T3HPD_HUMAN
ID T3HPD_HUMAN Reviewed; 354 AA.
AC Q96EM0; Q96LJ5;
DT 29-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 2.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=Trans-3-hydroxy-L-proline dehydratase {ECO:0000303|PubMed:22528483, ECO:0000303|PubMed:24649405};
DE EC=4.2.1.77 {ECO:0000269|PubMed:22528483, ECO:0000269|PubMed:24649405};
DE AltName: Full=Trans-L-3-hydroxyproline dehydratase;
GN Name=L3HYPDH; Synonyms=C14orf149;
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 [LARGE SCALE MRNA].
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skin;
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 [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE
RP SPECIFICITY, AND MUTAGENESIS OF THR-273.
RX PubMed=22528483; DOI=10.1074/jbc.m112.363218;
RA Visser W.F., Verhoeven-Duif N.M., de Koning T.J.;
RT "Identification of a human trans-3-Hydroxy-L-proline dehydratase, the first
RT characterized member of a novel family of proline racemase-like enzymes.";
RL J. Biol. Chem. 287:21654-21662(2012).
RN [6]
RP CATALYTIC ACTIVITY, AND SUBUNIT.
RX PubMed=24649405; DOI=10.1016/j.fob.2014.02.010;
RA Watanabe S., Tanimoto Y., Yamauchi S., Tozawa Y., Sawayama S., Watanabe Y.;
RT "Identification and characterization of trans-3-hydroxy-L-proline
RT dehydratase and Delta(1)-pyrroline-2-carboxylate reductase involved in
RT trans-3-hydroxy-L-proline metabolism of bacteria.";
RL FEBS Open Bio 4:240-250(2014).
CC -!- FUNCTION: Catalyzes the dehydration of trans-3-hydroxy-L-proline to
CC Delta(1)-pyrroline-2-carboxylate (Pyr2C). May be required to degrade
CC trans-3-hydroxy-L-proline from the diet and originating from the
CC degradation of proteins such as collagen-IV that contain it.
CC {ECO:0000269|PubMed:22528483}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=trans-3-hydroxy-L-proline = 1-pyrroline-2-carboxylate + H2O;
CC Xref=Rhea:RHEA:10320, ChEBI:CHEBI:15377, ChEBI:CHEBI:39785,
CC ChEBI:CHEBI:57938; EC=4.2.1.77;
CC Evidence={ECO:0000269|PubMed:22528483, ECO:0000269|PubMed:24649405};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=7.23 mM for trans-3-hydroxy-L-proline
CC {ECO:0000269|PubMed:22528483};
CC Vmax=39.5 umol/min/mg enzyme {ECO:0000269|PubMed:22528483};
CC pH dependence:
CC Optimum pH is 8.0. {ECO:0000269|PubMed:22528483};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:24649405}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC {ECO:0000269|PubMed:22528483}.
CC -!- MISCELLANEOUS: In contrast to the T.cruzi proline racemase enzyme,
CC lacks the conserved Cys at position 273 which is replaced by a Thr
CC residue, transforming the racemase activity into dehydratase activity.
CC {ECO:0000305|PubMed:22528483}.
CC -!- SIMILARITY: Belongs to the proline racemase family. {ECO:0000305}.
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DR EMBL; AK058165; BAB71696.1; -; mRNA.
DR EMBL; AL159140; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC012131; AAH12131.1; -; mRNA.
DR CCDS; CCDS9739.1; -.
DR RefSeq; NP_653182.1; NM_144581.1.
DR AlphaFoldDB; Q96EM0; -.
DR SMR; Q96EM0; -.
DR BioGRID; 125210; 35.
DR IntAct; Q96EM0; 12.
DR MINT; Q96EM0; -.
DR STRING; 9606.ENSP00000247194; -.
DR DrugBank; DB00172; Proline.
DR GlyGen; Q96EM0; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q96EM0; -.
DR PhosphoSitePlus; Q96EM0; -.
DR BioMuta; L3HYPDH; -.
DR DMDM; 296452868; -.
DR EPD; Q96EM0; -.
DR jPOST; Q96EM0; -.
DR MassIVE; Q96EM0; -.
DR MaxQB; Q96EM0; -.
DR PaxDb; Q96EM0; -.
DR PeptideAtlas; Q96EM0; -.
DR PRIDE; Q96EM0; -.
DR ProteomicsDB; 76425; -.
DR Antibodypedia; 68443; 52 antibodies from 14 providers.
DR DNASU; 112849; -.
DR Ensembl; ENST00000247194.9; ENSP00000247194.4; ENSG00000126790.12.
DR GeneID; 112849; -.
DR KEGG; hsa:112849; -.
DR MANE-Select; ENST00000247194.9; ENSP00000247194.4; NM_144581.2; NP_653182.1.
DR UCSC; uc001xee.2; human.
DR CTD; 112849; -.
DR DisGeNET; 112849; -.
DR GeneCards; L3HYPDH; -.
DR HGNC; HGNC:20488; L3HYPDH.
DR HPA; ENSG00000126790; Low tissue specificity.
DR MIM; 614811; gene.
DR neXtProt; NX_Q96EM0; -.
DR OpenTargets; ENSG00000126790; -.
DR PharmGKB; PA134961537; -.
DR VEuPathDB; HostDB:ENSG00000126790; -.
DR eggNOG; ENOG502QRPF; Eukaryota.
DR GeneTree; ENSGT00390000002032; -.
DR HOGENOM; CLU_036729_0_1_1; -.
DR InParanoid; Q96EM0; -.
DR OMA; SHVLWTG; -.
DR OrthoDB; 894373at2759; -.
DR PhylomeDB; Q96EM0; -.
DR TreeFam; TF329167; -.
DR BRENDA; 4.2.1.77; 2681.
DR PathwayCommons; Q96EM0; -.
DR SignaLink; Q96EM0; -.
DR BioGRID-ORCS; 112849; 13 hits in 1081 CRISPR screens.
DR ChiTaRS; L3HYPDH; human.
DR GenomeRNAi; 112849; -.
DR Pharos; Q96EM0; Tdark.
DR PRO; PR:Q96EM0; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q96EM0; protein.
DR Bgee; ENSG00000126790; Expressed in right uterine tube and 156 other tissues.
DR ExpressionAtlas; Q96EM0; baseline and differential.
DR Genevisible; Q96EM0; HS.
DR GO; GO:0016836; F:hydro-lyase activity; IDA:UniProtKB.
DR GO; GO:0050346; F:trans-L-3-hydroxyproline dehydratase activity; IEA:UniProtKB-EC.
DR InterPro; IPR008794; Pro_racemase_fam.
DR PANTHER; PTHR33442; PTHR33442; 1.
DR Pfam; PF05544; Pro_racemase; 1.
DR PIRSF; PIRSF029792; Pro_racemase; 1.
DR SFLD; SFLDS00028; Proline_Racemase; 1.
PE 1: Evidence at protein level;
KW Lyase; Reference proteome.
FT CHAIN 1..354
FT /note="Trans-3-hydroxy-L-proline dehydratase"
FT /id="PRO_0000288949"
FT ACT_SITE 104
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 105..106
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 269
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 274..275
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT VARIANT 42
FT /note="V -> A (in dbSNP:rs17096291)"
FT /id="VAR_032540"
FT VARIANT 125
FT /note="P -> S (in dbSNP:rs35622288)"
FT /id="VAR_062192"
FT VARIANT 315
FT /note="A -> V (in dbSNP:rs1046701)"
FT /id="VAR_032541"
FT VARIANT 341
FT /note="I -> V (in dbSNP:rs8660)"
FT /id="VAR_032542"
FT MUTAGEN 273
FT /note="T->C: Regains racemase activity, catalyzing the
FT conversion of trans-3-hydroxy-L-proline to cis-3-hydroxy-D-
FT proline. Also catalyzes racemization of L-proline to D-
FT proline, albeit at a very low level. Has lost its original
FT dehydratase activity."
FT /evidence="ECO:0000269|PubMed:22528483"
FT CONFLICT 9
FT /note="R -> W (in Ref. 3; AAH12131)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 354 AA; 38138 MW; D279EE0B7C679969 CRC64;
MESALAVPRL PPHDPGTPVL SVVDMHTGGE PLRIVLAGCP EVSGPTLLAK RRYMRQHLDH
VRRRLMFEPR GHRDMYGAVL VPSELPDAHL GVLFLHNEGY SSMCGHAVLA LGRFALDFGL
VPAPPAGTRE ARVNIHCPCG LVTAFVACED GRSHGPVRFH SVPAFVLATD LMVDVPGHGK
VMVDIAYGGA FYAFVTAEKL GLDICSAKTR DLVDAASAVT EAVKAQFKIN HPDSEDLAFL
YGTILTDGKD AYTKEPTTNI CVFADEQVDR SPTGSGVTAR IALQYHKGLL ELNQMRAFKS
SATGSVFTGK AVREAKCGDF KAVIVEVSGQ AHYTGTASFI IEDDDPLRDG FLLK
