Q6P587 (FAHD1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Acylpyruvase FAHD1, mitochondrial
EC=3.7.1.5

Alternative name(s):
Fumarylacetoacetate hydrolase domain-containing protein 1

Gene names

Name:	FAHD1
Synonyms:	C16orf36

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	224 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Probable mitochondrial acylpyruvase which is able to hydrolyze acetylpyruvate and fumarylpyruvate in vitro. Ref.9
Catalytic activity	A 3-acylpyruvate + H2O = a carboxylate + pyruvate. Ref.8
Cofactor	Magnesium or manganese Probable. Ref.8
Subunit structure	Homodimer. Ref.9
Subcellular location	Mitochondrion. Cytoplasm › cytosol Ref.8.
Tissue specificity	Ubiquitous (at protein level). Ref.8
Sequence similarities	Belongs to the FAH family.
Biophysicochemical properties	Kinetic parameters: KM=4.6 µM for acetylpyruvate Ref.8 Vmax=0.135 µmol/min/mg enzyme toward acetylpyruvate
Sequence caution	The sequence AAK61295.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
Cellular component	Cytoplasm Mitochondrion
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transit peptide
Ligand	Calcium Magnesium Metal-binding
Molecular function	Hydrolase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Cellular component	cytosol Inferred from direct assay Ref.8. Source: UniProtKB mitochondrion Inferred from direct assay Ref.8. Source: UniProtKB
Molecular function	acetylpyruvate hydrolase activity Inferred from direct assay Ref.8. Source: UniProtKB acylpyruvate hydrolase activity Inferred from electronic annotation. Source: EC fumarylpyruvate hydrolase activity Inferred from direct assay Ref.8. Source: UniProtKB metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
EXOSC4	Q9NPD3	1	EBI-597013,EBI-371823

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q6P587-1)

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.

Isoform 2 (identifier: Q6P587-2)

The sequence of this isoform differs from the canonical sequence as follows:
     213-224: VSMTFKVEKPEY → PKVSSATLPVRLQE

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 27

27

Mitochondrion Potential

Chain

28 – 224

197

Acylpyruvase FAHD1, mitochondrial

PRO_0000156829

Sites

Metal binding

71

1

Divalent metal cation

Metal binding

73

1

Divalent metal cation

Metal binding

102

1

Divalent metal cation

Natural variations

Alternative sequence

213 – 224

12

VSMTF…EKPEY → PKVSSATLPVRLQE in isoform 2.

VSP_013741

Natural variant

110

1

D → N.
Corresponds to variant rs3743853 [ dbSNP | Ensembl ].

VAR_049014

Experimental info

Mutagenesis

102

1

D → A: Loss of catalytic activity; when associated with A-106. Ref.8

Mutagenesis

106

1

R → A: Loss of catalytic activity; when associated with A-102. Ref.8

Sequence conflict

177

1

S → P in CAG38530. Ref.4

Secondary structure

1

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224

Helix Strand Turn

Details...

Helix

10 – 12

3

Helix

13 – 16

4

Beta strand

19 – 24

6

Beta strand

44 – 48

5

Helix

49 – 51

3

Beta strand

52 – 54

3

Beta strand

68 – 70

3

Beta strand

72 – 80

9

Turn

87 – 89

3

Helix

90 – 92

3

Beta strand

93 – 101

9

Helix

106 – 115

10

Helix

120 – 123

4

Beta strand

129 – 131

3

Beta strand

147 – 152

6

Beta strand

155 – 161

7

Helix

162 – 164

3

Beta strand

165 – 167

3

Helix

169 – 177

9

Beta strand

187 – 189

3

Beta strand

197 – 199

3

Beta strand

204 – 209

6

Turn

210 – 212

3

Beta strand

213 – 220

8

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 10, 2005. Version 2. Checksum: A005E4ECD613C72E	FASTA	224	24,843
	10 20 30 40 50 60 MGIMAASRPL SRFWEWGKNI VCVGRNYADH VREMRSAVLS EPVLFLKPST AYAPEGSPIL 70 80 90 100 110 120 MPAYTRNLHH ELELGVVMGK RCRAVPEAAA MDYVGGYALC LDMTARDVQD ECKKKGLPWT 130 140 150 160 170 180 LAKSFTASCP VSAFVPKEKI PDPHKLKLWL KVNGELRQEG ETSSMIFSIP YIISYVSKII 190 200 210 220 TLEEGDIILT GTPKGVGPVK ENDEIEAGIH GLVSMTFKVE KPEY
	Isoform 2 [UniParc]. Checksum: 899A2BAC58271420	FASTA	226	24,910
	10 20 30 40 50 60 MGIMAASRPL SRFWEWGKNI VCVGRNYADH VREMRSAVLS EPVLFLKPST AYAPEGSPIL 70 80 90 100 110 120 MPAYTRNLHH ELELGVVMGK RCRAVPEAAA MDYVGGYALC LDMTARDVQD ECKKKGLPWT 130 140 150 160 170 180 LAKSFTASCP VSAFVPKEKI PDPHKLKLWL KVNGELRQEG ETSSMIFSIP YIISYVSKII 190 200 210 220 TLEEGDIILT GTPKGVGPVK ENDEIEAGIH GLPKVSSATL PVRLQE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Sequence, structure and pathology of the fully annotated terminal 2 Mb of the short arm of human chromosome 16." Daniels R.J., Peden J.F., Lloyd C., Horsley S.W., Clark K., Tufarelli C., Kearney L., Buckle V.J., Doggett N.A., Flint J., Higgs D.R. Hum. Mol. Genet. 10:339-352(2001) [PubMed: 11157797] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[2]	"Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs." Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., Ottenwaelder B., Obermaier B. , Tampe J., Heubner D., Wambutt R., Korn B., Klein M., Poustka A. Genome Res. 11:422-435(2001) [PubMed: 11230166] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Kidney.
[3]	"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. , 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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Glial tumor.
[4]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[5]	"The sequence and analysis of duplication-rich human chromosome 16." Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A. Nature 432:988-994(2004) [PubMed: 15616553] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Pancreas.
[7]	"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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[8]	"Identification of human fumarylacetoacetate hydrolase domain containing protein 1 (FAHD1) as a novel mitochondrial acylpyruvase." Pircher H., Straganz G.D., Ehehalt D., Morrow G., Tanguay R.M., Jansen-Durr P. J. Biol. Chem. 286:36500-36508(2011) [PubMed: 21878618] [Abstract] Cited for: CATALYTIC ACTIVITY, KINETIC PARAMETERS, COFACTOR, MUTAGENESIS OF ASP-102 AND ARG-106, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[9]	"X-ray structure of fumarylacetoacetate hydrolase family member Homo sapiens FLJ36880." Manjasetty B.A., Niesen F.H., Delbrueck H., Goetz F., Sievert V., Buessow K., Behlke J., Heinemann U. Biol. Chem. 385:935-942(2004) [PubMed: 15551868] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) IN COMPLEX WITH MAGNESIUM, FUNCTION, DIMERIZATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AE006639 Genomic DNA. Translation: AAK61295.1. Different initiation.
AL136720 mRNA. Translation: CAB66654.1.
AK094199 mRNA. Translation: BAC04308.1.
CR533499 mRNA. Translation: CAG38530.1.
AL031722, AC012180 Genomic DNA. Translation: CAM26476.1.
BC063017 mRNA. Translation: AAH63017.1.

IPI

IPI00440828.
IPI00552360.

RefSeq

NP_001018114.1. NM_001018104.2.
NP_001135870.1. NM_001142398.1.
NP_112485.1. NM_031208.3.

UniGene

Hs.513265.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1SAW	X-ray	2.20	A/B	2-224	[»]

ProteinModelPortal

Q6P587.

SMR

Q6P587. Positions 6-224.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q6P587. 3 interactions.

STRING

Q6P587.

PTM databases

PhosphoSite

Q6P587.

Polymorphism databases

DMDM

68566321.

2D gel databases

UCD-2DPAGE

Q6P587.

Proteomic databases

PRIDE

Q6P587.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000427358; ENSP00000398053; ENSG00000180185.

GeneID

81889.

KEGG

hsa:81889.

NMPDR

fig|9606.3.peg.11514.

UCSC

uc002cnc.1. human.
uc010brz.1. human.

Organism-specific databases

CTD

81889.

GeneCards

GC16P001876.

HGNC

HGNC:14169. FAHD1.

HPA

CAB025530.

neXtProt

NX_Q6P587.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG19603.

GeneTree

ENSGT00530000063832.

HOVERGEN

HBG057495.

PhylomeDB

Q6P587.

Gene expression databases

ArrayExpress

Q6P587.

Bgee

Q6P587.

CleanEx

HS_FAHD1.

Genevestigator

Q6P587.

GermOnline

ENSG00000180185. Homo sapiens.

Family and domain databases

InterPro

IPR002529. Fumarylacetoacetase_C.
IPR011234. Fumarylacetoacetase_C-rel.
[Graphical view]

Gene3D

G3DSA:3.90.850.10. Fumarylacetoacetase_C-rel. 1 hit.

Pfam

PF01557. FAA_hydrolase. 1 hit.
[Graphical view]

SUPFAM

SSF56529. Fumarylacetoacetase_C-rel. 1 hit.

ProtoNet

Search...

Other

NextBio

72236.

Entry information

Entry name

FAHD1_HUMAN

Accession

Primary (citable) accession number: Q6P587
Secondary accession number(s): B1AK41 , Q6FIC7, Q96RY1, Q9H0N6

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 10, 2005
Last sequence update:	May 10, 2005
Last modified:	January 25, 2012
This is version 77 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.