TEPS1_ANOGA
ID TEPS1_ANOGA Reviewed; 1340 AA.
AC Q9GYW4;
DT 03-AUG-2022, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 113.
DE RecName: Full=Thioester-containing protein 1 allele S1 {ECO:0000303|PubMed:23055931};
DE Short=TEP1s {ECO:0000250|UniProtKB:C9XI63};
DE AltName: Full=TEP1-F {ECO:0000250|UniProtKB:C9XI63};
DE AltName: Full=Thioester-containing protein I {ECO:0000303|PubMed:11257225};
DE Contains:
DE RecName: Full=Thioester-containing protein 1 N-terminal {ECO:0000250|UniProtKB:C9XI63};
DE Short=TEP1-N {ECO:0000250|UniProtKB:C9XI63};
DE Contains:
DE RecName: Full=Thioester-containing protein 1 C-terminal {ECO:0000250|UniProtKB:C9XI63};
DE Short=TEP1-C {ECO:0000250|UniProtKB:C9XI63};
DE Flags: Precursor;
GN Name=TEP1 {ECO:0000303|PubMed:23055931};
GN Synonyms=TEP-I {ECO:0000303|PubMed:11257225};
OS Anopheles gambiae (African malaria mosquito).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Nematocera; Culicoidea; Culicidae;
OC Anophelinae; Anopheles.
OX NCBI_TaxID=7165 {ECO:0000312|EMBL:AAG00600.1};
RN [1] {ECO:0000312|EMBL:AAG00600.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, DEVELOPMENTAL STAGE, INDUCTION, PROTEOLYTIC CLEAVAGE, AND
RP GLYCOSYLATION.
RC STRAIN=Suakoko {ECO:0000312|EMBL:AAG00600.1};
RX PubMed=11257225; DOI=10.1016/s0092-8674(01)00267-7;
RA Levashina E.A., Moita L.F., Blandin S., Vriend G., Lagueux M.,
RA Kafatos F.C.;
RT "Conserved role of a complement-like protein in phagocytosis revealed by
RT dsRNA knockout in cultured cells of the mosquito, Anopheles gambiae.";
RL Cell 104:709-718(2001).
RN [2] {ECO:0000305}
RP NOMENCLATURE, AND POLYMORPHISM.
RX PubMed=19797663; DOI=10.1126/science.1175241;
RA Blandin S.A., Wang-Sattler R., Lamacchia M., Gagneur J., Lycett G.,
RA Ning Y., Levashina E.A., Steinmetz L.M.;
RT "Dissecting the genetic basis of resistance to malaria parasites in
RT Anopheles gambiae.";
RL Science 326:147-150(2009).
RN [3] {ECO:0000305}
RP FUNCTION, AND POLYMORPHISM.
RX PubMed=26394016; DOI=10.1371/journal.pbio.1002255;
RA Pompon J., Levashina E.A.;
RT "A New Role of the Mosquito Complement-like Cascade in Male Fertility in
RT Anopheles gambiae.";
RL PLoS Biol. 13:e1002255-e1002255(2015).
RN [4] {ECO:0007744|PDB:4LNV}
RP X-RAY CRYSTALLOGRAPHY (3.70 ANGSTROMS) OF 22-1338, IDENTIFICATION IN A
RP COMPLEX WITH LRIM1 AND APL1C, PROTEOLYTIC CLEAVAGE, POLYMORPHISM,
RP GLYCOSYLATION AT ASN-68; ASN-242; ASN-312; ASN-481; ASN-637; ASN-728 AND
RP ASN-813, DISULFIDE BONDS, AND THIOESTER BOND.
RX PubMed=23055931; DOI=10.1371/journal.ppat.1002958;
RA Le B.V., Williams M., Logarajah S., Baxter R.H.;
RT "Molecular basis for genetic resistance of Anopheles gambiae to Plasmodium:
RT structural analysis of TEP1 susceptible and resistant alleles.";
RL PLoS Pathog. 8:e1002958-e1002958(2012).
CC -!- FUNCTION: Plays an essential role in the innate immune response to
CC bacteria and protozoa infection (PubMed:11257225). After proteolytic
CC cleavage, the protein C-terminus binds covalently through a thioester
CC bond to the pathogen surface resulting in pathogen clearance either by
CC melanization or lysis (PubMed:11257225). Initiate the recruitment and
CC activation of a cascade of proteases, mostly of CLIP-domain serine
CC proteases, which leads to the proteolytic cleavage of the
CC prophenoloxidase (PPO) into active phenoloxidase (PO), the rate-
CC limiting enzyme in melanin biosynthesis (By similarity). In response to
CC parasite P.berghei-mediated infection, binds to and mediates killing of
CC ookinetes, as they egress from midgut epithelial cells into the basal
CC labyrinth, by both lysis and melanization (By similarity). During
CC bacterial infection, binds to both Gram-positive and Gram-negative
CC bacteria but only promotes phagocytosis of Gram-negative bacteria
CC (PubMed:11257225). Promotes the accumulation of SPCLIP1 onto the
CC surface of P.berghei ookinetes and bacterium E.coli which leads to the
CC melanization of the pathogen (By similarity). Recruits CLIPA2 to
CC bacteria surface (By similarity). In response to bacterial infection,
CC required for periostial hemocyte aggregation, but not for the
CC aggregation of sessile hemocytes in non-periostial regions (By
CC similarity). During the late stage of fungus B.bassiana-mediated
CC infection, required for the initiation of hyphae melanization by
CC binding to the surface of hyphae and recruiting prophenoloxidase PPO to
CC them (By similarity). Plays a role in male fertility by binding to
CC defective sperm cells and promoting their removal during
CC spermatogenesis (PubMed:26394016). {ECO:0000250|UniProtKB:C9XI63,
CC ECO:0000269|PubMed:11257225, ECO:0000269|PubMed:26394016}.
CC -!- FUNCTION: [Thioester-containing protein 1 C-terminal]: Binds covalently
CC through a thioester bond to the pathogen surface resulting in pathogen
CC clearance. {ECO:0000269|PubMed:11257225}.
CC -!- SUBUNIT: Heterodimer of a TEP1-N chain and an TEP1-C chain non-
CC covalently linked (By similarity). Forms a complex composed of TEP1-N
CC and TEP1-C heterodimer, LRIM1 and APL1C; the interaction stabilizes
CC TEP1-N and TEP1-C heterodimer, prevents its binding to tissues while
CC circulating in the hemolymph and protects the thioester bond from
CC hydrolysis (PubMed:23055931). Mature TEP1 and to a lesser extent full-
CC length TEP1 interact with SPCLIP1; the interaction is induced by
CC microbial infection (By similarity). {ECO:0000250|UniProtKB:C9XI63,
CC ECO:0000269|PubMed:23055931}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:11257225}.
CC Note=Secreted as a full-length protein into the hemolymph.
CC {ECO:0000269|PubMed:11257225}.
CC -!- TISSUE SPECIFICITY: Specifically expressed in hemocytes (at protein
CC level). {ECO:0000269|PubMed:11257225}.
CC -!- DEVELOPMENTAL STAGE: Expressed in embryos, fourth instar larvae (L4),
CC young white pupae, old tanned pupae and in blood fed and non-fed adult
CC females (at protein level). {ECO:0000269|PubMed:11257225}.
CC -!- INDUCTION: By bacterium E.coli infection.
CC {ECO:0000269|PubMed:11257225}.
CC -!- PTM: In the hemolymph, the full-length protein is cleaved by an unknow
CC protease into a 75kDa N-terminal (TEP1-N) chain and an 80kDa C-terminal
CC (TEP1-C) chain which remain non-covalently linked (PubMed:11257225,
CC PubMed:23055931). The TEP1-C chain contains the thioester bond which
CC covalently binds to the pathogen surface (PubMed:11257225). Cleavage is
CC induced by bacterial infection or aseptic wound injury
CC (PubMed:11257225). During embryonic and pupal development, the cleaved
CC form is the predominant form (PubMed:11257225).
CC {ECO:0000269|PubMed:11257225, ECO:0000269|PubMed:23055931}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:11257225}.
CC -!- POLYMORPHISM: TEP1 gene is highly polymorphic mainly in the region
CC surrounding the thioester bond (PubMed:19797663, PubMed:23055931). Two
CC main alleles have been described, TEP1*S and TEP1*R (PubMed:19797663).
CC After proteolytic cleavage, TEP1*S alleles are more susceptible to
CC hydrolysis of the intramolecular thioester bond than TEP1*R alleles
CC (PubMed:23055931). In TEP1*S2 male mosquitos, removal of defective
CC sperm is more efficient resulting in enhanced male fertility
CC (PubMed:26394016). {ECO:0000269|PubMed:19797663,
CC ECO:0000269|PubMed:23055931, ECO:0000269|PubMed:26394016}.
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DR EMBL; AF291654; AAG00600.1; -; mRNA.
DR PDB; 4LNV; X-ray; 3.70 A; A/B/C=22-1338.
DR PDBsum; 4LNV; -.
DR SMR; Q9GYW4; -.
DR DIP; DIP-59386N; -.
DR IntAct; Q9GYW4; 2.
DR VEuPathDB; VectorBase:AGAP010815; -.
DR HOGENOM; CLU_001634_5_3_1; -.
DR OMA; YDNMGSE; -.
DR EvolutionaryTrace; Q9GYW4; -.
DR Proteomes; UP000007062; Unplaced.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0004866; F:endopeptidase inhibitor activity; IEA:InterPro.
DR GO; GO:1903028; P:positive regulation of opsonization; IMP:UniProtKB.
DR GO; GO:0060100; P:positive regulation of phagocytosis, engulfment; IMP:UniProtKB.
DR CDD; cd02897; A2M_2; 1.
DR Gene3D; 2.60.40.10; -; 2.
DR Gene3D; 2.60.40.690; -; 1.
DR InterPro; IPR009048; A-macroglobulin_rcpt-bd.
DR InterPro; IPR036595; A-macroglobulin_rcpt-bd_sf.
DR InterPro; IPR011625; A2M_N_BRD.
DR InterPro; IPR041813; A2M_TED.
DR InterPro; IPR011626; Alpha-macroglobulin_TED.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR001599; Macroglobln_a2.
DR InterPro; IPR019742; MacrogloblnA2_CS.
DR InterPro; IPR002890; MG2.
DR InterPro; IPR041555; MG3.
DR InterPro; IPR040839; MG4.
DR InterPro; IPR008930; Terpenoid_cyclase/PrenylTrfase.
DR Pfam; PF00207; A2M; 1.
DR Pfam; PF07703; A2M_BRD; 1.
DR Pfam; PF07677; A2M_recep; 1.
DR Pfam; PF01835; MG2; 1.
DR Pfam; PF17791; MG3; 1.
DR Pfam; PF17789; MG4; 1.
DR Pfam; PF07678; TED_complement; 1.
DR SMART; SM01360; A2M; 1.
DR SMART; SM01359; A2M_N_2; 1.
DR SMART; SM01361; A2M_recep; 1.
DR SUPFAM; SSF48239; SSF48239; 1.
DR SUPFAM; SSF49410; SSF49410; 1.
DR PROSITE; PS00477; ALPHA_2_MACROGLOBULIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Disulfide bond; Glycoprotein; Immunity; Reference proteome;
KW Secreted; Signal; Thioester bond.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..1340
FT /note="Thioester-containing protein 1 allele S1"
FT /evidence="ECO:0000255"
FT /id="PRO_0000455722"
FT CHAIN 22..?
FT /note="Thioester-containing protein 1 N-terminal"
FT /evidence="ECO:0000305|PubMed:11257225"
FT /id="PRO_0000455723"
FT CHAIN ?..1340
FT /note="Thioester-containing protein 1 C-terminal"
FT /evidence="ECO:0000305|PubMed:11257225"
FT /id="PRO_0000455724"
FT REGION 580..609
FT /note="May contain the cleavage site"
FT /evidence="ECO:0000250|UniProtKB:C9XI66"
FT CARBOHYD 68
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:23055931,
FT ECO:0007744|PDB:4LNV"
FT CARBOHYD 199
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 242
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:23055931,
FT ECO:0007744|PDB:4LNV"
FT CARBOHYD 312
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:23055931,
FT ECO:0007744|PDB:4LNV"
FT CARBOHYD 481
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:23055931,
FT ECO:0007744|PDB:4LNV"
FT CARBOHYD 637
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:23055931,
FT ECO:0007744|PDB:4LNV"
FT CARBOHYD 728
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:23055931,
FT ECO:0007744|PDB:4LNV"
FT CARBOHYD 813
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:23055931,
FT ECO:0007744|PDB:4LNV"
FT CARBOHYD 828
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 1217..1283
FT /evidence="ECO:0000269|PubMed:23055931,
FT ECO:0007744|PDB:4LNV"
FT DISULFID 1326..1338
FT /evidence="ECO:0000269|PubMed:23055931,
FT ECO:0007744|PDB:4LNV"
FT DISULFID 1329..1334
FT /evidence="ECO:0000269|PubMed:23055931,
FT ECO:0007744|PDB:4LNV"
FT CROSSLNK 859..862
FT /note="Isoglutamyl cysteine thioester (Cys-Gln)"
FT /evidence="ECO:0000269|PubMed:23055931"
SQ SEQUENCE 1340 AA; 152370 MW; D85821E08E9A18D3 CRC64;
MWQFIRSRIL TVIIFIGAAH GLLVVGPKFI RANQEYTLVI SNFNSQLSKV DLLLKLEGET
DNGLSVLNVT KMVDVRRNMN RMINFNMPEE LTAGNYKITI DGQRGFSFHK EAELVYLSKS
ISGLIQVDKP VFKPGDTVNF RVILLDTELK PPARVKSVYV TIRDPQRNVI RKWSTAKLYA
GVFESDLQIV PTPMLGVWNI SVEVEGEELV SKTFEVKEYV LSTFDVQVMP SVIPLEEHQA
VNLTIEANYH FGKPVQGVAK VELYLDDDKL NQKKELTVYG KGQVELRFDN FAMDADQQDV
RVKVSFIEQY TNRTVVKQSQ ITVYRYAYRV ELIKESPQFR PGLPFKCALQ FTHHDGTPAK
GITGKVEVSD VGFETTTTSD NDGLIKLELQ PSEGTEQLGI NFNAVDGFFF YEDVNKVETV
TDAYIKLELK SPIKRNKLMR FMVTCTERMT FFVYYVMSKG NIIDAGFMRP NKQTKYLLQL
NATEKMIPKA KILIATVAGR TVVYDYADLD FQELRNNFDL SIDEQEIKPG RQIELSMSGR
PGAYVGLAAY DKALLLFNKN HDLFWEDIGQ VFDGFHAINE NEFDIFHSLG LFARTLDDIL
FDSANEKTGR NALQSGKPIG KLVSYRTNFQ ESWLWKNVSI GRSGSRKLIE VVPDTTTSWY
LTGFSIDPVY GLGIIKKPIQ FTTVQPFYIV ENLPYSIKRG EAVVLQFTLF NNLGAEYIAD
VTLYNVANQT EFVGRPDTDL SYTKSVSVPP KVGVPISFLI KARKLGEMAV RVKASIMLGH
ETDALEKVIR VMPESLAQPK MDTSFFCFDD YKNQTFPFNL DINKKADNGS KKIEFRLNPN
LLTMVIKNLD NLLAVPTGCG EQNMVKFVPN ILVLDYLYAT GSKEQHLIDK ATNLLRQGYQ
NQMRYRQTDG SFGVWEKSGS SVFLTAFVAT SMQTASKYMN DIDAAMVEKA LDWLASKQHS
SGRFDETGKV WHKDMQGGLR NGVALTSYVL TALLENDIAK VKHAVVIQNG MNYLSNQLAF
INNPYDLSIA TYAMMLNGHT MKKEALDKLI DMSISDNNKK ERYWGTTNQI ETTAYALLSF
VMAEKYLDGI PVMNWLVNQR YVTGSFPRTQ DTFVGLKALT KLAEKISPSR NDYTVQLKYK
KNTKYFNINS EQIDVQNFLE IPEDTKKLEI NVGGIGFGLL EVIYQFDLNL VNFEHRFKLD
LEKQNTGSDY ELRLRVCANY IPELTDSQSN MALIEVTLPS GYVVDRNPIS EQTTVNPIQN
MEIRYGGTSV VLYYYKMGTE RNCFTVTAYR RFKVALKRPA YVVVYDYYNT NLNAIKVYEV
DKQNVCEICE EEDCPAECKK
