ID   RB22A_HUMAN             Reviewed;         194 AA.
AC   Q9UL26; B3KR86; E1P605; Q8TF12; Q9H4E6;
DT   27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2001, sequence version 2.
DT   27-MAR-2024, entry version 191.
DE   RecName: Full=Ras-related protein Rab-22A;
DE            Short=Rab-22;
GN   Name=RAB22A; Synonyms=RAB22;
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].
RA   Ding J.B., Yu L., Zhao S.Y.;
RT   "Cloning of a novel human cDNA similar to Canis familiaris mRNA for Rab22
RT   protein.";
RL   Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Colon carcinoma;
RX   PubMed=10887961; DOI=10.1078/s0171-9335(04)70034-5;
RA   Opdam F.J.M., Kamps G., Croes H., van Bokhoven H., Ginsel L.A.,
RA   Fransen J.A.M.;
RT   "Expression of Rab small GTPases in epithelial Caco-2 cells: Rab21 is an
RT   apically located GTP-binding protein in polarised intestinal epithelial
RT   cells.";
RL   Eur. J. Cell Biol. 79:308-316(2000).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RA   Kussmann S., Hansmann I., Schlote D.;
RT   "Mapping and characterization of the human RAB22A gene.";
RL   Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
RN   [4]
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 (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Tongue;
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   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=11780052; DOI=10.1038/414865a;
RA   Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA   Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA   Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA   Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA   Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA   Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA   Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA   Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA   Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA   Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA   Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA   Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA   Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA   Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA   Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA   Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA   Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA   Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA   Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA   Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA   Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA   Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA   Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT   "The DNA sequence and comparative analysis of human chromosome 20.";
RL   Nature 414:865-871(2001).
RN   [7]
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   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Colon, and Uterus;
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   [9]
RP   FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF GLN-64.
RX   PubMed=16537905; DOI=10.1128/mcb.26.7.2595-2614.2006;
RA   Magadan J.G., Barbieri M.A., Mesa R., Stahl P.D., Mayorga L.S.;
RT   "Rab22a regulates the sorting of transferrin to recycling endosomes.";
RL   Mol. Cell. Biol. 26:2595-2614(2006).
RN   [10]
RP   INTERACTION WITH RINL, MUTAGENESIS OF SER-19 AND GLN-64, AND SUBCELLULAR
RP   LOCATION.
RX   PubMed=21419809; DOI=10.1016/j.bbamcr.2011.03.005;
RA   Woller B., Luiskandl S., Popovic M., Prieler B.E., Ikonge G., Mutzl M.,
RA   Rehmann H., Herbst R.;
RT   "Rin-like, a novel regulator of endocytosis, acts as guanine nucleotide
RT   exchange factor for Rab5a and Rab22.";
RL   Biochim. Biophys. Acta 1813:1198-1210(2011).
RN   [11]
RP   FUNCTION, AND INTERACTION WITH RABGEF1.
RX   PubMed=21849477; DOI=10.1091/mbc.e11-03-0277;
RA   Wang L., Liang Z., Li G.;
RT   "Rab22 controls NGF signaling and neurite outgrowth in PC12 cells.";
RL   Mol. Biol. Cell 22:3853-3860(2011).
RN   [12]
RP   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   [13]
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).
CC   -!- FUNCTION: Plays a role in endocytosis and intracellular protein
CC       transport. Mediates trafficking of TF from early endosomes to recycling
CC       endosomes (PubMed:16537905). Required for NGF-mediated endocytosis of
CC       NTRK1, and subsequent neurite outgrowth (PubMed:21849477). Binds GTP
CC       and GDP and has low GTPase activity. Alternates between a GTP-bound
CC       active form and a GDP-bound inactive form (PubMed:16537905).
CC       {ECO:0000269|PubMed:16537905, ECO:0000269|PubMed:21849477}.
CC   -!- SUBUNIT: Interacts directly with ZFYVE20 (By similarity). Binds EEA1
CC       (By similarity). Interacts (in its GTP-bound form) with RABGEF1
CC       (PubMed:21849477). Interacts (in its GTP-bound form) with RINL
CC       (PubMed:21419809). {ECO:0000250|UniProtKB:P35285,
CC       ECO:0000250|UniProtKB:P51154, ECO:0000269|PubMed:21419809,
CC       ECO:0000269|PubMed:21849477}.
CC   -!- INTERACTION:
CC       Q9UL26; Q60I27: ALS2CL; NbExp=3; IntAct=EBI-399456, EBI-12078276;
CC       Q9UL26; Q8NEU8: APPL2; NbExp=8; IntAct=EBI-399456, EBI-741261;
CC       Q9UL26; Q15075: EEA1; NbExp=3; IntAct=EBI-399456, EBI-298113;
CC   -!- SUBCELLULAR LOCATION: Endosome membrane {ECO:0000250|UniProtKB:P51154};
CC       Lipid-anchor {ECO:0000305}. Cell membrane
CC       {ECO:0000250|UniProtKB:P51154}; Lipid-anchor {ECO:0000305}. Early
CC       endosome {ECO:0000269|PubMed:16537905}. Late endosome
CC       {ECO:0000250|UniProtKB:P51154}. Cell projection, ruffle
CC       {ECO:0000269|PubMed:21419809}. Cytoplasmic vesicle
CC       {ECO:0000269|PubMed:21419809}. Cytoplasmic vesicle, phagosome
CC       {ECO:0000269|PubMed:21255211}. Cytoplasmic vesicle, phagosome membrane
CC       {ECO:0000305}; Lipid-anchor {ECO:0000305}; Cytoplasmic side
CC       {ECO:0000305}. Note=Recruited to phagosomes containing S.aureus or
CC       M.tuberculosis. {ECO:0000269|PubMed:21255211}.
CC   -!- SIMILARITY: Belongs to the small GTPase superfamily. Rab family.
CC       {ECO:0000305}.
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DR   EMBL; AF125104; AAL75941.1; -; mRNA.
DR   EMBL; AF091034; AAF00047.2; -; mRNA.
DR   EMBL; AJ276210; CAC10538.1; -; mRNA.
DR   EMBL; BT007046; AAP35695.1; -; mRNA.
DR   EMBL; AK091180; BAG52298.1; -; mRNA.
DR   EMBL; AL035455; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471077; EAW75496.1; -; Genomic_DNA.
DR   EMBL; CH471077; EAW75497.1; -; Genomic_DNA.
DR   EMBL; BC015710; AAH15710.1; -; mRNA.
DR   EMBL; BC063457; AAH63457.1; -; mRNA.
DR   CCDS; CCDS33497.1; -.
DR   RefSeq; NP_065724.1; NM_020673.2.
DR   AlphaFoldDB; Q9UL26; -.
DR   SMR; Q9UL26; -.
DR   BioGRID; 121505; 22.
DR   IntAct; Q9UL26; 11.
DR   MINT; Q9UL26; -.
DR   STRING; 9606.ENSP00000244040; -.
DR   ChEMBL; CHEMBL4295981; -.
DR   iPTMnet; Q9UL26; -.
DR   PhosphoSitePlus; Q9UL26; -.
DR   SwissPalm; Q9UL26; -.
DR   BioMuta; RAB22A; -.
DR   DMDM; 13633614; -.
DR   EPD; Q9UL26; -.
DR   jPOST; Q9UL26; -.
DR   MassIVE; Q9UL26; -.
DR   MaxQB; Q9UL26; -.
DR   PaxDb; 9606-ENSP00000244040; -.
DR   PeptideAtlas; Q9UL26; -.
DR   ProteomicsDB; 84935; -.
DR   Pumba; Q9UL26; -.
DR   Antibodypedia; 29093; 176 antibodies from 30 providers.
DR   DNASU; 57403; -.
DR   Ensembl; ENST00000244040.4; ENSP00000244040.3; ENSG00000124209.4.
DR   GeneID; 57403; -.
DR   KEGG; hsa:57403; -.
DR   MANE-Select; ENST00000244040.4; ENSP00000244040.3; NM_020673.3; NP_065724.1.
DR   UCSC; uc002xyz.4; human.
DR   AGR; HGNC:9764; -.
DR   CTD; 57403; -.
DR   DisGeNET; 57403; -.
DR   GeneCards; RAB22A; -.
DR   HGNC; HGNC:9764; RAB22A.
DR   HPA; ENSG00000124209; Low tissue specificity.
DR   MIM; 612966; gene.
DR   neXtProt; NX_Q9UL26; -.
DR   OpenTargets; ENSG00000124209; -.
DR   PharmGKB; PA34112; -.
DR   VEuPathDB; HostDB:ENSG00000124209; -.
DR   eggNOG; KOG0092; Eukaryota.
DR   GeneTree; ENSGT00940000157009; -.
DR   HOGENOM; CLU_041217_10_2_1; -.
DR   InParanoid; Q9UL26; -.
DR   OMA; CDLNDAR; -.
DR   OrthoDB; 5483572at2759; -.
DR   PhylomeDB; Q9UL26; -.
DR   TreeFam; TF331262; -.
DR   PathwayCommons; Q9UL26; -.
DR   Reactome; R-HSA-8873719; RAB geranylgeranylation.
DR   SignaLink; Q9UL26; -.
DR   SIGNOR; Q9UL26; -.
DR   BioGRID-ORCS; 57403; 11 hits in 1154 CRISPR screens.
DR   ChiTaRS; RAB22A; human.
DR   GeneWiki; RAB22A; -.
DR   GenomeRNAi; 57403; -.
DR   Pharos; Q9UL26; Tbio.
DR   PRO; PR:Q9UL26; -.
DR   Proteomes; UP000005640; Chromosome 20.
DR   RNAct; Q9UL26; Protein.
DR   Bgee; ENSG00000124209; Expressed in middle temporal gyrus and 210 other cell types or tissues.
DR   GO; GO:0015629; C:actin cytoskeleton; IEA:Ensembl.
DR   GO; GO:0005769; C:early endosome; IDA:UniProtKB.
DR   GO; GO:0012505; C:endomembrane system; IBA:GO_Central.
DR   GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0005770; C:late endosome; IEA:UniProtKB-SubCell.
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; IDA:UniProtKB.
DR   GO; GO:0001726; C:ruffle; IEA:UniProtKB-SubCell.
DR   GO; GO:0019003; F:GDP binding; IDA:UniProtKB.
DR   GO; GO:0005525; F:GTP binding; IMP:UniProtKB.
DR   GO; GO:0003924; F:GTPase activity; IMP:UniProtKB.
DR   GO; GO:0006897; P:endocytosis; IDA:UniProtKB.
DR   GO; GO:0007032; P:endosome organization; IEP:UniProtKB.
DR   GO; GO:0006886; P:intracellular protein transport; IBA:GO_Central.
DR   GO; GO:0097494; P:regulation of vesicle size; IMP:UniProtKB.
DR   CDD; cd01860; Rab5_related; 1.
DR   Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1.
DR   InterPro; IPR027417; P-loop_NTPase.
DR   InterPro; IPR005225; Small_GTP-bd_dom.
DR   InterPro; IPR001806; Small_GTPase.
DR   NCBIfam; TIGR00231; small_GTP; 1.
DR   PANTHER; PTHR47977; RAS-RELATED PROTEIN RAB; 1.
DR   PANTHER; PTHR47977:SF13; RAS-RELATED PROTEIN RAB-31 ISOFORM X1; 1.
DR   Pfam; PF00071; Ras; 1.
DR   PRINTS; PR00449; RASTRNSFRMNG.
DR   SMART; SM00175; RAB; 1.
DR   SMART; SM00176; RAN; 1.
DR   SMART; SM00173; RAS; 1.
DR   SMART; SM00174; RHO; 1.
DR   SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1.
DR   PROSITE; PS51419; RAB; 1.
DR   Genevisible; Q9UL26; HS.
PE   1: Evidence at protein level;
KW   Cell membrane; Cell projection; Cytoplasmic vesicle; Endocytosis; Endosome;
KW   GTP-binding; Lipoprotein; Membrane; Nucleotide-binding; Prenylation;
KW   Protein transport; Reference proteome; Transport.
FT   CHAIN           1..194
FT                   /note="Ras-related protein Rab-22A"
FT                   /id="PRO_0000121209"
FT   REGION          174..194
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           34..42
FT                   /note="Effector region"
FT                   /evidence="ECO:0000250"
FT   BINDING         12..20
FT                   /ligand="GTP"
FT                   /ligand_id="ChEBI:CHEBI:37565"
FT                   /evidence="ECO:0000250"
FT   BINDING         60..64
FT                   /ligand="GTP"
FT                   /ligand_id="ChEBI:CHEBI:37565"
FT                   /evidence="ECO:0000250"
FT   BINDING         118..121
FT                   /ligand="GTP"
FT                   /ligand_id="ChEBI:CHEBI:37565"
FT                   /evidence="ECO:0000250"
FT   BINDING         148..150
FT                   /ligand="GTP"
FT                   /ligand_id="ChEBI:CHEBI:37565"
FT                   /evidence="ECO:0000250"
FT   LIPID           193
FT                   /note="S-geranylgeranyl cysteine"
FT                   /evidence="ECO:0000250"
FT   LIPID           194
FT                   /note="S-geranylgeranyl cysteine"
FT                   /evidence="ECO:0000250"
FT   MUTAGEN         19
FT                   /note="S->L: Loss of GTPase activity."
FT                   /evidence="ECO:0000269|PubMed:21419809"
FT   MUTAGEN         64
FT                   /note="Q->L: Constitutive GTPase activity. Impairs normal
FT                   protein trafficking through early endosomes."
FT                   /evidence="ECO:0000269|PubMed:16537905,
FT                   ECO:0000269|PubMed:21419809"
FT   CONFLICT        184
FT                   /note="R -> K (in Ref. 3; CAC10538)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        192..193
FT                   /note="SC -> TA (in Ref. 1; AAL75941)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   194 AA;  21855 MW;  EBC84711DA3F839B CRC64;
     MALRELKVCL LGDTGVGKSS IVWRFVEDSF DPNINPTIGA SFMTKTVQYQ NELHKFLIWD
     TAGQERFRAL APMYYRGSAA AIIVYDITKE ETFSTLKNWV KELRQHGPPN IVVAIAGNKC
     DLIDVREVME RDAKDYADSI HAIFVETSAK NAININELFI EISRRIPSTD ANLPSGGKGF
     KLRRQPSEPK RSCC
//