Full text data of CNP
CNP
[Confidence: high (present in two of the MS resources)]
2',3'-cyclic-nucleotide 3'-phosphodiesterase; CNP; CNPase; 3.1.4.37; Flags: Precursor
2',3'-cyclic-nucleotide 3'-phosphodiesterase; CNP; CNPase; 3.1.4.37; Flags: Precursor
hRBCD
IPI00220993
IPI00220993 Splice isoform CNPI of P09543 2,3-cyclic-nucleotide 3-phosphodiesterase Splice isoform CNPI of P09543 2,3-cyclic-nucleotide 3-phosphodiesterase membrane n/a 4 4 1 3 n/a 3 n/a 2 n/a 1 5 7 5 3 3 3 5 3 n/a membrane bound splice isoform CNPI and CNPII expected molecular weight found in band ~ 31 kDa
IPI00220993 Splice isoform CNPI of P09543 2,3-cyclic-nucleotide 3-phosphodiesterase Splice isoform CNPI of P09543 2,3-cyclic-nucleotide 3-phosphodiesterase membrane n/a 4 4 1 3 n/a 3 n/a 2 n/a 1 5 7 5 3 3 3 5 3 n/a membrane bound splice isoform CNPI and CNPII expected molecular weight found in band ~ 31 kDa
Comments
Isoform P09543-2 was detected.
Isoform P09543-2 was detected.
UniProt
P09543
ID CN37_HUMAN Reviewed; 421 AA.
AC P09543;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-OCT-1996, sequence version 2.
DT 22-JAN-2014, entry version 147.
DE RecName: Full=2',3'-cyclic-nucleotide 3'-phosphodiesterase;
DE Short=CNP;
DE Short=CNPase;
DE EC=3.1.4.37;
DE Flags: Precursor;
GN Name=CNP;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1385234;
RA Thompson R.J.;
RT "2',3'-cyclic nucleotide-3'-phosphohydrolase and signal transduction
RT in central nervous system myelin.";
RL Biochem. Soc. Trans. 20:621-626(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CNPI).
RC TISSUE=Brain;
RX PubMed=2835044; DOI=10.1016/S0006-291X(88)80114-1;
RA Kurihara T., Takahashi Y., Nishiyama A., Kumanishi T.;
RT "cDNA cloning and amino acid sequence of human brain 2',3'-cyclic-
RT nucleotide 3'-phosphodiesterase.";
RL Biochem. Biophys. Res. Commun. 152:837-842(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8392017; DOI=10.1016/0378-1119(93)90283-9;
RA Monoh K., Kurihara T., Takahashi Y., Ichikawa T., Kumanishi T.,
RA Hayashi S., Minoshima S., Shimizu N.;
RT "Structure, expression and chromosomal localization of the gene
RT encoding human 2',3'-cyclic-nucleotide 3'-phosphodiesterase.";
RL Gene 129:297-301(1993).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1360194; DOI=10.1111/j.1469-1809.1992.tb01149.x;
RA Douglas A.J., Fox M.F., Abbott C.M., Hinks L.J., Sharpe G., Povey S.,
RA Thompson R.J.;
RT "Structure and chromosomal localization of the human 2',3'-cyclic
RT nucleotide 3'-phosphodiesterase gene.";
RL Ann. Hum. Genet. 56:243-254(1992).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R.,
RA Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N.,
RA Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B.,
RA Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J.,
RA Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E.,
RA Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J.,
RA Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C.,
RA Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in
RT the human lineage.";
RL Nature 440:1045-1049(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS CNPI AND CNPII).
RC TISSUE=Brain, and Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PROTEIN SEQUENCE OF 21-58.
RX PubMed=9268698; DOI=10.1006/bbrc.1997.7125;
RA Stricker R., Kalbacher H., Reiser G.;
RT "The epitope recognized by a monoclonal antibody in the myelin-
RT associated protein CNP.";
RL Biochem. Biophys. Res. Commun. 237:266-270(1997).
RN [8]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
RC TISSUE=Melanoma;
RX PubMed=12643545; DOI=10.1021/pr025562r;
RA Basrur V., Yang F., Kushimoto T., Higashimoto Y., Yasumoto K.,
RA Valencia J., Muller J., Vieira W.D., Watabe H., Shabanowitz J.,
RA Hearing V.J., Hunt D.F., Appella E.;
RT "Proteomic analysis of early melanosomes: identification of novel
RT melanosomal proteins.";
RL J. Proteome Res. 2:69-79(2003).
RN [9]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
RC TISSUE=Melanoma;
RX PubMed=17081065; DOI=10.1021/pr060363j;
RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H.,
RA Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R.,
RA Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E.,
RA Hunt D.F.;
RT "Proteomic and bioinformatic characterization of the biogenesis and
RT function of melanosomes.";
RL J. Proteome Res. 5:3135-3144(2006).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 186-399 IN COMPLEX WITH
RP PHOSPHATE.
RX PubMed=15713463; DOI=10.1016/j.jmb.2004.12.024;
RA Sakamoto Y., Tanaka N., Ichimiya T., Kurihara T., Nakamura K.T.;
RT "Crystal structure of the catalytic fragment of human brain 2',3'-
RT cyclic-nucleotide 3'-phosphodiesterase.";
RL J. Mol. Biol. 346:789-800(2005).
CC -!- FUNCTION: May participate in RNA metabolism in the myelinating
CC cell, CNP is the third most abundant protein in central nervous
CC system myelin (By similarity).
CC -!- CATALYTIC ACTIVITY: Nucleoside 2',3'-cyclic phosphate + H(2)O =
CC nucleoside 2'-phosphate.
CC -!- SUBUNIT: Exists as monomers and homodimers (By similarity).
CC -!- SUBCELLULAR LOCATION: Membrane; Lipid-anchor. Melanosome.
CC Note=Firmly bound to membrane structures of brain white matter.
CC Identified by mass spectrometry in melanosome fractions from stage
CC I to stage IV.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=CNPII; Synonyms=DNAII;
CC IsoId=P09543-1; Sequence=Displayed;
CC Name=CNPI; Synonyms=DNAI;
CC IsoId=P09543-2; Sequence=VSP_004171;
CC -!- SIMILARITY: Belongs to the cyclic nucleotide phosphodiesterase
CC family.
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DR EMBL; S46849; AAB23928.2; -; Genomic_DNA.
DR EMBL; S46843; AAB23928.2; JOINED; Genomic_DNA.
DR EMBL; S46845; AAB23928.2; JOINED; Genomic_DNA.
DR EMBL; S46846; AAB23928.2; JOINED; Genomic_DNA.
DR EMBL; M19650; AAA35704.1; -; mRNA.
DR EMBL; D13146; BAA39694.1; -; Genomic_DNA.
DR EMBL; D13146; BAA02435.1; -; Genomic_DNA.
DR EMBL; S50017; AAB24298.2; -; Genomic_DNA.
DR EMBL; S50013; AAB24298.2; JOINED; Genomic_DNA.
DR EMBL; S50014; AAB24298.2; JOINED; Genomic_DNA.
DR EMBL; S50016; AAB24298.2; JOINED; Genomic_DNA.
DR EMBL; AC125257; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC001362; AAH01362.1; -; mRNA.
DR EMBL; BC006392; AAH06392.1; -; mRNA.
DR EMBL; BC011046; AAH11046.1; -; mRNA.
DR EMBL; BC028040; AAH28040.1; -; mRNA.
DR PIR; JC1517; JC1517.
DR RefSeq; NP_149124.3; NM_033133.4.
DR RefSeq; XP_005257113.1; XM_005257056.1.
DR RefSeq; XP_005277063.1; XM_005277006.1.
DR UniGene; Hs.273621; -.
DR PDB; 1WOJ; X-ray; 1.80 A; A=186-399.
DR PDBsum; 1WOJ; -.
DR ProteinModelPortal; P09543; -.
DR SMR; P09543; 186-399.
DR IntAct; P09543; 4.
DR MINT; MINT-4999529; -.
DR STRING; 9606.ENSP00000377470; -.
DR PhosphoSite; P09543; -.
DR DMDM; 1705945; -.
DR UCD-2DPAGE; P09543; -.
DR PaxDb; P09543; -.
DR PRIDE; P09543; -.
DR DNASU; 1267; -.
DR Ensembl; ENST00000393888; ENSP00000377466; ENSG00000173786.
DR Ensembl; ENST00000393892; ENSP00000377470; ENSG00000173786.
DR Ensembl; ENST00000562963; ENSP00000457200; ENSG00000260283.
DR Ensembl; ENST00000563912; ENSP00000454542; ENSG00000260283.
DR GeneID; 1267; -.
DR KEGG; hsa:1267; -.
DR UCSC; uc002hyl.1; human.
DR CTD; 1267; -.
DR GeneCards; GC17P040118; -.
DR HGNC; HGNC:2158; CNP.
DR HPA; CAB002672; -.
DR HPA; HPA023266; -.
DR HPA; HPA023278; -.
DR HPA; HPA023280; -.
DR HPA; HPA023338; -.
DR MIM; 123830; gene.
DR neXtProt; NX_P09543; -.
DR PharmGKB; PA26680; -.
DR eggNOG; NOG314041; -.
DR HOGENOM; HOG000111838; -.
DR HOVERGEN; HBG001451; -.
DR InParanoid; P09543; -.
DR KO; K01121; -.
DR OMA; LWPNDVD; -.
DR ChiTaRS; CNP; human.
DR EvolutionaryTrace; P09543; -.
DR GeneWiki; 2%27,3%27-Cyclic-nucleotide_3%27-phosphodiesterase; -.
DR GenomeRNAi; 1267; -.
DR NextBio; 5129; -.
DR PRO; PR:P09543; -.
DR ArrayExpress; P09543; -.
DR Bgee; P09543; -.
DR CleanEx; HS_CNP; -.
DR Genevestigator; P09543; -.
DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005874; C:microtubule; IDA:UniProtKB.
DR GO; GO:0005902; C:microvillus; IEA:Ensembl.
DR GO; GO:0005743; C:mitochondrial inner membrane; IEA:Ensembl.
DR GO; GO:0005741; C:mitochondrial outer membrane; IEA:Ensembl.
DR GO; GO:0035748; C:myelin sheath abaxonal region; IEA:Ensembl.
DR GO; GO:0035749; C:myelin sheath adaxonal region; IEA:Ensembl.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IEA:Ensembl.
DR GO; GO:0031143; C:pseudopodium; IEA:Ensembl.
DR GO; GO:0004113; F:2',3'-cyclic-nucleotide 3'-phosphodiesterase activity; TAS:ProtInc.
DR GO; GO:0030551; F:cyclic nucleotide binding; IEA:Ensembl.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0008344; P:adult locomotory behavior; IEA:Ensembl.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0007409; P:axonogenesis; IEA:Ensembl.
DR GO; GO:0009214; P:cyclic nucleotide catabolic process; IEA:InterPro.
DR GO; GO:0030900; P:forebrain development; IEA:Ensembl.
DR GO; GO:0000226; P:microtubule cytoskeleton organization; IEA:Ensembl.
DR GO; GO:0046902; P:regulation of mitochondrial membrane permeability; IEA:Ensembl.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl.
DR GO; GO:0009636; P:response to toxic substance; IEA:Ensembl.
DR GO; GO:0007268; P:synaptic transmission; TAS:ProtInc.
DR InterPro; IPR008431; CNPase.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR009097; RNA_ligase/cNuc_Pdiesterase.
DR PANTHER; PTHR10156; PTHR10156; 1.
DR Pfam; PF05881; CNPase; 1.
DR PIRSF; PIRSF000970; CNPase; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR SUPFAM; SSF55144; SSF55144; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Complete proteome;
KW Direct protein sequencing; Hydrolase; Lipoprotein; Membrane;
KW Methylation; Phosphoprotein; Polymorphism; Prenylation;
KW Reference proteome; RNA-binding.
FT CHAIN 1 418 2',3'-cyclic-nucleotide 3'-
FT phosphodiesterase.
FT /FTId=PRO_0000089961.
FT PROPEP 419 421 Removed in mature form (By similarity).
FT /FTId=PRO_0000422296.
FT ACT_SITE 251 251 Proton acceptor.
FT ACT_SITE 330 330 Proton donor.
FT BINDING 253 253 Substrate.
FT BINDING 332 332 Substrate.
FT MOD_RES 110 110 Phosphotyrosine (By similarity).
FT MOD_RES 418 418 Cysteine methyl ester (By similarity).
FT LIPID 418 418 S-farnesyl cysteine (By similarity).
FT VAR_SEQ 1 20 Missing (in isoform CNPI).
FT /FTId=VSP_004171.
FT VARIANT 207 207 Q -> R (in dbSNP:rs34353668).
FT /FTId=VAR_033746.
FT STRAND 188 194
FT HELIX 196 215
FT HELIX 217 221
FT HELIX 223 226
FT HELIX 238 241
FT STRAND 251 256
FT HELIX 258 260
FT HELIX 265 270
FT HELIX 272 277
FT STRAND 281 291
FT STRAND 293 301
FT HELIX 306 309
FT TURN 325 328
FT STRAND 330 335
FT HELIX 343 356
FT STRAND 362 367
FT STRAND 370 376
FT STRAND 379 397
SQ SEQUENCE 421 AA; 47579 MW; CA6D0097DFD87255 CRC64;
MNRGFSRKSH TFLPKIFFRK MSSSGAKDKP ELQFPFLQDE DTVATLLECK TLFILRGLPG
SGKSTLARVI VDKYRDGTKM VSADAYKITP GARGAFSEEY KRLDEDLAAY CRRRDIRILV
LDDTNHERER LEQLFEMADQ YQYQVVLVEP KTAWRLDCAQ LKEKNQWQLS ADDLKKLKPG
LEKDFLPLYF GWFLTKKSSE TLRKAGQVFL EELGNHKAFK KELRQFVPGD EPREKMDLVT
YFGKRPPGVL HCTTKFCDYG KAPGAEEYAQ QDVLKKSYSK AFTLTISALF VTPKTTGARV
ELSEQQLQLW PSDVDKLSPT DNLPRGSRAH ITLGCAADVE AVQTGLDLLE ILRQEKGGSR
GEEVGELSRG KLYSLGNGRW MLTLAKNMEV RAIFTGYYGK GKPVPTQGSR KGGALQSCTI
I
//
ID CN37_HUMAN Reviewed; 421 AA.
AC P09543;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-OCT-1996, sequence version 2.
DT 22-JAN-2014, entry version 147.
DE RecName: Full=2',3'-cyclic-nucleotide 3'-phosphodiesterase;
DE Short=CNP;
DE Short=CNPase;
DE EC=3.1.4.37;
DE Flags: Precursor;
GN Name=CNP;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1385234;
RA Thompson R.J.;
RT "2',3'-cyclic nucleotide-3'-phosphohydrolase and signal transduction
RT in central nervous system myelin.";
RL Biochem. Soc. Trans. 20:621-626(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CNPI).
RC TISSUE=Brain;
RX PubMed=2835044; DOI=10.1016/S0006-291X(88)80114-1;
RA Kurihara T., Takahashi Y., Nishiyama A., Kumanishi T.;
RT "cDNA cloning and amino acid sequence of human brain 2',3'-cyclic-
RT nucleotide 3'-phosphodiesterase.";
RL Biochem. Biophys. Res. Commun. 152:837-842(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8392017; DOI=10.1016/0378-1119(93)90283-9;
RA Monoh K., Kurihara T., Takahashi Y., Ichikawa T., Kumanishi T.,
RA Hayashi S., Minoshima S., Shimizu N.;
RT "Structure, expression and chromosomal localization of the gene
RT encoding human 2',3'-cyclic-nucleotide 3'-phosphodiesterase.";
RL Gene 129:297-301(1993).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1360194; DOI=10.1111/j.1469-1809.1992.tb01149.x;
RA Douglas A.J., Fox M.F., Abbott C.M., Hinks L.J., Sharpe G., Povey S.,
RA Thompson R.J.;
RT "Structure and chromosomal localization of the human 2',3'-cyclic
RT nucleotide 3'-phosphodiesterase gene.";
RL Ann. Hum. Genet. 56:243-254(1992).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R.,
RA Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N.,
RA Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B.,
RA Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J.,
RA Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E.,
RA Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J.,
RA Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C.,
RA Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in
RT the human lineage.";
RL Nature 440:1045-1049(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS CNPI AND CNPII).
RC TISSUE=Brain, and Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PROTEIN SEQUENCE OF 21-58.
RX PubMed=9268698; DOI=10.1006/bbrc.1997.7125;
RA Stricker R., Kalbacher H., Reiser G.;
RT "The epitope recognized by a monoclonal antibody in the myelin-
RT associated protein CNP.";
RL Biochem. Biophys. Res. Commun. 237:266-270(1997).
RN [8]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
RC TISSUE=Melanoma;
RX PubMed=12643545; DOI=10.1021/pr025562r;
RA Basrur V., Yang F., Kushimoto T., Higashimoto Y., Yasumoto K.,
RA Valencia J., Muller J., Vieira W.D., Watabe H., Shabanowitz J.,
RA Hearing V.J., Hunt D.F., Appella E.;
RT "Proteomic analysis of early melanosomes: identification of novel
RT melanosomal proteins.";
RL J. Proteome Res. 2:69-79(2003).
RN [9]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
RC TISSUE=Melanoma;
RX PubMed=17081065; DOI=10.1021/pr060363j;
RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H.,
RA Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R.,
RA Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E.,
RA Hunt D.F.;
RT "Proteomic and bioinformatic characterization of the biogenesis and
RT function of melanosomes.";
RL J. Proteome Res. 5:3135-3144(2006).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 186-399 IN COMPLEX WITH
RP PHOSPHATE.
RX PubMed=15713463; DOI=10.1016/j.jmb.2004.12.024;
RA Sakamoto Y., Tanaka N., Ichimiya T., Kurihara T., Nakamura K.T.;
RT "Crystal structure of the catalytic fragment of human brain 2',3'-
RT cyclic-nucleotide 3'-phosphodiesterase.";
RL J. Mol. Biol. 346:789-800(2005).
CC -!- FUNCTION: May participate in RNA metabolism in the myelinating
CC cell, CNP is the third most abundant protein in central nervous
CC system myelin (By similarity).
CC -!- CATALYTIC ACTIVITY: Nucleoside 2',3'-cyclic phosphate + H(2)O =
CC nucleoside 2'-phosphate.
CC -!- SUBUNIT: Exists as monomers and homodimers (By similarity).
CC -!- SUBCELLULAR LOCATION: Membrane; Lipid-anchor. Melanosome.
CC Note=Firmly bound to membrane structures of brain white matter.
CC Identified by mass spectrometry in melanosome fractions from stage
CC I to stage IV.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=CNPII; Synonyms=DNAII;
CC IsoId=P09543-1; Sequence=Displayed;
CC Name=CNPI; Synonyms=DNAI;
CC IsoId=P09543-2; Sequence=VSP_004171;
CC -!- SIMILARITY: Belongs to the cyclic nucleotide phosphodiesterase
CC family.
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DR EMBL; S46849; AAB23928.2; -; Genomic_DNA.
DR EMBL; S46843; AAB23928.2; JOINED; Genomic_DNA.
DR EMBL; S46845; AAB23928.2; JOINED; Genomic_DNA.
DR EMBL; S46846; AAB23928.2; JOINED; Genomic_DNA.
DR EMBL; M19650; AAA35704.1; -; mRNA.
DR EMBL; D13146; BAA39694.1; -; Genomic_DNA.
DR EMBL; D13146; BAA02435.1; -; Genomic_DNA.
DR EMBL; S50017; AAB24298.2; -; Genomic_DNA.
DR EMBL; S50013; AAB24298.2; JOINED; Genomic_DNA.
DR EMBL; S50014; AAB24298.2; JOINED; Genomic_DNA.
DR EMBL; S50016; AAB24298.2; JOINED; Genomic_DNA.
DR EMBL; AC125257; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC001362; AAH01362.1; -; mRNA.
DR EMBL; BC006392; AAH06392.1; -; mRNA.
DR EMBL; BC011046; AAH11046.1; -; mRNA.
DR EMBL; BC028040; AAH28040.1; -; mRNA.
DR PIR; JC1517; JC1517.
DR RefSeq; NP_149124.3; NM_033133.4.
DR RefSeq; XP_005257113.1; XM_005257056.1.
DR RefSeq; XP_005277063.1; XM_005277006.1.
DR UniGene; Hs.273621; -.
DR PDB; 1WOJ; X-ray; 1.80 A; A=186-399.
DR PDBsum; 1WOJ; -.
DR ProteinModelPortal; P09543; -.
DR SMR; P09543; 186-399.
DR IntAct; P09543; 4.
DR MINT; MINT-4999529; -.
DR STRING; 9606.ENSP00000377470; -.
DR PhosphoSite; P09543; -.
DR DMDM; 1705945; -.
DR UCD-2DPAGE; P09543; -.
DR PaxDb; P09543; -.
DR PRIDE; P09543; -.
DR DNASU; 1267; -.
DR Ensembl; ENST00000393888; ENSP00000377466; ENSG00000173786.
DR Ensembl; ENST00000393892; ENSP00000377470; ENSG00000173786.
DR Ensembl; ENST00000562963; ENSP00000457200; ENSG00000260283.
DR Ensembl; ENST00000563912; ENSP00000454542; ENSG00000260283.
DR GeneID; 1267; -.
DR KEGG; hsa:1267; -.
DR UCSC; uc002hyl.1; human.
DR CTD; 1267; -.
DR GeneCards; GC17P040118; -.
DR HGNC; HGNC:2158; CNP.
DR HPA; CAB002672; -.
DR HPA; HPA023266; -.
DR HPA; HPA023278; -.
DR HPA; HPA023280; -.
DR HPA; HPA023338; -.
DR MIM; 123830; gene.
DR neXtProt; NX_P09543; -.
DR PharmGKB; PA26680; -.
DR eggNOG; NOG314041; -.
DR HOGENOM; HOG000111838; -.
DR HOVERGEN; HBG001451; -.
DR InParanoid; P09543; -.
DR KO; K01121; -.
DR OMA; LWPNDVD; -.
DR ChiTaRS; CNP; human.
DR EvolutionaryTrace; P09543; -.
DR GeneWiki; 2%27,3%27-Cyclic-nucleotide_3%27-phosphodiesterase; -.
DR GenomeRNAi; 1267; -.
DR NextBio; 5129; -.
DR PRO; PR:P09543; -.
DR ArrayExpress; P09543; -.
DR Bgee; P09543; -.
DR CleanEx; HS_CNP; -.
DR Genevestigator; P09543; -.
DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005874; C:microtubule; IDA:UniProtKB.
DR GO; GO:0005902; C:microvillus; IEA:Ensembl.
DR GO; GO:0005743; C:mitochondrial inner membrane; IEA:Ensembl.
DR GO; GO:0005741; C:mitochondrial outer membrane; IEA:Ensembl.
DR GO; GO:0035748; C:myelin sheath abaxonal region; IEA:Ensembl.
DR GO; GO:0035749; C:myelin sheath adaxonal region; IEA:Ensembl.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IEA:Ensembl.
DR GO; GO:0031143; C:pseudopodium; IEA:Ensembl.
DR GO; GO:0004113; F:2',3'-cyclic-nucleotide 3'-phosphodiesterase activity; TAS:ProtInc.
DR GO; GO:0030551; F:cyclic nucleotide binding; IEA:Ensembl.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0008344; P:adult locomotory behavior; IEA:Ensembl.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0007409; P:axonogenesis; IEA:Ensembl.
DR GO; GO:0009214; P:cyclic nucleotide catabolic process; IEA:InterPro.
DR GO; GO:0030900; P:forebrain development; IEA:Ensembl.
DR GO; GO:0000226; P:microtubule cytoskeleton organization; IEA:Ensembl.
DR GO; GO:0046902; P:regulation of mitochondrial membrane permeability; IEA:Ensembl.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl.
DR GO; GO:0009636; P:response to toxic substance; IEA:Ensembl.
DR GO; GO:0007268; P:synaptic transmission; TAS:ProtInc.
DR InterPro; IPR008431; CNPase.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR009097; RNA_ligase/cNuc_Pdiesterase.
DR PANTHER; PTHR10156; PTHR10156; 1.
DR Pfam; PF05881; CNPase; 1.
DR PIRSF; PIRSF000970; CNPase; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR SUPFAM; SSF55144; SSF55144; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Complete proteome;
KW Direct protein sequencing; Hydrolase; Lipoprotein; Membrane;
KW Methylation; Phosphoprotein; Polymorphism; Prenylation;
KW Reference proteome; RNA-binding.
FT CHAIN 1 418 2',3'-cyclic-nucleotide 3'-
FT phosphodiesterase.
FT /FTId=PRO_0000089961.
FT PROPEP 419 421 Removed in mature form (By similarity).
FT /FTId=PRO_0000422296.
FT ACT_SITE 251 251 Proton acceptor.
FT ACT_SITE 330 330 Proton donor.
FT BINDING 253 253 Substrate.
FT BINDING 332 332 Substrate.
FT MOD_RES 110 110 Phosphotyrosine (By similarity).
FT MOD_RES 418 418 Cysteine methyl ester (By similarity).
FT LIPID 418 418 S-farnesyl cysteine (By similarity).
FT VAR_SEQ 1 20 Missing (in isoform CNPI).
FT /FTId=VSP_004171.
FT VARIANT 207 207 Q -> R (in dbSNP:rs34353668).
FT /FTId=VAR_033746.
FT STRAND 188 194
FT HELIX 196 215
FT HELIX 217 221
FT HELIX 223 226
FT HELIX 238 241
FT STRAND 251 256
FT HELIX 258 260
FT HELIX 265 270
FT HELIX 272 277
FT STRAND 281 291
FT STRAND 293 301
FT HELIX 306 309
FT TURN 325 328
FT STRAND 330 335
FT HELIX 343 356
FT STRAND 362 367
FT STRAND 370 376
FT STRAND 379 397
SQ SEQUENCE 421 AA; 47579 MW; CA6D0097DFD87255 CRC64;
MNRGFSRKSH TFLPKIFFRK MSSSGAKDKP ELQFPFLQDE DTVATLLECK TLFILRGLPG
SGKSTLARVI VDKYRDGTKM VSADAYKITP GARGAFSEEY KRLDEDLAAY CRRRDIRILV
LDDTNHERER LEQLFEMADQ YQYQVVLVEP KTAWRLDCAQ LKEKNQWQLS ADDLKKLKPG
LEKDFLPLYF GWFLTKKSSE TLRKAGQVFL EELGNHKAFK KELRQFVPGD EPREKMDLVT
YFGKRPPGVL HCTTKFCDYG KAPGAEEYAQ QDVLKKSYSK AFTLTISALF VTPKTTGARV
ELSEQQLQLW PSDVDKLSPT DNLPRGSRAH ITLGCAADVE AVQTGLDLLE ILRQEKGGSR
GEEVGELSRG KLYSLGNGRW MLTLAKNMEV RAIFTGYYGK GKPVPTQGSR KGGALQSCTI
I
//
MIM
123830
*RECORD*
*FIELD* NO
123830
*FIELD* TI
*123830 CYCLIC NUCLEOTIDE PHOSPHODIESTERASE; CNP
;;CNP1;;
2-PRIME,3-PRIME @CYCLIC NUCLEOTIDE 3-PRIME PHOSPHOHYDROLASE
read more*FIELD* TX
CLONING
Cyclic nucleotide phosphodiesterase is a useful marker of myelin. CNPase
is a membrane-bound enzyme found at high concentrations in central
nervous system myelin and in the outer segments of photoreceptors in the
retina (Vogel and Thompson, 1988). Two proteins with CNP activity are
known to exist in brain and lymphoid tissues. They appear to be the
products of distinct but related mRNA species. Kurihara et al. (1990)
showed that the 2 gene products can arise by translation of 2 mRNAs
alternatively spliced from a single transcript. In bovine and human
brain, there appears to be a single species of mRNA (Vogel and Thompson,
1988), and the bovine brain and retinal forms of the enzyme appear to be
identical in sequence.
By Northern blot analysis, Miyoshi et al. (2001) determined that mouse
Cnp1 was expressed as a major 2.5-kb transcript and a minor 2.3-kb
transcript. Highest expression was in brain, followed by liver, lung,
spleen, and heart, with little to no expression in the other tissues
examined.
GENE FUNCTION
Bifulco et al. (2002) demonstrated that CNP is firmly associated with
tubulin (602529) from brain tissue and thyroid cells. They showed that
CNP acts as a microtubule-associated protein in promoting microtubule
assembly. This activity was found to reside in the C terminus of the
enzyme. The authors concluded that CNP is a membrane-bound
microtubule-associated protein that can link tubulin to membranes and
may regulate cytoplasmic microtubule distribution.
GENE STRUCTURE
Douglas et al. (1992) used human CNP cDNAs to isolate genomic clones
containing the CNP gene which they found to be 9 kb long, with 4 exons
separated by 3 introns. Using human CNP cDNA as probes, Monoh et al.
(1993) isolated genomic DNA clones. Restriction mapping and sequence
analysis demonstrated that the human CNP gene is about 8.5 kb long.
There are 2 transcription start points and, in human brain, 2 forms of
CNP mRNA are produced from a single gene by alternative splicing,
similar to the mouse.
Miyoshi et al. (2001) determined that the mouse Cnp1 gene contains 4
exons and spans 6.8 kb.
MAPPING
Using cDNA probes corresponding to CNP, Bernier et al. (1988) assigned
CNP genes to chromosomes 3 and 11 in the mouse. The gene on chromosome
11 is closely linked to the GFAP locus (137780).
Using a human partial cDNA to clone a genomic library, Douglas et al.
(1991, 1992) isolated a clone containing the entire structural gene for
human CNPase and constructed primers for polymerase chain reaction (PCR)
analysis of a panel of somatic cell hybrids, which showed that only
hybrids containing human chromosome 17 produced a PCR product. By
fluorescence in situ hybridization, they showed that the gene is located
at 17q21. Neither method showed evidence of a gene on human chromosome 1
in an area homologous to chromosome 3 of the mouse.
Sprinkle et al. (1992) confirmed the assignment of CNP to chromosome 17
by PCR used with 2 somatic cell hybrid DNA panels. They identified an
intron C-to-T polymorphism at nucleotide 1215 that might be useful in
mapping the CNP gene more precisely within chromosome 17. Sprinkle et
al. (1993) refined the assignment of CNP on chromosome 17 by a 2-step
strategy. First, dot blots containing DNA from the parents of 10
three-generation families were screened to identify informative
families. Second, 53 members of 4 selected families were typed at this
locus. In these 4 families, 29 sibs carried a total of 84 meiotic
breakpoints on chromosome 17. Based on the genotypes observed in these
29 sibs, the CNP gene was localized to a fragment bounded by thyroid
receptor A1 (THRA1; 190120) at 17q11.2 and nerve growth factor receptor
(NGFR; 162010) at 17q21-q22. The genetic distance separating these
flanking loci is approximately 6 cM.
By spot-blot hybridization of flow-sorted human chromosomes, Monoh et
al. (1993) demonstrated that the CNP gene is on chromosome 17.
Miyoshi et al. (2001) determined that the mouse Cnp1 gene lies in a
tail-to-tail orientation with the Dnajc7 gene (601964) on chromosome 11,
downstream of the Stat5b gene (604260).
ANIMAL MODEL
Myelination of axons by oligodendrocytes enables rapid impulse
propagation in the central nervous system. Lappe-Siefke et al. (2003)
showed that Cnp1 is essential for axonal survival but not for myelin
assembly. In the absence of glial cyclic nucleotide phosphodiesterase,
mice developed axonal swellings and neurodegeneration throughout the
brain, leading to hydrocephalus and premature death. But, in contrast to
previously studied myelin mutants, the ultrastructure, periodicity, and
physical stability of myelin were not altered in these mice. Therefore,
by genetic means, the chief function of glia in supporting axonal
integrity can be completely uncoupled from its function in maintaining
compact myelin. Oligodendrocyte dysfunction, such as that in the lesions
of multiple sclerosis, may suffice to cause secondary axonal loss.
*FIELD* RF
1. Bernier, L.; Colman, D. R.; D'Eustachio, P.: Chromosomal locations
of genes encoding 2-prime,3-prime cyclic nucleotide 3-prime-phosphodiesterase
and glial fibrillary acidic protein in the mouse. J. Neurosci. Res. 20:
497-504, 1988.
2. Bifulco, M.; Laezza, C.; Stingo, S.; Wolff, J.: 2-prime,3-prime-cyclic
nucleotide 3-prime-phosphodiesterase: a membrane-bound, microtubule-associated
protein and membrane anchor for tubulin. Proc. Nat. Acad. Sci. 99:
1807-1812, 2002.
3. Douglas, A. J.; Fox, M. F.; Abbott, C. M.; Hinks, L. J.; Sharpe,
G.; Povey, S.; Thompson, R. J.: Structure and chromosomal localization
of the human 2-prime,3-prime-cyclic nucleotide 3-prime-phosphodiesterase
gene. Ann. Hum. Genet. 56: 243-254, 1992.
4. Douglas, A. J.; Fox, M. F.; Hinks, L. J.; Povey, S.; Thompson,
R. J.: Localization of the myelin specific enzyme 2-prime,3-prime-cyclic
nucleotide-3-prime-phosphohydrolase to 17q21. (Abstract) Cytogenet.
Cell Genet. 58: 2004 only, 1991.
5. Kurihara, T.; Monoh, K.; Sakimura, K.; Takahashi, Y.: Alternative
splicing of mouse brain 2-prime,3-prime-cyclic nucleotide 3-prime-phosphodiesterase
mRNA. Biochem. Biophys. Res. Commun. 170: 1074-1081, 1990.
6. Lappe-Siefke, C.; Goebbels, S.; Gravel, M.; Nicksch, E.; Lee, J.;
Braun, P. E.; Griffiths, I. R.; Nave, K.-A.: Disruption of Cnp1 uncouples
oligodendroglial functions in axonal support and myelination. Nature
Genet. 33: 366-374, 2003.
7. Miyoshi, K.; Cui, Y.; Riedlinger, G.; Robinson, P.; Lehoczky, J.;
Zon, L.; Oka, T.; Dewar, K.; Hennighausen, L.: Structure of the mouse
Stat 3/5 locus: evolution from Drosophila to zebrafish to mouse. Genomics 71:
150-155, 2001.
8. Monoh, K.; Kurihara, T.; Takahashi, Y.; Ichikawa, T.; Kumanishi,
T.; Hayashi, S.; Minoshima, S.; Shimizu, N.: Structure, expression
and chromosomal localization of the gene encoding human 2-prime,3-prime-cyclic-nucleotide
3-prime-phosphodiesterase. Gene 129: 297-301, 1993.
9. Sprinkle, T. J.; Kouri, R. E.; Fain, P. D.; Stoming, T. A.; Whitney,
J. B., III: Chromosomal mapping of the human CNP gene using a meiotic
crossover DNA panel, PCR, and allele-specific probes. Genomics 16:
542-545, 1993.
10. Sprinkle, T. J.; Lanclos, K. D.; Lapp, D. F.: Assignment of the
human 2-prime,3-prime-cyclic nucleotide 3-prime-phosphohydrolase gene
to chromosome 17. Genomics 13: 877-880, 1992.
11. Vogel, U. S.; Thompson, R. J.: Molecular structure, localization,
and possible functions of the myelin-associated enzyme 2-prime,3-prime-cyclic
nucleotide 3-prime-phosphodiesterase. J. Neurochem. 50: 1667-1677,
1988.
*FIELD* CN
Patricia A. Hartz - updated: 4/1/2004
Victor A. McKusick - updated: 2/20/2003
Victor A. McKusick - updated: 3/5/2002
*FIELD* CD
Victor A. McKusick: 11/14/1988
*FIELD* ED
mgross: 04/20/2004
mgross: 4/16/2004
terry: 4/1/2004
alopez: 2/28/2003
alopez: 2/21/2003
terry: 2/20/2003
mgross: 3/11/2002
terry: 3/5/2002
carol: 1/13/1995
carol: 5/26/1993
carol: 4/7/1993
carol: 12/17/1992
carol: 8/11/1992
carol: 7/1/1992
*RECORD*
*FIELD* NO
123830
*FIELD* TI
*123830 CYCLIC NUCLEOTIDE PHOSPHODIESTERASE; CNP
;;CNP1;;
2-PRIME,3-PRIME @CYCLIC NUCLEOTIDE 3-PRIME PHOSPHOHYDROLASE
read more*FIELD* TX
CLONING
Cyclic nucleotide phosphodiesterase is a useful marker of myelin. CNPase
is a membrane-bound enzyme found at high concentrations in central
nervous system myelin and in the outer segments of photoreceptors in the
retina (Vogel and Thompson, 1988). Two proteins with CNP activity are
known to exist in brain and lymphoid tissues. They appear to be the
products of distinct but related mRNA species. Kurihara et al. (1990)
showed that the 2 gene products can arise by translation of 2 mRNAs
alternatively spliced from a single transcript. In bovine and human
brain, there appears to be a single species of mRNA (Vogel and Thompson,
1988), and the bovine brain and retinal forms of the enzyme appear to be
identical in sequence.
By Northern blot analysis, Miyoshi et al. (2001) determined that mouse
Cnp1 was expressed as a major 2.5-kb transcript and a minor 2.3-kb
transcript. Highest expression was in brain, followed by liver, lung,
spleen, and heart, with little to no expression in the other tissues
examined.
GENE FUNCTION
Bifulco et al. (2002) demonstrated that CNP is firmly associated with
tubulin (602529) from brain tissue and thyroid cells. They showed that
CNP acts as a microtubule-associated protein in promoting microtubule
assembly. This activity was found to reside in the C terminus of the
enzyme. The authors concluded that CNP is a membrane-bound
microtubule-associated protein that can link tubulin to membranes and
may regulate cytoplasmic microtubule distribution.
GENE STRUCTURE
Douglas et al. (1992) used human CNP cDNAs to isolate genomic clones
containing the CNP gene which they found to be 9 kb long, with 4 exons
separated by 3 introns. Using human CNP cDNA as probes, Monoh et al.
(1993) isolated genomic DNA clones. Restriction mapping and sequence
analysis demonstrated that the human CNP gene is about 8.5 kb long.
There are 2 transcription start points and, in human brain, 2 forms of
CNP mRNA are produced from a single gene by alternative splicing,
similar to the mouse.
Miyoshi et al. (2001) determined that the mouse Cnp1 gene contains 4
exons and spans 6.8 kb.
MAPPING
Using cDNA probes corresponding to CNP, Bernier et al. (1988) assigned
CNP genes to chromosomes 3 and 11 in the mouse. The gene on chromosome
11 is closely linked to the GFAP locus (137780).
Using a human partial cDNA to clone a genomic library, Douglas et al.
(1991, 1992) isolated a clone containing the entire structural gene for
human CNPase and constructed primers for polymerase chain reaction (PCR)
analysis of a panel of somatic cell hybrids, which showed that only
hybrids containing human chromosome 17 produced a PCR product. By
fluorescence in situ hybridization, they showed that the gene is located
at 17q21. Neither method showed evidence of a gene on human chromosome 1
in an area homologous to chromosome 3 of the mouse.
Sprinkle et al. (1992) confirmed the assignment of CNP to chromosome 17
by PCR used with 2 somatic cell hybrid DNA panels. They identified an
intron C-to-T polymorphism at nucleotide 1215 that might be useful in
mapping the CNP gene more precisely within chromosome 17. Sprinkle et
al. (1993) refined the assignment of CNP on chromosome 17 by a 2-step
strategy. First, dot blots containing DNA from the parents of 10
three-generation families were screened to identify informative
families. Second, 53 members of 4 selected families were typed at this
locus. In these 4 families, 29 sibs carried a total of 84 meiotic
breakpoints on chromosome 17. Based on the genotypes observed in these
29 sibs, the CNP gene was localized to a fragment bounded by thyroid
receptor A1 (THRA1; 190120) at 17q11.2 and nerve growth factor receptor
(NGFR; 162010) at 17q21-q22. The genetic distance separating these
flanking loci is approximately 6 cM.
By spot-blot hybridization of flow-sorted human chromosomes, Monoh et
al. (1993) demonstrated that the CNP gene is on chromosome 17.
Miyoshi et al. (2001) determined that the mouse Cnp1 gene lies in a
tail-to-tail orientation with the Dnajc7 gene (601964) on chromosome 11,
downstream of the Stat5b gene (604260).
ANIMAL MODEL
Myelination of axons by oligodendrocytes enables rapid impulse
propagation in the central nervous system. Lappe-Siefke et al. (2003)
showed that Cnp1 is essential for axonal survival but not for myelin
assembly. In the absence of glial cyclic nucleotide phosphodiesterase,
mice developed axonal swellings and neurodegeneration throughout the
brain, leading to hydrocephalus and premature death. But, in contrast to
previously studied myelin mutants, the ultrastructure, periodicity, and
physical stability of myelin were not altered in these mice. Therefore,
by genetic means, the chief function of glia in supporting axonal
integrity can be completely uncoupled from its function in maintaining
compact myelin. Oligodendrocyte dysfunction, such as that in the lesions
of multiple sclerosis, may suffice to cause secondary axonal loss.
*FIELD* RF
1. Bernier, L.; Colman, D. R.; D'Eustachio, P.: Chromosomal locations
of genes encoding 2-prime,3-prime cyclic nucleotide 3-prime-phosphodiesterase
and glial fibrillary acidic protein in the mouse. J. Neurosci. Res. 20:
497-504, 1988.
2. Bifulco, M.; Laezza, C.; Stingo, S.; Wolff, J.: 2-prime,3-prime-cyclic
nucleotide 3-prime-phosphodiesterase: a membrane-bound, microtubule-associated
protein and membrane anchor for tubulin. Proc. Nat. Acad. Sci. 99:
1807-1812, 2002.
3. Douglas, A. J.; Fox, M. F.; Abbott, C. M.; Hinks, L. J.; Sharpe,
G.; Povey, S.; Thompson, R. J.: Structure and chromosomal localization
of the human 2-prime,3-prime-cyclic nucleotide 3-prime-phosphodiesterase
gene. Ann. Hum. Genet. 56: 243-254, 1992.
4. Douglas, A. J.; Fox, M. F.; Hinks, L. J.; Povey, S.; Thompson,
R. J.: Localization of the myelin specific enzyme 2-prime,3-prime-cyclic
nucleotide-3-prime-phosphohydrolase to 17q21. (Abstract) Cytogenet.
Cell Genet. 58: 2004 only, 1991.
5. Kurihara, T.; Monoh, K.; Sakimura, K.; Takahashi, Y.: Alternative
splicing of mouse brain 2-prime,3-prime-cyclic nucleotide 3-prime-phosphodiesterase
mRNA. Biochem. Biophys. Res. Commun. 170: 1074-1081, 1990.
6. Lappe-Siefke, C.; Goebbels, S.; Gravel, M.; Nicksch, E.; Lee, J.;
Braun, P. E.; Griffiths, I. R.; Nave, K.-A.: Disruption of Cnp1 uncouples
oligodendroglial functions in axonal support and myelination. Nature
Genet. 33: 366-374, 2003.
7. Miyoshi, K.; Cui, Y.; Riedlinger, G.; Robinson, P.; Lehoczky, J.;
Zon, L.; Oka, T.; Dewar, K.; Hennighausen, L.: Structure of the mouse
Stat 3/5 locus: evolution from Drosophila to zebrafish to mouse. Genomics 71:
150-155, 2001.
8. Monoh, K.; Kurihara, T.; Takahashi, Y.; Ichikawa, T.; Kumanishi,
T.; Hayashi, S.; Minoshima, S.; Shimizu, N.: Structure, expression
and chromosomal localization of the gene encoding human 2-prime,3-prime-cyclic-nucleotide
3-prime-phosphodiesterase. Gene 129: 297-301, 1993.
9. Sprinkle, T. J.; Kouri, R. E.; Fain, P. D.; Stoming, T. A.; Whitney,
J. B., III: Chromosomal mapping of the human CNP gene using a meiotic
crossover DNA panel, PCR, and allele-specific probes. Genomics 16:
542-545, 1993.
10. Sprinkle, T. J.; Lanclos, K. D.; Lapp, D. F.: Assignment of the
human 2-prime,3-prime-cyclic nucleotide 3-prime-phosphohydrolase gene
to chromosome 17. Genomics 13: 877-880, 1992.
11. Vogel, U. S.; Thompson, R. J.: Molecular structure, localization,
and possible functions of the myelin-associated enzyme 2-prime,3-prime-cyclic
nucleotide 3-prime-phosphodiesterase. J. Neurochem. 50: 1667-1677,
1988.
*FIELD* CN
Patricia A. Hartz - updated: 4/1/2004
Victor A. McKusick - updated: 2/20/2003
Victor A. McKusick - updated: 3/5/2002
*FIELD* CD
Victor A. McKusick: 11/14/1988
*FIELD* ED
mgross: 04/20/2004
mgross: 4/16/2004
terry: 4/1/2004
alopez: 2/28/2003
alopez: 2/21/2003
terry: 2/20/2003
mgross: 3/11/2002
terry: 3/5/2002
carol: 1/13/1995
carol: 5/26/1993
carol: 4/7/1993
carol: 12/17/1992
carol: 8/11/1992
carol: 7/1/1992