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   13-FEB-2019, entry version 156.
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;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY,
RP   AND 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.,
RA   Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA   Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA   Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA   Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA   Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA   Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA   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
RT   project: 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;
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
RT   urine 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
RT   of consanguinity.";
RL   Nature 544:235-239(2017).
CC   -!- FUNCTION: Intestinal trehalase is probably involved in the
CC       hydrolysis 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,
CC         ChEBI:CHEBI:15903, ChEBI:CHEBI:16551, ChEBI:CHEBI:17925;
CC         EC=3.2.1.28; Evidence={ECO:0000269|PubMed:8773341,
CC         ECO:0000269|PubMed:9427547};
CC   -!- SUBUNIT: Homodimer; disulfide-linked.
CC       {ECO:0000250|UniProtKB:P19813}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane
CC       {ECO:0000250|UniProtKB:P19813}; Lipid-anchor, GPI-anchor
CC       {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         Note=No experimental confirmation available.;
CC   -!- TISSUE SPECIFICITY: Expressed in kidney, liver and small
CC       intestine. Also more weakly expressed in pancreas.
CC       {ECO:0000269|PubMed:9427547}.
CC   -!- DISEASE: Trehalase deficiency (TREHD) [MIM:612119]: An autosomal
CC       recessive condition characterized by the inability to digest
CC       trehalose, a disaccharide found in mushrooms, products containing
CC       baker's yeast, and dried food. Individuals with trehalase
CC       deficiency suffer from abdominal pain, increased rectal
CC       flatulence, and diarrhea due to osmotic water flow into the colon.
CC       {ECO:0000269|PubMed:28406212}. Note=The gene represented in this
CC       entry is involved in disease pathogenesis.
CC   -!- SIMILARITY: Belongs to the glycosyl hydrolase 37 family.
CC       {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   UniGene; Hs.129712; -.
DR   ProteinModelPortal; O43280; -.
DR   SMR; O43280; -.
DR   BioGrid; 116351; 1.
DR   STRING; 9606.ENSP00000264029; -.
DR   BindingDB; O43280; -.
DR   ChEMBL; CHEMBL3087; -.
DR   CAZy; GH37; Glycoside Hydrolase Family 37.
DR   iPTMnet; O43280; -.
DR   PhosphoSitePlus; O43280; -.
DR   BioMuta; TREH; -.
DR   PaxDb; O43280; -.
DR   PeptideAtlas; O43280; -.
DR   PRIDE; O43280; -.
DR   ProteomicsDB; 48848; -.
DR   ProteomicsDB; 48849; -. [O43280-2]
DR   DNASU; 11181; -.
DR   Ensembl; ENST00000264029; ENSP00000264029; ENSG00000118094. [O43280-1]
DR   Ensembl; ENST00000397925; ENSP00000381020; ENSG00000118094. [O43280-2]
DR   GeneID; 11181; -.
DR   KEGG; hsa:11181; -.
DR   UCSC; uc031ygn.2; human. [O43280-1]
DR   CTD; 11181; -.
DR   DisGeNET; 11181; -.
DR   EuPathDB; HostDB:ENSG00000118094.11; -.
DR   GeneCards; TREH; -.
DR   H-InvDB; HIX0010188; -.
DR   HGNC; HGNC:12266; TREH.
DR   HPA; HPA039913; -.
DR   HPA; HPA042045; -.
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   eggNOG; KOG0602; Eukaryota.
DR   eggNOG; COG1626; LUCA.
DR   GeneTree; ENSGT00390000006949; -.
DR   HOGENOM; HOG000215465; -.
DR   HOVERGEN; HBG014956; -.
DR   InParanoid; O43280; -.
DR   KO; K01194; -.
DR   OMA; NRYWDAS; -.
DR   OrthoDB; 417479at2759; -.
DR   PhylomeDB; O43280; -.
DR   TreeFam; TF314239; -.
DR   Reactome; R-HSA-189085; Digestion of dietary carbohydrate.
DR   GenomeRNAi; 11181; -.
DR   PRO; PR:O43280; -.
DR   Proteomes; UP000005640; Chromosome 11.
DR   Bgee; ENSG00000118094; Expressed in 83 organ(s), highest expression level in jejunal mucosa.
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; Complete proteome;
KW   Direct protein sequencing; Disulfide bond; Glycoprotein; Glycosidase;
KW   GPI-anchor; Hydrolase; Lipoprotein; Membrane; Polymorphism;
KW   Reference proteome; Signal.
FT   SIGNAL        1     23       {ECO:0000255}.
FT   CHAIN        24    556       Trehalase.
FT                                /FTId=PRO_0000012051.
FT   PROPEP      557    583       Removed in mature form. {ECO:0000255}.
FT                                /FTId=PRO_0000012052.
FT   REGION      175    176       Substrate binding.
FT                                {ECO:0000250|UniProtKB:P13482}.
FT   REGION      221    223       Substrate binding.
FT                                {ECO:0000250|UniProtKB:P13482}.
FT   REGION      286    288       Substrate binding.
FT                                {ECO:0000250|UniProtKB:P13482}.
FT   ACT_SITE    321    321       Proton donor/acceptor.
FT                                {ECO:0000250|UniProtKB:P13482}.
FT   ACT_SITE    514    514       Proton donor/acceptor.
FT                                {ECO:0000250|UniProtKB:P13482}.
FT   BINDING     168    168       Substrate.
FT                                {ECO:0000250|UniProtKB:P13482}.
FT   BINDING     212    212       Substrate.
FT                                {ECO:0000250|UniProtKB:P13482}.
FT   BINDING     319    319       Substrate; via carbonyl oxygen.
FT                                {ECO:0000250|UniProtKB:P13482}.
FT   BINDING     529    529       Substrate.
FT                                {ECO:0000250|UniProtKB:P13482}.
FT   LIPID       556    556       GPI-anchor amidated serine.
FT                                {ECO:0000255}.
FT   CARBOHYD     78     78       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00498}.
FT   CARBOHYD    239    239       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00498}.
FT   CARBOHYD    261    261       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00498}.
FT   CARBOHYD    369    369       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00498}.
FT   VAR_SEQ     175    206       WDSYWVMEGLLLSEMAETVKGMLQNFLDLVKT -> C (in
FT                                isoform 2).
FT                                {ECO:0000303|PubMed:15489334}.
FT                                /FTId=VSP_035440.
FT   VARIANT     389    389       T -> A (in dbSNP:rs2276065).
FT                                /FTId=VAR_049205.
FT   VARIANT     449    449       Y -> H (in dbSNP:rs11827611).
FT                                /FTId=VAR_049206.
FT   VARIANT     486    486       R -> W (in dbSNP:rs2276064).
FT                                /FTId=VAR_049207.
FT   VARIANT     558    558       A -> P (in dbSNP:rs6589671).
FT                                /FTId=VAR_049208.
FT   VARIANT     561    561       A -> P (in dbSNP:rs6589670).
FT                                /FTId=VAR_061191.
FT   CONFLICT    539    540       TN -> DE (in Ref. 1; BAA24381).
FT                                {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
//