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Gene Model: Hadha

NomenclatureGenomic Location
SymbolHadhaChromosome2
NameHydroxyacyl-Coenzyme A dehydrogenase/
3-ketoacyl-Coenzyme A thiolase/
enoyl-Coenzyme A hydratase
(trifunctional protein), alpha subunit		Linkage mapunknown
SpeciesDracomimus familiarisGenome CoordinatesChr2: 52 Mbp

Molecular Function

Bifunctional subunit.

(3S)-3-hydroxyacyl-CoA = trans-2(or 3)-enoyl-CoA + H2O.

(S)-3-hydroxyacyl-CoA + NAD+ = 3-oxoacyl-CoA + NADH.

Molecular Function Terms:

binding
   carboxylic acid binding
      monocarboxylic acid binding
         fatty acid binding
   cofactor binding
      coenzyme binding
   nucleotide binding
      NAD binding

catalytic activity
   oxidoreductase activity
      oxidoreductase activity, acting on CH-OH group of donors
   transferase activity
      transferase activity, transferring acyl groups
         transferase activity, transferring acyl groups other than amino-acyl groups
            acyltransferase activity
   lyase activity
      carbon-oxygen lyase activity
         hydro-lyase activity

Human Disease Association

Defects in HADHA are a cause of trifunctional protein deficiency (TFP deficiency) [MIM:609015]. The clinical manifestations are very variable and include hypoglycemia, cardiomyopathy and sudden death. Phenotypes with mainly hepatic and neuromyopathic involvement can also be distinguished. Biochemically, TFP deficiency is defined by the loss of all enzyme activities of the TFP complex.

Defects in HADHA are the cause of long-chain 3-hydroxyl-CoA dehydrogenase deficiency (LCHAD deficiency) [MIM:609016]. The clinical features are very similar to TFP deficiency. Biochemically, LCHAD deficiency is characterized by reduced long-chain 3-hydroxyl-CoA dehydrogenase activity, while the other enzyme activities of the TFP complex are normal or only slightly reduced.

Defects in HADHA are a cause of maternal acute fatty liver of pregnancy (AFLP) [MIM:609016]. AFLP is a severe maternal illness occurring during pregnancies with affected fetuses. This disease is associated with LCHAD deficiency and characterized by sudden unexplained infant death or hypoglycemia and abnormal liver enzymes (Reye-like syndrome).

Predicted Transcript
     1 CTTTTAGGCTATGCCTGCCGGAACCTCAGCACCTCCGCCCCTCTCAAATCTCGGACGCAT
    61 GTCAACTATGACGTCAAAGGCGACATTGCAGTTGTGCGGTTTAACTCTCCAAACTCCAAG
   121 GTGAACACACTCTCCAAGCAACTGCAAGCCGAATTCACAGAAGTCATGAACGAAATCTGG
   181 GCCAACGATGCCGTCAGCAGCGCCGTCCTCATCTCCGGAAAGCCGGGCTGCTTCATCGCT
   241 GGGGCCGACATCAACATGATTGAGGCCTGCAAATCGAGCGAAGAAATCACCCAGCTCTCT
   301 CAGGAGGGGCAGAAGATGATGGACAAGCTGGAGAAGTCCCCCAAGCCCATTGTGGCTGCC
   361 ATCAGTGGCTCCTGCCTGGGAGGGGGCCTGGAGGTGGCCATTGCCTGCCAGTACAGAATT
   421 GCCACCAAAGACAAGAAGACGGTCCTGGGGACGCCGGAGGTGCTGCTGGGGCTTTTGCCG
   481 GGGGCCGGGGGCACTCAGCGCCTGCCCAAGATGGTGGGGATCCCGGCGGCCTTTGACATG
   541 ATGCTGACCGGGCGCAACATTCGGGCCGACAAAGCCAAGAAGATGGGGCTGGTGGACCAG
   601 CTGGTGGACCCTCTGGGTCCGGGCATCAAGAGCCCCGAGGAGCGGACGATGGAGTACCTG
   661 GAGGAGGTGGCCGTGTTTTTCGCCCGGGGCCTGGCCAACAAGACCGTCTCCCACAAGAAG
   721 GACAAGGGCCTGGTCCAGAGGGTGACGGACTACGTCATGGCCATCCCCTTCGTGCGCCAA
   781 CAAATCTACAAAACGGTGGAGGGACGGGTCCAGAAGCAGACCAAAGGCCTCTACCCGGCA
   841 CCTCTGAACATCATTGCGGTTGCGAAGACGGGCCTGGAGCAGGGGAACGAAGCCGGGTAC
   901 CTTGCGGAGTCCCAGAGATTTGGGGAACTCGGGATGACCCCAGAGAGCCGGGCCCTGATC
   961 GGGCTCTACCACGGACAGGTCCAGTGCAAGAAGAACAAGTTCGGGCAGCCAAAGCAACCC
  1021 GTCAAGACGCTGGCCATCCTGGGGGCCGGCCTGATGGGGGCGGGCATTGCCCAGGTCTCT
  1081 GTGGACAAGGGACTGACCACTATCTTGAAGGACACGGCCCTGGAGGGCTTGAGCCGCGGG
  1141 CAGCAGCAGGTCTACAAGGGCTTGAACGACAAGGTGAAGAAGAAGAGCCTGACCTCCTTT
  1201 GAGCGGGACACCATCCTCAGCAACCTGACGGGGCAGCTGGACTACAAGGACTTTGGGAGG
  1261 GCCGACATGGTCATCGAGGCCGTCTTTGAGGACCTCAGCATCAAGCACAAAGTCCTGAAG
  1321 GAGGTGGAGGCGGTGGTGCCTCCTCACTGCATCTTCGCCAGCAACACCTCCGCCCTCCCC
  1381 ATCCATCAGATAGCGGCCGCCAGCCAAAGACCGGAGAAGGTGATCGGGATGCACTACTTC
  1441 TCTCCTGTGGACAAGATGCAGCTGCTGGAGATCATCACGACCGACAAGACCTCCCAGGAC
  1501 ACAGCGGCTTCCGCTGTTGCCGTGGGCCTCAAGCAAGGGAAAGTCATCATTGTGGTTAAG
  1561 GATGGTCCCGGTTTCTACACCACCAGGTGCCTCGCCCCCATGTTGGCTGAAATTGTCCGT
  1621 GTTCTCCAGGAAGGCACGGATCCCAAGAAGGTGGATGCCATCTCCACCGGCTTCGGCTTC
  1681 CCTGTCGGGGCGGCCACCCTGATCGACGAGGTGGGGGTGGACGTGGCCACGCACGTGGCG
  1741 GAGGACCTGGGCAAGGCCTTCGGGGAGCGCTTCAAGGGCGGGAATGTGGAGCTGATGAAG
  1801 GCCATGGTCGACAAGGGATTCCTGGGCCGCAAAGCAGGGAAGGGCTTCTACATCTACCAG
  1861 TCCGGGTCCAAGGAGCGCAGCCTCAACAGCGGCATGGATGAGATCCTGGAGAAGTTCCGG
  1921 GTGGAGGCCAAGCCGGAGGTGTAA

Predicted Protein Product
LLGYACRNLSTSAPLKSRTHVNYDVKGDIAVVRFNSPNSKVNTLSKQLQAEFTEVMNEIW
ANDAVSSAVLISGKPGCFIAGADINMIEACKSSEEITQLSQEGQKMMDKLEKSPKPIVAA
ISGSCLGGGLEVAIACQYRIATKDKKTVLGTPEVLLGLLPGAGGTQRLPKMVGIPAAFDM
MLTGRNIRADKAKKMGLVDQLVDPLGPGIKSPEERTMEYLEEVAVFFARGLANKTVSHKK
DKGLVQRVTDYVMAIPFVRQQIYKTVEGRVQKQTKGLYPAPLNIIAVAKTGLEQGNEAGY
LAESQRFGELGMTPESRALIGLYHGQVQCKKNKFGQPKQPVKTLAILGAGLMGAGIAQVS
VDKGLTTILKDTALEGLSRGQQQVYKGLNDKVKKKSLTSFERDTILSNLTGQLDYKDFGR
ADMVIEAVFEDLSIKHKVLKEVEAVVPPHCIFASNTSALPIHQIAAASQRPEKVIGMHYF
SPVDKMQLLEIITTDKTSQDTAASAVAVGLKQGKVIIVVKDGPGFYTTRCLAPMLAEIVR
VLQEGTDPKKVDAISTGFGFPVGAATLIDEVGVDVATHVAEDLGKAFGERFKGGNVELMK
AMVDKGFLGRKAGKGFYIYQSGSKERSLNSGMDEILEKFRVEAKPEV
Protein Alignment to Mouse
sp|Q8BMS1|ECHA_MOUSE Trifunctional enzyme subunit alpha, mitochondrial OS=Mus
            musculus GN=Hadha PE=1 SV=1
      MGI:2135593 Hadha hydroxyacyl-Coenzyme A dehydrogenase/
      3-ketoacyl-Coenzyme A thiolase/
      enoyl-Coenzyme A hydratase (trifunctional protein), alpha subunit (Chr 5)
        Length = 763

 Score = 2595 (918.5 bits), Expect = 1.5e-270, P = 1.5e-270
 Identities = 493/645 (76%), Positives = 568/645 (88%)

Query:     3 GYACRNLSTSAPLKSRTHVNYDVKGDIAVVRFNSPNSKVNTLSKQLQAEFTEVMNEIWAN 62
             G  CR+ +TS+ L +RTH+NY VKGD+AV+R NSPNSKVNTL+K++Q+EF EVMNEIWAN
Sbjct:    23 GCICRSFTTSSALLTRTHINYGVKGDVAVIRINSPNSKVNTLNKEVQSEFIEVMNEIWAN 82

Query:    63 DAVSSAVLISGKPGCFIAGADINMIEACKSSEEITQLSQEGQKMMDKLEKSPKPIVAAIS 122
             D + SAVLIS KPGCF+AGADINM+ +C + +E T++SQEGQ+M +KLEKSPKP+VAAIS
Sbjct:    83 DQIRSAVLISSKPGCFVAGADINMLSSCTTPQEATRISQEGQRMFEKLEKSPKPVVAAIS 142

Query:   123 GSCLGGGLEVAIACQYRIATKDKKTVLGTPEVLLGLLPGAGGTQRLPKMVGIPAAFDMML 182
             GSCLGGGLE+AIACQYRIATKD+KTVLG PEVLLG+LPGAGGTQRLPKMVG+PAAFDMML
Sbjct:   143 GSCLGGGLELAIACQYRIATKDRKTVLGVPEVLLGILPGAGGTQRLPKMVGVPAAFDMML 202

Query:   183 TGRNIRADKAKKMGLVDQLVDPLGPGIKSPEERTMEYLEEVAVFFARGLANKTVSHKKDK 242
             TGRNIRAD+AKKMGLVDQLV+PLGPGIKSPEERT+EYLEEVAV FA+GLA++ VS K+ K
Sbjct:   203 TGRNIRADRAKKMGLVDQLVEPLGPGIKSPEERTIEYLEEVAVNFAKGLADRKVSAKQSK 262

Query:   243 GLVQRVTDYVMAIPFVRQQIYKTVEGRVQKQTKGLYPAPLNIIAVAKTGLEQGNEAGYLA 302
             GLV+++T Y M +PFVRQQ+YKTVE +V+KQTKGLYPAPL II   K GLEQG++AGYLA
Sbjct:   263 GLVEKLTTYAMTVPFVRQQVYKTVEEKVKKQTKGLYPAPLKIIDAVKAGLEQGSDAGYLA 322

Query:   303 ESQRFGELGMTPESRALIGLYHGQVQCKKNKFGQPKQPVKTXXXXXXXXXXXXXXQVSVD 362
             ESQ+FGEL +T ES+AL+GLY+GQV CKKNKFG P++ V+               QVSVD
Sbjct:   323 ESQKFGELALTKESKALMGLYNGQVLCKKNKFGAPQKNVQQLAILGAGLMGAGIAQVSVD 382

Query:   363 KGLTTILKDTALEGLSRGQQQVYKGLNDKVKKKSLTSFERDTILSNLTGQLDYKDFGRAD 422
             KGL T+LKDT + GL RGQQQV+KGLNDKVKKK+LTSFERD+I SNL GQLDYK F +AD
Sbjct:   383 KGLKTLLKDTTVTGLGRGQQQVFKGLNDKVKKKALTSFERDSIFSNLIGQLDYKGFEKAD 442

Query:   423 MVIEAVFEDLSIKHKVLKEVEAVVPPHCIFASNTSALPIHQIAAASQRPEKVIGMHYFSP 482
             MVIEAVFEDL +KHKVLKEVE+V P HCIFASNTSALPI+QIAA S+RPEKVIGMHYFSP
Sbjct:   443 MVIEAVFEDLGVKHKVLKEVESVTPEHCIFASNTSALPINQIAAVSKRPEKVIGMHYFSP 502

Query:   483 VDKMQLLEIITTDKTSQDTAASAVAVGLKQGKVIIVVKDGPGFYTTRCLAPMLAEIVRVL 542
             VDKMQLLEIITTDKTS+DT ASAVAVGL+QGKVIIVVKDGPGFYTTRCLAPM++E++R+L
Sbjct:   503 VDKMQLLEIITTDKTSKDTTASAVAVGLRQGKVIIVVKDGPGFYTTRCLAPMMSEVMRIL 562

Query:   543 QEGTDPKKVDAISTGFGFPVGAATLIDEVGVDVATHVAEDLGKAFGERFKGGNVELMKAM 602
             QEG DPKK+DA++TGFGFPVGAATL DEVGVDVA HVAEDLGKAFGERF GG+VEL+K M
Sbjct:   563 QEGVDPKKLDALTTGFGFPVGAATLADEVGVDVAQHVAEDLGKAFGERFGGGSVELLKQM 622

Query:   603 VDKGFLGRKAGKGFYIYQSGSKERSLNSGMDEILEKFRVEAKPEV 647
             V KGFLGRK+GKGFYIYQ GSK +SLNS MD IL   R+ AKPEV
Sbjct:   623 VSKGFLGRKSGKGFYIYQEGSKNKSLNSEMDNILANLRLPAKPEV 667