ID A0A8M2BED6_DANRE Unreviewed; 517 AA. AC A0A8M2BED6; DT 03-AUG-2022, integrated into UniProtKB/TrEMBL. DT 03-AUG-2022, sequence version 1. DT 08-NOV-2023, entry version 8. DE RecName: Full=Metalloprotease TIKI {ECO:0000256|RuleBase:RU369069}; DE EC=3.4.-.- {ECO:0000256|RuleBase:RU369069}; DE AltName: Full=TRAB domain-containing protein 2 {ECO:0000256|RuleBase:RU369069}; GN Name=trabd2b {ECO:0000313|RefSeq:XP_005166934.1}; GN Synonyms=si:ch211-120j21.1 {ECO:0000313|RefSeq:XP_005166934.1}, TIKI2 GN {ECO:0000313|RefSeq:XP_005166934.1}; OS Danio rerio (Zebrafish) (Brachydanio rerio). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes; OC Danionidae; Danioninae; Danio. OX NCBI_TaxID=7955 {ECO:0000313|Proteomes:UP000000437, ECO:0000313|RefSeq:XP_005166934.1}; RN [1] {ECO:0000313|Proteomes:UP000000437} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=23594743; DOI=10.1038/nature12111; RG Genome Reference Consortium Zebrafish; RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M., RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I., RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J., RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y., RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B., RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S., RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M., RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J., RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Eliott D., RA Threadgold G., Harden G., Ware D., Begum S., Mortimore B., Mortimer B., RA Kerry G., Heath P., Phillimore B., Tracey A., Corby N., Dunn M., RA Johnson C., Wood J., Clark S., Pelan S., Griffiths G., Smith M., RA Glithero R., Howden P., Barker N., Lloyd C., Stevens C., Harley J., RA Holt K., Panagiotidis G., Lovell J., Beasley H., Henderson C., Gordon D., RA Auger K., Wright D., Collins J., Raisen C., Dyer L., Leung K., RA Robertson L., Ambridge K., Leongamornlert D., McGuire S., Gilderthorp R., RA Griffiths C., Manthravadi D., Nichol S., Barker G., Whitehead S., Kay M., RA Brown J., Murnane C., Gray E., Humphries M., Sycamore N., Barker D., RA Saunders D., Wallis J., Babbage A., Hammond S., Mashreghi-Mohammadi M., RA Barr L., Martin S., Wray P., Ellington A., Matthews N., Ellwood M., RA Woodmansey R., Clark G., Cooper J., Cooper J., Tromans A., Grafham D., RA Skuce C., Pandian R., Andrews R., Harrison E., Kimberley A., Garnett J., RA Fosker N., Hall R., Garner P., Kelly D., Bird C., Palmer S., Gehring I., RA Berger A., Dooley C.M., Ersan-Urun Z., Eser C., Geiger H., Geisler M., RA Karotki L., Kirn A., Konantz J., Konantz M., Oberlander M., RA Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G., Osoegawa K., Zhu B., RA Rapp A., Widaa S., Langford C., Yang F., Schuster S.C., Carter N.P., RA Harrow J., Ning Z., Herrero J., Searle S.M., Enright A., Geisler R., RA Plasterk R.H., Lee C., Westerfield M., de Jong P.J., Zon L.I., RA Postlethwait J.H., Nusslein-Volhard C., Hubbard T.J., Roest Crollius H., RA Rogers J., Stemple D.L.; RT "The zebrafish reference genome sequence and its relationship to the human RT genome."; RL Nature 496:498-503(2013). RN [2] {ECO:0000313|RefSeq:XP_005166934.1} RP IDENTIFICATION. RC STRAIN=Tuebingen {ECO:0000313|RefSeq:XP_005166934.1}; RG RefSeq; RL Submitted (JUL-2023) to UniProtKB. CC -!- FUNCTION: Metalloprotease that acts as a negative regulator of the Wnt CC signaling pathway by mediating the cleavage of the N-terminal residues CC of a subset of Wnt proteins. Following cleavage, Wnt proteins become CC oxidized and form large disulfide-bond oligomers, leading to their CC inactivation. {ECO:0000256|RuleBase:RU369069}. CC -!- COFACTOR: CC Name=Co(2+); Xref=ChEBI:CHEBI:48828; CC Evidence={ECO:0000256|ARBA:ARBA00001941}; CC -!- COFACTOR: CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; CC Evidence={ECO:0000256|RuleBase:RU369069}; CC Name=Co(2+); Xref=ChEBI:CHEBI:48828; CC Evidence={ECO:0000256|RuleBase:RU369069}; CC Note=Divalent metal cations. Mn(2+) or Co(2+). CC {ECO:0000256|RuleBase:RU369069}; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000256|RuleBase:RU369069}; CC Single-pass type I membrane protein {ECO:0000256|RuleBase:RU369069}. CC Membrane {ECO:0000256|ARBA:ARBA00004479}; Single-pass type I membrane CC protein {ECO:0000256|ARBA:ARBA00004479}. CC -!- SIMILARITY: Belongs to the TIKI family. {ECO:0000256|ARBA:ARBA00008261, CC ECO:0000256|RuleBase:RU369069}. 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 RefSeq; XP_005166934.1; XM_005166877.3. DR GeneID; 566028; -. DR CTD; 388630; -. DR Proteomes; UP000000437; Chromosome 8. DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-UniRule. DR GO; GO:0004222; F:metalloendopeptidase activity; IEA:UniProtKB-UniRule. DR GO; GO:0030178; P:negative regulation of Wnt signaling pathway; IEA:UniProtKB-UniRule. DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW. DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW. DR CDD; cd14789; Tiki; 1. DR InterPro; IPR040230; TIKI1/2-like. DR InterPro; IPR002816; TraB/PrgY/GumN_fam. DR PANTHER; PTHR31120; METALLOPROTEASE TIKI; 1. DR PANTHER; PTHR31120:SF8; METALLOPROTEASE TIKI2; 1. DR Pfam; PF01963; TraB_PrgY_gumN; 1. PE 3: Inferred from homology; KW Cell membrane {ECO:0000256|RuleBase:RU369069}; KW Glycoprotein {ECO:0000256|ARBA:ARBA00023180}; KW Hydrolase {ECO:0000256|ARBA:ARBA00022801, ECO:0000256|RuleBase:RU369069}; KW Membrane {ECO:0000256|ARBA:ARBA00023136}; KW Metal-binding {ECO:0000256|ARBA:ARBA00022723, KW ECO:0000256|RuleBase:RU369069}; KW Metalloprotease {ECO:0000256|RuleBase:RU369069, KW ECO:0000313|RefSeq:XP_005166934.1}; KW Protease {ECO:0000256|RuleBase:RU369069}; KW Reference proteome {ECO:0000313|Proteomes:UP000000437}; KW Signal {ECO:0000256|ARBA:ARBA00022729, ECO:0000256|RuleBase:RU369069}; KW Transmembrane {ECO:0000256|ARBA:ARBA00022692}; KW Transmembrane helix {ECO:0000256|ARBA:ARBA00022989}; KW Wnt signaling pathway {ECO:0000256|RuleBase:RU369069}. FT SIGNAL 1..22 FT /evidence="ECO:0000256|SAM:SignalP" FT CHAIN 23..517 FT /note="Metalloprotease TIKI" FT /evidence="ECO:0000256|SAM:SignalP" FT /id="PRO_5035474082" SQ SEQUENCE 517 AA; 59613 MW; 3088B99E652BFD35 CRC64; MNCQSGLRWL VTLCAFFQVG SARDTHESTR QCDKPVSKDM NSFLWTVKRP RPFPPSYLFG TIHVPYTRVW DYIPESSKRA FQTSNSVFFE LDLTDPLTIS KLTSCQLLPN GENLQTLLPR DLYRRLKRHL DYVKHMMPFW MTADQRGRGL YADYLFNAIA GNWERKRPVW VMLMVNSLTE ADVRSRGTPV LDLFLAQEAE RLGKQTGAVE RVEEQCHPLN GLNFSQVLFA LNQTLLQHES LRAGILQGTF TTEDLIAHYN CGDLNSIIFN HDTSQLPHFI NSSLPDHERL TAQQIDSYLR QELIYKRNER MARRVSALLQ RNPNQSFFFA FGAGHFLGNH SVLDILRQEG YEVEHTPPQE PIIQSWSERE ATTLNPTEDS FESVTEWTSE TPELEEISQE ELSHMLLPDS LSQLEEFGRY KHPRKTHHTH SRPRLFSDLW VRIGDSTTPH PSIRITNGYV TVEPPQIRQE QQQRLRERLK PLSEPTNPSA LDSAAPNPTY ALTCFLACLI SQLLFAS //