Protein: Breakpoint cluster region protein (EC 2.7.11.1) (Q6PAJ1)
Organism: Mus musculus (Mouse)
Function: Protein with a unique structure having two opposing regulatory activities toward small GTP-binding proteins. The C-terminus is a GTPase-activating protein (GAP) domain which stimulates GTP hydrolysis by RAC1, RAC2 and CDC42. Accelerates the intrinsic rate of GTP hydrolysis of RAC1 or CDC42, leading to down-regulation of the active GTP-bound form. The central Dbl homology (DH) domain functions as guanine nucleotide exchange factor (GEF) that modulates the GTPases CDC42, RHOA and RAC1. Promotes the conversion of CDC42, RHOA and RAC1 from the GDP-bound to the GTP-bound form. The amino terminus contains an intrinsic kinase activity (By similarity). Functions as an important negative regulator of neuronal RAC1 activity. Regulates macrophage functions such as CSF1-directed motility and phagocytosis through the modulation of RAC1 activity. Plays a major role as a RHOA GEF in keratinocytes being involved in focal adhesion formation and keratinocyte differentiation (By similarity).
Subcellular location: Postsynaptic density {ECO:0000269|PubMed:25331951}. Cell projection, dendritic spine {ECO:0000269|PubMed:20962234}. Cell projection, axon {ECO:0000269|PubMed:20962234}. Synapse {ECO:0000250|UniProtKB:F1LXF1}.
Sequence: MVDSVGFAEAWRAQFPDSEPPRMELRSVGDIEQELERCKASIRRLEQEVNQERFRMIYLQTLLAKEKKSYDRQRWGFRRAAQPPDGAAEPRASAPRPPPAPADGADPAPVEESEARPDGEGSPSKGRSASARRPAAAASADRDDRGPPTSVAALRSNFEKIRKGPAQPGSADAEKPFYVNVEFHHERGLVKVNDKEVSDRISSLGSQAMQMERKKSQQSAGQGLGEAPRPHYRGRSSESSCGLDGDYEDAELNPRFLKDNLINANGGNRPPWPPLEYQPYQSIYVGGMMVEGEGKSPLLRSQSTSEQEKRLTWPRRSYSPRSFEDSGGGYTPDCSSNENLTSSEEDFSSGQSSRVSPSPTTYRMFRDKSRSPSQNSQQSFDSSSPPTPQCQKRHRQCQVVVSEATIVGVRKTGQIWPSDGDSTFQGEADSSFGTPPGYGCAADQAEEQRRHQDGLPYIDDSPSSSPHLSSKGRGSLASGALDPTKVSELDLEKGLEMRKWVLSGILASEETYLSHLEALLLPMKPLKAAATTSQPVLTSQQIETIFFKVPELYEIHKEFYDGLFPRVQQWSHQQRVGDLFQKLASQLGVYRAFVDNYGVAMETAEKCCQANAQFAEISENLRARSNKDVKDSTTKNSLETLLYKPVDRVTRSTLVLHDLLKHTPSSHPDHSLLQDALRISQNFLSSINEEITPRRQSMTVKKGEHRQLLKDSFMVELVEGARKLRHIFLFTDLLLCTKLKKQSGGKTQQYDCKWYIPLTDLSFQMVDELEALPNIPLVPDEELDALKIKISQIKSDIQREKRANKGSKVMERLRKKLSEQESLLLLMSPSMAFRVHSRNGKSYTFLISSDYERAEWRESIREQQKKCFKSFSLTSVELQMLTNSCVKLQTVHHIPLTINKEDDESPGLYGFLHVIVHSATGFKQSSNLYCTLEVDSFGYFVNKAKTRVYRDTTEPNWNEEFEIELEGSQTLRILCYEKCYNKMKMTKEDGESADKLMGKGQVQLDPQTLQDRDWQRTVIDMNGIEVKLSVKFTSREFSLKRMPSRKQTGVFGVKIAVVTKRERSKVPYIVRQCVEEIERRGMEEVGIYRVSGVATDIQALKAAFDVNNKDVSVMMSEMDVNAIAGTLKLYFRELPEPLFTDEFYPNFAEGIALSDPVAKESCMLNLLLSLPEANLLTFLFLLDHLKRVAEKETVNKMSLHNLATVFGPTLLRPSEKESKLPANPSQPITMTDSWSLEVMSQVQVLLYFLQLEAIPAPDSKRQSILFSTEV
InterPro domains: - IPR000219: Dbl homology domain (domain) [497-690]
- IPR035892: C2 domain superfamily (homologous_superfamily) [909-1038]
- IPR015123: Bcr-Abl oncoprotein oligomerisation (domain) [4-75]
- IPR001849: Pleckstrin homology domain (domain) [707-867]
- IPR000008: C2 domain (domain) [892-1019]
- IPR000198: Rho GTPase-activating protein domain (domain) [1053-1248]
- IPR035899: Dbl homology (DH) domain superfamily (homologous_superfamily) [486-691]
- IPR001331: Guanine-nucleotide dissociation stimulator, CDC24, conserved site (conserved_site) [638-663]
- IPR008936: Rho GTPase activation protein (homologous_superfamily) [1039-1250]
- IPR037769: Abr/Bcr (family) [1-1267]
- IPR036481: Bcr-Abl oncoprotein oligomerisation domain superfamily (homologous_superfamily) [1-72]
- IPR011993: PH-like domain superfamily (homologous_superfamily) [691-894]
Interaction partners: - Growth factor receptor-bound protein 2
- Tyrosine-protein kinase ABL1
- Crk-like protein
- Adapter molecule crk
- Signal transducer and activator of transcription
- E3 ubiquitin-protein ligase CBL
- SHC-transforming protein 1
- Signal transducer and activator of transcription 5B
- SHC-transforming protein 3
- SHC-transforming protein 2
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0005515 (protein binding)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0050789 (regulation of biological process), GO:0023052 (signaling), GO:0032501 (multicellular organismal process), GO:0065007 (biological regulation), GO:0050896 (response to stimulus), GO:0032502 (developmental process), GO:0009987 (cellular process), GO:0048869 (cellular developmental process), GO:0048856 (anatomical structure development), GO:0007275 (multicellular organism development), GO:0009653 (anatomical structure morphogenesis), GO:0006807 (nitrogen compound metabolic process), GO:0071840 (cellular component organization or biogenesis), GO:0071704 (organic substance metabolic process), GO:0044237 (cellular metabolic process), GO:0050794 (regulation of cellular process), GO:0048583 (regulation of response to stimulus), GO:0051716 (cellular response to stimulus), GO:0023051 (regulation of signaling), GO:0065009 (regulation of molecular function), GO:0007154 (cell communication), GO:0007165 (signal transduction), GO:0044238 (primary metabolic process), GO:0050790 (regulation of catalytic activity), GO:0044093 (positive regulation of molecular function), GO:1901564 (organonitrogen compound metabolic process), GO:0035556 (intracellular signal transduction), GO:0048468 (cell development), GO:0030154 (cell differentiation), GO:0048731 (system development), GO:0019538 (protein metabolic process), GO:0048513 (animal organ development), GO:0009966 (regulation of signal transduction), GO:0043170 (macromolecule metabolic process), GO:0006793 (phosphorus metabolic process), GO:0009887 (animal organ morphogenesis), GO:0009888 (tissue development), GO:0010646 (regulation of cell communication), GO:0016043 (cellular component organization), GO:0060021 (roof of mouth development), GO:0030030 (cell projection organization), GO:0051336 (regulation of hydrolase activity), GO:0042476 (odontogenesis), GO:0006796 (phosphate-containing compound metabolic process), GO:0048666 (neuron development), GO:0036211 (protein modification process), GO:0022008 (neurogenesis), GO:0043412 (macromolecule modification), GO:0007399 (nervous system development), GO:0007264 (small GTPase mediated signal transduction), GO:0043085 (positive regulation of catalytic activity), GO:0060429 (epithelium development), GO:0030182 (neuron differentiation), GO:1902531 (regulation of intracellular signal transduction), GO:0006468 (protein phosphorylation), GO:0120036 (plasma membrane bounded cell projection organization), GO:0018193 (peptidyl-amino acid modification), GO:0016310 (phosphorylation), GO:0043087 (regulation of GTPase activity), GO:0031175 (neuron projection development), GO:0051056 (regulation of small GTPase mediated signal transduction), GO:0048699 (generation of neurons), GO:0051345 (positive regulation of hydrolase activity), GO:0042475 (odontogenesis of dentin-containing tooth), GO:0046578 (regulation of Ras protein signal transduction), GO:0043547 (positive regulation of GTPase activity), GO:0051924 (regulation of calcium ion transport), GO:0018210 (peptidyl-threonine modification), GO:0018105 (peptidyl-serine phosphorylation), GO:0018107 (peptidyl-threonine phosphorylation), GO:0018209 (peptidyl-serine modification), GO:0090630 (activation of GTPase activity)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0098794 (postsynapse), GO:0005737 (cytoplasm), GO:0071944 (cell periphery), GO:0030054 (cell junction), GO:0045202 (synapse), GO:0005938 (cell cortex), GO:0099572 (postsynaptic specialization), GO:0098984 (neuron to neuron synapse), GO:0098982 (GABA-ergic synapse), GO:0014069 (postsynaptic density), GO:0032279 (asymmetric synapse)