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UniProtKB/Swiss-Prot entry P06802


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name ENPP1_MOUSE
Primary accession number P06802
Secondary accession numbers Q542E9 Q924C4
Integrated into Swiss-Prot on January 1, 1988
Sequence was last modified on September 19, 2002 (Sequence version 4)
Annotations were last modified on    July 22, 2008 (Entry version 92)
Name and origin of the protein
Protein name Ectonucleotide pyrophosphatase/phosphodiesterase family member 1
Synonyms E-NPP 1
Phosphodiesterase I/nucleotide pyrophosphatase 1
Plasma-cell membrane glycoprotein PC-1
Lymphocyte antigen 41
Ly-41
Includes Alkaline phosphodiesterase I
     (EC 3.1.4.1)
Nucleotide pyrophosphatase
     (NPPase)
     (EC 3.6.1.9)
Gene name
Name: Enpp1
Synonyms: Npps, Pc1, Pdnp1
From
Mus musculus (Mouse) [TaxID: 10090] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; Muroidea; Muridae; Murinae; Mus.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
STRAIN=BALB/c;
PubMed=3104326 [NCBI, ExPASy, EBI, Israel, Japan]
van Driel I.R., Goding J.W.;
"Plasma cell membrane glycoprotein PC-1. Primary structure deduced from cDNA clones.";
J. Biol. Chem. 262:4882-4887(1987).
[2]
SEQUENCE REVISION TO 24; 46-47; 642 AND 693.
Goding J.W.;
Submitted (JAN-2001) to the EMBL/GenBank/DDBJ databases.
[3]
NUCLEOTIDE SEQUENCE [MRNA], GLYCOSYLATION, AND FUNCTION.
STRAIN=BALB/c;
TISSUE=Plasmacytoma;
PubMed=1647027 [NCBI, ExPASy, EBI, Israel, Japan]
Rebbe N.F., Tong B.D., Finley E.M., Hickman S.;
"Identification of nucleotide pyrophosphatase/alkaline phosphodiesterase I activity associated with the mouse plasma cell differentiation antigen PC-1.";
Proc. Natl. Acad. Sci. U.S.A. 88:5192-5196(1991).
[4]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANTS ARG-651 AND SER-680, AND ALTERNATIVE SPLICING.
DOI=10.1046/j.1365-2370.2002.00330.x; PubMed=12121276 [NCBI, ExPASy, EBI, Israel, Japan]
Banakh I., Sali A., Dubljevic V., Grobben B., Slegers H., Goding J.W.;
"Structural basis of allotypes of ecto-nucleotide pyrophosphatase/phosphodiesterase (plasma cell membrane glycoprotein PC-1) in the mouse and rat, and analysis of allele-specific xenogeneic antibodies.";
Eur. J. Immunogenet. 29:307-313(2002).
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
STRAIN=NOD;
TISSUE=Thymus;
DOI=10.1126/science.1112014; PubMed=16141072 [NCBI, ExPASy, EBI, Israel, Japan]
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.;
"The transcriptional landscape of the mammalian genome.";
Science 309:1559-1563(2005).
[6]
NUCLEOTIDE SEQUENCE [MRNA] OF 168-188.
PubMed=8223581 [NCBI, ExPASy, EBI, Israel, Japan]
Belli S.I., van Driel I.R., Goding J.W.;
"Identification and characterization of a soluble form of the plasma cell membrane glycoprotein PC-1 (5'-nucleotide phosphodiesterase).";
Eur. J. Biochem. 217:421-428(1993).
[7]
NUCLEOTIDE SEQUENCE [MRNA] OF 203-219.
PubMed=3001713 [NCBI, ExPASy, EBI, Israel, Japan]
van Driel I.R., Wilks A.F., Pietersz G.A., Goding J.W.;
"Murine plasma cell membrane antigen PC-1: molecular cloning of cDNA and analysis of expression.";
Proc. Natl. Acad. Sci. U.S.A. 82:8619-8623(1985).
[8]
PROTEIN SEQUENCE OF 204-219; 332-351; 486-509; 716-725; 803-818 AND 855-867.
PubMed=3917281 [NCBI, ExPASy, EBI, Israel, Japan]
Stearne P.A., van Driel I.R., Grego B., Simpson R.J., Goding J.W.;
"The murine plasma cell antigen PC-1: purification and partial amino acid sequence.";
J. Immunol. 134:443-448(1985).
[9]
IDENTIFICATION OF POSSIBLE INITIATION SITE.
PubMed=2211644 [NCBI, ExPASy, EBI, Israel, Japan]
Buckley M.F., Loveland K.A., McKinstry W.J., Garson O.M., Goding J.W.;
"Plasma cell membrane glycoprotein PC-1. cDNA cloning of the human molecule, amino acid sequence, and chromosomal location.";
J. Biol. Chem. 265:17506-17511(1990).
[10]
DISEASE.
DOI=10.1038/956; PubMed=9662402 [NCBI, ExPASy, EBI, Israel, Japan]
Okawa A., Nakamura I., Goto S., Moriya H., Nakamura Y., Ikegawa S.;
"Mutation in Npps in a mouse model of ossification of the posterior longitudinal ligament of the spine.";
Nat. Genet. 19:271-273(1998).
[11]
ACTIVE SITE, METAL-BINDING, AND MUTAGENESIS OF ASP-200; LYS-237; THR-238; PHE-239; ASP-358; HIS-362; ASP-405; HIS-406 AND HIS-517.
DOI=10.1074/jbc.M007552200; PubMed=11027689 [NCBI, ExPASy, EBI, Israel, Japan]
Gijsbers R., Ceulemans H., Stalmans W., Bollen M.;
"Structural and catalytic similarities between nucleotide pyrophosphatases/phosphodiesterases and alkaline phosphatases.";
J. Biol. Chem. 276:1361-1368(2001).
[12]
DI-LEUCINE MOTIF, MUTAGENESIS OF ALA-28; SER-30; LEU-31 AND LEU-32, AND SUBCELLULAR LOCATION.
PubMed=11598187 [NCBI, ExPASy, EBI, Israel, Japan]
Bello V., Goding J.W., Greengrass V., Sali A., Dubljevic V., Lenoir C., Trugnan G., Maurice M.;
"Characterization of a di-leucine-based signal in the cytoplasmic tail of the nucleotide-pyrophosphatase NPP1 that mediates basolateral targeting but not endocytosis.";
Mol. Biol. Cell 12:3004-3015(2001).
[13]
DI-LEUCINE MOTIF, MUTAGENESIS OF LEU-31; LEU-32; LEU-42 AND TYR-57, AND SUBCELLULAR LOCATION.
DOI=10.1152/ajpcell.00320.2003; PubMed=15075217 [NCBI, ExPASy, EBI, Israel, Japan]
Vaingankar S.M., Fitzpatrick T.A., Johnson K., Goding J.W., Maurice M., Terkeltaub R.;
"Subcellular targeting and function of osteoblast nucleotide pyrophosphatase phosphodiesterase 1.";
Am. J. Physiol. 286:C1177-C1187(2004).
Comments
  • FUNCTION: Involved primarily in ATP hydrolysis at the plasma membrane. Plays a role in regulating pyrophosphate levels, and functions in bone mineralization and soft tissue calcification. In vitro, has a broad specificity, hydrolyzing other nucleoside 5' triphosphates such as GTP, CTP, TTP and UTP to their corresponding monophosphates with release of pyrophosphate and diadenosine polyphosphates, and also 3',5'-cAMP to AMP. May also be involved in the regulation of the availability of nucleotide sugars in the endoplasmic reticulum and Golgi, and the regulation of purinergic signaling. Appears to modulate insulin sensitivity (By similarity).
  • CATALYTIC ACTIVITY: Hydrolytically removes 5'-nucleotides successively from the 3'-hydroxy termini of 3'-hydroxy-terminated oligonucleotides.
  • CATALYTIC ACTIVITY: A dinucleotide + H2O = 2 mononucleotides.
  • COFACTOR: Binds 2 divalent metal cations per subunit (Probable).
  • ENZYME REGULATION: At low concentrations of ATP, a phosphorylated intermediate is formed which inhibits further hydrolysis.
  • SUBUNIT: Homodimer; disulfide-linked.
  • SUBCELLULAR LOCATION: Membrane; Single-pass type II membrane protein. Note=Targeted to the basolateral membrane in polarized epithelial cells and in hepatocytes, and to matrix vesicles in osteoblasts. In bile duct cells and cancer cells, located to the apical cytoplasmic side (By similarity).
  • ALTERNATIVE PRODUCTS: 2 named isoforms [FASTA] produced by alternative splicing.
    Name2
    Isoform IDP06802-1
    This is the isoform sequence displayed in this entry.
    Name1
    Isoform IDP06802-2
    Features which should be applied to build the isoform sequence: VSP_006748.
  • TISSUE SPECIFICITY: Selectively expressed on the surface of antibody-secreting cells.
  • DOMAIN: The di-leucine motif is required for basolateral targeting in polarized epithelial cells, and for targeting to matrix vesicles derived from mineralizing cells.
  • PTM: The N-terminal is blocked.
  • PTM: N-glycosylated.
  • PTM: It has been suggested that the active SMB domain may be permitted considerable disulfide bond heterogeneity or variability, thus two alternate disulfide patterns based on 3D structures are described with 1 disulfide bond conserved in both.
  • DISEASE: Defects in Enpp1 are the cause of the tiptoe walking (ttw) phenotype. Ttw mice exhibit ossification of the spinal ligaments.
  • SIMILARITY: Belongs to the nucleotide pyrophosphatase/phosphodiesterase family.
  • SIMILARITY: Contains 2 SMB (somatomedin-B) domains.
  • CAUTION: It is uncertain whether Met-1 or Met-35 is the initiator.
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
J02700; AAA39893.2; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF339910; AAK84174.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AK088857; BAC40616.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
L04516; -; NOT_ANNOTATED_CDS; Unassigned_DNA.[EMBL / GenBank / DDBJ]
M12552; AAA39892.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
PIR A27410; A27410.
UniGene Mm.27254
3D structure databases
ModBase P06802.
PTM databases
PhosphoSite P06802; -.
Organism-specific databases
MGI MGI:97370; Enpp1.
Gene expression databases
ArrayExpress P06802; -.
GermOnline ENSMUSG00000037370; Mus musculus.
Ontologies
GO
GO:0009986; Cellular component: cell surface (inferred from direct assay from UniProtKB).
GO:0005615; Cellular component: extracellular space (inferred from direct assay from UniProtKB).
GO:0045599; Biological process: negative regulation of fat cell differentiation (inferred from mutant phenotype from UniProtKB).
GO:0030279; Biological process: negative regulation of ossification (inferred from mutant phenotype from MGI).
QuickGo view.
Family and domain databases
InterPro IPR017849; Alkaline_Pase-like_a/b/a.
IPR001604; Endonuclease.
IPR002591; Phosphodiest/P_Trfase.
IPR001212; Somatomedin_B.
Graphical view of domain structure.
Gene3D G3DSA:3.40.720.10; Alk_phosphtse; 1.
G3DSA:3.40.570.10; Endonuclease; 1.
Pfam PF01663; Phosphodiest; 1.
PF01033; Somatomedin_B; 2.
Pfam graphical view of domain structure.
PRINTS PR00022; SOMATOMEDINB.
SMART SM00477; NUC; 1.
SM00201; SO; 2.
SMART graphical view of domain structure.
PROSITE PS00524; SMB_1; 2.
PS50958; SMB_2; 2.
PROSITE graphical view of domain structure (profiles).
BLOCKS P06802.
Genome annotation databases
Ensembl ENSMUSG00000037370; Mus musculus. [Contig view]
Phylogenomic databases
HOGENOM P06802; -.
HOVERGEN P06802; -.
Other
SOURCE Enpp1; Mus musculus.
ProtoNet P06802.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
Alternative splicing; Biomineralization; Direct protein sequencing; Disease mutation; Glycoprotein; Hydrolase; Membrane; Metal-binding; Multifunctional enzyme; Phosphoprotein; Polymorphism; Repeat; Signal-anchor; Transmembrane.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom   To Length Description FTId
CHAIN   1   906  906     Ectonucleotide pyrophosphatase/phosphodiesterase family member 1. PRO_0000188565
TOPO_DOM   1    58  58     Cytoplasmic (Potential). 
TRANSMEM   59    79  21     Signal-anchor for type II membrane protein (Potential). 
TOPO_DOM   80   906  827     Extracellular (Potential). 
DOMAIN   86   126  41     SMB 1. 
DOMAIN   127   171  45     SMB 2. 
REGION   173   573  401     Phosphodiesterase. 
REGION   635   906  272     Nuclease. 
MOTIF   27    34  8     Di-leucine motif. 
ACT_SITE   238   238        AMP-threonine intermediate. 
METAL   200   200        Divalent metal cation 2 (Probable). 
METAL   358   358        Divalent metal cation 1 (Probable). 
METAL   362   362        Divalent metal cation 1 (Probable). 
METAL   405   405        Divalent metal cation 2 (Probable). 
METAL   406   406        Divalent metal cation 2 (Probable). 
METAL   517   517        Divalent metal cation 1 (Probable). 
CARBOHYD   161   161        N-linked (GlcNAc...) (Potential). 
CARBOHYD   267   267        N-linked (GlcNAc...) (Potential). 
CARBOHYD   323   323        N-linked (GlcNAc...) (Potential). 
CARBOHYD   459   459        N-linked (GlcNAc...) (Potential). 
CARBOHYD   567   567        N-linked (GlcNAc...) (Potential). 
CARBOHYD   624   624        N-linked (GlcNAc...) (Potential). 
DISULFID   90   104        Alternate (By similarity). 
DISULFID   90    94        Alternate (By similarity). 
DISULFID   94   122        Alternate (By similarity). 
DISULFID   102   115        Alternate (By similarity). 
DISULFID   102   104        Alternate (By similarity). 
DISULFID   108   114        By similarity. 
DISULFID   115   122        Alternate (By similarity). 
DISULFID   131   148        Alternate (By similarity). 
DISULFID   131   136        Alternate (By similarity). 
DISULFID   136   166        Alternate (By similarity). 
DISULFID   146   159        Alternate (By similarity). 
DISULFID   146   148        Alternate (By similarity). 
DISULFID   152   158        By similarity. 
DISULFID   159   166        Alternate (By similarity). 
VAR_SEQ   630   630        Missing (in isoform 1). VSP_006748
VARIANT   651   651  1     H -> R (in allele ENPP1b). 
VARIANT   680   680  1     R -> S (in allele ENPP1b). 
MUTAGEN   28    28        A->G: No effect on basolateral sorting in epithelial cells. 
MUTAGEN   30    30        S->A,D: Little change in baolateral sorting in epithelial cells. 
MUTAGEN   31    31        L->A: 60% of ENPP1 redirected to apical surface in epithelial cells. 75% of ENPP1 redirected to apical surface in epithelial cells; abrogation of increased NPP activity in oestoblastic matrix vesicles; when associated with A-32. 
MUTAGEN   32    32        L->A: 70% of ENPP1 redirected to apical surface in epithelial cells; abrogation of increased NPP activity in oestoblastic matrix vesicles. 75% of ENPP1 redirected to apical surface in epithelial cells; abrogation of increased NPP activity in oestoblastic matrix vesicles; when associated with A-31. 
MUTAGEN   42    42        L->A: No change in increased NPP activity in oestoblastic matrix vesicles. 
MUTAGEN   57    57        Y->G: No change in increased NPP activity in oestoblastic matrix vesicles. 
MUTAGEN   200   200        D->N: Decreases phosphodiesterase activity by 95%. Abolishes formation of nucleotidylated intermediate. 
MUTAGEN   237   237        K->A: Decreases phosphodiesterase activity by 40%. Decreased formation of nucleotidylated intermediate. 
MUTAGEN   238   238        T->A: Abolishes all phosphodiesterase activity. Abolishes formation of nucleotidylated intermediate. 
MUTAGEN   238   238        T->S: Decreases phosphodiesterase activity by 95%. Accumulates nucleotidylated intermediate. 
MUTAGEN   239   239        F->A: Decreases phosphodiesterase activity by 50%. Decreased formation of nucleotidylated intermediate. 
MUTAGEN   358   358        D->Q: Decreases phosphodiesterase activity by 90%. Accumulates nucleotidylated intermediate. 
MUTAGEN   362   362        H->Q: Decreases phosphodiesterase activity by 95%. 65% activity can be restored by addition of Zn2+ ions. Accumulates nucleotidylated intermediate. 
MUTAGEN   405   405        D->N: Abolishes all phosphodiesterase activity. 10% activity can be restored by addition of Zn2+ ions. Abolishes formation of nucleotidylated intermediate. 
MUTAGEN   406   406        H->Q: Abolishes all phosphodiesterase activity. 15% activity can be restored by addition of Zn2+ ions. Abolishes formation of nucleotidylated intermediate. 
MUTAGEN   517   517        H->Q: Abolishes all phosphodiesterase activity. 60% activity can be restored by addition of Zn2+ ions. Abolishes formation of nucleotidylated intermediate. 
Sequence information
Length: 906 AA [This is the length of the unprocessed precursor] Molecular weight: 103176 Da [This is the MW of the unprocessed precursor] CRC64: 068D45B0ED0F224D [This is a checksum on the sequence]
        10         20         30         40         50         60 
MERDGDQAGH GPRHGSAGNG RELESPAAAS LLAPMDLGEE PLEKAERARP AKDPNTYKVL 

        70         80         90        100        110        120 
SLVLSVCVLT TILGCIFGLK PSCAKEVKSC KGRCFERTFS NCRCDAACVS LGNCCLDFQE 

       130        140        150        160        170        180 
TCVEPTHIWT CNKFRCGEKR LSRFVCSCAD DCKTHNDCCI NYSSVCQDKK SWVEETCESI 

       190        200        210        220        230        240 
DTPECPAEFE SPPTLLFSLD GFRAEYLHTW GGLLPVISKL KNCGTYTKNM RPMYPTKTFP 

       250        260        270        280        290        300 
NHYSIVTGLY PESHGIIDNK MYDPKMNASF SLKSKEKFNP LWYKGQPIWV TANHQEVKSG 

       310        320        330        340        350        360 
TYFWPGSDVE IDGILPDIYK VYNGSVPFEE RILAVLEWLQ LPSHERPHFY TLYLEEPDSS 

       370        380        390        400        410        420 
GHSHGPVSSE VIKALQKVDR LVGMLMDGLK DLGLDKCLNL ILISDHGMEQ GSCKKYVYLN 

       430        440        450        460        470        480 
KYLGDVNNVK VVYGPAARLR PTDVPETYYS FNYEALAKNL SCREPNQHFR PYLKPFLPKR 

       490        500        510        520        530        540 
LHFAKSDRIE PLTFYLDPQW QLALNPSERK YCGSGFHGSD NLFSNMQALF IGYGPAFKHG 

       550        560        570        580        590        600 
AEVDSFENIE VYNLMCDLLG LIPAPNNGSH GSLNHLLKKP IYNPSHPKEE GFLSQCPIKS 

       610        620        630        640        650        660 
TSNDLGCTCD PWIVPIKDFE KQLNLTTEDV DDIYHMTVPY GRPRILLKQH HVCLLQQQQF 

       670        680        690        700        710        720 
LTGYSLDLLM PLWASYTFLR NDQFSRDDFS NCLYQDLRIP LSPVHKCSYY KSNSKLSYGF 

       730        740        750        760        770        780 
LTPPRLNRVS NHIYSEALLT SNIVPMYQSF QVIWHYLHDT LLQRYAHERN GINVVSGPVF 

       790        800        810        820        830        840 
DFDYDGRYDS LEILKQNSRV IRSQEILIPT HFFIVLTSCK QLSETPLECS ALESSAYILP 

       850        860        870        880        890        900 
HRPDNIESCT HGKRESSWVE ELLTLHRARV TDVELITGLS FYQDRQESVS ELLRLKTHLP 


IFSQED 

P06802 in FASTA format

View entry in original UniProtKB/Swiss-Prot format
View entry in raw text format (no links)
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