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Protein

Methylthioribulose-1-phosphate dehydratase

Gene

APIP

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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)
  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

  • apoptotic process Source: UniProtKB-KW
  • L-methionine biosynthetic process from methylthioadenosine Source: UniProtKB
  • L-methionine biosynthetic process from S-adenosylmethionine Source: UniProtKB-HAMAP
  • negative regulation of apoptotic process Source: UniProtKB
  • protein homotetramerization Source: UniProtKB
  • pyroptosis Source: UniProtKB
  • regulation of ERK1 and ERK2 cascade Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Lyase

Keywords - Biological processi

Amino-acid biosynthesis, Apoptosis, Methionine biosynthesis

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:ENSG00000149089-MONOMER.
ZFISH:G66-33956-MONOMER.
ReactomeiR-HSA-1237112. Methionine salvage pathway.
SIGNORiQ96GX9.
UniPathwayiUPA00904; 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

HGNCiHGNC:17581. APIP.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
Complete GO annotation...

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.

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.
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

WithEntry#Exp.IntActNotes
itself10EBI-359248,EBI-359248
C6orf165Q8IYR03EBI-359248,EBI-749051
IMPDH2P122683EBI-359248,EBI-353389
LNX1Q8TBB16EBI-359248,EBI-739832
NUDT18Q6ZVK83EBI-359248,EBI-740486
PDZD4Q17RL83EBI-359248,EBI-10239064
PSMA1P257863EBI-359248,EBI-359352
SDCBPO005605EBI-359248,EBI-727004
SKP1P632083EBI-359248,EBI-307486
TNPO2O147873EBI-359248,EBI-431907
TSC22D4Q9Y3Q83EBI-359248,EBI-739485
WDYHV1Q96HA83EBI-359248,EBI-741158
ZBTB25P242783EBI-359248,EBI-739899

GO - Molecular functioni

  • identical protein binding Source: IntAct

Protein-protein interaction databases

BioGridi119265. 30 interactors.
IntActiQ96GX9. 29 interactors.
MINTiMINT-1156691.
STRINGi9606.ENSP00000379133.

Structurei

Secondary structure

1242
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi24 – 37Combined sources14
Helixi42 – 44Combined sources3
Beta strandi47 – 52Combined sources6
Beta strandi55 – 58Combined sources4
Helixi65 – 67Combined sources3
Helixi70 – 72Combined sources3
Beta strandi74 – 76Combined sources3
Beta strandi82 – 84Combined sources3
Helixi88 – 90Combined sources3
Helixi98 – 108Combined sources11
Beta strandi111 – 116Combined sources6
Helixi119 – 127Combined sources9
Beta strandi130 – 137Combined sources8
Helixi139 – 143Combined sources5
Turni147 – 149Combined sources3
Beta strandi157 – 164Combined sources8
Helixi170 – 183Combined sources14
Beta strandi188 – 192Combined sources5
Turni193 – 195Combined sources3
Beta strandi196 – 203Combined sources8
Helixi204 – 226Combined sources23

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...

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.
OMAiNHPANLI.
OrthoDBiEOG091G0GMC.
PhylomeDBiQ96GX9.
TreeFamiTF105632.

Family and domain databases

Gene3Di3.40.225.10. 1 hit.
HAMAPiMF_03116. Salvage_MtnB_euk. 1 hit.
InterProiIPR001303. Aldolase_II/adducin_N.
IPR017714. MethylthioRu-1-P_deHdtase_MtnB.
IPR027514. Salvage_MtnB_euk.
[Graphical view]
PANTHERiPTHR10640. PTHR10640. 1 hit.
PfamiPF00596. Aldolase_II. 1 hit.
[Graphical view]
SMARTiSM01007. Aldolase_II. 1 hit.
[Graphical view]
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

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

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 → W.2 PublicationsCorresponds to variant rs2956114dbSNPEnsembl.1
Natural variantiVAR_02657623H → R.1 PublicationCorresponds to variant rs17850326dbSNPEnsembl.1
Natural variantiVAR_02657776C → Y.2 PublicationsCorresponds to variant rs1977420dbSNPEnsembl.1
Natural variantiVAR_026578181M → V.1 PublicationCorresponds to variant rs17850327dbSNPEnsembl.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

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. 30 interactors.
IntActiQ96GX9. 29 interactors.
MINTiMINT-1156691.
STRINGi9606.ENSP00000379133.

PTM databases

iPTMnetiQ96GX9.
PhosphoSitePlusiQ96GX9.

Polymorphism and mutation databases

BioMutaiAPIP.
DMDMi74731866.

Proteomic databases

EPDiQ96GX9.
MaxQBiQ96GX9.
PaxDbiQ96GX9.
PeptideAtlasiQ96GX9.
PRIDEiQ96GX9.

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.
GeneCardsiAPIP.
HGNCiHGNC:17581. APIP.
HPAiHPA021188.
HPA024131.
MIMi612491. gene.
neXtProtiNX_Q96GX9.
OpenTargetsiENSG00000149089.
PharmGKBiPA142672601.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

UniPathwayiUPA00904; UER00875.
BioCyciZFISH:ENSG00000149089-MONOMER.
ZFISH:G66-33956-MONOMER.
ReactomeiR-HSA-1237112. Methionine salvage pathway.
SIGNORiQ96GX9.

Miscellaneous databases

GeneWikiiAPIP.
GenomeRNAii51074.
PROiQ96GX9.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000149089.
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.
InterProiIPR001303. Aldolase_II/adducin_N.
IPR017714. MethylthioRu-1-P_deHdtase_MtnB.
IPR027514. Salvage_MtnB_euk.
[Graphical view]
PANTHERiPTHR10640. PTHR10640. 1 hit.
PfamiPF00596. Aldolase_II. 1 hit.
[Graphical view]
SMARTiSM01007. Aldolase_II. 1 hit.
[Graphical view]
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 historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2006
Last sequence update: December 1, 2001
Last modified: November 30, 2016
This is version 130 of the entry and version 1 of the sequence. [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. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  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. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.