You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Human Metabolome Database.
Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2013-05-29 19:30:19 UTC
HMDB IDHMDB01078
Secondary Accession NumbersNone
Metabolite Identification
Common NameMannose 6-phosphate
DescriptionMannose-6-phosphate is a potent competitive inhibitor of pinocytosis of human platelet beta-glucuronidase and it is a necessary component of the recognition marker on the enzyme for pinocytosis by human fibroblasts as well (PMID 908752 ).
Structure
Thumb
Synonyms
  1. alpha-D-Mannose-6-P
  2. alpha-D-Mannose-6-phosphate
  3. alpha-delta-Mannose-6-P
  4. alpha-delta-Mannose-6-phosphate
  5. D-Mannose 6-phosphate
  6. delta-Mannose 6-phosphate
  7. Man-6-p
  8. Mannose 6-phosphate
  9. Mannose-6-phosphate
Chemical FormulaC6H13O9P
Average Molecular Weight260.1358
Monoisotopic Molecular Weight260.029718526
IUPAC Name{[(2R,3S,4S,5S,6R)-3,4,5,6-tetrahydroxyoxan-2-yl]methoxy}phosphonic acid
Traditional IUPAC Name[(2R,3S,4S,5S,6R)-3,4,5,6-tetrahydroxyoxan-2-yl]methoxyphosphonic acid
CAS Registry Number3672-15-9
SMILES
O[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H](O)[C@@H]1O
InChI Identifier
InChI=1S/C6H13O9P/c7-3-2(1-14-16(11,12)13)15-6(10)5(9)4(3)8/h2-10H,1H2,(H2,11,12,13)/t2-,3-,4+,5+,6-/m1/s1
InChI KeyNBSCHQHZLSJFNQ-RWOPYEJCSA-N
Chemical Taxonomy
KingdomOrganic Compounds
Super ClassCarbohydrates and Carbohydrate Conjugates
ClassMonosaccharides
Sub ClassHexoses
Other Descriptors
  • Aliphatic Heteromonocyclic Compounds
  • Carbohydrates and Carbohydrate Conjugates
  • D-glucopyranose 6-phosphate(ChEBI)
Substituents
  • 1,2 Diol
  • Hemiacetal
  • Monosaccharide Phosphate
  • Organic Hypophosphite
  • Organic Phosphite
  • Oxane
  • Phosphoric Acid Ester
  • Secondary Alcohol
Direct ParentHexoses
Ontology
StatusExpected and Not Quantified
Origin
  • Endogenous
Biofunction
  • Component of Fructose and mannose metabolism
ApplicationNot Available
Cellular locations
  • Cytoplasm (predicted from logP)
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
water solubility31.4 g/LALOGPS
logP-2.1ALOGPS
logP-3.1ChemAxon
logS-0.92ALOGPS
pKa (strongest acidic)1.22ChemAxon
pKa (strongest basic)-3.6ChemAxon
physiological charge-2ChemAxon
hydrogen acceptor count8ChemAxon
hydrogen donor count6ChemAxon
polar surface area156.91ChemAxon
rotatable bond count3ChemAxon
refractivity46.8ChemAxon
polarizability20.43ChemAxon
Spectra
SpectraMS/MS1D NMR2D NMR
Biological Properties
Cellular Locations
  • Cytoplasm (predicted from logP)
Biofluid LocationsNot Available
Tissue Location
  • Fibroblasts
  • Intestine
  • Liver
  • Prostate
  • Spleen
  • Testes
Pathways
NameSMPDB LinkKEGG Link
Fructose and Mannose DegradationSMP00064map00051
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDNot Available
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB022411
KNApSAcK IDNot Available
Chemspider ID388338
KEGG Compound IDC00275
BioCyc IDMANNOSE-6P
BiGG ID34471
Wikipedia LinkMannose 6-phosphate
NuGOwiki LinkHMDB01078
Metagene LinkHMDB01078
METLIN ID5987
PubChem Compound439198
PDB IDM6D
ChEBI ID49728
References
Synthesis ReferencePascual, C.; Herrera, L. Use of permeabilized yeast cells as a system of enzyme immobilization. Its use for the preparation of mannose 6-phosphate. Folia Microbiologica (Prague, Czech Republic) (1981), 26(2), 103-6.
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Tiede S, Muschol N, Reutter G, Cantz M, Ullrich K, Braulke T: Missense mutations in N-acetylglucosamine-1-phosphotransferase alpha/beta subunit gene in a patient with mucolipidosis III and a mild clinical phenotype. Am J Med Genet A. 2005 Sep 1;137(3):235-40. Pubmed: 16094673
  2. Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK, Ahsan A, Kalyana-Sundaram S, Han B, Cao X, Byun J, Omenn GS, Ghosh D, Pennathur S, Alexander DC, Berger A, Shuster JR, Wei JT, Varambally S, Beecher C, Chinnaiyan AM: Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009 Feb 12;457(7231):910-4. Pubmed: 19212411
  3. DeRossi C, Bode L, Eklund EA, Zhang F, Davis JA, Westphal V, Wang L, Borowsky AD, Freeze HH: Ablation of mouse phosphomannose isomerase (Mpi) causes mannose 6-phosphate accumulation, toxicity, and embryonic lethality. J Biol Chem. 2006 Mar 3;281(9):5916-27. Epub 2005 Dec 8. Pubmed: 16339137
  4. Beljaars L, Molema G, Weert B, Bonnema H, Olinga P, Groothuis GM, Meijer DK, Poelstra K: Albumin modified with mannose 6-phosphate: A potential carrier for selective delivery of antifibrotic drugs to rat and human hepatic stellate cells. Hepatology. 1999 May;29(5):1486-93. Pubmed: 10216133
  5. van der Ploeg AT, van der Kraaij AM, Willemsen R, Kroos MA, Loonen MC, Koster JF, Reuser AJ: Rat heart perfusion as model system for enzyme replacement therapy in glycogenosis type II. Pediatr Res. 1990 Oct;28(4):344-7. Pubmed: 2235132
  6. Yatziv S, Barfi G, Newburg DS: Lysosomal hydrolases in blood-derived macrophages of patients with I-cell disease. J Lab Clin Med. 1986 Oct;108(4):365-8. Pubmed: 3093618
  7. Puolakkainen M, Kuo CC, Campbell LA: Chlamydia pneumoniae uses the mannose 6-phosphate/insulin-like growth factor 2 receptor for infection of endothelial cells. Infect Immun. 2005 Aug;73(8):4620-5. Pubmed: 16040974
  8. Holtta-Vuori M, Maatta J, Ullrich O, Kuismanen E, Ikonen E: Mobilization of late-endosomal cholesterol is inhibited by Rab guanine nucleotide dissociation inhibitor. Curr Biol. 2000 Jan 27;10(2):95-8. Pubmed: 10662671
  9. Harper J, Burns JL, Foulstone EJ, Pignatelli M, Zaina S, Hassan AB: Soluble IGF2 receptor rescues Apc(Min/+) intestinal adenoma progression induced by Igf2 loss of imprinting. Cancer Res. 2006 Feb 15;66(4):1940-8. Pubmed: 16488992
  10. Saris JJ, Derkx FH, De Bruin RJ, Dekkers DH, Lamers JM, Saxena PR, Schalekamp MA, Jan Danser AH: High-affinity prorenin binding to cardiac man-6-P/IGF-II receptors precedes proteolytic activation to renin. Am J Physiol Heart Circ Physiol. 2001 Apr;280(4):H1706-15. Pubmed: 11247783
  11. Bird CH, Sun J, Ung K, Karambalis D, Whisstock JC, Trapani JA, Bird PI: Cationic sites on granzyme B contribute to cytotoxicity by promoting its uptake into target cells. Mol Cell Biol. 2005 Sep;25(17):7854-67. Pubmed: 16107729
  12. Adrian JE, Poelstra K, Scherphof GL, Molema G, Meijer DK, Reker-Smit C, Morselt HW, Kamps JA: Interaction of targeted liposomes with primary cultured hepatic stellate cells: Involvement of multiple receptor systems. J Hepatol. 2006 Mar;44(3):560-7. Epub 2005 Oct 19. Pubmed: 16368158
  13. Ullrich K, Basner R, Gieselmann V, Von Figura K: Recognition of human urine alpha-N-acetylglucosaminidase by rat hepatocytes. Involvement of receptors specific for galactose, mannose 6-phosphate and mannose. Biochem J. 1979 May 15;180(2):413-9. Pubmed: 114170
  14. Davis JA, Wu XH, Wang L, DeRossi C, Westphal V, Wu R, Alton G, Srikrishna G, Freeze HH: Molecular cloning, gene organization, and expression of mouse Mpi encoding phosphomannose isomerase. Glycobiology. 2002 Jul;12(7):435-42. Pubmed: 12122025
  15. Kaplan A, Fischer D, Achord D, Sly W: Phosphohexosyl recognition is a general characteristic of pinocytosis of lysosomal glycosidases by human fibroblasts. J Clin Invest. 1977 Nov;60(5):1088-93. Pubmed: 908752
  16. Lobel P, Dahms NM, Breitmeyer J, Chirgwin JM, Kornfeld S: Cloning of the bovine 215-kDa cation-independent mannose 6-phosphate receptor. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2233-7. Pubmed: 2951738
  17. Maguchi S, Taniguchi N, Makita A: Elevated activity and increased mannose-6-phosphate in the carbohydrate moiety of cathepsin D from human hepatoma. Cancer Res. 1988 Jan 15;48(2):362-7. Pubmed: 2825973
  18. Sleat DE, Wang Y, Sohar I, Lackland H, Li Y, Li H, Zheng H, Lobel P: Identification and validation of mannose 6-phosphate glycoproteins in human plasma reveal a wide range of lysosomal and non-lysosomal proteins. Mol Cell Proteomics. 2006 Oct;5(10):1942-56. Epub 2006 May 17. Pubmed: 16709564
  19. Sleat DE, Sohar I, Lackland H, Majercak J, Lobel P: Rat brain contains high levels of mannose-6-phosphorylated glycoproteins including lysosomal enzymes and palmitoyl-protein thioesterase, an enzyme implicated in infantile neuronal lipofuscinosis. J Biol Chem. 1996 Aug 9;271(32):19191-8. Pubmed: 8702598

Enzymes

General function:
Involved in ATP binding
Specific function:
Catalyzes the initial step in utilization of glucose by the beta-cell and liver at physiological glucose concentration. Glucokinase has a high Km for glucose, and so it is effective only when glucose is abundant. The role of GCK is to provide G6P for the synthesis of glycogen. Pancreatic glucokinase plays an important role in modulating insulin secretion. Hepatic glucokinase helps to facilitate the uptake and conversion of glucose by acting as an insulin-sensitive determinant of hepatic glucose usage.
Gene Name:
GCK
Uniprot ID:
P35557
Molecular weight:
52191.07
General function:
Involved in ATP binding
Specific function:
Not Available
Gene Name:
HK3
Uniprot ID:
P52790
Molecular weight:
99024.56
Reactions
Adenosine triphosphate + D-Mannose → ADP + Mannose 6-phosphatedetails
General function:
Involved in ATP binding
Specific function:
Not Available
Gene Name:
HK2
Uniprot ID:
P52789
Molecular weight:
102379.06
Reactions
Adenosine triphosphate + D-Mannose → ADP + Mannose 6-phosphatedetails
General function:
Involved in ATP binding
Specific function:
Not Available
Gene Name:
HK1
Uniprot ID:
P19367
Molecular weight:
102485.1
Reactions
Adenosine triphosphate + D-Mannose → ADP + Mannose 6-phosphatedetails
General function:
Involved in mannose-6-phosphate isomerase activity
Specific function:
Involved in the synthesis of the GDP-mannose and dolichol-phosphate-mannose required for a number of critical mannosyl transfer reactions.
Gene Name:
MPI
Uniprot ID:
P34949
Molecular weight:
46655.44
Reactions
Mannose 6-phosphate → Fructose 6-phosphatedetails
Mannose 6-phosphate → Beta-D-Fructose 6-phosphatedetails
General function:
Involved in catalytic activity
Specific function:
Involved in the synthesis of the GDP-mannose and dolichol-phosphate-mannose required for a number of critical mannosyl transfer reactions (By similarity).
Gene Name:
PMM2
Uniprot ID:
O15305
Molecular weight:
28081.925
Reactions
D-Mannose 1-phosphate → Mannose 6-phosphatedetails
Mannose 6-phosphate → D-Mannose 1-phosphatedetails
General function:
Involved in metal ion binding
Specific function:
Involved in the synthesis of the GDP-mannose and dolichol-phosphate-mannose required for a number of critical mannosyl transfer reactions. In addition, may be responsible for the degradation of glucose-1,6-bisphosphate in ischemic brain.
Gene Name:
PMM1
Uniprot ID:
Q92871
Molecular weight:
29746.545
Reactions
D-Mannose 1-phosphate → Mannose 6-phosphatedetails
Mannose 6-phosphate → D-Mannose 1-phosphatedetails
General function:
Involved in protein binding
Specific function:
Required for the transport of mannose 6-phosphate receptors (MPR) from endosomes to the trans-Golgi network
Gene Name:
PLIN3
Uniprot ID:
O60664
Molecular weight:
47046.6
General function:
Involved in protein binding
Specific function:
Transport of phosphorylated lysosomal enzymes from the Golgi complex and the cell surface to lysosomes. Lysosomal enzymes bearing phosphomannosyl residues bind specifically to mannose-6- phosphate receptors in the Golgi apparatus and the resulting receptor-ligand complex is transported to an acidic prelyosomal compartment where the low pH mediates the dissociation of the complex
Gene Name:
M6PR
Uniprot ID:
P20645
Molecular weight:
30993.1
General function:
Involved in transporter activity
Specific function:
Transport of phosphorylated lysosomal enzymes from the Golgi complex and the cell surface to lysosomes. Lysosomal enzymes bearing phosphomannosyl residues bind specifically to mannose-6- phosphate receptors in the Golgi apparatus and the resulting receptor-ligand complex is transported to an acidic prelyosomal compartment where the low pH mediates the dissociation of the complex. This receptor also binds IGF2. Acts as a positive regulator of T-cell coactivation, by binding DPP4
Gene Name:
IGF2R
Uniprot ID:
P11717
Molecular weight:
274273.3
General function:
Involved in intramolecular transferase activity, phosphotransferases
Specific function:
Catalyzes the conversion of the nucleoside breakdown products ribose-1-phosphate and deoxyribose-1-phosphate to the corresponding 5-phosphopentoses. May also catalyze the interconversion of glucose-1-phosphate and glucose-6-phosphate. Has low glucose 1,6-bisphosphate synthase activity.
Gene Name:
PGM2
Uniprot ID:
Q96G03
Molecular weight:
68282.765
General function:
Involved in protein binding
Specific function:
Coat protein that is involved in the localization of trans-Golgi network (TGN) membrane proteins that contain acidic cluster sorting motifs. Controls the endosome-to-Golgi trafficking of furin and mannose-6-phosphate receptor by connecting the acidic-cluster-containing cytoplasmic domain of these molecules with the adapter-protein complex-1 (AP-1) of endosomal clathrin- coated membrane pits. Involved in HIV-1 nef-mediated removal of MHC-I from the cell surface to the TGN
Gene Name:
PACS1
Uniprot ID:
Q6VY07
Molecular weight:
104897.6
General function:
Involved in enzyme binding
Specific function:
Functions as a sorting receptor in the Golgi compartment and as a clearance receptor on the cell surface. Required for protein transport from the Golgi apparatus to the lysosomes by a pathway that is independent of the mannose-6-phosphate receptor (M6PR). Also required for protein transport from the Golgi apparatus to the endosomes. Promotes neuronal apoptosis by mediating endocytosis of the proapoptotic precursor forms of BDNF (proBDNF) and NGFB (proNGFB). Also acts as a receptor for neurotensin. May promote mineralization of the extracellular matrix during osteogenic differentiation by scavenging extracellular LPL. Probably required in adipocytes for the formation of specialized storage vesicles containing the glucose transporter SLC2A4/GLUT4 (GLUT4 storage vesicles, or GSVs). These vesicles provide a stable pool of SLC2A4 and confer increased responsiveness to insulin. May also mediate transport from the endoplasmic reticulum to the Golgi
Gene Name:
SORT1
Uniprot ID:
Q99523
Molecular weight:
92066.9
General function:
Involved in microtubule motor activity
Specific function:
Plus end-directed microtubule-dependent motor protein involved in mannose-6-phosphate receptor (M6PR) transport to the plasma membrane
Gene Name:
KIF13A
Uniprot ID:
Q9H1H9
Molecular weight:
202306.8
General function:
Involved in androgen receptor binding
Specific function:
May play a role in autophagy. May regulate the trafficking of proteins involved in the mannose-6-phosphate receptor (MPR) recycling pathway
Gene Name:
WIPI1
Uniprot ID:
Q5MNZ9
Molecular weight:
48672.6
General function:
Not Available
Specific function:
Not Available
Gene Name:
HKDC1
Uniprot ID:
Q2TB90
Molecular weight:
102513.88
Reactions
Adenosine triphosphate + D-Mannose → ADP + Mannose 6-phosphatedetails