Q9BV57 (MTND_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
1,2-dihydroxy-3-keto-5-methylthiopentene dioxygenase
EC=1.13.11.54

Alternative name(s):
Acireductone dioxygenase (Fe(2+)-requiring)
Short name=ARD
Short name=Fe-ARD
Membrane-type 1 matrix metalloproteinase cytoplasmic tail-binding protein 1
Short name=MTCBP-1
Submergence-induced protein-like factor
Short name=Sip-L

Gene names

Name:	ADI1
Synonyms:	MTCBP1
ORF Names:	HMFT1638

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	179 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes the formation of formate and 2-keto-4-methylthiobutyrate (KMTB) from 1,2-dihydroxy-3-keto-5-methylthiopentene (DHK-MTPene). Also down-regulates cell migration mediated by MMP14. Necessary for hepatitis C virus replication in an otherwise non-permissive cell line. Ref.10 Ref.11
Catalytic activity	1,2-dihydroxy-5-(methylthio)pent-1-en-3-one + O2 = 4-(methylthio)-2-oxobutanoate + formate. Ref.11
Cofactor	Binds 1 iron ion per monomer. Can also use other divalent metal cations By similarity.
Pathway	Amino-acid biosynthesis; L-methionine biosynthesis via salvage pathway; L-methionine from S-methyl-5-thio-alpha-D-ribose 1-phosphate: step 5/6. HAMAP-Rule MF_03154
Subunit structure	Monomer By similarity. Interacts with MMP14. Ref.1
Subcellular location	Cytoplasm. Nucleus. Cell membrane; Peripheral membrane protein; Cytoplasmic side. Note: Localizes to the plasma membrane when complexed to MMP14. Ref.1 Ref.10
Tissue specificity	Detected in heart, colon, lung, stomach, brain, spleen, liver, skeletal muscle and kidney. Ref.1 Ref.10
Sequence similarities	Belongs to the acireductone dioxygenase (ARD) family.
Sequence caution	The sequence AAL25800.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence BAD38646.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. The sequence BAD96187.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Biological process	Amino-acid biosynthesis Methionine biosynthesis
Cellular component	Cell membrane Cytoplasm Membrane Nucleus
Coding sequence diversity	Alternative splicing
Ligand	Iron Metal-binding
Molecular function	Dioxygenase Oxidoreductase
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	L-methionine salvage from methylthioadenosine Inferred from direct assay Ref.11. Source: UniProtKB polyamine metabolic process Traceable author statement. Source: Reactome
Cellular_component	Golgi apparatus Inferred from direct assay. Source: HPA cytosol Traceable author statement. Source: Reactome nucleus Inferred from direct assay Ref.10Ref.1. Source: UniProtKB plasma membrane Inferred from direct assay Ref.1. Source: UniProtKB
Molecular_function	acireductone dioxygenase [iron(II)-requiring] activity Traceable author statement. Source: Reactome metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
MMP14	P50281	4	EBI-992807,EBI-992788

Alternative products

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

Isoform 1 (identifier: Q9BV57-1)

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: Q9BV57-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-40: MVQAWYMDDAPGDPRQPHRPDPGRPVGLEQLRRLGVLYWK → MSVKSSKLMFLCHGSSRSLHSGSLTSCNTGVCCS

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 179	179	1,2-dihydroxy-3-keto-5-methylthiopentene dioxygenase HAMAP-Rule MF_03154		PRO_0000162942
Sites
	Metal binding	88	1	Iron or nickel By similarity
	Metal binding	90	1	Iron or nickel By similarity
	Metal binding	94	1	Iron or nickel By similarity
	Metal binding	133	1	Iron or nickel By similarity
Natural variations
	Alternative sequence	1 – 40	40	MVQAW…VLYWK → MSVKSSKLMFLCHGSSRSLH SGSLTSCNTGVCCS in isoform 2.		VSP_015822
Experimental info
	Mutagenesis	94	1	E → A: Loss of aci-reductone dioxygenase activity. Ref.11
	Sequence conflict	3	1	Q → L in BAA91901. Ref.4
	Sequence conflict	108	1	R → G in BAD96187. Ref.5
	Sequence conflict	170	1	Q → K in AAP97173. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 1, 2001. Version 1. Checksum: 92E13B9718D44C27	FASTA	179	21,498
	10 20 30 40 50 60 MVQAWYMDDA PGDPRQPHRP DPGRPVGLEQ LRRLGVLYWK LDADKYENDP ELEKIRRERN 70 80 90 100 110 120 YSWMDIITIC KDKLPNYEEK IKMFYEEHLH LDDEIRYILD GSGYFDVRDK EDQWIRIFME 130 140 150 160 170 KGDMVTLPAG IYHRFTVDEK NYTKAMRLFV GEPVWTAYNR PADHFEARGQ YVKFLAQTA
	Isoform 2 [UniParc]. Checksum: 5AE5570210391A36	FASTA	173	20,332
	10 20 30 40 50 60 MSVKSSKLMF LCHGSSRSLH SGSLTSCNTG VCCSLDADKY ENDPELEKIR RERNYSWMDI 70 80 90 100 110 120 ITICKDKLPN YEEKIKMFYE EHLHLDDEIR YILDGSGYFD VRDKEDQWIR IFMEKGDMVT 130 140 150 160 170 LPAGIYHRFT VDEKNYTKAM RLFVGEPVWT AYNRPADHFE ARGQYVKFLA QTA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Membrane-type 1 matrix metalloproteinase cytoplasmic tail-binding protein-1 is a new member of the cupin superfamily. A possible multifunctional protein acting as an invasion suppressor down-regulated in tumors." Uekita T., Gotoh I., Kinoshita T., Itoh Y., Sato H., Shiomi T., Okada Y., Seiki M. J. Biol. Chem. 279:12734-12743(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH MMP14, SUBCELLULAR LOCATION, TISSUE SPECIFICITY. Tissue: Fibroblast.
[2]	"Cloning and expression of a new human cDNA homologous to O.sativa submergence induced protein 2 (sip2) mRNA." Fan Y.X., Yu L., Ding J.B., Hu P.R., Fu S.N., Zhao S.Y. Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]	"Expression profiling and differential screening between hepatoblastomas and the corresponding normal livers: identification of high expression of the PLK1 oncogene as a poor-prognostic indicator of hepatoblastomas." Yamada S., Ohira M., Horie H., Ando K., Takayasu H., Suzuki Y., Sugano S., Hirata T., Goto T., Matsunaga T., Hiyama E., Hayashi Y., Ando H., Suita S., Kaneko M., Sasaki F., Hashizume K., Ohnuma N., Nakagawara A. Oncogene 23:5901-5911(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Hepatoblastoma.
[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. , 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] (ISOFORMS 1 AND 2). Tissue: Ovarian carcinoma and Thalamus.
[5]	Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Adipose tissue.
[6]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	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. , 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].
[8]	"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] (ISOFORM 1). Tissue: Placenta.
[9]	"Global profiling of protease cleavage sites by chemoselective labeling of protein N-termini." Xu G., Shin S.B., Jaffrey S.R. Proc. Natl. Acad. Sci. U.S.A. 106:19310-19315(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE [LARGE SCALE ANALYSIS] OF 2-30. Tissue: Leukemic T-cell.
[10]	"Identification of a hepatic factor capable of supporting hepatitis C virus replication in a nonpermissive cell line." Yeh C.-T., Lai H.-Y., Chen T.-C., Chu C.-M., Liaw Y.-F. J. Virol. 75:11017-11024(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 50-179, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY. Tissue: Liver.
[11]	"Membrane-type 1 matrix metalloproteinase cytoplasmic tail binding protein-1 (MTCBP-1) acts as an eukaryotic aci-reductone dioxygenase (ARD) in the methionine salvage pathway." Hirano W., Gotoh I., Uekita T., Seiki M. Genes Cells 10:565-574(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF GLU-94.
[12]	"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].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB158319 mRNA. Translation: BAD10866.1. AF087863 mRNA. Translation: AAP97173.1. AB073609 mRNA. Translation: BAD38646.1. Different initiation. AK001775 mRNA. Translation: BAA91901.1. AK127473 mRNA. Translation: BAC86996.1. AK222467 mRNA. Translation: BAD96187.1. Different initiation. AC142528 Genomic DNA. Translation: AAX82038.1. AC114810 Genomic DNA. Translation: AAY24022.1. CH471053 Genomic DNA. Translation: EAX01064.1. CH471053 Genomic DNA. Translation: EAX01065.1. BC001467 mRNA. Translation: AAH01467.1. AF403478 mRNA. Translation: AAL25800.1. Different initiation.
IPI	IPI00470791. IPI00651738.
RefSeq	NP_060739.2. NM_018269.3.
UniGene	Hs.502773.
3D structure databases
ProteinModelPortal	Q9BV57.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9BV57. 1 interaction.
PTM databases
PhosphoSite	Q9BV57.
Polymorphism databases
DMDM	74733289.
Proteomic databases
PaxDb	Q9BV57.
PRIDE	Q9BV57.
Protocols and materials databases
DNASU	55256.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000327435; ENSP00000333666; ENSG00000182551. ENST00000382093; ENSP00000371525; ENSG00000182551.
GeneID	55256.
KEGG	hsa:55256.
UCSC	uc002qxp.4. human.
Organism-specific databases
CTD	55256.
GeneCards	GC02M003501.
HGNC	HGNC:30576. ADI1.
HPA	HPA035403.
MIM	613400. gene.
neXtProt	NX_Q9BV57.
PharmGKB	PA143485291.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1791.
HOVERGEN	HBG081992.
InParanoid	Q9BV57.
KO	K08967.
OMA	MVRAWYM.
OrthoDB	EOG434W79.
PhylomeDB	Q9BV57.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism.
UniPathway	UPA00904; UER00878.
Gene expression databases
Bgee	Q9BV57.
CleanEx	HS_ADI1.
Genevestigator	Q9BV57.
GermOnline	ENSG00000182551. Homo sapiens.
Family and domain databases
Gene3D	2.60.120.10. 1 hit.
HAMAP	MF_03154. Salvage_MtnD_euk.
InterPro	IPR004313. Acireductn_dOase_family. IPR027496. MTCBP-1_eukaryotes. IPR014710. RmlC-like_jellyroll. IPR011051. RmlC_Cupin. [Graphical view]
PANTHER	PTHR23418. PTHR23418. 1 hit.
Pfam	PF03079. ARD. 1 hit. [Graphical view]
SUPFAM	SSF51182. RmlC_like_cupin. 1 hit.
ProtoNet	Search...
Other
ChiTaRS	ADI1. human.
GenomeRNAi	55256.
NextBio	59336.
SOURCE	Search...

Entry information

Entry name

MTND_HUMAN

Accession

Primary (citable) accession number: Q9BV57
Secondary accession number(s): D6W4Y3 , Q53HW3, Q53QD3, Q57YV7, Q68CK2, Q6ZSF7, Q7Z512, Q96P85, Q9NV57

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 11, 2005
Last sequence update:	June 1, 2001
Last modified:	May 29, 2013
This is version 108 of the entry and version 1 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.