Q99KK2 (NEUA_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
N-acylneuraminate cytidylyltransferase
EC=2.7.7.43

Alternative name(s):
CMP-N-acetylneuraminic acid synthase
Short name=CMP-NeuNAc synthase

Gene names

Name:

Cmas

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	432 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes the activation of N-acetylneuraminic acid (NeuNAc) to cytidine 5'-monophosphate N-acetylneuraminic acid (CMP-NeuNAc), a substrate required for the addition of sialic acid. Has some activity toward NeuNAc, N-glycolylneuraminic acid (Neu5Gc) or 2-keto-3-deoxy-D-glycero-D-galacto-nononic acid (KDN). Ref.1
Catalytic activity	CTP + N-acylneuraminate = diphosphate + CMP-N-acylneuraminate. Ref.1 Ref.4
Pathway	Amino-sugar metabolism; N-acetylneuraminate metabolism.
Subunit structure	Homotetramer; the active enzyme is formed by a dimer of dimers. Ref.5
Subcellular location	Nucleus Ref.1 Ref.4.
Tissue specificity	Highly expressed in brain and heart, and at intermediate level muscle and liver. Ref.1
Domain	The BC2 (basic cluster 2) motif is necessary and sufficient for the nuclear localization and contains the catalytic active site. The localization in the nucleus is however not required for the enzyme activity.
Sequence similarities	Belongs to the CMP-NeuNAc synthase family.

Ontologies

Keywords
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Molecular function	Nucleotidyltransferase Transferase
PTM	Acetylation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	CMP-N-acetylneuraminate biosynthetic process Inferred from sequence alignment PubMed 11602804. Source: MGI N-acetylneuraminate metabolic process Inferred from electronic annotation. Source: UniProtKB-UniPathway lipopolysaccharide biosynthetic process Inferred from electronic annotation. Source: InterPro
Cellular_component	nucleus Inferred from sequence alignment PubMed 11602804. Source: MGI
Molecular_function	N-acylneuraminate cytidylyltransferase activity Inferred from sequence alignment PubMed 11602804. Source: MGI
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q99KK2-1)

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: Q99KK2-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-232: Missing.

Note: Inactive. No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 432

432

N-acylneuraminate cytidylyltransferase

PRO_0000213200

Regions

Motif

15 – 31

17

BC1 motif

Motif

198 – 204

7

BC2 motif

Motif

267 – 274

8

BC3 motif

Sites

Active site

199

1

Binding site

50

1

Substrate

Binding site

60

1

Substrate

Binding site

109

1

Substrate

Binding site

118

1

Substrate

Binding site

120

1

Substrate

Binding site

141

1

Substrate

Amino acid modifications

Modified residue

1

1

N-acetylmethionine By similarity

Natural variations

Alternative sequence

1 – 232

232

Missing in isoform 2.

VSP_012765

Experimental info

Mutagenesis

196

1

P → A: Does not affect the nuclear localization.

Mutagenesis

198

1

K → A: Abolishes the nuclear localization but does not affect the enzyme activity; when associated with A-201. Ref.4

Mutagenesis

199

1

R → A: Abolishes both the nuclear localization and the enzyme activity. Ref.4

Mutagenesis

200

1

P → A: Does not affect neither the nuclear localization nor the enzyme activity. Ref.4

Mutagenesis

201

1

R → A: Abolishes the nuclear localization but does not affect the enzyme activity; when associated with A-198. Ref.4

Mutagenesis

202

1

R → A: Does not strongly affect the nuclear localization but strongly affects the enzyme activity. Ref.4

Mutagenesis

203

1

Q → A: Does not affect the nuclear localization but affects the enzyme activity. Ref.4

Mutagenesis

204

1

D → A: Does not affect the nuclear localization. Ref.4

Sequence conflict

9

1

V → A in AAH31500. Ref.3

Sequence conflict

9

1

V → A in AAH63776. Ref.3

Secondary structure

1

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432

Helix Strand Turn

Details...

Beta strand

43 – 48

6

Beta strand

54 – 57

4

Turn

59 – 61

3

Beta strand

62 – 64

3

Helix

69 – 80

12

Beta strand

84 – 91

8

Helix

93 – 101

9

Beta strand

105 – 108

4

Helix

111 – 113

3

Helix

120 – 128

9

Beta strand

135 – 140

6

Helix

149 – 160

12

Beta strand

165 – 173

9

Beta strand

191 – 195

5

Turn

202 – 204

3

Beta strand

208 – 219

12

Helix

220 – 224

5

Beta strand

231 – 237

7

Helix

240 – 242

3

Helix

246 – 249

4

Helix

252 – 262

11

Beta strand

275 – 279

5

Helix

280 – 284

5

Beta strand

298 – 302

5

Helix

303 – 314

12

Beta strand

318 – 322

5

Helix

329 – 333

5

Helix

348 – 358

11

Helix

363 – 365

3

Beta strand

366 – 369

4

Helix

373 – 375

3

Helix

376 – 381

6

Beta strand

382 – 387

6

Helix

393 – 396

4

Beta strand

400 – 402

3

Turn

407 – 410

4

Helix

411 – 426

16

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 1, 2005. Version 2. Checksum: BF7295535E7F6CE5	FASTA	432	48,058
	10 20 30 40 50 60 MDALEKGAVT SGPAPRGRPS RGRPPKLQRS RGAGRGLEKP PHLAALVLAR GGSKGIPLKN 70 80 90 100 110 120 IKRLAGVPLI GWVLRAALDA GVFQSVWVST DHDEIENVAK QFGAQVHRRS SETSKDSSTS 130 140 150 160 170 180 LDAIVEFLNY HNEVDIVGNI QATSPCLHPT DLQKVAEMIR EEGYDSVFSV VRRHQFRWSE 190 200 210 220 230 240 IQKGVREVTE PLNLNPAKRP RRQDWDGELY ENGSFYFAKR HLIEMGYLQG GKMAYYEMRA 250 260 270 280 290 300 EHSVDIDVDI DWPIAEQRVL RFGYFGKEKL KEIKLLVCNI DGCLTNGHIY VSGDQKEIIS 310 320 330 340 350 360 YDVKDAIGIS LLKKSGIEVR LISERACSKQ TLSALKLDCK TEVSVSDKLA TVDEWRKEMG 370 380 390 400 410 420 LCWKEVAYLG NEVSDEECLK RVGLSAVPAD ACSGAQKAVG YICKCSGGRG AIREFAEHIF 430 LLIEKVNNSC QK
	Isoform 2 [UniParc]. Checksum: 0D3C036CD8EC4F31	FASTA	200	22,277
	10 20 30 40 50 60 MAYYEMRAEH SVDIDVDIDW PIAEQRVLRF GYFGKEKLKE IKLLVCNIDG CLTNGHIYVS 70 80 90 100 110 120 GDQKEIISYD VKDAIGISLL KKSGIEVRLI SERACSKQTL SALKLDCKTE VSVSDKLATV 130 140 150 160 170 180 DEWRKEMGLC WKEVAYLGNE VSDEECLKRV GLSAVPADAC SGAQKAVGYI CKCSGGRGAI 190 200 REFAEHIFLL IEKVNNSCQK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Mammalian cytidine 5-prime-monophosphate N-acetylneuraminic acid synthetase: a nuclear protein with evolutionarily conserved structural motifs." Muenster A.-K., Eckhardt M., Potvin B., Muehlenhoff M., Stanley P., Gerardy-Schahn R. Proc. Natl. Acad. Sci. U.S.A. 95:9140-9145(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, ENZYME ACTIVITY, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Strain: C57BL/6J. Tissue: Lung.
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Strain: FVB/N. Tissue: Colon and Mammary tumor.
[4]	"Nuclear localization signal of murine CMP-Neu5Ac synthetase includes residues required for both nuclear targeting and enzymatic activity." Muenster A.-K., Weinhold B., Gotza B., Muehlenhoff M., Frosch M., Gerardy-Schahn R. J. Biol. Chem. 277:19688-19696(2002) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, ENZYME ACTIVITY, MUTAGENESIS OF LYS-198; ARG-199; PRO-200; ARG-201; ARG-202; GLN-203 AND ASP-204.
[5]	"The crystal structure of murine CMP-5-N-acetylneuraminic acid synthetase." Krapp S., Muenster-Kuehnel A.-K., Kaiser J.T., Huber R., Tiralongo J., Gerardy-Schahn R., Jacob U. J. Mol. Biol. 334:625-637(2003) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 40-268 IN COMPLEX WITH CMP-NEUNAC, SUBUNIT.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AJ006215 mRNA. Translation: CAA06915.1.
AK087150 mRNA. Translation: BAC39813.1.
BC004606 mRNA. Translation: AAH04606.1.
BC031500 mRNA. Translation: AAH31500.1.
BC063776 mRNA. Translation: AAH63776.1.

IPI

IPI00322206.
IPI00551142.

RefSeq

NP_034038.2. NM_009908.2.

UniGene

Mm.3820.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1QWJ	X-ray	2.80	A/B/C/D	40-268	[»]
3EWI	X-ray	1.90	A/B	267-432	[»]

ProteinModelPortal

Q99KK2.

SMR

Q99KK2. Positions 40-268, 272-429.

ModBase

Search...

Protein-protein interaction databases

MINT

MINT-4103350.

PTM databases

PhosphoSite

Q99KK2.

Proteomic databases

PaxDb

Q99KK2.

PRIDE

Q99KK2.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000032419; ENSMUSP00000032419; ENSMUSG00000030282.

GeneID

12764.

KEGG

mmu:12764.

UCSC

uc009eps.2. mouse.

Organism-specific databases

CTD

55907.

MGI

MGI:1337124. Cmas.

Phylogenomic databases

eggNOG

COG1083.

GeneTree

ENSGT00390000004237.

HOGENOM

HOG000284760.

HOVERGEN

HBG052605.

InParanoid

Q99KK2.

KO

K00983.

OrthoDB

EOG4W9J3W.

Enzyme and pathway databases

BioCyc

MetaCyc:MONOMER-14521.

UniPathway

UPA00628.

Gene expression databases

Bgee

Q99KK2.

Genevestigator

Q99KK2.

GermOnline

ENSMUSG00000030282. Mus musculus.

Family and domain databases

Gene3D

3.40.50.1000. 1 hit.

InterPro

IPR003329. Cytidylyl_trans.
IPR023214. HAD-like_dom.
[Graphical view]

Pfam

PF02348. CTP_transf_3. 1 hit.
[Graphical view]

SUPFAM

SSF56784. HAD-like_dom. 1 hit.

ProtoNet

Search...

Other

ChiTaRS

CMAS. mouse.

EvolutionaryTrace

Q99KK2.

NextBio

282118.

SOURCE

Search...

Entry information

Entry name

NEUA_MOUSE

Accession

Primary (citable) accession number: Q99KK2
Secondary accession number(s): O88719, Q8C330, Q8K2G7

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 2005
Last sequence update:	February 1, 2005
Last modified:	May 29, 2013
This is version 91 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program