Q8WVQ1 (CANT1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	401 AA.
Sequence status	Complete.
Protein existence	Evidence 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. Ref.1 Ref.6
Catalytic activity	A nucleoside diphosphate + H2O = a nucleotide + phosphate.
Cofactor	Calcium. Ref.1 Ref.6
Subunit structure	Monomer. Ref.1
Subcellular location	Endoplasmic reticulum membrane; Single-pass type II membrane protein. Golgi apparatus › Golgi 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	Defects in CANT1 are the cause of 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. Ref.7 Ref.9
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.

Ontologies

Keywords
Cellular component	Endoplasmic reticulum Golgi apparatus Membrane
Coding sequence diversity	Alternative splicing
Disease	Disease mutation Dwarfism
Domain	Signal-anchor Transmembrane Transmembrane helix
Ligand	Calcium Metal-binding
Molecular function	Hydrolase
PTM	Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from mutant phenotype Ref.2. Source: UniProtKB
Cellular component	Golgi cisterna membrane Inferred from electronic annotation. Source: UniProtKB-SubCell endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	calcium ion binding Inferred from electronic annotation. Source: InterPro signal transducer activity Inferred from mutant phenotype Ref.2. Source: UniProtKB uridine-diphosphatase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Alternative products

This entry describes 2 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.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 401

401

Soluble calcium-activated nucleotidase 1

PRO_0000209925

Regions

Topological domain

1 – 44

44

Cytoplasmic Potential

Transmembrane

45 – 62

18

Helical; Signal-anchor for type II membrane protein; Potential

Topological domain

63 – 401

339

Lumenal Potential

Sites

Metal binding

168

1

Calcium

Metal binding

215

1

Calcium

Metal binding

284

1

Calcium

Metal binding

345

1

Calcium

Metal binding

396

1

Calcium

Amino acid modifications

Glycosylation

88

1

N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence

220 – 245

26

KDERL…VNENP → REIVRKRWRLVKQVSHVGVL GQWIQR in isoform 2.

VSP_013760

Alternative sequence

246 – 401

156

Missing in isoform 2.

VSP_013761

Natural variant

299

1

P → L in DBQD. Ref.9

VAR_062980

Natural variant

300

1

R → C in DBQD. Ref.9

VAR_062981

Natural variant

300

1

R → H in DBQD. Ref.9

VAR_062982

Experimental info

Mutagenesis

112

1

D → A: Reduces activity by 99%. Ref.8

Mutagenesis

114

1

D → A: Reduces activity by 99%. Ref.6 Ref.8

Mutagenesis

152

1

G → E: Slightly reduced activity. Ref.6

Mutagenesis

160

1

E → Y: Increases GDPase activity 2-fold and ADPase activity 5-fold. Ref.6

Mutagenesis

163

1

R → A: Reduces activity by 98%. Ref.6

Mutagenesis

166

1

E → Q: Reduces activity by 95%. Ref.8

Mutagenesis

168

1

S → A: Reduces activity by over 99.9%. Ref.8

Mutagenesis

169

1

D → N: Reduces activity by 96%. Ref.8

Mutagenesis

181

1

D → A: Loss of activity. Ref.6

Mutagenesis

182

1

D → N: Reduces activity by over 99.9%. Ref.8

Mutagenesis

205

1

D → A: Slightly reduced activity. Ref.6

Mutagenesis

215

1

E → Q: Reduces activity by 99%. Ref.8

Mutagenesis

246

1

E → M: Increases activity 5-fold. Ref.8

Mutagenesis

301

1

R → A: Reduces activity by 99%. Ref.6 Ref.8

Secondary structure

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401

Helix Strand Turn

Details...

Beta strand

92 – 94

3

Beta strand

97 – 99

3

Beta strand

102 – 112

11

Helix

114 – 117

4

Beta strand

125 – 137

13

Beta strand

143 – 147

5

Beta strand

152 – 160

9

Beta strand

167 – 173

7

Beta strand

176 – 181

6

Turn

182 – 184

3

Beta strand

186 – 191

6

Beta strand

194 – 200

7

Turn

204 – 207

4

Beta strand

209 – 211

3

Beta strand

216 – 220

5

Beta strand

223 – 227

5

Beta strand

240 – 242

3

Helix

244 – 246

3

Beta strand

247 – 251

5

Beta strand

257 – 261

5

Helix

263 – 272

10

Beta strand

280 – 282

3

Beta strand

286 – 289

4

Turn

290 – 293

4

Beta strand

294 – 297

4

Beta strand

300 – 305

6

Helix

309 – 312

4

Beta strand

319 – 323

5

Beta strand

327 – 334

8

Beta strand

342 – 349

8

Beta strand

357 – 366

10

Beta strand

369 – 378

10

Beta strand

383 – 400

18

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 1, 2002. Version 1. Checksum: 5B78EB24C0B2C4CA	FASTA	401	44,840
	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
	Isoform 2 [UniParc]. Checksum: 0D53611DA70ADCAF	FASTA	245	27,762
	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 GFKAEWLAVR EIVRKRWRLV KQVSHVGVLG QWIQR

References

	« Hide 'large scale' referencesShow '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: 12234496] [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: 12761501] [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. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Mammary gland.
[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: 15489334] [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: 12167635] [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: 15248776] [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: 20425819] [Abstract] Cited for: INVOLVEMENT IN DBQD.
[8]	"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: 15006348] [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.
[9]	"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. , Paterlini-Brechot P., Munnich A., Cormier-Daire V. Am. J. Hum. Genet. 85:706-710(2009) [PubMed: 19853239] [Abstract] Cited for: VARIANTS DBQD LEU-299; CYS-300 AND HIS-300.
+	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.
BC005104 mRNA. Translation: AAH05104.1.
BC017655 mRNA. Translation: AAH17655.1.
BC065038 mRNA. Translation: AAH65038.1.
AJ312208 mRNA. Translation: CAC85468.1.

IPI

IPI00103175.
IPI00413533.

RefSeq

NP_001153244.1. NM_001159772.1.
NP_001153245.1. NM_001159773.1.
NP_620148.1. NM_138793.3.

UniGene

Hs.8859.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1S18	X-ray	1.70	A/B	71-401	[»]
1S1D	X-ray	1.60	A/B	71-401	[»]
2H2N	X-ray	2.30	A/B	69-401	[»]
2H2U	X-ray	2.40	A/B	69-401	[»]

ProteinModelPortal

Q8WVQ1.

SMR

Q8WVQ1. Positions 85-401.

ModBase

Search...

Protein-protein interaction databases

STRING

Q8WVQ1.

Polymorphism databases

DMDM

66774052.

Proteomic databases

PRIDE

Q8WVQ1.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000302345; ENSP00000307674; ENSG00000171302.
ENST00000392446; ENSP00000376241; ENSG00000171302.

GeneID

124583.

KEGG

hsa:124583.

UCSC

uc002jwj.1. human.

Organism-specific databases

CTD

124583.

GeneCards

GC17M076987.

H-InvDB

HIX0014230.

HGNC

HGNC:19721. CANT1.

HPA

HPA019627.
HPA019639.
HPA022818.

MIM

251450. phenotype.
613165. gene.

neXtProt

NX_Q8WVQ1.

Orphanet

1425. Desbuquois syndrome.

PharmGKB

PA134984439.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG19244.

GeneTree

ENSGT00390000012872.

HOGENOM

HBG435414.

HOVERGEN

HBG059824.

InParanoid

Q8WVQ1.

OMA

HESACWS.

OrthoDB

EOG48SGT5.

PhylomeDB

Q8WVQ1.

Gene expression databases

ArrayExpress

Q8WVQ1.

Bgee

Q8WVQ1.

CleanEx

HS_CANT1.

Genevestigator

Q8WVQ1.

GermOnline

ENSG00000171302. Homo sapiens.

Family and domain databases

InterPro

IPR009283. Apyrase.
[Graphical view]

KO

K12304.

PANTHER

PTHR13023. Apyrase. 1 hit.

Pfam

PF06079. Apyrase. 1 hit.
[Graphical view]

SUPFAM

SSF101887. Apyrase. 1 hit.

ProtoNet

Search...

Other

NextBio

81327.

SOURCE

Search...

Entry information

Entry name

CANT1_HUMAN

Accession

Primary (citable) accession number: Q8WVQ1
Secondary accession number(s): Q7Z2J7 , Q8NG05, Q8NHP0, Q9BSD5

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 10, 2005
Last sequence update:	March 1, 2002
Last modified:	January 25, 2012
This is version 84 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.