MORF4L2 Human

Mortality Factor 4 Like 2 Human Recombinant
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Description

Introduction to MORF4L2 Human

MORF4L2 (Mortality Factor 4-Like Protein 2) is a nuclear-localized transcriptional regulator encoded by the MORF4L2 gene (NCBI Gene ID: 9643) located on the human X chromosome . It belongs to the Mortality Factor (MORF) family and plays critical roles in epigenetic regulation, cell growth, and immune modulation. The protein is produced as a 308-amino acid polypeptide with a molecular weight of 34.4 kDa and contains a C-terminal His-tag when recombinantly expressed in E. coli .

Epigenetic Regulation

MORF4L2 interacts with the Rb tumor suppressor and exhibits histone deacetylase (HDAC) activity, modulating the B-Myb promoter’s transcriptional output in a tissue-specific manner . As part of the NuA4 complex, it facilitates histone acetylation, enabling chromatin remodeling and activation of oncogenes or tumor suppressors .

Immune Modulation

Recent studies highlight MORF4L2’s role in creating immunosuppressive microenvironments in triple-negative breast cancer (TNBC):

  • Upregulation in anti-PD1 resistance: Elevated MORF4L2 expression correlates with reduced responsiveness to PD1 inhibitors in TNBC patients .

  • CSF1/CSF1R axis activation: MORF4L2 promotes H4K12 acetylation, driving CSF1 transcription. CSF1 secretion by tumor cells recruits and polarizes macrophages toward the M2 phenotype, suppressing anti-tumor immunity .

Interaction Network and Protein Partners

MORF4L2 associates with key NuA4 complex components and regulatory proteins:

Interacting ProteinFunctional Role in NuA4 ComplexEvidence Source
KAT5 (TIIF2)Catalytic subunit for histone acetylation
TRRAPAdapter protein for chromatin remodeling
MRGBPStabilizes NuA4 complex assembly
Rb tumor suppressorRegulates cell cycle and senescence

Cancer Prognosis and Therapy Resistance

  • Breast cancer: High MORF4L2 expression is linked to poor survival outcomes and immune cell infiltration (e.g., M2 macrophages) .

  • TNBC immunotherapy resistance: MORF4L2-driven CSF1/CSF1R signaling counteracts PD1 blockade. Inhibiting CSF1R with BLZ549 restores anti-PD1 sensitivity .

  • miRNA regulation: miR-3156-5p directly represses MORF4L2 expression. Overexpression of this miRNA reduces MORF4L2 protein levels by 46% in BON-1 cells .

Therapeutic Targets

TargetMechanism of ActionApplication
CSF1R inhibitorsBlock tumor-derived CSF1 signaling, reducing M2 macrophagesRestores PD1 sensitivity in TNBC
miRNA mimicsDownregulate MORF4L2 expression via miR-3156-5pPotential for NET treatment

Research Challenges and Future Directions

  • Mechanistic gaps: The dual role of MORF4L2 as both a HDAC and HAT component remains poorly understood.

  • Biomarker potential: MORF4L2’s expression in serum or tumor tissues warrants validation as a predictive marker for immunotherapy response.

Product Specs

Introduction
MORF4L2, a member of the mortality factor (MORF) family, plays a crucial role in regulating cell growth, senescence, and overall regulation. This nuclear protein features phosphorylation sites for both protein kinase C and tyrosine kinases. Interacting with the Rb tumor suppressor through its helix-loop-helix and leucine zipper regions, MORF4L2 exhibits histone deacetylase activity. Its influence on the B-Myb promoter is context-dependent, capable of either repression or promotion based on the specific tissue.
Description
Produced in E. coli, our MORF4L2 is a non-glycosylated polypeptide chain consisting of 308 amino acids (specifically, residues 1-288). This single-chain protein has a molecular weight of 34.4 kDa. Please note that its apparent size on SDS-PAGE might appear larger. For purification, we've added a 20 amino acid His-tag at the N-terminus and employed proprietary chromatographic techniques.
Physical Appearance
The product is a clear, colorless solution that has been sterilized by filtration.
Formulation
Our MORF4L2 solution is provided at a concentration of 0.5 mg/ml. The storage buffer consists of 20mM Tris-HCl (pH 8.0), 20% glycerol, and 1mM DTT.
Stability
For short-term storage (up to 2-4 weeks), keep the vial refrigerated at 4°C. For extended storage, freeze the solution at -20°C. We recommend adding a carrier protein (either HSA or BSA) at a concentration of 0.1% for long-term storage. It's essential to minimize freeze-thaw cycles.
Purity
The purity of our MORF4L2 is greater than 85%, as determined by SDS-PAGE analysis.
Synonyms

Mortality factor 4-like protein 2, MORF-related gene X protein, Protein MSL3-2, Transcription factor-like protein MRGX, MORF4L2, KIAA0026, MRGX, MORFL2.

Source
Escherichia Coli.
Amino Acid Sequence

MGSSHHHHHH SSGLVPRGSH MSSRKQGSQP RGQQSAEEEN FKKPTRSNMQ RSKMRGASSG KKTAGPQQKN LEPALPGRWG GRSAENPPSG SVRKTRKNKQ KTPGNGDGGS TSEAPQPPRK KRARADPTVE SEEAFKNRME VKVKIPEELK PWLVEDWDLV TRQKQLFQLP AKKNVDAILE EYANCKKSQG NVDNKEYAVN EVVAGIKEYF NVMLGTQLLY KFERPQYAEI LLAHPDAPMS QVYGAPHLLR LFVRIGAMLA YTPLDEKSLA LLLGYLHDFL KYLAKNSASL FTASDYKVAS AEYHRKAL.

Product Science Overview

Introduction

Mortality Factor 4 Like 2, also known as MORF4L2, is a protein-coding gene that plays a significant role in various cellular processes. This protein is a component of the NuA4 histone acetyltransferase complex, which is involved in transcriptional activation of select genes by acetylation of nucleosomal histone H4 and H2A . This modification can alter nucleosome-DNA interactions and promote interaction of the modified histones with other proteins that positively regulate transcription .

Function and Importance

MORF4L2 is predicted to be involved in heterochromatin assembly and histone modification . It acts upstream of or within the positive regulation of striated muscle cell differentiation and transcription by RNA polymerase II . The protein is located in the nucleolus, nucleoplasm, and plasma membrane . It is also a component of the MSIN3A complex, which represses transcription by deacetylation of nucleosomal histones .

Diseases Associated

Diseases associated with MORF4L2 include Paraneoplastic Cerebellar Degeneration and Pelizaeus-Merzbacher Disease . The gene is also involved in pathways related to chromatin organization .

Preparation Methods

Recombinant Human Mortality Factor 4 Like 2 can be prepared using various methods. One common method involves expressing the protein in a suitable host system, such as Escherichia coli, followed by purification using affinity chromatography . The purified protein is then formulated in a buffer containing 20mM Tris-HCl (pH 8.0), 20% glycerol, and 1mM DTT .

Chemical Reactions

MORF4L2 is a part of the NuA4 histone acetyltransferase complex, which is involved in the acetylation of nucleosomal histone H4 and H2A . This acetylation process is crucial for transcriptional activation and can influence various cellular processes, including growth induction, tumor suppressor-mediated growth arrest, replicative senescence, apoptosis, and DNA repair . The NuA4 complex’s ATPase and helicase activities are contributed by the association of RUVBL1 and RUVBL2 with EP400 .

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