TTR52_CAEEL
ID TTR52_CAEEL Reviewed; 135 AA.
AC G5ED35;
DT 01-MAY-2013, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 1.
DT 03-AUG-2022, entry version 45.
DE RecName: Full=Transthyretin-like protein 52 {ECO:0000303|PubMed:20526330};
DE Flags: Precursor;
GN Name=ttr-52 {ECO:0000312|EMBL:CCO25654.1}; ORFNames=F11F1.7;
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1] {ECO:0000305, ECO:0000312|EMBL:ADO60154.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], FUNCTION, SUBCELLULAR LOCATION,
RP TISSUE SPECIFICITY, INTERACTION WITH CED-1, DISRUPTION PHENOTYPE, AND
RP MUTAGENESIS OF 11-PHE--PHE-12; VAL-43 AND 50-GLU--LEU-55.
RX PubMed=20526330; DOI=10.1038/ncb2068;
RA Wang X., Li W., Zhao D., Liu B., Shi Y., Chen B., Yang H., Guo P., Geng X.,
RA Shang Z., Peden E., Kage-Nakadai E., Mitani S., Xue D.;
RT "Caenorhabditis elegans transthyretin-like protein TTR-52 mediates
RT recognition of apoptotic cells by the CED-1 phagocyte receptor.";
RL Nat. Cell Biol. 12:655-664(2010).
RN [2] {ECO:0000312|EMBL:CCO25654.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|EMBL:CCO25654.1};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [3] {ECO:0000305}
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=22727702; DOI=10.1016/j.cub.2012.05.052;
RA Mapes J., Chen Y.Z., Kim A., Mitani S., Kang B.H., Xue D.;
RT "CED-1, CED-7, and TTR-52 regulate surface phosphatidylserine expression on
RT apoptotic and phagocytic cells.";
RL Curr. Biol. 22:1267-1275(2012).
RN [4] {ECO:0000305}
RP FUNCTION, AND INTERACTION WITH NRF-5.
RX PubMed=22727700; DOI=10.1016/j.cub.2012.06.004;
RA Zhang Y., Wang H., Kage-Nakadai E., Mitani S., Wang X.;
RT "C. elegans secreted lipid-binding protein NRF-5 mediates PS appearance on
RT phagocytes for cell corpse engulfment.";
RL Curr. Biol. 22:1276-1284(2012).
RN [5] {ECO:0000305, ECO:0000312|PDB:3UAF}
RP X-RAY CRYSTALLOGRAPHY (2.01 ANGSTROMS) OF 21-135 OF MUTANT 50-GLU--LEU-55,
RP INTERACTION WITH CED-1, HOMODIMERIZATION, SUBCELLULAR LOCATION, DISRUPTION
RP PHENOTYPE, AND MUTAGENESIS OF ASP-36; GLU-38; ASP-51; LEU-53; PRO-54;
RP LEU-55; ARG-63; TRP-65; GLN-73; ASP-80; PRO-83; ASN-85; ARG-100; ASP-101;
RP ILE-113; LEU-132 AND 131-TYR--TYR-135.
RX PubMed=22713871; DOI=10.1101/gad.187815.112;
RA Kang Y., Zhao D., Liang H., Liu B., Zhang Y., Liu Q., Wang X., Liu Y.;
RT "Structural study of TTR-52 reveals the mechanism by which a bridging
RT molecule mediates apoptotic cell engulfment.";
RL Genes Dev. 26:1339-1350(2012).
CC -!- FUNCTION: Plays a role as a bridging molecule that mediates recognition
CC and engulfment of apoptotic cells by cross-linking the surface-exposed
CC phosphatidylserine with the extracellular domain of the phagocyte
CC receptor ced-1. Important for the generation of extracellular
CC phosphatidylserine vesicles that promote loss of the exoplasmic leaflet
CC from apoptotic cells in a time-dependent manner. Required for the
CC exposure of exoplasmic leaflet on the phagocytic cells surrounding the
CC apoptotic cells. Does not affect the phosphatidylserine externalization
CC in living cells. May play a role in mediating transfer of
CC phosphatidylserine from phosphatidylserine vesicles to ced-1 bearing
CC phagocytes or alternatively result in the activation of a
CC phosphatidylserine transporter in the phagocyte that promotes
CC phosphatidylserine externalization. {ECO:0000269|PubMed:20526330,
CC ECO:0000269|PubMed:22727700, ECO:0000269|PubMed:22727702}.
CC -!- SUBUNIT: Homodimer. Interacts with ced-1. Interacts with nrf-5.
CC {ECO:0000269|PubMed:20526330, ECO:0000269|PubMed:22713871,
CC ECO:0000269|PubMed:22727700}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:20526330,
CC ECO:0000269|PubMed:22713871, ECO:0000269|PubMed:22727702}. Cell surface
CC {ECO:0000269|PubMed:20526330, ECO:0000269|PubMed:22713871,
CC ECO:0000269|PubMed:22727702}. Note=Detected almost exclusively on the
CC surface of apoptotic cells. In some embryos, also observed on surface
CC of cells adjacent to dying cells. {ECO:0000269|PubMed:20526330,
CC ECO:0000269|PubMed:22713871, ECO:0000269|PubMed:22727702}.
CC -!- TISSUE SPECIFICITY: Expressed in the intestine cells.
CC {ECO:0000269|PubMed:20526330}.
CC -!- DISRUPTION PHENOTYPE: Loses ability to bind apoptotic cells and results
CC in reduced ability of cell corpse engulfment.
CC {ECO:0000269|PubMed:20526330, ECO:0000269|PubMed:22713871}.
CC -!- SIMILARITY: Belongs to the nematode transthyretin-like family.
CC {ECO:0000255}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; HM130527; ADO60153.1; -; mRNA.
DR EMBL; HM130528; ADO60154.1; -; Genomic_DNA.
DR EMBL; Z81059; CCO25654.1; -; Genomic_DNA.
DR RefSeq; NP_001263732.1; NM_001276803.1.
DR PDB; 3UAF; X-ray; 2.01 A; A=21-135.
DR PDBsum; 3UAF; -.
DR AlphaFoldDB; G5ED35; -.
DR SMR; G5ED35; -.
DR STRING; 6239.F11F1.7; -.
DR PaxDb; G5ED35; -.
DR EnsemblMetazoa; F11F1.7.1; F11F1.7.1; WBGene00008719.
DR GeneID; 184363; -.
DR CTD; 184363; -.
DR WormBase; F11F1.7; CE47922; WBGene00008719; ttr-52.
DR eggNOG; ENOG502SV2S; Eukaryota.
DR HOGENOM; CLU_134800_0_0_1; -.
DR InParanoid; G5ED35; -.
DR OMA; DFGPFNT; -.
DR OrthoDB; 1575315at2759; -.
DR PRO; PR:G5ED35; -.
DR Proteomes; UP000001940; Chromosome III.
DR Bgee; WBGene00008719; Expressed in pharyngeal muscle cell (C elegans) and 3 other tissues.
DR GO; GO:0009986; C:cell surface; IDA:WormBase.
DR GO; GO:1903561; C:extracellular vesicle; IDA:WormBase.
DR GO; GO:0001786; F:phosphatidylserine binding; IDA:WormBase.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:WormBase.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; IPI:WormBase.
DR GO; GO:0005124; F:scavenger receptor binding; IPI:WormBase.
DR GO; GO:0015917; P:aminophospholipid transport; IMP:WormBase.
DR GO; GO:1902742; P:apoptotic process involved in development; IMP:UniProtKB.
DR GO; GO:0043654; P:recognition of apoptotic cell; IDA:WormBase.
DR Gene3D; 2.60.40.3330; -; 1.
DR InterPro; IPR001534; Transthyretin-like.
DR InterPro; IPR038479; Transthyretin-like_sf.
DR PANTHER; PTHR21700; PTHR21700; 1.
DR Pfam; PF01060; TTR-52; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Apoptosis; Reference proteome; Secreted; Signal.
FT SIGNAL 1..20
FT /evidence="ECO:0000269|PubMed:20526330"
FT CHAIN 21..135
FT /note="Transthyretin-like protein 52"
FT /evidence="ECO:0000269|PubMed:20526330"
FT /id="PRO_0000422246"
FT REGION 131..135
FT /note="Required for mediating binding of apoptotic cells by
FT ced-1"
FT /evidence="ECO:0000269|PubMed:22713871"
FT MUTAGEN 11..12
FT /note="FF->DD: Loss of cell corpse engulfment function."
FT /evidence="ECO:0000269|PubMed:20526330"
FT MUTAGEN 36
FT /note="D->A: Partial loss in ability to recognize apoptotic
FT cells. Partial rescue of engulfment defect of the deletion
FT mutant tm2078. Retains phosphatidylserine binding
FT specificity; when associated with A-38."
FT /evidence="ECO:0000269|PubMed:22713871"
FT MUTAGEN 38
FT /note="E->A: Partial loss in ability to recognize apoptotic
FT cells. Partial rescue of engulfment defect of the deletion
FT mutant tm2078. Retains phosphatidylserine binding
FT specificity; when associated with A-36."
FT /evidence="ECO:0000269|PubMed:22713871"
FT MUTAGEN 43
FT /note="V->M: In sm211; results in increased number of cell
FT corpses and abolishes secretion of the protein."
FT /evidence="ECO:0000269|PubMed:20526330"
FT MUTAGEN 50..55
FT /note="EDSLPL->AAAAA: In M5; Loss of binding to
FT phosphatidylserine and loss of ability to bind apoptotic
FT cells and rescue the engulfment defect in the sm211 mutant
FT phenotype."
FT /evidence="ECO:0000269|PubMed:20526330"
FT MUTAGEN 51
FT /note="D->A: Loss of function of engulfment of apoptotic
FT cells. Decreased membrane labeling and phosphatidylserine
FT binding and failure to rescue the engulfment defect of the
FT deletion mutant tm2078."
FT /evidence="ECO:0000269|PubMed:22713871"
FT MUTAGEN 53
FT /note="L->A: Reduced ability in identification of apoptotic
FT cells but can rescue the engulfment defect of the deletion
FT mutant tm2078."
FT /evidence="ECO:0000269|PubMed:22713871"
FT MUTAGEN 54
FT /note="P->A: Reduced ability in identification of apoptotic
FT cells but can partially rescue the engulfment defect of the
FT deletion mutant tm2078."
FT /evidence="ECO:0000269|PubMed:22713871"
FT MUTAGEN 55
FT /note="L->A: Reduced ability in identification of apoptotic
FT cells but can rescue the engulfment defect of the deletion
FT mutant tm2078."
FT /evidence="ECO:0000269|PubMed:22713871"
FT MUTAGEN 63
FT /note="R->D: Monomeric with defective clustering of ced-1
FT around apoptotic cells in the embryos of the deletion
FT mutant tm2078; when associated with Q-65 and A-73."
FT /evidence="ECO:0000269|PubMed:22713871"
FT MUTAGEN 65
FT /note="W->Q: Monomeric with defective clustering of ced-1
FT around apoptotic cells in the embryos of the deletion
FT mutant tm2078; when associated with D-63 and A-73."
FT /evidence="ECO:0000269|PubMed:22713871"
FT MUTAGEN 73
FT /note="Q->A: Monomeric with defective clustering of ced-1
FT around apoptotic cells in the embryos of the deletion
FT mutant tm2078; when associated with D-63 and Q-65."
FT /evidence="ECO:0000269|PubMed:22713871"
FT MUTAGEN 80
FT /note="D->A: Loss of function of engulfment of apoptotic
FT cells. Decreased membrane labeling and phosphatidylserine
FT binding and failure to rescue the engulment defect of the
FT deletion mutant tm2078."
FT /evidence="ECO:0000269|PubMed:22713871"
FT MUTAGEN 83
FT /note="P->D: Loss of ability to form ring around apoptotic
FT cells and abolished ability in cell corpse removal."
FT /evidence="ECO:0000269|PubMed:22713871"
FT MUTAGEN 85
FT /note="N->A: Loss of function of engulfment of apoptotic
FT cells. Decreased membrane labeling and phosphatidylserine
FT binding and failure to rescue the engulfment defect of the
FT deletion mutant tm2078."
FT /evidence="ECO:0000269|PubMed:22713871"
FT MUTAGEN 100
FT /note="R->A: Partial loss of ability to recognize apoptotic
FT cells. Partial rescue of the engulfment defect of the
FT deletion mutant tm2078. Retains phosphatidylserine binding
FT specificity; when associated with A-101."
FT /evidence="ECO:0000269|PubMed:22713871"
FT MUTAGEN 101
FT /note="D->A: Partial loss of ability to recognize apoptotic
FT cells. Partial rescue of the engulfment defect of the
FT deletion mutant tm2078. Retains phosphatidylserine binding
FT specificity; when associated with A-100."
FT /evidence="ECO:0000269|PubMed:22713871"
FT MUTAGEN 113
FT /note="I->R: Fails to rescue the decreased clustering of
FT ced-1 around apoptotic cells in the embryos of the deletion
FT mutant tm2078; when associated with K-132."
FT /evidence="ECO:0000269|PubMed:22713871"
FT MUTAGEN 131..135
FT /note="Missing: Fails to rescue decreased clustering of
FT ced-1 around apoptotic cells in the embryos of the deletion
FT mutant tm2078."
FT /evidence="ECO:0000269|PubMed:22713871"
FT MUTAGEN 132
FT /note="L->K: Fails to rescue decreased clustering of ced-1
FT around apoptotic cells in the embryos of the deletion
FT mutant tm2078; when associated with R-113."
FT /evidence="ECO:0000269|PubMed:22713871"
FT STRAND 23..32
FT /evidence="ECO:0007829|PDB:3UAF"
FT HELIX 37..40
FT /evidence="ECO:0007829|PDB:3UAF"
FT STRAND 44..49
FT /evidence="ECO:0007829|PDB:3UAF"
FT HELIX 50..54
FT /evidence="ECO:0007829|PDB:3UAF"
FT STRAND 60..65
FT /evidence="ECO:0007829|PDB:3UAF"
FT STRAND 70..78
FT /evidence="ECO:0007829|PDB:3UAF"
FT STRAND 89..94
FT /evidence="ECO:0007829|PDB:3UAF"
FT TURN 100..102
FT /evidence="ECO:0007829|PDB:3UAF"
FT STRAND 108..111
FT /evidence="ECO:0007829|PDB:3UAF"
FT STRAND 119..130
FT /evidence="ECO:0007829|PDB:3UAF"
FT HELIX 132..135
FT /evidence="ECO:0007829|PDB:3UAF"
SQ SEQUENCE 135 AA; 15379 MW; 4B4C46FD94AAF55B CRC64;
MSRFLIYFLP FFIYSGNVLS KTSCLMATGV LKCPTDPEAV KKVHIDLWDE DSLPLESDDL
MGRTWSDRNG NFQVTGCASD FGPINTPDPY LYIQHNCPHR DSNATNPIQI DVIPLFLPSI
VRLGNVYLDR YLEDY
