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METAP1D Gene

protein-coding   GIFtS: 51
GCID: GC02P172865

Methionyl Aminopeptidase Type 1D (Mitochondrial)

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(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Methionyl Aminopeptidase Type 1D (Mitochondrial)1 2     Methionine Aminopeptidase 1D1
MAP1D2 3 5     Metap1l2
Methionyl Aminopeptidase Type 1D, Mitochondrial2 3     CDS Of MetAP-3 Within PCR Fragment2
Peptidase M 1D2 3     Methionine Aminopeptidase 1D, Mitochondrial2
MAP 1D2 3     EC 3.4.11.183
MetAP 1D2 3     

External Ids:    HGNC: 325831   Entrez Gene: 2540422   Ensembl: ENSG000001728787   OMIM: 6102675   UniProtKB: Q6UB283   

Export aliases for METAP1D gene to outside databases

Previous GC identifer: GC02P164748


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for METAP1D Gene:
The N-terminal methionine excision pathway is an essential process in which the N-terminal methionine is removed
from many proteins, thus facilitating subsequent protein modification. In mitochondria, enzymes that catalyze
this reaction are celled methionine aminopeptidases (MetAps, or MAPs; EC 3.4.11.18) (Serero et al., 2003 (PubMed
14532271)).(supplied by OMIM, Mar 2008)

GeneCards Summary for METAP1D Gene:
METAP1D (methionyl aminopeptidase type 1D (mitochondrial)) is a protein-coding gene. GO annotations related to this gene include metalloexopeptidase activity and aminopeptidase activity. An important paralog of this gene is METAP1.

UniProtKB/Swiss-Prot: MAP12_HUMAN, Q6UB28
Function: Removes the N-terminal methionine from nascent proteins. The N-terminal methionine is often cleaved when
the second residue in the primary sequence is small and uncharged (Met-Ala-, Cys, Gly, Pro, Ser, Thr, or Val).
Requires deformylation of the N(alpha)-formylated initiator methionine before it can be hydrolyzed (By
similarity). May play a role in colon tumorigenesis




(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:
NC_000002.11  NC_018913.2  NT_005403.18  
Regulatory elements:
   Search for regulatory transcription factor binding sites for METAP1D
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidMETAP1D promoter sequence
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Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat METAP1D


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 2q31.1   Ensembl cytogenetic band:  2q31.1   HGNC cytogenetic band: 2q31.1

METAP1D Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
METAP1D gene location

GeneLoc information about chromosome 2         GeneLoc Exon Structure

GeneLoc location for GC02P172865:  view genomic region     (about GC identifiers)

Start:
172,864,490 bp from pter      End:
172,947,158 bp from pter
Size:
82,669 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., and/or eBioscience,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., and/or eBioscience, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: MAP12_HUMAN, Q6UB28 (See protein sequence)
Recommended Name: Methionine aminopeptidase 1D, mitochondrial precursor  
Size: 335 amino acids; 37088 Da
Cofactor: Binds 2 divalent metal cations per subunit. Has a high-affinity and a low affinity metal-binding site.
The true nature of the physiological cofactor is under debate. The enzyme is active with cobalt, zinc, manganese
or divalent iron ions. Most likely, methionine aminopeptidases function as mononuclear Fe(2+)-metalloproteases
under physiological conditions, and the catalytically relevant metal-binding site has been assigned to the
histidine-containing high-affinity site (By similarity)
Caution: It is uncertain whether Met-1 or a Met upstream of this sequence is the initiator
Sequence caution: Sequence=AAY55948.1; Type=Erroneous initiation;
Secondary accessions: Q1WNX3

Explore the universe of human proteins at neXtProt for METAP1D: NX_Q6UB28

Explore proteomics data for METAP1D at MOPED


See METAP1D Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

REFSEQ proteins: NP_954697.1  
ENSEMBL proteins: 
 ENSP00000315152  

METAP1D Human Recombinant Protein Products:

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(According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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IUPHAR Guide to PHARMACOLOGY protein family classification: Methionyl aminopeptidase type 1D (mitochondrial)
Aminopeptidases

3 InterPro protein domains:
 IPR000994 Pept_M24_structural-domain
 IPR002467 Pept_M24A_MAP1
 IPR001714 Pept_M24_MAP

Graphical View of Domain Structure for InterPro Entry Q6UB28

ProtoNet protein and cluster: Q6UB28

2 Blocks protein domains:
IPB001714 Methionine aminopeptidase-1 signature
IPB002467 Methionine aminopeptidase


UniProtKB/Swiss-Prot: MAP12_HUMAN, Q6UB28
Similarity: Belongs to the peptidase M24A family. Methionine aminopeptidase type 1 subfamily


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(According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Molecular Function:

     UniProtKB/Swiss-Prot Summary: MAP12_HUMAN, Q6UB28
Function: Removes the N-terminal methionine from nascent proteins. The N-terminal methionine is often cleaved when
the second residue in the primary sequence is small and uncharged (Met-Ala-, Cys, Gly, Pro, Ser, Thr, or Val).
Requires deformylation of the N(alpha)-formylated initiator methionine before it can be hydrolyzed (By
similarity). May play a role in colon tumorigenesis
Catalytic activity: Release of N-terminal amino acids, preferentially methionine, from peptides and arylamides
Biophysicochemical properties: Kinetic parameters: KM=573 uM for Met-pro-p-nitroanilide (at pH 8); pH dependence:
Optimum pH is 7.5-8.0;

     Enzyme Number (IUBMB): EC 3.4.11.181

     Gene Ontology (GO): 3 molecular function terms:    About this table

GO IDQualified GO termEvidencePubMed IDs
GO:0004177aminopeptidase activity TAS14532271
GO:0008235metalloexopeptidase activity TAS14532271
GO:0046872metal ion binding IEA--
     
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Phenotypes:
     1 GenomeRNAi human phenotype for METAP1D:
 Increased G1 DNA content 

Animal Models:
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(According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Subcellular locations from UniProtKB/Swiss-Prot
MAP12_HUMAN, Q6UB28: Mitochondrion

Gene Ontology (GO): 1 cellular component term:    About this table

GO IDQualified GO termEvidencePubMed IDs
GO:0005739mitochondrion IDA14532271

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(SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    Custom Pathway & Disease-focused RT2 Profiler PCR Arrays for METAP1D
Interactions:

    Search GeneGlobe Interaction Network for METAP1D

STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

Selected Interacting proteins for METAP1D (ENSP000003151524) via UniProtKB, MINT, STRING, and/or I2D (see all 68)
InteractantInteraction Details
GeneCardExternal ID(s)
METAP2ENSP000003253124STRING: ENSP00000325312
EIF6ENSP000003635594STRING: ENSP00000363559
GTPBP4ENSP000003540404STRING: ENSP00000354040
NMD3ENSP000003075254STRING: ENSP00000307525
PES1ENSP000003467254STRING: ENSP00000346725
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Gene Ontology (GO): 3 biological process terms:    About this table

GO IDQualified GO termEvidencePubMed IDs
GO:0006508proteolysis ----
GO:0018206peptidyl-methionine modification TAS14532271
GO:0031365N-terminal protein amino acid modification TAS14532271

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(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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Browse Small Molecules at EMD Millipore
   Browse drugs & compounds from Enzo Life Sciences
  Browse compounds at ApexBio 

Browse Tocris compounds for METAP1D (MAP12)



(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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REFSEQ mRNAs for METAP1D gene: 
NM_199227.1  

Unigene Cluster for METAP1D:

Methionyl aminopeptidase type 1D (mitochondrial)
Hs.298250  [show with all ESTs]
Unigene Representative Sequence: AK095742
7 Ensembl transcripts including schematic representations, and UCSC links where relevant:
ENST00000315796(uc002uhk.3 uc010zdw.2) ENST00000493035 ENST00000493742
ENST00000491440 ENST00000488581 ENST00000392582 ENST00000468537
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Additional mRNA sequence: 

AK095742.1 AY374142.1 BC029123.1 BC113644.1 BC143913.1 DQ005576.1 

7 DOTS entries:

DT.99935544  DT.75115530  DT.425367  DT.97811824  DT.91800477  DT.95219382  DT.99934620 

Selected AceView cDNA sequences (see all 62):

AA442892 AI049781 AY374142 BQ718186 AA887324 AI936541 BX106042 AI362530 
BM982111 BU632792 AI863797 NM_199227 BQ445926 BU623229 BF438491 AA022781 
AV681871 AI370447 AW304423 AA779679 AI080410 N51684 AI192607 W84858 

GeneLoc Exon Structure

4 Alternative Splicing Database (ASD) splice patterns (SP) for METAP1D    About this scheme

ExUns: 1a · 1b ^ 2a · 2b ^ 3a · 3b ^ 4 ^ 5 ^ 6a · 6b ^ 7 ^ 8 ^ 9 ^ 10a · 10b · 10c
SP1:                                -                 -                                             
SP2:                                -     -           -                                             
SP3:                                                                                                
SP4:                                                                                                


ECgene alternative splicing isoforms for METAP1D

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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METAP1D expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS <intensity>2/3
CGAP TAG: AGGCCTGAGG
METAP1D Expression
About this image

METAP1D Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

METAP1D Protein Expression

SOURCE GeneReport for Unigene cluster: Hs.298250

UniProtKB/Swiss-Prot: MAP12_HUMAN, Q6UB28
Tissue specificity: Overexpressed in colon cancer cell lines and colon tumors as compared to normal tissues (at
protein level)

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(Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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This gene was present in the common ancestor of eukaryotes.

Orthologs for METAP1D gene from Selected species (see all 24)    About this table
Organism Taxonomic
classification
Gene Description Human
Similarity
Orthology
Type
Details
mouse
(Mus musculus)
Mammalia Metap1d1 , 5 methionyl aminopeptidase type 1D (mitochondrial)1, 5 90.45(n)1
91.04(a)1
  2 (42.42 cM)5
665591  NM_025633.31  NP_079909.11 
 714532765 
chicken
(Gallus gallus)
Aves METAP1D1 methionyl aminopeptidase type 1D (mitochondrial) 81.24(n)
80.54(a)
  424150  XM_421997.4  XP_421997.2 
lizard
(Anolis carolinensis)
Reptilia METAP1D6
methionyl aminopeptidase type 1D (mitochondrial)
78(a)
1 ↔ 1
GL343353.1(472542-496225)
tropical clawed frog
(Xenopus tropicalis)
Amphibia metap1d1 methionyl aminopeptidase type 1D (mitochondrial) 80.37(n)
80.37(a)
  100496112  XM_002934608.2  XP_002934654.1 
zebrafish
(Danio rerio)
Actinopterygii metap1d1 methionyl aminopeptidase type 1D (mitochondrial) 64.87(n)
66.47(a)
  554090  NM_001024392.1  NP_001019563.1 
fruit fly
(Drosophila melanogaster)
Insecta CG51881 CG5188 54.92(n)
51.6(a)
  34428  NM_135557.4  NP_609401.2 
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes MAP16
Methionine aminopeptidase, catalyzes the cotransla...
31(a)
1 → many
XII(625168-626331) YLR244C
thale cress
(Arabidopsis thaliana)
eudicotyledons MAP1D1 MAP1D 54.95(n)
52.9(a)
  829858  NM_119867.2  NP_568014.1 
rice
(Oryza sativa)
Liliopsida Os.107272 Oryza sativa (japonica cultivar-group) cDNA clone0 more 73.28(n)    AK066289.1 


ENSEMBL Gene Tree for METAP1D (if available)
TreeFam Gene Tree for METAP1D (if available)

(Paralogs according to 1HomoloGene,
2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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Paralogs for METAP1D gene
METAP12  
2 SIMAP similar genes for METAP1D using alignment to 1 protein entry:     MAP12_HUMAN:
DKFZp781C0419    METAP1

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(SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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Selected SNPs for METAP1D (see all 1715)    About this table                                 

Genomic DataTranscription Related DataAllele Frequencies
SNP IDValidClinical
significance
Chr 2 posSequence#AA
Chg
TypeMore#Allele
freq
PopTotal
sample
More
----------
rs2000080751,2
Cuntested1172935747(+) AGCAAC/TTGCAG 2 T I mis10--------
rs343833521,2
C--164802906(+) TTTTT-/TGAGAC 1 -- int10--------
rs1423362751,2
--172862876(+) ACCCAA/GCTTAT 1 -- us2k10--------
rs1466117311,2
C--172862906(+) TTGGCC/GGACAT 1 -- us2k10--------
rs1479097771,2
C--172862926(+) GCTTTG/TAACCC 1 -- us2k10--------
rs1404817371,2
--172862936(+) CTTCTG/TCGGTG 1 -- us2k10--------
rs762154301,2
F--172862992(+) GCTATC/AACCTG 1 -- us2k11Minor allele frequency- A:0.01WA 118
rs1503531771,2
C--172863054(+) ATGCCA/GAACTT 1 -- us2k10--------
rs573776751,2
C,F--172863132(+) CCTTTT/CAGTTG 1 -- us2k12Minor allele frequency- C:0.24NA EA 240
rs798512101,2
F--172863279(+) ACACTT/GCTTAA 1 -- us2k11Minor allele frequency- G:0.12WA 118

HapMap Linkage Disequilibrium report for METAP1D (172864490 - 172947158 bp)

Structural Variations
     Database of Genomic Variants (DGV) Selected variations for METAP1D (see all 19):    About this table    
Variant IDTypeSubtypePubMed ID
dgv746e199CNV Deletion23128226
esv2721135CNV Deletion23290073
esv2458501CNV Deletion19546169
nsv820939CNV Deletion20802225
dgv747e199CNV Deletion23128226
esv2662767CNV Deletion23128226
esv2721131CNV Deletion23290073
esv2721134CNV Deletion23290073
esv2721132CNV Deletion23290073
esv2721136CNV Deletion23290073

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(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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OMIM gene information: 610267    OMIM disorders: --


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Genetic Association Database (GAD): METAP1D

Export disorders for METAP1D gene to outside databases

(in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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PubMed articles for METAP1D gene, integrated from 10 sources (see all 12):
(articles sorted by number of sources associating them with METAP1D)
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  1. An unusual peptide deformylase features in the human mitochondrial N- terminal methionine excision pathway. (PubMed id 14532271)1, 2, 3, 9 Serero A.... Meinnel T. (J. Biol. Chem. 2003)
  2. MAP1D, a novel methionine aminopeptidase family member is overexpressed in colon cancer. (PubMed id 16568094)1, 2, 3 Leszczyniecka M.... Phillips P.E. (Oncogene 2006)
  3. Large-scale genotyping identifies 41 new loci associated with breast cancer risk. (PubMed id 23535729)1 Michailidou K....Easton D.F. (Nat. Genet. 2013)
  4. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PubMed id 20379614)1 Rose J.E....Uhl G.R. (Mol. Med. 2010)
  5. Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression. (PubMed id 20877624)1 Hendrickson S.L....O'Brien S.J. (PLoS ONE 2010)
  6. Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study. (PubMed id 20628086)1 Bailey S.D....Anand S. (Diabetes Care 2010)
  7. Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip. (PubMed id 19913121)1 Talmud P.J.... . (Am. J. Hum. Genet. 2009)
  8. Genome-wide association to body mass index and waist circumference: the Framingham Heart Study 100K project. (PubMed id 17903300)4 Fox C.S....Atwood L.D. (BMC Med. Genet. 2007)
  9. Kinetic and mutational studies of the number of interacting divalent cations required by bacterial and human methionine aminopeptidases. (PubMed id 17929833)2 Hu X.V.... Liu J.O. (Biochemistry 2007)
  10. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PubMed id 15489334)2 Gerhard D.S.... Malek J. (Genome Res. 2004)

(in PubMed, OMIM, and NCBI Bookshelf)
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(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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Entrez Gene: 254042 HGNC: 32583 AceView: MAP1D Ensembl:ENSG00000172878 euGenes: HUgn254042
ECgene: METAP1D H-InvDB: METAP1D

(According to HUGE)
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(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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NameDescription
PharmGKB entry for METAP1D Pharmacogenomics, SNPs, Pathways

(Patent information from GeneIP,
Licensable technologies from WIS Yeda, Salk, Tufts,
IP news from LifeMap Sciences, Inc.)
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Patent Information for METAP1D gene:
Search GeneIP for patents involving METAP1D

GeneCards and IP:
Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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Advanced Cell Diagnostics, Animal models from inGenious Targeting Laboratory, genOway)
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