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7  structures 819  species 0  interactions 5684  sequences 80  architectures

Family: Tub (PF01167)

Summary: Tub family

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "Tubby protein". More...

Tubby protein Edit Wikipedia article

The tubby protein is an upstream cell signaling protein common to multicellular eukaryotes. The original tubby gene was identified in mice, but proteins that are homologous to tubby are known as "tubby-like proteins" (TULPs) and share a common and characteristic tertiary structure that consists of a beta barrel packed around an alpha helix in the central pore.


Tubby proteins are classified as α+β proteins and have a 12-beta stranded barrel surrounding a central alpha helix. Tubby proteins can bind the small cell signaling molecule phosphatidylinositol, which is typically localized to the cell membrane.


Tubby proteins have been implicated as transcription factors[1] and as potential signaling factors coupled to G-protein activity[2]. They are associated with neuronal differentiation and development, and in mammals are implicated in three disease processes when mutated: obesity, retinal degeneration, and hearing loss[3]. In mice, mutations in tubby proteins are known to affect lifespan and fat storage[4] as well as carbohydrate metabolism[5].


  1. ^ Boggon TJ, Shan WS, Santagata S, Myers SC, Shapiro L. (1999). Implication of tubby proteins as transcription factors by structure-based functional analysis. Science 286(5447):2119-25.
  2. ^ Carroll K, Gomez C, Shapiro L. (2004). Tubby proteins: the plot thickens. Nat Rev Mol Cell Biol5(1):55-63.
  3. ^ Mukhopadhyay A, Deplancke B, Walhout AJ, Tissenbaum HA. (2005). C. elegans tubby regulates life span and fat storage by two independent mechanisms. Cell Metab 2(1):35-42.
  4. ^ Wang Y, Seburn K, Bechtel L, Lee BY, Szatkiewicz JP, Nishina PM, Naggert JK. (2006). Defective carbohydrate metabolism in mice homozygous for the tubby mutation. Physiol Genomics Epub.

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

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.

Tub family Provide feedback

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Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR000007

Tubby, an autosomal recessive mutation, mapping to mouse chromosome 7, was recently found to be the result of a splicing defect in a novel gene with unknown function. This mutation maps to the tub gene [ PUBMED:8612280 , PUBMED:8606774 ]. The mouse tubby mutation is the cause of maturity-onset obesity, insulin resistance and sensory deficits. By contrast with the rapid juvenile-onset weight gain seen in diabetes (db) and obese (ob) mice, obesity in tubby mice develops gradually, and strongly resembles the late-onset obesity observed in the human population. Excessive deposition of adipose tissue culminates in a two-fold increase of body weight. Tubby mice also suffer retinal degeneration and neurosensory hearing loss. The tripartite character of the tubby phenotype is highly similar to human obesity syndromes, such as Alstrom and Bardet-Biedl. Although these phenotypes indicate a vital role for tubby proteins, no biochemical function has yet been ascribed to any family member [ PUBMED:10591637 ], although it has been suggested that the phenotypic features of tubby mice may be the result of cellular apoptosis triggered by expression of the mutated tub gene. TUB is the founding-member of the tubby-like proteins, the TULPs. TULPs are found in multicellular organisms from both the plant and animal kingdoms. Ablation of members of this protein family cause disease phenotypes that are indicative of their importance in nervous-system function and development [ PUBMED:14708010 ].

Mammalian TUB is a hydrophilic protein of ~500 residues. The N-terminal ( INTERPRO ) portion of the protein is conserved neither in length nor sequence, but, in TUB, contains the nuclear localisation signal and may have transcriptional-activation activity. The C-terminal 250 residues are highly conserved. The C-terminal extremity contains a cysteine residue that might play an important role in the normal functioning of these proteins. The crystal structure of the C-terminal core domain from mouse tubby has been determined to 1.9A resolution. This domain is arranged as a 12-stranded, all anti-parallel, closed beta-barrel that surrounds a central alpha helix, (which is at the extreme carboxyl terminus of the protein) that forms most of the hydrophobic core. Structural analyses suggest that TULPs constitute a unique family of bipartite transcription factors [ PUBMED:10591637 ].

Domain organisation

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

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Pfam Clan

This family is a member of clan Tubby_C (CL0395), which has the following description:

This superfamily contains the scramblase protein family, the Tub family and the DUF567, a family of plant and bacterial proteins of hitherto unknown function. All members are membrane-tethered transcription factors.

The clan contains the following 4 members:

DUF3527 LOR Scramblase Tub


We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

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Representative proteomes UniProt

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

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...


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.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Prosite
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Finn RD , Bateman A
Number in seed: 127
Number in full: 5684
Average length of the domain: 233.9 aa
Average identity of full alignment: 35 %
Average coverage of the sequence by the domain: 44.44 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 27.0 27.0
Trusted cut-off 27.0 27.0
Noise cut-off 26.9 26.9
Model length: 263
Family (HMM) version: 21
Download: download the raw HMM for this family

Species distribution

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Colour assignments

Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence


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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

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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 Tub domain has been found. There are 7 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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AlphaFold Structure Predictions

The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.

Protein Predicted structure External Information
A0A044R8J2 View 3D Structure Click here
A0A044UCG4 View 3D Structure Click here
A0A077YUM5 View 3D Structure Click here
A0A077ZD09 View 3D Structure Click here
A0A096S4N1 View 3D Structure Click here
A0A0B4KI44 View 3D Structure Click here
A0A0G2K250 View 3D Structure Click here
A0A0G2L6N8 View 3D Structure Click here
A0A0K0DS17 View 3D Structure Click here
A0A0K0DWX8 View 3D Structure Click here
A0A0K0JQQ8 View 3D Structure Click here
A0A0N4ULX3 View 3D Structure Click here
A0A0R0FIB7 View 3D Structure Click here
A0A0R0J9S7 View 3D Structure Click here
A0A158Q3X8 View 3D Structure Click here
A0A1D6E527 View 3D Structure Click here
A0A1D6F3U2 View 3D Structure Click here
A0A1D6G8B7 View 3D Structure Click here
A0A1D6K2H7 View 3D Structure Click here
A0A1D6K358 View 3D Structure Click here
A0A1D6NFY2 View 3D Structure Click here
A0A2R8S085 View 3D Structure Click here
A0A368UH94 View 3D Structure Click here
A0A3P7EAA1 View 3D Structure Click here
A0A3P7EKS5 View 3D Structure Click here
A0A3P7GEX9 View 3D Structure Click here
A0A3Q0KGF1 View 3D Structure Click here
A0A5S6PTV4 View 3D Structure Click here
A4HW61 View 3D Structure Click here
A8WN62 View 3D Structure Click here
B0WI30 View 3D Structure Click here
B0XFQ9 View 3D Structure Click here
B3MDU3 View 3D Structure Click here
B4F9I7 View 3D Structure Click here
B4FAL2 View 3D Structure Click here
B4FAS5 View 3D Structure Click here
B4FG04 View 3D Structure Click here
B4FSQ3 View 3D Structure Click here
B4FXU9 View 3D Structure Click here
B4H4X0 View 3D Structure Click here