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Protein

Thyrotropin-releasing hormone-degrading ectoenzyme

Gene

TRHDE

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

Functioni

Specific inactivation of TRH after its release.

Catalytic activityi

Release of the N-terminal pyroglutamyl group from pGlu-|-His-Xaa tripeptides and pGlu-|-His-Xaa-Gly tetrapeptides.

Cofactori

Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi440 – 4401Zinc; catalyticPROSITE-ProRule annotation
Active sitei441 – 4411Proton acceptorPROSITE-ProRule annotation
Metal bindingi444 – 4441Zinc; catalyticPROSITE-ProRule annotation
Metal bindingi463 – 4631Zinc; catalyticPROSITE-ProRule annotation
Sitei527 – 5271Transition state stabilizerBy similarity

GO - Molecular functioni

  • aminopeptidase activity Source: ProtInc
  • metalloaminopeptidase activity Source: GO_Central
  • peptide binding Source: GO_Central
  • zinc ion binding Source: GO_Central

GO - Biological processi

  • cell-cell signaling Source: ProtInc
  • peptide catabolic process Source: GO_Central
  • regulation of blood pressure Source: GO_Central
  • signal transduction Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Aminopeptidase, Hydrolase, Metalloprotease, Protease

Keywords - Ligandi

Metal-binding, Zinc

Protein family/group databases

MEROPSiM01.008.

Names & Taxonomyi

Protein namesi
Recommended name:
Thyrotropin-releasing hormone-degrading ectoenzyme (EC:3.4.19.6)
Short name:
TRH-DE
Short name:
TRH-degrading ectoenzyme
Alternative name(s):
Pyroglutamyl-peptidase II
Short name:
PAP-II
TRH-specific aminopeptidase
Thyroliberinase
Gene namesi
Name:TRHDE
ORF Names:UNQ2507/PRO5995
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:30748. TRHDE.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 4040CytoplasmicSequence analysisAdd
BLAST
Transmembranei41 – 6121Helical; Signal-anchor for type II membrane proteinSequence analysisAdd
BLAST
Topological domaini62 – 1024963ExtracellularSequence analysisAdd
BLAST

GO - Cellular componenti

  • cytoplasm Source: GO_Central
  • extracellular exosome Source: UniProtKB
  • integral component of plasma membrane Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA142670702.

Polymorphism and mutation databases

BioMutaiTRHDE.
DMDMi11387208.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 10241024Thyrotropin-releasing hormone-degrading ectoenzymePRO_0000095118Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi68 – 68InterchainBy similarity
Glycosylationi89 – 891N-linked (GlcNAc...)Sequence analysis
Glycosylationi160 – 1601N-linked (GlcNAc...)Sequence analysis
Glycosylationi175 – 1751N-linked (GlcNAc...)Sequence analysis
Glycosylationi222 – 2221N-linked (GlcNAc...)Sequence analysis
Glycosylationi338 – 3381N-linked (GlcNAc...)Sequence analysis
Glycosylationi605 – 6051N-linked (GlcNAc...)Sequence analysis
Glycosylationi634 – 6341N-linked (GlcNAc...)Sequence analysis
Glycosylationi649 – 6491N-linked (GlcNAc...)Sequence analysis
Glycosylationi663 – 6631N-linked (GlcNAc...)Sequence analysis
Glycosylationi684 – 6841N-linked (GlcNAc...)Sequence analysis
Glycosylationi800 – 8001N-linked (GlcNAc...)Sequence analysis
Glycosylationi906 – 9061N-linked (GlcNAc...)Sequence analysis

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ9UKU6.
PRIDEiQ9UKU6.

PTM databases

PhosphoSiteiQ9UKU6.

Expressioni

Tissue specificityi

Predominantly expressed in brain.

Gene expression databases

BgeeiQ9UKU6.
CleanExiHS_TRHDE.
ExpressionAtlasiQ9UKU6. baseline and differential.
GenevisibleiQ9UKU6. HS.

Interactioni

Subunit structurei

Homodimer; disulfide-linked.By similarity

Protein-protein interaction databases

BioGridi118990. 13 interactions.
IntActiQ9UKU6. 2 interactions.
STRINGi9606.ENSP00000261180.

Structurei

3D structure databases

ProteinModelPortaliQ9UKU6.
SMRiQ9UKU6. Positions 135-1018.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni404 – 4085Substrate bindingBy similarity

Sequence similaritiesi

Belongs to the peptidase M1 family.Curated

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1046. Eukaryota.
COG0308. LUCA.
GeneTreeiENSGT00760000119082.
HOGENOMiHOG000106482.
HOVERGENiHBG095698.
InParanoidiQ9UKU6.
KOiK01306.
OMAiKYNVFNE.
OrthoDBiEOG754HNR.
PhylomeDBiQ9UKU6.
TreeFamiTF300395.

Family and domain databases

InterProiIPR024571. ERAP1-like_C_dom.
IPR001930. Peptidase_M1.
IPR014782. Peptidase_M1_N.
IPR015570. TRH-DE.
[Graphical view]
PANTHERiPTHR11533. PTHR11533. 2 hits.
PTHR11533:SF40. PTHR11533:SF40. 2 hits.
PfamiPF11838. ERAP1_C. 1 hit.
PF01433. Peptidase_M1. 1 hit.
[Graphical view]
PRINTSiPR00756. ALADIPTASE.
PROSITEiPS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9UKU6-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGEDDAALRA GSRGLSDPWA DSVGVRPRTT ERHIAVHKRL VLAFAVSLVA
60 70 80 90 100
LLAVTMLAVL LSLRFDECGA SATPGADGGP SGFPERGGNG SLPGSARRNH
110 120 130 140 150
HAGGDSWQPE AGGVASPGTT SAQPPSEEER EPWEPWTQLR LSGHLKPLHY
160 170 180 190 200
NLMLTAFMEN FTFSGEVNVE IACRNATRYV VLHASRVAVE KVQLAEDRAF
210 220 230 240 250
GAVPVAGFFL YPQTQVLVVV LNRTLDAQRN YNLKIIYNAL IENELLGFFR
260 270 280 290 300
SSYVLHGERR FLGVTQFSPT HARKAFPCFD EPIYKATFKI SIKHQATYLS
310 320 330 340 350
LSNMPVETSV FEEDGWVTDH FSQTPLMSTY YLAWAICNFT YRETTTKSGV
360 370 380 390 400
VVRLYARPDA IRRGSGDYAL HITKRLIEFY EDYFKVPYSL PKLDLLAVPK
410 420 430 440 450
HPYAAMENWG LSIFVEQRIL LDPSVSSISY LLDVTMVIVH EICHQWFGDL
460 470 480 490 500
VTPVWWEDVW LKEGFAHYFE FVGTDYLYPG WNMEKQRFLT DVLHEVMLLD
510 520 530 540 550
GLASSHPVSQ EVLQATDIDR VFDWIAYKKG AALIRMLANF MGHSVFQRGL
560 570 580 590 600
QDYLTIHKYG NAARNDLWNT LSEALKRNGK YVNIQEVMDQ WTLQMGYPVI
610 620 630 640 650
TILGNTTAEN RIIITQQHFI YDISAKTKAL KLQNNSYLWQ IPLTIVVGNR
660 670 680 690 700
SHVSSEAIIW VSNKSEHHRI TYLDKGSWLL GNINQTGYFR VNYDLRNWRL
710 720 730 740 750
LIDQLIRNHE VLSVSNRAGL IDDAFSLARA GYLPQNIPLE IIRYLSEEKD
760 770 780 790 800
FLPWHAASRA LYPLDKLLDR MENYNIFNEY ILKQVATTYI KLGWPKNNFN
810 820 830 840 850
GSLVQASYQH EELRREVIML ACSFGNKHCH QQASTLISDW ISSNRNRIPL
860 870 880 890 900
NVRDIVYCTG VSLLDEDVWE FIWMKFHSTT AVSEKKILLE ALTCSDDRNL
910 920 930 940 950
LNRLLNLSLN SEVVLDQDAI DVIIHVARNP HGRDLAWKFF RDKWKILNTR
960 970 980 990 1000
YGEALFMNSK LISGVTEFLN TEGELKELKN FMKNYDGVAA ASFSRAVETV
1010 1020
EANVRWKMLY QDELFQWLGK ALRH
Length:1,024
Mass (Da):117,000
Last modified:May 1, 2000 - v1
Checksum:iB82FBBC93927F6DC
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti958 – 9581N → Y in AAQ89125 (PubMed:12975309).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF126372 mRNA. Translation: AAF13141.1.
AY358765 mRNA. Translation: AAQ89125.1.
BC142706 mRNA. Translation: AAI42707.1.
BC150181 mRNA. Translation: AAI50182.1.
CCDSiCCDS9004.1.
RefSeqiNP_037513.1. NM_013381.2.
UniGeneiHs.199814.

Genome annotation databases

EnsembliENST00000261180; ENSP00000261180; ENSG00000072657.
GeneIDi29953.
KEGGihsa:29953.
UCSCiuc001sxa.4. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF126372 mRNA. Translation: AAF13141.1.
AY358765 mRNA. Translation: AAQ89125.1.
BC142706 mRNA. Translation: AAI42707.1.
BC150181 mRNA. Translation: AAI50182.1.
CCDSiCCDS9004.1.
RefSeqiNP_037513.1. NM_013381.2.
UniGeneiHs.199814.

3D structure databases

ProteinModelPortaliQ9UKU6.
SMRiQ9UKU6. Positions 135-1018.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi118990. 13 interactions.
IntActiQ9UKU6. 2 interactions.
STRINGi9606.ENSP00000261180.

Protein family/group databases

MEROPSiM01.008.

PTM databases

PhosphoSiteiQ9UKU6.

Polymorphism and mutation databases

BioMutaiTRHDE.
DMDMi11387208.

Proteomic databases

PaxDbiQ9UKU6.
PRIDEiQ9UKU6.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000261180; ENSP00000261180; ENSG00000072657.
GeneIDi29953.
KEGGihsa:29953.
UCSCiuc001sxa.4. human.

Organism-specific databases

CTDi29953.
GeneCardsiTRHDE.
H-InvDBHIX0010824.
HGNCiHGNC:30748. TRHDE.
MIMi606950. gene.
neXtProtiNX_Q9UKU6.
PharmGKBiPA142670702.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1046. Eukaryota.
COG0308. LUCA.
GeneTreeiENSGT00760000119082.
HOGENOMiHOG000106482.
HOVERGENiHBG095698.
InParanoidiQ9UKU6.
KOiK01306.
OMAiKYNVFNE.
OrthoDBiEOG754HNR.
PhylomeDBiQ9UKU6.
TreeFamiTF300395.

Miscellaneous databases

GenomeRNAii29953.
NextBioi52655.
PROiQ9UKU6.
SOURCEiSearch...

Gene expression databases

BgeeiQ9UKU6.
CleanExiHS_TRHDE.
ExpressionAtlasiQ9UKU6. baseline and differential.
GenevisibleiQ9UKU6. HS.

Family and domain databases

InterProiIPR024571. ERAP1-like_C_dom.
IPR001930. Peptidase_M1.
IPR014782. Peptidase_M1_N.
IPR015570. TRH-DE.
[Graphical view]
PANTHERiPTHR11533. PTHR11533. 2 hits.
PTHR11533:SF40. PTHR11533:SF40. 2 hits.
PfamiPF11838. ERAP1_C. 1 hit.
PF01433. Peptidase_M1. 1 hit.
[Graphical view]
PRINTSiPR00756. ALADIPTASE.
PROSITEiPS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Human TRH-degrading ectoenzyme cDNA cloning, functional expression, genomic structure and chromosomal assignment."
    Schomburg L., Turwitt S., Prescher G., Lohmann D., Horsthemke B., Bauer K.
    Eur. J. Biochem. 265:415-422(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Lung.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].

Entry informationi

Entry nameiTRHDE_HUMAN
AccessioniPrimary (citable) accession number: Q9UKU6
Secondary accession number(s): A5PL19, Q6UWJ4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: May 1, 2000
Last modified: March 16, 2016
This is version 138 of the entry and version 1 of the sequence. [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 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. Peptidase families
    Classification of peptidase families and list of entries
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.