Protein: Thioester-containing protein 1 allele S3 (TEP1s) (TEP1-F) [Cleaved into: Thioester-containing protein 1 N-terminal (TEP1-N); Thioester-containing protein 1 C-terminal (TEP1-C)] (C9XI63)
Organism: Anopheles gambiae (African malaria mosquito)
Function: Plays an essential role in the innate immune response against bacteria, fungi and protozoa infection. After proteolytic cleavage, the protein C-terminus binds covalently through a thioester bond to the pathogen surface resulting in pathogen clearance either by melanization or lysis. Initiate the recruitment and activation of a cascade of proteases, mostly of CLIP-domain serine proteases, which leads to the proteolytic cleavage of the prophenoloxidase (PPO) into active phenoloxidase (PO), the rate-limiting enzyme in melanin biosynthesis. In response to parasite P.berghei-mediated infection, binds to and mediates killing of ookinetes, as they egress from midgut epithelial cells into the basal labyrinth, by both lysis and melanization. During bacterial infection, binds to both Gram-positive and Gram-negative bacteria but only promotes phagocytosis of Gram-negative bacteria. Promotes the accumulation of SPCLIP1 onto the surface of P.berghei ookinetes and bacterium E.coli which leads to the melanization of the pathogen. Recruits CLIPA2 to bacteria surface. In response to bacterial infection, required for periostial hemocyte aggregation, but not for the aggregation of sessile hemocytes in non-periostial regions. During the late stage of fungus B.bassiana-mediated infection, required for the initiation of hyphae melanization by binding to the surface of hyphae and recruiting prophenoloxidase PPO to them. Plays a role in male fertility by binding to defective sperm cells and promoting their removal during spermatogenesis (By similarity).
Subcellular location: Secreted {ECO:0000269|PubMed:15006349, ECO:0000269|PubMed:19286136, ECO:0000269|PubMed:23166497, ECO:0000269|PubMed:24039584, ECO:0000269|PubMed:25012124}. Note=Secreted as a full-length protein into the hemolymph. {ECO:0000269|PubMed:15006349, ECO:0000269|PubMed:19286136, ECO:0000269|PubMed:23166497, ECO:0000269|PubMed:24039584, ECO:0000269|PubMed:25012124}.
Sequence: MWQFIRSRILTVIIFIGAAHGLLVVGPKFIRANQEYTLVISNFNSQLSKVDLLLKLEGETDNGLSVLNVTKMVDVRRNMNRMINFNMPEDLTAGNYKITIDGQRGFSFHKEAELVYLSKSISGLIQVDKPVFKPGDTVNFRVIVLDTELKPPARVKSVHVTIRDPQRNVIRKWSTAKLYAGVFESDLQIAPTPMLGVWNISVEVEGEELVSKTFEVKEYVLSTFDVQVMPSVIPLEEHQAVNLTIEANYHFGKPVQGVAKVELYLDDDKLNQKKELTVYGKGQVELRFDNFAMDADQQDVRVKVSFIEQYTNRTVVKQSQITVYRYAYRVELIKESPQFRPGLPFKCALQFTHHDGTPAKGITGKVEVSDVGFETTKTSDNDGLIKLELQPSEGSEQLGINFNAVDGFFFYEDVNKVETVTDAYIKLELKSPIKRNKLMRFMVTCTERMTFFVYYVMSKGNIIDAGFMRPNKQTKYLLQLNATEKMIPKAKILIATVAGRTVVYDYADLDFQELRNNFDLSIDEQEIKPGRQIELSMSGRPGAYVGLAAYDKALLLFNKNHDLFWEDIGQVFDGFHAINENEFDIFHSLGLFARTLDDILFDSANEKTGRNALQSGKPIGKLVSYRTNFQESWLWKNVSIGRSGSRKLIEVVPDTTTSWYLTGFSIDPVYGLGIIKKPIQFTTVQPFYIVENLPYSIKRGEAVVLQFTLFNNLGAEYIADVTLYNVANQTEFVGRPDTDLSYTKSVSVPPKVGVPISFLIKARKLGEMAVRVKASIMLGHETDALEKVIRVMPESLAQPKMDTSFFCFDDYKNQTFPFNLDINKKADNGSKKIEFRLNPNLLTMVIKNLDNLLAVPTGCGEQNMVKFVPNILVLDYLYATGSKEQHLIDKATNLLRQGYQNQMRYRQTDGSFGVWEKSGSSVFLTAFVATSMQTASKYMNDIDAAMVEKALDWLASKQHSSGRFDETGKVWHKDMQGGLRNGVALTSYVLTALLENDIAKVKHAVVIQNGMNYLSNQLAFINNAYDLSIATYAMMLNGHTMKKEALDKLIDMSISDNNKKERYWGTTNQIETTAYALLSFVMAEKYLDGIPIMNWLVNQRYVTGSFPRTQDTFVGLKALTKLAEKISPSRNDYTVQLKYKKSTKYFNINSEQIDFQNFLEIPEDTKKLEINVGGIGFGLLEVIYQFDLNLVNFEHRFKLDLEKQNTGSDYELRLRVCANYIPELTDSQSNMALIEVTLPSGYVVDRNPISEQTTVNPIQNMEIRYGGTSVVLYYYNMGTERNCFTVTAYRRFKVALKRPAYVVVYDYYNTNLNAIKVYEVDKQNVCEICEEEDCPAEC
InterPro domains: - IPR008930: Terpenoid cyclases/protein prenyltransferase alpha-alpha toroid (homologous_superfamily) [845-1125]
- IPR050473: Alpha-2-macroglobulin/Complement system (family) [20-1335]
- IPR009048: Alpha-macroglobulin, receptor-binding (domain) [1228-1319]
- IPR041813: Alpha-2-macroglobulin, TED domain (domain) [845-1122]
- IPR036595: Alpha-macroglobulin, receptor-binding domain superfamily (homologous_superfamily) [1194-1338]
- IPR041555: Macroglobulin domain MG3 (domain) [218-293]
- IPR013783: Immunoglobulin-like fold (homologous_superfamily) [327-791]
- IPR001599: Alpha-2-macroglobulin (domain) [632-723]
- IPR011626: Alpha-macroglobulin-like, TED domain (domain) [844-1121]
- IPR019742: Alpha-2-macroglobulin, conserved site (conserved_site) [856-864]
- IPR011625: Alpha-2-macroglobulin, bait region domain (domain) [425-557]
- IPR049135: TEP1, second CUB domain (domain) [1127-1186]
- IPR002890: Macroglobulin domain (domain) [124-216]
- IPR047565: Alpha-macroglobulin-like, thiol-ester bond-forming region (conserved_site) [848-877]
- IPR040839: Macroglobulin domain MG4 (domain) [332-407]
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:0050789 (regulation of biological process), GO:0032879 (regulation of localization), GO:0002684 (positive regulation of immune system process), GO:0050794 (regulation of cellular process), GO:0002682 (regulation of immune system process), GO:0051050 (positive regulation of transport), GO:0048522 (positive regulation of cellular process), GO:0051049 (regulation of transport), GO:0002697 (regulation of immune effector process), GO:0050766 (positive regulation of phagocytosis), GO:0060627 (regulation of vesicle-mediated transport), GO:0051130 (positive regulation of cellular component organization), GO:0002699 (positive regulation of immune effector process), GO:0045807 (positive regulation of endocytosis), GO:0051128 (regulation of cellular component organization), GO:0030100 (regulation of endocytosis), GO:0050764 (regulation of phagocytosis), GO:0060100 (positive regulation of phagocytosis, engulfment), GO:1905153 (regulation of membrane invagination), GO:1905155 (positive regulation of membrane invagination), GO:0060099 (regulation of phagocytosis, engulfment)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005576 (extracellular region), GO:0005615 (extracellular space)