Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Trifunctional enzyme subunit beta, mitochondrial

Gene

HADHB

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalytic activityi

Acyl-CoA + acetyl-CoA = CoA + 3-oxoacyl-CoA.1 Publication

Pathwayi: fatty acid beta-oxidation

This protein is involved in the pathway fatty acid beta-oxidation, which is part of Lipid metabolism.
View all proteins of this organism that are known to be involved in the pathway fatty acid beta-oxidation and in Lipid metabolism.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei138Acyl-thioester intermediateBy similarity1
Active sitei428Proton acceptorPROSITE-ProRule annotation1
Active sitei458Proton acceptorPROSITE-ProRule annotation1

GO - Molecular functioni

  • 3-hydroxyacyl-CoA dehydrogenase activity Source: ProtInc
  • acetyl-CoA C-acyltransferase activity Source: ProtInc
  • enoyl-CoA hydratase activity Source: ProtInc
  • long-chain-3-hydroxyacyl-CoA dehydrogenase activity Source: Ensembl
  • poly(A) RNA binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Acyltransferase, Transferase

Keywords - Biological processi

Fatty acid metabolism, Lipid metabolism

Enzyme and pathway databases

BioCyciMetaCyc:HS06436-MONOMER.
ZFISH:HS06436-MONOMER.
ReactomeiR-HSA-1482798. Acyl chain remodeling of CL.
R-HSA-77285. Beta oxidation of myristoyl-CoA to lauroyl-CoA.
R-HSA-77288. mitochondrial fatty acid beta-oxidation of unsaturated fatty acids.
R-HSA-77305. Beta oxidation of palmitoyl-CoA to myristoyl-CoA.
R-HSA-77310. Beta oxidation of lauroyl-CoA to decanoyl-CoA-CoA.
R-HSA-77346. Beta oxidation of decanoyl-CoA to octanoyl-CoA-CoA.
R-HSA-77348. Beta oxidation of octanoyl-CoA to hexanoyl-CoA.
R-HSA-77350. Beta oxidation of hexanoyl-CoA to butanoyl-CoA.
UniPathwayiUPA00659.

Names & Taxonomyi

Protein namesi
Recommended name:
Trifunctional enzyme subunit beta, mitochondrial
Alternative name(s):
TP-beta
Including the following 1 domains:
3-ketoacyl-CoA thiolase (EC:2.3.1.16)
Alternative name(s):
Acetyl-CoA acyltransferase
Beta-ketothiolase
Gene namesi
Name:HADHB
ORF Names:MSTP029
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:4803. HADHB.

Subcellular locationi

GO - Cellular componenti

  • endoplasmic reticulum Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • mitochondrial envelope Source: ProtInc
  • mitochondrial inner membrane Source: UniProtKB
  • mitochondrial nucleoid Source: BHF-UCL
  • mitochondrial outer membrane Source: UniProtKB
  • mitochondrion Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Mitochondrion, Mitochondrion inner membrane, Mitochondrion outer membrane

Pathology & Biotechi

Involvement in diseasei

Mitochondrial trifunctional protein deficiency (MTPD)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disease biochemically characterized by loss of all enzyme activities of the mitochondrial trifunctional protein complex. Variable clinical manifestations include hypoglycemia, cardiomyopathy, delayed psychomotor development, sensorimotor axonopathy, generalized weakness, hepatic dysfunction, respiratory failure. Sudden infant death may occur. Most patients die from heart failure.
See also OMIM:609015
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02112859G → D in MTPD. 1 Publication1
Natural variantiVAR_02112961R → C in MTPD. 1 PublicationCorresponds to variant rs780351691dbSNPEnsembl.1
Natural variantiVAR_00749361R → H in MTPD. 2 PublicationsCorresponds to variant rs121913132dbSNPEnsembl.1
Natural variantiVAR_021130117R → G in MTPD. 1 Publication1
Natural variantiVAR_021131121L → P in MTPD. 1 PublicationCorresponds to variant rs773127211dbSNPEnsembl.1
Natural variantiVAR_021132133T → P in MTPD. 1 PublicationCorresponds to variant rs371159065dbSNPEnsembl.1
Natural variantiVAR_021133242D → G in MTPD. 1 Publication1
Natural variantiVAR_007494247R → H in MTPD. 2 PublicationsCorresponds to variant rs121913133dbSNPEnsembl.1
Natural variantiVAR_021134259 – 270Missing in MTPD. 1 PublicationAdd BLAST12
Natural variantiVAR_007495263D → G in MTPD. 2 PublicationsCorresponds to variant rs121913131dbSNPEnsembl.1
Natural variantiVAR_021135280G → D in MTPD. 1 PublicationCorresponds to variant rs751772298dbSNPEnsembl.1
Natural variantiVAR_021136294P → L in MTPD. 1 Publication1
Natural variantiVAR_021137294P → R in MTPD. 1 Publication1
Natural variantiVAR_021138301G → S in MTPD. 1 Publication1
Natural variantiVAR_017409444R → K in MTPD. 2 PublicationsCorresponds to variant rs121913134dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi3032.
MalaCardsiHADHB.
MIMi609015. phenotype.
OpenTargetsiENSG00000138029.
Orphaneti746. Mitochondrial trifunctional protein deficiency.
PharmGKBiPA29177.

Polymorphism and mutation databases

BioMutaiHADHB.
DMDMi116241345.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 33MitochondrionCombined sources1 PublicationAdd BLAST33
ChainiPRO_000003408034 – 474Trifunctional enzyme subunit beta, mitochondrialAdd BLAST441

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei72N6-acetyllysine; alternateCombined sources1
Modified residuei72N6-succinyllysine; alternateBy similarity1
Modified residuei188N6-acetyllysine; alternateCombined sources1
Modified residuei188N6-succinyllysine; alternateBy similarity1
Modified residuei190N6-succinyllysineBy similarity1
Modified residuei272N6-succinyllysineBy similarity1
Modified residuei291N6-succinyllysineBy similarity1
Modified residuei293N6-acetyllysine; alternateBy similarity1
Modified residuei293N6-succinyllysine; alternateBy similarity1
Modified residuei298N6-acetyllysineBy similarity1
Modified residuei332N6-acetyllysine; alternateBy similarity1
Modified residuei332N6-succinyllysine; alternateBy similarity1
Modified residuei348N6-acetyllysineBy similarity1
Modified residuei361N6-acetyllysineBy similarity1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiP55084.
MaxQBiP55084.
PaxDbiP55084.
PeptideAtlasiP55084.
PRIDEiP55084.

2D gel databases

UCD-2DPAGEP55084.

PTM databases

iPTMnetiP55084.
PhosphoSitePlusiP55084.
SwissPalmiP55084.

Expressioni

Gene expression databases

BgeeiENSG00000138029.
CleanExiHS_HADHB.
ExpressionAtlasiP55084. baseline and differential.
GenevisibleiP55084. HS.

Organism-specific databases

HPAiHPA037539.
HPA037540.
HPA066099.

Interactioni

Subunit structurei

Octamer of 4 alpha (HADHA) and 4 beta (HADHB) subunits. Interacts with RSAD2/viperin.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
GABARAPL1Q9H0R84EBI-356635,EBI-746969

Protein-protein interaction databases

BioGridi109282. 82 interactors.
IntActiP55084. 45 interactors.
MINTiMINT-1154861.
STRINGi9606.ENSP00000325136.

Structurei

3D structure databases

ProteinModelPortaliP55084.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the thiolase family.Curated

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG1392. Eukaryota.
COG0183. LUCA.
GeneTreeiENSGT00760000119318.
HOGENOMiHOG000012240.
HOVERGENiHBG104782.
InParanoidiP55084.
KOiK07509.
OMAiMTAFPEP.
OrthoDBiEOG091G09R7.
PhylomeDBiP55084.
TreeFamiTF315243.

Family and domain databases

Gene3Di3.40.47.10. 4 hits.
InterProiIPR002155. Thiolase.
IPR016039. Thiolase-like.
IPR020615. Thiolase_acyl_enz_int_AS.
IPR020610. Thiolase_AS.
IPR020617. Thiolase_C.
IPR020613. Thiolase_CS.
IPR020616. Thiolase_N.
[Graphical view]
PfamiPF02803. Thiolase_C. 1 hit.
PF00108. Thiolase_N. 1 hit.
[Graphical view]
SUPFAMiSSF53901. SSF53901. 2 hits.
TIGRFAMsiTIGR01930. AcCoA-C-Actrans. 1 hit.
PROSITEiPS00098. THIOLASE_1. 1 hit.
PS00737. THIOLASE_2. 1 hit.
PS00099. THIOLASE_3. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P55084-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MTILTYPFKN LPTASKWALR FSIRPLSCSS QLRAAPAVQT KTKKTLAKPN
60 70 80 90 100
IRNVVVVDGV RTPFLLSGTS YKDLMPHDLA RAALTGLLHR TSVPKEVVDY
110 120 130 140 150
IIFGTVIQEV KTSNVAREAA LGAGFSDKTP AHTVTMACIS ANQAMTTGVG
160 170 180 190 200
LIASGQCDVI VAGGVELMSD VPIRHSRKMR KLMLDLNKAK SMGQRLSLIS
210 220 230 240 250
KFRFNFLAPE LPAVSEFSTS ETMGHSADRL AAAFAVSRLE QDEYALRSHS
260 270 280 290 300
LAKKAQDEGL LSDVVPFKVP GKDTVTKDNG IRPSSLEQMA KLKPAFIKPY
310 320 330 340 350
GTVTAANSSF LTDGASAMLI MAEEKALAMG YKPKAYLRDF MYVSQDPKDQ
360 370 380 390 400
LLLGPTYATP KVLEKAGLTM NDIDAFEFHE AFSGQILANF KAMDSDWFAE
410 420 430 440 450
NYMGRKTKVG LPPLEKFNNW GGSLSLGHPF GATGCRLVMA AANRLRKEGG
460 470
QYGLVAACAA GGQGHAMIVE AYPK
Length:474
Mass (Da):51,294
Last modified:October 17, 2006 - v3
Checksum:iA7B41C37BEC1E6AD
GO
Isoform 2 (identifier: P55084-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-36: MTILTYPFKNLPTASKWALRFSIRPLSCSSQLRAAP → MTLVSGWLLYGWII

Note: No experimental confirmation available.
Show »
Length:452
Mass (Da):48,880
Checksum:i3633B6AE6528FC78
GO

Sequence cautioni

The sequence BAA22061 differs from that shown. Reason: Erroneous gene model prediction.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti1M → MT in AAG39280 (Ref. 3) Curated1
Sequence conflicti1M → MT in AAH14572 (PubMed:15489334).Curated1
Sequence conflicti1M → MT in AAH17564 (PubMed:15489334).Curated1
Sequence conflicti1M → MT in AAH30824 (PubMed:15489334).Curated1
Sequence conflicti1M → MT in AAH66963 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02112859G → D in MTPD. 1 Publication1
Natural variantiVAR_02112961R → C in MTPD. 1 PublicationCorresponds to variant rs780351691dbSNPEnsembl.1
Natural variantiVAR_00749361R → H in MTPD. 2 PublicationsCorresponds to variant rs121913132dbSNPEnsembl.1
Natural variantiVAR_021130117R → G in MTPD. 1 Publication1
Natural variantiVAR_035705119A → V in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_021131121L → P in MTPD. 1 PublicationCorresponds to variant rs773127211dbSNPEnsembl.1
Natural variantiVAR_021132133T → P in MTPD. 1 PublicationCorresponds to variant rs371159065dbSNPEnsembl.1
Natural variantiVAR_028231209P → S.1 PublicationCorresponds to variant rs17851200dbSNPEnsembl.1
Natural variantiVAR_021133242D → G in MTPD. 1 Publication1
Natural variantiVAR_007494247R → H in MTPD. 2 PublicationsCorresponds to variant rs121913133dbSNPEnsembl.1
Natural variantiVAR_021134259 – 270Missing in MTPD. 1 PublicationAdd BLAST12
Natural variantiVAR_007495263D → G in MTPD. 2 PublicationsCorresponds to variant rs121913131dbSNPEnsembl.1
Natural variantiVAR_061897277K → R.Corresponds to variant rs57969630dbSNPEnsembl.1
Natural variantiVAR_021135280G → D in MTPD. 1 PublicationCorresponds to variant rs751772298dbSNPEnsembl.1
Natural variantiVAR_021136294P → L in MTPD. 1 Publication1
Natural variantiVAR_021137294P → R in MTPD. 1 Publication1
Natural variantiVAR_021138301G → S in MTPD. 1 Publication1
Natural variantiVAR_017409444R → K in MTPD. 2 PublicationsCorresponds to variant rs121913134dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0544261 – 36MTILT…LRAAP → MTLVSGWLLYGWII in isoform 2. 1 PublicationAdd BLAST36

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D16481 mRNA. Translation: BAA03942.1.
D86850 Genomic DNA. Translation: BAA22061.1. Sequence problems.
AF113209 mRNA. Translation: AAG39280.1.
AK304455 mRNA. Translation: BAG65272.1.
AK314455 mRNA. Translation: BAG37063.1.
AC010896 Genomic DNA. Translation: AAY14644.1.
BC014572 mRNA. Translation: AAH14572.1.
BC017564 mRNA. Translation: AAH17564.1.
BC030824 mRNA. Translation: AAH30824.1.
BC066963 mRNA. Translation: AAH66963.1.
CCDSiCCDS1722.1. [P55084-1]
CCDS62872.1. [P55084-2]
PIRiJC2109.
RefSeqiNP_000174.1. NM_000183.2. [P55084-1]
NP_001268441.1. NM_001281512.1.
NP_001268442.1. NM_001281513.1. [P55084-2]
XP_011531105.1. XM_011532803.1. [P55084-1]
UniGeneiHs.515848.

Genome annotation databases

EnsembliENST00000317799; ENSP00000325136; ENSG00000138029. [P55084-1]
ENST00000545822; ENSP00000442665; ENSG00000138029. [P55084-2]
GeneIDi3032.
KEGGihsa:3032.
UCSCiuc002rgz.4. human. [P55084-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D16481 mRNA. Translation: BAA03942.1.
D86850 Genomic DNA. Translation: BAA22061.1. Sequence problems.
AF113209 mRNA. Translation: AAG39280.1.
AK304455 mRNA. Translation: BAG65272.1.
AK314455 mRNA. Translation: BAG37063.1.
AC010896 Genomic DNA. Translation: AAY14644.1.
BC014572 mRNA. Translation: AAH14572.1.
BC017564 mRNA. Translation: AAH17564.1.
BC030824 mRNA. Translation: AAH30824.1.
BC066963 mRNA. Translation: AAH66963.1.
CCDSiCCDS1722.1. [P55084-1]
CCDS62872.1. [P55084-2]
PIRiJC2109.
RefSeqiNP_000174.1. NM_000183.2. [P55084-1]
NP_001268441.1. NM_001281512.1.
NP_001268442.1. NM_001281513.1. [P55084-2]
XP_011531105.1. XM_011532803.1. [P55084-1]
UniGeneiHs.515848.

3D structure databases

ProteinModelPortaliP55084.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109282. 82 interactors.
IntActiP55084. 45 interactors.
MINTiMINT-1154861.
STRINGi9606.ENSP00000325136.

PTM databases

iPTMnetiP55084.
PhosphoSitePlusiP55084.
SwissPalmiP55084.

Polymorphism and mutation databases

BioMutaiHADHB.
DMDMi116241345.

2D gel databases

UCD-2DPAGEP55084.

Proteomic databases

EPDiP55084.
MaxQBiP55084.
PaxDbiP55084.
PeptideAtlasiP55084.
PRIDEiP55084.

Protocols and materials databases

DNASUi3032.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000317799; ENSP00000325136; ENSG00000138029. [P55084-1]
ENST00000545822; ENSP00000442665; ENSG00000138029. [P55084-2]
GeneIDi3032.
KEGGihsa:3032.
UCSCiuc002rgz.4. human. [P55084-1]

Organism-specific databases

CTDi3032.
DisGeNETi3032.
GeneCardsiHADHB.
HGNCiHGNC:4803. HADHB.
HPAiHPA037539.
HPA037540.
HPA066099.
MalaCardsiHADHB.
MIMi143450. gene.
609015. phenotype.
neXtProtiNX_P55084.
OpenTargetsiENSG00000138029.
Orphaneti746. Mitochondrial trifunctional protein deficiency.
PharmGKBiPA29177.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1392. Eukaryota.
COG0183. LUCA.
GeneTreeiENSGT00760000119318.
HOGENOMiHOG000012240.
HOVERGENiHBG104782.
InParanoidiP55084.
KOiK07509.
OMAiMTAFPEP.
OrthoDBiEOG091G09R7.
PhylomeDBiP55084.
TreeFamiTF315243.

Enzyme and pathway databases

UniPathwayiUPA00659.
BioCyciMetaCyc:HS06436-MONOMER.
ZFISH:HS06436-MONOMER.
ReactomeiR-HSA-1482798. Acyl chain remodeling of CL.
R-HSA-77285. Beta oxidation of myristoyl-CoA to lauroyl-CoA.
R-HSA-77288. mitochondrial fatty acid beta-oxidation of unsaturated fatty acids.
R-HSA-77305. Beta oxidation of palmitoyl-CoA to myristoyl-CoA.
R-HSA-77310. Beta oxidation of lauroyl-CoA to decanoyl-CoA-CoA.
R-HSA-77346. Beta oxidation of decanoyl-CoA to octanoyl-CoA-CoA.
R-HSA-77348. Beta oxidation of octanoyl-CoA to hexanoyl-CoA.
R-HSA-77350. Beta oxidation of hexanoyl-CoA to butanoyl-CoA.

Miscellaneous databases

ChiTaRSiHADHB. human.
GeneWikiiHADHB.
GenomeRNAii3032.
PROiP55084.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000138029.
CleanExiHS_HADHB.
ExpressionAtlasiP55084. baseline and differential.
GenevisibleiP55084. HS.

Family and domain databases

Gene3Di3.40.47.10. 4 hits.
InterProiIPR002155. Thiolase.
IPR016039. Thiolase-like.
IPR020615. Thiolase_acyl_enz_int_AS.
IPR020610. Thiolase_AS.
IPR020617. Thiolase_C.
IPR020613. Thiolase_CS.
IPR020616. Thiolase_N.
[Graphical view]
PfamiPF02803. Thiolase_C. 1 hit.
PF00108. Thiolase_N. 1 hit.
[Graphical view]
SUPFAMiSSF53901. SSF53901. 2 hits.
TIGRFAMsiTIGR01930. AcCoA-C-Actrans. 1 hit.
PROSITEiPS00098. THIOLASE_1. 1 hit.
PS00737. THIOLASE_2. 1 hit.
PS00099. THIOLASE_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiECHB_HUMAN
AccessioniPrimary (citable) accession number: P55084
Secondary accession number(s): B2RB16
, B4E2W0, O14969, Q53TA6, Q96C77, Q9H3F5, Q9T2V8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 17, 2006
Last modified: November 30, 2016
This is version 169 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.