UFM1 Human

Ubiquitin-Fold Modifier 1 Human Recombinant
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Cat. No.
BT23053
Source
Escherichia Coli.
Synonyms
Ubiquitin-fold modifier 1, UFM1, C13orf20, BM-002, bA131P10.1.
Appearance
Sterile Filtered colorless solution.
Purity
Greater than 95.0% as determined by SDS-PAGE.
Usage
THE BioTek's products are furnished for LABORATORY RESEARCH USE ONLY. The product may not be used as drugs, agricultural or pesticidal products, food additives or household chemicals.
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Description

Overview and Molecular Structure

UFM1 (Ubiquitin-fold modifier 1) is a 9.1 kDa ubiquitin-like protein (UBL) encoded by the UFM1 gene (HGNC:20597; UniProt:P61960) . Despite lacking sequence similarity, UFM1 shares structural homology with ubiquitin, featuring a β-grasp fold critical for its conjugation to target proteins . Synthesized as an 85-amino acid precursor (proUFM1), it undergoes proteolytic cleavage by UFSP1 or UFSP2 to expose a C-terminal glycine residue (Gly83), enabling activation and conjugation .

The UFMylation Cascade

UFM1 conjugation (ufmylation) involves three enzymatic steps:

  1. Activation: UBA5 (E1) adenylates UFM1, forming a thioester bond via its catalytic cysteine .

  2. Conjugation: UFC1 (E2) transfers UFM1 to the E3 ligase complex (UFL1-UFBP1-CDK5RAP3), which mediates substrate attachment .

  3. Deconjugation: UFSP2 reverses ufmylation by cleaving UFM1 from substrates .

Critical Components of the UFM1 System:

  • E3 Ligase Complex: UFL1 (catalytic subunit), UFBP1/DDRGK1 (ER membrane anchor), and CDK5RAP3 (regulator) .

  • Proteases: UFSP1 (primary UFM1 maturation) and UFSP2 (deconjugation) .

Endoplasmic Reticulum (ER) Homeostasis

  • ER-Phagy: UFM1 modifies CYB5R3, triggering lysosomal degradation of ER membranes via CDK5RAP3-mediated autophagy .

  • Ribosome Quality Control: UFM1 conjugates to ribosomal protein RPL26 during stalling at the ER translocon, facilitating ribosome recycling .

Developmental Regulation

  • Knockout mice lacking UFM1 system components exhibit microcephaly, anemia, and liver defects .

  • UFM1 regulates neurogenesis and erythroid differentiation via interactions with ribosomal and ER-associated proteins .

Key Substrates and Pathways

SubstrateFunctionConsequence of Ufmylation
CYB5R3ER membrane redox regulationInactivation, ER-phagy induction
RPL26Ribosomal subunit stabilityRibosome recycling during ER stress
UFC1E2 enzyme autoregulationProteasomal degradation

Regulatory Mechanisms

  • UFBP1-UFL1 Interaction: UFBP1 anchors UFL1 to the ER and enhances E3 ligase activity via its UFM1-interacting motif (UFIM) .

  • UFIM Structural Role: Crystal structures reveal UFBP1’s β-strand (residues 194–202) forms an anti-parallel β-sheet with UFM1, stabilizing substrate recognition .

  • Feedback Loops: UFMylated UFC1 is cleaved by UFSP1, linking UFM1 maturation to E2 enzyme turnover .

Genetic Disorders

  • Mutations in UFM1, UBA5, or UFC1 cause hypomyelinating leukodystrophy and developmental epileptic encephalopathy .

  • UFSP2 mutations are linked to skeletal dysplasia (e.g., Schohat-type osteochondrodysplasia) .

Cancer and Metabolic Disease

  • UFM1 is upregulated in hepatocellular carcinoma and modulates apoptosis .

  • Dysregulation of ER-phagy via UFM1 contributes to diabetes and ischemic heart disease .

Research Advances and Therapeutic Potential

  • Structural Insights: Cryo-EM studies resolved UFM1 E3 ligase (UREL) bound to 60S ribosomes, revealing how UFL1 remodels the peptidyl transferase center to monitor translation .

  • Therapeutic Targets: Small-molecule inhibitors of UBA5 or UFSP2 are under investigation for leukemia and neurodegenerative diseases .

Product Specs

Introduction
UFM1, a ubiquitin-like protein, undergoes conjugation with target proteins via a ubiquitylation-like process. This involves the E1-like activating enzyme UBA5 and the E2-like conjugating enzyme UFC1. While primarily localized in the nucleus, UFM1 is also found diffusely in the cytoplasm and is expressed in various tissues such as the kidney, brain, heart, liver, and lung.
Description
Recombinant human UFM1, with a 20 amino acid His tag at the N-terminus, is produced in E. coli. This non-glycosylated polypeptide chain consists of 103 amino acids (1-83 a.a), resulting in a molecular mass of 11.1 kDa. Purification is achieved through proprietary chromatographic techniques.
Physical Appearance
A sterile, colorless solution.
Formulation
The UFM1 solution is provided at a concentration of 1 mg/ml in a buffer containing 20mM Tris (pH 8.0) and 10% glycerol.
Stability
For optimal storage, refrigerate at 4°C if the entire vial will be used within 2-4 weeks. For longer-term storage, freeze at -20°C. Adding a carrier protein (0.1% HSA or BSA) is recommended for extended storage. Avoid repeated freeze-thaw cycles.
Purity
Purity exceeds 95.0% as assessed by SDS-PAGE.
Synonyms
Ubiquitin-fold modifier 1, UFM1, C13orf20, BM-002, bA131P10.1.
Source
Escherichia Coli.
Amino Acid Sequence
MGSSHHHHHH SSGLVPRGSH MSKVSFKITL TSDPRLPYKV LSVPESTPFT AVLKFAAEEF KVPAATSAII TNDGIGINPA QTAGNVFLKH GSELRIIPRD RVG.

Product Science Overview

Introduction

Ubiquitin-Fold Modifier 1 (UFM1) is a ubiquitin-like protein that plays a crucial role in various cellular processes. It is a small protein consisting of 85 amino acids and is highly conserved across multicellular organisms . UFM1 is involved in a post-translational modification process known as ufmylation, which is analogous to ubiquitination.

Structure and Expression

UFM1 is synthesized as a precursor protein (pro-UFM1) and undergoes processing to become the mature form. The mature UFM1 can be covalently attached to target proteins via an isopeptide bond to lysine residues . This attachment can occur as a monomer or as a lysine-linked polymer . The recombinant form of UFM1 is typically expressed in Escherichia coli and purified to high levels of purity (>95%) for research purposes .

Ufmylation Process

The ufmylation process involves several key enzymes:

  1. UFM1-activating enzyme (UBA5): This enzyme activates UFM1 in an ATP-dependent manner.
  2. UFM1-conjugating enzyme (UFC1): This enzyme transfers the activated UFM1 to the target protein.
  3. UFM1-ligase (UFL1): This enzyme facilitates the attachment of UFM1 to the substrate protein .
Biological Functions

Ufmylation is implicated in various cellular functions, including:

  • Endoplasmic Reticulum (ER) Stress Response: Ufmylation is involved in reticulophagy (ER-phagy), a process that helps cells cope with ER stress .
  • Transcription Regulation: Ufmylation of TRIP4 regulates nuclear receptor-mediated transcription .
  • Protein Quality Control: Ufmylation plays a role in maintaining protein homeostasis by targeting misfolded proteins for degradation .
Clinical Significance

Mutations or dysregulation of the UFM1 pathway have been associated with several diseases, including:

  • Leukodystrophy, Hypomyelinating, 14: A genetic disorder characterized by abnormal development of the white matter in the brain .
  • Leukodystrophy, Hypomyelinating, 6: Another genetic disorder affecting the myelin sheath of nerve cells .
Research Applications

Recombinant UFM1 is widely used in research to study the mechanisms of ufmylation and its role in various cellular processes. It is also used to investigate the potential therapeutic targets for diseases associated with UFM1 dysregulation .

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