Reviewed, UniProtKB/Swiss-Prot Q9BV57 (MTND_HUMAN)

Names and origin

Protein names

Recommended name:
    1,2-dihydroxy-3-keto-5-methylthiopentene dioxygenase
    EC=1.13.-.-
Alternative name(s):
    Aci-reductone dioxygenase
      Short name=ARD
    Membrane-type 1 matrix metalloproteinase cytoplasmic tail-binding protein 1
      Short name=MTCBP-1
    Submergence-induced protein 2 homolog
      Short name=SIPL

Gene names

Name:	ADI1
Synonyms:	MTCBP1
ORF Names:	HMFT1638

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	179 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Has aci-reductone dioxygenase (ARD) activity and can function in the 5-methylthioadenosine (MTA) methionine salvage pathway. Down-regulates cell migration mediated by MMP14. Necessary for hepatitis C virus replication in an otherwise non-permissive cell line. Ref.8 Ref.9
Cofactor	Binds 1 nickel 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.
Subunit structure	Interacts with MMP14. Ref.1
Subcellular location	Cell membrane; Peripheral membrane protein; Cytoplasmic side. Nucleus. Ref.8 Ref.1
Tissue specificity	Detected in heart, colon, lung, stomach, brain, spleen, liver, skeletal muscle and kidney. Ref.8 Ref.1
Sequence similarities	Belongs to the acireductone dioxygenase (ARD) family.

Ontologies

Keywords
Biological process	Amino-acid biosynthesis Methionine biosynthesis
Cellular component	Cell membrane Membrane Nucleus
Coding sequence diversity	Alternative splicing
Ligand	Metal-binding Nickel
Molecular function	Dioxygenase Oxidoreductase
Gene Ontology (GO)
Biological process	methionine biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW methionine salvage Ref.9 Inferred from direct assay. Source: UniProtKB oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Ref.1 Ref.8 Inferred from direct assay. Source: UniProtKB nucleus Ref.1 Ref.8 Inferred from direct assay. Source: UniProtKB plasma membrane Ref.1 Inferred from direct assay. Source: UniProtKB
Molecular function	nickel ion binding Inferred from electronic annotation. Source: UniProtKB-KW oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen Inferred from electronic annotation. Source: UniProtKB-KW protein binding Ref.1 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
MMP14	P50281	2	EBI-992807,EBI-992788
OSTF1	Q92882	1	EBI-992807,EBI-1051152

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		PRO_0000162942
Sites
	Metal binding	88	1	Nickel By similarity
	Metal binding	90	1	Nickel By similarity
	Metal binding	94	1	Nickel By similarity
	Metal binding	133	1	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.9
	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. 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: 14718544] [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: 15221005] [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: 14702039] [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: 15815621] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Placenta.
[8]	"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: 11602742] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 50-179, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY. Tissue: Liver.
[9]	"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: 15938715] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF GLU-94.
[10]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	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. BC001467 mRNA. Translation: AAH01467.1. AF403478 mRNA. Translation: AAL25800.1. Different initiation.
IPI	IPI00470791. IPI00651738.
RefSeq	NP_060739.2.
UniGene	Hs.502773
3D structure databases
SMR	Q9BV57. Positions 1-179.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9BV57. 3 interactions.
PTM databases
PhosphoSite	Q9BV57.
Proteomic databases
PRIDE	Q9BV57.
Genome annotation databases
Ensembl	ENSG00000182551. Homo sapiens. [Contig view]
GeneID	55256.
KEGG	hsa:55256.
NMPDR	fig|9606.3.peg.17470.
Organism-specific databases
GeneCards	GC02M003480.
H-InvDB	HIX0017215.
HGNC	HGNC:30576. ADI1.
PharmGKB	PA32899.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	Q9BV57.
OMA	Q9BV57. PARKEYV.
Gene expression databases
ArrayExpress	Q9BV57.
Bgee	Q9BV57.
CleanEx	HS_ADI1.
GermOnline	ENSG00000182551. Homo sapiens.
Family and domain databases
InterPro	IPR004313. Acireductn_dOase. IPR014710. RmlC-like_jellyroll. [Graphical view]
Gene3D	G3DSA:2.60.120.10. RmlC-like_jellyroll. 1 hit.
PANTHER	PTHR23418. Acireductn_dOase. 1 hit.
Pfam	PF03079. ARD. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	59336.

Entry information

Entry name

MTND_HUMAN

Accession

Primary (citable) accession number: Q9BV57
Secondary accession number(s): 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:	June 16, 2009
This is version 65 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)