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Q8WVQ1 (CANT1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 107. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Soluble calcium-activated nucleotidase 1

Short name=SCAN-1
EC=3.6.1.6
Alternative name(s):
Apyrase homolog
Putative MAPK-activating protein PM09
Putative NF-kappa-B-activating protein 107
Gene names
Name:CANT1
Synonyms:SHAPY
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length401 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Calcium-dependent nucleotidase with a preference for UDP. The order of activity with different substrates is UDP > GDP > UTP > GTP. Has very low activity towards ADP and even lower activity towards ATP. Does not hydrolyze AMP and GMP. Involved in proteoglycan synthesis. Ref.1 Ref.6 Ref.8

Catalytic activity

A nucleoside diphosphate + H2O = a nucleoside phosphate + phosphate.

Cofactor

Calcium. Ref.1 Ref.6

Subunit structure

Monomer. Ref.1

Subcellular location

Endoplasmic reticulum membrane; Single-pass type II membrane protein. Golgi apparatusGolgi stack membrane; Single-pass type II membrane protein. Note: Processed form: Secreted. Ref.1

Tissue specificity

Widely expressed. Ref.1

Post-translational modification

N-glycosylated. Ref.1

Involvement in disease

Desbuquois dysplasia (DBQD) [MIM:251450]: A chondrodysplasia characterized by severe prenatal and postnatal growth retardation (less than -5 SD), joint laxity, short extremities, progressive scoliosis, round face, midface hypoplasia, prominent bulging eyes. The main radiologic features are short long bones with metaphyseal splay, a 'Swedish key' appearance of the proximal femur (exaggerated trochanter), and advance carpal and tarsal bone age. Two forms of Desbuquois dysplasia are distinguished on the basis of the presence (type 1) or absence (type 2) of characteristic hand anomalies: an extra ossification center distal to the second metacarpal, delta phalanx, bifid distal thumb phalanx, and phalangeal dislocations.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7 Ref.8 Ref.10 Ref.11 Ref.12 Ref.13

Miscellaneous

Not inhibited by azide.

Sequence similarities

Belongs to the apyrase family.

Biophysicochemical properties

pH dependence:

Optimum pH is 6.8.

Sequence caution

The sequence AAM94564.1 differs from that shown. Reason: Erroneous initiation.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8WVQ1-1)

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: Q8WVQ1-2)

The sequence of this isoform differs from the canonical sequence as follows:
     220-245: KDERLYVGGLGKEWTTTTGDVVNENP → REIVRKRWRLVKQVSHVGVLGQWIQR
     246-401: Missing.
Isoform 3 (identifier: Q8WVQ1-3)

The sequence of this isoform differs from the canonical sequence as follows:
     41-91: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 401401Soluble calcium-activated nucleotidase 1
PRO_0000209925

Regions

Topological domain1 – 4444Cytoplasmic Potential
Transmembrane45 – 6218Helical; Signal-anchor for type II membrane protein; Potential
Topological domain63 – 401339Lumenal Potential

Sites

Metal binding1681Calcium
Metal binding2151Calcium
Metal binding2841Calcium
Metal binding3451Calcium
Metal binding3961Calcium

Amino acid modifications

Glycosylation881N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence41 – 9151Missing in isoform 3.
VSP_054260
Alternative sequence220 – 24526KDERL…VNENP → REIVRKRWRLVKQVSHVGVL GQWIQR in isoform 2.
VSP_013760
Alternative sequence246 – 401156Missing in isoform 2.
VSP_013761
Natural variant1121D → E in DBQD. Ref.11
VAR_068655
Natural variant1251W → C in DBQD; severely affects activity. Ref.13
VAR_068656
Natural variant1651M → T in DBQD; severely affects activity. Ref.13
VAR_068657
Natural variant2241L → P in DBQD; affects protein stability and secretion. Ref.13
Corresponds to variant rs150181226 [ dbSNP | Ensembl ].
VAR_068658
Natural variant2261V → M in DBQD; severely affects activity. Ref.12 Ref.13
VAR_068659
Natural variant2991P → L in DBQD. Ref.10
VAR_062980
Natural variant3001R → C in DBQD; severely affects activity. Ref.10 Ref.13
VAR_062981
Natural variant3001R → H in DBQD. Ref.8 Ref.10
VAR_062982
Natural variant3031S → R in DBQD. Ref.8
VAR_068660
Natural variant3231A → T Polymorphism that does not affect activity. Ref.13
Corresponds to variant rs9903215 [ dbSNP | Ensembl ].
VAR_068661
Natural variant3601A → D in DBQD; affects protein secretion. Ref.13
VAR_068662
Natural variant3741I → N in DBQD. Ref.8
VAR_068663
Natural variant3911G → E Polymorphism that does not affect activity. Ref.13
Corresponds to variant rs34082669 [ dbSNP | Ensembl ].
VAR_068664

Experimental info

Mutagenesis1121D → A: Reduces activity by 99%. Ref.9
Mutagenesis1141D → A: Reduces activity by 99%. Ref.6 Ref.9
Mutagenesis1521G → E: Slightly reduced activity. Ref.6
Mutagenesis1601E → Y: Increases GDPase activity 2-fold and ADPase activity 5-fold. Ref.6
Mutagenesis1631R → A: Reduces activity by 98%. Ref.6
Mutagenesis1661E → Q: Reduces activity by 95%. Ref.9
Mutagenesis1681S → A: Reduces activity by over 99.9%. Ref.9
Mutagenesis1691D → N: Reduces activity by 96%. Ref.9
Mutagenesis1811D → A: Loss of activity. Ref.6
Mutagenesis1821D → N: Reduces activity by over 99.9%. Ref.9
Mutagenesis2051D → A: Slightly reduced activity. Ref.6
Mutagenesis2151E → Q: Reduces activity by 99%. Ref.9
Mutagenesis2461E → M: Increases activity 5-fold. Ref.9
Mutagenesis3011R → A: Reduces activity by 99%. Ref.6 Ref.9

Secondary structure

............................................................... 401
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified March 1, 2002. Version 1.
Checksum: 5B78EB24C0B2C4CA

FASTA40144,840
        10         20         30         40         50         60 
MPVQLSEHPE WNESMHSLRI SVGGLPVLAS MTKAADPRFR PRWKVILTFF VGAAILWLLC 

        70         80         90        100        110        120 
SHRPAPGRPP THNAHNWRLG QAPANWYNDT YPLSPPQRTP AGIRYRIAVI ADLDTESRAQ 

       130        140        150        160        170        180 
EENTWFSYLK KGYLTLSDSG DKVAVEWDKD HGVLESHLAE KGRGMELSDL IVFNGKLYSV 

       190        200        210        220        230        240 
DDRTGVVYQI EGSKAVPWVI LSDGDGTVEK GFKAEWLAVK DERLYVGGLG KEWTTTTGDV 

       250        260        270        280        290        300 
VNENPEWVKV VGYKGSVDHE NWVSNYNALR AAAGIQPPGY LIHESACWSD TLQRWFFLPR 

       310        320        330        340        350        360 
RASQERYSEK DDERKGANLL LSASPDFGDI AVSHVGAVVP THGFSSFKFI PNTDDQIIVA 

       370        380        390        400 
LKSEEDSGRV ASYIMAFTLD GRFLLPETKI GSVKYEGIEF I 

« Hide

Isoform 2 [UniParc].

Checksum: 0D53611DA70ADCAF
Show »

FASTA24527,762
Isoform 3 [UniParc].

Checksum: 3E074A6D59449646
Show »

FASTA35038,946

References

« Hide 'large scale' references
[1]"Cloning, expression, and characterization of a soluble calcium-activated nucleotidase, a human enzyme belonging to a new family of extracellular nucleotidases."
Smith T., Hicks-Berger C., Kim S., Kirley T.
Arch. Biochem. Biophys. 406:105-115(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBUNIT, COFACTOR, SUBCELLULAR LOCATION, GLYCOSYLATION, TISSUE SPECIFICITY.
Tissue: Mammary tumor.
[2]"Large-scale identification and characterization of human genes that activate NF-kappaB and MAPK signaling pathways."
Matsuda A., Suzuki Y., Honda G., Muramatsu S., Matsuzaki O., Nagano Y., Doi T., Shimotohno K., Harada T., Nishida E., Hayashi H., Sugano S.
Oncogene 22:3307-3318(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Lung fibroblast.
[3]"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. expand/collapse author list , 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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
Tissue: Mammary gland and Substantia nigra.
[4]"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).
Tissue: Ovary, Pancreas and Skin.
[5]"Cloning, expression, and functional characterization of a Ca2+-dependent endoplasmic reticulum nucleoside diphosphatase."
Failer B.U., Braun N., Zimmermann H.
J. Biol. Chem. 277:36978-36986(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 141-401 (ISOFORM 1).
Tissue: Brain.
[6]"Site-directed mutagenesis of human soluble calcium-activated nucleotidase 1 (hSCAN-1): identification of residues essential for enzyme activity and the Ca(2+)-induced conformational change."
Yang M., Kirley T.L.
Biochemistry 43:9185-9194(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, COFACTOR, MUTAGENESIS OF ASP-114; GLY-152; GLU-160; ARG-163; ASP-181; ASP-205 AND ARG-301.
[7]"Mutation of CANT1 causes Desbuquois dysplasia."
Faden M., Al-Zahrani F., Arafah D., Alkuraya F.S.
Am. J. Med. Genet. A 152:1157-1160(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN DBQD.
[8]"Further delineation of CANT1 phenotypic spectrum and demonstration of its role in proteoglycan synthesis."
Nizon M., Huber C., De Leonardis F., Merrina R., Forlino A., Fradin M., Tuysuz B., Abu-Libdeh B.Y., Alanay Y., Albrecht B., Al-Gazali L., Basaran S.Y., Clayton-Smith J., Desir J., Gill H., Greally M.T., Koparir E., van Maarle M.C. expand/collapse author list , Mackay S., Mortier G., Morton J., Sillence D., Vilain C., Young I., Zerres K., Le Merrer M., Munnich A., Le Goff C., Rossi A., Cormier-Daire V.
Hum. Mutat. 33:1261-1266(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PROTEOGLYCAN SYNTHESIS, VARIANTS DBQD HIS-300; ARG-303 AND ASN-374.
[9]"Structure and protein design of a human platelet function inhibitor."
Dai J., Liu J., Deng Y., Smith T.M., Lu M.
Cell 116:649-659(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 71-401 IN COMPLEX WITH SUBSTRATE ANALOG AND CALCIUM IONS, MUTAGENESIS OF ASP-112; ASP-114; GLU-166; SER-168; ASP-169; ASP-182; GLU-215; GLU-246 AND ARG-301.
[10]"Identification of CANT1 mutations in Desbuquois dysplasia."
Huber C., Oules B., Bertoli M., Chami M., Fradin M., Alanay Y., Al-Gazali L.I., Ausems M.G., Bitoun P., Cavalcanti D.P., Krebs A., Le Merrer M., Mortier G., Shafeghati Y., Superti-Furga A., Robertson S.P., Le Goff C., Muda A.O. expand/collapse author list , Paterlini-Brechot P., Munnich A., Cormier-Daire V.
Am. J. Hum. Genet. 85:706-710(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS DBQD LEU-299; CYS-300 AND HIS-300.
[11]"Desbuquois dysplasia type I and fetal hydrops due to novel mutations in the CANT1 gene."
Laccone F., Schoner K., Krabichler B., Kluge B., Schwerdtfeger R., Schulze B., Zschocke J., Rehder H.
Eur. J. Hum. Genet. 19:1133-1137(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT DBQD GLU-112.
[12]"A founder mutation of CANT1 common in Korean and Japanese Desbuquois dysplasia."
Dai J., Kim O.H., Cho T.J., Miyake N., Song H.R., Karasugi T., Sakazume S., Ikema M., Matsui Y., Nagai T., Matsumoto N., Ohashi H., Kamatani N., Nishimura G., Furuichi T., Takahashi A., Ikegawa S.
J. Hum. Genet. 56:398-400(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT DBQD MET-226.
[13]"CANT1 mutation is also responsible for Desbuquois dysplasia, type 2 and Kim variant."
Furuichi T., Dai J., Cho T.J., Sakazume S., Ikema M., Matsui Y., Baynam G., Nagai T., Miyake N., Matsumoto N., Ohashi H., Unger S., Superti-Furga A., Kim O.H., Nishimura G., Ikegawa S.
J. Med. Genet. 48:32-37(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS DBQD CYS-125; THR-165; PRO-224; MET-226 AND ASP-360, CHARACTERIZATION OF VARIANTS DBQD CYS-125; THR-165; PRO-224; MET-226; CYS-300 AND ASP-360, CHARACTERIZATION OF VARIANTS THR-323 AND GLU-391.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF328554 mRNA. Translation: AAM94564.1. Different initiation.
AB097006 mRNA. Translation: BAC77359.1.
AB097033 mRNA. Translation: BAC77386.1.
AK074687 mRNA. Translation: BAC11139.1.
AK295930 mRNA. Translation: BAG58716.1.
BC005104 mRNA. Translation: AAH05104.1.
BC017655 mRNA. Translation: AAH17655.1.
BC065038 mRNA. Translation: AAH65038.1.
AJ312208 mRNA. Translation: CAC85468.1.
CCDSCCDS11760.1. [Q8WVQ1-1]
RefSeqNP_001153244.1. NM_001159772.1. [Q8WVQ1-1]
NP_001153245.1. NM_001159773.1. [Q8WVQ1-1]
NP_620148.1. NM_138793.3. [Q8WVQ1-1]
XP_005257077.1. XM_005257020.1. [Q8WVQ1-1]
XP_005257078.1. XM_005257021.1. [Q8WVQ1-1]
XP_005257079.1. XM_005257022.1. [Q8WVQ1-1]
XP_006721745.1. XM_006721682.1. [Q8WVQ1-1]
XP_006721746.1. XM_006721683.1. [Q8WVQ1-1]
UniGeneHs.8859.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1S18X-ray1.70A/B71-401[»]
1S1DX-ray1.60A/B71-401[»]
2H2NX-ray2.30A/B69-401[»]
2H2UX-ray2.40A/B69-401[»]
ProteinModelPortalQ8WVQ1.
SMRQ8WVQ1. Positions 85-401.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid125875. 2 interactions.
STRING9606.ENSP00000307674.

PTM databases

PhosphoSiteQ8WVQ1.

Polymorphism databases

DMDM66774052.

Proteomic databases

MaxQBQ8WVQ1.
PaxDbQ8WVQ1.
PRIDEQ8WVQ1.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000302345; ENSP00000307674; ENSG00000171302. [Q8WVQ1-1]
ENST00000392446; ENSP00000376241; ENSG00000171302. [Q8WVQ1-1]
ENST00000591773; ENSP00000467437; ENSG00000171302. [Q8WVQ1-1]
GeneID124583.
KEGGhsa:124583.
UCSCuc002jwj.3. human. [Q8WVQ1-1]

Organism-specific databases

CTD124583.
GeneCardsGC17M076987.
HGNCHGNC:19721. CANT1.
HPAHPA019627.
HPA019639.
HPA022818.
MIM251450. phenotype.
613165. gene.
neXtProtNX_Q8WVQ1.
Orphanet1425. Desbuquois syndrome.
PharmGKBPA134984439.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG264398.
HOGENOMHOG000008129.
HOVERGENHBG059824.
InParanoidQ8WVQ1.
KOK12304.
OMAVVPTHGF.
OrthoDBEOG7T1RBF.
PhylomeDBQ8WVQ1.
TreeFamTF315248.

Gene expression databases

ArrayExpressQ8WVQ1.
BgeeQ8WVQ1.
CleanExHS_CANT1.
GenevestigatorQ8WVQ1.

Family and domain databases

InterProIPR009283. Apyrase.
[Graphical view]
PANTHERPTHR13023. PTHR13023. 1 hit.
PfamPF06079. Apyrase. 1 hit.
[Graphical view]
SUPFAMSSF101887. SSF101887. 1 hit.
ProtoNetSearch...

Other

EvolutionaryTraceQ8WVQ1.
GeneWikiCANT1.
GenomeRNAi124583.
NextBio35472441.
PROQ8WVQ1.
SOURCESearch...

Entry information

Entry nameCANT1_HUMAN
AccessionPrimary (citable) accession number: Q8WVQ1
Secondary accession number(s): B4DJ54 expand/collapse secondary AC list , Q7Z2J7, Q8NG05, Q8NHP0, Q9BSD5
Entry history
Integrated into UniProtKB/Swiss-Prot: May 10, 2005
Last sequence update: March 1, 2002
Last modified: July 9, 2014
This is version 107 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM