According to Entrez Gene MAPK3 gene maps to NC_000016.9 and spans a region of 9.21 kb. According to Spidey mRNA-to-genomic alignment program ERK1 (MAPK3) variant 1 (the most common variant) has 8 exons, the sizes being 170, 183, 190, 117, 115, 132, 110, 123 bps (mRNA coordinates).

The promoter analysis of the human MAPK3 has shown that the elements responsible for basal transcriptional activity are located within 200 bp upstream of the initiation codon in the 5 UTR and rich in G/C content (80.5%). The sequence has four SP1 sites and an E box as the most relevant motifs. Site-directed mutagenesis, EMSA, and DNase I footprinting experiments proved that all these elements are required to achieve a significant level of transcription. It has also been reported that the promoter activity is strongly repressed when the cells are grown under growth arrest conditions, such as confluence or serum withdrawal.

No pseudogenes have been reported for MAPK3.

ERK1 (MAPK3) is identified by the specific TEY (Thr-Glu-Tyr) sequence in its activation loop. ERK1 (MAPK3) is activated by dual phosphorylation of tyrosine (Tyr204) and threonine (Thr202) residues which is required for complete activation of the protein. Activated ERK1 (MAPK3) migrates into the nucleus and phosphorylates transcription factors.

ERK1 (MAPK3) is a 43 kDa protein consisting of 379 amino acids. ERK1 (MAPK3) protein is 85% identical to ERK2 (MAPK1) (another MAP kinase family member) and the two proteins have even higher levels of similarity in their substrate binding regions. ERK1 (MAPK3) and ERK2 (MAPK1) both possess 2 DXXD docking sites that provide interaction sites with a Kinase Interaction Motif (KIM), which can be found on activators (MAPKK), inhibitors (PTP-SL (PTPRR) and dual specificity phosphatases) and substrates (ELK-1).

Ubiquitously expressed with varying levels in different tissues.

Subcellular location of ERK1 (MAPK3) protein is the cytoplasm, and the nucleus. Upon activation by dual phosphorylation on its Tyr and Thr residues by upstream kinases, ERK1 (MAPK3) is translocated into the nucleus from cytoplasm where it phosphorylates its nuclear targets.

Being one of the most studied cytoplasmic signaling pathways, the ERK pathway is activated via GTP-loading of RAS at the plasma membrane and sequential activation of a series of protein kinases. Activated RAS recruits the RAF family of kinases such as RAF1 to the plasma membrane which in turn acts as a MAPKKK and activates MAP kinase/ERK kinase 1 and 2 (MEK1 (MAP2K1) and MEK2 (MAP2K2)) by serine phosphorylation. MEK1/2 catalyze the phosphorylation of ERK1 (MAPK3) and ERK2 (MAPK1). Activated ERK1/2 (MAPK3/1) phosphorylates many different substrates involved in various cellular responses from cytoskeletal changes to gene transcription. ERK1 (MAPK3) was initially identified as an insulin-stimulated protein kinase which has an activity towards microtubule-associated protein-2. Today, it is well known that ERK1/2 (MAPK3/1) is especially involved in the control of cell proliferation, cell differentiation and cell survival.
It has been shown that activation of ERK1/2 (MAPK3/1) is crucial for cyclin D1 induction, providing a molecular link between ERK signaling and cell cycle control as cyclin D1 gene is essential for G1 to S-phase progression.
In response to Angiotensin II, ERK1/2 (MAPK3/1) regulates cell proliferation by either one of two signaling pathways which are heterotrimeric G protein/PKC zeta-dependent signaling and SRC/YES1/FYN signaling. ERK1/2 (MAPK3/1) phosphorylates specific transcription factors ELK-1 (leading to c-FOS transcriptional activity) following its translocation into the nucleus due to heterotrimeric G protein/PKC zeta-dependent signaling. Due to its phosphorylation in the cytoplasm by SRC/YES1/FYN signaling, ERK1/2 (MAPK3/1) complexes with RSK2 (RPS6KA), which in turn becomes activated and translocates into the nucleus to modulate c-FOS transcription and c-FOS protein activity.
The ERK pathway has been found to be responsible for the phosphorylation of BCL2 that contributes to cell survival, the suppression of the apoptotic effect of BAD, the up-regulation of the antiapoptotic protein MCL-1. Moreover, it has been also shown that ERK1/2 (MAPK3/1) is one of the regulators of TP53 protein accumulation and activation during the DNA damage response.
ERK1/2 (MAPK3/1) induces expression of PAI-1 (plasminogen activator type-1 inhibitor) which is closely associated with dynamic changes in cellular morphology and shape-altering physiologic processes.
ERK1/2 (MAPK3/1) has been shown to regulate PPARg1 following EGF stimulation.
CIITA is a critical transcription factor that initiates the expression of MHC class II genes and the subsequent induction of the immune response. Studies have indicated that ERK1/2 (MAPK3/1) negatively regulates CIITA by blocking expression of the CIITA gene and/or by phosphorylating CIITA at residues including serine 288, resulting in the loss of CIITA transactivation potential by enabling it to interact with CRM1 (XPO1) which causes export of CIITA protein from the nucleus.

- P. troglodytes, MAPK3, mitogen-activated protein kinase 3
- C. lupus familiaris, MAPK3, mitogen-activated protein kinase 3
- B. taurus, MAPK3, mitogen-activated protein kinase 3
- M. musculus, MAPK3, mitogen-activated protein kinase 3
- R. norvegicus, MAPK3, mitogen activated protein kinase 3
- D. rerio, MAPK3, mitogen-activated protein kinase 3
- S. pombe, spk1, MAP kinase Spk1
- S. cerevisiae, FUS3, Fus3p
- K. lactis, KLLA0E10527g, hypothetical protein
- E. gossypii, AGOS_AFR019W, AFR019Wp
- M. grisea, MGG_09565, mitogen-activated protein kinase
- N. crassa, NCU02393.1, hypothetical protein ((AF348490) MAP kinase [Neurospora crassa OR74A])
- A. thaliana, ATMPK13, ATMPK13; MAP kinase/ kinase