; -; mRNA.
DR EMBL; AF482426; AAO15716.1; -; Genomic_DNA.
DR EMBL; AK314125; BAG36816.1; -; mRNA.
DR EMBL; AL133390; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471098; EAW70100.1; -; Genomic_DNA.
DR EMBL; BC117360; AAI17361.1; -; mRNA.
DR CCDS; CCDS31073.1; -.
DR PIR; S23754; S38787.
DR RefSeq; NP_001812.2; NM_001821.3.
DR AlphaFoldDB; P26374; -.
DR SMR; P26374; -.
DR BioGRID; 107546; 56.
DR IntAct; P26374; 23.
DR STRING; 9606.ENSP00000355511; -.
DR GlyGen; P26374; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P26374; -.
DR PhosphoSitePlus; P26374; -.
DR BioMuta; CHML; -.
DR DMDM; 47117837; -.
DR EPD; P26374; -.
DR jPOST; P26374; -.
DR MassIVE; P26374; -.
DR MaxQB; P26374; -.
DR PaxDb; P26374; -.
DR PeptideAtlas; P26374; -.
DR PRIDE; P26374; -.
DR ProteomicsDB; 54329; -.
DR Antibodypedia; 20821; 177 antibodies from 31 providers.
DR DNASU; 1122; -.
DR Ensembl; ENST00000366553.3; ENSP00000355511.1; ENSG00000203668.3.
DR GeneID; 1122; -.
DR KEGG; hsa:1122; -.
DR MANE-Select; ENST00000366553.3; ENSP00000355511.1; NM_001381853.1; NP_001368782.1.
DR UCSC; uc001hzd.4; human.
DR CTD; 1122; -.
DR DisGeNET; 1122; -.
DR GeneCards; CHML; -.
DR HGNC; HGNC:1941; CHML.
DR HPA; ENSG00000203668; Low tissue specificity.
DR MIM; 118825; gene.
DR neXtProt; NX_P26374; -.
DR OpenTargets; ENSG00000203668; -.
DR PharmGKB; PA26472; -.
DR VEuPathDB; HostDB:ENSG00000203668; -.
DR eggNOG; KOG4405; Eukaryota.
DR GeneTree; ENSGT00950000182994; -.
DR HOGENOM; CLU_021695_4_1_1; -.
DR InParanoid; P26374; -.
DR OMA; IKSNICR; -.
DR OrthoDB; 1017439at2759; -.
DR PhylomeDB; P26374; -.
DR TreeFam; TF320813; -.
DR PathwayCommons; P26374; -.
DR Reactome; R-HSA-8873719; RAB geranylgeranylation.
DR Reactome; R-HSA-8876198; RAB GEFs exchange GTP for GDP on RABs.
DR SignaLink; P26374; -.
DR BioGRID-ORCS; 1122; 11 hits in 1071 CRISPR screens.
DR GeneWiki; CHML_(gene); -.
DR GenomeRNAi; 1122; -.
DR Pharos; P26374; Tbio.
DR PRO; PR:P26374; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P26374; protein.
DR Bgee; ENSG00000203668; Expressed in sperm and 179 other tissues.
DR ExpressionAtlas; P26374; baseline and differential.
DR Genevisible; P26374; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005968; C:Rab-protein geranylgeranyltransferase complex; IMP:UniProtKB.
DR GO; GO:0005092; F:GDP-dissociation inhibitor activity; IEA:InterPro.
DR GO; GO:0005096; F:GTPase activator activity; IEA:UniProtKB-KW.
DR GO; GO:0031267; F:small GTPase binding; IDA:UniProtKB.
DR GO; GO:0006886; P:intracellular protein transport; IEA:InterPro.
DR GO; GO:0018344; P:protein geranylgeranylation; IDA:UniProtKB.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; IEA:InterPro.
DR GO; GO:0016192; P:vesicle-mediated transport; IBA:GO_Central.
DR Gene3D; 3.50.50.60; -; 2.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR018203; GDP_dissociation_inhibitor.
DR InterPro; IPR001738; Rab_escort.
DR PANTHER; PTHR11787; PTHR11787; 1.
DR Pfam; PF00996; GDI; 2.
DR PIRSF; PIRSF016550; Rab_ger_ger_transf_A_euk; 1.
DR PRINTS; PR00893; RABESCORT.
DR PRINTS; PR00891; RABGDIREP.
DR SUPFAM; SSF51905; SSF51905; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; GTPase activation; Phosphoprotein; Reference proteome.
FT CHAIN 1..656
FT /note="Rab proteins geranylgeranyltransferase component A
FT 2"
FT /id="PRO_0000056689"
FT REGION 188..209
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 609..656
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 641..656
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 649
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT CONFLICT 103
FT /note="C -> P (in Ref. 1; CAA45979)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 656 AA; 74071 MW; 478481966E30BE49 CRC64;
MADNLPTEFD VVIIGTGLPE SILAAACSRS GQRVLHIDSR SYYGGNWASF SFSGLLSWLK
EYQQNNDIGE ESTVVWQDLI HETEEAITLR KKDETIQHTE AFCYASQDME DNVEEIGALQ
KNPSLGVSNT FTEVLDSALP EESQLSYFNS DEMPAKHTQK SDTEISLEVT DVEESVEKEK
YCGDKTCMHT VSDKDGDKDE SKSTVEDKAD EPIRNRITYS QIVKEGRRFN IDLVSKLLYS
QGLLIDLLIK SDVSRYVEFK NVTRILAFRE GKVEQVPCSR ADVFNSKELT MVEKRMLMKF
LTFCLEYEQH PDEYQAFRQC SFSEYLKTKK LTPNLQHFVL HSIAMTSESS CTTIDGLNAT
KNFLQCLGRF GNTPFLFPLY GQGEIPQGFC RMCAVFGGIY CLRHKVQCFV VDKESGRCKA
IIDHFGQRIN AKYFIVEDSY LSEETCSNVQ YKQISRAVLI TDQSILKTDL DQQTSILIVP
PAEPGACAVR VTELCSSTMT CMKDTYLVHL TCSSSKTARE DLESVVKKLF TPYTETEINE
EELTKPRLLW ALYFNMRDSS GISRSSYNGL PSNVYVCSGP DCGLGNEHAV KQAETLFQEI
FPTEEFCPPP PNPEDIIFDG DDKQPEAPGT NNVVMAKLES SEESKNLESP EKHLQN
