TIKI1_HUMAN
ID TIKI1_HUMAN Reviewed; 505 AA.
AC Q86V40; B4DKK8; I6UMB9;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 23-MAR-2010, sequence version 3.
DT 03-AUG-2022, entry version 120.
DE RecName: Full=Metalloprotease TIKI1;
DE EC=3.4.-.-;
DE AltName: Full=TRAB domain-containing protein 2A;
DE Flags: Precursor;
GN Name=TRABD2A; Synonyms=C2orf89, TIKI1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, AND
RP COFACTOR.
RX PubMed=22726442; DOI=10.1016/j.cell.2012.04.039;
RA Zhang X., Abreu J.G., Yokota C., Macdonald B.T., Singh S., Coburn K.L.,
RA Cheong S.M., Zhang M.M., Ye Q.Z., Hang H.C., Steen H., He X.;
RT "Tiki1 is required for head formation via Wnt cleavage-oxidation and
RT inactivation.";
RL Cell 149:1565-1577(2012).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Colon;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT HIS-143.
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
CC -!- FUNCTION: Metalloprotease that acts as a negative regulator of the Wnt
CC signaling pathway by mediating the cleavage of the 8 N-terminal
CC residues of a subset of Wnt proteins. Following cleavage, Wnt proteins
CC become oxidized and form large disulfide-bond oligomers, leading to
CC their inactivation. Able to cleave WNT3A, WNT5, but not WNT11. Required
CC for head formation. {ECO:0000269|PubMed:22726442}.
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:22726442};
CC Name=Co(2+); Xref=ChEBI:CHEBI:48828;
CC Evidence={ECO:0000269|PubMed:22726442};
CC Note=Divalent metal cations. Mn(2+) or Co(2+).
CC {ECO:0000269|PubMed:22726442};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:22726442};
CC Single-pass type I membrane protein {ECO:0000269|PubMed:22726442}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q86V40-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q86V40-2; Sequence=VSP_038837;
CC -!- MISCELLANEOUS: Was named TIKI in reference to large-headed humanoid in
CC Polynesian mythology. {ECO:0000305|PubMed:22726442}.
CC -!- SIMILARITY: Belongs to the TIKI family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH51789.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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; JQ653415; AFN02881.1; -; mRNA.
DR EMBL; AK296608; BAG59220.1; -; mRNA.
DR EMBL; AC010087; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471053; EAW99551.1; -; Genomic_DNA.
DR EMBL; BC051789; AAH51789.1; ALT_INIT; mRNA.
DR CCDS; CCDS46349.1; -. [Q86V40-2]
DR CCDS; CCDS62946.1; -. [Q86V40-1]
DR RefSeq; NP_001074293.1; NM_001080824.2. [Q86V40-2]
DR RefSeq; NP_001263982.1; NM_001277053.1. [Q86V40-1]
DR RefSeq; NP_001294907.1; NM_001307978.1.
DR AlphaFoldDB; Q86V40; -.
DR BioGRID; 126188; 1.
DR IntAct; Q86V40; 1.
DR STRING; 9606.ENSP00000387075; -.
DR MEROPS; G04.001; -.
DR GlyGen; Q86V40; 4 sites.
DR iPTMnet; Q86V40; -.
DR PhosphoSitePlus; Q86V40; -.
DR BioMuta; TRABD2A; -.
DR DMDM; 292495086; -.
DR EPD; Q86V40; -.
DR MassIVE; Q86V40; -.
DR MaxQB; Q86V40; -.
DR PeptideAtlas; Q86V40; -.
DR PRIDE; Q86V40; -.
DR ProteomicsDB; 69961; -. [Q86V40-1]
DR ProteomicsDB; 69962; -. [Q86V40-2]
DR Antibodypedia; 56499; 65 antibodies from 13 providers.
DR DNASU; 129293; -.
DR Ensembl; ENST00000335459.9; ENSP00000335004.5; ENSG00000186854.11. [Q86V40-2]
DR Ensembl; ENST00000409520.7; ENSP00000387075.2; ENSG00000186854.11. [Q86V40-1]
DR GeneID; 129293; -.
DR KEGG; hsa:129293; -.
DR MANE-Select; ENST00000409520.7; ENSP00000387075.2; NM_001277053.2; NP_001263982.1.
DR UCSC; uc002sou.6; human. [Q86V40-1]
DR CTD; 129293; -.
DR DisGeNET; 129293; -.
DR GeneCards; TRABD2A; -.
DR HGNC; HGNC:27013; TRABD2A.
DR HPA; ENSG00000186854; Group enriched (intestine, lymphoid tissue, ovary).
DR MIM; 614912; gene.
DR neXtProt; NX_Q86V40; -.
DR OpenTargets; ENSG00000186854; -.
DR PharmGKB; PA165696373; -.
DR VEuPathDB; HostDB:ENSG00000186854; -.
DR eggNOG; ENOG502QPR1; Eukaryota.
DR GeneTree; ENSGT00940000162805; -.
DR HOGENOM; CLU_035548_1_0_1; -.
DR InParanoid; Q86V40; -.
DR OMA; DHYDESP; -.
DR OrthoDB; 1407303at2759; -.
DR PhylomeDB; Q86V40; -.
DR TreeFam; TF313392; -.
DR PathwayCommons; Q86V40; -.
DR SignaLink; Q86V40; -.
DR BioGRID-ORCS; 129293; 14 hits in 1059 CRISPR screens.
DR ChiTaRS; TRABD2A; human.
DR GenomeRNAi; 129293; -.
DR Pharos; Q86V40; Tbio.
DR PRO; PR:Q86V40; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q86V40; protein.
DR Bgee; ENSG00000186854; Expressed in mucosa of transverse colon and 111 other tissues.
DR ExpressionAtlas; Q86V40; baseline and differential.
DR Genevisible; Q86V40; HS.
DR GO; GO:0031301; C:integral component of organelle membrane; IDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0004175; F:endopeptidase activity; IDA:ParkinsonsUK-UCL.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004222; F:metalloendopeptidase activity; IDA:UniProtKB.
DR GO; GO:0017147; F:Wnt-protein binding; IDA:UniProtKB.
DR GO; GO:0060322; P:head development; ISS:UniProtKB.
DR GO; GO:0030178; P:negative regulation of Wnt signaling pathway; IDA:UniProtKB.
DR GO; GO:1904808; P:positive regulation of protein oxidation; ISS:ParkinsonsUK-UCL.
DR GO; GO:0031334; P:positive regulation of protein-containing complex assembly; ISS:ParkinsonsUK-UCL.
DR GO; GO:0006508; P:proteolysis; IDA:ParkinsonsUK-UCL.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR InterPro; IPR040230; TIKI1/2-like.
DR InterPro; IPR002816; TraB/PrgY/GumN_fam.
DR PANTHER; PTHR31120; PTHR31120; 1.
DR Pfam; PF01963; TraB_PrgY_gumN; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Cell membrane; Glycoprotein; Hydrolase; Membrane;
KW Metal-binding; Metalloprotease; Protease; Reference proteome; Signal;
KW Transmembrane; Transmembrane helix; Wnt signaling pathway.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..505
FT /note="Metalloprotease TIKI1"
FT /id="PRO_0000325807"
FT TOPO_DOM 20..477
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 478..498
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 499..505
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 389..428
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 220
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 229
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 278
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 336
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 225..273
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_038837"
FT VARIANT 143
FT /note="R -> H (in dbSNP:rs1863772)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_039920"
FT VARIANT 428
FT /note="R -> Q (in dbSNP:rs2288352)"
FT /id="VAR_039921"
FT VARIANT 430
FT /note="P -> L (in dbSNP:rs1649292)"
FT /id="VAR_039922"
FT CONFLICT 322
FT /note="K -> R (in Ref. 2; BAG59220)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 505 AA; 57676 MW; DDDC36FC40CBDA91 CRC64;
MSPWSWFLLQ TLCLLPTGAA SRRGAPGTAN CELKPQQSEL NSFLWTIKRD PPSYFFGTIH
VPYTRVWDFI PDNSKEAFLQ SSIVYFELDL TDPYTISALT SCQMLPQGEN LQDVLPRDIY
CRLKRHLEYV KLMMPLWMTP DQRGKGLYAD YLFNAIAGNW ERKRPVWVML MVNSLTEVDI
KSRGVPVLDL FLAQEAERLR KQTGAVEKVE EQCHPLNGLN FSQVIFALNQ TLLQQESLRA
GSLQIPYTTE DLIKHYNCGD LSSVILSHDS SQVPNFINAT LPPQERITAQ EIDSYLRREL
IYKRNERIGK RVKALLEEFP DKGFFFAFGA GHFMGNNTVL DVLRREGYEV EHAPAGRPIH
KGKSKKTSTR PTLSTIFAPK VPTLEVPAPE AVSSGHSTLP PLVSRPGSAD TPSEAEQRFR
KKRRRSQRRP RLRQFSDLWV RLEESDIVPQ LQVPVLDRHI STELRLPRRG HSHHSQMVAS
SACLSLWTPV FWVLVLAFQT ETPLL
