P63000 · RAC1_HUMAN
- ProteinRas-related C3 botulinum toxin substrate 1
- GeneRAC1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids192 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Rac1 p21/rho GDI heterodimer is the active component of the cytosolic factor sigma 1, which is involved in stimulation of the NADPH oxidase activity in macrophages. Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. Stimulates PKN2 kinase activity (PubMed:9121475).
In concert with RAB7A, plays a role in regulating the formation of RBs (ruffled borders) in osteoclasts (PubMed:1643658).
In podocytes, promotes nuclear shuttling of NR3C2; this modulation is required for a proper kidney functioning. Required for atypical chemokine receptor ACKR2-induced LIMK1-PAK1-dependent phosphorylation of cofilin (CFL1) and for up-regulation of ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation. In neurons, is involved in dendritic spine formation and synaptic plasticity (By similarity).
In hippocampal neurons, involved in spine morphogenesis and synapse formation, through local activation at synapses by guanine nucleotide exchange factors (GEFs), such as ARHGEF6/ARHGEF7/PIX (PubMed:12695502).
In synapses, seems to mediate the regulation of F-actin cluster formation performed by SHANK3. In neurons, plays a crucial role in regulating GABA(A) receptor synaptic stability and hence GABAergic inhibitory synaptic transmission through its role in PAK1 activation and eventually F-actin stabilization (By similarity).
Isoform B
It is able to bind to the GTPase-binding domain of PAK but not full-length PAK in a GTP-dependent manner, suggesting that the insertion does not completely abolish effector interaction (PubMed:14625275).
Catalytic activity
- GTP + H2O = GDP + H+ + phosphateThis reaction proceeds in the forward direction.
Activity regulation
Features
Showing features for binding site.
GO annotations
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameRas-related C3 botulinum toxin substrate 1
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP63000
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Identified by mass spectrometry in melanosome fractions from stage I to stage IV (PubMed:17081065).
Found in the ruffled border (a late endosomal-like compartment in the plasma membrane) of bone-resorbing osteoclasts. Localizes to the lamellipodium in a SH3RF1-dependent manner (By similarity).
In macrophages, cytoplasmic location increases upon CSF1 stimulation (By similarity).
Activation by GTP-binding promotes nuclear localization (PubMed:12551911).
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Intellectual developmental disorder, autosomal dominant 48 (MRD48)
- Note
- DescriptionA disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD48 patients manifest global developmental delay and moderate to severe intellectual disability.
- See alsoMIM:617751
Natural variants in MRD48
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_080454 | 18 | C>Y | in MRD48; decreased substrate adhesion-dependent cell spreading; dominant-negative effect; reduced neuronal proliferation; dbSNP:rs1554263326 | |
VAR_080455 | 39 | N>S | in MRD48; decreased substrate adhesion-dependent cell spreading; dominant-negative effect; reduced neuronal proliferation; dbSNP:rs1554263624 | |
VAR_080456 | 51 | V>L | in MRD48; uncertain significance; dbSNP:rs1554263625 | |
VAR_080457 | 51 | V>M | in MRD48; decreased substrate adhesion-dependent cell spreading; weak dominant-negative effect; dbSNP:rs1554263625 | |
VAR_080458 | 64 | Y>D | in MRD48; increased substrate adhesion-dependent cell spreading; constitutively active; dbSNP:rs1554263626 | |
VAR_080459 | 73 | P>L | in MRD48; decreased substrate adhesion-dependent cell spreading; weak dominant-negative effect; dbSNP:rs2115201441 | |
VAR_080460 | 157 | C>Y | in MRD48; decreased substrate adhesion-dependent cell spreading; weak dominant-negative effect; dbSNP:rs1554264268 |
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 12 | Constitutively active. Interacts with PARD6 proteins. Increases nuclear localization and up-regulates transcriptional activity of NR3C2. Doesn't interact with CYRIB. Increases interaction with GARRE1. | ||||
Sequence: G → V | ||||||
Mutagenesis | 17 | Constitutively inactivated. Abolishes interaction with PARD6 proteins. No effect on NR3C2 transcriptional activity. No interaction with PPP5C. Doesn't activate PPP5C phosphatase activity and translocate PPP5C to the plasma membrane. Doesn't interact with CYRIB. | ||||
Sequence: T → N | ||||||
Natural variant | VAR_080454 | 18 | in MRD48; decreased substrate adhesion-dependent cell spreading; dominant-negative effect; reduced neuronal proliferation; dbSNP:rs1554263326 | |||
Sequence: C → Y | ||||||
Natural variant | VAR_014540 | 26 | in dbSNP:rs2115193158 | |||
Sequence: N → D | ||||||
Natural variant | VAR_014541 | 28 | in dbSNP:rs2115193183 | |||
Sequence: F → L | ||||||
Mutagenesis | 30 | No interaction with PPP5C; when associated with L-61. Translocates to the plasma membrane; also when associated with L-61. | ||||
Sequence: G → V | ||||||
Mutagenesis | 32 | Abolishes AMPylation by Haemophilus IbpA. | ||||
Sequence: Y → F | ||||||
Mutagenesis | 35 | Abolishes AMPylation by Vibrio VopS. | ||||
Sequence: T → A | ||||||
Mutagenesis | 35 | No interaction with PPP5C; when associated with L-61. Translocates to the plasma membrane; also when associated with L-61. | ||||
Sequence: T → S | ||||||
Mutagenesis | 37 | Strongly reduced interaction with PLCB2. | ||||
Sequence: F → A | ||||||
Natural variant | VAR_080455 | 39 | in MRD48; decreased substrate adhesion-dependent cell spreading; dominant-negative effect; reduced neuronal proliferation; dbSNP:rs1554263624 | |||
Sequence: N → S | ||||||
Natural variant | VAR_080456 | 51 | in MRD48; uncertain significance; dbSNP:rs1554263625 | |||
Sequence: V → L | ||||||
Natural variant | VAR_080457 | 51 | in MRD48; decreased substrate adhesion-dependent cell spreading; weak dominant-negative effect; dbSNP:rs1554263625 | |||
Sequence: V → M | ||||||
Mutagenesis | 56 | Strongly reduced interaction with PLCB2. | ||||
Sequence: W → A | ||||||
Natural variant | VAR_014542 | 59 | in dbSNP:rs5837 | |||
Sequence: A → T | ||||||
Mutagenesis | 61 | Constitutively active. Interacts with PARD6 proteins. Interacts with PPP5C, activates its phosphatase activity and translocates PPP5C to the plasma membrane. No effect on interaction with RAPH1. Interacts with CYRIB. No interaction with PPP5C; when associated with V-30 or S-35. Translocates to the plasma membrane; also when associated with V-30 or S-35. | ||||
Sequence: Q → L | ||||||
Natural variant | VAR_014543 | 63 | in dbSNP:rs5831 | |||
Sequence: D → G | ||||||
Natural variant | VAR_080458 | 64 | in MRD48; increased substrate adhesion-dependent cell spreading; constitutively active; dbSNP:rs1554263626 | |||
Sequence: Y → D | ||||||
Mutagenesis | 67 | Strongly reduced interaction with PLCB2. | ||||
Sequence: L → A | ||||||
Mutagenesis | 70 | Strongly reduced interaction with PLCB2. | ||||
Sequence: L → A | ||||||
Mutagenesis | 71 | Loss of AKT-mediated phosphorylation and FBXL19-induced polyubiquitination. | ||||
Sequence: S → A | ||||||
Natural variant | VAR_080459 | 73 | in MRD48; decreased substrate adhesion-dependent cell spreading; weak dominant-negative effect; dbSNP:rs2115201441 | |||
Sequence: P → L | ||||||
Natural variant | VAR_014545 | 93 | in dbSNP:rs5826 | |||
Sequence: V → G | ||||||
Natural variant | VAR_014544 | 93 | in dbSNP:rs5825 | |||
Sequence: V → I | ||||||
Natural variant | VAR_014546 | 108 | in dbSNP:rs2115217353 | |||
Sequence: T → I | ||||||
Natural variant | VAR_014547 | 130 | in dbSNP:rs5828 | |||
Sequence: K → R | ||||||
Natural variant | VAR_014548 | 133 | in dbSNP:rs5835 | |||
Sequence: K → E | ||||||
Natural variant | VAR_033303 | 135 | in dbSNP:rs11540455 | |||
Sequence: T → I | ||||||
Natural variant | VAR_080460 | 157 | in MRD48; decreased substrate adhesion-dependent cell spreading; weak dominant-negative effect; dbSNP:rs1554264268 | |||
Sequence: C → Y | ||||||
Mutagenesis | 166 | Loss of FBXL19-induced polyubiquitination. | ||||
Sequence: K → R | ||||||
Natural variant | VAR_014549 | 180 | in dbSNP:rs16063 | |||
Sequence: P → S | ||||||
Natural variant | VAR_014550 | 182 | in dbSNP:rs5836 | |||
Sequence: V → E | ||||||
Mutagenesis | 183 | Slightly decreased palmitoylation by the V.cholerae toxin RtxA. | ||||
Sequence: K → A | ||||||
Mutagenesis | 183-188 | In 4KA mutant; abolished palmitoylation by the V.cholerae toxin RtxA. | ||||
Sequence: KKRKRK → AARARA | ||||||
Mutagenesis | 184 | Slightly decreased palmitoylation by the V.cholerae toxin RtxA. | ||||
Sequence: K → A | ||||||
Mutagenesis | 185-187 | In 2RA mutant; does not affect palmitoylation by the V.cholerae toxin RtxA. | ||||
Sequence: RKR → AKA | ||||||
Mutagenesis | 186 | Decreased palmitoylation by the V.cholerae toxin RtxA. | ||||
Sequence: K → A | ||||||
Mutagenesis | 188 | Decreased palmitoylation by the V.cholerae toxin RtxA. | ||||
Sequence: K → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 387 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue, glycosylation, modified residue (large scale data), cross-link, lipidation, propeptide.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000042036 | 1-189 | UniProt | Ras-related C3 botulinum toxin substrate 1 | |||
Sequence: MQAIKCVVVGDGAVGKTCLLISYTTNAFPGEYIPTVFDNYSANVMVDGKPVNLGLWDTAGQEDYDRLRPLSYPQTDVFLICFSLVSPASFENVRAKWYPEVRHHCPNTPIILVGTKLDLRDDKDTIEKLKEKKLTPITYPQGLAMAKEIGAVKYLECSALTQRGLKTVFDEAIRAVLCPPPVKKRKRKC | |||||||
Modified residue | 32 | UniProt | (Microbial infection) O-AMP-tyrosine; by Haemophilus IbpA; alternate | ||||
Sequence: Y | |||||||
Glycosylation | 32 | UniProt | (Microbial infection) O-linked (GlcNAc) tyrosine; by Photorhabdus PAU_02230; alternate | ||||
Sequence: Y | |||||||
Modified residue | 35 | UniProt | (Microbial infection) O-AMP-threonine; by Vibrio VopS | ||||
Sequence: T | |||||||
Glycosylation | 35 | UniProt | (Microbial infection) O-alpha-linked (GlcNAc) threonine; by C.novyi toxin TcdA; alternate | ||||
Sequence: T | |||||||
Glycosylation | 35 | UniProt | (Microbial infection) O-linked (Glc) threonine; by C.difficile toxins TcdA and TcdB, and by P.sordellii toxin TcsL; alternate | ||||
Sequence: T | |||||||
Modified residue | 71 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 71 | UniProt | In isoform P63000-2; Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 108 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Cross-link | 147 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | ||||
Sequence: K | |||||||
Modified residue (large scale data) | 161 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Cross-link | 166 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | ||||
Sequence: K | |||||||
Modified residue (large scale data) | 167 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Lipidation | 183 | UniProt | (Microbial infection) N6-palmitoyl lysine | ||||
Sequence: K | |||||||
Lipidation | 184 | UniProt | (Microbial infection) N6-palmitoyl lysine | ||||
Sequence: K | |||||||
Modified residue | 189 | UniProt | Cysteine methyl ester | ||||
Sequence: C | |||||||
Lipidation | 189 | UniProt | S-geranylgeranyl cysteine | ||||
Sequence: C | |||||||
Propeptide | PRO_0000042037 | 190-192 | UniProt | Removed in mature form | |||
Sequence: LLL |
Post-translational modification
Monoglucosylation completely prevents the recognition of the downstream effector, blocking the GTPases in their inactive form, leading to actin cytoskeleton disruption and cell death, resulting in the loss of colonic epithelial barrier function (PubMed:7775453, PubMed:7777059).
O-GlcNAcylation completely prevents the recognition of the downstream effector, blocking the GTPases in their inactive form, leading to actin cytoskeleton disruption (PubMed:8810274).
Palmitoylation inhibits activation by guanine nucleotide exchange factors (GEFs), preventing Rho GTPase signaling (PubMed:29074776).
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Gene expression databases
Organism-specific databases
Interaction
Subunit
Interacts with MTSS2 (via IMD domain); this interaction may be important to potentiate PDGF-induced RAC1 activation (PubMed:20875796).
Interacts with PAK2 (PubMed:20696164).
Interacts (GTP-bound form) with SH3RF1 and SH3RF3 (PubMed:20696164).
Found in a complex with SH3RF1, MAPK8IP1/JIP1, MAP3K11/MLK3, MAP2K7/MKK7 and MAPK8/JNK1. Interacts (both active GTP- or inactive GDP-bound forms) with SH3RF2 (By similarity).
Interacts (GTP-bound form preferentially) with CYRIB (PubMed:30250061, PubMed:31285585).
Interacts with DOCK4 (via DOCKER domain); functions as a guanine nucleotide exchange factor (GEF) for RAC1 (PubMed:16464467).
Interacts with GARRE1 (PubMed:31871319).
Interacts with RAP1GDS1 (PubMed:12551911, PubMed:20709748).
Interacts with TNFAIP8L2 (PubMed:32460619).
May interact with ARHGAP36 (PubMed:35986704).
Interacts with CD151 and integrin beta1/ITGB1 (PubMed:22843693).
Binary interactions
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Motif | 32-40 | Effector region | ||||
Sequence: YIPTVFDNY | ||||||
Motif | 179-188 | Polybasic region; required for nuclear import | ||||
Sequence: PPPVKKRKRK |
Domain
Sequence similarities
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
This entry describes 2 isoforms produced by Alternative splicing.
P63000-1
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.
- NameA
- SynonymsRac1A
- Length192
- Mass (Da)21,450
- Last updated2004-08-31 v1
- ChecksumACEDF83A45E5EA67
P63000-2
- NameB
- SynonymsRac1B, Rac1ins
- Differences from canonical
- 75-75: T → TVGETYGKDITSRGKDKPIA
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A994J6T1 | A0A994J6T1_HUMAN | RAC1 | 225 | ||
A0A994J4S4 | A0A994J4S4_HUMAN | RAC1 | 42 |
Sequence caution
Features
Showing features for alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_005710 | 75 | in isoform B | |||
Sequence: T → TVGETYGKDITSRGKDKPIA | ||||||
Sequence conflict | 192 | in Ref. 2; AAA36544 | ||||
Sequence: Missing |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
M29870 EMBL· GenBank· DDBJ | AAA36537.1 EMBL· GenBank· DDBJ | mRNA | ||
M31467 EMBL· GenBank· DDBJ | AAA36544.1 EMBL· GenBank· DDBJ | mRNA | ||
AJ132694 EMBL· GenBank· DDBJ | CAA10732.1 EMBL· GenBank· DDBJ | mRNA | ||
AJ132695 EMBL· GenBank· DDBJ | CAB53579.5 EMBL· GenBank· DDBJ | Genomic DNA | ||
AJ132695 EMBL· GenBank· DDBJ | CAA10733.6 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF136373 EMBL· GenBank· DDBJ | AAD30547.1 EMBL· GenBank· DDBJ | mRNA | ||
AY279384 EMBL· GenBank· DDBJ | AAQ16632.1 EMBL· GenBank· DDBJ | mRNA | ||
AF498964 EMBL· GenBank· DDBJ | AAM21111.1 EMBL· GenBank· DDBJ | mRNA | ||
BT007121 EMBL· GenBank· DDBJ | AAP35785.1 EMBL· GenBank· DDBJ | mRNA | ||
DQ165078 EMBL· GenBank· DDBJ | AAZ80485.1 EMBL· GenBank· DDBJ | Genomic DNA | Different initiation | |
AC009412 EMBL· GenBank· DDBJ | AAS07511.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AC009412 EMBL· GenBank· DDBJ | AAS07512.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC004247 EMBL· GenBank· DDBJ | AAH04247.1 EMBL· GenBank· DDBJ | mRNA | ||
BC050687 EMBL· GenBank· DDBJ | AAH50687.1 EMBL· GenBank· DDBJ | mRNA | ||
BC107748 EMBL· GenBank· DDBJ | AAI07749.1 EMBL· GenBank· DDBJ | mRNA |