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Protein

GTP-binding protein Rit1

Gene

RIT1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Plays a crucial role in coupling NGF stimulation to the activation of both EPHB2 and MAPK14 signaling pathways and in NGF-dependent neuronal differentiation. Involved in ELK1 transactivation through the Ras-MAPK signaling cascade that mediates a wide variety of cellular functions, including cell proliferation, survival, and differentiation.2 Publications

Miscellaneous

Stimulation of the NGF and EGF receptor signaling pathways results in rapid and prolonged activation.
Shows rapid uncatalyzed guanine nucleotide dissociation rates, which are much faster than those of most Ras subfamily members.

Activity regulationi

Alternates between an inactive form bound to GDP and an active form bound to GTP.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi28 – 35GTPBy similarity8
Nucleotide bindingi75 – 79GTPBy similarity5
Nucleotide bindingi134 – 137GTPBy similarity4

GO - Molecular functioni

  • calmodulin binding Source: ProtInc
  • GTPase activity Source: ParkinsonsUK-UCL
  • GTP binding Source: ParkinsonsUK-UCL

GO - Biological processi

Keywordsi

LigandGTP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-187706 Signalling to p38 via RIT and RIN
SIGNORiQ92963

Names & Taxonomyi

Protein namesi
Recommended name:
GTP-binding protein Rit1
Alternative name(s):
Ras-like protein expressed in many tissues
Ras-like without CAAX protein 1
Gene namesi
Name:RIT1
Synonyms:RIBB, RIT, ROC1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000143622.10
HGNCiHGNC:10023 RIT1
MIMi609591 gene
neXtProtiNX_Q92963

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Noonan syndrome 8 (NS8)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of Noonan syndrome, a disease characterized by short stature, facial dysmorphic features such as hypertelorism, a downward eyeslant and low-set posteriorly rotated ears, and a high incidence of congenital heart defects and hypertrophic cardiomyopathy. Other features can include a short neck with webbing or redundancy of skin, deafness, motor delay, variable intellectual deficits, multiple skeletal defects, cryptorchidism, and bleeding diathesis. Individuals with Noonan syndrome are at risk of juvenile myelomonocytic leukemia, a myeloproliferative disorder characterized by excessive production of myelomonocytic cells.
See also OMIM:615355
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07015057A → G in NS8; results in increased ELK1 transcriptional activation; results in increased MAPK-ERK signaling. 2 PublicationsCorresponds to variant dbSNP:rs672601334EnsemblClinVar.1
Natural variantiVAR_07015181E → G in NS8; results in increased ELK1 transcriptional activation. 1 PublicationCorresponds to variant dbSNP:rs869025193EnsemblClinVar.1
Natural variantiVAR_07015282F → L in NS8; results in increased ELK1 transcriptional activation. 1 PublicationCorresponds to variant dbSNP:rs730881014EnsemblClinVar.1
Natural variantiVAR_07015690M → I in NS8; results in increased MAPK-ERK signaling. 2 PublicationsCorresponds to variant dbSNP:rs483352822EnsemblClinVar.1
Natural variantiVAR_07015795G → A in NS8; results in increased ELK1 transcriptional activation. 1 PublicationCorresponds to variant dbSNP:rs672601335EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi35S → N: Dominant negative. Loss of interaction with AFDN, RLF and RALGDS. 1 Publication1
Mutagenesisi53T → S: Loss of interaction with AFDN, RLF and RALGDS; when associated with L-79. 1 Publication1
Mutagenesisi55E → G: Loss of interaction with AFDN, but not with RLF and RALGDS; when associated with L-79. 1 Publication1
Mutagenesisi79Q → L: Constitutively active. Dramatic reduction of the rate of GTP hydrolysis. Loss of interaction with AFDN, RLF and RALGDS; when associated with S-53. Loss of interaction with AFDN; when associated with G-55. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi6016
MalaCardsiRIT1
MIMi615355 phenotype
OpenTargetsiENSG00000143622
Orphaneti648 Noonan syndrome
PharmGKBiPA35528

Polymorphism and mutation databases

BioMutaiRIT1
DMDMi38258628

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000827251 – 219GTP-binding protein Rit1Add BLAST219

Proteomic databases

EPDiQ92963
MaxQBiQ92963
PaxDbiQ92963
PeptideAtlasiQ92963
PRIDEiQ92963
ProteomicsDBi75632

PTM databases

iPTMnetiQ92963
PhosphoSitePlusiQ92963

Expressioni

Tissue specificityi

Expressed in many tissues.

Gene expression databases

BgeeiENSG00000143622 Expressed in 214 organ(s), highest expression level in ectocervix
CleanExiHS_RIT1
ExpressionAtlasiQ92963 baseline and differential
GenevisibleiQ92963 HS

Organism-specific databases

HPAiHPA053249

Interactioni

Subunit structurei

Interacts with AFDN, the C-terminal domain of RALGDS and RLF, but not with RIN1 and PIK3CA. RLF binds exclusively to the active GTP-bound form. Strongly interacts with BRAF, but only weakly with RAF1. BARF and RAF1 association is dependent upon the GTP-bound state. Interacts with RGL3 (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
RLFQ131293EBI-365845,EBI-958266

GO - Molecular functioni

Protein-protein interaction databases

BioGridi111948, 14 interactors
IntActiQ92963, 12 interactors
STRINGi9606.ENSP00000357306

Structurei

Secondary structure

1219
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ92963
SMRiQ92963
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the small GTPase superfamily. Ras family.Curated

Phylogenomic databases

eggNOGiKOG0395 Eukaryota
COG1100 LUCA
GeneTreeiENSGT00860000133678
HOGENOMiHOG000233973
HOVERGENiHBG009351
InParanoidiQ92963
KOiK07832
OMAiFRYYIDD
OrthoDBiEOG091G0UAU
PhylomeDBiQ92963
TreeFamiTF315072

Family and domain databases

InterProiView protein in InterPro
IPR027417 P-loop_NTPase
IPR005225 Small_GTP-bd_dom
IPR001806 Small_GTPase
IPR020849 Small_GTPase_Ras-type
PANTHERiPTHR24070 PTHR24070, 1 hit
PfamiView protein in Pfam
PF00071 Ras, 1 hit
SUPFAMiSSF52540 SSF52540, 1 hit
TIGRFAMsiTIGR00231 small_GTP, 1 hit
PROSITEiView protein in PROSITE
PS51421 RAS, 1 hit

Sequences (3+)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q92963-1) [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
MDSGTRPVGS CCSSPAGLSR EYKLVMLGAG GVGKSAMTMQ FISHRFPEDH
60 70 80 90 100
DPTIEDAYKI RIRIDDEPAN LDILDTAGQA EFTAMRDQYM RAGEGFIICY
110 120 130 140 150
SITDRRSFHE VREFKQLIYR VRRTDDTPVV LVGNKSDLKQ LRQVTKEEGL
160 170 180 190 200
ALAREFSCPF FETSAAYRYY IDDVFHALVR EIRRKEKEAV LAMEKKSKPK
210
NSVWKRLKSP FRKKKDSVT
Length:219
Mass (Da):25,145
Last modified:February 1, 1997 - v1
Checksum:i7F957871F836AE92
GO
Isoform 2 (identifier: Q92963-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-36: Missing.

Show »
Length:183
Mass (Da):21,633
Checksum:i61CFC2E07B180267
GO
Isoform 3 (identifier: Q92963-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MERWLFLGATEEGPKRTM

Note: No experimental confirmation available.
Show »
Length:236
Mass (Da):27,148
Checksum:iB6B991C6D3668388
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
V9GY29V9GY29_HUMAN
GTP-binding protein Rit1
RIT1
92Annotation score:
V9GYC3V9GYC3_HUMAN
GTP-binding protein Rit1
RIT1
151Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07014935S → T Probable disease-associated mutation found in patients with features of Noonan syndrome. 1 PublicationCorresponds to variant dbSNP:rs869025189EnsemblClinVar.1
Natural variantiVAR_07015057A → G in NS8; results in increased ELK1 transcriptional activation; results in increased MAPK-ERK signaling. 2 PublicationsCorresponds to variant dbSNP:rs672601334EnsemblClinVar.1
Natural variantiVAR_07015181E → G in NS8; results in increased ELK1 transcriptional activation. 1 PublicationCorresponds to variant dbSNP:rs869025193EnsemblClinVar.1
Natural variantiVAR_07015282F → L in NS8; results in increased ELK1 transcriptional activation. 1 PublicationCorresponds to variant dbSNP:rs730881014EnsemblClinVar.1
Natural variantiVAR_07015382F → V Probable disease-associated mutation found in patients with features of Noonan syndrome. 1 PublicationCorresponds to variant dbSNP:rs869025194EnsemblClinVar.1
Natural variantiVAR_07015483T → P Probable disease-associated mutation found in patients with features of Noonan syndrome. Corresponds to variant dbSNP:rs869025195EnsemblClinVar.1
Natural variantiVAR_07015589Y → H Probable disease-associated mutation found in patients with features of Noonan syndrome. 1 PublicationCorresponds to variant dbSNP:rs869025197EnsemblClinVar.1
Natural variantiVAR_07015690M → I in NS8; results in increased MAPK-ERK signaling. 2 PublicationsCorresponds to variant dbSNP:rs483352822EnsemblClinVar.1
Natural variantiVAR_07015795G → A in NS8; results in increased ELK1 transcriptional activation. 1 PublicationCorresponds to variant dbSNP:rs672601335EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0453061 – 36Missing in isoform 2. 1 PublicationAdd BLAST36
Alternative sequenceiVSP_0471141M → MERWLFLGATEEGPKRTM in isoform 3. Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U71203 mRNA Translation: AAB42213.1
Y07566 mRNA Translation: CAA68851.1
U78165 mRNA Translation: AAB64246.1
AF084462 mRNA Translation: AAD13021.1
AF493923 mRNA Translation: AAM12637.1
AK298768 mRNA Translation: BAG60910.1
AK314239 mRNA Translation: BAG36908.1
CR407639 mRNA Translation: CAG28567.1
AL139128 Genomic DNA No translation available.
AL355388 Genomic DNA No translation available.
CH471121 Genomic DNA Translation: EAW53024.1
BC104186 mRNA Translation: AAI04187.1
BC104187 mRNA Translation: AAI04188.1
CCDSiCCDS1123.1 [Q92963-1]
CCDS58036.1 [Q92963-2]
CCDS58037.1 [Q92963-3]
RefSeqiNP_001243749.1, NM_001256820.1 [Q92963-2]
NP_001243750.1, NM_001256821.1 [Q92963-3]
NP_008843.1, NM_006912.5 [Q92963-1]
UniGeneiHs.491234

Genome annotation databases

EnsembliENST00000368322; ENSP00000357305; ENSG00000143622 [Q92963-3]
ENST00000368323; ENSP00000357306; ENSG00000143622 [Q92963-1]
ENST00000539040; ENSP00000441950; ENSG00000143622 [Q92963-2]
GeneIDi6016
KEGGihsa:6016
UCSCiuc001fmh.3 human [Q92963-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U71203 mRNA Translation: AAB42213.1
Y07566 mRNA Translation: CAA68851.1
U78165 mRNA Translation: AAB64246.1
AF084462 mRNA Translation: AAD13021.1
AF493923 mRNA Translation: AAM12637.1
AK298768 mRNA Translation: BAG60910.1
AK314239 mRNA Translation: BAG36908.1
CR407639 mRNA Translation: CAG28567.1
AL139128 Genomic DNA No translation available.
AL355388 Genomic DNA No translation available.
CH471121 Genomic DNA Translation: EAW53024.1
BC104186 mRNA Translation: AAI04187.1
BC104187 mRNA Translation: AAI04188.1
CCDSiCCDS1123.1 [Q92963-1]
CCDS58036.1 [Q92963-2]
CCDS58037.1 [Q92963-3]
RefSeqiNP_001243749.1, NM_001256820.1 [Q92963-2]
NP_001243750.1, NM_001256821.1 [Q92963-3]
NP_008843.1, NM_006912.5 [Q92963-1]
UniGeneiHs.491234

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4KLZX-ray2.30A19-189[»]
ProteinModelPortaliQ92963
SMRiQ92963
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111948, 14 interactors
IntActiQ92963, 12 interactors
STRINGi9606.ENSP00000357306

PTM databases

iPTMnetiQ92963
PhosphoSitePlusiQ92963

Polymorphism and mutation databases

BioMutaiRIT1
DMDMi38258628

Proteomic databases

EPDiQ92963
MaxQBiQ92963
PaxDbiQ92963
PeptideAtlasiQ92963
PRIDEiQ92963
ProteomicsDBi75632

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000368322; ENSP00000357305; ENSG00000143622 [Q92963-3]
ENST00000368323; ENSP00000357306; ENSG00000143622 [Q92963-1]
ENST00000539040; ENSP00000441950; ENSG00000143622 [Q92963-2]
GeneIDi6016
KEGGihsa:6016
UCSCiuc001fmh.3 human [Q92963-1]

Organism-specific databases

CTDi6016
DisGeNETi6016
EuPathDBiHostDB:ENSG00000143622.10
GeneCardsiRIT1
HGNCiHGNC:10023 RIT1
HPAiHPA053249
MalaCardsiRIT1
MIMi609591 gene
615355 phenotype
neXtProtiNX_Q92963
OpenTargetsiENSG00000143622
Orphaneti648 Noonan syndrome
PharmGKBiPA35528
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0395 Eukaryota
COG1100 LUCA
GeneTreeiENSGT00860000133678
HOGENOMiHOG000233973
HOVERGENiHBG009351
InParanoidiQ92963
KOiK07832
OMAiFRYYIDD
OrthoDBiEOG091G0UAU
PhylomeDBiQ92963
TreeFamiTF315072

Enzyme and pathway databases

ReactomeiR-HSA-187706 Signalling to p38 via RIT and RIN
SIGNORiQ92963

Miscellaneous databases

ChiTaRSiRIT1 human
GeneWikiiRIT1
GenomeRNAii6016
PROiPR:Q92963
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000143622 Expressed in 214 organ(s), highest expression level in ectocervix
CleanExiHS_RIT1
ExpressionAtlasiQ92963 baseline and differential
GenevisibleiQ92963 HS

Family and domain databases

InterProiView protein in InterPro
IPR027417 P-loop_NTPase
IPR005225 Small_GTP-bd_dom
IPR001806 Small_GTPase
IPR020849 Small_GTPase_Ras-type
PANTHERiPTHR24070 PTHR24070, 1 hit
PfamiView protein in Pfam
PF00071 Ras, 1 hit
SUPFAMiSSF52540 SSF52540, 1 hit
TIGRFAMsiTIGR00231 small_GTP, 1 hit
PROSITEiView protein in PROSITE
PS51421 RAS, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiRIT1_HUMAN
AccessioniPrimary (citable) accession number: Q92963
Secondary accession number(s): B4DQE8
, O00646, O00720, Q5VY89, Q5VY90
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 31, 2003
Last sequence update: February 1, 1997
Last modified: November 7, 2018
This is version 163 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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Main funding by: National Institutes of Health

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