MTR

Protein identityUniProt · HPA

UniProt accession

Q99707

Gene

MTR

Ensembl

ENSG00000116984

Chromosome

1

Canonical length

1265 aa

Protein class

Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Metabolic proteins, Predicted intracellular proteins

Subcellular location

Microtubules,Cytokinetic bridge,Primary cilium,Basal body,Cytosol

OverviewNCBI Gene

This gene encodes the 5-methyltetrahydrofolate-homocysteine methyltransferase. This enzyme, also known as cobalamin-dependent methionine synthase, catalyzes the final step in methionine biosynthesis. Mutations in MTR have been identified as the underlying cause of methylcobalamin deficiency complementation group G. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, May 2014]

Canonical amino-acid sequenceUniProt

1265 residues, UniProt reviewed canonical sequence.

>Q99707|MTR
     1  MSPALQDLSQ PEGLKKTLRD EINAILQKRI MVLDGGMGTM IQREKLNEEH FRGQEFKDHA
    61  RPLKGNNDIL SITQPDVIYQ IHKEYLLAGA DIIETNTFSS TSIAQADYGL EHLAYRMNMC
   121  SAGVARKAAE EVTLQTGIKR FVAGALGPTN KTLSVSPSVE RPDYRNITFD ELVEAYQEQA
   181  KGLLDGGVDI LLIETIFDTA NAKAALFALQ NLFEEKYAPR PIFISGTIVD KSGRTLSGQT
   241  GEGFVISVSH GEPLCIGLNC ALGAAEMRPF IEIIGKCTTA YVLCYPNAGL PNTFGDYDET
   301  PSMMAKHLKD FAMDGLVNIV GGCCGSTPDH IREIAEAVKN CKPRVPPATA FEGHMLLSGL
   361  EPFRIGPYTN FVNIGERCNV AGSRKFAKLI MAGNYEEALC VAKVQVEMGA QVLDVNMDDG
   421  MLDGPSAMTR FCNLIASEPD IAKVPLCIDS SNFAVIEAGL KCCQGKCIVN SISLKEGEDD
   481  FLEKARKIKK YGAAMVVMAF DEEGQATETD TKIRVCTRAY HLLVKKLGFN PNDIIFDPNI
   541  LTIGTGMEEH NLYAINFIHA TKVIKETLPG ARISGGLSNL SFSFRGMEAI REAMHGVFLY
   601  HAIKSGMDMG IVNAGNLPVY DDIHKELLQL CEDLIWNKDP EATEKLLRYA QTQGTGGKKV
   661  IQTDEWRNGP VEERLEYALV KGIEKHIIED TEEARLNQKK YPRPLNIIEG PLMNGMKIVG
   721  DLFGAGKMFL PQVIKSARVM KKAVGHLIPF MEKEREETRV LNGTVEEEDP YQGTIVLATV
   781  KGDVHDIGKN IVGVVLGCNN FRVIDLGVMT PCDKILKAAL DHKADIIGLS GLITPSLDEM
   841  IFVAKEMERL AIRIPLLIGG ATTSKTHTAV KIAPRYSAPV IHVLDASKSV VVCSQLLDEN
   901  LKDEYFEEIM EEYEDIRQDH YESLKERRYL PLSQARKSGF QMDWLSEPHP VKPTFIGTQV
   961  FEDYDLQKLV DYIDWKPFFD VWQLRGKYPN RGFPKIFNDK TVGGEARKVY DDAHNMLNTL
  1021  ISQKKLRARG VVGFWPAQSI QDDIHLYAEA AVPQAAEPIA TFYGLRQQAE KDSASTEPYY
  1081  CLSDFIAPLH SGIRDYLGLF AVACFGVEEL SKAYEDDGDD YSSIMVKALG DRLAEAFAEE
  1141  LHERVRRELW AYCGSEQLDV ADLRRLRYKG IRPAPGYPSQ PDHTEKLTMW RLADIEQSTG
  1201  IRLTESLAMA PASAVSGLYF SNLKSKYFAV GKISKDQVED YALRKNISVA EVEKWLGPIL
  1261  GYDTD

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against MTR can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.19

Highest tissue expression

19 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about MTR.

Disease | AllUniProt

Conditions MTR is implicated in, by any mechanism.

• Homocystinuria-megaloblastic anemia, cblG type (HMAG) MIM:250940
• Neural tube defects, folate-sensitive (NTDFS) MIM:601634

Disease | GeneticClinVar

106 pathogenic / likely-pathogenic of 1,470 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Methylcobalamin deficiency type cblG
• Neural tube defects, folate-sensitive
• MTR-related disorder
• Homocystinuria
• Decreased methionine synthase activity

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.63

gnomAD pLI

0

gnomAD missense Z

2.04

DepMap mean gene effect

0.02

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 7% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• axon regeneration
• cellular response to nitric oxide
• cobalamin metabolic process
• homocysteine metabolic process
• methionine biosynthetic process
• methylation
• nervous system development
• response to axon injury
• tetrahydrofolate metabolic process
• sulfur amino acid metabolic process

Molecular functions

• cobalamin binding
• zinc ion binding
• methionine synthase activity

Cellular components

• cytosol

Protein domainsUniProt · Pfam · InterPro

• Homocysteine-binding domain
• Cobalamin (vitamin B12)-binding domain
• Homocysteine-binding domain superfamily
• Cobalamin-binding domain superfamily
• B12 binding domain
• Homocysteine S-methyltransferase
• Pterin-binding domain
• Cobalamin (vitamin B12)-binding module, cap domain
• Vitamin B12-dependent methionine synthase, activation domain
• Dihydropteroate synthase-like superfamily
• Cobalamin-dependent methionine synthase
• Methionine synthase, B12-binding domain
• Methionine synthase domain
• Vitamin B12-dependent methionine synthase, activation domain superfamily
• Methionine Synthase/Corrinoid
• Pterin binding enzyme
• B12 binding domain
• Vitamin B12 dependent methionine synthase, activation domain

KeywordsUniProt

• Amino-acid biosynthesis
• Cobalamin
• Cobalt
• Cytoplasm
• Metal-binding
• Methionine biosynthesis
• Methyltransferase
• Phosphoprotein
• Repeat
• S-adenosyl-L-methionine
• Transferase
• Zinc