TRHDE_RAT
ID TRHDE_RAT Reviewed; 1025 AA.
AC Q10836;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 158.
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;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RC STRAIN=Sprague-Dawley; TISSUE=Pituitary;
RX PubMed=7937801; DOI=10.1073/pnas.91.20.9534;
RA Schauder B., Schomburg L., Koehrle J., Bauer K.;
RT "Cloning of a cDNA encoding an ectoenzyme that degrades thyrotropin-
RT releasing hormone.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:9534-9538(1994).
RN [2]
RP INTERCHAIN DISULFIDE BOND.
RX PubMed=10785382; DOI=10.1046/j.1432-1327.2000.01277.x;
RA Papadopoulos T., Heuer H., Bauer K.;
RT "Analysis of the thyrotropin-releasing hormone-degrading ectoenzyme by
RT site-directed mutagenesis of cysteine residues. Cys68 is involved in
RT disulfide-linked dimerization.";
RL Eur. J. Biochem. 267:2617-2623(2000).
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.
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type II membrane protein.
CC -!- TISSUE SPECIFICITY: Predominantly expressed in brain and pituitary.
CC Lower levels in lung and liver.
CC -!- SIMILARITY: Belongs to the peptidase M1 family. {ECO:0000305}.
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DR EMBL; X80535; CAA56675.1; -; mRNA.
DR PIR; I59331; I59331.
DR AlphaFoldDB; Q10836; -.
DR SMR; Q10836; -.
DR STRING; 10116.ENSRNOP00000007461; -.
DR MEROPS; M01.008; -.
DR GlyGen; Q10836; 12 sites.
DR iPTMnet; Q10836; -.
DR PhosphoSitePlus; Q10836; -.
DR PaxDb; Q10836; -.
DR PRIDE; Q10836; -.
DR RGD; 728895; Trhde.
DR eggNOG; KOG1046; Eukaryota.
DR InParanoid; Q10836; -.
DR PhylomeDB; Q10836; -.
DR BRENDA; 3.4.19.6; 5301.
DR PRO; PR:Q10836; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0004177; F:aminopeptidase activity; TAS:RGD.
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: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 1: Evidence at protein level;
KW Aminopeptidase; Direct protein sequencing; Disulfide bond; Glycoprotein;
KW Hydrolase; Membrane; Metal-binding; Metalloprotease; Phosphoprotein;
KW Protease; Reference proteome; Signal-anchor; Transmembrane;
KW Transmembrane helix; Zinc.
FT CHAIN 1..1025
FT /note="Thyrotropin-releasing hormone-degrading ectoenzyme"
FT /id="PRO_0000095120"
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..1025
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT REGION 76..136
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 442
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 405..409
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 441
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 445
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 464
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT SITE 528
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250"
FT MOD_RES 30
FT /note="Phosphothreonine; by PKC"
FT /evidence="ECO:0000255"
FT CARBOHYD 90
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 161
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 176
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 223
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 339
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 606
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 635
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 650
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 664
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 685
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 801
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 907
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 68
FT /note="Interchain"
SQ SEQUENCE 1025 AA; 117287 MW; 4024EB262608D16B CRC64;
MGEDDAALRA SGRGLSDPWA DSVGVRPRTT ERHIAVHKRL VLAFAVSIVA LLAVTMLAVL
LSLRFDECGA SAAMPGTDGG LGGFPERGGN SSYPGSARRN HHAGEESSQR EIGEVGTAGT
PSAHPPSEEE QEQWQPWTQL RLSGHLKPLH YNLMLTAFME NFTFSGEVNV EIACQNATRY
VVLHASRVAV EKVQVAEDRA FGAVPVAGFF LYPQTQVLVV VLNRTLDAQR HYNLKIIYNA
LIENELLGFF RSSYVIHGER RFLGVTQFSP THARKAFPCF DEPIYKATFK ISIKHQATYL
SLSNMPVETS VFEEDGWVTD HFSQTPLMST YYLAWAICNF TYRETTTKSG VVVRLYARPD
AIRRGSGDYA LHITKRLIEF YEDYFKVPYS LPKLDLLAVP KHPYAAMENW GLSIFVEQRI
LLDPSVSSIS YLLDVTMVIV HEICHQWFGD LVTPVWWEDV WLKEGFAHYF EFVGTDYLYP
SWNMEKQRFL TDVLHEVMLL DGLASSHPVS QEVLRATDID KVFDWIAYKK GAALIRMLAN
FMGHSVFQRG LQDYLTIHKY GNAARNDLWN TLSEALKRNG KYVNIQEVMD QWTLQMGYPV
ITILGNMTAE NRILITQQHF IYDIGAKTKA LQLQNSSYLW QIPLTIVVGN RSHVSSEAII
WVSNKSEHHR ITYLDKGSWI LGNINQTGYF RVNYDLRNWR LLIDQLIRNH EVLSVSNRAG
LIDDAFSLAR AGYLPQNIPL EIIRYLSEEK DFLPWHAASR ALYPLDKLLD RMENYNIFNE
YILKQVATTY SKLGWPKNNF NGSVVQASYQ HEELRREVIM LACSFGNKHC HQQASTLISD
WISSNRNRIP LNVRDIVYCT GVSLLDEDVW EFIWMKFHST TAVSEKKILL EALTCSDDRN
LLSRLLNLSL NSEVVLDQDA IDVIIHVARN PHGRDLAWKF FRDKWKILNT RYGEALFMNS
KLISGVTEFL NTEGELKELK NFMKSYDGVA SASFSRAVET VEANVRWKRL YQDELFQWLG
KAMRH
