SH3RF1

This gene encodes a protein containing an N-terminus RING-finger, four SH3 domains, and a region implicated in binding of the Rho GTPase Rac. Via the RING-finger, the encoded protein has been shown to function as an ubiquitin-protein ligase involved in protein sorting at the trans-Golgi network. The encoded protein may also act as a scaffold for the c-Jun N-terminal kinase signaling pathway, facilitating the formation of a functional signaling module.

Full Name

SH3 Domain Containing Ring Finger 1

Function

Has E3 ubiquitin-protein ligase activity. In the absence of an external substrate, it can catalyze self-ubiquitination (PubMed:15659549, PubMed:20696164).
Stimulates ubiquitination of potassium channel KCNJ1, enhancing it's dynamin-dependent and clathrin-independent endocytosis (PubMed:19710010).
Acts as a scaffold protein that coordinates with MAPK8IP1/JIP1 in organizing different components of the JNK pathway, including RAC1 or RAC2, MAP3K11/MLK3 or MAP3K7/TAK1, MAP2K7/MKK7, MAPK8/JNK1 and/or MAPK9/JNK2 into a functional multiprotein complex to ensure the effective activation of the JNK signaling pathway. Regulates the differentiation of CD4+ and CD8+ T-cells and promotes T-helper 1 (Th1) cell differentiation. Regulates the activation of MAPK8/JNK1 and MAPK9/JNK2 in CD4+ T-cells and the activation of MAPK8/JNK1 in CD8+ T-cells. Plays a crucial role in the migration of neocortical neurons in the developing brain. Controls proper cortical neuronal migration and the formation of proximal cytoplasmic dilation in the leading process (PCDLP) in migratory neocortical neurons by regulating the proper localization of activated RAC1 and F-actin assembly (By similarity).
(Microbial infection) Plays an essential role in the targeting of HIV-1 Gag to the plasma membrane, this function is dependent on it's RING domain, and hence it's E3 ligase activity.

Biological Process

Biological Process negative regulation of apoptotic processManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process negative regulation of cysteine-type endopeptidase activity involved in apoptotic processManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process negative regulation of extrinsic apoptotic signaling pathwayManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process neuron migrationISS:UniProtKB
Biological Process positive regulation of JNK cascadeISS:UniProtKB
Biological Process positive regulation of proteasomal ubiquitin-dependent protein catabolic processManual Assertion Based On ExperimentIBA:GO_Central
Biological Process protein autoubiquitinationManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process protein ubiquitinationManual Assertion Based On ExperimentIBA:GO_Central
Biological Process regulation of CD4-positive, alpha-beta T cell differentiationISS:UniProtKB
Biological Process regulation of CD8-positive, alpha-beta T cell proliferationISS:UniProtKB

Cellular Location

Cytoplasm, perinuclear region
Cell projection, lamellipodium
Golgi apparatus, trans-Golgi network
Colocalizes, with AKT2, in lamellipodia (By similarity).
Colocalizes, with HERP1, in trans-Golgi network

PTM

Phosphorylated at Ser-304 by AKT1 and AKT2. When phosphorylated, it has reduced ability to bind Rac.
Autoubiquitinated (PubMed:20696164).
Ubiquitinated by SH3RF2, leading to proteasome-mediated degradation (By similarity).