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12  structures 86  species 0  interactions 515  sequences 28  architectures

Family: BTK (PF00779)

Summary: BTK motif

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This is the Wikipedia entry entitled "Btk-type zinc finger". More...

Btk-type zinc finger Edit Wikipedia article

Btk motif
PDB 1bwn EBI.jpg
ph domain and btk motif from bruton's tyrosine kinase mutant e41k in complex with ins(1,3,4,5)p4
Identifiers
Symbol BTK
Pfam PF00779
InterPro IPR001562
SMART BTK
SCOP 1btk
SUPERFAMILY 1btk

In molecular biology, the Btk-type zinc finger or Btk motif (BM) is a conserved zinc-binding motif containing conserved cysteines and a histidine that is present in certain eukaryotic signalling proteins. The motif is named after Bruton's tyrosine kinase (Btk), an enzyme which is essential for B cell maturation in humans and mice.[1][2] Btk is a member of the Tec family of protein tyrosine kinases (PTK). These kinases contain a conserved Tec homology (TH) domain between the N-terminal pleckstrin homology (PH) domain and the Src homology 3 (SH3) domain. The N-terminal of the TH domain is highly conserved and known as the Btf motif, while the C-terminal region of the TH domain contains a proline-rich region (PRR). The Btk motif contains a conserved His and three Cys residues that form a zinc finger (although these differ from known zinc finger topologies), while PRRs are commonly involved in protein-protein interactions, including interactions with G proteins.[3][4] The TH domain may be of functional importance in various signalling pathways in different species.[1] A complete TH domain, containing both the Btk and PRR regions, has not been found outside the Tec family; however, the Btk motif on its own does occur in other proteins, usually C-terminal to a PH domain (note that although a Btk motif always occurs C-terminal to a PH domain, not all PH domains are followed by a Btk motif).

The crystal structures of Btk show that the Btk-type zinc finger has a globular core, formed by a long loop which is held together by a zinc ion, and that the Btk motif is packed against the PH domain.[1] The zinc-binding residues are a histidine and three cysteines, which are fully conserved in the Btk motif.[5]

Proteins known to contain a Btk-type zinc finger include:

  • Mammalian Bruton's tyrosine kinase (Btk), a protein tyrosine kinase involved in modulation of diverse cellular processes. Mutations affecting Btk are the cause of X-linked agammaglobulinemia (XLA) in humans and X-linked immunodeficiency in mice.
  • Drosophila tyrosine-protein kinase Btk29A, which is required for the development of proper ring canals and of male genitalia and required for adult survival.
  • Mammalian Ras GTPase-activating proteins (RasGAP), which regulate the activation of inactive GDP-bound Ras by converting GDP to GTP.

References[edit]

  1. ^ a b c Vihinen M, Nilsson L, Smith CI (August 1994). "Tec homology (TH) adjacent to the PH domain". FEBS Lett. 350 (2-3): 263–5. doi:10.1016/0014-5793(94)00783-7. PMID 8070576. 
  2. ^ Lindvall JM, Blomberg KE, Valiaho J, Vargas L, Heinonen JE, Berglof A, Mohamed AJ, Nore BF, Vihinen M, Smith CI (February 2005). "Bruton's tyrosine kinase: cell biology, sequence conservation, mutation spectrum, siRNA modifications, and expression profiling". Immunol. Rev. 203: 200–15. doi:10.1111/j.0105-2896.2005.00225.x. PMID 15661031. 
  3. ^ Vihinen M, Nore BF, Mattsson PT, Backesjo CM, Nars M, Koutaniemi S, Watanabe C, Lester T, Jones A, Ochs HD, Smith CI (August 1997). "Missense mutations affecting a conserved cysteine pair in the TH domain of Btk". FEBS Lett. 413 (2): 205–10. doi:10.1016/S0014-5793(97)00912-5. PMID 9280283. 
  4. ^ Jiang Y, Ma W, Wan Y, Kozasa T, Hattori S, Huang XY (October 1998). "The G protein G alpha12 stimulates Bruton's tyrosine kinase and a rasGAP through a conserved PH/BM domain". Nature 395 (6704): 808–13. doi:10.1038/27454. PMID 9796816. 
  5. ^ Hyvonen M, Saraste M (June 1997). "Structure of the PH domain and Btk motif from Bruton's tyrosine kinase: molecular explanations for X-linked agammaglobulinaemia". EMBO J. 16 (12): 3396–404. doi:10.1093/emboj/16.12.3396. PMC 1169965. PMID 9218782. 

This article incorporates text from the public domain Pfam and InterPro IPR001562

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.

BTK motif Provide feedback

Zinc-binding motif containing conserved cysteines and a histidine. Always found C-terminal to PH domains. The crystal structure [1] shows this motif packs against the PH domain. The PH+Btk module pair has been called the Tec homology (TH) region [3].

Literature references

  1. Hyvonen M, Saraste M; , EMBO J 1997;16:3396-3404.: Structure of the PH domain and Btk motif from Bruton's tyrosine kinase: molecular explanations for X-linked agammaglobulinaemia. PUBMED:9218782 EPMC:9218782

  2. Vihinen M, Nore BF, Mattsson PT, Backesjo CM, Nars M, Koutaniemi S, Watanabe C, Lester T, Jones A, Ochs HD, Smith CI; , FEBS Lett 1997;413:205-210.: Missense mutations affecting a conserved cysteine pair in the TH domain of Btk. PUBMED:9280283 EPMC:9280283

  3. Vihinen M, Nilsson L, Smith CI; , FEBS Lett 1994;350:263-265.: Tec homology (TH) adjacent to the PH domain. PUBMED:8070576 EPMC:8070576


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR001562

The Btk-type zinc finger or Btk motif (BM) is a conserved zinc-binding motif containing conserved cysteines and a histidine that is present in certain eukaryotic signalling proteins. The motif is named after Bruton's tyrosine kinase (Btk), an enzyme which is essential for B cell maturation in humans and mice [PUBMED:8070576, PUBMED:15661031]. Btk is a member of the Tec family of protein tyrosine kinases (PTK). These kinases contain a conserved Tec homology (TH) domain between the N-terminal pleckstrin homology (PH) domain (INTERPRO) and the Src homology 3 (SH3) domain (INTERPRO). The N-terminal of the TH domain is highly conserved and known as the Btf motif, while the C-terminal region of the TH domain contains a proline-rich region (PRR). The Btk motif contains a conserved His and three Cys residues that form a zinc finger (although these differ from known zinc finger topologies), while PRRs are commonly involved in protein-protein interactions, including interactions with G proteins [PUBMED:9280283, PUBMED:9796816]. The TH domain may be of functional importance in various signalling pathways in different species [PUBMED:8070576]. A complete TH domain, containing both the Btk and PRR regions, has not been found outside the Tec family; however, the Btk motif on its own does occur in other proteins, usually C-terminal to a PH domain (note that although a Btk motif always occurs C-terminal to a PH domain, not all PH domains are followed by a Btk motif).

The crystal structures of Btk show that the Btk-type zinc finger has a globular core, formed by a long loop which is held together by a zinc ion, and that the Btk motif is packed against the PH domain [PUBMED:8070576]. The zinc-binding residues are a histidine and three cysteines, which are fully conserved in the Btk motif [PUBMED:9218782].

Proteins known to contain a Btk-type zinc finger include:

  • Mammalian Bruton's tyrosine kinase (Btk), a protein tyrosine kinase involved in modulation of diverse cellular processes. Mutations affecting Btk are the cause of X-linked agammaglobulinemia (XLA) in humans and X-linked immunodeficiency in mice.
  • Mammalian Tec, Bmx, and Itk proteins, which are tyrosine protein kinases of the Tec subfamily.
  • Drosophila tyrosine-protein kinase Btk29A, which is required for the development of proper ring canals and of male genitalia and required for adult survival.
  • Mammalian Ras GTPase-activating proteins (RasGAP), which regulate the activation of inactive GDP-bound Ras by converting GDP to GTP.

Gene Ontology

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Domain organisation

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  Seed
(26)
Full
(515)
Representative proteomes NCBI
(461)
Meta
(0)
RP15
(41)
RP35
(60)
RP55
(128)
RP75
(259)
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External links

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Seed source: Alignment kindly provided by SMART
Previous IDs: none
Type: Motif
Author: SMART
Number in seed: 26
Number in full: 515
Average length of the domain: 31.70 aa
Average identity of full alignment: 38 %
Average coverage of the sequence by the domain: 4.63 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 21.8 21.8
Trusted cut-off 21.9 21.8
Noise cut-off 21.7 21.7
Model length: 32
Family (HMM) version: 14
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Species distribution

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Structures

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 BTK domain has been found. There are 12 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 seqence.

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