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Ras-associated & pleckstrin homology domains-containing protein 1; RAPH1; ALS 2 chromosomal region candidate gene 9/18 protein; lamellipodin; proline-rich EVH1 ligand 2; PREL-2; protein RMO1 (RAPH1, ALS2CR18, ALS2CR9, KIAA1681, LPD, PREL2, RMO1)
Function:
1) mediator of localized membrane signals
2) regulation of lamellipodial dynamics
3) negatively regulates cell adhesion
4) interacts with EVL & VASP and targets them to the leading edge
Structure:
- belongs to the MRL family
- contains 1 PH domain
- contains 1 Ras-associating domain
Compartment:
- cell membrane, peripheral membrane.
- recruited to the membrane, via the PH domain, by PI(3,4)P2
- colocalizes with VASP at the tips of lamellipodia & filopodia
- also colocalizes with pathogens, Vaccinia & enteropathogenic E.col at the interface between the pathogen & their actin
Alternative splicing: named isoforms=9
Expression:
- isoform RMO1-RAPH1 is ubiquitously expressed; highest levels in brain, heart, ovary, developing embryo
- isoform RMO1 is widely expressed; highest levels in liver
- low expression in B-cells
Pathology:
down-regulated in some cancers
1) diminished expression in metastatic osteosarcomas relative to primary osteosarcoma tumors
2) down-regulated in 43% of breast cancers
3) down-regulated in 25% of ovarian cancers
Related
amyotrophic lateral sclerosis (ALS); Lou Gerig's disease
amyotrophic lateral sclerosis [ALS] 2 chromosomal region candidate gene
General
cytoskeletal protein
phosphoprotein
Properties
SIZE: entity length = 1250 aa
MW = 135 kD
COMPARTMENT: cytoplasm
MOTIF: acetylation site
SITE: N-TERMINUS
EFFECTOR-BOUND: acetyl
Ser phosphorylation site {S5}
Ser phosphorylation site {S17}
Ser phosphorylation site {S54}
Ras-associating {269-355}
PH domain {396-505}
MOTIF: Tyr phosphorylation site {Y426}
Tyr phosphorylation site {Y456}
Ser phosphorylation site {S610}
Ser phosphorylation site {S827}
Thr phosphorylation site {T830}
Ser phosphorylation site {S853}
Ser phosphorylation site {S856}
Ser phosphorylation site {S860}
Ser phosphorylation site {S894}
Ser phosphorylation site {S965}
Thr phosphorylation site {T974}
Ser phosphorylation site {S1154}
Tyr phosphorylation site {Y1226}
Database Correlations
OMIM 609035
UniProt Q70E73
PFAM correlations
Entrez Gene 65059
Kegg hsa:65059
References
UniProt :accession Q70E73