LOCUS       NM_000182               2943 bp    mRNA    linear   PRI 12-NOV-2024
DEFINITION  Homo sapiens hydroxyacyl-CoA dehydrogenase trifunctional
            multienzyme complex subunit alpha (HADHA), mRNA; nuclear gene for
            mitochondrial product.
ACCESSION   NM_000182
VERSION     NM_000182.5
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 2943)
  AUTHORS   Chen,R., Chen,H. and Hu,C.
  TITLE     HADHA promotes glioma progression by accelerating MDM2-mediated p53
            ubiquitination
  JOURNAL   Cancer Gene Ther 31 (9), 1380-1389 (2024)
   PUBMED   39039194
  REMARK    GeneRIF: HADHA promotes glioma progression by accelerating
            MDM2-mediated p53 ubiquitination.
REFERENCE   2  (bases 1 to 2943)
  AUTHORS   Elizondo,G., Saini,A., Gonzalez de Alba,C., Gregor,A.,
            Harding,C.O., Gillingham,M.B. and Vinocur,J.M.
  TITLE     Cardiac phenotype in adolescents and young adults with long-chain
            3-hydroxyacyl CoA dehydrogenase (LCHAD) deficiency
  JOURNAL   Genet Med 26 (6), 101123 (2024)
   PUBMED   38501492
  REMARK    GeneRIF: Cardiac phenotype in adolescents and young adults with
            long-chain 3-hydroxyacyl CoA dehydrogenase (LCHAD) deficiency.
REFERENCE   3  (bases 1 to 2943)
  AUTHORS   Zhang,Q., Yao,N., Liu,Z., Xu,C. and Ding,Z.
  TITLE     An Autopsy Analysis of a Patient With Long-Chain 3-Hydroxyacyl-CoA
            Dehydrogenase Deficiency Caused by Compound Heterozygous HADHA Gene
            Mutations
  JOURNAL   Am J Forensic Med Pathol 44 (4), 336-339 (2023)
   PUBMED   37549033
  REMARK    GeneRIF: An Autopsy Analysis of a Patient With Long-Chain
            3-Hydroxyacyl-CoA Dehydrogenase Deficiency Caused by Compound
            Heterozygous HADHA Gene Mutations.
REFERENCE   4  (bases 1 to 2943)
  AUTHORS   Wang,X., Sun,L., Yang,B., Li,W., Zhang,C., Yang,X., Sun,Y.,
            Shen,X., Gao,Y., Ju,B., Gao,Y., Liu,D., Song,J., Jia,X., Su,Y.,
            Jiao,A., Liu,H., Zhang,L., He,L., Lei,L., Chen,W. and Zhang,B.
  TITLE     Zfp335 establishes eTreg lineage and neonatal immune tolerance by
            targeting Hadha-mediated fatty acid oxidation
  JOURNAL   J Clin Invest 133 (20), e166628 (2023)
   PUBMED   37843279
  REMARK    GeneRIF: Zfp335 establishes eTreg lineage and neonatal immune
            tolerance by targeting Hadha-mediated fatty acid oxidation.
            Publication Status: Online-Only
REFERENCE   5  (bases 1 to 2943)
  AUTHORS   Wu,Z.H., Wang,Y.H., Liu,T.H., Ruan,L.L., Xie,Y.L., Li,F.F. and
            Ding,Y.B.
  TITLE     [HADHA Inhibits the Migration and Invasion of HTR-8/SVneo Cells by
            Regulating PI3K/AKT Signaling Pathway]
  JOURNAL   Sichuan Da Xue Xue Bao Yi Xue Ban 53 (5), 805-814 (2022)
   PUBMED   36224682
  REMARK    GeneRIF: [HADHA Inhibits the Migration and Invasion of HTR-8/SVneo
            Cells by Regulating PI3K/AKT Signaling Pathway].
REFERENCE   6  (bases 1 to 2943)
  AUTHORS   Brackett,J.C., Sims,H.F., Rinaldo,P., Shapiro,S., Powell,C.K.,
            Bennett,M.J. and Strauss,A.W.
  TITLE     Two alpha subunit donor splice site mutations cause human
            trifunctional protein deficiency
  JOURNAL   J Clin Invest 95 (5), 2076-2082 (1995)
   PUBMED   7738175
REFERENCE   7  (bases 1 to 2943)
  AUTHORS   Sims,H.F., Brackett,J.C., Powell,C.K., Treem,W.R., Hale,D.E.,
            Bennett,M.J., Gibson,B., Shapiro,S. and Strauss,A.W.
  TITLE     The molecular basis of pediatric long chain 3-hydroxyacyl-CoA
            dehydrogenase deficiency associated with maternal acute fatty liver
            of pregnancy
  JOURNAL   Proc Natl Acad Sci U S A 92 (3), 841-845 (1995)
   PUBMED   7846063
REFERENCE   8  (bases 1 to 2943)
  AUTHORS   IJlst,L., Wanders,R.J., Ushikubo,S., Kamijo,T. and Hashimoto,T.
  TITLE     Molecular basis of long-chain 3-hydroxyacyl-CoA dehydrogenase
            deficiency: identification of the major disease-causing mutation in
            the alpha-subunit of the mitochondrial trifunctional protein
  JOURNAL   Biochim Biophys Acta 1215 (3), 347-350 (1994)
   PUBMED   7811722
REFERENCE   9  (bases 1 to 2943)
  AUTHORS   Prasun,P., LoPiccolo,M.K. and Ginevic,I.
  TITLE     Long-Chain Hydroxyacyl-CoA Dehydrogenase Deficiency / Trifunctional
            Protein Deficiency
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   36063482
REFERENCE   10 (bases 1 to 2943)
  AUTHORS   Carpenter,K., Pollitt,R.J. and Middleton,B.
  TITLE     Human liver long-chain 3-hydroxyacyl-coenzyme A dehydrogenase is a
            multifunctional membrane-bound beta-oxidation enzyme of
            mitochondria
  JOURNAL   Biochem Biophys Res Commun 183 (2), 443-448 (1992)
   PUBMED   1550553
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from CN264228.1, BC009235.2,
            AC011742.3 and AI972144.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 23, 2018 this sequence version replaced NM_000182.4.
            
            Summary: This gene encodes the alpha subunit of the mitochondrial
            trifunctional protein, which catalyzes the last three steps of
            mitochondrial beta-oxidation of long chain fatty acids. The
            mitochondrial membrane-bound heterocomplex is composed of four
            alpha and four beta subunits, with the alpha subunit catalyzing the
            3-hydroxyacyl-CoA dehydrogenase and enoyl-CoA hydratase activities.
            Mutations in this gene result in trifunctional protein deficiency
            or LCHAD deficiency. The genes of the alpha and beta subunits of
            the mitochondrial trifunctional protein are located adjacent to
            each other in the human genome in a head-to-head orientation.
            [provided by RefSeq, Jul 2008].
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: GU727642.1, BC009235.2 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            gene product(s) localized to mito. :: reported by MitoCarta
            MANE Ensembl match                 :: ENST00000380649.8/
                                                  ENSP00000370023.3
            RefSeq Select criteria             :: based on single
                                                  protein-coding transcript
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-11                CN264228.1         95-105
            12-2529             BC009235.2         1-2518
            2530-2745           AC011742.3         140622-140837       c
            2746-2943           AI972144.1         12-209              c
FEATURES             Location/Qualifiers
     source          1..2943
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="2"
                     /map="2p23.3"
     gene            1..2943
                     /gene="HADHA"
                     /gene_synonym="ECHA; GBP; HADH; LCEH; LCHAD; MTPA;
                     TP-ALPHA"
                     /note="hydroxyacyl-CoA dehydrogenase trifunctional
                     multienzyme complex subunit alpha"
                     /db_xref="GeneID:3030"
                     /db_xref="HGNC:HGNC:4801"
                     /db_xref="MIM:600890"
     exon            1..103
                     /gene="HADHA"
                     /gene_synonym="ECHA; GBP; HADH; LCEH; LCHAD; MTPA;
                     TP-ALPHA"
                     /inference="alignment:Splign:2.1.0"
     CDS             37..2328
                     /gene="HADHA"
                     /gene_synonym="ECHA; GBP; HADH; LCEH; LCHAD; MTPA;
                     TP-ALPHA"
                     /EC_number="4.2.1.17"
                     /EC_number="1.1.1.211"
                     /note="gastrin-binding protein; long-chain 2-enoyl-CoA
                     hydratase; hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA
                     thiolase/enoyl-CoA hydratase (trifunctional protein),
                     alpha subunit; long-chain-3-hydroxyacyl-CoA dehydrogenase;
                     hydroxyacyl-Coenzyme A dehydrogenase/3-ketoacyl-Coenzyme A
                     thiolase/enoyl-Coenzyme A hydratase (trifunctional
                     protein), alpha subunit; mitochondrial long-chain
                     L-3-hydroxyacyl-Coenzyme A (CoA) dehydrogenase, alpha
                     subunit; 3-ketoacyl-Coenzyme A (CoA) thiolase, alpha
                     subunit; 3-oxoacyl-CoA thiolase; mitochondrial long-chain
                     2-enoyl-Coenzyme A (CoA) hydratase, alpha subunit;
                     mitochondrial trifunctional protein, alpha subunit;
                     mitochondrial trifunctional enzyme, alpha subunit; 78 kDa
                     gastrin-binding protein; monolysocardiolipin
                     acyltransferase"
                     /codon_start=1
                     /product="trifunctional enzyme subunit alpha,
                     mitochondrial precursor"
                     /protein_id="NP_000173.2"
                     /db_xref="CCDS:CCDS1721.1"
                     /db_xref="GeneID:3030"
                     /db_xref="HGNC:HGNC:4801"
                     /db_xref="MIM:600890"
                     /translation="MVACRAIGILSRFSAFRILRSRGYICRNFTGSSALLTRTHINYG
                     VKGDVAVVRINSPNSKVNTLSKELHSEFSEVMNEIWASDQIRSAVLISSKPGCFIAGA
                     DINMLAACKTLQEVTQLSQEAQRIVEKLEKSTKPIVAAINGSCLGGGLEVAISCQYRI
                     ATKDRKTVLGTPEVLLGALPGAGGTQRLPKMVGVPAALDMMLTGRSIRADRAKKMGLV
                     DQLVEPLGPGLKPPEERTIEYLEEVAITFAKGLADKKISPKRDKGLVEKLTAYAMTIP
                     FVRQQVYKKVEEKVRKQTKGLYPAPLKIIDVVKTGIEQGSDAGYLCESQKFGELVMTK
                     ESKALMGLYHGQVLCKKNKFGAPQKDVKHLAILGAGLMGAGIAQVSVDKGLKTILKDA
                     TLTALDRGQQQVFKGLNDKVKKKALTSFERDSIFSNLTGQLDYQGFEKADMVIEAVFE
                     DLSLKHRVLKEVEAVIPDHCIFASNTSALPISEIAAVSKRPEKVIGMHYFSPVDKMQL
                     LEIITTEKTSKDTSASAVAVGLKQGKVIIVVKDGPGFYTTRCLAPMMSEVIRILQEGV
                     DPKKLDSLTTSFGFPVGAATLVDEVGVDVAKHVAEDLGKVFGERFGGGNPELLTQMVS
                     KGFLGRKSGKGFYIYQEGVKRKDLNSDMDSILASLKLPPKSEVSSDEDIQFRLVTRFV
                     NEAVMCLQEGILATPAEGDIGAVFGLGFPPCLGGPFRFVDLYGAQKIVDRLKKYEAAY
                     GKQFTPCQLLADHANSPNKKFYQ"
     exon            104..145
                     /gene="HADHA"
                     /gene_synonym="ECHA; GBP; HADH; LCEH; LCHAD; MTPA;
                     TP-ALPHA"
                     /inference="alignment:Splign:2.1.0"
     exon            146..216
                     /gene="HADHA"
                     /gene_synonym="ECHA; GBP; HADH; LCEH; LCHAD; MTPA;
                     TP-ALPHA"
                     /inference="alignment:Splign:2.1.0"
     exon            217..350
                     /gene="HADHA"
                     /gene_synonym="ECHA; GBP; HADH; LCEH; LCHAD; MTPA;
                     TP-ALPHA"
                     /inference="alignment:Splign:2.1.0"
     exon            351..489
                     /gene="HADHA"
                     /gene_synonym="ECHA; GBP; HADH; LCEH; LCHAD; MTPA;
                     TP-ALPHA"
                     /inference="alignment:Splign:2.1.0"
     exon            490..609
                     /gene="HADHA"
                     /gene_synonym="ECHA; GBP; HADH; LCEH; LCHAD; MTPA;
                     TP-ALPHA"
                     /inference="alignment:Splign:2.1.0"
     exon            610..712
                     /gene="HADHA"
                     /gene_synonym="ECHA; GBP; HADH; LCEH; LCHAD; MTPA;
                     TP-ALPHA"
                     /inference="alignment:Splign:2.1.0"
     exon            713..835
                     /gene="HADHA"
                     /gene_synonym="ECHA; GBP; HADH; LCEH; LCHAD; MTPA;
                     TP-ALPHA"
                     /inference="alignment:Splign:2.1.0"
     exon            836..954
                     /gene="HADHA"
                     /gene_synonym="ECHA; GBP; HADH; LCEH; LCHAD; MTPA;
                     TP-ALPHA"
                     /inference="alignment:Splign:2.1.0"
     exon            955..1011
                     /gene="HADHA"
                     /gene_synonym="ECHA; GBP; HADH; LCEH; LCHAD; MTPA;
                     TP-ALPHA"
                     /inference="alignment:Splign:2.1.0"
     exon            1012..1121
                     /gene="HADHA"
                     /gene_synonym="ECHA; GBP; HADH; LCEH; LCHAD; MTPA;
                     TP-ALPHA"
                     /inference="alignment:Splign:2.1.0"
     exon            1122..1256
                     /gene="HADHA"
                     /gene_synonym="ECHA; GBP; HADH; LCEH; LCHAD; MTPA;
                     TP-ALPHA"
                     /inference="alignment:Splign:2.1.0"
     exon            1257..1428
                     /gene="HADHA"
                     /gene_synonym="ECHA; GBP; HADH; LCEH; LCHAD; MTPA;
                     TP-ALPHA"
                     /inference="alignment:Splign:2.1.0"
     exon            1429..1515
                     /gene="HADHA"
                     /gene_synonym="ECHA; GBP; HADH; LCEH; LCHAD; MTPA;
                     TP-ALPHA"
                     /inference="alignment:Splign:2.1.0"
     exon            1516..1656
                     /gene="HADHA"
                     /gene_synonym="ECHA; GBP; HADH; LCEH; LCHAD; MTPA;
                     TP-ALPHA"
                     /inference="alignment:Splign:2.1.0"
     exon            1657..1725
                     /gene="HADHA"
                     /gene_synonym="ECHA; GBP; HADH; LCEH; LCHAD; MTPA;
                     TP-ALPHA"
                     /inference="alignment:Splign:2.1.0"
     exon            1726..1921
                     /gene="HADHA"
                     /gene_synonym="ECHA; GBP; HADH; LCEH; LCHAD; MTPA;
                     TP-ALPHA"
                     /inference="alignment:Splign:2.1.0"
     exon            1922..2036
                     /gene="HADHA"
                     /gene_synonym="ECHA; GBP; HADH; LCEH; LCHAD; MTPA;
                     TP-ALPHA"
                     /inference="alignment:Splign:2.1.0"
     exon            2037..2182
                     /gene="HADHA"
                     /gene_synonym="ECHA; GBP; HADH; LCEH; LCHAD; MTPA;
                     TP-ALPHA"
                     /inference="alignment:Splign:2.1.0"
     exon            2183..2943
                     /gene="HADHA"
                     /gene_synonym="ECHA; GBP; HADH; LCEH; LCHAD; MTPA;
                     TP-ALPHA"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2684..2689
                     /regulatory_class="polyA_signal_sequence"
                     /gene="HADHA"
                     /gene_synonym="ECHA; GBP; HADH; LCEH; LCHAD; MTPA;
                     TP-ALPHA"
                     /note="hexamer: AATAAA"
     polyA_site      2709
                     /gene="HADHA"
                     /gene_synonym="ECHA; GBP; HADH; LCEH; LCHAD; MTPA;
                     TP-ALPHA"
                     /note="major polyA site"
     regulatory      2919..2924
                     /regulatory_class="polyA_signal_sequence"
                     /gene="HADHA"
                     /gene_synonym="ECHA; GBP; HADH; LCEH; LCHAD; MTPA;
                     TP-ALPHA"
                     /note="hexamer: ATTAAA"
     polyA_site      2943
                     /gene="HADHA"
                     /gene_synonym="ECHA; GBP; HADH; LCEH; LCHAD; MTPA;
                     TP-ALPHA"
ORIGIN      
        1 agaggcgctc tccactgctg tcctcttcag ctcaagatgg tggcctgccg ggcgattggc
       61 atcctcagcc gcttttctgc cttcaggatc ctccgctccc gaggttatat atgccgcaat
      121 tttacagggt cttctgcttt gctgaccaga acccatatta actatggagt caaaggggat
      181 gtggcagttg ttcgaattaa ctctcccaat tcaaaggtaa atacactgag taaagagcta
      241 cattcagagt tctcagaagt tatgaatgaa atctgggcta gtgatcaaat cagaagtgcc
      301 gtccttatct catcaaagcc aggctgcttt attgcaggtg ctgatatcaa catgttagcc
      361 gcttgcaaga cccttcaaga agtaacacag ctatcacaag aagcacagag aatagttgag
      421 aaacttgaaa agtccacaaa gcctattgtg gctgccatca atggatcctg cctgggagga
      481 ggacttgagg ttgccatttc atgccaatac agaatagcaa caaaagacag aaaaacagta
      541 ttaggtaccc ctgaagtttt gctgggggcc ttaccaggag caggaggcac acaaaggctg
      601 cccaaaatgg tgggtgtgcc tgctgctttg gacatgatgc tgactggtag aagcattcgt
      661 gcagacaggg caaagaaaat gggactggtt gaccaactgg tggaacccct gggaccagga
      721 ctaaaacctc cagaggaacg gacaatagaa tacctagaag aagttgcaat tacttttgcc
      781 aaaggactag ctgataagaa gatctctcca aagagagaca agggattggt ggaaaaattg
      841 acagcgtatg ccatgactat tccatttgtc aggcaacagg tttacaaaaa agtggaagaa
      901 aaagtgcgaa agcagactaa aggcctttat cctgcacctc tgaaaataat tgatgtggta
      961 aagactggaa ttgagcaagg gagtgatgcc ggttatctct gtgaatctca gaaatttgga
     1021 gagcttgtaa tgaccaaaga atcaaaggcc ttgatgggac tctaccatgg tcaggtcctg
     1081 tgcaagaaga ataaatttgg agctccacag aaggatgtta agcatctggc tattcttggt
     1141 gcagggctga tgggagcagg catcgcccaa gtctccgtgg ataaggggct aaagactata
     1201 cttaaagatg ccaccctcac tgcgctagac cgaggacagc aacaagtgtt caaaggattg
     1261 aatgacaaag tgaagaagaa agctctaaca tcatttgaaa gggattccat cttcagcaac
     1321 ttgactgggc agcttgatta ccaaggtttt gaaaaggccg acatggtgat tgaagctgtg
     1381 tttgaggacc ttagtcttaa gcacagagtg ctaaaggaag tagaagcggt gattccagat
     1441 cactgtatct ttgccagtaa cacatctgct ctcccaatca gtgaaatcgc tgctgtcagc
     1501 aaaagacctg agaaggtgat tggcatgcac tacttctctc ccgtggacaa gatgcagctg
     1561 ctggagatta tcacgaccga gaaaacttcc aaagacacca gtgcttcagc tgtagcagtt
     1621 ggtctcaagc aggggaaggt catcattgtg gttaaggatg gacctggctt ctatactacc
     1681 aggtgtcttg cgcccatgat gtctgaagtc atccgaatcc tccaggaagg agttgacccg
     1741 aagaagctgg attccctgac cacaagcttt ggctttcctg tgggtgccgc cacactggtg
     1801 gatgaagttg gtgtggatgt agcgaaacat gtggcggaag atctgggcaa agtctttggg
     1861 gagcggtttg gaggtggaaa cccagaactg ctgacacaga tggtgtccaa gggcttccta
     1921 ggtcgtaaat ctgggaaggg cttttacatc tatcaggagg gtgtgaagag gaaggatttg
     1981 aattctgaca tggatagtat tttagcgagt ctgaagctgc ctcctaagtc tgaagtctca
     2041 tcagacgaag acatccagtt ccgcctggtg acaagatttg tgaatgaggc agtcatgtgc
     2101 ctgcaagagg ggatcttggc cacacctgca gagggagaca tcggagccgt ctttgggctt
     2161 ggcttcccgc cttgtctggg agggcctttc cgctttgtgg atctgtatgg cgcccagaag
     2221 atagtggacc ggctcaagaa atatgaagct gcctatggaa aacagttcac cccatgccag
     2281 ctgctagctg accatgctaa cagccctaac aagaagttct accagtgagc aggcctcatg
     2341 cctcgctcag tcagtgcact aaccccagct gccggcagtg ctggttctcc aacagagtgg
     2401 tgtctagatt tatcagagta acgagaagac aaactccggc actgggtttg ctccctgatt
     2461 aaagtgcctt cagccaagac catctctccc tcctggtgaa gtgtgacttc gaattagttt
     2521 gcacttcctg ttggaaggta gagcccactg ctcattgtat aagccccgag gcctagagtg
     2581 gcagccaaga gccatctgaa gccacctctc tgcctgttcc tcccaagagg ccagggtggc
     2641 caggggtggt gagggcagtt ctgcacccag ccaaacacat aacaataaaa accaaactct
     2701 gtgtcagcat ctttgccctt ctggtttaaa cgcctccttc aaaaagcaat ctggaagaaa
     2761 gccctgtgct ttgggggagt aagaatgtgt gtgcagaatt ctaggcagca ccttagggag
     2821 ggactgggat gagagaaagt gggacctggt gggctcaacc acacacacct gtctgtgcag
     2881 atgctttgcc caggcttctc accacggtgt accgggatat taaacctctt tccccagcct
     2941 gga
//
