Contents

Search

rac1 proto-oncogene protein; Ras-related C3 botulinum toxin substrate 1; p21-Rac1; Ras-like protein TC25; cell migration-inducing gene 5 protein (RAC1)

Function: - plasma membrane-associated small GTPase - p21rac has relatively high intrinsic GTPase activity - cycles between active GTP-bound & inactive GDP-bound states - GTP-bound form binds to a variety of effector proteins to regulate cellular responses including: a) secretory processes b) phagocytosis of apoptotic cells c) epithelial cell polarization d) growth-factor induced formation of membrane ruffles - isoform B has an accelerated GEF-independent GDP/GTP exchange & an impaired GTP hydrolysis, partiallt restored by GTPase-activating proteins - regulated by: a) guanine nucleotide exchange factors (GEFs) b) GDP dissociation inhibitors - interacts with the GEF proteins PREX1, RASGRF2, DOCK1, DOCK2 & DOCK7, which promote the exchange between GDP & GTP, & therefore activate it - interacts with PARD6A, PARD6B & PARD6G (GTP-dependent) - part of a quaternary complex containing PARD3, some PARD6 protein (PARD6A, PARD6B or PARD6G) & some atypical PKC protein (PRKCI or PRKCZ), which plays a central role in epithelial cell polarization - found in a trimeric complex composed of DOCK1 & ELMO1, which plays a role in phagocytosis of apoptotic cells - interacts with RALBP1 via its effector domain - interacts with PLXNB1 - part of a complex with MAP2K3, MAP3K3, CCM2 & DEF6 - interacts with BAIAP2, BAIAP2L1, CYFIP1/SRA-1 & DEF6 - interacts with Y. pseudotuberculosis YPKA & PLCB2. - interacts with NOXA1 - interacts with ARHGEF2 - interacts with NISCH (putative) Structure: - the effector region mediates interaction with DEF6 - belongs to the small GTPase superfamily, Rho family Compartment: - cell membrane; lipid-anchor; cytoplasmic side (putative) - attachment to inner surface of plasma membrane requires prenylation of the C-terminal Cys (putative) - melanosome, stage 1 to stage 4 Alternative splicing: named isoforms=2; Rac1A, Rac1B Expression: - isoform B is predominantly identified in skin & epithelial tissues from the intestinal tract Pathology: - expression of isoform B is elevated in colorectal tumors at various stages of neoplastic progression

General

rac proto-oncogene protein (p21rac)

Properties

SIZE: entity length = 192 aa MW = 21 kD COMPARTMENT: plasma membrane MOTIF: GTP-binding site SITE: 10-17 Effector region {32-40} GTP-binding site SITE: 57-61 Ser phosphorylation site {S71} GTP-binding site SITE: 115-118 CaaX motif SITE: C-TERMINUS QUALITIES: AAX-TRUNCATED CARBOXYMETHYLATED EFFECTOR-BOUND: geranylgeranyl{C20} BOUND-VIA: cysteine residue

Database Correlations

OMIM 602048 UniProt P63000 Pfam PF00071 Entrez Gene 5879 Kegg hsa:5879

References

  1. UniProt :accession P63000
  2. NIEHS-SNPs http://egp.gs.washington.edu/data/rac1/
  3. Kahn RA, Der CJ, Bokoch GM. The ras superfamily of GTP-binding proteins: guidelines on nomenclature. FASEB J. 1992 May;6(8):2512-3. PMID: 1592203
  4. Segal AW, Abo A. The biochemical basis of the NADPH oxidase of phagocytes. Trends Biochem Sci. 1993 Feb;18(2):43-7. Review. PMID: 8488557
  5. Manser E, Leung T, Salihuddin H, Zhao ZS, Lim L. A brain serine/threonine protein kinase activated by Cdc42 and Rac1. Nature. 1994 Jan 6;367(6458):40-6. PMID: 8107774