Q9Y223 (GLCNE_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Bifunctional UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase

Alternative name(s):
UDP-GlcNAc-2-epimerase/ManAc kinase

Including the following 2 domains:

1. UDP-N-acetylglucosamine 2-epimerase
   EC=5.1.3.14
   Alternative name(s):
   UDP-GlcNAc-2-epimerase
   Uridine diphosphate-N-acetylglucosamine-2-epimerase
2. N-acetylmannosamine kinase
   EC=2.7.1.60
   Alternative name(s):
   ManAc kinase

Gene names

Name:	GNE
Synonyms:	GLCNE

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	722 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Regulates and initiates biosynthesis of N-acetylneuraminic acid (NeuAc), a precursor of sialic acids. Plays an essential role in early development By similarity. Required for normal sialylation in hematopoietic cells. Sialylation is implicated in cell adhesion, signal transduction, tumorigenicity and metastatic behavior of malignant cells. Ref.11
Catalytic activity	UDP-N-acetyl-D-glucosamine = UDP-N-acetyl-D-mannosamine. ATP + N-acyl-D-mannosamine = ADP + N-acyl-D-mannosamine 6-phosphate.
Enzyme regulation	Allosterically regulated Probable; feedback inhibited by cytidine monophosphate-N-acetylneuraminic acid (CMP-Neu5Ac), the end product of neuraminic acid biosynthesis. Activity is dependent on oligomerization. The monomer is inactive, whereas the dimer catalyzes only the phosphorylation of N-acetylmannosamine; the hexamer is fully active for both enzyme activities By similarity. Up-regulated after PKC-dependent phosphorylation. Ref.10
Pathway	Amino-sugar metabolism; N-acetylneuraminate biosynthesis.
Subunit structure	Homodimer and homohexamer. Ref.13
Subcellular location	Cytoplasm By similarity.
Tissue specificity	Highest expression in liver and placenta. Also found in heart, brain, lung, kidney, skeletal muscle and pancreas. Isoform 1 is expressed in heart, brain, kidney, liver, placenta, lung, spleen, pancreas, skeletal muscle and colon. Isoform 2 is expressed mainly in placenta, but also in brain, kidney, liver, lung, pancreas and colon. Isoform 3 is expressed at low level in kidney, liver, placenta and colon. Ref.1 Ref.2 Ref.6
Post-translational modification	Phosphorylated by PKC By similarity.
Involvement in disease	Defects in GNE are a cause of sialuria (SIALURIA) [MIM:269921]; also known as sialuria French type. In sialuria, free sialic acid accumulates in the cytoplasm and gram quantities of neuraminic acid are secreted in the urine. The metabolic defect involves lack of feedback inhibition of UDP-GlcNAc 2-epimerase by CMP-Neu5Ac, resulting in constitutive overproduction of free Neu5Ac. Clinical features include variable degrees of developmental delay, coarse facial features and hepatomegaly. Sialuria inheritance is autosomal dominant. Ref.2 Ref.10 Ref.14 Ref.15 Defects in GNE are the cause of inclusion body myopathy type 2 (IBM2) [MIM:600737]. Hereditary inclusion body myopathies are a group of neuromuscular disorders characterized by adult onset, slowly progressive distal and proximal weakness and a typical muscle pathology including rimmed vacuoles and filamentous inclusions. IBM2 is an autosomal recessive disorder affecting mainly leg muscles, but with an unusual distribution that spares the quadriceps as also observed in Nonaka myopathy. Ref.16 Ref.19 Ref.22 Ref.23 Ref.24 Ref.25 Ref.27 Defects in GNE are the cause of Nonaka myopathy (NM) [MIM:605820]; also known as distal myopathy with rimmed vacuoles (DMRV). NM is an autosomal recessive muscular disorder, allelic to inclusion body myopathy 2. It is characterized by weakness of the anterior compartment of the lower limbs with onset in early adulthood, and sparing of the quadriceps muscles. As the inclusion body myopathy, NM is histologically characterized by the presence of numerous rimmed vacuoles without inflammatory changes in muscle specimens. Ref.17 Ref.18 Ref.20 Ref.21 Ref.26
Sequence similarities	In the N-terminal section; belongs to the UDP-N-acetylglucosamine 2-epimerase family. In the C-terminal section; belongs to the ROK (nagC/xylR) family.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing
Disease	Disease mutation
Ligand	ATP-binding Nucleotide-binding
Molecular function	Isomerase Kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Allosteric enzyme Complete proteome Multifunctional enzyme Reference proteome
Gene Ontology (GO)
Biological process	N-acetylneuraminate metabolic process Traceable author statement. Source: ProtInc UDP-N-acetylglucosamine metabolic process Inferred from electronic annotation. Source: InterPro cell adhesion Traceable author statement. Source: ProtInc lipopolysaccharide biosynthetic process Inferred from electronic annotation. Source: InterPro
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW N-acylmannosamine kinase activity Traceable author statement. Source: ProtInc UDP-N-acetylglucosamine 2-epimerase activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9Y223-1)

Also known as: GNE1;

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: Q9Y223-2)

Also known as: GNE2;

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → METYGYLQRESCFQGPHELYFKNLSKRNKQIM

Isoform 3 (identifier: Q9Y223-3)

Also known as: GNE3;

The sequence of this isoform differs from the canonical sequence as follows:
     1-55: MEKNGNNRKLRVCVATCNRADYSKLAPIMFGIKTEPEFFELDVVVLGSHLIDDYG → MVICRGSHAFKDLI

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 722

722

Bifunctional UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase

PRO_0000095716

Regions

Nucleotide binding

411 – 418

8

ATP Potential

Nucleotide binding

545 – 552

8

ATP Potential

Region

1 – ?

UDP-N-acetylglucosamine 2-epimerase

Region

406 – 722

317

N-acetylmannosamine kinase

Natural variations

Alternative sequence

1 – 55

55

MEKNG…IDDYG → MVICRGSHAFKDLI in isoform 3.

VSP_041028

Alternative sequence

1

1

M → METYGYLQRESCFQGPHELY FKNLSKRNKQIM in isoform 2.

VSP_041027

Natural variant

27

1

P → S in IBM2. Ref.27

VAR_021771

Natural variant

36

1

P → L in IBM2. Ref.24

VAR_017945

Natural variant

132

1

H → Q in NM. Ref.21

VAR_021772

Natural variant

162

1

R → C in IBM2. Ref.25

VAR_021773

Natural variant

171

1

M → V in IBM2. Ref.23

VAR_021774

Natural variant

176

1

D → V in NM. Ref.21

VAR_021775

Natural variant

177

1

R → C in NM. Ref.21

VAR_021776

Natural variant

200

1

I → F in IBM2. Ref.24

VAR_017946

Natural variant

206

1

G → S in IBM2; moderate phenotype with unusual involvement of quadriceps. Ref.27

VAR_021777

Natural variant

216

1

V → A in IBM2. Ref.22

VAR_021778

Natural variant

225

1

D → N in IBM2. Ref.16 Ref.19 Ref.24

VAR_017947

Natural variant

246

1

R → Q in IBM2. Ref.16 Ref.19 Ref.24 Ref.27

VAR_017948

Natural variant

246

1

R → W in IBM2. Ref.19

VAR_017949

Natural variant

263

1

R → L in SIALURIA; strong reduction of feedback inhibition by CMP-Neu5Ac. Ref.2

VAR_017950

Natural variant

266

1

R → Q in SIALURIA; abolishes feedback inhibition by CMP-Neu5Ac. Ref.2 Ref.14 Ref.15

VAR_017951

Natural variant

266

1

R → W in sialuria. Ref.2

VAR_017952

Natural variant

303

1

C → V in IBM2; requires 2 nucleotide substitutions. Ref.24

VAR_017953

Natural variant

306

1

R → Q in NM. Ref.21

VAR_021779

Natural variant

331

1

V → A in NM. Ref.21

VAR_021780

Natural variant

378

1

D → Y in IBM2 and NM. Ref.21 Ref.24

VAR_017954

Natural variant

460

1

A → V in NM and IBM2. Ref.18 Ref.19 Ref.24

VAR_017955

Natural variant

472

1

I → T in NM. Ref.21 Ref.26

VAR_021781

Natural variant

519

1

N → S in IBM2. Ref.27

VAR_021782

Natural variant

524

1

A → V in IBM2. Ref.19

VAR_017956

Natural variant

528

1

F → C in IBM2. Ref.24

VAR_017957

Natural variant

557

1

I → T in IBM2. Ref.24

VAR_017958

Natural variant

572

1

V → L in NM and IBM2. Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.24 Ref.26

VAR_017959

Natural variant

576

1

G → E in IBM2. Ref.16 Ref.19 Ref.24

VAR_017960

Natural variant

587

1

I → T in IBM2. Ref.24

VAR_017961

Natural variant

600

1

A → T in IBM2. Ref.27

VAR_021783

Natural variant

630

1

A → T in NM. Ref.21

VAR_021784

Natural variant

631

1

A → T in IBM2. Ref.16 Ref.19 Ref.24

VAR_017962

Natural variant

631

1

A → V in NM and IBM2. Ref.20 Ref.21 Ref.22 Ref.24

VAR_017963

Natural variant

675

1

Y → H in IBM2. Ref.19

VAR_017964

Natural variant

696

1

V → M in IBM2. Ref.16 Ref.19 Ref.24

VAR_017965

Natural variant

712

1

M → T in IBM2. Ref.16 Ref.19 Ref.23 Ref.24
Corresponds to variant rs28937594 [ dbSNP | Ensembl ].

VAR_017966

Secondary structure

1

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722

Helix Strand Turn

Details...

Beta strand

408 – 413

6

Beta strand

418 – 425

8

Beta strand

430 – 437

8

Helix

442 – 462

21

Helix

501 – 508

8

Helix

520 – 528

9

Beta strand

536 – 542

7

Helix

587 – 591

5

Helix

595 – 605

11

Helix

625 – 632

8

Helix

636 – 644

9

Helix

654 – 660

7

Beta strand

663 – 668

6

Helix

672 – 686

15

Helix

689 – 691

3

Beta strand

695 – 698

4

Turn

704 – 706

3

Helix

710 – 716

7

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (GNE1) [UniParc]. Last modified November 1, 1999. Version 1. Checksum: 4D7D049B06B00077	FASTA	722	79,275
	10 20 30 40 50 60 MEKNGNNRKL RVCVATCNRA DYSKLAPIMF GIKTEPEFFE LDVVVLGSHL IDDYGNTYRM 70 80 90 100 110 120 IEQDDFDINT RLHTIVRGED EAAMVESVGL ALVKLPDVLN RLKPDIMIVH GDRFDALALA 130 140 150 160 170 180 TSAALMNIRI LHIEGGEVSG TIDDSIRHAI TKLAHYHVCC TRSAEQHLIS MCEDHDRILL 190 200 210 220 230 240 AGCPSYDKLL SAKNKDYMSI IRMWLGDDVK SKDYIVALQH PVTTDIKHSI KMFELTLDAL 250 260 270 280 290 300 ISFNKRTLVL FPNIDAGSKE MVRVMRKKGI EHHPNFRAVK HVPFDQFIQL VAHAGCMIGN 310 320 330 340 350 360 SSCGVREVGA FGTPVINLGT RQIGRETGEN VLHVRDADTQ DKILQALHLQ FGKQYPCSKI 370 380 390 400 410 420 YGDGNAVPRI LKFLKSIDLQ EPLQKKFCFP PVKENISQDI DHILETLSAL AVDLGGTNLR 430 440 450 460 470 480 VAIVSMKGEI VKKYTQFNPK TYEERINLIL QMCVEAAAEA VKLNCRILGV GISTGGRVNP 490 500 510 520 530 540 REGIVLHSTK LIQEWNSVDL RTPLSDTLHL PVWVDNDGNC AALAERKFGQ GKGLENFVTL 550 560 570 580 590 600 ITGTGIGGGI IHQHELIHGS SFCAAELGHL VVSLDGPDCS CGSHGCIEAY ASGMALQREA 610 620 630 640 650 660 KKLHDEDLLL VEGMSVPKDE AVGALHLIQA AKLGNAKAQS ILRTAGTALG LGVVNILHTM 670 680 690 700 710 720 NPSLVILSGV LASHYIHIVK DVIRQQALSS VQDVDVVVSD LVDPALLGAA SMVLDYTTRR IY
	Isoform 2 (GNE2) [UniParc]. Checksum: 034C9CEFB1A403DC	FASTA	753	83,066
	10 20 30 40 50 60 METYGYLQRE SCFQGPHELY FKNLSKRNKQ IMEKNGNNRK LRVCVATCNR ADYSKLAPIM 70 80 90 100 110 120 FGIKTEPEFF ELDVVVLGSH LIDDYGNTYR MIEQDDFDIN TRLHTIVRGE DEAAMVESVG 130 140 150 160 170 180 LALVKLPDVL NRLKPDIMIV HGDRFDALAL ATSAALMNIR ILHIEGGEVS GTIDDSIRHA 190 200 210 220 230 240 ITKLAHYHVC CTRSAEQHLI SMCEDHDRIL LAGCPSYDKL LSAKNKDYMS IIRMWLGDDV 250 260 270 280 290 300 KSKDYIVALQ HPVTTDIKHS IKMFELTLDA LISFNKRTLV LFPNIDAGSK EMVRVMRKKG 310 320 330 340 350 360 IEHHPNFRAV KHVPFDQFIQ LVAHAGCMIG NSSCGVREVG AFGTPVINLG TRQIGRETGE 370 380 390 400 410 420 NVLHVRDADT QDKILQALHL QFGKQYPCSK IYGDGNAVPR ILKFLKSIDL QEPLQKKFCF 430 440 450 460 470 480 PPVKENISQD IDHILETLSA LAVDLGGTNL RVAIVSMKGE IVKKYTQFNP KTYEERINLI 490 500 510 520 530 540 LQMCVEAAAE AVKLNCRILG VGISTGGRVN PREGIVLHST KLIQEWNSVD LRTPLSDTLH 550 560 570 580 590 600 LPVWVDNDGN CAALAERKFG QGKGLENFVT LITGTGIGGG IIHQHELIHG SSFCAAELGH 610 620 630 640 650 660 LVVSLDGPDC SCGSHGCIEA YASGMALQRE AKKLHDEDLL LVEGMSVPKD EAVGALHLIQ 670 680 690 700 710 720 AAKLGNAKAQ SILRTAGTAL GLGVVNILHT MNPSLVILSG VLASHYIHIV KDVIRQQALS 730 740 750 SVQDVDVVVS DLVDPALLGA ASMVLDYTTR RIY
	Isoform 3 (GNE3) [UniParc]. Checksum: 567EE37FEC342E81	FASTA	681	74,645
	10 20 30 40 50 60 MVICRGSHAF KDLINTYRMI EQDDFDINTR LHTIVRGEDE AAMVESVGLA LVKLPDVLNR 70 80 90 100 110 120 LKPDIMIVHG DRFDALALAT SAALMNIRIL HIEGGEVSGT IDDSIRHAIT KLAHYHVCCT 130 140 150 160 170 180 RSAEQHLISM CEDHDRILLA GCPSYDKLLS AKNKDYMSII RMWLGDDVKS KDYIVALQHP 190 200 210 220 230 240 VTTDIKHSIK MFELTLDALI SFNKRTLVLF PNIDAGSKEM VRVMRKKGIE HHPNFRAVKH 250 260 270 280 290 300 VPFDQFIQLV AHAGCMIGNS SCGVREVGAF GTPVINLGTR QIGRETGENV LHVRDADTQD 310 320 330 340 350 360 KILQALHLQF GKQYPCSKIY GDGNAVPRIL KFLKSIDLQE PLQKKFCFPP VKENISQDID 370 380 390 400 410 420 HILETLSALA VDLGGTNLRV AIVSMKGEIV KKYTQFNPKT YEERINLILQ MCVEAAAEAV 430 440 450 460 470 480 KLNCRILGVG ISTGGRVNPR EGIVLHSTKL IQEWNSVDLR TPLSDTLHLP VWVDNDGNCA 490 500 510 520 530 540 ALAERKFGQG KGLENFVTLI TGTGIGGGII HQHELIHGSS FCAAELGHLV VSLDGPDCSC 550 560 570 580 590 600 GSHGCIEAYA SGMALQREAK KLHDEDLLLV EGMSVPKDEA VGALHLIQAA KLGNAKAQSI 610 620 630 640 650 660 LRTAGTALGL GVVNILHTMN PSLVILSGVL ASHYIHIVKD VIRQQALSSV QDVDVVVSDL 670 680 VDPALLGAAS MVLDYTTRRI Y

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Primary structure and expression analysis of human UDP-N-acetyl-glucosamine-2-epimerase/N-acetylmannosamine kinase, the bifunctional enzyme in neuraminic acid biosynthesis." Lucka L., Krause M., Danker K., Reutter W., Horstkorte R. FEBS Lett. 454:341-344(1999) [PubMed: 10431835] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY. Tissue: Liver.
[2]	"Mutations in the human UDP-N-acetylglucosamine 2-epimerase gene define the disease sialuria and the allosteric site of the enzyme." Seppala R., Lehto V.-P., Gahl W.A. Am. J. Hum. Genet. 64:1563-1569(1999) [PubMed: 10330343] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, VARIANTS SIALURIA LEU-263; GLN-266 AND TRP-266.
[3]	Wang S.S., Ryll T. Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Small intestine.
[4]	"Organization of the human UDP-N-acetylglucosamine 2-epimerase gene and characterization of a related pseudogene; relevance for mutation detection in patients with sialuria." Huizing M., Anikster Y., Gahl W.A. Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
[5]	"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. , 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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Tongue.
[6]	"Prediction of three different isoforms of the human UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase." Reinke S.O., Hinderlich S. FEBS Lett. 581:3327-3331(2007) [PubMed: 17597614] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3), TISSUE SPECIFICITY.
[7]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed: 15164053] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	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. , 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].
[9]	"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] (ISOFORM 1).
[10]	"Identification of the metabolic defect in sialuria." Weiss P., Tietze F., Gahl W.A., Seppala R., Ashwell G. J. Biol. Chem. 264:17635-17636(1989) [PubMed: 2808337] [Abstract] Cited for: ENZYME REGULATION, INVOLVEMENT IN SIALURIA.
[11]	"UDP-GlcNAc 2-epimerase: a regulator of cell surface sialylation." Keppler O.T., Hinderlich S., Langner J., Schwartz-Albiez R., Reutter W., Pawlita M. Science 284:1372-1376(1999) [PubMed: 10334995] [Abstract] Cited for: FUNCTION.
[12]	"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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]	"Crystal structure of the N-acetylmannosamine kinase domain of GNE." Tong Y., Tempel W., Nedyalkova L., Mackenzie F., Park H.W. PLoS ONE 4:E7165-E7165(2009) [PubMed: 19841673] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.84 ANGSTROMS) OF 406-720, SUBUNIT.
[14]	"Sialuria in a Portuguese girl: clinical, biochemical, and molecular characteristics." Ferreira H., Seppala R., Pinto R., Huizing M., Martins E., Braga A.C., Gomes L., Krasnewich D.M., Sa Miranda M.C., Gahl W.A. Mol. Genet. Metab. 67:131-137(1999) [PubMed: 10356312] [Abstract] Cited for: VARIANT SIALURIA GLN-266.
[15]	"Dominant inheritance of sialuria, an inborn error of feedback inhibition." Leroy J.G., Seppala R., Huizing M., Dacremont G., De Simpel H., Van Coster R.N., Orvisky E., Krasnewich D.M., Gahl W.A. Am. J. Hum. Genet. 68:1419-1427(2001) [PubMed: 11326336] [Abstract] Cited for: CHARACTERIZATION OF VARIANT SIALURIA GLN-266.
[16]	"The UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase gene is mutated in recessive hereditary inclusion body myopathy." Eisenberg I., Avidan N., Potikha T., Hochner H., Chen M., Olender T., Barash M., Shemesh M., Sadeh M., Grabov-Nardini G., Shmilevich I., Friedmann A., Karpati G., Bradley W.G., Baumbach L., Lancet D., Asher E.B., Beckmann J.S., Argov Z., Mitrani-Rosenbaum S. Nat. Genet. 29:83-87(2001) [PubMed: 11528398] [Abstract] Cited for: VARIANTS IBM2 ASN-225; GLN-246; GLU-576; THR-631; MET-696 AND THR-712.
[17]	"A novel mutation in the GNE gene and a linkage disequilibrium in Japanese pedigrees." Arai A., Tanaka K., Ikeuchi T., Igarashi S., Kobayashi H., Asaka T., Date H., Saito M., Tanaka H., Kawasaki S., Uyama E., Mizusawa H., Fukuhara N., Tsuji S. Ann. Neurol. 52:516-519(2002) [PubMed: 12325084] [Abstract] Cited for: VARIANT NM LEU-572.
[18]	"Nonaka myopathy is caused by mutations in the UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase gene (GNE)." Kayashima T., Matsuo H., Satoh A., Ohta T., Yoshiura K., Matsumoto N., Nakane Y., Niikawa N., Kishino T. J. Hum. Genet. 47:77-79(2002) [PubMed: 11916006] [Abstract] Cited for: VARIANTS NM VAL-460 AND LEU-572.
[19]	"Four novel mutations associated with autosomal recessive inclusion body myopathy (MIM: 600737)." Darvish D., Vahedifar P., Huo Y. Mol. Genet. Metab. 77:252-256(2002) [PubMed: 12409274] [Abstract] Cited for: VARIANTS IBM2 ASN-225; GLN-246; TRP-246; VAL-460; VAL-524; LEU-572; GLU-576; THR-631; HIS-675; MET-696 AND THR-712.
[20]	"Distal myopathy with rimmed vacuoles: novel mutations in the GNE gene." Tomimitsu H., Ishikawa K., Shimizu J., Ohkoshi N., Kanazawa I., Mizusawa H. Neurology 59:451-454(2002) [PubMed: 12177386] [Abstract] Cited for: VARIANTS NM LEU-572 AND VAL-631.
[21]	"Distal myopathy with rimmed vacuoles is allelic to hereditary inclusion body myopathy." Nishino I., Noguchi S., Murayama K., Driss A., Sugie K., Oya Y., Nagata T., Chida K., Takahashi T., Takusa Y., Ohi T., Nishimiya J., Sunohara N., Ciafaloni E., Kawai M., Aoki M., Nonaka I. Neurology 59:1689-1693(2002) [PubMed: 12473753] [Abstract] Cited for: VARIANTS NM GLN-132; VAL-176; CYS-177; GLN-306; ALA-331; TYR-378; THR-472; LEU-572; THR-630 AND VAL-631.
[22]	"GNE mutations in an American family with quadriceps-sparing IBM and lack of mutations in s-IBM." Vasconcelos O.M., Raju R., Dalakas M.C. Neurology 59:1776-1779(2002) [PubMed: 12473769] [Abstract] Cited for: VARIANTS IBM2 ALA-216 AND VAL-631.
[23]	"An Italian family with autosomal recessive inclusion-body myopathy and mutations in the GNE gene." Broccolini A., Pescatori M., D'Amico A., Sabino A., Silvestri G., Ricci E., Servidei S., Tonali P.A., Mirabella M. Neurology 59:1808-1809(2002) [PubMed: 12473780] [Abstract] Cited for: VARIANTS IBM2 VAL-171 AND THR-712.
[24]	"Mutations spectrum of GNE in hereditary inclusion body myopathy sparing the quadriceps." Eisenberg I., Grabov-Nardini G., Hochner H., Korner M., Sadeh M., Bertorini T., Bushby K., Castellan C., Felice K., Mendell J., Merlini L., Shilling C., Wirguin I., Argov Z., Mitrani-Rosenbaum S. Hum. Mutat. 21:99-99(2003) [PubMed: 12497639] [Abstract] Cited for: VARIANTS IBM2 LEU-36; PHE-200; ASN-225; GLN-246; VAL-303; TYR-378; VAL-460; CYS-528; THR-557; LEU-572; GLU-576; THR-587; THR-631; VAL-631; MET-696 AND THR-712.
[25]	"Novel missense mutation and large deletion of GNE gene in autosomal-recessive inclusion-body myopathy." Del Bo R., Baron P., Prelle A., Serafini M., Moggio M., Di Fonzo A., Castagni M., Bresolin N., Comi G.P. Muscle Nerve 28:113-117(2003) [PubMed: 12811782] [Abstract] Cited for: VARIANT IBM2 CYS-162.
[26]	"GNE mutations causing distal myopathy with rimmed vacuoles with inflammation." Yabe I., Higashi T., Kikuchi S., Sasaki H., Fukazawa T., Yoshida K., Tashiro K. Neurology 61:384-386(2003) [PubMed: 12913203] [Abstract] Cited for: VARIANTS NM THR-472 AND LEU-572.
[27]	"Novel GNE mutations in Italian families with autosomal recessive hereditary inclusion-body myopathy." Broccolini A., Ricci E., Cassandrini D., Gliubizzi C., Bruno C., Tonoli E., Silvestri G., Pescatori M., Rodolico C., Sinicropi S., Servidei S., Zara F., Minetti C., Tonali P.A., Mirabella M. Hum. Mutat. 23:632-632(2004) [PubMed: 15146476] [Abstract] Cited for: VARIANTS IBM2 SER-27; SER-206; GLN-246; SER-519 AND THR-600.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AJ238764 mRNA. Translation: CAB42607.1.
AF051852 mRNA. Translation: AAD32251.1.
AF155663 mRNA. Translation: AAD38197.1.
AF317635 Genomic DNA. Translation: AAG31661.1.
AK312539 mRNA. Translation: BAG35438.1.
AM697708 mRNA. Translation: CAM91424.1.
AM697709 mRNA. Translation: CAM91425.1.
AL158830 Genomic DNA. Translation: CAD13389.1.
CH471071 Genomic DNA. Translation: EAW58307.1.
CH471071 Genomic DNA. Translation: EAW58309.1.
BC121179 mRNA. Translation: AAI21180.1.

IPI

IPI00023162.
IPI00896504.
IPI00982551.

RefSeq

NP_001121699.1. NM_001128227.2.
NP_001177313.1. NM_001190384.1.
NP_001177317.1. NM_001190388.1.
NP_005467.1. NM_005476.5.

UniGene

Hs.5920.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3EO3	X-ray	2.84	A/B/C	406-720	[»]

ProteinModelPortal

Q9Y223.

SMR

Q9Y223. Positions 7-717.

ModBase

Search...

Protein-protein interaction databases

STRING

Q9Y223.

PTM databases

PhosphoSite

Q9Y223.

Polymorphism databases

DMDM

45476991.

Proteomic databases

PeptideAtlas

Q9Y223.

PRIDE

Q9Y223.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000339267; ENSP00000340770; ENSG00000159921.
ENST00000377902; ENSP00000367134; ENSG00000159921.
ENST00000396594; ENSP00000379839; ENSG00000159921.

GeneID

10020.

KEGG

hsa:10020.

NMPDR

fig|9606.3.peg.31271.

UCSC

uc010mlh.1. human.

Organism-specific databases

CTD

10020.

GeneCards

GC09M036204.

H-InvDB

HIX0008031.

HGNC

HGNC:23657. GNE.

HPA

HPA007045.
HPA027258.

MIM

269921. phenotype.
600737. phenotype.
603824. gene.
605820. phenotype.

neXtProt

NX_Q9Y223.

Orphanet

602. Distal myopathy, Nonaka type.
3166. Sialuria, French type.

PharmGKB

PA134987566.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG04689.

GeneTree

ENSGT00390000017246.

HOVERGEN

HBG051733.

InParanoid

Q9Y223.

OMA

DHILETQ.

OrthoDB

EOG4QFWCN.

PhylomeDB

Q9Y223.

Gene expression databases

ArrayExpress

Q9Y223.

Bgee

Q9Y223.

CleanEx

HS_GNE.

Genevestigator

Q9Y223.

GermOnline

ENSG00000159921. Homo sapiens.

Family and domain databases

InterPro

IPR001312. Hexokinase.
IPR000600. ROK.
IPR020004. UDP-GlcNAc_Epase.
IPR003331. UDP_GlcNAc_Epimerase_2.
[Graphical view]

KO

K12409.

Pfam

PF02350. Epimerase_2. 1 hit.
PF00480. ROK. 1 hit.
[Graphical view]

PRINTS

PR00475. HEXOKINASE.

TIGRFAMs

TIGR03568. NeuC_NnaA. 1 hit.

PROSITE

PS01125. ROK. False negative.
[Graphical view]

ProtoNet

Search...

Other

NextBio

37861.

SOURCE

Search...

Entry information

Entry name

GLCNE_HUMAN

Accession

Primary (citable) accession number: Q9Y223
Secondary accession number(s): A6PZH2 , A6PZH3, B2R6E1, D3DRP7, Q0VA94

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 15, 2004
Last sequence update:	November 1, 1999
Last modified:	December 14, 2011
This is version 97 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.