Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P34949 (MPI_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 154. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Mannose-6-phosphate isomerase

EC=5.3.1.8
Alternative name(s):
Phosphohexomutase
Phosphomannose isomerase
Short name=PMI
Gene names
Name:MPI
Synonyms:PMI1
OrganismHomo sapiens (Human) [Reference 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-alpha-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

Congenital disorder of glycosylation 1B (CDG1B) [MIM:602579]: A multisystem disorder caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. Congenital disorder of glycosylation type 1B is clinically characterized by protein-losing enteropathy.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.2 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13

Sequence similarities

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

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 Ref.6
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

Amino acid modifications

Modified residue21N-acetylalanine Ref.6

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.8
VAR_012338
Natural variant1291Y → C in CDG1B. Ref.12
VAR_022517
Natural variant1311D → N in CDG1B. Ref.2
VAR_022518
Natural variant1381M → T in CDG1B. Ref.8
VAR_012339
Natural variant1401I → T in CDG1B. Ref.11
VAR_012345
Natural variant1521R → Q in CDG1B. Ref.2
VAR_022519
Natural variant2191R → Q in CDG1B. Ref.9 Ref.11
VAR_012340
Natural variant2501G → S in CDG1B. Ref.2
VAR_022520
Natural variant2551Y → C in CDG1B. Ref.10
VAR_022521
Natural variant2951R → H in CDG1B. Ref.13
Corresponds to variant rs28928906 [ dbSNP | Ensembl ].
VAR_022522
Natural variant3981I → T in CDG1B. Ref.10
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 [UniParc].

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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS CDG1B THR-51; ASN-131; GLN-152; SER-250 AND HIS-418.
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Testis.
[4]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Tissue: Blood and Brain.
[6]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
[7]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[8]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS CDG1B LEU-102 AND THR-138.
[9]"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] [Europe PMC] [Abstract]
Cited for: VARIANT CDG1B GLN-219.
[10]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS CDG1B CYS-255 AND THR-398.
[11]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS CDG1B THR-140 AND GLN-219.
[12]"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] [Europe PMC] [Abstract]
Cited for: VARIANT CDG1B CYS-129.
[13]"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] [Europe PMC] [Abstract]
Cited for: VARIANT CDG1B HIS-295.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X76057 mRNA. Translation: CAA53657.1.
AF227218, AF227216, AF227217 Genomic DNA. Translation: AAF37697.1.
AK292374 mRNA. Translation: BAF85063.1.
CH471136 Genomic DNA. Translation: EAW99296.1.
BC017351 mRNA. Translation: AAH17351.1.
BC046357 mRNA. Translation: AAH46357.1.
PIRS41122.
RefSeqNP_002426.1. NM_002435.2.
UniGeneHs.75694.

3D structure databases

ProteinModelPortalP34949.
SMRP34949. Positions 2-419.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110491. 3 interactions.
STRING9606.ENSP00000318318.

Chemistry

BindingDBP34949.
ChEMBLCHEMBL2758.

PTM databases

PhosphoSiteP34949.

Polymorphism databases

DMDM462567.

2D gel databases

OGPP34949.

Proteomic databases

PaxDbP34949.
PRIDEP34949.

Protocols and materials databases

DNASU4351.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000323744; ENSP00000318192; ENSG00000178802. [P34949-2]
ENST00000352410; ENSP00000318318; ENSG00000178802. [P34949-1]
GeneID4351.
KEGGhsa:4351.
UCSCuc002azc.1. human. [P34949-1]
uc002aze.1. human. [P34949-2]

Organism-specific databases

CTD4351.
GeneCardsGC15P075182.
HGNCHGNC:7216. MPI.
HPAHPA007200.
MIM154550. gene.
602579. phenotype.
neXtProtNX_P34949.
Orphanet79319. MPI-CDG.
PharmGKBPA30922.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1482.
HOGENOMHOG000241277.
HOVERGENHBG000367.
InParanoidP34949.
KOK01809.
OMAFKVLCAD.
PhylomeDBP34949.
TreeFamTF312831.

Enzyme and pathway databases

ReactomeREACT_17015. Metabolism of proteins.
UniPathwayUPA00126; UER00423.

Gene expression databases

ArrayExpressP34949.
BgeeP34949.
CleanExHS_MPI.
GenevestigatorP34949.

Family and domain databases

Gene3D2.60.120.10. 3 hits.
InterProIPR001250. Man6P_Isoase-1.
IPR016305. Mannose-6-P_Isomerase.
IPR018050. Pmannose_isomerase-type1_CS.
IPR014710. RmlC-like_jellyroll.
IPR011051. RmlC_Cupin.
[Graphical view]
PANTHERPTHR10309. PTHR10309. 1 hit.
PfamPF01238. PMI_typeI. 1 hit.
[Graphical view]
PIRSFPIRSF001480. Mannose-6-phosphate_isomerase. 1 hit.
PRINTSPR00714. MAN6PISMRASE.
SUPFAMSSF51182. SSF51182. 1 hit.
TIGRFAMsTIGR00218. manA. 1 hit.
PROSITEPS00965. PMI_I_1. 1 hit.
PS00966. PMI_I_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi4351.
NextBio17118.
PROP34949.
SOURCESearch...

Entry information

Entry nameMPI_HUMAN
AccessionPrimary (citable) accession number: P34949
Secondary accession number(s): A8K8K9, Q96AB0
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: January 23, 2007
Last modified: April 16, 2014
This is version 154 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 15

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