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Protein

Mannose-6-phosphate isomerase

Gene

MPI

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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

Catalytic activityi

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

Cofactori

Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity

Pathwayi: GDP-alpha-D-mannose biosynthesis

This protein is involved in step 1 of the subpathway that synthesizes alpha-D-mannose 1-phosphate from D-fructose 6-phosphate.
Proteins known to be involved in the 2 steps of the subpathway in this organism are:
  1. Mannose-6-phosphate isomerase (MPI), Mannose-6-phosphate isomerase (MPI), Mannose-6-phosphate isomerase (MPI), Mannose-6-phosphate isomerase, Mannose-6-phosphate isomerase (MPI)
  2. Phosphomannomutase 2 (PMM2), Phosphomannomutase 1 (PMM1), Phosphomannomutase (PMM2), Phosphomannomutase, Phosphomannomutase, Phosphomannomutase (PMM2), Phosphomannomutase, Phosphomannomutase (PMM2), Phosphomannomutase (PMM2), Phosphomannomutase (PMM2), Phosphomannomutase, Phosphomannomutase, Phosphomannomutase, Phosphomannomutase (PMM1), Phosphomannomutase (PMM2), Phosphomannomutase (PMM2), Phosphomannomutase (PMM2), Phosphomannomutase (PMM2), Phosphomannomutase (PMM2)
This subpathway is part of the pathway GDP-alpha-D-mannose biosynthesis, which is itself part of Nucleotide-sugar biosynthesis.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes alpha-D-mannose 1-phosphate from D-fructose 6-phosphate, the pathway GDP-alpha-D-mannose biosynthesis and in Nucleotide-sugar biosynthesis.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi110ZincBy similarity1
Metal bindingi112ZincBy similarity1
Metal bindingi137ZincBy similarity1
Metal bindingi276ZincBy similarity1
Active sitei295By similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionIsomerase
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-4043916 Defective MPI causes MPI-CDG (CDG-1b)
R-HSA-446205 Synthesis of GDP-mannose
UniPathwayi
UPA00126;UER00423

Names & Taxonomyi

Protein namesi
Recommended name:
Mannose-6-phosphate isomerase (EC:5.3.1.8)
Alternative name(s):
Phosphohexomutase
Phosphomannose isomerase
Short name:
PMI
Gene namesi
Name:MPI
Synonyms:PMI1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 15

Organism-specific databases

EuPathDBiHostDB:ENSG00000178802.17
HGNCiHGNC:7216 MPI
MIMi154550 gene
neXtProtiNX_P34949

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Involvement in diseasei

Congenital disorder of glycosylation 1B (CDG1B)7 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of congenital disorder of glycosylation, 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. CDG1B is clinically characterized by protein-losing enteropathy.
See also OMIM:602579
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02251651M → T in CDG1B. 1 PublicationCorresponds to variant dbSNP:rs764835081Ensembl.1
Natural variantiVAR_012338102S → L in CDG1B. 1 PublicationCorresponds to variant dbSNP:rs104894494EnsemblClinVar.1
Natural variantiVAR_022517129Y → C in CDG1B. 1 PublicationCorresponds to variant dbSNP:rs887249336Ensembl.1
Natural variantiVAR_022518131D → N in CDG1B. 1 PublicationCorresponds to variant dbSNP:rs566620411Ensembl.1
Natural variantiVAR_012339138M → T in CDG1B. 1 PublicationCorresponds to variant dbSNP:rs104894495EnsemblClinVar.1
Natural variantiVAR_012345140I → T in CDG1B. 1 PublicationCorresponds to variant dbSNP:rs773678732Ensembl.1
Natural variantiVAR_022519152R → Q in CDG1B. 1 PublicationCorresponds to variant dbSNP:rs766458792Ensembl.1
Natural variantiVAR_012340219R → Q in CDG1B. 2 PublicationsCorresponds to variant dbSNP:rs104894489EnsemblClinVar.1
Natural variantiVAR_022520250G → S in CDG1B. 1 PublicationCorresponds to variant dbSNP:rs748090636EnsemblClinVar.1
Natural variantiVAR_022521255Y → C in CDG1B. 1 Publication1
Natural variantiVAR_022522295R → H in CDG1B. 1 PublicationCorresponds to variant dbSNP:rs28928906EnsemblClinVar.1
Natural variantiVAR_022523398I → T in CDG1B. 1 PublicationCorresponds to variant dbSNP:rs369326210Ensembl.1
Natural variantiVAR_022524418R → H in CDG1B. 1 PublicationCorresponds to variant dbSNP:rs863225087EnsemblClinVar.1

Keywords - Diseasei

Congenital disorder of glycosylation, Disease mutation

Organism-specific databases

DisGeNETi4351
GeneReviewsiMPI
MalaCardsiMPI
MIMi602579 phenotype
OpenTargetsiENSG00000178802
Orphaneti79319 MPI-CDG
PharmGKBiPA30922

Chemistry databases

ChEMBLiCHEMBL2758

Polymorphism and mutation databases

BioMutaiMPI
DMDMi462567

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00001942352 – 423Mannose-6-phosphate isomeraseAdd BLAST422

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei102PhosphoserineCombined sources1
Modified residuei108PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP34949
MaxQBiP34949
PaxDbiP34949
PeptideAtlasiP34949
PRIDEiP34949
ProteomicsDBi54959
54960 [P34949-2]

2D gel databases

OGPiP34949

PTM databases

iPTMnetiP34949
PhosphoSitePlusiP34949

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000178802 Expressed in 193 organ(s), highest expression level in heart left ventricle
CleanExiHS_MPI
ExpressionAtlasiP34949 baseline and differential
GenevisibleiP34949 HS

Organism-specific databases

HPAiHPA007200

Interactioni

Protein-protein interaction databases

BioGridi110491, 21 interactors
IntActiP34949, 2 interactors
MINTiP34949
STRINGi9606.ENSP00000318318

Chemistry databases

BindingDBiP34949

Structurei

3D structure databases

ProteinModelPortaliP34949
SMRiP34949
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG2757 Eukaryota
COG1482 LUCA
GeneTreeiENSGT00390000016075
HOGENOMiHOG000241277
HOVERGENiHBG000367
InParanoidiP34949
KOiK01809
OMAiMGTHPSN
OrthoDBiEOG091G078D
PhylomeDBiP34949
TreeFamiTF312831

Family and domain databases

Gene3Di2.60.120.10, 4 hits
InterProiView protein in InterPro
IPR001250 Man6P_Isoase-1
IPR016305 Mannose-6-P_Isomerase
IPR018050 Pmannose_isomerase-type1_CS
IPR014710 RmlC-like_jellyroll
IPR011051 RmlC_Cupin_sf
PANTHERiPTHR10309 PTHR10309, 1 hit
PfamiView protein in Pfam
PF01238 PMI_typeI, 1 hit
PIRSFiPIRSF001480 Mannose-6-phosphate_isomerase, 1 hit
PRINTSiPR00714 MAN6PISMRASE
SUPFAMiSSF51182 SSF51182, 1 hit
TIGRFAMsiTIGR00218 manA, 1 hit
PROSITEiView protein in PROSITE
PS00965 PMI_I_1, 1 hit
PS00966 PMI_I_2, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 17 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: P34949-1) [UniParc]FASTAAdd to basket

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.

« Hide
        10         20         30         40         50
MAAPRVFPLS CAVQQYAWGK MGSNSEVARL LASSDPLAQI AEDKPYAELW
60 70 80 90 100
MGTHPRGDAK ILDNRISQKT LSQWIAENQD SLGSKVKDTF NGNLPFLFKV
110 120 130 140 150
LSVETPLSIQ AHPNKELAEK LHLQAPQHYP DANHKPEMAI ALTPFQGLCG
160 170 180 190 200
FRPVEEIVTF LKKVPEFQFL IGDEAATHLK QTMSHDSQAV ASSLQSCFSH
210 220 230 240 250
LMKSEKKVVV EQLNLLVKRI SQQAAAGNNM EDIFGELLLQ LHQQYPGDIG
260 270 280 290 300
CFAIYFLNLL TLKPGEAMFL EANVPHAYLK GDCVECMACS DNTVRAGLTP
310 320 330 340 350
KFIDVPTLCE MLSYTPSSSK DRLFLPTRSQ EDPYLSIYDP PVPDFTIMKT
360 370 380 390 400
EVPGSVTEYK VLALDSASIL LMVQGTVIAS TPTTQTPIPL QRGGVLFIGA
410 420
NESVSLKLTE PKDLLIFRAC CLL
Length:423
Mass (Da):46,656
Last modified:January 23, 2007 - v2
Checksum:i1612DD966B86D3AC
GO
Isoform 2 (identifier: P34949-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     163-224: KVPEFQFLIGDEAATHLKQTMSHDSQAVASSLQSCFSHLMKSEKKVVVEQLNLLVKRISQQA → T

Note: No experimental confirmation available.
Show »
Length:362
Mass (Da):39,834
Checksum:i58CA9B39BF20C459
GO

Computationally mapped potential isoform sequencesi

There are 17 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H3BPB8H3BPB8_HUMAN
Mannose-6-phosphate isomerase
MPI hCG_2006995
403Annotation score:
F5GX71F5GX71_HUMAN
Mannose-6-phosphate isomerase
MPI
373Annotation score:
H3BP57H3BP57_HUMAN
Mannose-6-phosphate isomerase
MPI
288Annotation score:
H3BUZ9H3BUZ9_HUMAN
Mannose-6-phosphate isomerase
MPI
339Annotation score:
H3BPP3H3BPP3_HUMAN
Mannose-6-phosphate isomerase
MPI
287Annotation score:
H3BNY8H3BNY8_HUMAN
Mannose-6-phosphate isomerase
MPI
185Annotation score:
H3BT48H3BT48_HUMAN
Mannose-6-phosphate isomerase
MPI
319Annotation score:
H3BPM5H3BPM5_HUMAN
Mannose-6-phosphate isomerase
MPI
173Annotation score:
H3BN01H3BN01_HUMAN
Mannose-6-phosphate isomerase
MPI
174Annotation score:
H3BMZ9H3BMZ9_HUMAN
Mannose-6-phosphate isomerase
MPI
264Annotation score:
There are more potential isoformsShow all

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02251651M → T in CDG1B. 1 PublicationCorresponds to variant dbSNP:rs764835081Ensembl.1
Natural variantiVAR_012338102S → L in CDG1B. 1 PublicationCorresponds to variant dbSNP:rs104894494EnsemblClinVar.1
Natural variantiVAR_022517129Y → C in CDG1B. 1 PublicationCorresponds to variant dbSNP:rs887249336Ensembl.1
Natural variantiVAR_022518131D → N in CDG1B. 1 PublicationCorresponds to variant dbSNP:rs566620411Ensembl.1
Natural variantiVAR_012339138M → T in CDG1B. 1 PublicationCorresponds to variant dbSNP:rs104894495EnsemblClinVar.1
Natural variantiVAR_012345140I → T in CDG1B. 1 PublicationCorresponds to variant dbSNP:rs773678732Ensembl.1
Natural variantiVAR_022519152R → Q in CDG1B. 1 PublicationCorresponds to variant dbSNP:rs766458792Ensembl.1
Natural variantiVAR_012340219R → Q in CDG1B. 2 PublicationsCorresponds to variant dbSNP:rs104894489EnsemblClinVar.1
Natural variantiVAR_022520250G → S in CDG1B. 1 PublicationCorresponds to variant dbSNP:rs748090636EnsemblClinVar.1
Natural variantiVAR_022521255Y → C in CDG1B. 1 Publication1
Natural variantiVAR_022522295R → H in CDG1B. 1 PublicationCorresponds to variant dbSNP:rs28928906EnsemblClinVar.1
Natural variantiVAR_022523398I → T in CDG1B. 1 PublicationCorresponds to variant dbSNP:rs369326210Ensembl.1
Natural variantiVAR_022524418R → H in CDG1B. 1 PublicationCorresponds to variant dbSNP:rs863225087EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_013357163 – 224KVPEF…ISQQA → T in isoform 2. 1 PublicationAdd BLAST62

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS10272.1 [P34949-1]
CCDS73757.1 [P34949-2]
PIRiS41122
RefSeqiNP_001276085.1, NM_001289156.1
NP_001276086.1, NM_001289157.1 [P34949-2]
NP_002426.1, NM_002435.2 [P34949-1]
UniGeneiHs.75694

Genome annotation databases

EnsembliENST00000323744; ENSP00000318192; ENSG00000178802 [P34949-2]
ENST00000352410; ENSP00000318318; ENSG00000178802 [P34949-1]
GeneIDi4351
KEGGihsa:4351
UCSCiuc002azc.3 human [P34949-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS10272.1 [P34949-1]
CCDS73757.1 [P34949-2]
PIRiS41122
RefSeqiNP_001276085.1, NM_001289156.1
NP_001276086.1, NM_001289157.1 [P34949-2]
NP_002426.1, NM_002435.2 [P34949-1]
UniGeneiHs.75694

3D structure databases

ProteinModelPortaliP34949
SMRiP34949
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110491, 21 interactors
IntActiP34949, 2 interactors
MINTiP34949
STRINGi9606.ENSP00000318318

Chemistry databases

BindingDBiP34949
ChEMBLiCHEMBL2758

PTM databases

iPTMnetiP34949
PhosphoSitePlusiP34949

Polymorphism and mutation databases

BioMutaiMPI
DMDMi462567

2D gel databases

OGPiP34949

Proteomic databases

EPDiP34949
MaxQBiP34949
PaxDbiP34949
PeptideAtlasiP34949
PRIDEiP34949
ProteomicsDBi54959
54960 [P34949-2]

Protocols and materials databases

DNASUi4351
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000323744; ENSP00000318192; ENSG00000178802 [P34949-2]
ENST00000352410; ENSP00000318318; ENSG00000178802 [P34949-1]
GeneIDi4351
KEGGihsa:4351
UCSCiuc002azc.3 human [P34949-1]

Organism-specific databases

CTDi4351
DisGeNETi4351
EuPathDBiHostDB:ENSG00000178802.17
GeneCardsiMPI
GeneReviewsiMPI
HGNCiHGNC:7216 MPI
HPAiHPA007200
MalaCardsiMPI
MIMi154550 gene
602579 phenotype
neXtProtiNX_P34949
OpenTargetsiENSG00000178802
Orphaneti79319 MPI-CDG
PharmGKBiPA30922
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2757 Eukaryota
COG1482 LUCA
GeneTreeiENSGT00390000016075
HOGENOMiHOG000241277
HOVERGENiHBG000367
InParanoidiP34949
KOiK01809
OMAiMGTHPSN
OrthoDBiEOG091G078D
PhylomeDBiP34949
TreeFamiTF312831

Enzyme and pathway databases

UniPathwayi
UPA00126;UER00423

ReactomeiR-HSA-4043916 Defective MPI causes MPI-CDG (CDG-1b)
R-HSA-446205 Synthesis of GDP-mannose

Miscellaneous databases

GenomeRNAii4351
PROiPR:P34949
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000178802 Expressed in 193 organ(s), highest expression level in heart left ventricle
CleanExiHS_MPI
ExpressionAtlasiP34949 baseline and differential
GenevisibleiP34949 HS

Family and domain databases

Gene3Di2.60.120.10, 4 hits
InterProiView protein in InterPro
IPR001250 Man6P_Isoase-1
IPR016305 Mannose-6-P_Isomerase
IPR018050 Pmannose_isomerase-type1_CS
IPR014710 RmlC-like_jellyroll
IPR011051 RmlC_Cupin_sf
PANTHERiPTHR10309 PTHR10309, 1 hit
PfamiView protein in Pfam
PF01238 PMI_typeI, 1 hit
PIRSFiPIRSF001480 Mannose-6-phosphate_isomerase, 1 hit
PRINTSiPR00714 MAN6PISMRASE
SUPFAMiSSF51182 SSF51182, 1 hit
TIGRFAMsiTIGR00218 manA, 1 hit
PROSITEiView protein in PROSITE
PS00965 PMI_I_1, 1 hit
PS00966 PMI_I_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiMPI_HUMAN
AccessioniPrimary (citable) accession number: P34949
Secondary accession number(s): A8K8K9, Q96AB0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: January 23, 2007
Last modified: September 12, 2018
This is version 191 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. SIMILARITY comments
    Index of protein domains and families
  3. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  4. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
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