[1]	NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS CDG1A. DOI=10.1038/ng0597-88; PubMed=9140401 [NCBI, ExPASy, EBI, Israel, Japan] Matthijs G., Schollen E., Pardon E., Veiga-Da-Cunha M., Jaeken J., Cassiman J.-J., van Schaftingen E.; "Mutations in PMM2, a phosphomannomutase gene on chromosome 16p13, in carbohydrate-deficient glycoprotein type I syndrome (Jaeken syndrome)."; Nat. Genet. 16:88-92(1997).
[2]	ERRATUM. Matthijs G., Schollen E., Pardon E., Veiga-Da-Cunha M., Jaeken J., Cassiman J.-J., van Schaftingen E.; Nat. Genet. 16:316-316(1997).
[3]	NUCLEOTIDE SEQUENCE [GENOMIC DNA]. DOI=10.1093/hmg/7.2.157; PubMed=9425221 [NCBI, ExPASy, EBI, Israel, Japan] Schollen E., Pardon E., Heykants L., Renard J., Doggett N.A., Callen D.F., Cassiman J.J., Matthijs G.; "Comparative analysis of the phosphomannomutase genes PMM1, PMM2 and PMM2psi: the sequence variation in the processed pseudogene is a reflection of the mutations found in the functional gene."; Hum. Mol. Genet. 7:157-164(1998).
[4]	NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. TISSUE=Pancreas; DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan] The MGC Project Team; "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."; Genome Res. 14:2121-2127(2004).
[5]	REVIEW ON VARIANTS CDG1A. DOI=10.1006/mgme.1999.2914; PubMed=10527672 [NCBI, ExPASy, EBI, Israel, Japan] Matthijs G., Schollen E., Heykants L., Gruenewald S.; "Phosphomannomutase deficiency: the molecular basis of the classical Jaeken syndrome (CDGS type Ia)."; Mol. Genet. Metab. 68:220-226(1999).
[6]	VARIANTS CDG1A. DOI=10.1086/301763; PubMed=9497260 [NCBI, ExPASy, EBI, Israel, Japan] Matthijs G., Schollen E., van Schaftingen E., Cassiman J.-J., Jaeken J.; "Lack of homozygotes for the most frequent disease allele in carbohydrate-deficient glycoprotein syndrome type 1A."; Am. J. Hum. Genet. 62:542-550(1998).
[7]	VARIANTS CDG1A ARG-117 AND GLU-223. DOI=10.1038/sj.ejhg.5200194; PubMed=9781039 [NCBI, ExPASy, EBI, Israel, Japan] Kjaergaard S., Skovby F., Schwartz M.; "Absence of homozygosity for predominant mutations in PMM2 in Danish patients with carbohydrate-deficient glycoprotein syndrome type 1."; Eur. J. Hum. Genet. 6:331-336(1998).
[8]	VARIANTS CDG1A LEU-144; SER-229 AND PRO-238. PubMed=10066032 [NCBI, ExPASy, EBI, Israel, Japan] Kondo I., Mizugishi K., Yoneda Y., Hashimoto T., Kuwajima K., Yuasa I., Shigemoto K., Kuroda Y.; "Missense mutations in phosphomannomutase 2 gene in two Japanese families with carbohydrate-deficient glycoprotein syndrome type 1."; Clin. Genet. 55:50-54(1999).
[9]	VARIANT CDG1A GLY-192, AND CHARACTERIZATION OF VARIANTS CDG1A ARG-117; LEU-119; HIS-141; GLY-192; GLU-223 AND ARG-237. DOI=10.1038/sj.ejhg.5200398; PubMed=10602363 [NCBI, ExPASy, EBI, Israel, Japan] Kjaergaard S., Skovby F., Schwartz M.; "Carbohydrate-deficient glycoprotein syndrome type 1A: expression and characterisation of wild type and mutant PMM2 in E. coli."; Eur. J. Hum. Genet. 7:884-888(1999).
[10]	VARIANTS CDG1A LYS-139 AND HIS-141. DOI=10.1002/(SICI)1098-1004(199912)14:6<543::AID-HUMU17>3.3.CO;2-J; PubMed=10571956 [NCBI, ExPASy, EBI, Israel, Japan] Vuillaumier-Barrot S., Barnier A., Cuer M., Durand G., Grandchamp B., Seta N.; "Characterization of the 415G>A (E139K) PMM2 mutation in carbohydrate-deficient glycoprotein syndrome type Ia disrupting a splicing enhancer resulting in exon 5 skipping."; Hum. Mutat. 14:543-544(1999).
[11]	VARIANTS CDG1A TYR-9; CYS-11; ARG-32; ALA-44; TYR-65; MET-67; SER-69; CYS-76; LYS-101; PHE-103; CYS-106; VAL-108; LEU-113; ARG-117; LEU-119; THR-120; GLN-123; MET-129; ALA-131; ASN-132; THR-132; LYS-139; HIS-141; ASN-148; GLY-151; THR-153; SER-157; TRP-162; VAL-172; ARG-175; SER-183; GLY-185; GLY-188; GLY-192; ARG-195; ALA-197; SER-206; ALA-208; ILE-216; SER-216; GLU-217; LEU-218; GLU-223; SER-226; ARG-228; CYS-228; SER-229; MET-231; THR-233; ARG-237; MET-237; GLY-238 AND SER-241. DOI=10.1002/1098-1004(200011)16:5<386::AID-HUMU2>3.0.CO;2-Y; PubMed=11058895 [NCBI, ExPASy, EBI, Israel, Japan] Matthijs G., Schollen E., Bjursell C., Erlandson A., Freeze H., Imtiaz F., Kjaergaard S., Martinsson T., Schwartz M., Seta N., Vuillaumier-Barrot S., Westphal V., Winchester B.; "Mutations in PMM2 that cause congenital disorders of glycosylation, type Ia (CDG-Ia)."; Hum. Mutat. 16:386-394(2000).
[12]	VARIANTS CDG1A TYR-9; CYS-11; MET-67; LEU-113; ARG-117; LEU-119; GLN-123; MET-129; HIS-141; VAL-172; ARG-175; SER-183; GLY-185; GLY-192; SER-216; GLU-217; GLU-223; ARG-228; MET-231 AND ARG-237. DOI=10.1002/1098-1004(200011)16:5<395::AID-HUMU3>3.3.CO;2-K; PubMed=11058896 [NCBI, ExPASy, EBI, Israel, Japan] Bjursell C., Erlandson A., Nordling M., Nilsson S., Wahlstroem J., Stibler H., Kristiansson B., Martinsson T.; "PMM2 mutation spectrum, including 10 novel mutations, in a large CDG type 1A family material with a focus on Scandinavian families."; Hum. Mutat. 16:395-400(2000).
[13]	VARIANTS CDG1A LEU-119; ASN-132; HIS-141; ASN-148; SER-183; ALA-208; MET-231 AND MET-237. DOI=10.1023/A:1005669900330; PubMed=10801058 [NCBI, ExPASy, EBI, Israel, Japan] Imtiaz F., Worthington V., Champion M., Beesley C., Charlwood J., Clayton P., Keir G., Mian N., Winchester B.; "Genotypes and phenotypes of patients in the UK with carbohydrate-deficient glycoprotein syndrome type 1."; J. Inherit. Metab. Dis. 23:162-174(2000).
[14]	VARIANT CDG1A VAL-104. DOI=10.1006/mgme.2001.3174; PubMed=11350185 [NCBI, ExPASy, EBI, Israel, Japan] Westphal V., Enns G.M., McCracken M.F., Freeze H.H.; "Functional analysis of novel mutations in a congenital disorder of glycosylation Ia patient with mixed Asian ancestry."; Mol. Genet. Metab. 73:71-76(2001).
[15]	VARIANTS CDG1A GLU-15; CYS-64; ALA-93; SER-214 AND ASN-223, AND VARIANT ARG-42. DOI=10.1038/sj.ejhg.5200858; PubMed=12357336 [NCBI, ExPASy, EBI, Israel, Japan] Schollen E., Martens K., Geuzens E., Matthijs G.; "DHPLC analysis as a platform for molecular diagnosis of congenital disorders of glycosylation (CDG)."; Eur. J. Hum. Genet. 10:643-648(2002).
[16]	VARIANTS CDG1A TYR-9; SER-20; ARG-32; HIS-37; LEU-44; TYR-65; SER-69; PHE-103; VAL-108; LEU-113; LEU-119; GLN-123; MET-129; ALA-131; THR-132; PHE-132; LYS-139; CYS-141; HIS-141; THR-153; SER-157; TRP-162; VAL-176; HIS-177; ALA-197; SER-214; SER-226; MET-231; ARG-237; MET-237 AND SER-241, VARIANT ARG-42, AND CHARACTERIZATION OF VARIANTS CDG1A SER-20; HIS-37; PHE-132; LYS-139; CYS-141; HIS-141; VAL-176 AND HIS-177. DOI=10.1002/humu.9336; PubMed=15844218 [NCBI, ExPASy, EBI, Israel, Japan] Le Bizec C., Vuillaumier-Barrot S., Barnier A., Dupre T., Durand G., Seta N.; "A new insight into PMM2 mutations in the French population."; Hum. Mutat. 25:504-505(2005).
[17]	VARIANTS CDG1A ALA-44 AND MET-231. DOI=10.1016/j.ymgme.2007.01.003; PubMed=17307006 [NCBI, ExPASy, EBI, Israel, Japan] Schollen E., Keldermans L., Foulquier F., Briones P., Chabas A., Sanchez-Valverde F., Adamowicz M., Pronicka E., Wevers R., Matthijs G.; "Characterization of two unusual truncating PMM2 mutations in two CDG-Ia patients."; Mol. Genet. Metab. 90:408-413(2007).

Comments

FUNCTION: Involved in the synthesis of the GDP-mannose and dolichol-phosphate-mannose required for a number of critical mannosyl transfer reactions (By similarity).
CATALYTIC ACTIVITY: Alpha-D-mannose 1-phosphate = D-mannose 6-phosphate.
PATHWAY: Protein modification; protein glycosylation .
SUBCELLULAR LOCATION: Cytoplasm.
DISEASE: Defects in PMM2 are the cause of congenital disorder of glycosylation type 1A (CDG1A) [MIM:212065]; also known as carbohydrate-deficient glycoprotein syndrome type Ia (CDGS1A) or Jaeken syndrome. 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. CDG1A is an autosomal recessive disorder characterized by a severe encephalopathy with axial hypotonia, abnormal eye movement, and pronounced psychomotor retardation, as well as peripheral neuropathy, cerebellar hypoplasia, and retinitis pigmentosa. Patients show a peculiar distribution of subcutaneous fat, nipple retraction, and hypogonadism.
SIMILARITY: Belongs to the eukaryotic PMM family.
WEB RESOURCE: Name=GeneReviews; URL="http://www.genetests.org/query?gene=PMM2";.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

U85773; AAC51368.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF157796; AAD45895.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF157790; AAD45895.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF157791; AAD45895.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF157792; AAD45895.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF157793; AAD45895.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF157794; AAD45895.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF157795; AAD45895.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BC008310; AAH08310.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

RefSeq

NP_000294.1; -.

UniGene

Hs.659263

3D structure databases

PDB

2AMY; X-ray; 2.09 A; A=2-246.	[ExPASy / RCSB / EBI]
2Q4R; X-ray; 2.09 A; A=2-246.	[ExPASy / RCSB / EBI]

Detailed list of linked structures.

2AMY; -.
2Q4R; -.

PTM databases

O15305; -.

Organism-specific databases

HIX0012808; -.

HGNC:9115; PMM2.

212065; phenotype. [NCBI / EBI]
601785; gene. [NCBI / EBI]

Orphanet

137; CDG syndrome.
79318; CDG syndrome type Ia.
102; Multiple system atrophy.

PharmGKB

PA33441; -.

GeneCards

O15305.

Gene expression databases

ArrayExpress

O15305; -.

CleanEx

HS_PMM2; -.

GermOnline

ENSG00000140650; Homo sapiens.

Ontologies

GO:0004615;	Molecular function: phosphomannomutase activity (traceable author statement from ProtInc).
GO:0009298;	Biological process: GDP-mannose biosynthetic process (traceable author statement from ProtInc).
GO:0006486;	Biological process: protein amino acid glycosylation (traceable author statement from ProtInc).
QuickGo view.

Family and domain databases

InterPro

IPR006379; HAD-SF_hydro_IIB.
IPR005002; PMM.
Graphical view of domain structure.

PANTHER

PTHR10466; PMM; 1.

Pfam

PF03332; PMM; 1.
Pfam graphical view of domain structure.

TIGRFAMs

TIGR01484; HAD-SF-IIB; 1.

BLOCKS

O15305.

Proteomic databases

PeptideAtlas

O15305; -.

Genome annotation databases

Ensembl

ENSG00000140650; Homo sapiens. [Contig view]

GeneID

5373; -.

KEGG

hsa:5373; -.

NMPDR

fig|9606.3.peg.11694; -.

Phylogenomic databases

HOGENOM

O15305; -.

HOVERGEN

O15305; -.

Other

O15305; -.

PMM2; Homo sapiens.

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

3D-structure; Congenital disorder of glycosylation; Cytoplasm; Disease mutation; Isomerase; Polymorphism.

Features

Feature table viewer

`Key`	`From To`	`Length`	`Description`	`FTId`
`CHAIN`	`1 246`	`246`	`Phosphomannomutase 2.`	`PRO_0000199694`
`VARIANT`	`9 9`	`1`	`C -> Y (in CDG1A).`	`VAR_022469 [3D]`
`VARIANT`	`11 11`	`1`	`F -> C (in CDG1A).`	`VAR_022470 [3D]`
`VARIANT`	`15 15`	`1`	`G -> E (in CDG1A).`	`VAR_022471 [3D]`
`VARIANT`	`20 20`	`1`	`P -> S (in CDG1A; reduction of activity).`	`VAR_022472 [3D]`
`VARIANT`	`32 32`	`1`	`L -> R (in CDG1A).`	`VAR_022473 [3D]`
`VARIANT`	`37 37`	`1`	`Q -> H (in CDG1A; partial loss of activity).`	`VAR_022474 [3D]`
`VARIANT`	`37 37`	`1`	`Q -> L (in dbSNP:rs2304472 [NCBI]).`	`VAR_022133 [3D]`
`VARIANT`	`42 42`	`1`	`G -> R.`	`VAR_022475 [3D]`
`VARIANT`	`44 44`	`1`	`V -> A (in CDG1A).`	`VAR_006093 [3D]`
`VARIANT`	`44 44`	`1`	`V -> L (in CDG1A).`	`VAR_022563 [3D]`
`VARIANT`	`64 64`	`1`	`Y -> C (in CDG1A).`	`VAR_022476 [3D]`
`VARIANT`	`65 65`	`1`	`D -> Y (in CDG1A).`	`VAR_006094 [3D]`
`VARIANT`	`67 67`	`1`	`V -> M (in CDG1A).`	`VAR_022477 [3D]`
`VARIANT`	`69 69`	`1`	`P -> S (in CDG1A).`	`VAR_022478 [3D]`
`VARIANT`	`76 76`	`1`	`Y -> C (in CDG1A).`	`VAR_022479 [3D]`
`VARIANT`	`93 93`	`1`	`E -> A (in CDG1A).`	`VAR_022480 [3D]`
`VARIANT`	`101 101`	`1`	`N -> K (in CDG1A).`	`VAR_006095 [3D]`
`VARIANT`	`103 103`	`1`	`C -> F (in CDG1A).`	`VAR_022481 [3D]`
`VARIANT`	`104 104`	`1`	`L -> V (in CDG1A).`	`VAR_012344 [3D]`
`VARIANT`	`106 106`	`1`	`Y -> C (in CDG1A).`	`VAR_006096 [3D]`
`VARIANT`	`108 108`	`1`	`A -> V (in CDG1A).`	`VAR_006097 [3D]`
`VARIANT`	`113 113`	`1`	`P -> L (in CDG1A).`	`VAR_006098 [3D]`
`VARIANT`	`117 117`	`1`	`G -> R (in CDG1A; loss of activity).`	`VAR_006099 [3D]`
`VARIANT`	`119 119`	`1`	`F -> L (in CDG1A; partial loss of activity).`	`VAR_006100 [3D]`
`VARIANT`	`120 120`	`1`	`I -> T (in CDG1A).`	`VAR_022482 [3D]`
`VARIANT`	`123 123`	`1`	`R -> Q (in CDG1A).`	`VAR_006101 [3D]`
`VARIANT`	`129 129`	`1`	`V -> M (in CDG1A).`	`VAR_006102 [3D]`
`VARIANT`	`131 131`	`1`	`P -> A (in CDG1A).`	`VAR_006103 [3D]`
`VARIANT`	`132 132`	`1`	`I -> F (in CDG1A; slightly reduced activity).`	`VAR_022483 [3D]`
`VARIANT`	`132 132`	`1`	`I -> N (in CDG1A).`	`VAR_022484 [3D]`
`VARIANT`	`132 132`	`1`	`I -> T (in CDG1A).`	`VAR_006104 [3D]`
`VARIANT`	`139 139`	`1`	`E -> K (in CDG1A; this mutation seems to disrupt a splicing enhancer sequence and thus results in most cases in a protein with exon 5 skipped; slightly reduced activity).`	`VAR_009232 [3D]`
`VARIANT`	`141 141`	`1`	`R -> C (in CDG1A; loss of activity).`	`VAR_022485 [3D]`
`VARIANT`	`141 141`	`1`	`R -> H (in CDG1A; frequent mutation; loss of activity; observed in heterozygous patients; homozygosis of this mutation is incompatible with life).`	`VAR_006105 [3D]`
`VARIANT`	`144 144`	`1`	`F -> L (in CDG1A).`	`VAR_022486 [3D]`
`VARIANT`	`148 148`	`1`	`D -> N (in CDG1A).`	`VAR_022487 [3D]`
`VARIANT`	`151 151`	`1`	`E -> G (in CDG1A).`	`VAR_022488 [3D]`
`VARIANT`	`153 153`	`1`	`I -> T (in CDG1A).`	`VAR_022489 [3D]`
`VARIANT`	`157 157`	`1`	`F -> S (in CDG1A).`	`VAR_022490 [3D]`
`VARIANT`	`162 162`	`1`	`R -> W (in CDG1A).`	`VAR_006106 [3D]`
`VARIANT`	`172 172`	`1`	`F -> V (in CDG1A).`	`VAR_022491 [3D]`
`VARIANT`	`175 175`	`1`	`G -> R (in CDG1A).`	`VAR_006107 [3D]`
`VARIANT`	`176 176`	`1`	`G -> V (in CDG1A; loss of activity).`	`VAR_022492 [3D]`
`VARIANT`	`177 177`	`1`	`Q -> H (in CDG1A; partial loss of activity).`	`VAR_022493 [3D]`
`VARIANT`	`183 183`	`1`	`F -> S (in CDG1A).`	`VAR_022494 [3D]`
`VARIANT`	`185 185`	`1`	`D -> G (in CDG1A).`	`VAR_022495 [3D]`
`VARIANT`	`188 188`	`1`	`D -> G (in CDG1A; severe).`	`VAR_006108 [3D]`
`VARIANT`	`192 192`	`1`	`C -> G (in CDG1A; normal activity but lower affinity for alpha-D-mannose 1-phosphate).`	`VAR_022496 [3D]`
`VARIANT`	`195 195`	`1`	`H -> R (in CDG1A).`	`VAR_022497 [3D]`
`VARIANT`	`197 197`	`1`	`E -> A (in CDG1A; dbSNP:rs34258285 [NCBI]).`	`VAR_022498 [3D]`
`VARIANT`	`206 206`	`1`	`F -> S (in CDG1A).`	`VAR_022499 [3D]`
`VARIANT`	`208 208`	`1`	`G -> A (in CDG1A).`	`VAR_006109 [3D]`
`VARIANT`	`212 212`	`1`	`M -> V (in dbSNP:rs3743808 [NCBI]).`	`VAR_022134 [3D]`
`VARIANT`	`214 214`	`1`	`G -> S (in CDG1A).`	`VAR_022500 [3D]`
`VARIANT`	`216 216`	`1`	`N -> I (in CDG1A).`	`VAR_006110 [3D]`
`VARIANT`	`216 216`	`1`	`N -> S (in CDG1A).`	`VAR_022501 [3D]`
`VARIANT`	`217 217`	`1`	`D -> E (in CDG1A).`	`VAR_022502 [3D]`
`VARIANT`	`218 218`	`1`	`H -> L (in CDG1A).`	`VAR_022503 [3D]`
`VARIANT`	`223 223`	`1`	`D -> E (in CDG1A; normal activity but lower affinity for alpha-D-mannose 1-phosphate).`	`VAR_006111 [3D]`
`VARIANT`	`223 223`	`1`	`D -> N (in CDG1A).`	`VAR_022504 [3D]`
`VARIANT`	`226 226`	`1`	`T -> S (in CDG1A).`	`VAR_022505 [3D]`
`VARIANT`	`228 228`	`1`	`G -> C (in CDG1A).`	`VAR_022506 [3D]`
`VARIANT`	`228 228`	`1`	`G -> R (in CDG1A).`	`VAR_022507 [3D]`
`VARIANT`	`229 229`	`1`	`Y -> S (in CDG1A).`	`VAR_006112 [3D]`
`VARIANT`	`231 231`	`1`	`V -> M (in CDG1A).`	`VAR_006113 [3D]`
`VARIANT`	`233 233`	`1`	`A -> T (in CDG1A; could be a rare polymorphism).`	`VAR_006114 [3D]`
`VARIANT`	`237 237`	`1`	`T -> M (in CDG1A).`	`VAR_006115 [3D]`
`VARIANT`	`237 237`	`1`	`T -> R (in CDG1A; loss of activity).`	`VAR_022508 [3D]`
`VARIANT`	`238 238`	`1`	`R -> G (in CDG1A).`	`VAR_022509 [3D]`
`VARIANT`	`238 238`	`1`	`R -> P (in CDG1A).`	`VAR_006116 [3D]`
`VARIANT`	`241 241`	`1`	`C -> S (in CDG1A).`	`VAR_022510 [3D]`
`STRAND`	`6 14`	`9`
`TURN`	`15 17`	`3`
`HELIX`	`26 35`	`10`
`TURN`	`36 38`	`3`
`STRAND`	`39 44`	`6`
`HELIX`	`49 56`	`8`
`HELIX`	`60 63`	`4`
`STRAND`	`65 69`	`5`
`HELIX`	`70 72`	`3`
`STRAND`	`74 77`	`4`
`STRAND`	`80 84`	`5`
`HELIX`	`87 91`	`5`
`HELIX`	`93 109`	`17`
`STRAND`	`119 123`	`5`
`STRAND`	`126 129`	`4`
`HELIX`	`138 151`	`14`
`HELIX`	`153 164`	`12`