RAP2A_MOUSE
ID RAP2A_MOUSE Reviewed; 183 AA.
AC Q80ZJ1; Q3USK1; Q7TSK4; Q810A2; Q9D3D5;
DT 12-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 2.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Ras-related protein Rap-2a;
DE EC=3.6.5.2 {ECO:0000250|UniProtKB:P10114};
DE Flags: Precursor;
GN Name=Rap2a;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Adipose tissue, and Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; 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 [3]
RP PROTEIN SEQUENCE OF 6-16; 109-124 AND 151-162, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC STRAIN=C57BL/6J; TISSUE=Brain;
RA Lubec G., Kang S.U.;
RL Submitted (APR-2007) to UniProtKB.
RN [4]
RP INTERACTION WITH RUNDC3A, DOMAIN, AND MUTAGENESIS OF SER-17 AND THR-35.
RX PubMed=9523700; DOI=10.1046/j.1432-1327.1998.2520290.x;
RA Janoueix-Lerosey I., Pasheva E., de Tand M.-F., Tavitian A.,
RA de Gunzburg J.;
RT "Identification of a specific effector of the small GTP-binding protein
RT Rap2.";
RL Eur. J. Biochem. 252:290-298(1998).
RN [5]
RP INTERACTION WITH RGS14, AND TISSUE SPECIFICITY.
RX PubMed=10926822; DOI=10.1042/bj3500019;
RA Traver S., Bidot C., Spassky N., Baltauss T., De Tand M.F., Thomas J.L.,
RA Zalc B., Janoueix-Lerosey I., Gunzburg J.D.;
RT "RGS14 is a novel Rap effector that preferentially regulates the GTPase
RT activity of galphao.";
RL Biochem. J. 350:19-29(2000).
RN [6]
RP FUNCTION.
RX PubMed=12133960; DOI=10.4049/jimmunol.169.3.1365;
RA McLeod S.J., Li A.H., Lee R.L., Burgess A.E., Gold M.R.;
RT "The Rap GTPases regulate B cell migration toward the chemokine stromal
RT cell-derived factor-1 (CXCL12): potential role for Rap2 in promoting B cell
RT migration.";
RL J. Immunol. 169:1365-1371(2002).
RN [7]
RP FUNCTION, AND TRANSGENIC MICE.
RX PubMed=18701680; DOI=10.1523/jneurosci.1944-08.2008;
RA Ryu J., Futai K., Feliu M., Weinberg R., Sheng M.;
RT "Constitutively active Rap2 transgenic mice display fewer dendritic spines,
RT reduced extracellular signal-regulated kinase signaling, enhanced long-term
RT depression, and impaired spatial learning and fear extinction.";
RL J. Neurosci. 28:8178-8188(2008).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, ISOPRENYLATION AT CYS-180, METHYLATION AT
RP CYS-180, PALMITOYLATION AT CYS-176 AND CYS-177, AND MUTAGENESIS OF CYS-176;
RP CYS-177 AND CYS-180.
RX PubMed=19061864; DOI=10.1016/j.bbrc.2008.11.107;
RA Uechi Y., Bayarjargal M., Umikawa M., Oshiro M., Takei K., Yamashiro Y.,
RA Asato T., Endo S., Misaki R., Taguchi T., Kariya K.;
RT "Rap2 function requires palmitoylation and recycling endosome
RT localization.";
RL Biochem. Biophys. Res. Commun. 378:732-737(2009).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Liver, Lung, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [10]
RP INTERACTION WITH NEDD4 AND TNIK, AND UBIQUITINATION BY NEDD4.
RX PubMed=20159449; DOI=10.1016/j.neuron.2010.01.007;
RA Kawabe H., Neeb A., Dimova K., Young S.M. Jr., Takeda M.,
RA Katsurabayashi S., Mitkovski M., Malakhova O.A., Zhang D.E., Umikawa M.,
RA Kariya K., Goebbels S., Nave K.A., Rosenmund C., Jahn O., Rhee J.,
RA Brose N.;
RT "Regulation of Rap2A by the ubiquitin ligase Nedd4-1 controls neurite
RT development.";
RL Neuron 65:358-372(2010).
CC -!- FUNCTION: Small GTP-binding protein which cycles between a GDP-bound
CC inactive and a GTP-bound active form. In its active form interacts with
CC and regulates several effectors including MAP4K4, MINK1 and TNIK. Part
CC of a signaling complex composed of NEDD4, RAP2A and TNIK which
CC regulates neuronal dendrite extension and arborization during
CC development. More generally, it is part of several signaling cascades
CC and may regulate cytoskeletal rearrangements, cell migration, cell
CC adhesion and cell spreading. {ECO:0000269|PubMed:12133960,
CC ECO:0000269|PubMed:18701680, ECO:0000269|PubMed:19061864}.
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:P10114};
CC -!- ACTIVITY REGULATION: Activated by the guanine nucleotide-exchange
CC factors RAPGEF3 and RAPGEF4 in a cAMP-dependent manner. Nucleotide
CC exchange is also specifically stimulated by RAPGEF5, RASGEF1A and
CC RASGEF1B (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Interacts with PLCE1. Interacts with ARHGAP29, SGSM1, SGSM2
CC and SGSM3. Interacts (GTP-bound form preferentially) with MAP4K4.
CC Interacts with MINK1. Interacts with cytoskeletal actin (By
CC similarity). Interacts (GTP-bound form) with RUNDC3A. Interacts (GTP-
CC bound form preferentially) with TNIK (via the CNH domain); the
CC interaction is direct and recruits RAP2A to the E3 ubiquitin ligase
CC NEDD4. Interacts with RGS14; the interaction is GTP-dependent.
CC {ECO:0000250, ECO:0000269|PubMed:10926822, ECO:0000269|PubMed:20159449,
CC ECO:0000269|PubMed:9523700}.
CC -!- SUBCELLULAR LOCATION: Midbody {ECO:0000250}. Recycling endosome
CC membrane {ECO:0000269|PubMed:19061864}; Lipid-anchor
CC {ECO:0000269|PubMed:19061864}; Cytoplasmic side
CC {ECO:0000269|PubMed:19061864}. Note=Localizes to midbody at telophase.
CC May also localize to the Golgi and the gelatinase-containing granules
CC of neutrophils. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q80ZJ1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q80ZJ1-2; Sequence=VSP_013381;
CC -!- TISSUE SPECIFICITY: Expressed in granular layer of the cerebellum,
CC forebrain, striatum, layer V of the cortex, olfactory cortex,
CC tubercules, subthalamic and hippocampus, particularly in the CA2
CC region, to a lesser extent in the CA1 region and the external layer of
CC the dentate gyrus. Expressed in neurons. {ECO:0000269|PubMed:10926822}.
CC -!- DOMAIN: The effector domain mediates the interaction with RUNDC3A.
CC {ECO:0000269|PubMed:9523700}.
CC -!- PTM: Ubiquitinated; undergoes 'Lys-63' monoubiquitination and
CC diubiquitination by NEDD4. Multiple lysine residues are probably
CC modified. Ubiquitination requires TNIK, prevents interaction with
CC effectors and inactivates RAP2A. {ECO:0000269|PubMed:20159449}.
CC -!- PTM: Palmitoylated. Palmitoylation is required for association with
CC recycling endosome membranes and activation of TNIK.
CC {ECO:0000269|PubMed:19061864}.
CC -!- MISCELLANEOUS: Transgenic mice expressing a constitutively active form
CC of Rap2a display impaired spatial learning and defective extinction of
CC contextual fear.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Ras family.
CC {ECO:0000305}.
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DR EMBL; AK018024; BAB31042.1; -; mRNA.
DR EMBL; AK140318; BAE24330.1; -; mRNA.
DR EMBL; BC043066; AAH43066.2; -; mRNA.
DR EMBL; BC049084; AAH49084.2; -; mRNA.
DR EMBL; BC053003; AAH53003.1; -; mRNA.
DR CCDS; CCDS27341.1; -. [Q80ZJ1-1]
DR RefSeq; NP_083795.2; NM_029519.3. [Q80ZJ1-1]
DR AlphaFoldDB; Q80ZJ1; -.
DR SMR; Q80ZJ1; -.
DR BioGRID; 217966; 6.
DR IntAct; Q80ZJ1; 2.
DR MINT; Q80ZJ1; -.
DR STRING; 10090.ENSMUSP00000056433; -.
DR iPTMnet; Q80ZJ1; -.
DR PhosphoSitePlus; Q80ZJ1; -.
DR SwissPalm; Q80ZJ1; -.
DR EPD; Q80ZJ1; -.
DR jPOST; Q80ZJ1; -.
DR MaxQB; Q80ZJ1; -.
DR PaxDb; Q80ZJ1; -.
DR PeptideAtlas; Q80ZJ1; -.
DR PRIDE; Q80ZJ1; -.
DR ProteomicsDB; 254981; -. [Q80ZJ1-1]
DR Antibodypedia; 10676; 147 antibodies from 28 providers.
DR DNASU; 76108; -.
DR Ensembl; ENSMUST00000062117; ENSMUSP00000056433; ENSMUSG00000051615. [Q80ZJ1-1]
DR GeneID; 76108; -.
DR KEGG; mmu:76108; -.
DR UCSC; uc007uzx.1; mouse. [Q80ZJ1-1]
DR CTD; 5911; -.
DR MGI; MGI:97855; Rap2a.
DR VEuPathDB; HostDB:ENSMUSG00000051615; -.
DR eggNOG; KOG0395; Eukaryota.
DR GeneTree; ENSGT00940000160594; -.
DR HOGENOM; CLU_041217_9_8_1; -.
DR InParanoid; Q80ZJ1; -.
DR OMA; EYSPTIE; -.
DR OrthoDB; 1353024at2759; -.
DR PhylomeDB; Q80ZJ1; -.
DR TreeFam; TF313014; -.
DR BRENDA; 3.6.5.2; 3474.
DR BioGRID-ORCS; 76108; 3 hits in 74 CRISPR screens.
DR ChiTaRS; Rap2a; mouse.
DR PRO; PR:Q80ZJ1; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; Q80ZJ1; protein.
DR Bgee; ENSMUSG00000051615; Expressed in sciatic nerve and 239 other tissues.
DR Genevisible; Q80ZJ1; MM.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0030496; C:midbody; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0055037; C:recycling endosome; IDA:MGI.
DR GO; GO:0055038; C:recycling endosome membrane; IDA:UniProtKB.
DR GO; GO:0003925; F:G protein activity; IEA:UniProtKB-EC.
DR GO; GO:0019003; F:GDP binding; ISO:MGI.
DR GO; GO:0005525; F:GTP binding; ISO:MGI.
DR GO; GO:0003924; F:GTPase activity; ISS:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; ISO:MGI.
DR GO; GO:0031532; P:actin cytoskeleton reorganization; ISS:UniProtKB.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; ISO:MGI.
DR GO; GO:0045184; P:establishment of protein localization; ISO:MGI.
DR GO; GO:0030033; P:microvillus assembly; ISO:MGI.
DR GO; GO:0030336; P:negative regulation of cell migration; IDA:MGI.
DR GO; GO:0031954; P:positive regulation of protein autophosphorylation; IDA:MGI.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:MGI.
DR GO; GO:0008104; P:protein localization; ISS:UniProtKB.
DR GO; GO:0072659; P:protein localization to plasma membrane; ISO:MGI.
DR GO; GO:0032486; P:Rap protein signal transduction; IDA:UniProtKB.
DR GO; GO:0048814; P:regulation of dendrite morphogenesis; ISS:UniProtKB.
DR GO; GO:0046328; P:regulation of JNK cascade; ISS:UniProtKB.
DR CDD; cd04176; Rap2; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR041840; Rap2.
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; Direct protein sequencing; Endosome; GTP-binding;
KW Hydrolase; Lipoprotein; Membrane; Methylation; Nucleotide-binding;
KW Palmitate; Prenylation; Reference proteome; Ubl conjugation.
FT CHAIN 1..180
FT /note="Ras-related protein Rap-2a"
FT /id="PRO_0000082688"
FT PROPEP 181..183
FT /note="Removed in mature form"
FT /evidence="ECO:0000305|PubMed:19061864"
FT /id="PRO_0000281337"
FT MOTIF 32..40
FT /note="Effector region"
FT BINDING 10..17
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 57..61
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 116..119
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT MOD_RES 180
FT /note="Cysteine methyl ester"
FT /evidence="ECO:0000305|PubMed:19061864"
FT LIPID 176
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:19061864"
FT LIPID 177
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:19061864"
FT LIPID 180
FT /note="S-farnesyl cysteine"
FT /evidence="ECO:0000269|PubMed:19061864"
FT VAR_SEQ 106..183
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_013381"
FT MUTAGEN 17
FT /note="S->N: Loss of affinity for GTP and loss of
FT interaction with RUNDC3A."
FT /evidence="ECO:0000269|PubMed:9523700"
FT MUTAGEN 35
FT /note="T->A: Loss of interaction with RUNDC3A."
FT /evidence="ECO:0000269|PubMed:9523700"
FT MUTAGEN 176
FT /note="C->G: Loss of association with the recycling
FT endosome membranes and loss of TNIK activation; when
FT associated with C-177."
FT /evidence="ECO:0000269|PubMed:19061864"
FT MUTAGEN 177
FT /note="C->G: Loss of association with the recycling
FT endosome membranes and loss of TNIK activation; when
FT associated with C-176."
FT /evidence="ECO:0000269|PubMed:19061864"
FT MUTAGEN 180
FT /note="C->A: Loss of association with membranes."
FT /evidence="ECO:0000269|PubMed:19061864"
SQ SEQUENCE 183 AA; 20642 MW; A46054762765E431 CRC64;
MREYKVVVLG SGGVGKSALT VQFVTGTFIE KYDPTIEDFY RKEIEVDSSP SVLEILDTAG
TEQFASMRDL YIKNGQGFIL VYSLVNQQSF QDIKPMRDQI IRVKRYEKVP VILVGNKVDL
ESEREVSSNE GRALAEEWGC PFMETSAKSK TMVDELFAEI VRQMNYAAQP DKDDPCCSAC
NIQ
