HTD2_HUMAN
ID HTD2_HUMAN Reviewed; 168 AA.
AC P86397;
DT 15-DEC-2009, integrated into UniProtKB/Swiss-Prot.
DT 15-DEC-2009, sequence version 1.
DT 03-AUG-2022, entry version 78.
DE RecName: Full=Hydroxyacyl-thioester dehydratase type 2, mitochondrial {ECO:0000303|PubMed:17898086};
DE Short=HsHTD2 {ECO:0000303|PubMed:17898086};
DE EC=4.2.1.59 {ECO:0000269|PubMed:17898086};
DE AltName: Full=3-hydroxyacyl-[acyl-carrier-protein] dehydratase {ECO:0000250|UniProtKB:P38790};
DE Flags: Precursor;
GN Name=HTD2 {ECO:0000303|PubMed:17898086};
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] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA], POSSIBLE FUNCTION, CATALYTIC ACTIVITY,
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, IDENTIFICATION OF BICISTRONIC
RP GENE, AND MUTAGENESIS OF ASP-62 AND HIS-67.
RC TISSUE=Cerebellum {ECO:0000269|PubMed:17898086}, and
RC Kidney {ECO:0000269|PubMed:17898086};
RX PubMed=17898086; DOI=10.1096/fj.07-8986;
RA Autio K.J., Kastaniotis A.J., Pospiech H., Miinalainen I.J.,
RA Schonauer M.S., Dieckmann C.L., Hiltunen J.K.;
RT "An ancient genetic link between vertebrate mitochondrial fatty acid
RT synthesis and RNA processing.";
RL FASEB J. 22:569-578(2008).
RN [2] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [3] {ECO:0000305}
RP X-RAY CRYSTALLOGRAPHY (1.99 ANGSTROMS) OF 23-168.
RG Structural genomics consortium (SGC);
RA Ugochukwu E., Cocking R., Burgess-Brown N., Pilka E., Muniz J., Krojer T.,
RA Chaikuad A., Gileadi O., Bountra C., Arrowsmith C.H., Weigelt J.,
RA Edwards A., Kavanagh K.L., Oppermann U.;
RT "Crystal structure of human 3-hydroxyacyl-thioester dehydratase 2 (HTD2).";
RL Submitted (AUG-2009) to the PDB data bank.
CC -!- FUNCTION: Mitochondrial 3-hydroxyacyl-thioester dehydratase, which may
CC be involved in fatty acid biosynthesis. {ECO:0000269|PubMed:17898086}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a (3R)-hydroxyacyl-[ACP] = a (2E)-enoyl-[ACP] + H2O;
CC Xref=Rhea:RHEA:13097, Rhea:RHEA-COMP:9925, Rhea:RHEA-COMP:9945,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:78784, ChEBI:CHEBI:78827; EC=4.2.1.59;
CC Evidence={ECO:0000269|PubMed:17898086};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3R)-hydroxyhexanoyl-[ACP] = (2E)-hexenoyl-[ACP] + H2O;
CC Xref=Rhea:RHEA:41828, Rhea:RHEA-COMP:9630, Rhea:RHEA-COMP:9631,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:78457, ChEBI:CHEBI:78458;
CC Evidence={ECO:0000269|PubMed:17898086};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41829;
CC Evidence={ECO:0000305|PubMed:17898086};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3R)-hydroxydecanoyl-[ACP] = (2E)-decenoyl-[ACP] + H2O;
CC Xref=Rhea:RHEA:41860, Rhea:RHEA-COMP:9638, Rhea:RHEA-COMP:9639,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:78466, ChEBI:CHEBI:78467;
CC Evidence={ECO:0000269|PubMed:17898086};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41861;
CC Evidence={ECO:0000305|PubMed:17898086};
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:17898086}.
CC -!- TISSUE SPECIFICITY: Highly expressed in heart and liver. Expressed at
CC lower levels in skeletal muscle, spleen, kidney and placenta.
CC {ECO:0000269|PubMed:17898086}.
CC -!- MISCELLANEOUS: This protein is produced by a bicistronic gene which
CC also produces the RPP14 protein from an overlapping reading frame.
CC {ECO:0000269|PubMed:17898086}.
CC -!- SIMILARITY: Belongs to the HTD2 family. {ECO:0000255}.
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DR EMBL; AC098479; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS87096.1; -.
DR RefSeq; NP_001335641.1; NM_001348712.1.
DR RefSeq; NP_001335642.1; NM_001348713.1.
DR RefSeq; NP_001335643.1; NM_001348714.1.
DR RefSeq; NP_001335644.1; NM_001348715.1.
DR PDB; 3IR3; X-ray; 1.99 A; A/B=23-168.
DR PDBsum; 3IR3; -.
DR AlphaFoldDB; P86397; -.
DR SMR; P86397; -.
DR IntAct; P86397; 1.
DR STRING; 9606.ENSP00000481593; -.
DR SwissLipids; SLP:000001096; -.
DR BioMuta; HTD2; -.
DR DMDM; 281312149; -.
DR EPD; P86397; -.
DR jPOST; P86397; -.
DR MassIVE; P86397; -.
DR MaxQB; P86397; -.
DR PaxDb; P86397; -.
DR PeptideAtlas; P86397; -.
DR PRIDE; P86397; -.
DR ProteomicsDB; 57772; -.
DR Antibodypedia; 69913; 17 antibodies from 4 providers.
DR DNASU; 109703458; -.
DR Ensembl; ENST00000461393.7; ENSP00000484277.1; ENSG00000255154.9.
DR Ensembl; ENST00000477305.5; ENSP00000481593.1; ENSG00000255154.9.
DR Ensembl; ENST00000481972.5; ENSP00000482940.1; ENSG00000255154.9.
DR GeneID; 109703458; -.
DR KEGG; hsa:109703458; -.
DR MANE-Select; ENST00000461393.7; ENSP00000484277.1; NM_001348712.2; NP_001335641.1.
DR UCSC; uc010hni.4; human.
DR CTD; 109703458; -.
DR DisGeNET; 109703458; -.
DR GeneCards; HTD2; -.
DR HGNC; HGNC:53111; HTD2.
DR HPA; ENSG00000255154; Tissue enhanced (skeletal).
DR neXtProt; NX_P86397; -.
DR OpenTargets; ENSG00000255154; -.
DR VEuPathDB; HostDB:ENSG00000255154; -.
DR eggNOG; KOG1206; Eukaryota.
DR GeneTree; ENSGT00530000065109; -.
DR HOGENOM; CLU_094876_3_4_1; -.
DR InParanoid; P86397; -.
DR OMA; PGPGCIY; -.
DR OrthoDB; 1326407at2759; -.
DR PhylomeDB; P86397; -.
DR BioCyc; MetaCyc:G66-33210-MON; -.
DR PathwayCommons; P86397; -.
DR Reactome; R-HSA-75105; Fatty acyl-CoA biosynthesis.
DR BioGRID-ORCS; 109703458; 3 hits in 15 CRISPR screens.
DR EvolutionaryTrace; P86397; -.
DR GenomeRNAi; 109703458; -.
DR Pharos; P86397; Tdark.
DR PRO; PR:P86397; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; P86397; protein.
DR Bgee; ENSG00000255154; Expressed in muscle of leg and 110 other tissues.
DR ExpressionAtlas; P86397; baseline and differential.
DR Genevisible; P86397; HS.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0008659; F:(3R)-hydroxymyristoyl-[acyl-carrier-protein] dehydratase activity; IEA:UniProtKB-EC.
DR GO; GO:0019171; F:3-hydroxyacyl-[acyl-carrier-protein] dehydratase activity; IBA:GO_Central.
DR GO; GO:0018812; F:3-hydroxyacyl-CoA dehydratase activity; TAS:Reactome.
DR GO; GO:0008693; F:3-hydroxydecanoyl-[acyl-carrier-protein] dehydratase activity; IEA:UniProtKB-EC.
DR GO; GO:0047451; F:3-hydroxyoctanoyl-[acyl-carrier-protein] dehydratase activity; IEA:UniProtKB-EC.
DR GO; GO:0004317; F:3-hydroxypalmitoyl-[acyl-carrier-protein] dehydratase activity; IEA:UniProtKB-EC.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IBA:GO_Central.
DR GO; GO:0046949; P:fatty-acyl-CoA biosynthetic process; TAS:Reactome.
DR InterPro; IPR029069; HotDog_dom_sf.
DR InterPro; IPR002539; MaoC-like_dom.
DR Pfam; PF01575; MaoC_dehydratas; 1.
DR SUPFAM; SSF54637; SSF54637; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Fatty acid metabolism; Lipid metabolism; Lyase;
KW Mitochondrion; Reference proteome; Transit peptide.
FT TRANSIT 1..?
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:17898086"
FT CHAIN ?..168
FT /note="Hydroxyacyl-thioester dehydratase type 2,
FT mitochondrial"
FT /evidence="ECO:0000269|PubMed:17898086"
FT /id="PRO_0000390489"
FT DOMAIN 41..146
FT /note="MaoC-like"
FT MUTAGEN 62
FT /note="D->A: Abolishes ability to complement a htd2-delta
FT mutant yeast."
FT /evidence="ECO:0000269|PubMed:17898086"
FT MUTAGEN 67
FT /note="H->A: Abolishes ability to complement a htd2-delta
FT mutant yeast."
FT /evidence="ECO:0000269|PubMed:17898086"
FT STRAND 41..47
FT /evidence="ECO:0007829|PDB:3IR3"
FT HELIX 50..60
FT /evidence="ECO:0007829|PDB:3IR3"
FT HELIX 66..68
FT /evidence="ECO:0007829|PDB:3IR3"
FT HELIX 85..98
FT /evidence="ECO:0007829|PDB:3IR3"
FT STRAND 106..113
FT /evidence="ECO:0007829|PDB:3IR3"
FT STRAND 123..134
FT /evidence="ECO:0007829|PDB:3IR3"
FT STRAND 137..146
FT /evidence="ECO:0007829|PDB:3IR3"
FT TURN 147..149
FT /evidence="ECO:0007829|PDB:3IR3"
FT STRAND 152..161
FT /evidence="ECO:0007829|PDB:3IR3"
SQ SEQUENCE 168 AA; 18559 MW; 6AAB9445C17F4FD7 CRC64;
MFPLISSHHL WWGGLRRTVC LNLPVLTLQH FQHMHIKVGD RAELRRAFTQ TDVATFSELT
GDVNPLHLNE DFAKHTKFGN TIVHGVLING LISALLGTKM PGPGCVFLSQ EISFPAPLYI
GEVVLASAEV KKLKRFIAII AVSCSVIESK KTVMEGWVKV MVPEASKS