Q96GX9 (MTNB_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Methylthioribulose-1-phosphate dehydratase
Short name=MTRu-1-P dehydratase
EC=4.2.1.109

Alternative name(s):
APAF1-interacting protein
Short name=hAPIP

Gene names

Name:	APIP
ORF Names:	CGI-29

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	242 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes the dehydration of methylthioribulose-1-phosphate (MTRu-1-P) into 2,3-diketo-5-methylthiopentyl-1-phosphate (DK-MTP-1-P). Functions in the methionine salvage pathway, which plays a key role in cancer, apoptosis, microbial proliferation and inflammation. May inhibit the CASP1-related inflammatory response (pyroptosis), the CASP9-dependent apoptotic pathway and the cytochrome c-dependent and APAF1-mediated cell death. Ref.5 Ref.8 Ref.9
Catalytic activity	S-methyl-5-thio-D-ribulose 1-phosphate = 5-(methylthio)-2,3-dioxopentyl phosphate + H2O. HAMAP-Rule MF_03116
Cofactor	Binds 1 zinc ion per subunit 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 2/6. Ref.8
Subunit structure	Interacts with APAF1. May interact with CASP1. Ref.5 Ref.9
Subcellular location	Cytoplasm Ref.5 Ref.8.
Tissue specificity	Isoform 1 is ubiquitously expressed. Isoform 2 is expressed at lower levels and detected in heart, brain, pancreas, liver, placenta, skeletal muscle and kidney. Ref.5 Ref.8
Sequence similarities	Belongs to the aldolase class II family. MtnB subfamily.

Ontologies

Keywords
Biological process	Amino-acid biosynthesis Apoptosis Methionine biosynthesis
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	Metal-binding Zinc
Molecular function	Lyase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	L-methionine salvage from methylthioadenosine Inferred from mutant phenotype Ref.9Ref.8. Source: UniProtKB apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of apoptotic process Inferred from mutant phenotype Ref.9. Source: UniProtKB polyamine metabolic process Traceable author statement. Source: Reactome regulation of ERK1 and ERK2 cascade Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	cytosol Traceable author statement. Source: Reactome
Molecular_function	metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW methylthioribulose 1-phosphate dehydratase activity Traceable author statement. Source: Reactome
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		4	EBI-359248,EBI-359248
NUDT18	Q6ZVK8	3	EBI-359248,EBI-740486

Alternative products

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

Isoform 1 (identifier: Q96GX9-1)

Also known as: Long;

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: Q96GX9-3)

Also known as: Short;

The sequence of this isoform differs from the canonical sequence as follows:
     1-53: MSGCDAREGDCCSRRCGAQDKEHPRYLIPELCKQFYHLGWVTGTGGGISLKHG → MLGRETVVPGDAARS

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 242	242	Methylthioribulose-1-phosphate dehydratase HAMAP-Rule MF_03116		PRO_0000239022
Sites
	Metal binding	115	1	Zinc Probable
	Metal binding	117	1	Zinc Probable
Amino acid modifications
	Modified residue	87	1	Phosphoserine Ref.7
Natural variations
	Alternative sequence	1 – 53	53	MSGCD…SLKHG → MLGRETVVPGDAARS in isoform 2.		VSP_044403
	Natural variant	7	1	R → W. Ref.2 Ref.4 Corresponds to variant rs2956114 [ dbSNP | Ensembl ].		VAR_026575
	Natural variant	23	1	H → R. Ref.4 Corresponds to variant rs17850326 [ dbSNP | Ensembl ].		VAR_026576
	Natural variant	76	1	C → Y. Ref.2 Ref.4 Corresponds to variant rs1977420 [ dbSNP | Ensembl ].		VAR_026577
	Natural variant	181	1	M → V. Ref.4 Corresponds to variant rs17850327 [ dbSNP | Ensembl ].		VAR_026578
Experimental info
	Mutagenesis	84	1	S → A or D: Does not affect ability of cells to grow in media where methionine is replaced by 5-methylthioadenosine; when associated with A,D-87 and A,D-89. Ref.8
	Mutagenesis	87	1	S → A or D: Does not affect ability of cells to grow in media where methionine is replaced by 5-methylthioadenosine; when associated with A,D-84 and A,D-89. Ref.8
	Mutagenesis	89	1	S → A or D: Does not affect ability of cells to grow in media where methionine is replaced by 5-methylthioadenosine; when associated with A,D-84 and A,D-87. Ref.8
	Mutagenesis	97	1	C → A: Acts as a dominant negative mutant; unable to use 5'-methylthioadenosine as source of methionine. Does not affect the ability to bind CASP1 and to inhibit cell death induced by CASP9 overexpression. Ref.9
	Mutagenesis	115	1	H → A: Impaired ability of cells to grow in media where methionine is replaced by 5-methylthioadenosine; when associated with A-117 and A-195. Unable to inhibit both CASP1 and CASP9 mediated cell death. Ref.8 Ref.9
	Mutagenesis	117	1	H → A: Impaired ability of cells to grow in media where methionine is replaced by 5-methylthioadenosine; when associated with A-115 and A-195. Ref.8
	Mutagenesis	195	1	H → A: Impaired ability of cells to grow in media where methionine is replaced by 5-methylthioadenosine; when associated with 87-A--A-89. Ref.8
	Sequence conflict	7	1	R → G in AAD27738. Ref.1
	Sequence conflict	172	1	D → T in AAD27738. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Long) [UniParc]. Last modified December 1, 2001. Version 1. Checksum: 9B8D5D1435D6775A	FASTA	242	27,125
	10 20 30 40 50 60 MSGCDAREGD CCSRRCGAQD KEHPRYLIPE LCKQFYHLGW VTGTGGGISL KHGDEIYIAP 70 80 90 100 110 120 SGVQKERIQP EDMFVCDINE KDISGPSPSK KLKKSQCTPL FMNAYTMRGA GAVIHTHSKA 130 140 150 160 170 180 AVMATLLFPG REFKITHQEM IKGIKKCTSG GYYRYDDMLV VPIIENTPEE KDLKDRMAHA 190 200 210 220 230 240 MNEYPDSCAV LVRRHGVYVW GETWEKAKTM CECYDYLFDI AVSMKKVGLD PSQLPVGENG IV
	Isoform 2 (Short) [UniParc]. Checksum: 82FC4E97BC6C2853	FASTA	204	22,858
	10 20 30 40 50 60 MLGRETVVPG DAARSDEIYI APSGVQKERI QPEDMFVCDI NEKDISGPSP SKKLKKSQCT 70 80 90 100 110 120 PLFMNAYTMR GAGAVIHTHS KAAVMATLLF PGREFKITHQ EMIKGIKKCT SGGYYRYDDM 130 140 150 160 170 180 LVVPIIENTP EEKDLKDRMA HAMNEYPDSC AVLVRRHGVY VWGETWEKAK TMCECYDYLF 190 200 DIAVSMKKVG LDPSQLPVGE NGIV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of novel human genes evolutionarily conserved in Caenorhabditis elegans by comparative proteomics." Lai C.-H., Chou C.-Y., Ch'ang L.-Y., Liu C.-S., Lin W.-C. Genome Res. 10:703-713(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[2]	"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] (ISOFORM 1), VARIANTS TRP-7 AND TYR-76. Tissue: Thymus.
[3]	"Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y. Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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), VARIANTS TRP-7; ARG-23; TYR-76 AND VAL-181. Tissue: Bone marrow, Colon and Eye.
[5]	"Induced inhibition of ischemic/hypoxic injury by APIP, a novel Apaf-1-interacting protein." Cho D.-H., Hong Y.-M., Lee H.-J., Woo H.-N., Pyo J.-O., Mak T.W., Jung Y.-K. J. Biol. Chem. 279:39942-39950(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH APAF1, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, ALTERNATIVE SPLICING (ISOFORM 2).
[6]	"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].
[7]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-87, MASS SPECTROMETRY.
[8]	"Functional identification of APIP as human mtnB, a key enzyme in the methionine salvage pathway." Mary C., Duek P., Salleron L., Tienz P., Bumann D., Bairoch A., Lane L. PLoS ONE 7:E52877-E52877(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, PATHWAY, ALTERNATIVE SPLICING (ISOFORM 2), SUBCELLULAR LOCATION, TISSUE SPECIFICITY, MUTAGENESIS OF SER-84; SER-87; SER-89; HIS-115; HIS-117 AND HIS-195.
[9]	"Functional genetic screen of human diversity reveals that a methionine salvage enzyme regulates inflammatory cell death." Ko D.C., Gamazon E.R., Shukla K.P., Pfuetzner R.A., Whittington D., Holden T.D., Brittnacher M.J., Fong C., Radey M., Ogohara C., Stark A.L., Akey J.M., Dolan M.E., Wurfel M.M., Miller S.I. Proc. Natl. Acad. Sci. U.S.A. 109:E2343-E2352(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH CASP1, MUTAGENESIS OF CYS-97 AND HIS-115.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF132963 mRNA. Translation: AAD27738.1. AK292648 mRNA. Translation: BAF85337.1. AC107928 Genomic DNA. No translation available. BC008440 mRNA. Translation: AAH08440.1. BC009077 mRNA. Translation: AAH09077.1. BC017594 mRNA. Translation: AAH17594.1.
IPI	IPI00549730.
RefSeq	NP_057041.2. NM_015957.2.
UniGene	Hs.447794.
3D structure databases
ProteinModelPortal	Q96GX9.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q96GX9. 14 interactions.
MINT	MINT-1156691.
STRING	9606.ENSP00000278359.
PTM databases
PhosphoSite	Q96GX9.
Polymorphism databases
DMDM	74731866.
Proteomic databases
PaxDb	Q96GX9.
PeptideAtlas	Q96GX9.
PRIDE	Q96GX9.
Protocols and materials databases
DNASU	51074.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000395787; ENSP00000379133; ENSG00000149089.
GeneID	51074.
KEGG	hsa:51074.
UCSC	uc001mvs.2. human.
Organism-specific databases
CTD	51074.
GeneCards	GC11M034861.
HGNC	HGNC:17581. APIP.
HPA	HPA021188. HPA024131.
MIM	612491. gene.
neXtProt	NX_Q96GX9.
PharmGKB	PA142672601.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0235.
HOGENOM	HOG000192424.
HOVERGEN	HBG080536.
InParanoid	Q96GX9.
KO	K08964.
OrthoDB	EOG4ZCT5D.
PhylomeDB	Q96GX9.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism.
UniPathway	UPA00904; UER00875.
Gene expression databases
Bgee	Q96GX9.
CleanEx	HS_APIP.
Genevestigator	Q96GX9.
GermOnline	ENSG00000149089. Homo sapiens.
Family and domain databases
Gene3D	3.40.225.10. 1 hit.
HAMAP	MF_03116. Salvage_MtnB_euk.
InterPro	IPR001303. Aldolase_II/adducin_N. IPR017714. MethylthioRu-1-P_deHdtase_MtnB. [Graphical view]
PANTHER	PTHR10640. PTHR10640. 1 hit.
Pfam	PF00596. Aldolase_II. 1 hit. [Graphical view]
SMART	SM01007. Aldolase_II. 1 hit. [Graphical view]
SUPFAM	SSF53639. Aldolase_II_N. 1 hit.
TIGRFAMs	TIGR03328. salvage_mtnB. 1 hit.
ProtoNet	Search...
Other
GenomeRNAi	51074.
NextBio	53699.
SOURCE	Search...

Entry information

Entry name

MTNB_HUMAN

Accession

Primary (citable) accession number: Q96GX9
Secondary accession number(s): A8K9D3 , Q6PJX6, Q8WVU2, Q96HK2, Q9Y318

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2006
Last sequence update:	December 1, 2001
Last modified:	May 1, 2013
This is version 93 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.