Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Ras-related protein Rap-2a

Gene

Rap2a

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Small GTP-binding protein which cycles between a GDP-bound inactive and a GTP-bound active form. In its active form interacts with and regulates several effectors including MAP4K4, MINK1 and TNIK. Part of a signaling complex composed of NEDD4, RAP2A and TNIK which regulates neuronal dendrite extension and arborization during development. More generally, it is part of several signaling cascades and may regulate cytoskeletal rearrangements, cell migration, cell adhesion and cell spreading.3 Publications

Enzyme regulationi

Activated by the guanine nucleotide-exchange factors RAPGEF3 and RAPGEF4 in a cAMP-dependent manner. Nucleotide exchange is also specifically stimulated by RAPGEF5, RASGEF1A and RASGEF1B (By similarity).By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi10 – 178GTPBy similarity
Nucleotide bindingi57 – 615GTPBy similarity
Nucleotide bindingi116 – 1194GTPBy similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Ligandi

GTP-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Ras-related protein Rap-2a
Gene namesi
Name:Rap2a
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 14

Organism-specific databases

MGIiMGI:97855. Rap2a.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: MGI
  • extracellular exosome Source: MGI
  • membrane Source: MGI
  • midbody Source: UniProtKB-SubCell
  • plasma membrane Source: MGI
  • recycling endosome Source: MGI
  • recycling endosome membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Endosome, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi17 – 171S → N: Loss of affinity for GTP and loss of interaction with RUNDC3A. 1 Publication
Mutagenesisi35 – 351T → A: Loss of interaction with RUNDC3A. 1 Publication
Mutagenesisi176 – 1761C → G: Loss of association with the recycling endosome membranes and loss of TNIK activation; when associated with C-177. 1 Publication
Mutagenesisi177 – 1771C → G: Loss of association with the recycling endosome membranes and loss of TNIK activation; when associated with C-176. 1 Publication
Mutagenesisi180 – 1801C → A: Loss of association with membranes. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 180180Ras-related protein Rap-2aPRO_0000082688Add
BLAST
Propeptidei181 – 1833Removed in mature form1 PublicationPRO_0000281337

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi176 – 1761S-palmitoyl cysteine1 Publication
Lipidationi177 – 1771S-palmitoyl cysteine1 Publication
Modified residuei180 – 1801Cysteine methyl ester1 Publication
Lipidationi180 – 1801S-farnesyl cysteine1 Publication

Post-translational modificationi

Ubiquitinated; undergoes 'Lys-63' monoubiquitination and diubiquitination by NEDD4. Multiple lysine residues are probably modified. Ubiquitination requires TNIK, prevents interaction with effectors and inactivates RAP2A.1 Publication
Palmitoylated. Palmitoylation is required for association with recycling endosome membranes and activation of TNIK.1 Publication

Keywords - PTMi

Lipoprotein, Methylation, Palmitate, Prenylation, Ubl conjugation

Proteomic databases

EPDiQ80ZJ1.
MaxQBiQ80ZJ1.
PaxDbiQ80ZJ1.
PRIDEiQ80ZJ1.

PTM databases

iPTMnetiQ80ZJ1.
PhosphoSiteiQ80ZJ1.
SwissPalmiQ80ZJ1.

Expressioni

Tissue specificityi

Expressed in granular layer of the cerebellum, forebrain, striatum, layer V of the cortex, olfactory cortex, tubercules, subthalamic and hippocampus, particularly in the CA2 region, to a lesser extent in the CA1 region and the external layer of the dentate gyrus. Expressed in neurons.1 Publication

Gene expression databases

BgeeiQ80ZJ1.
CleanExiMM_RAP2A.
ExpressionAtlasiQ80ZJ1. baseline and differential.
GenevisibleiQ80ZJ1. MM.

Interactioni

Subunit structurei

Interacts with PLCE1. Interacts with ARHGAP29, SGSM1, SGSM2 and SGSM3. Interacts (GTP-bound form preferentially) with MAP4K4. Interacts with MINK1. Interacts with cytoskeletal actin (By similarity). Interacts (GTP-bound form) with RUNDC3A. Interacts (GTP-bound form preferentially) with TNIK (via the CNH domain); the interaction is direct and recruits RAP2A to the E3 ubiquitin ligase NEDD4. Interacts with RGS14; the interaction is GTP-dependent.By similarity3 Publications

Protein-protein interaction databases

BioGridi217966. 4 interactions.
IntActiQ80ZJ1. 3 interactions.
STRINGi10090.ENSMUSP00000056433.

Structurei

3D structure databases

ProteinModelPortaliQ80ZJ1.
SMRiQ80ZJ1. Positions 1-167.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi32 – 409Effector region

Domaini

The effector domain mediates the interaction with RUNDC3A.1 Publication

Sequence similaritiesi

Belongs to the small GTPase superfamily. Ras family.Curated

Phylogenomic databases

eggNOGiKOG0395. Eukaryota.
COG1100. LUCA.
GeneTreeiENSGT00780000121857.
HOGENOMiHOG000233973.
HOVERGENiHBG009351.
InParanoidiQ80ZJ1.
KOiK07837.
OMAiEINGASW.
PhylomeDBiQ80ZJ1.
TreeFamiTF313014.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
InterProiIPR027417. P-loop_NTPase.
IPR005225. Small_GTP-bd_dom.
IPR001806. Small_GTPase.
IPR020849. Small_GTPase_Ras.
[Graphical view]
PANTHERiPTHR24070. PTHR24070. 1 hit.
PfamiPF00071. Ras. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 1 hit.
TIGRFAMsiTIGR00231. small_GTP. 1 hit.
PROSITEiPS51421. RAS. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q80ZJ1-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MREYKVVVLG SGGVGKSALT VQFVTGTFIE KYDPTIEDFY RKEIEVDSSP
60 70 80 90 100
SVLEILDTAG TEQFASMRDL YIKNGQGFIL VYSLVNQQSF QDIKPMRDQI
110 120 130 140 150
IRVKRYEKVP VILVGNKVDL ESEREVSSNE GRALAEEWGC PFMETSAKSK
160 170 180
TMVDELFAEI VRQMNYAAQP DKDDPCCSAC NIQ
Length:183
Mass (Da):20,642
Last modified:December 21, 2004 - v2
Checksum:iA46054762765E431
GO
Isoform 2 (identifier: Q80ZJ1-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     106-183: Missing.

Show »
Length:105
Mass (Da):11,945
Checksum:iAB9A25820AFB5A0B
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei106 – 18378Missing in isoform 2. 1 PublicationVSP_013381Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK018024 mRNA. Translation: BAB31042.1.
AK140318 mRNA. Translation: BAE24330.1.
BC043066 mRNA. Translation: AAH43066.2.
BC049084 mRNA. Translation: AAH49084.2.
BC053003 mRNA. Translation: AAH53003.1.
CCDSiCCDS27341.1. [Q80ZJ1-1]
RefSeqiNP_083795.2. NM_029519.3. [Q80ZJ1-1]
UniGeneiMm.261448.

Genome annotation databases

EnsembliENSMUST00000062117; ENSMUSP00000056433; ENSMUSG00000051615. [Q80ZJ1-1]
GeneIDi76108.
KEGGimmu:76108.
UCSCiuc007uzx.1. mouse. [Q80ZJ1-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK018024 mRNA. Translation: BAB31042.1.
AK140318 mRNA. Translation: BAE24330.1.
BC043066 mRNA. Translation: AAH43066.2.
BC049084 mRNA. Translation: AAH49084.2.
BC053003 mRNA. Translation: AAH53003.1.
CCDSiCCDS27341.1. [Q80ZJ1-1]
RefSeqiNP_083795.2. NM_029519.3. [Q80ZJ1-1]
UniGeneiMm.261448.

3D structure databases

ProteinModelPortaliQ80ZJ1.
SMRiQ80ZJ1. Positions 1-167.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi217966. 4 interactions.
IntActiQ80ZJ1. 3 interactions.
STRINGi10090.ENSMUSP00000056433.

PTM databases

iPTMnetiQ80ZJ1.
PhosphoSiteiQ80ZJ1.
SwissPalmiQ80ZJ1.

Proteomic databases

EPDiQ80ZJ1.
MaxQBiQ80ZJ1.
PaxDbiQ80ZJ1.
PRIDEiQ80ZJ1.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000062117; ENSMUSP00000056433; ENSMUSG00000051615. [Q80ZJ1-1]
GeneIDi76108.
KEGGimmu:76108.
UCSCiuc007uzx.1. mouse. [Q80ZJ1-1]

Organism-specific databases

CTDi5911.
MGIiMGI:97855. Rap2a.

Phylogenomic databases

eggNOGiKOG0395. Eukaryota.
COG1100. LUCA.
GeneTreeiENSGT00780000121857.
HOGENOMiHOG000233973.
HOVERGENiHBG009351.
InParanoidiQ80ZJ1.
KOiK07837.
OMAiEINGASW.
PhylomeDBiQ80ZJ1.
TreeFamiTF313014.

Miscellaneous databases

ChiTaRSiRap2a. mouse.
PROiQ80ZJ1.
SOURCEiSearch...

Gene expression databases

BgeeiQ80ZJ1.
CleanExiMM_RAP2A.
ExpressionAtlasiQ80ZJ1. baseline and differential.
GenevisibleiQ80ZJ1. MM.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
InterProiIPR027417. P-loop_NTPase.
IPR005225. Small_GTP-bd_dom.
IPR001806. Small_GTPase.
IPR020849. Small_GTPase_Ras.
[Graphical view]
PANTHERiPTHR24070. PTHR24070. 1 hit.
PfamiPF00071. Ras. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 1 hit.
TIGRFAMsiTIGR00231. small_GTP. 1 hit.
PROSITEiPS51421. RAS. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
    Strain: C57BL/6J.
    Tissue: Adipose tissue and Thymus.
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Strain: C57BL/6J.
    Tissue: Brain.
  3. Lubec G., Kang S.U.
    Submitted (APR-2007) to UniProtKB
    Cited for: PROTEIN SEQUENCE OF 6-16; 109-124 AND 151-162, IDENTIFICATION BY MASS SPECTROMETRY.
    Strain: C57BL/6J.
    Tissue: Brain.
  4. "Identification of a specific effector of the small GTP-binding protein Rap2."
    Janoueix-Lerosey I., Pasheva E., de Tand M.-F., Tavitian A., de Gunzburg J.
    Eur. J. Biochem. 252:290-298(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH RUNDC3A, DOMAIN, MUTAGENESIS OF SER-17 AND THR-35.
  5. "RGS14 is a novel Rap effector that preferentially regulates the GTPase activity of galphao."
    Traver S., Bidot C., Spassky N., Baltauss T., De Tand M.F., Thomas J.L., Zalc B., Janoueix-Lerosey I., Gunzburg J.D.
    Biochem. J. 350:19-29(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH RGS14, TISSUE SPECIFICITY.
  6. "The Rap GTPases regulate B cell migration toward the chemokine stromal cell-derived factor-1 (CXCL12): potential role for Rap2 in promoting B cell migration."
    McLeod S.J., Li A.H., Lee R.L., Burgess A.E., Gold M.R.
    J. Immunol. 169:1365-1371(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  7. "Constitutively active Rap2 transgenic mice display fewer dendritic spines, reduced extracellular signal-regulated kinase signaling, enhanced long-term depression, and impaired spatial learning and fear extinction."
    Ryu J., Futai K., Feliu M., Weinberg R., Sheng M.
    J. Neurosci. 28:8178-8188(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TRANSGENIC MICE.
  8. Cited for: FUNCTION, SUBCELLULAR LOCATION, ISOPRENYLATION AT CYS-180, PALMITOYLATION AT CYS-176 AND CYS-177, MUTAGENESIS OF CYS-176; CYS-177 AND CYS-180.
  9. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brain, Liver, Lung and Spleen.
  10. Cited for: INTERACTION WITH NEDD4 AND TNIK, UBIQUITINATION BY NEDD4.

Entry informationi

Entry nameiRAP2A_MOUSE
AccessioniPrimary (citable) accession number: Q80ZJ1
Secondary accession number(s): Q3USK1
, Q7TSK4, Q810A2, Q9D3D5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 12, 2005
Last sequence update: December 21, 2004
Last modified: June 8, 2016
This is version 119 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

Transgenic mice expressing a constitutively active form of Rap2a display impaired spatial learning and defective extinction of contextual fear.

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.