3bun: Difference between revisions
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{{STRUCTURE_3bun| PDB=3bun | SCENE= }} | {{STRUCTURE_3bun| PDB=3bun | SCENE= }} | ||
===Crystal structure of c-Cbl-TKB domain complexed with its binding motif in Sprouty4=== | ===Crystal structure of c-Cbl-TKB domain complexed with its binding motif in Sprouty4=== | ||
{{ABSTRACT_PUBMED_18273061}} | |||
==Disease== | |||
[[http://www.uniprot.org/uniprot/CBL_HUMAN CBL_HUMAN]] Defects in CBL are the cause of Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia (NSLL) [MIM:[http://omim.org/entry/613563 613563]]. A syndrome characterized by a phenotype reminiscent of Noonan syndrome. Clinical features are highly variable, including facial dysmorphism, short neck, developmental delay, hyperextensible joints and thorax abnormalities with widely spaced nipples. The facial features consist of triangular face with hypertelorism, large low-set ears, ptosis, and flat nasal bridge. Some patients manifest cardiac defects.<ref>PMID:20619386</ref> | |||
==Function== | |||
[[http://www.uniprot.org/uniprot/SPY4_HUMAN SPY4_HUMAN]] Suppresses the insulin receptor and EGFR-transduced MAPK signaling pathway, but does not inhibit MAPK activation by a constitutively active mutant Ras. Probably impairs the formation of GTP-Ras. Inhibits Ras-independent, but not Ras-dependent, activation of RAF1.<ref>PMID:12717443</ref> [[http://www.uniprot.org/uniprot/CBL_HUMAN CBL_HUMAN]] Adapter protein that functions as a negative regulator of many signaling pathways that are triggered by activation of cell surface receptors. Acts as an E3 ubiquitin-protein ligase, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and then transfers it to substrates promoting their degradation by the proteasome. Recognizes activated receptor tyrosine kinases, including KIT, FLT1, FGFR1, FGFR2, PDGFRA, PDGFRB, EGFR, CSF1R, EPHA8 and KDR and terminates signaling. Recognizes membrane-bound HCK and other kinases of the SRC family and mediates their ubiquitination and degradation. Participates in signal transduction in hematopoietic cells. Plays an important role in the regulation of osteoblast differentiation and apoptosis. Essential for osteoclastic bone resorption. The Tyr-731 phosphorylated form induces the activation and recruitment of phosphatidylinositol 3-kinase to the cell membrane in a signaling pathway that is critical for osteoclast function.<ref>PMID:10514377</ref><ref>PMID:11896602</ref><ref>PMID:14739300</ref><ref>PMID:15190072</ref><ref>PMID:17509076</ref><ref>PMID:18374639</ref><ref>PMID:19689429</ref><ref>PMID:21596750</ref> | |||
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==About this Structure== | ==About this Structure== | ||
[[3bun]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BUN OCA]. | |||
==Reference== | ==Reference== | ||
<ref group="xtra">PMID: | <ref group="xtra">PMID:018273061</ref><references group="xtra"/><references/> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Buschdorf, J P.]] | [[Category: Buschdorf, J P.]] | ||
| Line 31: | Line 21: | ||
[[Category: Sivaraman, J.]] | [[Category: Sivaraman, J.]] | ||
[[Category: Sun, Q.]] | [[Category: Sun, Q.]] | ||
[[Category: Cbl]] | [[Category: Cbl]] | ||
[[Category: Complex]] | [[Category: Complex]] | ||
[[Category: Developmental protein]] | [[Category: Developmental protein]] | ||
[[Category: Ligase]] | [[Category: Ligase]] | ||
[[Category: Ligase | [[Category: Ligase-signaling protein complex]] | ||
[[Category: Membrane]] | [[Category: Membrane]] | ||
[[Category: Metal-binding]] | [[Category: Metal-binding]] | ||
| Line 47: | Line 34: | ||
[[Category: Tkb]] | [[Category: Tkb]] | ||
[[Category: Ubl conjugation pathway]] | [[Category: Ubl conjugation pathway]] | ||
[[Category: Zinc-finger]] | [[Category: Zinc-finger]] | ||