GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms.

InterPro domain IPR001562 (Btk zinc finger) maps to signal transduction
InterPro domain IPR037776 (RASAL RasGAP) maps to negative regulation of Ras signaling and calcium response

GO_REF:0000033

Annotation inferences using phylogenetic trees

PAINT/IBA annotations from GO_Central based on phylogenetic analysis
GTPase activator activity inferred from orthology to characterized RasGAP family members

GO_REF:0000043

Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping

Zinc-finger keyword maps to zinc ion binding
Metal-binding keyword maps to metal ion binding
Differentiation keyword maps to cell differentiation

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

Cytosol localization inferred by ARBA model

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods.

GTPase activator activity from combined ARBA, InterPro, and UniProtKB keyword evidence

PMID:16009725

CAPRI and RASAL impose different modes of information processing on Ras due to contrasting temporal filtering of Ca2+.

RASAL1 tracks Ca2+ oscillations with rapid in-phase membrane translocations

"RASAL is a Ca2+ sensor responding in-phase to repetitive Ca2+ signals by associating with the plasma membrane and deactivating Ras (Walker et al., 2004)."
Half-maximal dissociation from membrane is ~17 seconds for RASAL1 vs >280 seconds for CAPRI

"Half-maximal dissociation back to the cytosol was >280 s, contrasting with half-maximal dissociation of 17 s for GFP-RASAL and 13 s for GFP-PKCγ (Fig"
Demonstrated cytosolic localization at rest and plasma membrane translocation upon Ca2+ elevation

"(A) Confocal images of HeLa cells expressing GFP-CAPRI (left) or GFP-RASAL (right) before (T = 0) or after 100 μM histamine stimulation"
TIRFM imaging confirmed oscillatory membrane association patterns

"GFP-RASAL exhibited rapid oscillations in parallel experiments (Fig"
Domain-swapping experiments showed C2 domains mediate Ca2+-dependent translocation

"We found the CAPRI/RASAL chimera to be a sensitive tracker of repetitive cytosolic Ca2+ oscillations like RASAL (Fig"

PMID:23999003

SYT14L, especially its C2 domain, is involved in regulating melanocyte differentiation.

RASAL1 (called SYT14L) overexpression induces dendrite extension in melanocytes

"Forced expression of full length SYT14L or the C2 domain of SYT14L induced a significant elongation of dendrite length accompanied by the induction of melanocyte differentiation-related markers, including melanin synthesis, tyrosinase catalytic activity and the expression of tyrosinase (TYR), tyrosinase related protein-1 (TRP-1) and TRP-2."
C2 domain alone is sufficient for dendrite-promoting activity

"Forced expression of full length SYT14L or the C2 domain of SYT14L induced a significant elongation of dendrite length accompanied by the induction of melanocyte differentiation-related markers, including melanin synthesis, tyrosinase catalytic activity and the expression of tyrosinase (TYR), tyrosinase related protein-1 (TRP-1) and TRP-2."
Induces melanocyte differentiation markers including tyrosinase activity

"Forced expression of full length SYT14L or the C2 domain of SYT14L induced a significant elongation of dendrite length accompanied by the induction of melanocyte differentiation-related markers, including melanin synthesis, tyrosinase catalytic activity and the expression of tyrosinase (TYR), tyrosinase related protein-1 (TRP-1) and TRP-2."
Increases ERK and CREB phosphorylation

"In addition, over-expression of either the C2 domain or the full length form of SYT14L significantly increased the phosphorylation of ERK and CREB."

PMID:9751798

Restricted tissue expression pattern of a novel human rasGAP-related gene and its murine ortholog.

Initial characterization of RASAL1 (then called RASAL) as a novel RasGAP

"In this study we have isolated a novel human gene, RASAL (Ras GTPase-activating-like) and its murine ortholog, MRASAL which are most similar to the GAP1 family of rasGAP proteins, based upon the presence and organization of specific conserved domains."
Contains two C2 domains, GAP-related domain, and PH domain

"Sequence analysis of these two proteins revealed the presence of two N-terminal calcium-dependent phospholipid binding C2 domains, a conserved GAP related domain (GRD) and a C-terminal pleckstrin homology (PH) domain."
Member of GAP1 family of RasGAP proteins

"In this study we have isolated a novel human gene, RASAL (Ras GTPase-activating-like) and its murine ortholog, MRASAL which are most similar to the GAP1 family of rasGAP proteins, based upon the presence and organization of specific conserved domains."
Highly expressed in thyroid and adrenal medulla

"Northern blot and mRNA in situ hybridization analyses indicate that RASAL, in contrast to other mammalian rasGAP proteins, has a limited expression pattern; RASAL is highly expressed in the follicular cells of the thyroid and the adrenal medulla and expressed at lower levels in brain, spinal cord and trachea"
Lower expression in brain, spinal cord, and trachea

"Northern blot and mRNA in situ hybridization analyses indicate that RASAL, in contrast to other mammalian rasGAP proteins, has a limited expression pattern; RASAL is highly expressed in the follicular cells of the thyroid and the adrenal medulla and expressed at lower levels in brain, spinal cord and trachea"

Reactome:R-HSA-5658231

RAS GAPs stimulate RAS GTPase activity

RASAL1 included as a RasGAP in Ras regulation pathway

Reactome:R-HSA-5658435

RAS GAPs bind RAS:GTP

RASAL1 modeled as binding to active Ras-GTP

file:human/RASAL1/RASAL1-deep-research-falcon.md

Deep research summary on RASAL1 function

Tumor suppressor frequently silenced by promoter hypermethylation
Critical role in kidney fibrosis through TGF-beta-DNMT1 pathway
Neuronal roles in microtubule stabilization and synaptic function
Interactions with PKC, tubulin, and CaMKII identified

file:human/RASAL1/RASAL1-deep-research-cyberian.md

Cyberian deep research on RASAL1 function