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Q96GX9 (MTNB_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 103. 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·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length242 AA.
Sequence statusComplete.
Protein existenceEvidence 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. HAMAP-Rule MF_03116

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 processAmino-acid biosynthesis
Apoptosis
Methionine biosynthesis
   Cellular componentCytoplasm
   Coding sequence diversityAlternative splicing
Polymorphism
   LigandMetal-binding
Zinc
   Molecular functionLyase
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processL-methionine biosynthetic process from S-adenosylmethionine

Inferred from electronic annotation. Source: UniProtKB-HAMAP

L-methionine salvage from methylthioadenosine

Inferred from mutant phenotype Ref.9Ref.8. Source: UniProtKB

apoptotic process

Inferred from electronic annotation. Source: UniProtKB-KW

cellular nitrogen compound metabolic process

Traceable author statement. Source: Reactome

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

small molecule metabolic process

Traceable author statement. Source: Reactome

sulfur amino acid metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

   Molecular_functionidentical protein binding

Inferred from physical interaction PubMed 16189514PubMed 19060904. Source: IntAct

methylthioribulose 1-phosphate dehydratase activity

Traceable author statement. Source: Reactome

zinc ion binding

Inferred from electronic annotation. Source: UniProtKB-HAMAP

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

itself4EBI-359248,EBI-359248
NUDT18Q6ZVK83EBI-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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 242242Methylthioribulose-1-phosphate dehydratase HAMAP-Rule MF_03116
PRO_0000239022

Sites

Metal binding1151Zinc Probable
Metal binding1171Zinc Probable

Amino acid modifications

Modified residue871Phosphoserine Ref.7

Natural variations

Alternative sequence1 – 5353MSGCD…SLKHG → MLGRETVVPGDAARS in isoform 2.
VSP_044403
Natural variant71R → W. Ref.2 Ref.4
Corresponds to variant rs2956114 [ dbSNP | Ensembl ].
VAR_026575
Natural variant231H → R. Ref.4
Corresponds to variant rs17850326 [ dbSNP | Ensembl ].
VAR_026576
Natural variant761C → Y. Ref.2 Ref.4
Corresponds to variant rs1977420 [ dbSNP | Ensembl ].
VAR_026577
Natural variant1811M → V. Ref.4
Corresponds to variant rs17850327 [ dbSNP | Ensembl ].
VAR_026578

Experimental info

Mutagenesis841S → 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
Mutagenesis871S → 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
Mutagenesis891S → 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
Mutagenesis971C → 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
Mutagenesis1151H → 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
Mutagenesis1171H → 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
Mutagenesis1951H → 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 conflict71R → G in AAD27738. Ref.1
Sequence conflict1721D → T in AAD27738. Ref.1

Secondary structure

........................................ 242
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Long) [UniParc].

Last modified December 1, 2001. Version 1.
Checksum: 9B8D5D1435D6775A

FASTA24227,125
        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 

« Hide

Isoform 2 (Short) [UniParc].

Checksum: 82FC4E97BC6C2853
Show »

FASTA20422,858

References

« Hide '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. 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] (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. expand/collapse author list , 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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[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.
RefSeqNP_057041.2. NM_015957.3.
UniGeneHs.447794.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4M6RX-ray2.00A/B/C/D20-242[»]
ProteinModelPortalQ96GX9.
SMRQ96GX9. Positions 28-224.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid119265. 10 interactions.
IntActQ96GX9. 14 interactions.
MINTMINT-1156691.
STRING9606.ENSP00000278359.

PTM databases

PhosphoSiteQ96GX9.

Polymorphism databases

DMDM74731866.

Proteomic databases

PaxDbQ96GX9.
PeptideAtlasQ96GX9.
PRIDEQ96GX9.

Protocols and materials databases

DNASU51074.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000395787; ENSP00000379133; ENSG00000149089. [Q96GX9-1]
GeneID51074.
KEGGhsa:51074.
UCSCuc001mvs.2. human. [Q96GX9-1]

Organism-specific databases

CTD51074.
GeneCardsGC11M034861.
HGNCHGNC:17581. APIP.
HPAHPA021188.
HPA024131.
MIM612491. gene.
neXtProtNX_Q96GX9.
PharmGKBPA142672601.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0235.
HOGENOMHOG000192424.
HOVERGENHBG080536.
InParanoidQ96GX9.
KOK08964.
OrthoDBEOG74TX0H.
PhylomeDBQ96GX9.
TreeFamTF105632.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.
UniPathwayUPA00904; UER00875.

Gene expression databases

ArrayExpressQ96GX9.
BgeeQ96GX9.
CleanExHS_APIP.
GenevestigatorQ96GX9.

Family and domain databases

Gene3D3.40.225.10. 1 hit.
HAMAPMF_03116. Salvage_MtnB_euk.
InterProIPR001303. Aldolase_II/adducin_N.
IPR017714. MethylthioRu-1-P_deHdtase_MtnB.
IPR027514. Salvage_MtnB_euk.
[Graphical view]
PANTHERPTHR10640. PTHR10640. 1 hit.
PfamPF00596. Aldolase_II. 1 hit.
[Graphical view]
SMARTSM01007. Aldolase_II. 1 hit.
[Graphical view]
SUPFAMSSF53639. SSF53639. 1 hit.
TIGRFAMsTIGR03328. salvage_mtnB. 1 hit.
ProtoNetSearch...

Other

GeneWikiAPIP.
GenomeRNAi51074.
NextBio53699.
PROQ96GX9.
SOURCESearch...

Entry information

Entry nameMTNB_HUMAN
AccessionPrimary (citable) accession number: Q96GX9
Secondary accession number(s): A8K9D3 expand/collapse secondary AC list , Q6PJX6, Q8WVU2, Q96HK2, Q9Y318
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2006
Last sequence update: December 1, 2001
Last modified: April 16, 2014
This is version 103 of the entry and version 1 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 11

Human chromosome 11: entries, gene names and cross-references to MIM