CANT1_HUMAN
ID CANT1_HUMAN Reviewed; 401 AA.
AC Q8WVQ1; B4DJ54; Q7Z2J7; Q8NG05; Q8NHP0; Q9BSD5;
DT 10-MAY-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Soluble calcium-activated nucleotidase 1;
DE Short=SCAN-1;
DE EC=3.6.1.6 {ECO:0000269|PubMed:12234496, ECO:0000269|PubMed:15006348, ECO:0000269|PubMed:15248776, ECO:0000269|PubMed:16835225};
DE AltName: Full=Apyrase homolog;
DE AltName: Full=Putative MAPK-activating protein PM09;
DE AltName: Full=Putative NF-kappa-B-activating protein 107;
GN Name=CANT1; Synonyms=SHAPY;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY,
RP COFACTOR, SUBUNIT, SUBCELLULAR LOCATION, GLYCOSYLATION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Mammary tumor;
RX PubMed=12234496; DOI=10.1016/s0003-9861(02)00420-4;
RA Smith T., Hicks-Berger C., Kim S., Kirley T.;
RT "Cloning, expression, and characterization of a soluble calcium-activated
RT nucleotidase, a human enzyme belonging to a new family of extracellular
RT nucleotidases.";
RL Arch. Biochem. Biophys. 406:105-115(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Lung fibroblast;
RX PubMed=12761501; DOI=10.1038/sj.onc.1206406;
RA Matsuda A., Suzuki Y., Honda G., Muramatsu S., Matsuzaki O., Nagano Y.,
RA Doi T., Shimotohno K., Harada T., Nishida E., Hayashi H., Sugano S.;
RT "Large-scale identification and characterization of human genes that
RT activate NF-kappaB and MAPK signaling pathways.";
RL Oncogene 22:3307-3318(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Mammary gland, and Substantia nigra;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Ovary, Pancreas, 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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 141-401 (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=12167635; DOI=10.1074/jbc.m201656200;
RA Failer B.U., Braun N., Zimmermann H.;
RT "Cloning, expression, and functional characterization of a Ca2+-dependent
RT endoplasmic reticulum nucleoside diphosphatase.";
RL J. Biol. Chem. 277:36978-36986(2002).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND MUTAGENESIS OF ASP-114;
RP GLY-152; GLU-160; ARG-163; ASP-181; ASP-205 AND ARG-301.
RX PubMed=15248776; DOI=10.1021/bi049565o;
RA Yang M., Kirley T.L.;
RT "Site-directed mutagenesis of human soluble calcium-activated nucleotidase
RT 1 (hSCAN-1): identification of residues essential for enzyme activity and
RT the Ca(2+)-induced conformational change.";
RL Biochemistry 43:9185-9194(2004).
RN [7]
RP INVOLVEMENT IN DBQD1.
RX PubMed=20425819; DOI=10.1002/ajmg.a.33404;
RA Faden M., Al-Zahrani F., Arafah D., Alkuraya F.S.;
RT "Mutation of CANT1 causes Desbuquois dysplasia.";
RL Am. J. Med. Genet. A 152:1157-1160(2010).
RN [8]
RP FUNCTION IN PROTEOGLYCAN SYNTHESIS, AND VARIANTS DBQD1 HIS-300; ARG-303 AND
RP ASN-374.
RX PubMed=22539336; DOI=10.1002/humu.22104;
RA Nizon M., Huber C., De Leonardis F., Merrina R., Forlino A., Fradin M.,
RA Tuysuz B., Abu-Libdeh B.Y., Alanay Y., Albrecht B., Al-Gazali L.,
RA Basaran S.Y., Clayton-Smith J., Desir J., Gill H., Greally M.T.,
RA Koparir E., van Maarle M.C., Mackay S., Mortier G., Morton J., Sillence D.,
RA Vilain C., Young I., Zerres K., Le Merrer M., Munnich A., Le Goff C.,
RA Rossi A., Cormier-Daire V.;
RT "Further delineation of CANT1 phenotypic spectrum and demonstration of its
RT role in proteoglycan synthesis.";
RL Hum. Mutat. 33:1261-1266(2012).
RN [9]
RP INVOLVEMENT IN EDM7, AND VARIANTS EDM7 PHE-171 AND MET-226.
RX PubMed=28742282; DOI=10.1002/ajmg.a.38349;
RA Balasubramanian K., Li B., Krakow D., Nevarez L., Ho P.J., Ainsworth J.A.,
RA Nickerson D.A., Bamshad M.J., Immken L., Lachman R.S., Cohn D.H.;
RT "MED resulting from recessively inherited mutations in the gene encoding
RT calcium-activated nucleotidase CANT1.";
RL Am. J. Med. Genet. A 173:2415-2421(2017).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 71-401 IN COMPLEX WITH SUBSTRATE
RP ANALOG AND CALCIUM IONS, CATALYTIC ACTIVITY, COFACTOR, SUBUNIT, AND
RP MUTAGENESIS OF ASP-112; ASP-114; GLU-166; SER-168; ASP-169; ASP-182;
RP GLU-215; GLU-246 AND ARG-301.
RX PubMed=15006348; DOI=10.1016/s0092-8674(04)00172-2;
RA Dai J., Liu J., Deng Y., Smith T.M., Lu M.;
RT "Structure and protein design of a human platelet function inhibitor.";
RL Cell 116:649-659(2004).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 69-401 IN COMPLEX WITH CALCIUM,
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, DIMERIZATION, SUBCELLULAR LOCATION,
RP DISULFIDE BOND, AND MUTAGENESIS OF CYS-60; SER-139; GLU-160; ILE-200;
RP SER-202; SER-256; CYS-287; SER-308 AND ALA-317.
RX PubMed=16835225; DOI=10.1074/jbc.m604413200;
RA Yang M., Horii K., Herr A.B., Kirley T.L.;
RT "Calcium-dependent dimerization of human soluble calcium activated
RT nucleotidase: characterization of the dimer interface.";
RL J. Biol. Chem. 281:28307-28317(2006).
RN [12]
RP VARIANTS DBQD1 LEU-299; CYS-300 AND HIS-300.
RX PubMed=19853239; DOI=10.1016/j.ajhg.2009.10.001;
RA Huber C., Oules B., Bertoli M., Chami M., Fradin M., Alanay Y.,
RA Al-Gazali L.I., Ausems M.G., Bitoun P., Cavalcanti D.P., Krebs A.,
RA Le Merrer M., Mortier G., Shafeghati Y., Superti-Furga A., Robertson S.P.,
RA Le Goff C., Muda A.O., Paterlini-Brechot P., Munnich A., Cormier-Daire V.;
RT "Identification of CANT1 mutations in Desbuquois dysplasia.";
RL Am. J. Hum. Genet. 85:706-710(2009).
RN [13]
RP VARIANT DBQD1 GLU-112.
RX PubMed=21654728; DOI=10.1038/ejhg.2011.101;
RA Laccone F., Schoner K., Krabichler B., Kluge B., Schwerdtfeger R.,
RA Schulze B., Zschocke J., Rehder H.;
RT "Desbuquois dysplasia type I and fetal hydrops due to novel mutations in
RT the CANT1 gene.";
RL Eur. J. Hum. Genet. 19:1133-1137(2011).
RN [14]
RP VARIANT DBQD1 MET-226.
RX PubMed=21412251; DOI=10.1038/jhg.2011.28;
RA Dai J., Kim O.H., Cho T.J., Miyake N., Song H.R., Karasugi T., Sakazume S.,
RA Ikema M., Matsui Y., Nagai T., Matsumoto N., Ohashi H., Kamatani N.,
RA Nishimura G., Furuichi T., Takahashi A., Ikegawa S.;
RT "A founder mutation of CANT1 common in Korean and Japanese Desbuquois
RT dysplasia.";
RL J. Hum. Genet. 56:398-400(2011).
RN [15]
RP VARIANTS DBQD1 CYS-125; THR-165; PRO-224; MET-226 AND ASP-360,
RP CHARACTERIZATION OF VARIANTS DBQD1 CYS-125; THR-165; PRO-224; MET-226;
RP CYS-300 AND ASP-360, AND CHARACTERIZATION OF VARIANTS THR-323 AND GLU-391.
RX PubMed=21037275; DOI=10.1136/jmg.2010.080226;
RA Furuichi T., Dai J., Cho T.J., Sakazume S., Ikema M., Matsui Y., Baynam G.,
RA Nagai T., Miyake N., Matsumoto N., Ohashi H., Unger S., Superti-Furga A.,
RA Kim O.H., Nishimura G., Ikegawa S.;
RT "CANT1 mutation is also responsible for Desbuquois dysplasia, type 2 and
RT Kim variant.";
RL J. Med. Genet. 48:32-37(2011).
CC -!- FUNCTION: Calcium-dependent nucleotidase with a preference for UDP. The
CC order of activity with different substrates is UDP > GDP > UTP > GTP.
CC Has very low activity towards ADP and even lower activity towards ATP.
CC Does not hydrolyze AMP and GMP (PubMed:12234496, PubMed:15248776,
CC PubMed:15006348, PubMed:16835225). Involved in proteoglycan synthesis
CC (PubMed:22539336). {ECO:0000269|PubMed:12234496,
CC ECO:0000269|PubMed:15006348, ECO:0000269|PubMed:15248776,
CC ECO:0000269|PubMed:16835225, ECO:0000269|PubMed:22539336}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a ribonucleoside 5'-diphosphate + H2O = a ribonucleoside 5'-
CC phosphate + H(+) + phosphate; Xref=Rhea:RHEA:36799,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57930, ChEBI:CHEBI:58043; EC=3.6.1.6;
CC Evidence={ECO:0000269|PubMed:12234496, ECO:0000269|PubMed:15248776,
CC ECO:0000269|PubMed:16835225};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000269|PubMed:12234496, ECO:0000269|PubMed:15006348,
CC ECO:0000269|PubMed:15248776, ECO:0000269|PubMed:16835225};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 6.8.;
CC -!- SUBUNIT: Monomer (PubMed:12234496, PubMed:15006348). Homodimer;
CC dimerization is Ca(2+)-dependent (PubMed:16835225). Homodimer;
CC disulfide-linked (membrane form) (PubMed:16835225).
CC {ECO:0000269|PubMed:12234496, ECO:0000269|PubMed:15006348,
CC ECO:0000269|PubMed:16835225}.
CC -!- INTERACTION:
CC Q8WVQ1; P58418: CLRN1; NbExp=3; IntAct=EBI-16770554, EBI-17274839;
CC Q8WVQ1; Q5JX71: FAM209A; NbExp=3; IntAct=EBI-16770554, EBI-18304435;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:12234496}; Single-pass type II membrane protein
CC {ECO:0000269|PubMed:12234496}. Golgi apparatus, Golgi stack membrane
CC {ECO:0000269|PubMed:12234496}; Single-pass type II membrane protein
CC {ECO:0000269|PubMed:12234496}. Cell membrane
CC {ECO:0000269|PubMed:16835225}. Note=Processed form: Secreted.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8WVQ1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8WVQ1-2; Sequence=VSP_013760, VSP_013761;
CC Name=3;
CC IsoId=Q8WVQ1-3; Sequence=VSP_054260;
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:12234496}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:12234496}.
CC -!- DISEASE: Desbuquois dysplasia 1 (DBQD1) [MIM:251450]: A
CC chondrodysplasia characterized by severe prenatal and postnatal growth
CC retardation (less than -5 SD), joint laxity, short extremities,
CC progressive scoliosis, round face, midface hypoplasia, prominent
CC bulging eyes. The main radiologic features are short long bones with
CC metaphyseal splay, a 'Swedish key' appearance of the proximal femur
CC (exaggerated trochanter), and advance carpal and tarsal bone age. Two
CC forms of Desbuquois dysplasia are distinguished on the basis of the
CC presence or absence of characteristic hand anomalies: an extra
CC ossification center distal to the second metacarpal, delta phalanx,
CC bifid distal thumb phalanx, and phalangeal dislocations.
CC {ECO:0000269|PubMed:19853239, ECO:0000269|PubMed:20425819,
CC ECO:0000269|PubMed:21037275, ECO:0000269|PubMed:21412251,
CC ECO:0000269|PubMed:21654728, ECO:0000269|PubMed:22539336}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Epiphyseal dysplasia, multiple, 7 (EDM7) [MIM:617719]: A form
CC of multiple epiphyseal dysplasia, a generalized skeletal dysplasia
CC associated with significant morbidity. Joint pain, joint deformity,
CC waddling gait, and short stature are the main clinical signs and
CC symptoms. Radiological examination of the skeleton shows delayed,
CC irregular mineralization of the epiphyseal ossification centers and of
CC the centers of the carpal and tarsal bones. Multiple epiphyseal
CC dysplasia is broadly categorized into the more severe Fairbank and the
CC milder Ribbing types. The Fairbank type is characterized by shortness
CC of stature, short and stubby fingers, small epiphyses in several
CC joints, including the knee, ankle, hand, and hip. The Ribbing type is
CC confined predominantly to the hip joints and is characterized by hands
CC that are normal and stature that is normal or near-normal. EDM7
CC inheritance is autosomal recessive. {ECO:0000269|PubMed:28742282}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- MISCELLANEOUS: Not inhibited by azide.
CC -!- SIMILARITY: Belongs to the apyrase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAM94564.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF328554; AAM94564.1; ALT_INIT; mRNA.
DR EMBL; AB097006; BAC77359.1; -; mRNA.
DR EMBL; AB097033; BAC77386.1; -; mRNA.
DR EMBL; AK074687; BAC11139.1; -; mRNA.
DR EMBL; AK295930; BAG58716.1; -; mRNA.
DR EMBL; BC005104; AAH05104.1; -; mRNA.
DR EMBL; BC017655; AAH17655.1; -; mRNA.
DR EMBL; BC065038; AAH65038.1; -; mRNA.
DR EMBL; AJ312208; CAC85468.1; -; mRNA.
DR CCDS; CCDS11760.1; -. [Q8WVQ1-1]
DR RefSeq; NP_001153244.1; NM_001159772.1. [Q8WVQ1-1]
DR RefSeq; NP_001153245.1; NM_001159773.1. [Q8WVQ1-1]
DR RefSeq; NP_620148.1; NM_138793.3. [Q8WVQ1-1]
DR RefSeq; XP_005257078.1; XM_005257021.1. [Q8WVQ1-1]
DR RefSeq; XP_005257079.1; XM_005257022.1. [Q8WVQ1-1]
DR RefSeq; XP_006721746.1; XM_006721683.1. [Q8WVQ1-1]
DR RefSeq; XP_011522593.1; XM_011524291.1. [Q8WVQ1-1]
DR RefSeq; XP_011522595.1; XM_011524293.1. [Q8WVQ1-1]
DR RefSeq; XP_011522596.1; XM_011524294.1. [Q8WVQ1-1]
DR RefSeq; XP_011522597.1; XM_011524295.2. [Q8WVQ1-1]
DR PDB; 1S18; X-ray; 1.70 A; A/B=71-401.
DR PDB; 1S1D; X-ray; 1.60 A; A/B=71-401.
DR PDB; 2H2N; X-ray; 2.30 A; A/B=69-401.
DR PDB; 2H2U; X-ray; 2.40 A; A/B=69-401.
DR PDBsum; 1S18; -.
DR PDBsum; 1S1D; -.
DR PDBsum; 2H2N; -.
DR PDBsum; 2H2U; -.
DR AlphaFoldDB; Q8WVQ1; -.
DR SMR; Q8WVQ1; -.
DR BioGRID; 125875; 84.
DR IntAct; Q8WVQ1; 16.
DR MINT; Q8WVQ1; -.
DR STRING; 9606.ENSP00000307674; -.
DR DrugBank; DB03486; Phosphomethylphosphonic acid guanosyl ester.
DR GlyConnect; 1760; 4 N-Linked glycans (1 site).
DR GlyGen; Q8WVQ1; 2 sites, 4 N-linked glycans (1 site).
DR iPTMnet; Q8WVQ1; -.
DR PhosphoSitePlus; Q8WVQ1; -.
DR BioMuta; CANT1; -.
DR DMDM; 66774052; -.
DR EPD; Q8WVQ1; -.
DR jPOST; Q8WVQ1; -.
DR MassIVE; Q8WVQ1; -.
DR MaxQB; Q8WVQ1; -.
DR PaxDb; Q8WVQ1; -.
DR PeptideAtlas; Q8WVQ1; -.
DR PRIDE; Q8WVQ1; -.
DR ProteomicsDB; 74813; -. [Q8WVQ1-1]
DR ProteomicsDB; 74814; -. [Q8WVQ1-2]
DR Antibodypedia; 19748; 334 antibodies from 31 providers.
DR DNASU; 124583; -.
DR Ensembl; ENST00000302345.6; ENSP00000307674.2; ENSG00000171302.17. [Q8WVQ1-1]
DR Ensembl; ENST00000392446.10; ENSP00000376241.4; ENSG00000171302.17. [Q8WVQ1-1]
DR Ensembl; ENST00000591773.5; ENSP00000467437.1; ENSG00000171302.17. [Q8WVQ1-1]
DR Ensembl; ENST00000620915.4; ENSP00000477798.1; ENSG00000171302.17. [Q8WVQ1-1]
DR GeneID; 124583; -.
DR KEGG; hsa:124583; -.
DR MANE-Select; ENST00000392446.10; ENSP00000376241.4; NM_001159773.2; NP_001153245.1.
DR UCSC; uc002jwj.4; human. [Q8WVQ1-1]
DR CTD; 124583; -.
DR DisGeNET; 124583; -.
DR GeneCards; CANT1; -.
DR HGNC; HGNC:19721; CANT1.
DR HPA; ENSG00000171302; Low tissue specificity.
DR MalaCards; CANT1; -.
DR MIM; 251450; phenotype.
DR MIM; 613165; gene.
DR MIM; 617719; phenotype.
DR neXtProt; NX_Q8WVQ1; -.
DR OpenTargets; ENSG00000171302; -.
DR Orphanet; 1425; Desbuquois syndrome.
DR PharmGKB; PA134984439; -.
DR VEuPathDB; HostDB:ENSG00000171302; -.
DR eggNOG; KOG4494; Eukaryota.
DR GeneTree; ENSGT00390000012872; -.
DR HOGENOM; CLU_047493_0_0_1; -.
DR InParanoid; Q8WVQ1; -.
DR OMA; MGMISTT; -.
DR OrthoDB; 1579117at2759; -.
DR PhylomeDB; Q8WVQ1; -.
DR TreeFam; TF315248; -.
DR BRENDA; 3.6.1.5; 2681.
DR PathwayCommons; Q8WVQ1; -.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR SignaLink; Q8WVQ1; -.
DR BioGRID-ORCS; 124583; 18 hits in 1075 CRISPR screens.
DR ChiTaRS; CANT1; human.
DR EvolutionaryTrace; Q8WVQ1; -.
DR GeneWiki; CANT1; -.
DR GenomeRNAi; 124583; -.
DR Pharos; Q8WVQ1; Tbio.
DR PRO; PR:Q8WVQ1; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q8WVQ1; protein.
DR Bgee; ENSG00000171302; Expressed in pancreatic ductal cell and 190 other tissues.
DR ExpressionAtlas; Q8WVQ1; baseline and differential.
DR Genevisible; Q8WVQ1; HS.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:1904813; C:ficolin-1-rich granule lumen; TAS:Reactome.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0032580; C:Golgi cisterna membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0035580; C:specific granule lumen; TAS:Reactome.
DR GO; GO:1904724; C:tertiary granule lumen; TAS:Reactome.
DR GO; GO:0043262; F:adenosine-diphosphatase activity; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0004382; F:guanosine-diphosphatase activity; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0045134; F:uridine-diphosphatase activity; IBA:GO_Central.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; HMP:UniProtKB.
DR GO; GO:0030166; P:proteoglycan biosynthetic process; IMP:UniProtKB.
DR Gene3D; 2.120.10.100; -; 1.
DR InterPro; IPR009283; Apyrase.
DR InterPro; IPR036258; Apyrase_sf.
DR PANTHER; PTHR13023; PTHR13023; 1.
DR SUPFAM; SSF101887; SSF101887; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Calcium; Cell membrane;
KW Disease variant; Disulfide bond; Dwarfism; Endoplasmic reticulum;
KW Glycoprotein; Golgi apparatus; Hydrolase; Membrane; Metal-binding;
KW Reference proteome; Signal-anchor; Transmembrane; Transmembrane helix.
FT CHAIN 1..401
FT /note="Soluble calcium-activated nucleotidase 1"
FT /id="PRO_0000209925"
FT TOPO_DOM 1..44
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 45..62
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 63..401
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT BINDING 168
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:15006348,
FT ECO:0000269|PubMed:16835225, ECO:0007744|PDB:1S18,
FT ECO:0007744|PDB:1S1D, ECO:0007744|PDB:2H2N,
FT ECO:0007744|PDB:2H2U"
FT BINDING 169
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:15006348,
FT ECO:0000269|PubMed:16835225, ECO:0007744|PDB:1S18,
FT ECO:0007744|PDB:2H2N, ECO:0007744|PDB:2H2U"
FT BINDING 215
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:15006348,
FT ECO:0000269|PubMed:16835225, ECO:0007744|PDB:1S18,
FT ECO:0007744|PDB:1S1D, ECO:0007744|PDB:2H2N,
FT ECO:0007744|PDB:2H2U"
FT BINDING 284
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:15006348,
FT ECO:0000269|PubMed:16835225, ECO:0007744|PDB:1S18,
FT ECO:0007744|PDB:1S1D, ECO:0007744|PDB:2H2N,
FT ECO:0007744|PDB:2H2U"
FT BINDING 345
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:15006348,
FT ECO:0000269|PubMed:16835225, ECO:0007744|PDB:1S18,
FT ECO:0007744|PDB:1S1D, ECO:0007744|PDB:2H2N,
FT ECO:0007744|PDB:2H2U"
FT BINDING 396
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:15006348,
FT ECO:0000269|PubMed:16835225, ECO:0007744|PDB:1S18,
FT ECO:0007744|PDB:1S1D, ECO:0007744|PDB:2H2N,
FT ECO:0007744|PDB:2H2U"
FT SITE 160
FT /note="Important for dimer formation"
FT /evidence="ECO:0000269|PubMed:16835225"
FT SITE 200
FT /note="Important for dimer formation"
FT /evidence="ECO:0000269|PubMed:16835225"
FT SITE 202
FT /note="Important for dimer formation"
FT /evidence="ECO:0000269|PubMed:16835225"
FT SITE 256
FT /note="Important for dimer formation"
FT /evidence="ECO:0000269|PubMed:16835225"
FT CARBOHYD 88
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 60
FT /note="Interchain"
FT /evidence="ECO:0000269|PubMed:16835225"
FT VAR_SEQ 41..91
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_054260"
FT VAR_SEQ 220..245
FT /note="KDERLYVGGLGKEWTTTTGDVVNENP -> REIVRKRWRLVKQVSHVGVLGQ
FT WIQR (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12761501"
FT /id="VSP_013760"
FT VAR_SEQ 246..401
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12761501"
FT /id="VSP_013761"
FT VARIANT 112
FT /note="D -> E (in DBQD1; dbSNP:rs749246739)"
FT /evidence="ECO:0000269|PubMed:21654728"
FT /id="VAR_068655"
FT VARIANT 125
FT /note="W -> C (in DBQD1; severely affects activity;
FT dbSNP:rs587776898)"
FT /evidence="ECO:0000269|PubMed:21037275"
FT /id="VAR_068656"
FT VARIANT 165
FT /note="M -> T (in DBQD1; severely affects activity)"
FT /evidence="ECO:0000269|PubMed:21037275"
FT /id="VAR_068657"
FT VARIANT 171
FT /note="I -> F (in EDM7; unknown pathological significance;
FT dbSNP:rs1014317450)"
FT /evidence="ECO:0000269|PubMed:28742282"
FT /id="VAR_080400"
FT VARIANT 224
FT /note="L -> P (in DBQD1; affects protein stability and
FT secretion; dbSNP:rs150181226)"
FT /evidence="ECO:0000269|PubMed:21037275"
FT /id="VAR_068658"
FT VARIANT 226
FT /note="V -> M (in DBQD1 and EDM7; severely affects
FT activity; dbSNP:rs377546036)"
FT /evidence="ECO:0000269|PubMed:21037275,
FT ECO:0000269|PubMed:21412251, ECO:0000269|PubMed:28742282"
FT /id="VAR_068659"
FT VARIANT 299
FT /note="P -> L (in DBQD1; dbSNP:rs267606700)"
FT /evidence="ECO:0000269|PubMed:19853239"
FT /id="VAR_062980"
FT VARIANT 300
FT /note="R -> C (in DBQD1; severely affects activity;
FT dbSNP:rs267606701)"
FT /evidence="ECO:0000269|PubMed:19853239,
FT ECO:0000269|PubMed:21037275"
FT /id="VAR_062981"
FT VARIANT 300
FT /note="R -> H (in DBQD1; dbSNP:rs267606699)"
FT /evidence="ECO:0000269|PubMed:19853239,
FT ECO:0000269|PubMed:22539336"
FT /id="VAR_062982"
FT VARIANT 303
FT /note="S -> R (in DBQD1)"
FT /evidence="ECO:0000269|PubMed:22539336"
FT /id="VAR_068660"
FT VARIANT 323
FT /note="A -> T (does not affect activity; dbSNP:rs9903215)"
FT /evidence="ECO:0000269|PubMed:21037275"
FT /id="VAR_068661"
FT VARIANT 360
FT /note="A -> D (in DBQD1; affects protein secretion;
FT dbSNP:rs387907081)"
FT /evidence="ECO:0000269|PubMed:21037275"
FT /id="VAR_068662"
FT VARIANT 374
FT /note="I -> N (in DBQD1)"
FT /evidence="ECO:0000269|PubMed:22539336"
FT /id="VAR_068663"
FT VARIANT 391
FT /note="G -> E (does not affect activity; dbSNP:rs34082669)"
FT /evidence="ECO:0000269|PubMed:21037275"
FT /id="VAR_068664"
FT MUTAGEN 60
FT /note="C->S: Loss of dimer formation."
FT /evidence="ECO:0000269|PubMed:16835225"
FT MUTAGEN 112
FT /note="D->A: Reduces activity by 99%."
FT /evidence="ECO:0000269|PubMed:15006348"
FT MUTAGEN 114
FT /note="D->A: Reduces activity by 99%."
FT /evidence="ECO:0000269|PubMed:15006348,
FT ECO:0000269|PubMed:15248776"
FT MUTAGEN 139
FT /note="S->C: Reduces GDPase and ADPase activities 1.7-fold.
FT Severe loss of dimer formation; when associated with S-
FT 287."
FT /evidence="ECO:0000269|PubMed:16835225"
FT MUTAGEN 152
FT /note="G->E: Slightly reduced activity."
FT /evidence="ECO:0000269|PubMed:15248776"
FT MUTAGEN 160
FT /note="E->Y: Increases GDPase activity 2-fold and ADPase
FT activity 5-fold. Forms dimer even at suboptimal Ca(2+)
FT concentrations."
FT /evidence="ECO:0000269|PubMed:15248776,
FT ECO:0000269|PubMed:16835225"
FT MUTAGEN 163
FT /note="R->A: Reduces activity by 98%."
FT /evidence="ECO:0000269|PubMed:15248776"
FT MUTAGEN 166
FT /note="E->Q: Reduces activity by 95%."
FT /evidence="ECO:0000269|PubMed:15006348"
FT MUTAGEN 168
FT /note="S->A: Reduces activity by over 99.9%."
FT /evidence="ECO:0000269|PubMed:15006348"
FT MUTAGEN 169
FT /note="D->N: Reduces activity by 96%."
FT /evidence="ECO:0000269|PubMed:15006348"
FT MUTAGEN 181
FT /note="D->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:15248776"
FT MUTAGEN 182
FT /note="D->N: Reduces activity by over 99.9%."
FT /evidence="ECO:0000269|PubMed:15006348"
FT MUTAGEN 200
FT /note="I->C: Reduces GDPase activity 2-fold and ADPase
FT activity 2.5-fold. No effect on dimer formation; when
FT associated with S-287."
FT /evidence="ECO:0000269|PubMed:16835225"
FT MUTAGEN 202
FT /note="S->C: Reduces GDPase activity 1.7-fold and ADPase
FT activity 1.5-fold. No effect on dimer formation; when
FT associated with S-287."
FT /evidence="ECO:0000269|PubMed:16835225"
FT MUTAGEN 205
FT /note="D->A: Slightly reduced activity."
FT /evidence="ECO:0000269|PubMed:15248776"
FT MUTAGEN 215
FT /note="E->Q: Reduces activity by 99%."
FT /evidence="ECO:0000269|PubMed:15006348"
FT MUTAGEN 246
FT /note="E->M: Increases activity 5-fold."
FT /evidence="ECO:0000269|PubMed:15006348"
FT MUTAGEN 256
FT /note="S->C: No effect on GDPase and ADPase activities. No
FT effect on dimer formation; when associated with S-287."
FT /evidence="ECO:0000269|PubMed:16835225"
FT MUTAGEN 287
FT /note="C->S: Reduces GDPase and ADPase activities 1.3-
FT fold."
FT /evidence="ECO:0000269|PubMed:16835225"
FT MUTAGEN 301
FT /note="R->A: Reduces activity by 99%."
FT /evidence="ECO:0000269|PubMed:15006348,
FT ECO:0000269|PubMed:15248776"
FT MUTAGEN 308
FT /note="S->C: Reduces GDPase activity 1.3-fold and ADPase
FT activity 2-fold. Severe loss of dimer formation; when
FT associated with S-287."
FT /evidence="ECO:0000269|PubMed:16835225"
FT MUTAGEN 317
FT /note="A->C: Reduces GDPase activity 1.7-fold and ADPase
FT activity 1.5-fold. Severe loss of dimer formation; when
FT associated with S-287."
FT /evidence="ECO:0000269|PubMed:16835225"
FT STRAND 92..94
FT /evidence="ECO:0007829|PDB:1S1D"
FT STRAND 97..99
FT /evidence="ECO:0007829|PDB:1S1D"
FT STRAND 102..112
FT /evidence="ECO:0007829|PDB:1S1D"
FT HELIX 114..117
FT /evidence="ECO:0007829|PDB:1S1D"
FT STRAND 125..137
FT /evidence="ECO:0007829|PDB:1S1D"
FT STRAND 143..147
FT /evidence="ECO:0007829|PDB:1S1D"
FT STRAND 152..157
FT /evidence="ECO:0007829|PDB:1S1D"
FT STRAND 158..160
FT /evidence="ECO:0007829|PDB:2H2U"
FT STRAND 167..173
FT /evidence="ECO:0007829|PDB:1S1D"
FT STRAND 176..181
FT /evidence="ECO:0007829|PDB:1S1D"
FT TURN 182..184
FT /evidence="ECO:0007829|PDB:1S1D"
FT STRAND 186..191
FT /evidence="ECO:0007829|PDB:1S1D"
FT STRAND 194..200
FT /evidence="ECO:0007829|PDB:1S1D"
FT TURN 204..207
FT /evidence="ECO:0007829|PDB:1S1D"
FT STRAND 208..211
FT /evidence="ECO:0007829|PDB:1S1D"
FT STRAND 216..220
FT /evidence="ECO:0007829|PDB:1S1D"
FT STRAND 223..227
FT /evidence="ECO:0007829|PDB:1S1D"
FT STRAND 240..242
FT /evidence="ECO:0007829|PDB:1S1D"
FT HELIX 244..246
FT /evidence="ECO:0007829|PDB:1S1D"
FT STRAND 247..251
FT /evidence="ECO:0007829|PDB:1S1D"
FT STRAND 257..261
FT /evidence="ECO:0007829|PDB:1S1D"
FT HELIX 263..272
FT /evidence="ECO:0007829|PDB:1S1D"
FT STRAND 280..282
FT /evidence="ECO:0007829|PDB:1S1D"
FT STRAND 286..289
FT /evidence="ECO:0007829|PDB:1S1D"
FT TURN 290..293
FT /evidence="ECO:0007829|PDB:1S1D"
FT STRAND 294..297
FT /evidence="ECO:0007829|PDB:1S1D"
FT STRAND 300..305
FT /evidence="ECO:0007829|PDB:1S1D"
FT HELIX 309..312
FT /evidence="ECO:0007829|PDB:1S1D"
FT STRAND 319..323
FT /evidence="ECO:0007829|PDB:1S1D"
FT STRAND 330..334
FT /evidence="ECO:0007829|PDB:1S1D"
FT STRAND 342..349
FT /evidence="ECO:0007829|PDB:1S1D"
FT STRAND 357..366
FT /evidence="ECO:0007829|PDB:1S1D"
FT STRAND 369..378
FT /evidence="ECO:0007829|PDB:1S1D"
FT STRAND 383..400
FT /evidence="ECO:0007829|PDB:1S1D"
SQ SEQUENCE 401 AA; 44840 MW; 5B78EB24C0B2C4CA CRC64;
MPVQLSEHPE WNESMHSLRI SVGGLPVLAS MTKAADPRFR PRWKVILTFF VGAAILWLLC
SHRPAPGRPP THNAHNWRLG QAPANWYNDT YPLSPPQRTP AGIRYRIAVI ADLDTESRAQ
EENTWFSYLK KGYLTLSDSG DKVAVEWDKD HGVLESHLAE KGRGMELSDL IVFNGKLYSV
DDRTGVVYQI EGSKAVPWVI LSDGDGTVEK GFKAEWLAVK DERLYVGGLG KEWTTTTGDV
VNENPEWVKV VGYKGSVDHE NWVSNYNALR AAAGIQPPGY LIHESACWSD TLQRWFFLPR
RASQERYSEK DDERKGANLL LSASPDFGDI AVSHVGAVVP THGFSSFKFI PNTDDQIIVA
LKSEEDSGRV ASYIMAFTLD GRFLLPETKI GSVKYEGIEF I
