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Q93099 (HGD_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 138. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Homogentisate 1,2-dioxygenase

EC=1.13.11.5
Alternative name(s):
Homogentisate oxygenase
Homogentisic acid oxidase
Homogentisicase
Gene names
Name:HGD
Synonyms:HGO
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length445 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Catalytic activity

Homogentisate + O2 = 4-maleylacetoacetate.

Cofactor

Iron.

Pathway

Amino-acid degradation; L-phenylalanine degradation; acetoacetate and fumarate from L-phenylalanine: step 4/6.

Subunit structure

Homohexamer arranged as a dimer of trimers. Ref.10

Tissue specificity

Highest expression in the prostate, small intestine, colon, kidney and liver.

Involvement in disease

Alkaptonuria (AKU) [MIM:203500]: An autosomal recessive error of metabolism characterized by an increase in the level of homogentisic acid. The clinical manifestations are urine that turns dark on standing and alkalinization, black ochronotic pigmentation of cartilage and collagenous tissues, and spine arthritis.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17

Sequence similarities

Belongs to the homogentisate dioxygenase family.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 445445Homogentisate 1,2-dioxygenase
PRO_0000220240

Sites

Metal binding3351Iron
Metal binding3411Iron
Metal binding3711Iron

Amino acid modifications

Modified residue981N6-acetyllysine Ref.8
Modified residue4141N6-succinyllysine By similarity

Natural variations

Natural variant251L → P in AKU. Ref.15 Ref.16
VAR_009618
Natural variant421E → A in AKU. Ref.12
VAR_005272
Natural variant601W → G in AKU. Ref.14
VAR_005273
Natural variant621Y → C in AKU. Ref.14
VAR_005274
Natural variant801Q → H. Ref.1 Ref.2 Ref.3 Ref.4 Ref.6 Ref.7
Corresponds to variant rs2255543 [ dbSNP | Ensembl ].
VAR_049353
Natural variant971W → G in AKU. Ref.12
VAR_005275
Natural variant1221A → D in AKU. Ref.14
VAR_005276
Natural variant1531D → G in AKU. Ref.12
VAR_005277
Natural variant1611G → R in AKU; loss of activity; most prevalent mutation in Slovak and Czech patients. Ref.11 Ref.16
Corresponds to variant rs28941783 [ dbSNP | Ensembl ].
VAR_005278
Natural variant1681E → K in AKU; loss of activity. Ref.13
VAR_009619
Natural variant1891S → I in AKU. Ref.12
VAR_005279
Natural variant2161I → T in AKU. Ref.12
VAR_005280
Natural variant2251R → H in AKU. Ref.12
VAR_005281
Natural variant2271F → S in AKU. Ref.12
VAR_005282
Natural variant2301P → S in AKU; complete loss of activity. Ref.1 Ref.16
Corresponds to variant rs28942100 [ dbSNP | Ensembl ].
VAR_005283
Natural variant2301P → T in AKU. Ref.14
VAR_005284
Natural variant2701G → R in AKU. Ref.16
VAR_009620
Natural variant2911D → E in AKU. Ref.14
VAR_005285
Natural variant3001V → G in AKU. Ref.1 Ref.16
VAR_005286
Natural variant3301R → S in AKU. Ref.17
VAR_008744
Natural variant3681M → V in AKU; loss of activity. Ref.12 Ref.15 Ref.16 Ref.17
Corresponds to variant rs120074173 [ dbSNP | Ensembl ].
VAR_005287
Natural variant3711H → R in AKU. Ref.17
VAR_008745

Experimental info

Sequence conflict3831K → R in BAF83471. Ref.4

Secondary structure

........................................................................... 445
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q93099 [UniParc].

Last modified May 18, 2010. Version 2.
Checksum: F99B51C134FFF965

FASTA44549,964
        10         20         30         40         50         60 
MAELKYISGF GNECSSEDPR CPGSLPEGQN NPQVCPYNLY AEQLSGSAFT CPRSTNKRSW 

        70         80         90        100        110        120 
LYRILPSVSH KPFESIDEGQ VTHNWDEVDP DPNQLRWKPF EIPKASQKKV DFVSGLHTLC 

       130        140        150        160        170        180 
GAGDIKSNNG LAIHIFLCNT SMENRCFYNS DGDFLIVPQK GNLLIYTEFG KMLVQPNEIC 

       190        200        210        220        230        240 
VIQRGMRFSI DVFEETRGYI LEVYGVHFEL PDLGPIGANG LANPRDFLIP IAWYEDRQVP 

       250        260        270        280        290        300 
GGYTVINKYQ GKLFAAKQDV SPFNVVAWHG NYTPYKYNLK NFMVINSVAF DHADPSIFTV 

       310        320        330        340        350        360 
LTAKSVRPGV AIADFVIFPP RWGVADKTFR PPYYHRNCMS EFMGLIRGHY EAKQGGFLPG 

       370        380        390        400        410        420 
GGSLHSTMTP HGPDADCFEK ASKVKLAPER IADGTMAFMF ESSLSLAVTK WGLKASRCLD 

       430        440 
ENYHKCWEPL KSHFTPNSRN PAEPN 

« Hide

References

« Hide 'large scale' references
[1]"The molecular basis of alkaptonuria."
Fernandez-Canon J.M., Granadino B., Beltran-Valero de Bernabe D., Renedo M., Fernandez-Ruiz E., Penalva M.A., Rodriguez de Cordoba S.
Nat. Genet. 14:19-24(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS HIS-80; AKU SER-230 AND GLY-300.
[2]"Homogentisate 1,2-dioxygenase human cDNA sequence."
Ramos S., Hernandez M., Rozes A., Larruga J., Gonzalez P., Cabrera V.M.
Submitted (SEP-1996) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT HIS-80.
Tissue: Liver.
[3]"The human homogentisate 1,2-dioxygenase (HGO) gene."
Granadino B., Beltran-Valero de Bernabe D., Fernandez-Canon J.M., Penalva M.A., Rodriguez de Cordoba S.
Genomics 43:115-122(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT HIS-80.
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT HIS-80.
Tissue: Kidney and Prostate.
[5]"The DNA sequence, annotation and analysis of human chromosome 3."
Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. expand/collapse author list , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.
Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT HIS-80.
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT HIS-80.
[8]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-98, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]"Crystal structure of human homogentisate dioxygenase."
Titus G.P., Mueller H.A., Burgner J., Rodriguez de Cordoba S., Penalva M.A., Timm D.E.
Nat. Struct. Biol. 7:542-546(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS), METAL-BINDING SITES, SUBUNIT.
[11]"Molecular defects in alkaptonuria."
Gehrig A., Schmidt S.R., Mueller C.R., Srsen S., Srsnova K., Kress W.
Cytogenet. Cell Genet. 76:14-16(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AKU ARG-161.
[12]"Mutation and polymorphism analysis of the human homogentisate 1, 2-dioxygenase gene in alkaptonuria patients."
Beltran-Valero de Bernabe D., Granadino B., Chiarelli I., Porfirio B., Mayatepek E., Aquaron R., Moore M.M., Festen J.J.M., Sanmarti R., Penalva M.A., de Cordoba S.R.
Am. J. Hum. Genet. 62:776-784(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS AKU ALA-42; GLY-97; GLY-153; ILE-189; THR-216; HIS-225; SER-227 AND VAL-368.
[13]"A novel point mutation associated with alkaptonuria."
Higashino K., Liu W., Ohkawa T., Yamamoto T., Fukui K., Ohno M., Imanishi H., Iwasaki A., Amuro Y., Hada T.
Clin. Genet. 53:228-229(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AKU LYS-168.
[14]"Analysis of alkaptonuria (AKU) mutations and polymorphisms reveals that the CCC sequence motif is a mutational hot spot in the homogentisate 1,2 dioxygenase gene (HGO)."
Beltran-Valero de Bernabe D., Jimenez F.J., Aquaron R., Rodriguez de Cordoba S.
Am. J. Hum. Genet. 64:1316-1322(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS AKU GLY-60; CYS-62; ASP-122; THR-230 AND GLU-291.
[15]"Ocular ochronosis in alkaptonuria patients carrying mutations in the homogentisate 1,2-dioxygenase gene."
Felbor U., Mutsch Y., Grehn F., Mueller C.R., Kress W.
Br. J. Ophthalmol. 83:680-683(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS AKU PRO-25 AND VAL-368.
Tissue: Leukocyte.
[16]"Allelic heterogeneity of alkaptonuria in Central Europe."
Mueller C.R., Fregin A., Srsen S., Srsnova K., Halliger-Keller B., Felbor U., Seemanova E., Kress W.
Eur. J. Hum. Genet. 7:645-651(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS AKU PRO-25; ARG-161; SER-230; ARG-270; GLY-300 AND VAL-368.
Tissue: Lymphocyte.
[17]"Mutational analysis of the HGO gene in Finnish alkaptonuria patients."
Beltran-Valero de Bernabe D., Peterson P., Luopajarvi K., Matintalo P., Alho A., Konttinen Y., Krohn K., Rodriguez de Cordoba S., Ranki A.
J. Med. Genet. 36:922-923(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS AKU SER-330; VAL-368 AND ARG-371.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U63008 mRNA. Translation: AAB16836.1.
Z75048 mRNA. Translation: CAA99340.1.
AF000573 Genomic DNA. Translation: AAC51650.1.
AF045167 mRNA. Translation: AAC02698.1.
AK290782 mRNA. Translation: BAF83471.1.
AK313563 mRNA. Translation: BAG36337.1.
AC126182 Genomic DNA. No translation available.
AC133474 Genomic DNA. No translation available.
CH471052 Genomic DNA. Translation: EAW79524.1.
BC071757 mRNA. Translation: AAH71757.1.
RefSeqNP_000178.2. NM_000187.3.
UniGeneHs.368254.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1EY2X-ray2.30A1-445[»]
1EYBX-ray1.90A1-445[»]
ProteinModelPortalQ93099.
SMRQ93099. Positions 2-440.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109329. 7 interactions.
IntActQ93099. 4 interactions.
MINTMINT-3049945.
STRING9606.ENSP00000283871.

PTM databases

PhosphoSiteQ93099.

Proteomic databases

PaxDbQ93099.
PRIDEQ93099.

Protocols and materials databases

DNASU3081.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000283871; ENSP00000283871; ENSG00000113924.
GeneID3081.
KEGGhsa:3081.
UCSCuc003edv.3. human.

Organism-specific databases

CTD3081.
GeneCardsGC03M120347.
H-InvDBHIX0003593.
HGNCHGNC:4892. HGD.
HPAHPA047374.
MIM203500. phenotype.
607474. gene.
neXtProtNX_Q93099.
Orphanet56. Alkaptonuria.
PharmGKBPA29268.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG3508.
HOGENOMHOG000139824.
HOVERGENHBG005965.
InParanoidQ93099.
KOK00451.
OMACWEPLKS.
OrthoDBEOG7PP58Z.
PhylomeDBQ93099.
TreeFamTF300490.

Enzyme and pathway databases

BioCycMetaCyc:HS03728-MONOMER.
ReactomeREACT_111217. Metabolism.
UniPathwayUPA00139; UER00339.

Gene expression databases

ArrayExpressQ93099.
BgeeQ93099.
CleanExHS_HGD.
GenevestigatorQ93099.

Family and domain databases

Gene3D2.60.120.10. 2 hits.
InterProIPR005708. Homogentis_dOase.
IPR014710. RmlC-like_jellyroll.
IPR011051. RmlC_Cupin.
[Graphical view]
PANTHERPTHR11056. PTHR11056. 1 hit.
PfamPF04209. HgmA. 1 hit.
[Graphical view]
SUPFAMSSF51182. SSF51182. 1 hit.
TIGRFAMsTIGR01015. hmgA. 1 hit.
ProtoNetSearch...

Other

EvolutionaryTraceQ93099.
GenomeRNAi3081.
NextBio12197.
PROQ93099.
SOURCESearch...

Entry information

Entry nameHGD_HUMAN
AccessionPrimary (citable) accession number: Q93099
Secondary accession number(s): A8K417, B2R8Z0
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: May 18, 2010
Last modified: April 16, 2014
This is version 138 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM