TRHDE_HUMAN
ID TRHDE_HUMAN Reviewed; 1024 AA.
AC Q9UKU6; A5PL19; Q6UWJ4;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=Thyrotropin-releasing hormone-degrading ectoenzyme;
DE Short=TRH-DE;
DE Short=TRH-degrading ectoenzyme;
DE EC=3.4.19.6;
DE AltName: Full=Pyroglutamyl-peptidase II;
DE Short=PAP-II;
DE AltName: Full=TRH-specific aminopeptidase;
DE AltName: Full=Thyroliberinase;
GN Name=TRHDE; ORFNames=UNQ2507/PRO5995;
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].
RC TISSUE=Lung;
RX PubMed=10491199; DOI=10.1046/j.1432-1327.1999.00753.x;
RA Schomburg L., Turwitt S., Prescher G., Lohmann D., Horsthemke B., Bauer K.;
RT "Human TRH-degrading ectoenzyme cDNA cloning, functional expression,
RT genomic structure and chromosomal assignment.";
RL Eur. J. Biochem. 265:415-422(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
CC -!- FUNCTION: Specific inactivation of TRH after its release.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Release of the N-terminal pyroglutamyl group from pGlu-|-His-
CC Xaa tripeptides and pGlu-|-His-Xaa-Gly tetrapeptides.; EC=3.4.19.6;
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC -!- SUBUNIT: Homodimer; disulfide-linked. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type II membrane protein.
CC -!- TISSUE SPECIFICITY: Predominantly expressed in brain.
CC -!- SIMILARITY: Belongs to the peptidase M1 family. {ECO:0000305}.
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DR EMBL; AF126372; AAF13141.1; -; mRNA.
DR EMBL; AY358765; AAQ89125.1; -; mRNA.
DR EMBL; BC142706; AAI42707.1; -; mRNA.
DR EMBL; BC150181; AAI50182.1; -; mRNA.
DR RefSeq; NP_037513.1; NM_013381.2.
DR AlphaFoldDB; Q9UKU6; -.
DR SMR; Q9UKU6; -.
DR BioGRID; 118990; 135.
DR IntAct; Q9UKU6; 16.
DR MINT; Q9UKU6; -.
DR STRING; 9606.ENSP00000261180; -.
DR ChEMBL; CHEMBL3886123; -.
DR MEROPS; M01.008; -.
DR GlyGen; Q9UKU6; 13 sites, 1 O-linked glycan (1 site).
DR iPTMnet; Q9UKU6; -.
DR PhosphoSitePlus; Q9UKU6; -.
DR BioMuta; TRHDE; -.
DR DMDM; 11387208; -.
DR jPOST; Q9UKU6; -.
DR MassIVE; Q9UKU6; -.
DR PaxDb; Q9UKU6; -.
DR PeptideAtlas; Q9UKU6; -.
DR PRIDE; Q9UKU6; -.
DR ProteomicsDB; 84878; -.
DR Antibodypedia; 52788; 83 antibodies from 14 providers.
DR DNASU; 29953; -.
DR Ensembl; ENST00000261180.10; ENSP00000261180.5; ENSG00000072657.10.
DR GeneID; 29953; -.
DR KEGG; hsa:29953; -.
DR UCSC; uc001sxa.4; human.
DR CTD; 29953; -.
DR DisGeNET; 29953; -.
DR GeneCards; TRHDE; -.
DR HGNC; HGNC:30748; TRHDE.
DR HPA; ENSG00000072657; Tissue enhanced (brain, pancreas).
DR MIM; 606950; gene.
DR neXtProt; NX_Q9UKU6; -.
DR PharmGKB; PA142670702; -.
DR VEuPathDB; HostDB:ENSG00000072657; -.
DR eggNOG; KOG1046; Eukaryota.
DR HOGENOM; CLU_003705_2_2_1; -.
DR InParanoid; Q9UKU6; -.
DR OMA; ATDINRV; -.
DR OrthoDB; 110058at2759; -.
DR PhylomeDB; Q9UKU6; -.
DR TreeFam; TF300395; -.
DR PathwayCommons; Q9UKU6; -.
DR SignaLink; Q9UKU6; -.
DR BioGRID-ORCS; 29953; 12 hits in 1072 CRISPR screens.
DR ChiTaRS; TRHDE; human.
DR GenomeRNAi; 29953; -.
DR Pharos; Q9UKU6; Tbio.
DR PRO; PR:Q9UKU6; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q9UKU6; protein.
DR Bgee; ENSG00000072657; Expressed in jejunal mucosa and 139 other tissues.
DR ExpressionAtlas; Q9UKU6; baseline and differential.
DR Genevisible; Q9UKU6; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0004177; F:aminopeptidase activity; TAS:ProtInc.
DR GO; GO:0070006; F:metalloaminopeptidase activity; IBA:GO_Central.
DR GO; GO:0042277; F:peptide binding; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IBA:GO_Central.
DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
DR GO; GO:0043171; P:peptide catabolic process; IBA:GO_Central.
DR GO; GO:0006508; P:proteolysis; IBA:GO_Central.
DR GO; GO:0008217; P:regulation of blood pressure; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR CDD; cd09601; M1_APN-Q_like; 1.
DR Gene3D; 1.10.390.10; -; 1.
DR Gene3D; 2.60.40.1730; -; 1.
DR InterPro; IPR045357; Aminopeptidase_N-like_N.
DR InterPro; IPR042097; Aminopeptidase_N-like_N_sf.
DR InterPro; IPR024571; ERAP1-like_C_dom.
DR InterPro; IPR034016; M1_APN-typ.
DR InterPro; IPR001930; Peptidase_M1.
DR InterPro; IPR014782; Peptidase_M1_dom.
DR InterPro; IPR027268; Peptidase_M4/M1_CTD_sf.
DR InterPro; IPR015570; TRH-DE.
DR PANTHER; PTHR11533:SF40; PTHR11533:SF40; 1.
DR Pfam; PF11838; ERAP1_C; 1.
DR Pfam; PF01433; Peptidase_M1; 1.
DR Pfam; PF17900; Peptidase_M1_N; 1.
DR PRINTS; PR00756; ALADIPTASE.
DR SUPFAM; SSF63737; SSF63737; 1.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 2: Evidence at transcript level;
KW Aminopeptidase; Disulfide bond; Glycoprotein; Hydrolase; Membrane;
KW Metal-binding; Metalloprotease; Protease; Reference proteome;
KW Signal-anchor; Transmembrane; Transmembrane helix; Zinc.
FT CHAIN 1..1024
FT /note="Thyrotropin-releasing hormone-degrading ectoenzyme"
FT /id="PRO_0000095118"
FT TOPO_DOM 1..40
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 41..61
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 62..1024
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT REGION 72..135
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 441
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 404..408
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 440
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 444
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 463
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT SITE 527
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250"
FT CARBOHYD 89
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 160
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 175
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 222
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 338
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 605
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 634
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 649
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 663
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 684
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 800
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 906
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 68
FT /note="Interchain"
FT /evidence="ECO:0000250"
FT CONFLICT 958
FT /note="N -> Y (in Ref. 2; AAQ89125)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1024 AA; 117000 MW; B82FBBC93927F6DC CRC64;
MGEDDAALRA GSRGLSDPWA DSVGVRPRTT ERHIAVHKRL VLAFAVSLVA LLAVTMLAVL
LSLRFDECGA SATPGADGGP SGFPERGGNG SLPGSARRNH HAGGDSWQPE AGGVASPGTT
SAQPPSEEER EPWEPWTQLR LSGHLKPLHY NLMLTAFMEN FTFSGEVNVE IACRNATRYV
VLHASRVAVE KVQLAEDRAF GAVPVAGFFL YPQTQVLVVV LNRTLDAQRN YNLKIIYNAL
IENELLGFFR SSYVLHGERR FLGVTQFSPT HARKAFPCFD EPIYKATFKI SIKHQATYLS
LSNMPVETSV FEEDGWVTDH FSQTPLMSTY YLAWAICNFT YRETTTKSGV VVRLYARPDA
IRRGSGDYAL HITKRLIEFY EDYFKVPYSL PKLDLLAVPK HPYAAMENWG LSIFVEQRIL
LDPSVSSISY LLDVTMVIVH EICHQWFGDL VTPVWWEDVW LKEGFAHYFE FVGTDYLYPG
WNMEKQRFLT DVLHEVMLLD GLASSHPVSQ EVLQATDIDR VFDWIAYKKG AALIRMLANF
MGHSVFQRGL QDYLTIHKYG NAARNDLWNT LSEALKRNGK YVNIQEVMDQ WTLQMGYPVI
TILGNTTAEN RIIITQQHFI YDISAKTKAL KLQNNSYLWQ IPLTIVVGNR SHVSSEAIIW
VSNKSEHHRI TYLDKGSWLL GNINQTGYFR VNYDLRNWRL LIDQLIRNHE VLSVSNRAGL
IDDAFSLARA GYLPQNIPLE IIRYLSEEKD FLPWHAASRA LYPLDKLLDR MENYNIFNEY
ILKQVATTYI KLGWPKNNFN GSLVQASYQH EELRREVIML ACSFGNKHCH QQASTLISDW
ISSNRNRIPL NVRDIVYCTG VSLLDEDVWE FIWMKFHSTT AVSEKKILLE ALTCSDDRNL
LNRLLNLSLN SEVVLDQDAI DVIIHVARNP HGRDLAWKFF RDKWKILNTR YGEALFMNSK
LISGVTEFLN TEGELKELKN FMKNYDGVAA ASFSRAVETV EANVRWKMLY QDELFQWLGK
ALRH
