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Protein

Metalloprotease TIKI2

Gene

TRABD2B

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein 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

Activity regulationi

Inhibited by 1,10-phenanthroline, a metalloprotease inhibitor which is a divalent metal chelator. Also inhibited by EDTA. Not inhibited by Bestatin, an aminopeptidase inhibitor, nor to a mixture of inhibitors for serine, cysteine, and aspartic proteases and aminopeptidases.1 Publication

GO - Molecular functioni

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

GO - Biological processi

Keywordsi

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

Protein family/group databases

MEROPSiM96.002

Names & Taxonomyi

Protein namesi
Recommended name:
Metalloprotease TIKI2 (EC:3.4.-.-)
Alternative name(s):
Heart, kidney and adipose-enriched transmembrane protein homolog
TRAB domain-containing protein 2B
Gene namesi
Name:TRABD2B
Synonyms:HKAT, TIKI2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000269113.3
HGNCiHGNC:44200 TRABD2B
MIMi614913 gene
neXtProtiNX_A6NFA1

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 – 494ExtracellularSequence analysisAdd BLAST475
Transmembranei495 – 515HelicalSequence analysisAdd BLAST21
Topological domaini516 – 517CytoplasmicSequence analysis2

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

OpenTargetsiENSG00000269113

Polymorphism and mutation databases

BioMutaiTRABD2B

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 19Sequence analysisAdd BLAST19
ChainiPRO_000034643620 – 517Metalloprotease TIKI2Add BLAST498

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi228N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi335N-linked (GlcNAc...) asparagineSequence analysis1

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiA6NFA1
PRIDEiA6NFA1
ProteomicsDBi1034

PTM databases

iPTMnetiA6NFA1
PhosphoSitePlusiA6NFA1

Expressioni

Gene expression databases

BgeeiENSG00000269113 Expressed in 99 organ(s), highest expression level in popliteal artery
GenevisibleiA6NFA1 HS

Organism-specific databases

HPAiHPA045817

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
Wnt3aP274672EBI-6257471,EBI-2899665From Mus musculus.

GO - Molecular functioni

Protein-protein interaction databases

IntActiA6NFA1, 4 interactors
STRINGi9606.ENSP00000456730

Structurei

3D structure databases

ProteinModelPortaliA6NFA1
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the TIKI family.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IF3M Eukaryota
ENOG410ZH8D LUCA
GeneTreeiENSGT00390000017525
HOVERGENiHBG108634
InParanoidiA6NFA1
OMAiLWTIRRH
OrthoDBiEOG091G0AY8
PhylomeDBiA6NFA1

Family and domain databases

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

Sequencei

Sequence statusi: Complete.

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

A6NFA1-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MHAALAGPLL AALLATARAR PQPPDGGQCR PPGSQRDLNS FLWTIRRDPP
60 70 80 90 100
AYLFGTIHVP YTRVWDFIPD NSKAAFQAST RVYFELDLTD PYTISALASC
110 120 130 140 150
QLLPHGENLQ DVLPHELYWR LKRHLDYVKL MMPSWMTPAQ RGKGLYADYL
160 170 180 190 200
FNAIAGNWER KRPVWVMLMV NSLTERDVRF RGVPVLDLYL AQQAEKMKKT
210 220 230 240 250
TGAVEQVEEQ CHPLNNGLNF SQVLFALNQT LLQQESVRAG SLQASYTTED
260 270 280 290 300
LIKHYNCGDL SAVIFNHDTS QLPNFINTTL PPHEQVTAQE IDSYFRQELI
310 320 330 340 350
YKRNERMGKR VMALLRENED KICFFAFGAG HFLGNNTVID ILRQAGLEVD
360 370 380 390 400
HTPAGQAIHS PAPQSPAPSP EGTSTSPAPV TPAAAVPEAP SVTPTAPPED
410 420 430 440 450
EDPALSPHLL LPDSLSQLEE FGRQRKWHKR QSTHQRPRQF NDLWVRIEDS
460 470 480 490 500
TTASPPPLPL QPTHSSGTAK PPFQLSDQLQ QQDPPGPASS SAPTLGLLPA
510
IATTIAVCFL LHSLGPS
Length:517
Mass (Da):57,421
Last modified:September 2, 2008 - v2
Checksum:iE06AC08A4CC61840
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
JQ653416 mRNA Translation: AFN02882.1
AC096541 Genomic DNA No translation available.
AC099679 Genomic DNA No translation available.
AL691459 Genomic DNA No translation available.
CCDSiCCDS58000.1
RefSeqiNP_001181915.1, NM_001194986.1
UniGeneiHs.61504

Genome annotation databases

EnsembliENST00000606738; ENSP00000476820; ENSG00000269113
GeneIDi388630
KEGGihsa:388630
UCSCiuc021ong.2 human

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
JQ653416 mRNA Translation: AFN02882.1
AC096541 Genomic DNA No translation available.
AC099679 Genomic DNA No translation available.
AL691459 Genomic DNA No translation available.
CCDSiCCDS58000.1
RefSeqiNP_001181915.1, NM_001194986.1
UniGeneiHs.61504

3D structure databases

ProteinModelPortaliA6NFA1
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiA6NFA1, 4 interactors
STRINGi9606.ENSP00000456730

Protein family/group databases

MEROPSiM96.002

PTM databases

iPTMnetiA6NFA1
PhosphoSitePlusiA6NFA1

Polymorphism and mutation databases

BioMutaiTRABD2B

Proteomic databases

PaxDbiA6NFA1
PRIDEiA6NFA1
ProteomicsDBi1034

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000606738; ENSP00000476820; ENSG00000269113
GeneIDi388630
KEGGihsa:388630
UCSCiuc021ong.2 human

Organism-specific databases

CTDi388630
EuPathDBiHostDB:ENSG00000269113.3
GeneCardsiTRABD2B
HGNCiHGNC:44200 TRABD2B
HPAiHPA045817
MIMi614913 gene
neXtProtiNX_A6NFA1
OpenTargetsiENSG00000269113
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IF3M Eukaryota
ENOG410ZH8D LUCA
GeneTreeiENSGT00390000017525
HOVERGENiHBG108634
InParanoidiA6NFA1
OMAiLWTIRRH
OrthoDBiEOG091G0AY8
PhylomeDBiA6NFA1

Miscellaneous databases

ChiTaRSiTRABD2B human
GenomeRNAii388630
PROiPR:A6NFA1
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000269113 Expressed in 99 organ(s), highest expression level in popliteal artery
GenevisibleiA6NFA1 HS

Family and domain databases

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

Entry informationi

Entry nameiTIKI2_HUMAN
AccessioniPrimary (citable) accession number: A6NFA1
Secondary accession number(s): I6U4Y0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 2, 2008
Last sequence update: September 2, 2008
Last modified: November 7, 2018
This is version 84 of the entry and version 2 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. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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Main funding by: National Institutes of Health

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