Letunic et al. (2017) Nucleic Acids Res doi: 10.1093/nar/gkx922
Letunic et al. (2020) Nucleic Acids Res doi: 10.1093/nar/gkaa937

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ML Domain involved in innate immunity and lipid metabolism.

SMART accession number:	SM00737
Description:	ML (MD-2-related lipid-recognition) is a novel domain identified in MD-1, MD-2, GM2A, Npc2 and multiple proteins of unknown function in plants, animals and fungi. These single-domain proteins were predicted to form a beta-rich fold containing multiple strands, and to mediate diverse biological functions through interacting with specific lipids.
Interpro abstract (IPR003172):	The MD-2-related lipid-recognition (ML) domain is implicated in lipid recognition, particularly in the recognition of pathogen related products. It has an immunoglobulin-like beta-sandwich fold similar to that of E-set Ig domains. This domain is present in proteins from plants, animals and fungi, including the following proteins: Epididymal secretory protein E1 (also known as Niemann-Pick C2 protein - Npc2), which is known to bind cholesterol. Niemann-Pick disease type C2 is a fatal hereditary disease characterised by accumulation of low-density lipoprotein-derived cholesterol in lysosomes [ (PUBMED:12591954) ]. House-dust mite allergen proteins such as Der f 2 from Dermatophagoides farinae and Der p 2 from Dermatophagoides pteronyssinus [ (PUBMED:15710415) ].
Family alignment:	View or CHROMA formatHMM/Web logoCLUSTALW formatMSF formatFASTA formatPIR format

There are 2836 ML domains in 2744 proteins in SMART's nrdb database.

Click on the following links for more information.

• Evolution (species in which this domain is found)

• Taxonomic distribution of proteins containing ML domain.

  This tree includes only several representative species. The complete taxonomic breakdown of all proteins with ML domain is also avaliable.

  Click on the protein counts, or double click on taxonomic names to display all proteins containing ML domain in the selected taxonomic class.

• Cellular role (predicted cellular role)

• Cellular role: signalling
  Binding / catalysis: Lipid-binding

• Literature (relevant references for this domain)

• Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

  • Inohara N, Nunez G
  • ML -- a conserved domain involved in innate immunity and lipid metabolism.
  • Trends Biochem Sci. 2002; 27: 219-21
  • Display abstract

  • ML (MD-2-related lipid-recognition) is a novel domain identified in MD-1, MD-2, GM2A, Npc2 and multiple proteins of unknown function in plants, animals and fungi. These single-domain proteins were predicted to form a beta-rich fold containing multiple strands, and to mediate diverse biological functions through interacting with specific lipids.

• Metabolism (metabolic pathways involving proteins which contain this domain)

• % proteins involved KEGG pathway ID Description 100.00 map04620 Toll-like receptor signaling pathway This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with ML domain which could be assigned to a KEGG orthologous group, and not all proteins containing ML domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.

• Structure (3D structures containing this domain)

• 3D Structures of ML domains in PDB

  PDB code	Main view	Title
  1a9v		TERTIARY STRUCTURE OF THE MAJOR HOUSE DUST MITE ALLERGEN DER P 2, NMR, 10 STRUCTURES
  1ahk		DER F 2, THE MAJOR MITE ALLERGEN FROM DERMATOPHAGOIDES FARINAE, NMR, MINIMIZED AVERAGE STRUCTURE
  1ahm		DER F 2, THE MAJOR MITE ALLERGEN FROM DERMATOPHAGOIDES FARINAE, NMR, 10 STRUCTURES
  1g13		HUMAN GM2 ACTIVATOR STRUCTURE
  1ktj		X-ray Structure Of Der P 2, The Major House Dust Mite Allergen
  1nep		Crystal Structure Analysis of the Bovine NPC2 (Niemann-Pick C2) Protein
  1pu5		GM2-activator Protein crystal structure
  1pub		GM2-activator Protein crystal structure
  1tjj		Human GM2 Activator Protein PAF complex
  1wrf		Refined solution structure of Der f 2, The Major Mite Allergen from Dermatophagoides farinae
  1xwv		Structure of the house dust mite allergen Der f 2: Implications for function and molecular basis of IgE cross-reactivity
  2af9		Crystal Structure analysis of GM2-Activator protein complexed with phosphatidylcholine
  2ag2		Crystal Structure Analysis of GM2-activator protein complexed with Phosphatidylcholine
  2ag4		Crystal Structure Analysis of GM2-activator protein complexed with phosphatidylcholine
  2ag9		Crystal Structure of the Y137S mutant of GM2-Activator Protein
  2agc		Crystal Structure of mouse GM2- activator Protein
  2e56		Crystal structure of human MD-2
  2e59		Crystal structure of human MD-2 in complex with lipid IVa
  2f08		Crystal structure of a major house dust mite allergen, Derf 2
  2hka		Crystal structure of bovine NPC2 and cholesterol sulfate complex
  2z64		Crystal structure of mouse TLR4 and mouse MD-2 complex
  2z65		Crystal structure of the human TLR4 TV3 hybrid-MD-2-Eritoran complex
  3b2d		Crystal structure of human RP105/MD-1 complex
  3fxi		Crystal structure of the human TLR4-human MD-2-E.coli LPS Ra complex
  3m7o		Crystal structure of mouse MD-1 in complex with phosphatidylcholine
  3mtx		Crystal structure of chicken MD-1
  3mu3		Crystal structure of chicken MD-1 complexed with lipid IVa
  3rg1		Crystal structure of the RP105/MD-1 complex
  3t6q		Crystal structure of mouse RP105/MD-1 complex
  3ula		Crystal structure of the TV3 mutant F63W-MD-2-Eritoran complex
  3vq1		Crystal structure of mouse TLR4/MD-2/lipid IVa complex
  3vq2		Crystal structure of mouse TLR4/MD-2/LPS complex
  3wea		Crystal structure of a Niemann-Pick type C2 protein from Japanese carpenter ant
  3web		Crystal structure of a Niemann-Pick type C2 protein from Japanese carpenter ant in complex with oleic acid
  4g8a		Crystal structure of human TLR4 polymorphic variant D299G and T399I in complex with MD-2 and LPS
  5ijb		5IJB
  5ijc		5IJC
  5ijd		5IJD
  5kwy		5KWY

• Links (links to other resources describing this domain)

• INTERPRO	IPR003172
  PFAM	E1_DerP2_DerF2

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