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4  structures 456  species 0  interactions 1214  sequences 20  architectures

Family: MENTAL (PF10457)

Summary: Cholesterol-capturing domain

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This is the Wikipedia entry entitled "MENTAL domain". More...

MENTAL domain Edit Wikipedia article

MENTAL domain
Pfam PF10457
InterPro IPR019498

The MENTAL or MLN64 NH2-terminal domain is a membrane-spanning domain that is conserved in two late endosomal proteins in vertebrates, MLN64 and MENTHO.[1] The domain is 170 amino acids long.

Current data indicates that this domain allows for dimerization between MLN64 and MENTHO molecules and with themselves.[2] The domain may also direct cholesterol transport.


  1. ^ Alpy F, Wendling C, Rio MC, Tomasetto C (2002). "MENTHO, a MLN64 Homologue Devoid of the START Domain.". J. Biol. Chem. 277 (18): 50780–7. doi:10.1074/jbc.M208290200. PMID 12393907. 
  2. ^ Alpy F, Latchumanan VK, Kedinger V, Janoshazi A, Thiele C, Wendling C, Rio MC, Tomasetto C (2005). "Functional characterization of the MENTAL domain.". J. Biol. Chem. 280 (18): 17945–52. doi:10.1074/jbc.M500723200. PMID 15718238. 

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This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Cholesterol-capturing domain Provide feedback

Human meta-static lymph node (MLN) 64 is a late endosomal membrane protein, and carries this MENTAL (MLN64N-terminal) domain at its N-terminus. The domain is composed of four trans-membrane helices with three short intervening loops [1]. The function of the domain is to capture cholesterol and pass it to the associated START domain PF01852 for transfer to a cytosolic acceptor protein or membrane. In mammals, the MENTAL domain is involved in the localisation of MLN64 and MENTHO in late endosomes, and also in homo-and of hetero-interactions of these two proteins [2].

Literature references

  1. Alpy F, Wendling C, Rio MC, Tomasetto C; , J Biol Chem. 2002;277:50780-50787.: MENTHO, a MLN64 homologue devoid of the START domain. PUBMED:12393907 EPMC:12393907

  2. Alpy F, Latchumanan VK, Kedinger V, Janoshazi A, Thiele C, Wendling C, Rio MC, Tomasetto C; , J Biol Chem. 2005;280:17945-17952.: Functional characterization of the MENTAL domain. PUBMED:15718238 EPMC:15718238

This tab holds annotation information from the InterPro database.

InterPro entry IPR019498

The following proteins share a conserved region called the MENTAL (MLN64 N-terminal) domain, composed of four transmembrane helices with three short intervening loops [ PUBMED:12393907 , PUBMED:15718238 , PUBMED:16709157 ]:

  • Animal MLN64 (metastatic lymph node 64), a late endosomal membrane protein containing a carboxyl-terminal cholesterol binding START domain ( INTERPRO ). It is probably involved in intracellular cholesterol transport.
  • Mammalian MENTHO (MLN64 N-terminal domain homologue), a late endosomal protein containing only the MENTAL domain. It is probably involved in cellular cholesterol homoeostasis.
The ~170-amino acid MENTAL domain mediates MLN64 and MENTHO homo- and hetero- interactions, targets both proteins to late endosomes and binds cholesterol. The MENTAL domain might serve to maintain cholesterol at the membrane of late endosomes prior to its shuttle to cytoplasmic acceptor(s) through the START domain.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

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This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

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Curation and family details

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Curation View help on the curation process

Seed source: Pfam-B_16187 (release 22.0)
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Coggill P
Number in seed: 26
Number in full: 1214
Average length of the domain: 138.30 aa
Average identity of full alignment: 48 %
Average coverage of the sequence by the domain: 43.67 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 21.6 21.6
Trusted cut-off 21.6 21.7
Noise cut-off 21.5 21.5
Model length: 178
Family (HMM) version: 11
Download: download the raw HMM for this family

Species distribution

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Archea Archea Eukaryota Eukaryota
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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the MENTAL domain has been found. There are 4 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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trRosetta Structure

The structural model below was generated by the Baker group with the trRosetta software using the Pfam UniProt multiple sequence alignment.

The InterPro website shows the contact map for the Pfam SEED alignment. Hovering or clicking on a contact position will highlight its connection to other residues in the alignment, as well as on the 3D structure.

Improved protein structure prediction using predicted inter-residue orientations. Jianyi Yang, Ivan Anishchenko, Hahnbeom Park, Zhenling Peng, Sergey Ovchinnikov, David Baker Proceedings of the National Academy of Sciences Jan 2020, 117 (3) 1496-1503; DOI: 10.1073/pnas.1914677117;