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Protein

Methylthioribulose-1-phosphate dehydratase

Gene

APIP

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.UniRule annotation4 Publications

Catalytic activityi

S-methyl-5-thio-D-ribulose 1-phosphate = 5-(methylthio)-2,3-dioxopentyl phosphate + H2O.UniRule annotation1 Publication

Cofactori

Zn2+UniRule annotation1 PublicationNote: Binds 1 zinc ion per subunit.UniRule annotation1 Publication

Kineticsi

  1. KM=9.3 µM for S-methyl-5-thio-D-ribulose 1-phosphate
  1. Vmax=1.39 µmol/min/mg enzyme

Pathwayi: L-methionine biosynthesis via salvage pathway

This protein is involved in step 2 of the subpathway that synthesizes L-methionine from S-methyl-5-thio-alpha-D-ribose 1-phosphate.UniRule annotation2 Publications
Proteins known to be involved in the 6 steps of the subpathway in this organism are:
  1. Methylthioribose-1-phosphate isomerase (MRI1), Methylthioribose-1-phosphate isomerase (mtnA)
  2. Methylthioribulose-1-phosphate dehydratase (APIP), Methylthioribulose-1-phosphate dehydratase (APIP)
  3. Enolase-phosphatase E1 (ENOPH1)
  4. Enolase-phosphatase E1 (ENOPH1)
  5. 1,2-dihydroxy-3-keto-5-methylthiopentene dioxygenase (ADI1)
  6. no protein annotated in this organism
This subpathway is part of the pathway L-methionine biosynthesis via salvage pathway, which is itself part of Amino-acid biosynthesis.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes L-methionine from S-methyl-5-thio-alpha-D-ribose 1-phosphate, the pathway L-methionine biosynthesis via salvage pathway and in Amino-acid biosynthesis.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei97SubstrateUniRule annotation1 Publication1
Metal bindingi115Zinc; via tele nitrogenUniRule annotationCombined sources1 Publication1
Metal bindingi117Zinc; via tele nitrogenUniRule annotationCombined sources1 Publication1
Active sitei139Proton donor/acceptorUniRule annotation1 Publication1
Metal bindingi195Zinc; via tele nitrogenUniRule annotationCombined sources1 Publication1

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • methylthioribulose 1-phosphate dehydratase activity Source: UniProtKB
  • zinc ion binding Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionLyase
Biological processAmino-acid biosynthesis, Apoptosis, Methionine biosynthesis
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-1237112 Methionine salvage pathway
SIGNORiQ96GX9
UniPathwayi
UPA00904;UER00875

Names & Taxonomyi

Protein namesi
Recommended name:
Methylthioribulose-1-phosphate dehydrataseUniRule annotation (EC:4.2.1.109UniRule annotation1 Publication)
Short name:
MTRu-1-P dehydrataseUniRule annotation
Alternative name(s):
APAF1-interacting proteinUniRule annotation
Short name:
hAPIP
Gene namesi
Name:APIPUniRule annotation
ORF Names:CGI-29
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

EuPathDBiHostDB:ENSG00000149089.12
HGNCiHGNC:17581 APIP
MIMi612491 gene
neXtProtiNX_Q96GX9

Subcellular locationi

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi84S → 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. 1 Publication1
Mutagenesisi87S → 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. 1 Publication1
Mutagenesisi89S → 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. 1 Publication1
Mutagenesisi96Q → A: Mildly reduced enzyme activity. 1 Publication1
Mutagenesisi97C → 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. 1 Publication1
Mutagenesisi97C → A: Almost complete loss of enzyme activity. Abolishes protection against pyroptosis. No effect on anti-apoptotic activity. 1 Publication1
Mutagenesisi115H → A: Almost complete loss of enzyme activity. Abolishes protection against pyroptosis. No effect on anti-apoptotic activity. 1 Publication1
Mutagenesisi115H → 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. 2 Publications1
Mutagenesisi117H → A: Impaired ability of cells to grow in media where methionine is replaced by 5-methylthioadenosine; when associated with A-115 and A-195. 1 Publication1
Mutagenesisi139E → A: Almost complete loss of enzyme activity. Abolishes protection against pyroptosis. No effect on anti-apoptotic activity. 1 Publication1
Mutagenesisi195H → A: Impaired ability of cells to grow in media where methionine is replaced by 5-methylthioadenosine; when associated with 87-A--A-89. 1 Publication1

Organism-specific databases

DisGeNETi51074
OpenTargetsiENSG00000149089
PharmGKBiPA142672601

Polymorphism and mutation databases

BioMutaiAPIP
DMDMi74731866

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002390221 – 242Methylthioribulose-1-phosphate dehydrataseAdd BLAST242

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei87PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ96GX9
MaxQBiQ96GX9
PaxDbiQ96GX9
PeptideAtlasiQ96GX9
PRIDEiQ96GX9
ProteomicsDBi76681

PTM databases

iPTMnetiQ96GX9
PhosphoSitePlusiQ96GX9

Expressioni

Tissue specificityi

Isoform 1 is ubiquitously expressed. Isoform 2 is expressed at lower levels and detected in heart, brain, pancreas, liver, placenta, skeletal muscle and kidney.2 Publications

Gene expression databases

BgeeiENSG00000149089 Expressed in 95 organ(s), highest expression level in C1 segment of cervical spinal cord
CleanExiHS_APIP
ExpressionAtlasiQ96GX9 baseline and differential
GenevisibleiQ96GX9 HS

Organism-specific databases

HPAiHPA021188
HPA024131

Interactioni

Subunit structurei

Homotetramer (PubMed:24367089). Interacts with APAF1 (PubMed:15262985). May interact with CASP1 (PubMed:22837397).UniRule annotation3 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi119265, 32 interactors
IntActiQ96GX9, 29 interactors
STRINGi9606.ENSP00000379133

Structurei

Secondary structure

1242
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ96GX9
SMRiQ96GX9
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the aldolase class II family. MtnB subfamily.UniRule annotation

Phylogenomic databases

eggNOGiKOG2631 Eukaryota
COG0235 LUCA
GeneTreeiENSGT00390000001680
HOGENOMiHOG000192424
HOVERGENiHBG080536
InParanoidiQ96GX9
KOiK08964
OMAiGHGLYTW
OrthoDBiEOG091G0GMC
PhylomeDBiQ96GX9
TreeFamiTF105632

Family and domain databases

Gene3Di3.40.225.10, 1 hit
HAMAPiMF_03116 Salvage_MtnB_euk, 1 hit
InterProiView protein in InterPro
IPR001303 Aldolase_II/adducin_N
IPR036409 Aldolase_II/adducin_N_sf
IPR017714 MethylthioRu-1-P_deHdtase_MtnB
IPR027514 Salvage_MtnB_euk
PANTHERiPTHR10640 PTHR10640, 1 hit
PfamiView protein in Pfam
PF00596 Aldolase_II, 1 hit
SMARTiView protein in SMART
SM01007 Aldolase_II, 1 hit
SUPFAMiSSF53639 SSF53639, 1 hit
TIGRFAMsiTIGR03328 salvage_mtnB, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform 1 (identifier: Q96GX9-1) [UniParc]FASTAAdd to basket
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.

« Hide
        10         20         30         40         50
MSGCDAREGD CCSRRCGAQD KEHPRYLIPE LCKQFYHLGW VTGTGGGISL
60 70 80 90 100
KHGDEIYIAP SGVQKERIQP EDMFVCDINE KDISGPSPSK KLKKSQCTPL
110 120 130 140 150
FMNAYTMRGA GAVIHTHSKA AVMATLLFPG REFKITHQEM IKGIKKCTSG
160 170 180 190 200
GYYRYDDMLV VPIIENTPEE KDLKDRMAHA MNEYPDSCAV LVRRHGVYVW
210 220 230 240
GETWEKAKTM CECYDYLFDI AVSMKKVGLD PSQLPVGENG IV
Length:242
Mass (Da):27,125
Last modified:December 1, 2001 - v1
Checksum:i9B8D5D1435D6775A
GO
Isoform 2 (identifier: Q96GX9-3) [UniParc]FASTAAdd to basket
Also known as: Short

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

Show »
Length:204
Mass (Da):22,858
Checksum:i82FC4E97BC6C2853
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
S4R3D6S4R3D6_HUMAN
Methylthioribulose-1-phosphate dehy...
APIP
195Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti7R → G in AAD27738 (PubMed:10810093).Curated1
Sequence conflicti172D → T in AAD27738 (PubMed:10810093).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0265757R → W2 PublicationsCorresponds to variant dbSNP:rs2956114Ensembl.1
Natural variantiVAR_02657623H → R1 PublicationCorresponds to variant dbSNP:rs17850326Ensembl.1
Natural variantiVAR_02657776C → Y2 PublicationsCorresponds to variant dbSNP:rs1977420Ensembl.1
Natural variantiVAR_026578181M → V1 PublicationCorresponds to variant dbSNP:rs17850327Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0444031 – 53MSGCD…SLKHG → MLGRETVVPGDAARS in isoform 2. CuratedAdd BLAST53

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS7895.1 [Q96GX9-1]
RefSeqiNP_057041.2, NM_015957.3 [Q96GX9-1]
UniGeneiHs.447794

Genome annotation databases

EnsembliENST00000395787; ENSP00000379133; ENSG00000149089 [Q96GX9-1]
GeneIDi51074
KEGGihsa:51074
UCSCiuc001mvs.4 human [Q96GX9-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS7895.1 [Q96GX9-1]
RefSeqiNP_057041.2, NM_015957.3 [Q96GX9-1]
UniGeneiHs.447794

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4M6RX-ray2.00A/B/C/D20-242[»]
ProteinModelPortaliQ96GX9
SMRiQ96GX9
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi119265, 32 interactors
IntActiQ96GX9, 29 interactors
STRINGi9606.ENSP00000379133

PTM databases

iPTMnetiQ96GX9
PhosphoSitePlusiQ96GX9

Polymorphism and mutation databases

BioMutaiAPIP
DMDMi74731866

Proteomic databases

EPDiQ96GX9
MaxQBiQ96GX9
PaxDbiQ96GX9
PeptideAtlasiQ96GX9
PRIDEiQ96GX9
ProteomicsDBi76681

Protocols and materials databases

DNASUi51074
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000395787; ENSP00000379133; ENSG00000149089 [Q96GX9-1]
GeneIDi51074
KEGGihsa:51074
UCSCiuc001mvs.4 human [Q96GX9-1]

Organism-specific databases

CTDi51074
DisGeNETi51074
EuPathDBiHostDB:ENSG00000149089.12
GeneCardsiAPIP
HGNCiHGNC:17581 APIP
HPAiHPA021188
HPA024131
MIMi612491 gene
neXtProtiNX_Q96GX9
OpenTargetsiENSG00000149089
PharmGKBiPA142672601
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2631 Eukaryota
COG0235 LUCA
GeneTreeiENSGT00390000001680
HOGENOMiHOG000192424
HOVERGENiHBG080536
InParanoidiQ96GX9
KOiK08964
OMAiGHGLYTW
OrthoDBiEOG091G0GMC
PhylomeDBiQ96GX9
TreeFamiTF105632

Enzyme and pathway databases

UniPathwayi
UPA00904;UER00875

ReactomeiR-HSA-1237112 Methionine salvage pathway
SIGNORiQ96GX9

Miscellaneous databases

GeneWikiiAPIP
GenomeRNAii51074
PROiPR:Q96GX9
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000149089 Expressed in 95 organ(s), highest expression level in C1 segment of cervical spinal cord
CleanExiHS_APIP
ExpressionAtlasiQ96GX9 baseline and differential
GenevisibleiQ96GX9 HS

Family and domain databases

Gene3Di3.40.225.10, 1 hit
HAMAPiMF_03116 Salvage_MtnB_euk, 1 hit
InterProiView protein in InterPro
IPR001303 Aldolase_II/adducin_N
IPR036409 Aldolase_II/adducin_N_sf
IPR017714 MethylthioRu-1-P_deHdtase_MtnB
IPR027514 Salvage_MtnB_euk
PANTHERiPTHR10640 PTHR10640, 1 hit
PfamiView protein in Pfam
PF00596 Aldolase_II, 1 hit
SMARTiView protein in SMART
SM01007 Aldolase_II, 1 hit
SUPFAMiSSF53639 SSF53639, 1 hit
TIGRFAMsiTIGR03328 salvage_mtnB, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiMTNB_HUMAN
AccessioniPrimary (citable) accession number: Q96GX9
Secondary accession number(s): A8K9D3
, Q6PJX6, Q8WVU2, Q96HK2, Q9Y318
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2006
Last sequence update: December 1, 2001
Last modified: October 10, 2018
This is version 143 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
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