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	PROSITE documentation PDOC00923

The mouse tubby mutation is the cause of maturity-onset obesity, insulin resistance and sensory deficits. This mutation maps to a gene, tub [1,2], which codes for a protein that belongs to a family which currently consists of the following members:

• Mammalian tub, an hydrophilic protein of about 500 residues, which could be involved in the hypothalamic regulation of body weight.
• Human protein TULP1 [3] is involved in retinis pigmentosa 14 (RP14), a retinal degeneration disease.
• Human protein TULP2 [3].
• Mammalian protein TULP3 [4].
• Mouse protein p4-6 whose function is not known.
• Caenorhabditis elegans hypothetical protein F10B5.4.
• Several fragmentary sequences from plants, Drosophila and human ESTs.

While the N-terminal part of these protein is not conserved in length nor in the sequence, the C-terminal 250 residues are highly conserved. We therefore selected two regions in the C-terminal part as signature patterns. The second region is located at the C-terminal extremity and contains a penultimate cysteine residue that could be critical to the normal functioning of these proteins.

Last update:

December 2001 / Patterns and text revised.

PROSITE methods (with tools and information) covered by this documentation:

TUB_1, PS01200; Tub family signature 1  (PATTERN)

• Consensus pattern:
  F-[KRHQ]-G-R-V-[ST]-x-A-S-V-K-N-F-Q
• Sequences in UniProtKB/Swiss-Prot known to belong to this class: 51
  • detected by PS01200: 48 (true positives)
  • undetected by PS01200: 3 (3 false negatives and 0 'partial')
• Other sequence(s) in UniProtKB/Swiss-Prot detected by PS01200:
  NONE.
• Retrieve an alignment of UniProtKB/Swiss-Prot true positive hits:
  Clustal format, color, condensed view  /  Clustal format, color  /  Clustal format, plain text  /  Fasta format
• Retrieve the sequence logo from the alignment
• Taxonomic distribution of all UniProtKB (Swiss-Prot + TrEMBL) entries matching PS01200
• Retrieve a list of all UniProtKB (Swiss-Prot + TrEMBL) entries matching PS01200
• Scan UniProtKB (Swiss-Prot and/or TrEMBL) entries against PS01200
• View ligand binding statistics of PS01200
• Matching PDB structures: 1C8Z 1I7E 1S31 2FIM ... [ALL]

TUB_2, PS01201; Tub family signature 2  (PATTERN)

• Consensus pattern:
  A-F-[AG]-I-[GSAC]-[LIVM]-[ST]-S-F-x-[GST]-K-x-A-C-E
• Sequences in UniProtKB/Swiss-Prot known to belong to this class: 51
  • detected by PS01201: 41 (true positives)
  • undetected by PS01201: 10 (10 false negatives and 0 'partial')
• Other sequence(s) in UniProtKB/Swiss-Prot detected by PS01201:
  NONE.
• Retrieve an alignment of UniProtKB/Swiss-Prot true positive hits:
  Clustal format, color, condensed view  /  Clustal format, color  /  Clustal format, plain text  /  Fasta format
• Retrieve the sequence logo from the alignment
• Taxonomic distribution of all UniProtKB (Swiss-Prot + TrEMBL) entries matching PS01201
• Retrieve a list of all UniProtKB (Swiss-Prot + TrEMBL) entries matching PS01201
• Scan UniProtKB (Swiss-Prot and/or TrEMBL) entries against PS01201
• View ligand binding statistics of PS01201
• Matching PDB structures: 1C8Z 1S31 [ALL]

1	Authors	Kleyn P.W., Fan W., Kovats S.G., Lee J.J., Pulido J.C., Wu Y., Berkemeier L.R., Misumi D.J., Holmgren L., Charlat O., Woolf E.A., Tayber O., Brody T., Shu P., Hawkins F., Kennedy B., Baldini L., Ebeling C., Alperin G.D., Deeds J., Lakey N.D., Culpepper J., Chen H., Glucksmann-Kuis M.A., Carlson G.A., Duyk G.M., Moore K.J.
	Title	Identification and characterization of the mouse obesity gene tubby: a member of a novel gene family.
	Source	Cell 85:281-290(1996).
	PubMed ID	8612280

2	Authors	Noben-Trauth K., Naggert J.K., North M.A., Nishina P.M.
	Source	Nature 380:534-538(1996).

3	Authors	North M.A., Naggert J.K., Yan Y., Noben-Trauth K., Nishina P.M.
	Title	Molecular characterization of TUB, TULP1, and TULP2, members of the novel tubby gene family and their possible relation to ocular diseases.
	Source	Proc. Natl. Acad. Sci. U.S.A. 94:3128-3133(1997).
	PubMed ID	9096357

4	Authors	Nishina P.M., North M.A., Ikeda A., Yan Y., Naggert J.K.
	Title	Molecular characterization of a novel tubby gene family member, TULP3, in mouse and humans.
	Source	Genomics 54:215-220(1998).
	PubMed ID	9828123

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