Reviewed, UniProtKB/Swiss-Prot P34949 (MPI_HUMAN)

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	423 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 component	Cytoplasm
Coding sequence diversity	Alternative splicing
Disease	Congenital disorder of glycosylation Disease mutation
Ligand	Metal-binding Zinc
Molecular function	Isomerase
Technical term	Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	carbohydrate metabolic process Inferred from electronic annotation. Source: InterPro
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	mannose-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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed Probable
	Chain	2 – 423	422	Mannose-6-phosphate isomerase		PRO_0000194235
Sites
	Active site	295	1	By similarity
	Metal binding	110	1	Zinc By similarity
	Metal binding	112	1	Zinc By similarity
	Metal binding	137	1	Zinc By similarity
	Metal binding	276	1	Zinc By similarity
Natural variations
	Alternative sequence	163 – 224	62	KVPEF…ISQQA → T in isoform 2.		VSP_013357
	Natural variant	51	1	M → T in CDG1B. Ref.2		VAR_022516
	Natural variant	102	1	S → L in CDG1B. Ref.5		VAR_012338
	Natural variant	129	1	Y → C in CDG1B. Ref.9		VAR_022517
	Natural variant	131	1	D → N in CDG1B. Ref.2		VAR_022518
	Natural variant	138	1	M → T in CDG1B. Ref.5		VAR_012339
	Natural variant	140	1	I → T in CDG1B. Ref.8		VAR_012345
	Natural variant	152	1	R → Q in CDG1B. Ref.2		VAR_022519
	Natural variant	219	1	R → Q in CDG1B. Ref.6 Ref.8		VAR_012340
	Natural variant	250	1	G → S in CDG1B. Ref.2		VAR_022520
	Natural variant	255	1	Y → C in CDG1B. Ref.7		VAR_022521
	Natural variant	295	1	R → H in CDG1B. dbSNP rs28928906. Ref.10		VAR_022522
	Natural variant	398	1	I → T in CDG1B. Ref.7		VAR_022523
	Natural variant	418	1	R → H in CDG1B. Ref.2		VAR_022524

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 23, 2007. Version 2. Checksum: 1612DD966B86D3AC	FASTA	423	46,656
	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
	Isoform 2. Checksum: 58CA9B39BF20C459	FASTA	362	39,834
	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 LKTAAGNNME DIFGELLLQL 190 200 210 220 230 240 HQQYPGDIGC FAIYFLNLLT LKPGEAMFLE ANVPHAYLKG DCVECMACSD NTVRAGLTPK 250 260 270 280 290 300 FIDVPTLCEM LSYTPSSSKD RLFLPTRSQE DPYLSIYDPP VPDFTIMKTE VPGSVTEYKV 310 320 330 340 350 360 LALDSASILL MVQGTVIAST PTTQTPIPLQ RGGVLFIGAN ESVSLKLTEP KDLLIFRACC LL

References

	« Hide 'large scale' referencesShow '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. , 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

GeneReviews

Cross-references

Sequence databases
EMBLGenBankDDBJ	X76057 mRNA. Translation: CAA53657.1. AF227218, AF227216, AF227217 Genomic DNA. Translation: AAF37697.1. BC017351 mRNA. Translation: AAH17351.1. BC046357 mRNA. Translation: AAH46357.1.
IPI	IPI00219358. IPI00332187.
PIR	S41122.
RefSeq	NP_002426.1.
UniGene	Hs.75694
3D structure databases
HSSP	HSSP built from PDB template 1PMI based on UniProtKB P34948.
ModBase	Search...
2-D gel databases
OGP	P34949.
Proteomic databases
PRIDE	P34949.
Genome annotation databases
Ensembl	ENSG00000178802. Homo sapiens. [Contig view]
GeneID	4351.
KEGG	hsa:4351.
NMPDR	fig|9606.3.peg.10994.
UCSC	uc002azc.1. human. uc002aze.1. human.
Organism-specific databases
GeneCards	GC15P072969.
H-InvDB	HIX0018037.
HGNC	HGNC:7216. MPI.
HPA	HPA007200.
MIM	154550. gene. 602579. phenotype.
Orphanet	137. CDG syndrome. 79319. CDG syndrome, type Ib.
PharmGKB	PA30922.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	P34949.
HOVERGEN	P34949.
OMA	P34949. MGSNSEV.
Enzyme and pathway databases
BRENDA	5.3.1.8. 247.
Gene expression databases
ArrayExpress	P34949.
Bgee	P34949.
CleanEx	HS_MPI.
GermOnline	ENSG00000178802. Homo sapiens.
Family and domain databases
InterPro	IPR001250. Man6P_Isoase-1. IPR016305. Mannose-6-P_Isomerase. IPR018050. Pmannose_isomerase-type1_CS. IPR014710. RmlC-like_jellyroll. [Graphical view]
Gene3D	G3DSA:2.60.120.10. RmlC-like_jellyroll. 2 hits.
Pfam	PF01238. PMI_typeI. 1 hit. [Graphical view]
PIRSF	PIRSF001480. Mannose-6-phosphate_isomerase. 1 hit.
PRINTS	PR00714. MAN6PISMRASE.
TIGRFAMs	TIGR00218. manA. 1 hit.
PROSITE	PS00965. PMI_I_1. 1 hit. PS00966. PMI_I_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	17118.
SOURCE	Search...

Entry information

Entry name

MPI_HUMAN

Accession

Primary (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 status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)