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Protein

Metalloprotease TIKI1

Gene

TRABD2A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Metalloprotease that acts as a negative regulator of the Wnt signaling pathway by mediating the cleavage of the 8 N-terminal residues of a subset of Wnt proteins. Following cleavage, Wnt proteins become oxidized and form large disulfide-bond oligomers, leading to their inactivation. Able to cleave WNT3A, WNT5, but not WNT11. Required for head formation.1 Publication

Miscellaneous

Was named TIKI in reference to large-headed humanoid in Polynesian mythology.1 Publication

Cofactori

Mn2+1 Publication, Co2+1 PublicationNote: Divalent metal cations. Mn2+ or Co2+.1 Publication

GO - Molecular functioni

  • endopeptidase activity Source: ParkinsonsUK-UCL
  • metal ion binding Source: UniProtKB-KW
  • metalloendopeptidase activity Source: UniProtKB
  • Wnt-protein binding Source: UniProtKB

GO - Biological processi

  • head development Source: UniProtKB
  • negative regulation of Wnt signaling pathway Source: UniProtKB
  • positive regulation of protein oligomerization Source: ParkinsonsUK-UCL
  • positive regulation of protein oxidation Source: ParkinsonsUK-UCL
  • proteolysis Source: ParkinsonsUK-UCL
  • Wnt signaling pathway Source: UniProtKB-KW

Keywordsi

Molecular functionHydrolase, Metalloprotease, Protease
Biological processWnt signaling pathway
LigandMetal-binding

Protein family/group databases

MEROPSiM96.001.

Names & Taxonomyi

Protein namesi
Recommended name:
Metalloprotease TIKI1 (EC:3.4.-.-)
Alternative name(s):
TRAB domain-containing protein 2A
Gene namesi
Name:TRABD2A
Synonyms:C2orf89, TIKI1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000186854.10.
HGNCiHGNC:27013. TRABD2A.
MIMi614912. gene.
neXtProtiNX_Q86V40.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini20 – 477ExtracellularSequence analysisAdd BLAST458
Transmembranei478 – 498HelicalSequence analysisAdd BLAST21
Topological domaini499 – 505CytoplasmicSequence analysis7

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

OpenTargetsiENSG00000186854.
PharmGKBiPA165696373.

Polymorphism and mutation databases

DMDMi292495086.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 19Sequence analysisAdd BLAST19
ChainiPRO_000032580720 – 505Metalloprotease TIKI1Add BLAST486

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi220N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi229N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi278N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi336N-linked (GlcNAc...) asparagineSequence analysis1

Keywords - PTMi

Glycoprotein

Proteomic databases

MaxQBiQ86V40.
PeptideAtlasiQ86V40.
PRIDEiQ86V40.

PTM databases

iPTMnetiQ86V40.
PhosphoSitePlusiQ86V40.

Expressioni

Gene expression databases

BgeeiENSG00000186854.
ExpressionAtlasiQ86V40. baseline and differential.
GenevisibleiQ86V40. HS.

Organism-specific databases

HPAiHPA045817.

Interactioni

GO - Molecular functioni

  • Wnt-protein binding Source: UniProtKB

Protein-protein interaction databases

IntActiQ86V40. 1 interactor.

Structurei

3D structure databases

ProteinModelPortaliQ86V40.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the TIKI family.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

GeneTreeiENSGT00390000017525.
HOGENOMiHOG000154747.
HOVERGENiHBG108634.
InParanoidiQ86V40.
OMAiASANCEL.
OrthoDBiEOG091G0AY8.
PhylomeDBiQ86V40.
TreeFamiTF313392.

Family and domain databases

InterProiView protein in InterPro
IPR002816. Pheromone_shutdown_TraB.
PfamiView protein in Pfam
PF01963. TraB. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q86V40-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSPWSWFLLQ TLCLLPTGAA SRRGAPGTAN CELKPQQSEL NSFLWTIKRD
60 70 80 90 100
PPSYFFGTIH VPYTRVWDFI PDNSKEAFLQ SSIVYFELDL TDPYTISALT
110 120 130 140 150
SCQMLPQGEN LQDVLPRDIY CRLKRHLEYV KLMMPLWMTP DQRGKGLYAD
160 170 180 190 200
YLFNAIAGNW ERKRPVWVML MVNSLTEVDI KSRGVPVLDL FLAQEAERLR
210 220 230 240 250
KQTGAVEKVE EQCHPLNGLN FSQVIFALNQ TLLQQESLRA GSLQIPYTTE
260 270 280 290 300
DLIKHYNCGD LSSVILSHDS SQVPNFINAT LPPQERITAQ EIDSYLRREL
310 320 330 340 350
IYKRNERIGK RVKALLEEFP DKGFFFAFGA GHFMGNNTVL DVLRREGYEV
360 370 380 390 400
EHAPAGRPIH KGKSKKTSTR PTLSTIFAPK VPTLEVPAPE AVSSGHSTLP
410 420 430 440 450
PLVSRPGSAD TPSEAEQRFR KKRRRSQRRP RLRQFSDLWV RLEESDIVPQ
460 470 480 490 500
LQVPVLDRHI STELRLPRRG HSHHSQMVAS SACLSLWTPV FWVLVLAFQT

ETPLL
Length:505
Mass (Da):57,676
Last modified:March 23, 2010 - v3
Checksum:iDDDC36FC40CBDA91
GO
Isoform 2 (identifier: Q86V40-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     225-273: Missing.

Show »
Length:456
Mass (Da):52,246
Checksum:i7882EAF5910841BF
GO

Sequence cautioni

The sequence AAH51789 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti322K → R in BAG59220 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_039920143R → H1 PublicationCorresponds to variant dbSNP:rs1863772Ensembl.1
Natural variantiVAR_039921428R → Q. Corresponds to variant dbSNP:rs2288352Ensembl.1
Natural variantiVAR_039922430P → L. Corresponds to variant dbSNP:rs1649292Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_038837225 – 273Missing in isoform 2. 1 PublicationAdd BLAST49

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
JQ653415 mRNA. Translation: AFN02881.1.
AK296608 mRNA. Translation: BAG59220.1.
AC010087 Genomic DNA. No translation available.
CH471053 Genomic DNA. Translation: EAW99551.1.
BC051789 mRNA. Translation: AAH51789.1. Different initiation.
CCDSiCCDS46349.1. [Q86V40-2]
CCDS62946.1. [Q86V40-1]
RefSeqiNP_001074293.1. NM_001080824.2. [Q86V40-2]
NP_001263982.1. NM_001277053.1. [Q86V40-1]
NP_001294907.1. NM_001307978.1.
UniGeneiHs.469134.

Genome annotation databases

EnsembliENST00000335459; ENSP00000335004; ENSG00000186854. [Q86V40-2]
ENST00000409520; ENSP00000387075; ENSG00000186854. [Q86V40-1]
GeneIDi129293.
KEGGihsa:129293.
UCSCiuc002sou.6. human. [Q86V40-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiTIKI1_HUMAN
AccessioniPrimary (citable) accession number: Q86V40
Secondary accession number(s): B4DKK8, I6UMB9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 18, 2008
Last sequence update: March 23, 2010
Last modified: September 27, 2017
This is version 95 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families
  6. Uncharacterized protein families (UPF)
    List of uncharacterized protein family (UPF) entries