RIT2_HUMAN
ID RIT2_HUMAN Reviewed; 217 AA.
AC Q99578; B2R9L1; O15295; Q8TD69; Q8WVF6; Q92964;
DT 31-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 187.
DE RecName: Full=GTP-binding protein Rit2;
DE EC=3.6.5.2 {ECO:0000250|UniProtKB:P70425};
DE AltName: Full=Ras-like protein expressed in neurons;
DE AltName: Full=Ras-like without CAAX protein 2;
GN Name=RIT2; Synonyms=RIN, ROC2;
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] (ISOFORM 1), AND CHARACTERIZATION.
RX PubMed=8824319; DOI=10.1523/jneurosci.16-21-06784.1996;
RA Lee C.H.J., Della N.G., Chew C.E., Zack D.J.;
RT "Rin, a neuron-specific and calmodulin-binding small G-protein, and Rit
RT define a novel subfamily of ras proteins.";
RL J. Neurosci. 16:6784-6794(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=8918462; DOI=10.1002/j.1460-2075.1996.tb00971.x;
RA Wes P.D., Yu M., Montell C.;
RT "RIC, a calmodulin-binding Ras-like GTPase.";
RL EMBO J. 15:5839-5848(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Neuron;
RA Kawasaki H., Housman D.E., Graybiel A.M.;
RT "Characterization of new small G proteins in the Ras subfamily.";
RL Submitted (JUL-1997) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Puhl H.L. III, Ikeda S.R., Aronstam R.S.;
RT "cDNA clones of human proteins involved in signal transduction sequenced by
RT the Guthrie cDNA resource center (www.cdna.org).";
RL Submitted (FEB-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
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].
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [8]
RP SUBCELLULAR LOCATION.
RX PubMed=12934100; DOI=10.1038/sj.onc.1206635;
RA Calissano M., Latchman D.S.;
RT "Functional interaction between the small GTP-binding protein Rin and the
RT N-terminal of Brn-3a transcription factor.";
RL Oncogene 22:5408-5414(2003).
RN [9]
RP INTERACTION WITH PLXNB3, AND SUBCELLULAR LOCATION.
RX PubMed=16122393; DOI=10.1186/1471-2202-6-53;
RA Hartwig C., Veske A., Krejcova S., Rosenberger G., Finckh U.;
RT "Plexin B3 promotes neurite outgrowth, interacts homophilically, and
RT interacts with Rin.";
RL BMC Neurosci. 6:53-53(2005).
CC -!- FUNCTION: Binds and exchanges GTP and GDP. Binds and modulates the
CC activation of POU4F1 as gene expression regulator.
CC {ECO:0000250|UniProtKB:P70425}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GTP + H2O = GDP + H(+) + phosphate; Xref=Rhea:RHEA:19669,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58189; EC=3.6.5.2;
CC Evidence={ECO:0000250|UniProtKB:P70425};
CC -!- SUBUNIT: Interacts with AFDN, the C-terminal domain of RALGDS and RLF,
CC but not with RIN1 and PIK3CA. RLF binds exclusively to the active GTP-
CC bound form (By similarity). Binds calmodulin. Interacts with PLXNB3.
CC Interacts with POU4F1 (via N-terminus); the interaction controls POU4F1
CC transactivation activity on some neuronal target genes (By similarity).
CC {ECO:0000250|UniProtKB:P70425, ECO:0000269|PubMed:16122393}.
CC -!- INTERACTION:
CC Q99578; Q3MIN7: RGL3; NbExp=3; IntAct=EBI-365914, EBI-2856274;
CC Q99578; Q01959: SLC6A3; NbExp=5; IntAct=EBI-365914, EBI-6661445;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12934100,
CC ECO:0000269|PubMed:16122393}. Cell membrane
CC {ECO:0000269|PubMed:16122393}. Note=Colocalizes with PLXNB3 at the
CC plasma membrane (PubMed:16122393). {ECO:0000269|PubMed:16122393}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q99578-1; Sequence=Displayed;
CC Name=2; Synonyms=RIBA;
CC IsoId=Q99578-2; Sequence=VSP_018102, VSP_018103;
CC -!- TISSUE SPECIFICITY: Neuron-specific.
CC -!- MISCELLANEOUS: Shows rapid uncatalyzed guanine nucleotide dissociation
CC rates, which are much faster than those of most Ras subfamily members.
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Ras family.
CC {ECO:0000305}.
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DR EMBL; U71204; AAB42214.1; -; mRNA.
DR EMBL; Y07565; CAA68850.1; -; mRNA.
DR EMBL; U78164; AAB64245.1; -; mRNA.
DR EMBL; U78166; AAB64247.1; -; mRNA.
DR EMBL; AF493922; AAM12636.1; -; mRNA.
DR EMBL; AY563951; AAS75332.1; -; mRNA.
DR EMBL; AK313823; BAG36558.1; -; mRNA.
DR EMBL; CH471088; EAX01432.1; -; Genomic_DNA.
DR EMBL; BC018060; AAH18060.1; -; mRNA.
DR CCDS; CCDS11921.1; -. [Q99578-1]
DR CCDS; CCDS62431.1; -. [Q99578-2]
DR RefSeq; NP_001259006.1; NM_001272077.1. [Q99578-2]
DR RefSeq; NP_002921.1; NM_002930.3. [Q99578-1]
DR AlphaFoldDB; Q99578; -.
DR SMR; Q99578; -.
DR BioGRID; 111946; 21.
DR IntAct; Q99578; 6.
DR STRING; 9606.ENSP00000321805; -.
DR iPTMnet; Q99578; -.
DR PhosphoSitePlus; Q99578; -.
DR BioMuta; RIT2; -.
DR DMDM; 38258639; -.
DR MassIVE; Q99578; -.
DR PaxDb; Q99578; -.
DR PeptideAtlas; Q99578; -.
DR PRIDE; Q99578; -.
DR ProteomicsDB; 78338; -. [Q99578-1]
DR ProteomicsDB; 78339; -. [Q99578-2]
DR Antibodypedia; 8862; 287 antibodies from 29 providers.
DR DNASU; 6014; -.
DR Ensembl; ENST00000326695.10; ENSP00000321805.4; ENSG00000152214.14. [Q99578-1]
DR Ensembl; ENST00000589109.5; ENSP00000467217.1; ENSG00000152214.14. [Q99578-2]
DR GeneID; 6014; -.
DR KEGG; hsa:6014; -.
DR MANE-Select; ENST00000326695.10; ENSP00000321805.4; NM_002930.4; NP_002921.1.
DR UCSC; uc002lav.5; human. [Q99578-1]
DR CTD; 6014; -.
DR DisGeNET; 6014; -.
DR GeneCards; RIT2; -.
DR HGNC; HGNC:10017; RIT2.
DR HPA; ENSG00000152214; Group enriched (brain, choroid plexus).
DR MIM; 609592; gene.
DR neXtProt; NX_Q99578; -.
DR OpenTargets; ENSG00000152214; -.
DR PharmGKB; PA35527; -.
DR VEuPathDB; HostDB:ENSG00000152214; -.
DR eggNOG; KOG0395; Eukaryota.
DR GeneTree; ENSGT00940000161402; -.
DR HOGENOM; CLU_041217_9_5_1; -.
DR InParanoid; Q99578; -.
DR OMA; QFVSHRF; -.
DR OrthoDB; 1259506at2759; -.
DR PhylomeDB; Q99578; -.
DR TreeFam; TF315072; -.
DR PathwayCommons; Q99578; -.
DR Reactome; R-HSA-187706; Signalling to p38 via RIT and RIN.
DR SignaLink; Q99578; -.
DR SIGNOR; Q99578; -.
DR BioGRID-ORCS; 6014; 14 hits in 1076 CRISPR screens.
DR ChiTaRS; RIT2; human.
DR GeneWiki; RIT2; -.
DR GenomeRNAi; 6014; -.
DR Pharos; Q99578; Tbio.
DR PRO; PR:Q99578; -.
DR Proteomes; UP000005640; Chromosome 18.
DR RNAct; Q99578; protein.
DR Bgee; ENSG00000152214; Expressed in cerebellar cortex and 101 other tissues.
DR ExpressionAtlas; Q99578; baseline and differential.
DR Genevisible; Q99578; HS.
DR GO; GO:0044297; C:cell body; ISS:ParkinsonsUK-UCL.
DR GO; GO:0005737; C:cytoplasm; ISS:ParkinsonsUK-UCL.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0097447; C:dendritic tree; ISS:ParkinsonsUK-UCL.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0045121; C:membrane raft; IDA:ParkinsonsUK-UCL.
DR GO; GO:0043005; C:neuron projection; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005886; C:plasma membrane; IDA:ParkinsonsUK-UCL.
DR GO; GO:0045202; C:synapse; IEA:GOC.
DR GO; GO:0005516; F:calmodulin binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl.
DR GO; GO:0003925; F:G protein activity; IEA:UniProtKB-EC.
DR GO; GO:0019003; F:GDP binding; IBA:GO_Central.
DR GO; GO:0005525; F:GTP binding; ISS:ParkinsonsUK-UCL.
DR GO; GO:0003924; F:GTPase activity; ISS:ParkinsonsUK-UCL.
DR GO; GO:0030215; F:semaphorin receptor binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0007268; P:chemical synaptic transmission; TAS:ProtInc.
DR GO; GO:0035556; P:intracellular signal transduction; IDA:ParkinsonsUK-UCL.
DR GO; GO:0032507; P:maintenance of protein location in cell; IMP:ParkinsonsUK-UCL.
DR GO; GO:0010977; P:negative regulation of neuron projection development; IEA:Ensembl.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISS:ParkinsonsUK-UCL.
DR GO; GO:0010976; P:positive regulation of neuron projection development; IGI:ParkinsonsUK-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0007265; P:Ras protein signal transduction; ISS:ParkinsonsUK-UCL.
DR GO; GO:0050848; P:regulation of calcium-mediated signaling; ISS:ParkinsonsUK-UCL.
DR GO; GO:0032489; P:regulation of Cdc42 protein signal transduction; ISS:ParkinsonsUK-UCL.
DR GO; GO:0030100; P:regulation of endocytosis; IMP:ParkinsonsUK-UCL.
DR GO; GO:0001932; P:regulation of protein phosphorylation; IEA:Ensembl.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; NAS:UniProtKB.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR005225; Small_GTP-bd_dom.
DR InterPro; IPR001806; Small_GTPase.
DR InterPro; IPR020849; Small_GTPase_Ras-type.
DR PANTHER; PTHR24070; PTHR24070; 1.
DR Pfam; PF00071; Ras; 1.
DR SMART; SM00174; RHO; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00231; small_GTP; 1.
DR PROSITE; PS51421; RAS; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Calmodulin-binding; Cell membrane; GTP-binding;
KW Hydrolase; Membrane; Nucleotide-binding; Nucleus; Reference proteome.
FT CHAIN 1..217
FT /note="GTP-binding protein Rit2"
FT /id="PRO_0000082727"
FT BINDING 27..34
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 74..78
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 133..136
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT VAR_SEQ 143..153
FT /note="VSTEEGLSLAQ -> PTLKEFGREEF (in isoform 2)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_018102"
FT VAR_SEQ 154..217
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_018103"
FT CONFLICT 39
FT /note="Q -> L (in Ref. 4; AAM12636)"
FT /evidence="ECO:0000305"
FT CONFLICT 76
FT /note="A -> D (in Ref. 1; AAB42214)"
FT /evidence="ECO:0000305"
FT CONFLICT 200
FT /note="S -> C (in Ref. 7; AAH18060)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 217 AA; 24668 MW; CD2A9ECE4AEAA792 CRC64;
MEVENEASCS PGSASGGSRE YKVVMLGAGG VGKSAMTMQF ISHQFPDYHD PTIEDAYKTQ
VRIDNEPAYL DILDTAGQAE FTAMREQYMR GGEGFIICYS VTDRQSFQEA AKFKELIFQV
RHTYEIPLVL VGNKIDLEQF RQVSTEEGLS LAQEYNCGFF ETSAALRFCI DDAFHGLVRE
IRKKESMPSL MEKKLKRKDS LWKKLKGSLK KKRENMT
