Tyrosine kinase

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{{STRUCTURE_3ac1| PDB=3ac1 | SIZE=400| SCENE= |right|CAPTION=Human lymphocyte-specific tyrosine kinase Lck kinase domain with phosphotyrosine complex with inhibitor, MPD, dimethyl sulfoxide and sulfate, [[3ac1]] }}
{{STRUCTURE_3ac1| PDB=3ac1 | SIZE=400| SCENE= |right|CAPTION=Human lymphocyte-specific tyrosine kinase Lck kinase domain with phosphotyrosine complex with inhibitor, MPD, dimethyl sulfoxide and sulfate, [[3ac1]] }}
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'''Tyrosine kinase''' (TK) transfers a phosphate group from ATP to tyrosine residues of proteins. Mutated TK can cause unregulated growth of the cell and their inhibitors can be effective cancer treatment.<br />
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'''Tyrosine kinase''' (TK) transfers a phosphate group from ATP to tyrosine residues of proteins. Mutated TK can cause unregulated growth of the cell and their inhibitors can be effective cancer treatment. TKs are classified as receptor-TK which are membrane-attached and cytoplasmic non-receptor TKs. TK contains, starting from the N-terminal, SH4 – a membrane attachment domain; SH3 and SH2 domains which are a sequence-specific phosphotyrosine binding domains with roles in protein-protein interactions and the SH1 catalytic kinase domain.br />
For Abelson tyrosine kinase see:<br />
For Abelson tyrosine kinase see:<br />
*[[Bcr-Abl and Imatinib (STI571 or Gleevec)]].<br />
*[[Bcr-Abl and Imatinib (STI571 or Gleevec)]].<br />
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Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
 +
 +
'''Non-receptor tyrosine kinases - nRTK'''
===Fyn tyrosine kinase===
===Fyn tyrosine kinase===
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[[2yfx]], [[4anq]], [[4ans]] - hTK kinase domain (mutant) + cancer drug<br />
[[2yfx]], [[4anq]], [[4ans]] - hTK kinase domain (mutant) + cancer drug<br />
[[3l9p]], [[3lcs]], [[3lct]], [[2yhv]], [[2yjr]], [[2yjs]], [[4fnw]], [[4fnx]], [[4anl]] - hTK kinase domain (mutant)<br />
[[3l9p]], [[3lcs]], [[3lct]], [[2yhv]], [[2yjr]], [[2yjs]], [[4fnw]], [[4fnx]], [[4anl]] - hTK kinase domain (mutant)<br />
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===Bruton’s tyrosine kinase===
 
- 
-
[[2z0p]] - hTK Btk PH domain<br />
 
-
[[1btk]] – hTK Btk PH domain (mutant) <br />
 
-
[[3p08]] - hTK Btk kinase domain<br />
 
-
[[1aww]], [[1awx]], [[1qly]] - hTK Btk SH3 domain – NMR<BR />
 
-
[[2ge9]] - hTK Btk SH2 domain – NMR<BR />
 
- 
-
''Btk complex''
 
- 
-
[[1b55]] - hTK Btk PH domain + inositol-tetrakisphosphate<br />
 
-
[[1bwn]] - hTK Btk PH domain (mutant) + inositol-tetrakisphosphate<br />
 
-
[[3gen]], [[3ocs]], [[3pix]], [[3piy]], [[3piz]], [[3pj1]], [[3pj2]], [[3pj3]] - hTK Btk kinase domain + inhibitor<br />
 
-
[[3k54]], [[3t9t]] - hTK Btk kinase domain (mutant) + inhibitor<br />
 
-
[[3oct]] - hTK Btk kinase domain (mutant) + cancer drug<br />
 
===Csk tyrosine kinase===
===Csk tyrosine kinase===
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[[4fl3]] - Syk kinase domain (mutant) + ANP<br />
[[4fl3]] - Syk kinase domain (mutant) + ANP<br />
[[1a81]] – Syk tandem SH2 domain + T-cell surface peptide <br />
[[1a81]] – Syk tandem SH2 domain + T-cell surface peptide <br />
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===Fms tyrosine kinase===
 
-
 
-
[[2i0v]] - hTK Fms kinase domain
 
- 
-
''Fms complex''
 
- 
-
[[2i0y]], [[2i1m]] - hTK Fms kinase domain + inhibitor<br />
 
-
[[3dpk]] - hTK Fms kinase domain (mutant) + inhibitor<br />
 
-
[[1flt]] – hTK Fms Igg-like domain + VEGF<br />
 
-
[[1qty]] - hTK Fms domain 2 + VEGF
 
===Itk tyrosine kinase===
===Itk tyrosine kinase===
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[[2oq1]] - hTK Zap SH2 domain + peptide<br />
[[2oq1]] - hTK Zap SH2 domain + peptide<br />
[[1u59]] - hTK Zap catalytic domain + staurosporin
[[1u59]] - hTK Zap catalytic domain + staurosporin
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-
===Mer tyrosine kinase===
 
- 
-
[[2dbj]] - hTK Mer FN2 domain – NMR<BR />
 
-
[[2p0c]] - hTK Mer catalytic domain
 
- 
-
''Mer complex''
 
- 
-
[[3brb]] - hTK Mer catalytic domain + ADP<br />
 
-
[[3bpr]] - hTK Mer catalytic domain + inhibitor<br />
 
- 
-
===Bone marrow tyrosine kinase===
 
- 
-
[[2ekx]] - hTK Bmx SH2 domain – NMR<BR />
 
-
[[2ys2]] - hTK Bmx Btk motif – NMR<BR />
 
- 
-
''Bmx complex''
 
- 
-
[[3sxr]] - hTK Bmx kinase domain (mutant) + dasatinib<br />
 
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[[3sxs]] - hTK Bmx kinase domain (mutant) + inhibitor<br />
 
===2β tyrosine kinase===
===2β tyrosine kinase===
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[[1ad5]] - hTK SH3-SH2-kinase-tail domain + AMPPNP<BR />
[[1ad5]] - hTK SH3-SH2-kinase-tail domain + AMPPNP<BR />
[[2hck]] - hTK SH3-SH2-kinase-tail domain + quercetin<BR />
[[2hck]] - hTK SH3-SH2-kinase-tail domain + quercetin<BR />
 +
 +
'''Receptor tyrosine kinases - RTK'''
 +
 +
===Bruton’s tyrosine kinase===
 +
 +
[[2z0p]] - hTK Btk PH domain<br />
 +
[[1btk]] – hTK Btk PH domain (mutant) <br />
 +
[[3p08]] - hTK Btk kinase domain<br />
 +
[[1aww]], [[1awx]], [[1qly]] - hTK Btk SH3 domain – NMR<BR />
 +
[[2ge9]] - hTK Btk SH2 domain – NMR<BR />
 +
 +
''Btk complex''
 +
 +
[[1b55]] - hTK Btk PH domain + inositol-tetrakisphosphate<br />
 +
[[1bwn]] - hTK Btk PH domain (mutant) + inositol-tetrakisphosphate<br />
 +
[[3gen]], [[3ocs]], [[3pix]], [[3piy]], [[3piz]], [[3pj1]], [[3pj2]], [[3pj3]] - hTK Btk kinase domain + inhibitor<br />
 +
[[3k54]], [[3t9t]] - hTK Btk kinase domain (mutant) + inhibitor<br />
 +
[[3oct]] - hTK Btk kinase domain (mutant) + cancer drug<br />
 +
 +
===Fms tyrosine kinase===
 +
 +
[[2i0v]] - hTK Fms kinase domain
 +
 +
''Fms complex''
 +
 +
[[2i0y]], [[2i1m]] - hTK Fms kinase domain + inhibitor<br />
 +
[[3dpk]] - hTK Fms kinase domain (mutant) + inhibitor<br />
 +
[[1flt]] – hTK Fms Igg-like domain + VEGF<br />
 +
[[1qty]] - hTK Fms domain 2 + VEGF
 +
 +
===Mer tyrosine kinase===
 +
 +
[[2dbj]] - hTK Mer FN2 domain – NMR<BR />
 +
[[2p0c]] - hTK Mer catalytic domain
 +
 +
''Mer complex''
 +
 +
[[3brb]] - hTK Mer catalytic domain + ADP<br />
 +
[[3bpr]] - hTK Mer catalytic domain + inhibitor<br />
 +
 +
===Bone marrow tyrosine kinase===
 +
 +
[[2ekx]] - hTK Bmx SH2 domain – NMR<BR />
 +
[[2ys2]] - hTK Bmx Btk motif – NMR<BR />
 +
 +
''Bmx complex''
 +
 +
[[3sxr]] - hTK Bmx kinase domain (mutant) + dasatinib<br />
 +
[[3sxs]] - hTK Bmx kinase domain (mutant) + inhibitor<br />
 +
[[Category:Topic Page]]
[[Category:Topic Page]]

Revision as of 07:57, 24 November 2013

Template:STRUCTURE 3ac1

Tyrosine kinase (TK) transfers a phosphate group from ATP to tyrosine residues of proteins. Mutated TK can cause unregulated growth of the cell and their inhibitors can be effective cancer treatment. TKs are classified as receptor-TK which are membrane-attached and cytoplasmic non-receptor TKs. TK contains, starting from the N-terminal, SH4 – a membrane attachment domain; SH3 and SH2 domains which are a sequence-specific phosphotyrosine binding domains with roles in protein-protein interactions and the SH1 catalytic kinase domain.br /> For Abelson tyrosine kinase see:

For Src tyrosine kinase see:

See also

For references see Treatments:TYKI References.


3D structures of tyrosine kinase

Updated on 24-November-2013

Non-receptor tyrosine kinases - nRTK

Fyn tyrosine kinase

1shf, 3ua6 – hTK Fyn SH3 domain – human
3h0f, 3h0h, 3h0i - hTK Fyn SH3 domain (mutant)
2l2p, 2lp5 - cTK Fyn SH3 domain (mutant)- chicken - NMR
3uf4 – mTK Fyn SH3-SH2 domain – mouse

Fyn complex

1fyn - hTK Fyn SH3 domain + peptide
1efn, 1avz - hTK Fyn SH3 domain + HIV Nef protein
4d8d - hTK Fyn SH3 domain (mutant) + HIV Nef protein
3ua7 – hTK Fyn SH3 domain + hepatitis virus peptide
4eik - hTK Fyn SH3 domain + VSL12 peptide
1aot, 1aou - hTK Fyn SH2 domain + phosphopeptide - NMR

Abelson tyrosine kinase

Abl1 SH2 domain

1ab2 - hTK SH2 domain – NMR
3egu, 3eg2, 3eg3, 3eg0, 3eg1 - hTK SH2 domain (mutant)
3uyo, 3t04, 3k2m - hTK SH2 domain + monobody

Abl1 SH3 domain

1ju5 - hTK SH3 domain (mutant) + CRK SH2 domain + phosphopeptide - NMR
1awo - hTK SH3 domain + phosphopeptide – NMR
1bbz - hTK SH3 domain + peptide
2o88 - hTK SH3 domain (mutant} + peptide
1abo - mTK SH3 domain + peptide
1abq - mTK SH3 domain

Abl1 SH3-SH2 domain

2abl - hTK SH3-SH2 domain
2fo0 - hTK SH3-SH2 domain (mutant)

Abl1 kinase domain

2g2h - hTK kinase domain (mutant)
1opj, 1opk - mTK kinase domain
2g1t - hTK kinase domain + peptide
2g2i, 2g2f - hTK kinase domain (mutant) + peptide
3ue4, 3cs9, 2hzi, 2hz4, 2hz0, 2hyy, 2gqg - hTK kinase domain + cancer drug
2f4j - hTK kinase domain (mutant) + cancer drug
3qrk, 3qri, 3qrj, 2v7a, 2e2b, 2hiw - hTK kinase domain + inhibitor
1fpu, 1m52, 2qoh, 3kf4, 3kfa - mTK kinase domain + inhibitor
2z60, 3dk3, 3dk6, 3dk7 - mTK kinase domain (mutant) + inhibitor
1iep, 2hzn, 3k5v, 3ms9, 3mss, 3oxz - mTK kinase domain + cancer drug
3ik3, 3oy3 - mTK kinase domain (mutant) + cancer drug

Abl1 SH3-SH2-kinase domain

1opl - hTK SH3-SH2-kinase domain (mutant}

Abl2 SH2 domain

4eih - hTK SH2 domain
2ecd - hTK SH2 domain – NMR

Abl2 kinase domain

3gvu - hTK kinase domain + Gleevec
3hmi - hTK kinase domain + inhibitor
2xyn - hTK kinase domain + cancer drug

Abl2 C-terminal

2kk1 – hTK C terminal – NMR

Anaplastic lymphoma kinase (Alk)

2xb7, 2xba, 3aox - hTK kinase domain + inhibitor
4dce, 4fob, 4foc, 4fod, 4fny, 4fnz, 4joa - hTK kinase domain (mutant) + inhibitor
2xp2 - hTK kinase domain + cancer drug
2yfx, 4anq, 4ans - hTK kinase domain (mutant) + cancer drug
3l9p, 3lcs, 3lct, 2yhv, 2yjr, 2yjs, 4fnw, 4fnx, 4anl - hTK kinase domain (mutant)

Csk tyrosine kinase

3eac - hTK SH2 domain
3eaz - hTK SH2 domain (mutant)
2rsy - hTK SH2 domain + CBP phosphopeptide - NMR
1csk - hTK SH3 domain
1jeg - hTK SH3 domain + tyrosine phosphatase peptide - NMR
1byg - hTK kinase domain + staurosporine
3d7t, 3d7u - hTK kinase domain (mutant) + C-Src
1k9a - TK C terminal - rat

Jak tyrosine kinase

See Janus kinase

p55-blk tyrosine kinase

1blj, 1blk - mTK p55-blk SH2 domain – NMR

Src tyrosine kinase

Src tyrosine kinase SH2 domain

4f59 - hTK (mutant)
1f2f - cTK (mutant)
1spr - RsvTK + phosphate – Rous sarcoma virus
1kc2 - RsvTK + peptide
1shd - cTK + TRKA receptor
4f5b - hTK (mutant) + phosphotyrosine
4f5a - hTK (mutant) + phosphate
1o4c - hTK + phosphate
1o41, 1o42, 1o43, 1o44, 1o45, 1o46, 1o47, 1o48, 1o49 1o4a, 1o4b, 1o4d 1o4e, 1o4f, 1o4g 1o4h, 1o4i, 1o4j 1o4k, 1o4l, 1o4m 1o4n, 1o4o, 1o4p 1o4q, 1o4r - hTK + inhibitor
1hcs, 1hct - hTK + peptide - NMR
1a07, 1a08, 1a09, 1a1a, 1a1b, 1a1c, 1a1e - hTK + peptide
1f1w - cTK (mutant) + peptide
1p13 - cTK + peptide

Src tyrosine kinase SH3 domain

1srl, 1srm - cTK – NMR
3fj5 - cTK
4hxj, 1prl - cTK + peptide
1prm, 1rlp, 1rlq, 1nlo, 1nlp - cTK + peptide - NMR
4hvu, 4hvv, 4hvw - cTK (mutant) + peptide

Src tyrosine kinase kinase domain

3of0, 2qi8 - cTK (mutant)
1yoj - hTK (mutant)
3tz7, 3tz8, 3tz9, 4dgg – cTK (mutant) + pyrazolin derivative
4fic, 3uqg, 3uqf, 3u51, 3u4w, 4agw, 3qlg, 3qlf, 3g6g, 3el8, 3f6x, 2hwo, 2hwp, 2oiq, 3en4, 3en5, 3en6, 3en7, 3el7 – cTK + inhibitor
4lgg, 4lgh, 3svv, 3oez, 3lok, 3g5d, 3f3w, 3f3v, 3geq, 3g6h, 3f3t, 3f3u, 2qlq, 2qq7, 4lgg, 4lgh – cTK (mutant) + inhibitor
1yol, 1yom – hTK (mutant) + inhibitor
2bdf, 2bdj – hTK + inhibitor
3d7t, 3d7u – cTK + Csk
3dqw, 3dqx - cTK (mutant) + ATP

Src tyrosine kinase C terminal domain

1yi6 - hTK

Src tyrosine kinase SH2+SH3+kinase domains

1ksw – hTK (mutant)+ ADP derivative

Src tyrosine kinase SH2+SH3+kinase+C terminal domains

1fmk – hTK
2ptk – cTK
2src – hTK + AMPPNP

Src tyrosine kinase N terminal+SH2+SH3+kinase domains

2h8h – hTK + inhibitor

Lymphocyte-specific tyrosine kinase Lck

1kik, 1h92 - hTK Lck SH3 domain – NMR
2iim - hTK Lck SH3 domain
4d8k, 1x27 - hTK Lck SH3-SH2 domain
3lck - hTK Lck kinase domain

Lck complex

1lcj, 1lkk, 1lkl - hTK Lck SH2 domain (mutant) + phosphopeptide
1cwd, 1cwe, 1ijr - hTK Lck SH2 domain + phosphopeptide
1bhf - hTK Lck SH2 domain + peptide inhibitor
1fbz - hTK Lck SH2 domain + inhibitor
1bhh - hTK Lck SH2 domain + T-lymphocyte-specific TK
1lck - hTK Lck SH3-SH2 domain (mutant) + phosphopeptide
1x27 - hTK Lck SH3-SH2 domain + peptide
1qpj - hTK Lck kinase domain + staurosporin
2of2, 2of4, 2ofu, 2ofv, 2og8, 3b2w, 3bym, 3bys, 3byu, 2zm1, 2zm4, 3byo, 2zyb, 3ac1, 3ac2, 3ac3, 3ac4, 3ac5, 3ac8, 3acj, 3ack, 3kmm, 3ad4, 3ad5, 3ad6, 1qpc, 1qpd, 1qpe - hTK Lck kinase domain + inhibitor
3mpm - hTK Lck kinase domain (mutant) + inhibitor
4c3f - hTK Lck kinase domain (mutant) + chemotype
2pl0 - hTK Lck kinase domain + imatinib
3kxz - hTK Lck kinase domain + probe molecule

Syk - spleen tyrosine kinase

1xba – Syk kinase domain

Syk complex

1xbb - Syk kinase domain + Gleevec
1xbc - Syk kinase domain + staurosporin
3emg, 3fqe, 3fqh, 3fqs, 3srv, 4dfl, 4dfn, 3vf8, 3vf9, 3tub, 3tuc, 3tud, 4f4p, 4fyn, 4fyo, 4fz6, 4fz7, 4gfg - Syk kinase domain + inhibitor
1csy, 1csz - Syk SH2 domain + phosphopeptide – NMR
4fl1, 4fl2 - Syk kinase domain + ANP
4fl3 - Syk kinase domain (mutant) + ANP
1a81 – Syk tandem SH2 domain + T-cell surface peptide

Itk tyrosine kinase

1lui, 1luk, 1lum, 1lun – mTK Itk SH2 domain – NMR
3s9k – mTK Itk SH2 domain
2etz, 2eu0 – hTK Itk SH2 domain + phosphopeptide – NMR
1awj, 2rn8, 2rna – mTK Itk SH3 domain – NMR
2yuq, 2lmj – hTK Itk SH3 domain – NMR
2k79, 2k7a – mTK Itk SH2+SH3 domains – NMR
1sm2, 1snu, 1snx – hTK Itk kinase domain
3miy – hTK Itk kinase domain + cancer drug
3v5j, 3v5l, 3v8t, 3v8w – hTK Itk kinase domain + inhibitor
3mj1, 3mj2, 3qgw, 3qgy, 4hct, 4hcu, 4hcv, 4kio – hTK Itk kinase domain (mutant) + inhibitor
3t9t – hTK Itk kinase domain (mutant) + arthritis drug
2e6i – hTK Itk BTK motif – NMR

Zap tyrosine kinase

2ozo - hTK Zap (mutant)
1m61 - hTK Zap SH2 domain

Zap complex

2oq1 - hTK Zap SH2 domain + peptide
1u59 - hTK Zap catalytic domain + staurosporin

2β tyrosine kinase

3cc6, 3fzo - hTK Pyk2 kinase domain
3gm2 - hTK Pyk2 FAT domain
3gm3 - hTK Pyk2 FAT domain (mutant)

Pyk2 complex

3fzp - hTK Pyk2 kinase domain + ATPγS
3fzr, 3fzs, 3fzt, 3h3c, 3et7 - hTK Pyk2 kinase domain + inhibitor
3gm1 - hTK Pyk2 FAT domain + paxillin peptide

CapAB tyrosine kinase

3bfv - SaTK CapA1/CapB2 – Staphylococcus aureus
2ved - SaTK CapA1/CapB2 + Mg + ADP

Fer tyrosine kinase

2kk6 - hTK Fer SH2 domain – NMR

Hck tyrosine kinase

3hck - hTK SH2 domain - NMR
1bu1 - hTK SH3 domain
4hck, 5hck - hTK SH3 domain - NMR
2oj2, 2oi3 - hTK SH3 domain + peptide - NMR
3rbb, 3rea, 3reb - hTK SH3 domain (mutant) + HIV NEF
3nhn - hTK SH3-SH2-linker domain
2c0i, 2c0o, 2c0t - hTK SH3-SH2-SH1 domain + inhibitor
2hk5 - hTK kinase domain + inhibitor
1qcf, 3vry, 3vrz, 3vs0, 3vs1, 3vs2, 3vs3, 3vs4, 3vs5, 3vs6, 3vs7 - hTK SH3-SH2-kinase-tail domain + inhibitor
1ad5 - hTK SH3-SH2-kinase-tail domain + AMPPNP
2hck - hTK SH3-SH2-kinase-tail domain + quercetin

Receptor tyrosine kinases - RTK

Bruton’s tyrosine kinase

2z0p - hTK Btk PH domain
1btk – hTK Btk PH domain (mutant)
3p08 - hTK Btk kinase domain
1aww, 1awx, 1qly - hTK Btk SH3 domain – NMR
2ge9 - hTK Btk SH2 domain – NMR

Btk complex

1b55 - hTK Btk PH domain + inositol-tetrakisphosphate
1bwn - hTK Btk PH domain (mutant) + inositol-tetrakisphosphate
3gen, 3ocs, 3pix, 3piy, 3piz, 3pj1, 3pj2, 3pj3 - hTK Btk kinase domain + inhibitor
3k54, 3t9t - hTK Btk kinase domain (mutant) + inhibitor
3oct - hTK Btk kinase domain (mutant) + cancer drug

Fms tyrosine kinase

2i0v - hTK Fms kinase domain

Fms complex

2i0y, 2i1m - hTK Fms kinase domain + inhibitor
3dpk - hTK Fms kinase domain (mutant) + inhibitor
1flt – hTK Fms Igg-like domain + VEGF
1qty - hTK Fms domain 2 + VEGF

Mer tyrosine kinase

2dbj - hTK Mer FN2 domain – NMR
2p0c - hTK Mer catalytic domain

Mer complex

3brb - hTK Mer catalytic domain + ADP
3bpr - hTK Mer catalytic domain + inhibitor

Bone marrow tyrosine kinase

2ekx - hTK Bmx SH2 domain – NMR
2ys2 - hTK Bmx Btk motif – NMR

Bmx complex

3sxr - hTK Bmx kinase domain (mutant) + dasatinib
3sxs - hTK Bmx kinase domain (mutant) + inhibitor

Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky, Joel L. Sussman

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