TIKI2_HUMAN
ID TIKI2_HUMAN Reviewed; 517 AA.
AC A6NFA1; I6U4Y0;
DT 02-SEP-2008, integrated into UniProtKB/Swiss-Prot.
DT 02-SEP-2008, sequence version 2.
DT 03-AUG-2022, entry version 103.
DE RecName: Full=Metalloprotease TIKI2;
DE EC=3.4.-.-;
DE AltName: Full=Heart, kidney and adipose-enriched transmembrane protein homolog;
DE AltName: Full=TRAB domain-containing protein 2B;
DE Flags: Precursor;
GN Name=TRABD2B; Synonyms=HKAT, TIKI2;
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], FUNCTION, SUBCELLULAR LOCATION, COFACTOR, AND
RP ACTIVITY REGULATION.
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 GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
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 -!- ACTIVITY REGULATION: Inhibited by 1,10-phenanthroline, a
CC metalloprotease inhibitor which is a divalent metal chelator. Also
CC inhibited by EDTA. Not inhibited by Bestatin, an aminopeptidase
CC inhibitor, nor to a mixture of inhibitors for serine, cysteine, and
CC aspartic proteases and aminopeptidases. {ECO:0000269|PubMed:22726442}.
CC -!- INTERACTION:
CC A6NFA1; P27467: Wnt3a; Xeno; NbExp=2; IntAct=EBI-6257471, EBI-2899665;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:22726442};
CC Single-pass type I membrane protein {ECO:0000269|PubMed:22726442}.
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}.
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DR EMBL; JQ653416; AFN02882.1; -; mRNA.
DR EMBL; AC096541; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC099679; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL691459; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS58000.1; -.
DR RefSeq; NP_001181915.1; NM_001194986.1.
DR AlphaFoldDB; A6NFA1; -.
DR IntAct; A6NFA1; 4.
DR STRING; 9606.ENSP00000476820; -.
DR MEROPS; G04.002; -.
DR GlyGen; A6NFA1; 3 sites, 1 O-linked glycan (1 site).
DR iPTMnet; A6NFA1; -.
DR PhosphoSitePlus; A6NFA1; -.
DR BioMuta; TRABD2B; -.
DR MassIVE; A6NFA1; -.
DR PaxDb; A6NFA1; -.
DR PeptideAtlas; A6NFA1; -.
DR PRIDE; A6NFA1; -.
DR Antibodypedia; 75203; 12 antibodies from 7 providers.
DR DNASU; 388630; -.
DR Ensembl; ENST00000606738.3; ENSP00000476820.1; ENSG00000269113.4.
DR GeneID; 388630; -.
DR KEGG; hsa:388630; -.
DR MANE-Select; ENST00000606738.3; ENSP00000476820.1; NM_001194986.2; NP_001181915.1.
DR UCSC; uc021ong.2; human.
DR CTD; 388630; -.
DR DisGeNET; 388630; -.
DR GeneCards; TRABD2B; -.
DR HGNC; HGNC:44200; TRABD2B.
DR HPA; ENSG00000269113; Tissue enhanced (kidney).
DR MIM; 614913; gene.
DR neXtProt; NX_A6NFA1; -.
DR OpenTargets; ENSG00000269113; -.
DR VEuPathDB; HostDB:ENSG00000269113; -.
DR eggNOG; ENOG502QPR1; Eukaryota.
DR GeneTree; ENSGT00940000161273; -.
DR HOGENOM; CLU_035548_1_0_1; -.
DR InParanoid; A6NFA1; -.
DR OMA; FVKSSHQ; -.
DR OrthoDB; 1407303at2759; -.
DR PhylomeDB; A6NFA1; -.
DR PathwayCommons; A6NFA1; -.
DR SignaLink; A6NFA1; -.
DR BioGRID-ORCS; 388630; 12 hits in 1047 CRISPR screens.
DR ChiTaRS; TRABD2B; human.
DR GenomeRNAi; 388630; -.
DR Pharos; A6NFA1; Tbio.
DR PRO; PR:A6NFA1; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; A6NFA1; protein.
DR Bgee; ENSG00000269113; Expressed in popliteal artery and 86 other tissues.
DR Genevisible; A6NFA1; 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: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:0030178; P:negative regulation of Wnt signaling pathway; IDA:UniProtKB.
DR GO; GO:1904808; P:positive regulation of protein oxidation; IDA:ParkinsonsUK-UCL.
DR GO; GO:0031334; P:positive regulation of protein-containing complex assembly; IDA: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 1: Evidence at protein level;
KW Cell membrane; Glycoprotein; Hydrolase; Membrane; Metal-binding;
KW Metalloprotease; Protease; Reference proteome; Signal; Transmembrane;
KW Transmembrane helix; Wnt signaling pathway.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..517
FT /note="Metalloprotease TIKI2"
FT /id="PRO_0000346436"
FT TOPO_DOM 20..494
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 495..515
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 516..517
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 354..409
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 422..441
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 450..492
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 463..489
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 228
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 335
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 517 AA; 57421 MW; E06AC08A4CC61840 CRC64;
MHAALAGPLL AALLATARAR PQPPDGGQCR PPGSQRDLNS FLWTIRRDPP AYLFGTIHVP
YTRVWDFIPD NSKAAFQAST RVYFELDLTD PYTISALASC QLLPHGENLQ DVLPHELYWR
LKRHLDYVKL MMPSWMTPAQ RGKGLYADYL FNAIAGNWER KRPVWVMLMV NSLTERDVRF
RGVPVLDLYL AQQAEKMKKT TGAVEQVEEQ CHPLNNGLNF SQVLFALNQT LLQQESVRAG
SLQASYTTED LIKHYNCGDL SAVIFNHDTS QLPNFINTTL PPHEQVTAQE IDSYFRQELI
YKRNERMGKR VMALLRENED KICFFAFGAG HFLGNNTVID ILRQAGLEVD HTPAGQAIHS
PAPQSPAPSP EGTSTSPAPV TPAAAVPEAP SVTPTAPPED EDPALSPHLL LPDSLSQLEE
FGRQRKWHKR QSTHQRPRQF NDLWVRIEDS TTASPPPLPL QPTHSSGTAK PPFQLSDQLQ
QQDPPGPASS SAPTLGLLPA IATTIAVCFL LHSLGPS
