TREA_HUMAN
ID TREA_HUMAN Reviewed; 583 AA.
AC O43280; Q32MB9; Q53FY8;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 23-SEP-2008, sequence version 2.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=Trehalase {ECO:0000303|PubMed:9427547};
DE EC=3.2.1.28 {ECO:0000269|PubMed:8773341, ECO:0000269|PubMed:9427547};
DE AltName: Full=Alpha,alpha-trehalase;
DE AltName: Full=Alpha,alpha-trehalose glucohydrolase;
DE Flags: Precursor;
GN Name=TREH {ECO:0000312|HGNC:HGNC:12266}; Synonyms=TREA;
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] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY, AND
RP TISSUE SPECIFICITY.
RC TISSUE=Kidney;
RX PubMed=9427547; DOI=10.1016/s0378-1119(97)00455-1;
RA Ishihara R., Taketani S., Sasai-Takedatsu M., Kino M., Tokunaga R.,
RA Kobayashi Y.;
RT "Molecular cloning, sequencing and expression of cDNA encoding human
RT trehalase.";
RL Gene 202:69-74(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Kidney;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 [5]
RP PARTIAL PROTEIN SEQUENCE, FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=8773341; DOI=10.1159/000189037;
RA Sasai-Takedatsu M., Taketani S., Nagata N., Furukawa T., Tokunaga R.,
RA Kojima T., Kobayashi Y.;
RT "Human trehalase: characterization, localization, and its increase in urine
RT by renal proximal tubular damage.";
RL Nephron 73:179-185(1996).
RN [6]
RP INVOLVEMENT IN TREHD.
RX PubMed=28406212; DOI=10.1038/nature22034;
RA Saleheen D., Natarajan P., Armean I.M., Zhao W., Rasheed A.,
RA Khetarpal S.A., Won H.H., Karczewski K.J., O'Donnell-Luria A.H.,
RA Samocha K.E., Weisburd B., Gupta N., Zaidi M., Samuel M., Imran A.,
RA Abbas S., Majeed F., Ishaq M., Akhtar S., Trindade K., Mucksavage M.,
RA Qamar N., Zaman K.S., Yaqoob Z., Saghir T., Rizvi S.N.H., Memon A.,
RA Hayyat Mallick N., Ishaq M., Rasheed S.Z., Memon F.U., Mahmood K.,
RA Ahmed N., Do R., Krauss R.M., MacArthur D.G., Gabriel S., Lander E.S.,
RA Daly M.J., Frossard P., Danesh J., Rader D.J., Kathiresan S.;
RT "Human knockouts and phenotypic analysis in a cohort with a high rate of
RT consanguinity.";
RL Nature 544:235-239(2017).
CC -!- FUNCTION: Intestinal trehalase is probably involved in the hydrolysis
CC of ingested trehalose. {ECO:0000269|PubMed:8773341,
CC ECO:0000269|PubMed:9427547}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=alpha,alpha-trehalose + H2O = alpha-D-glucose + beta-D-
CC glucose; Xref=Rhea:RHEA:32675, ChEBI:CHEBI:15377, ChEBI:CHEBI:15903,
CC ChEBI:CHEBI:16551, ChEBI:CHEBI:17925; EC=3.2.1.28;
CC Evidence={ECO:0000269|PubMed:8773341, ECO:0000269|PubMed:9427547};
CC -!- SUBUNIT: Homodimer; disulfide-linked. {ECO:0000250|UniProtKB:P19813}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P19813};
CC Lipid-anchor, GPI-anchor {ECO:0000250|UniProtKB:P19813}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O43280-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O43280-2; Sequence=VSP_035440;
CC -!- TISSUE SPECIFICITY: Expressed in kidney, liver and small intestine.
CC Also more weakly expressed in pancreas. {ECO:0000269|PubMed:9427547}.
CC -!- DISEASE: Trehalase deficiency (TREHD) [MIM:612119]: An autosomal
CC recessive condition characterized by the inability to digest trehalose,
CC a disaccharide found in mushrooms, products containing baker's yeast,
CC and dried food. Individuals with trehalase deficiency suffer from
CC abdominal pain, increased rectal flatulence, and diarrhea due to
CC osmotic water flow into the colon. {ECO:0000269|PubMed:28406212}.
CC Note=The gene represented in this entry is involved in disease
CC pathogenesis.
CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 37 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Trehalase entry;
CC URL="https://en.wikipedia.org/wiki/Trehalase";
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DR EMBL; AB000824; BAA24381.1; -; mRNA.
DR EMBL; AK223140; BAD96860.1; -; mRNA.
DR EMBL; AK223143; BAD96863.1; -; mRNA.
DR EMBL; CH471065; EAW67409.1; -; Genomic_DNA.
DR EMBL; BC109206; AAI09207.1; -; mRNA.
DR CCDS; CCDS73401.1; -. [O43280-2]
DR CCDS; CCDS73402.1; -. [O43280-1]
DR PIR; JC6504; JC6504.
DR RefSeq; NP_001287994.1; NM_001301065.1. [O43280-2]
DR RefSeq; NP_009111.2; NM_007180.2. [O43280-1]
DR AlphaFoldDB; O43280; -.
DR SMR; O43280; -.
DR BioGRID; 116351; 6.
DR IntAct; O43280; 2.
DR STRING; 9606.ENSP00000264029; -.
DR BindingDB; O43280; -.
DR ChEMBL; CHEMBL3087; -.
DR CAZy; GH37; Glycoside Hydrolase Family 37.
DR GlyGen; O43280; 4 sites.
DR iPTMnet; O43280; -.
DR PhosphoSitePlus; O43280; -.
DR BioMuta; TREH; -.
DR MassIVE; O43280; -.
DR PaxDb; O43280; -.
DR PeptideAtlas; O43280; -.
DR PRIDE; O43280; -.
DR ProteomicsDB; 48848; -. [O43280-1]
DR ProteomicsDB; 48849; -. [O43280-2]
DR Antibodypedia; 48758; 123 antibodies from 20 providers.
DR DNASU; 11181; -.
DR Ensembl; ENST00000264029.9; ENSP00000264029.5; ENSG00000118094.12. [O43280-1]
DR Ensembl; ENST00000397925.2; ENSP00000381020.2; ENSG00000118094.12. [O43280-2]
DR GeneID; 11181; -.
DR KEGG; hsa:11181; -.
DR MANE-Select; ENST00000264029.9; ENSP00000264029.5; NM_007180.3; NP_009111.2.
DR UCSC; uc031ygn.2; human. [O43280-1]
DR CTD; 11181; -.
DR DisGeNET; 11181; -.
DR GeneCards; TREH; -.
DR HGNC; HGNC:12266; TREH.
DR HPA; ENSG00000118094; Tissue enriched (intestine).
DR MalaCards; TREH; -.
DR MIM; 275360; gene.
DR MIM; 612119; phenotype.
DR neXtProt; NX_O43280; -.
DR OpenTargets; ENSG00000118094; -.
DR Orphanet; 103909; Trehalase deficiency.
DR PharmGKB; PA36946; -.
DR VEuPathDB; HostDB:ENSG00000118094; -.
DR eggNOG; KOG0602; Eukaryota.
DR GeneTree; ENSGT00390000006949; -.
DR HOGENOM; CLU_006451_4_3_1; -.
DR InParanoid; O43280; -.
DR OMA; TNGVLIW; -.
DR OrthoDB; 417479at2759; -.
DR PhylomeDB; O43280; -.
DR TreeFam; TF314239; -.
DR BRENDA; 3.2.1.28; 2681.
DR PathwayCommons; O43280; -.
DR Reactome; R-HSA-189085; Digestion of dietary carbohydrate.
DR SignaLink; O43280; -.
DR BioGRID-ORCS; 11181; 6 hits in 306 CRISPR screens.
DR GenomeRNAi; 11181; -.
DR Pharos; O43280; Tchem.
DR PRO; PR:O43280; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; O43280; protein.
DR Bgee; ENSG00000118094; Expressed in jejunal mucosa and 94 other tissues.
DR ExpressionAtlas; O43280; baseline and differential.
DR Genevisible; O43280; HS.
DR GO; GO:0031225; C:anchored component of membrane; ISS:UniProtKB.
DR GO; GO:0046658; C:anchored component of plasma membrane; TAS:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0004555; F:alpha,alpha-trehalase activity; IDA:UniProtKB.
DR GO; GO:0009887; P:animal organ morphogenesis; IEA:Ensembl.
DR GO; GO:0005993; P:trehalose catabolic process; IDA:UniProtKB.
DR GO; GO:0005991; P:trehalose metabolic process; NAS:UniProtKB.
DR Gene3D; 1.50.10.10; -; 1.
DR InterPro; IPR008928; 6-hairpin_glycosidase_sf.
DR InterPro; IPR012341; 6hp_glycosidase-like_sf.
DR InterPro; IPR001661; Glyco_hydro_37.
DR InterPro; IPR018232; Glyco_hydro_37_CS.
DR PANTHER; PTHR23403; PTHR23403; 1.
DR Pfam; PF01204; Trehalase; 1.
DR PRINTS; PR00744; GLHYDRLASE37.
DR SUPFAM; SSF48208; SSF48208; 1.
DR PROSITE; PS00927; TREHALASE_1; 1.
DR PROSITE; PS00928; TREHALASE_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Direct protein sequencing;
KW Disulfide bond; Glycoprotein; Glycosidase; GPI-anchor; Hydrolase;
KW Lipoprotein; Membrane; Reference proteome; Signal.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..556
FT /note="Trehalase"
FT /id="PRO_0000012051"
FT PROPEP 557..583
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000012052"
FT ACT_SITE 321
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:P13482"
FT ACT_SITE 514
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:P13482"
FT BINDING 168
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P13482"
FT BINDING 175..176
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P13482"
FT BINDING 212
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P13482"
FT BINDING 221..223
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P13482"
FT BINDING 286..288
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P13482"
FT BINDING 319
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P13482"
FT BINDING 529
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P13482"
FT LIPID 556
FT /note="GPI-anchor amidated serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 78
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 239
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 261
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 369
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT VAR_SEQ 175..206
FT /note="WDSYWVMEGLLLSEMAETVKGMLQNFLDLVKT -> C (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_035440"
FT VARIANT 389
FT /note="T -> A (in dbSNP:rs2276065)"
FT /id="VAR_049205"
FT VARIANT 449
FT /note="Y -> H (in dbSNP:rs11827611)"
FT /id="VAR_049206"
FT VARIANT 486
FT /note="R -> W (in dbSNP:rs2276064)"
FT /id="VAR_049207"
FT VARIANT 558
FT /note="A -> P (in dbSNP:rs6589671)"
FT /id="VAR_049208"
FT VARIANT 561
FT /note="A -> P (in dbSNP:rs6589670)"
FT /id="VAR_061191"
FT CONFLICT 539..540
FT /note="TN -> DE (in Ref. 1; BAA24381)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 583 AA; 66568 MW; 3EE4D312B82185F9 CRC64;
MPGRTWELCL LLLLGLGLGS QEALPPPCES EIYCHGELLN QVQMAKLYQD DKQFVDMPLS
IAPEQVLQTF TELSRDHNHS IPREQLQAFV HEHFQAKGQE LQPWTPADWK DSPQFLQKIS
DAKLRAWAGQ LHQLWKKLGK KMKPEVLSHP ERFSLIYSEH PFIVPGGRFV EFYYWDSYWV
MEGLLLSEMA ETVKGMLQNF LDLVKTYGHV PNGGRVYYLQ RSQPPLLTLM MDCYLTHTND
TAFLQENIET LALELDFWTK NRTVSVSLEG KNYLLNRYYV PYGGPRPESY SKDVELADTL
PEGDREALWA ELKAGAESGW DFSSRWLIGG PNPNSLSGIR TSKLVPVDLN AFLCQAEELM
SNFYSRLGND SQATKYRILR SQRLAALNTV LWDEQTGAWF DYDLEKKKKN REFYPSNLTP
LWAGCFSDPG VADKALKYLE DNRILTYQYG IPTSLQKTGQ QWDFPNAWAP LQDLVIRGLA
KAPLRRAQEV AFQLAQNWIR TNFDVYSQKS AMYEKYDVSN GGQPGGGGEY EVQEGFGWTN
GVVLMLLDRY GDRLTSGAKL AFLEPHCLAA TLLPSLLLSL LPW
