Protein: Malignant fibrous histiocytoma-amplified sequence 1 (Malignant fibrous histiocytoma-amplified sequence with leucine-rich tandem repeats 1) (Q9Y4C4)
Organism: Homo sapiens (Human)
Function: Probable GTP-binding protein. Functions in innate immunity and more specifically the inflammatory response as a regulator of the Toll-like receptor TLR2 and TLR4 signaling pathways. Negatively regulates the part of the TLR4 signaling pathway that leads to the activation of the transcription factor AP-1. By retaining the phosphatase complex PP2A into the cytoplasm, prevents the dephosphorylation of the AP-1 subunit JUN which is required for proper activation of the transcription factor. Both inhibits and activates the TLR2-dependent signaling pathway. Positively regulates the TLR2 signaling pathway to activate specifically the downstream p38 and JNK MAP kinases and promote the polarization of macrophages toward the pro-inflammatory M1 phenotype. It may also play a role in the regulation of inflammation induced by high glucose through the PKB/AKT signaling pathway. Also involved in erythrocyte differentiation through activation of the ERK1/ERK2 signaling pathway.
Subcellular location: Cytoplasm {ECO:0000269|PubMed:24286120}.
Sequence: MAGMDSGNLKTARLWRDAALRARKLRSNLRQLTLTAAGACPGAGADALESPASPQLVLPANLGDIEALNLGNNGLEEVPEGLGSALGSLRVLVLRRNRFARLPPAVAELGHHLTELDVSHNRLTALGAEVVSALRELRKLNLSHNQLPALPAQLGALAHLEELDVSFNRLAHLPDSLSCLSRLRTLDVDHNQLTAFPRQLLQLVALEELDVSSNRLRGLPEDISALRALKILWLSGAELGTLPAGFCELASLESLMLDNNGLQALPAQFSCLQRLKMLNLSSNLFEEFPAALLPLAGLEELYLSRNQLTSVPSLISGLGRLLTLWLDNNRIRYLPDSIVELTGLEELVLQGNQIAVLPDHFGQLSRVGLWKIKDNPLIQPPYEVCMKGIPYIAAYQKELAHSQPAVQPRLKLLLMGHKAAGKTLLRHCLTEERVEGCPGGGDKEKCYPPSPPPVSKGIEVTSWTADASRGLRFIVYDLAGDESYEVIQPFFLSPGALYVLVVNLATYEPRHFPTTVGSFLHRVGARVPHAVVCIVGTHADLCGERELEEKCLDIHRQIALQEKHDAEGLSRLAKVVDEALARDFELRSASPHAAYYGVSDKNLRRRKAHFQYLLNHRLQILSPVLPVSCRDPRHLRRLRDKLLSVAEHREIFPNLHRVLPRSWQVLEELHFQPPQAQRLWLSWWDSARLGLQAGLTEDRLQSALSYLHESGKLLYFEDSPALKEHVFHNLTRLIDILNVFFQRDPSLLLHKLLLGTSGEGKAEGESSPPMARSTPSQELLRATQLHQYVEGFLLHGLLPAHVIRLLLKPHVQAQQDLQLLLELLEKMGLCYCLNKPKGKPLNGSTAWYKFPCYVQNEVPHAEAWINGTNLAGQSFVAEQLQIEYSFPFTFPLGLFARYSVQINSHVVHRSDGKFQIFAYRGKVPVVVSYRPARGVLQPDTLSIASHASLPNIWTAWQAITPLVEELNVLLQEWPGLHYTVHILCSKCLKRGSPNPHAFPGELLSQPRPEGVAEIICPKNGSERVNVALVYPPTPTVISPCSKKNVGEKHRNQ
InterPro domains: - IPR032675: Leucine-rich repeat domain superfamily (homologous_superfamily) [46-387]
- IPR020859: Roc domain (domain) [403-649]
- IPR003591: Leucine-rich repeat, typical subtype (repeat) [62-364]
- IPR027417: P-loop containing nucleoside triphosphate hydrolase (homologous_superfamily) [408-670]
- IPR001611: Leucine-rich repeat (repeat) [112-341]
- IPR050216: Leucine-rich repeat domain-containing protein (family) [239-512]
Interaction partners: - Claudin-23
- Protein phosphatase 1 regulatory subunit 3B
- E3 ubiquitin-protein ligase Praja-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:0065007 (biological regulation), GO:0048518 (positive regulation of biological process), GO:0050896 (response to stimulus), GO:0050789 (regulation of biological process), GO:0044419 (biological process involved in interspecies interaction between organisms), GO:0002376 (immune system process), GO:0048519 (negative regulation of biological process), GO:0009605 (response to external stimulus), GO:0023056 (positive regulation of signaling), GO:0023057 (negative regulation of signaling), GO:0048584 (positive regulation of response to stimulus), GO:0002683 (negative regulation of immune system process), GO:0009607 (response to biotic stimulus), GO:0006955 (immune response), GO:0002684 (positive regulation of immune system process), GO:0050794 (regulation of cellular process), GO:0048583 (regulation of response to stimulus), GO:0002682 (regulation of immune system process), GO:0023051 (regulation of signaling), GO:0006950 (response to stress), GO:0048523 (negative regulation of cellular process), GO:0051707 (response to other organism), GO:0048585 (negative regulation of response to stimulus), GO:0048522 (positive regulation of cellular process), GO:0009967 (positive regulation of signal transduction), GO:0009968 (negative regulation of signal transduction), GO:0010648 (negative regulation of cell communication), GO:0002831 (regulation of response to biotic stimulus), GO:0032103 (positive regulation of response to external stimulus), GO:0050776 (regulation of immune response), GO:0043207 (response to external biotic stimulus), GO:0010646 (regulation of cell communication), GO:0080134 (regulation of response to stress), GO:0002833 (positive regulation of response to biotic stimulus), GO:0009966 (regulation of signal transduction), GO:0006952 (defense response), GO:0050778 (positive regulation of immune response), GO:0032101 (regulation of response to external stimulus), GO:0010647 (positive regulation of cell communication), GO:0031349 (positive regulation of defense response), GO:0045087 (innate immune response), GO:0098542 (defense response to other organism), GO:0031347 (regulation of defense response), GO:0045089 (positive regulation of innate immune response), GO:0006954 (inflammatory response), GO:0045088 (regulation of innate immune response), GO:0062207 (regulation of pattern recognition receptor signaling pathway), GO:0062208 (positive regulation of pattern recognition receptor signaling pathway), GO:0034121 (regulation of toll-like receptor signaling pathway)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0005737 (cytoplasm), GO:0012505 (endomembrane system), GO:0005794 (Golgi apparatus), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle)