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   16-JAN-2019, entry version 86.
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;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, COFACTOR,
RP   AND 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.,
RA   Coburn K.L., Cheong S.M., Zhang M.M., Ye Q.Z., Hang H.C., Steen H.,
RA   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.,
RA   Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA   Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA   McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA   Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA   Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA   Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA   Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA   Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA   Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA   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.,
RA   Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA   Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA   Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA   Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA   Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA   Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA   Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA   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.,
RA   Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA   Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA   Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA   Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA   Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA   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
CC       Wnt signaling pathway by mediating the cleavage of the 8 N-
CC       terminal residues of a subset of Wnt proteins. Following cleavage,
CC       Wnt proteins become oxidized and form large disulfide-bond
CC       oligomers, leading to their inactivation. Able to cleave WNT3A,
CC       WNT5, but not WNT11. Required for head formation.
CC       {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,
CC       and aspartic proteases and aminopeptidases.
CC       {ECO:0000269|PubMed:22726442}.
CC   -!- INTERACTION:
CC       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
CC       humanoid in 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   UniGene; Hs.61504; -.
DR   ProteinModelPortal; A6NFA1; -.
DR   IntAct; A6NFA1; 4.
DR   STRING; 9606.ENSP00000456730; -.
DR   MEROPS; M96.002; -.
DR   iPTMnet; A6NFA1; -.
DR   PhosphoSitePlus; A6NFA1; -.
DR   BioMuta; TRABD2B; -.
DR   PaxDb; A6NFA1; -.
DR   PRIDE; A6NFA1; -.
DR   ProteomicsDB; 1034; -.
DR   Ensembl; ENST00000606738; ENSP00000476820; ENSG00000269113.
DR   GeneID; 388630; -.
DR   KEGG; hsa:388630; -.
DR   UCSC; uc021ong.2; human.
DR   CTD; 388630; -.
DR   EuPathDB; HostDB:ENSG00000269113.3; -.
DR   GeneCards; TRABD2B; -.
DR   HGNC; HGNC:44200; TRABD2B.
DR   HPA; HPA045817; -.
DR   MIM; 614913; gene.
DR   neXtProt; NX_A6NFA1; -.
DR   OpenTargets; ENSG00000269113; -.
DR   eggNOG; ENOG410IF3M; Eukaryota.
DR   eggNOG; ENOG410ZH8D; LUCA.
DR   GeneTree; ENSGT00940000161273; -.
DR   HOVERGEN; HBG108634; -.
DR   InParanoid; A6NFA1; -.
DR   OMA; LWTIRRH; -.
DR   OrthoDB; 1407303at2759; -.
DR   PhylomeDB; A6NFA1; -.
DR   ChiTaRS; TRABD2B; human.
DR   GenomeRNAi; 388630; -.
DR   PRO; PR:A6NFA1; -.
DR   Proteomes; UP000005640; Chromosome 1.
DR   Bgee; ENSG00000269113; Expressed in 99 organ(s), highest expression level in popliteal artery.
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:0032461; P:positive regulation of protein oligomerization; IDA:ParkinsonsUK-UCL.
DR   GO; GO:1904808; P:positive regulation of protein oxidation; 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_fam.
DR   PANTHER; PTHR31120; PTHR31120; 1.
DR   Pfam; PF01963; TraB; 1.
PE   1: Evidence at protein level;
KW   Cell membrane; Complete proteome; Glycoprotein; Hydrolase; Membrane;
KW   Metal-binding; Metalloprotease; Protease; Reference proteome; Signal;
KW   Transmembrane; Transmembrane helix; Wnt signaling pathway.
FT   SIGNAL        1     19       {ECO:0000255}.
FT   CHAIN        20    517       Metalloprotease TIKI2.
FT                                /FTId=PRO_0000346436.
FT   TOPO_DOM     20    494       Extracellular. {ECO:0000255}.
FT   TRANSMEM    495    515       Helical. {ECO:0000255}.
FT   TOPO_DOM    516    517       Cytoplasmic. {ECO:0000255}.
FT   CARBOHYD    228    228       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    335    335       N-linked (GlcNAc...) asparagine.
FT                                {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
//