TRHDE_MOUSE
ID TRHDE_MOUSE Reviewed; 1025 AA.
AC Q8K093;
DT 09-NOV-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 146.
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye;
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).
RN [2]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Specific inactivation of TRH after its release.
CC {ECO:0000250}.
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 {ECO:0000250}; Single-pass type II
CC membrane protein {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the peptidase M1 family. {ECO:0000305}.
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DR EMBL; BC032288; AAH32288.1; -; mRNA.
DR RefSeq; NP_666353.1; NM_146241.2.
DR AlphaFoldDB; Q8K093; -.
DR SMR; Q8K093; -.
DR STRING; 10090.ENSMUSP00000057449; -.
DR ChEMBL; CHEMBL3600275; -.
DR MEROPS; M01.008; -.
DR GlyGen; Q8K093; 12 sites.
DR PhosphoSitePlus; Q8K093; -.
DR jPOST; Q8K093; -.
DR PaxDb; Q8K093; -.
DR PRIDE; Q8K093; -.
DR ProteomicsDB; 259311; -.
DR Antibodypedia; 52788; 83 antibodies from 14 providers.
DR DNASU; 237553; -.
DR Ensembl; ENSMUST00000061632; ENSMUSP00000057449; ENSMUSG00000050663.
DR GeneID; 237553; -.
DR KEGG; mmu:237553; -.
DR UCSC; uc007hat.2; mouse.
DR CTD; 29953; -.
DR MGI; MGI:2384311; Trhde.
DR VEuPathDB; HostDB:ENSMUSG00000050663; -.
DR eggNOG; KOG1046; Eukaryota.
DR GeneTree; ENSGT00940000155878; -.
DR HOGENOM; CLU_003705_2_2_1; -.
DR InParanoid; Q8K093; -.
DR OrthoDB; 110058at2759; -.
DR PhylomeDB; Q8K093; -.
DR TreeFam; TF300395; -.
DR BioGRID-ORCS; 237553; 3 hits in 73 CRISPR screens.
DR ChiTaRS; Trhde; mouse.
DR PRO; PR:Q8K093; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q8K093; protein.
DR Bgee; ENSMUSG00000050663; Expressed in pigmented layer of retina and 54 other tissues.
DR ExpressionAtlas; Q8K093; baseline and differential.
DR Genevisible; Q8K093; MM.
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: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; Disulfide bond; Glycoprotein; Hydrolase; Membrane;
KW Metal-binding; Metalloprotease; Phosphoprotein; Protease;
KW Reference proteome; Signal-anchor; Transmembrane; Transmembrane helix;
KW Zinc.
FT CHAIN 1..1025
FT /note="Thyrotropin-releasing hormone-degrading ectoenzyme"
FT /id="PRO_0000095119"
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 77..135
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 110..135
FT /note="Polar residues"
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"
FT /evidence="ECO:0000250"
SQ SEQUENCE 1025 AA; 117458 MW; 0990B2A78A13B8AB CRC64;
MGEDDAALRA SGRGLSDPWA DSVGVRPRTT ERHIAVHKRL VLAFAVSIVA LLAVTMLAVL
LSLRFDECGA SAAMPGTDGG LGGFPERDSN SSFPGSARRN HHAGGESSQR ESGEVGTPGT
PSAQPPSEEE REQWQPWTQL RLSGHLKPLH YNLMLTAFME NFTFSGEVNV EIACRNATRY
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
AWNMEKQRFL TDVLHEVMLL DGLASSHPVS QEVLRATDID RVFDWIAYKK GAALIRMLAN
FMGHSVFQRG LQDYLTIHKY GNAARNDLWN TLSEALRRNG KYVNIQEVMD QWTLQMGYPV
ITILGNTTAE NRILITQQHF IYDIGAKTKA LQLQNSSYLW QIPLTIVVGN RSHVSSEAII
WVSNKSEHHR IAYLDRGSWI LGNINQTGYF RVNYDLRNWR LLIDQLIRNH EVLSVSNRAA
LIDDAFSLAR AGYLPQNIPL EIIRYLSEEK DFLPWHAASR ALYPLDKLLD RMENYNIFNE
YILKQVATTY IKLGWPRNNF NGSLVQASYQ HEELRREVIM LACSFGNKHC HQQASTLISD
WISSNRNRIP LNVRDIVYCT GVSLLDEDVW EFIWMKFHST TAVSEKKILL EALTCSDDRN
LLSRLLNLSL NSEVVLDQDA IDVIIHVARN PHGRDLAWKF FRDKWKILNT RYGEALFMNS
KLISGVTEFL NTEGELKELK NFMKSYDGVA SASFSRAVET VEANVRWKRF YQDELFQWLG
KAMRH
