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Reviewed, UniProtKB/Swiss-Prot P34949 (MPI_HUMAN)

Last modified July 7, 2009. Version 102. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Mannose-6-phosphate isomerase
    EC=5.3.1.8
Alternative name(s):
    Phosphomannose isomerase
      Short name=PMI
    Phosphohexomutase
Gene names
Name: MPI
Synonyms: PMI1
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length423 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Involved in the synthesis of the GDP-mannose and dolichol-phosphate-mannose required for a number of critical mannosyl transfer reactions.

Catalytic activity

D-mannose 6-phosphate = D-fructose 6-phosphate.

Cofactor

Binds 1 zinc ion per subunit By similarity.

Pathway

Nucleotide-sugar biosynthesis; GDP-D-mannose biosynthesis; alpha-D-mannose 1-phosphate from D-fructose 6-phosphate: step 1/2.

Subcellular location

Cytoplasm Probable.

Tissue specificity

Expressed in all tissues, but more abundant in heart, brain and skeletal muscle.

Involvement in disease

Defects in MPI are the cause of congenital disorder of glycosylation type 1B (CDG1B) [MIM:602579]; also known as carbohydrate-deficient glycoprotein syndrome type Ib (CDGS1B). Congenital disorders of glycosylation are metabolic deficiencies in glycoprotein biosynthesis that usually cause severe mental and psychomotor retardation. They are characterized by under-glycosylated serum glycoproteins. CDG1B is clinically characterized by protein-losing enteropathy. Ref.2 Ref.5 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10

Sequence similarities

Belongs to the mannose-6-phosphate isomerase type 1 family.

Ontologies

Keywords
   Cellular componentCytoplasm
   Coding sequence diversityAlternative splicing
   DiseaseCongenital disorder of glycosylation
Disease mutation
   LigandMetal-binding
Zinc
   Molecular functionIsomerase
   Technical termComplete proteome
Direct protein sequencing
Gene Ontology (GO)
   Biological processcarbohydrate metabolic process

Inferred from electronic annotation. Source: InterPro

   Cellular componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular functionmannose-6-phosphate isomerase activity Ref.1

Traceable author statement. Source: ProtInc

zinc ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P34949-1)

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.
Isoform 2 (identifier: P34949-2)

The sequence of this isoform differs from the canonical sequence as follows:
     163-224: KVPEFQFLIGDEAATHLKQTMSHDSQAVASSLQSCFSHLMKSEKKVVVEQLNLLVKRISQQA → T
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Probable
Chain2 – 423422Mannose-6-phosphate isomerase
PRO_0000194235

Sites

Active site2951 By similarity
Metal binding1101Zinc By similarity
Metal binding1121Zinc By similarity
Metal binding1371Zinc By similarity
Metal binding2761Zinc By similarity

Natural variations

Alternative sequence163 – 22462KVPEF…ISQQA → T in isoform 2.
VSP_013357
Natural variant511M → T in CDG1B. Ref.2
VAR_022516
Natural variant1021S → L in CDG1B. Ref.5
VAR_012338
Natural variant1291Y → C in CDG1B. Ref.9
VAR_022517
Natural variant1311D → N in CDG1B. Ref.2
VAR_022518
Natural variant1381M → T in CDG1B. Ref.5
VAR_012339
Natural variant1401I → T in CDG1B. Ref.8
VAR_012345
Natural variant1521R → Q in CDG1B. Ref.2
VAR_022519
Natural variant2191R → Q in CDG1B. Ref.6 Ref.8
VAR_012340
Natural variant2501G → S in CDG1B. Ref.2
VAR_022520
Natural variant2551Y → C in CDG1B. Ref.7
VAR_022521
Natural variant2951R → H in CDG1B. dbSNP rs28928906. Ref.10
VAR_022522
Natural variant3981I → T in CDG1B. Ref.7
VAR_022523
Natural variant4181R → H in CDG1B. Ref.2
VAR_022524

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified January 23, 2007. Version 2.
Checksum: 1612DD966B86D3AC

FASTA42346,656
        10         20         30         40         50         60 
MAAPRVFPLS CAVQQYAWGK MGSNSEVARL LASSDPLAQI AEDKPYAELW MGTHPRGDAK 

        70         80         90        100        110        120 
ILDNRISQKT LSQWIAENQD SLGSKVKDTF NGNLPFLFKV LSVETPLSIQ AHPNKELAEK 

       130        140        150        160        170        180 
LHLQAPQHYP DANHKPEMAI ALTPFQGLCG FRPVEEIVTF LKKVPEFQFL IGDEAATHLK 

       190        200        210        220        230        240 
QTMSHDSQAV ASSLQSCFSH LMKSEKKVVV EQLNLLVKRI SQQAAAGNNM EDIFGELLLQ 

       250        260        270        280        290        300 
LHQQYPGDIG CFAIYFLNLL TLKPGEAMFL EANVPHAYLK GDCVECMACS DNTVRAGLTP 

       310        320        330        340        350        360 
KFIDVPTLCE MLSYTPSSSK DRLFLPTRSQ EDPYLSIYDP PVPDFTIMKT EVPGSVTEYK 

       370        380        390        400        410        420 
VLALDSASIL LMVQGTVIAS TPTTQTPIPL QRGGVLFIGA NESVSLKLTE PKDLLIFRAC 


CLL 

« Hide

Isoform 2.

Checksum: 58CA9B39BF20C459
Show »

FASTA36239,834

References

« Hide 'large scale' references
[1]"Purification, cDNA cloning and heterologous expression of human phosphomannose isomerase."
Proudfoot A.E.I., Turcatti G., Wells T.N.C., Payton M.A., Smith D.J.
Eur. J. Biochem. 219:415-423(1994) [PubMed: 8307007] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE.
Tissue: Placenta and Testis.
[2]"Genomic organization of the human phosphomannose isomerase (MPI) gene and mutation analysis in patients with congenital disorders of glycosylation type Ib (CDG-Ib)."
Schollen E., Dorland L., de Koning T.J., Van Diggelen O.P., Huijmans J.G.M., Marquardt T., Babovic-Vuksanovic D., Patterson M., Imtiaz F., Winchester B., Adamowicz M., Pronicka E., Freeze H., Matthijs G.
Hum. Mutat. 16:247-252(2000) [PubMed: 10980531] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS CDG1B THR-51; ASN-131; GLN-152; SER-250 AND HIS-418.
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Tissue: Blood and Brain.
[4]Colinge J., Superti-Furga G., Bennett K.L.
Submitted (OCT-2008) to UniProtKB
Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[5]"Phosphomannose isomerase deficiency: a carbohydrate-deficient glycoprotein syndrome with hepatic-intestinal presentation."
Jaeken J., Matthijs G., Saudubray J.-M., Dionisi-Vici C., Bertini E., de Lonlay P., Henri H., Carchon H., Schollen E., Van Schaftingen E.
Am. J. Hum. Genet. 62:1535-1539(1998) [PubMed: 9585601] [Abstract]
Cited for: VARIANTS CDG1B LEU-102 AND THR-138.
[6]"Carbohydrate-deficient glycoprotein syndrome type Ib: phosphomannose isomerase deficiency and mannose therapy."
Niehues R., Hasilik M., Alton G., Koerner C., Schiebe-Sukumar M., Koch H.G., Zimmer K.-P., Wu R., Harms E., Reiter K., von Figura K., Freeze H.H., Harms H.K., Marquardt T.
J. Clin. Invest. 101:1414-1420(1998) [PubMed: 9525984] [Abstract]
Cited for: VARIANT CDG1B GLN-219.
[7]"A broad spectrum of clinical presentations in congenital disorders of glycosylation I: a series of 26 cases."
de Lonlay P., Seta N., Barrot S., Chabrol B., Drouin V., Gabriel B.M., Journel H., Kretz M., Laurent J., Le Merrer M., Leroy A., Pedespan D., Sarda P., Villeneuve N., Schmitz J., van Schaftingen E., Matthijs G., Jaeken J. expand/collapse author list , Koerner C., Munnich A., Saudubray J.-M., Cormier-Daire V.
J. Med. Genet. 38:14-19(2001) [PubMed: 11134235] [Abstract]
Cited for: VARIANTS CDG1B CYS-255 AND THR-398.
[8]"Genetic and metabolic analysis of the first adult with congenital disorder of glycosylation type Ib: long-term outcome and effects of mannose supplementation."
Westphal V., Kjaergaard S., Davis J.A., Peterson S.M., Skovby F., Freeze H.H.
Mol. Genet. Metab. 73:77-85(2001) [PubMed: 11350186] [Abstract]
Cited for: VARIANTS CDG1B THR-140 AND GLN-219.
[9]"DHPLC analysis as a platform for molecular diagnosis of congenital disorders of glycosylation (CDG)."
Schollen E., Martens K., Geuzens E., Matthijs G.
Eur. J. Hum. Genet. 10:643-648(2002) [PubMed: 12357336] [Abstract]
Cited for: VARIANT CDG1B CYS-129.
[10]"Protein losing enteropathy-hepatic fibrosis syndrome in Saguenay-Lac St-Jean, Quebec is a congenital disorder of glycosylation type Ib."
Vuillaumier-Barrot S., Le Bizec C., de Lonlay P., Barnier A., Mitchell G., Pelletier V., Prevost C., Saudubray J.-M., Durand G., Seta N.
J. Med. Genet. 39:849-851(2002) [PubMed: 12414827] [Abstract]
Cited for: VARIANT CDG1B HIS-295.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

X76057 mRNA. Translation: CAA53657.1.
AF227218, AF227216, AF227217 Genomic DNA. Translation: AAF37697.1.
BC017351 mRNA. Translation: AAH17351.1.
BC046357 mRNA. Translation: AAH46357.1.
IPIIPI00219358.
IPI00332187.
PIRS41122.
RefSeqNP_002426.1.
UniGeneHs.75694

3D structure databases

HSSPHSSP built from PDB template 1PMI based on UniProtKB P34948.
ModBaseSearch...

2-D gel databases

OGPP34949.

Proteomic databases

PRIDEP34949.

Genome annotation databases

EnsemblENSG00000178802. Homo sapiens. [Contig view]
GeneID4351.
KEGGhsa:4351.
NMPDRfig|9606.3.peg.10994.
UCSCuc002azc.1. human.
uc002aze.1. human.

Organism-specific databases

GeneCardsGC15P072969.
H-InvDBHIX0018037.
HGNCHGNC:7216. MPI.
HPAHPA007200.
MIM154550. gene.
602579. phenotype.
Orphanet137. CDG syndrome.
79319. CDG syndrome, type Ib.
PharmGKBPA30922.
GenAtlasSearch...

Phylogenomic databases

HOGENOMP34949.
HOVERGENP34949.
OMAP34949. MGSNSEV.

Enzyme and pathway databases

BRENDA5.3.1.8. 247.

Gene expression databases

ArrayExpressP34949.
BgeeP34949.
CleanExHS_MPI.
GermOnlineENSG00000178802. Homo sapiens.

Family and domain databases

InterProIPR001250. Man6P_Isoase-1.
IPR016305. Mannose-6-P_Isomerase.
IPR018050. Pmannose_isomerase-type1_CS.
IPR014710. RmlC-like_jellyroll.
[Graphical view]
Gene3DG3DSA:2.60.120.10. RmlC-like_jellyroll. 2 hits.
PfamPF01238. PMI_typeI. 1 hit.
[Graphical view]
PIRSFPIRSF001480. Mannose-6-phosphate_isomerase. 1 hit.
PRINTSPR00714. MAN6PISMRASE.
TIGRFAMsTIGR00218. manA. 1 hit.
PROSITEPS00965. PMI_I_1. 1 hit.
PS00966. PMI_I_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio17118.
SOURCESearch...

Entry information

Entry nameMPI_HUMAN
AccessionPrimary (citable) accession number: P34949
Secondary accession number(s): Q96AB0
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: January 23, 2007
Last modified: July 7, 2009
This is version 102 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 15

Human chromosome 15: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PATHWAY comments

Index of metabolic and biosynthesis pathways

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents