Full text data of ASNA1
ASNA1
(ARSA, TRC40)
[Confidence: low (only semi-automatic identification from reviews)]
ATPase ASNA1; 3.6.-.- (Arsenical pump-driving ATPase; Arsenite-stimulated ATPase; Transmembrane domain recognition complex 40 kDa ATPase subunit; hARSA-I; hASNA-I)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
ATPase ASNA1; 3.6.-.- (Arsenical pump-driving ATPase; Arsenite-stimulated ATPase; Transmembrane domain recognition complex 40 kDa ATPase subunit; hARSA-I; hASNA-I)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
O43681
ID ASNA_HUMAN Reviewed; 348 AA.
AC O43681; A6NHP8; A8K740; Q53FC6; Q92849;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
read moreDT 30-MAY-2000, sequence version 2.
DT 22-JAN-2014, entry version 127.
DE RecName: Full=ATPase ASNA1;
DE EC=3.6.-.-;
DE AltName: Full=Arsenical pump-driving ATPase;
DE AltName: Full=Arsenite-stimulated ATPase;
DE AltName: Full=Transmembrane domain recognition complex 40 kDa ATPase subunit;
DE AltName: Full=hARSA-I;
DE AltName: Full=hASNA-I;
GN Name=ASNA1; Synonyms=ARSA, TRC40;
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 [MRNA].
RA Hu G.;
RT "Human homolog of bacterial and mouse arsenite translocating ATPase
RT gene, ArsA.";
RL Submitted (FEB-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Salivary gland;
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cerebellum;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT SER-332.
RG NIEHS SNPs program;
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J.,
RA Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M.,
RA Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E.,
RA Caenepeel S., Carrano A.V., Caoile C., Chan Y.M., Christensen M.,
RA Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C.,
RA Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M.,
RA Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H.,
RA Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S.,
RA Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J.,
RA Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M.,
RA Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J.,
RA Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D.,
RA Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A.,
RA Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I.,
RA Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Uterus;
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 [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 18-348.
RX PubMed=8884272; DOI=10.1006/geno.1996.0494;
RA Kurdi-Haidar B., Aebi S., Heath D., Enns R.E., Naredi P., Hom D.K.,
RA Howell S.B.;
RT "Isolation of the ATP-binding human homolog of the arsA component of
RT the bacterial arsenite transporter.";
RL Genomics 36:486-491(1996).
RN [9]
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=9712828; DOI=10.1074/jbc.273.35.22173;
RA Kurdi-Haidar B., Heath D., Aebi S., Howell S.B.;
RT "Biochemical characterization of the human arsenite-stimulated ATPase
RT (hASNA-I).";
RL J. Biol. Chem. 273:22173-22176(1998).
RN [10]
RP SUBCELLULAR LOCATION.
RX PubMed=9736449;
RX DOI=10.1002/(SICI)1097-4644(19981001)71:1<1::AID-JCB1>3.3.CO;2-R;
RA Kurdi-Haidar B., Hom D.K., Flittner D.E., Heath D., Fink L.,
RA Naredi P., Howell S.B.;
RT "Dual cytoplasmic and nuclear distribution of the novel arsenite-
RT stimulated human ATPase (hASNA-I).";
RL J. Cell. Biochem. 71:1-10(1998).
RN [11]
RP TISSUE SPECIFICITY.
RX PubMed=9774623;
RA Kurdi-Haidar B., Heath D., Naredi P., Varki N., Howell S.B.;
RT "Immunohistochemical analysis of the distribution of the human ATPase
RT (hASNA-I) in normal tissues and its overexpression in breast adenomas
RT and carcinomas.";
RL J. Histochem. Cytochem. 46:1243-1248(1998).
RN [12]
RP FUNCTION, IDENTIFICATION IN THE TRC COMPLEX, MUTAGENESIS OF GLY-46,
RP SUBCELLULAR LOCATION, AND INTERACTION WITH SEC61B.
RX PubMed=17382883; DOI=10.1016/j.cell.2007.01.036;
RA Stefanovic S., Hegde R.S.;
RT "Identification of a targeting factor for posttranslational membrane
RT protein insertion into the ER.";
RL Cell 128:1147-1159(2007).
RN [13]
RP FUNCTION, AND INTERACTION WITH SERP1 AND SEC61B.
RX PubMed=18477612; DOI=10.1242/jcs.020321;
RA Favaloro V., Spasic M., Schwappach B., Dobberstein B.;
RT "Distinct targeting pathways for the membrane insertion of tail-
RT anchored (TA) proteins.";
RL J. Cell Sci. 121:1832-1840(2008).
RN [14]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
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 [15]
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 [16]
RP INTERACTION WITH WRB, AND SUBCELLULAR LOCATION.
RX PubMed=21444755; DOI=10.1242/jcs.084277;
RA Vilardi F., Lorenz H., Dobberstein B.;
RT "WRB is the receptor for TRC40/Asna1-mediated insertion of tail-
RT anchored proteins into the ER membrane.";
RL J. Cell Sci. 124:1301-1307(2011).
CC -!- FUNCTION: ATPase required for the post-translational delivery of
CC tail-anchored (TA) proteins to the endoplasmic reticulum.
CC Recognizes and selectively binds the transmembrane domain of TA
CC proteins in the cytosol. This complex then targets to the
CC endoplasmic reticulum by membrane-bound receptors, where the tail-
CC anchored protein is released for insertion. This process is
CC regulated by ATP binding and hydrolysis. ATP binding drives the
CC homodimer towards the closed dimer state, facilitating recognition
CC of newly synthesized TA membrane proteins. ATP hydrolysis is
CC required for insertion. Subsequently, the homodimer reverts
CC towards the open dimer state, lowering its affinity for the
CC membrane-bound receptor, and returning it to the cytosol to
CC initiate a new round of targeting (By similarity). May be involved
CC in insulin signaling.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.22 mM for ATP;
CC Vmax=16.6 nmol/min/mg enzyme for ATP;
CC -!- SUBUNIT: Homodimer (By similarity). Component of a transmembrane
CC domain recognition complex (TRC) (By similarity). Interacts with
CC SERP1 and SEC61B (By similarity). Interacts with WRB.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Endoplasmic reticulum. Nucleus,
CC nucleolus.
CC -!- TISSUE SPECIFICITY: Expressed in the epithelial cells of the
CC liver, kidney, and stomach wall, in the adrenal medulla, in the
CC islet cells of the pancreas, in the red pulp of the spleen, and in
CC cardiac and skeletal muscle.
CC -!- SIMILARITY: Belongs to the arsA ATPase family.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC50731.1; Type=Frameshift; Positions=19;
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/asna1/";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AF047469; AAC03551.1; -; mRNA.
DR EMBL; AK291855; BAF84544.1; -; mRNA.
DR EMBL; AK223363; BAD97083.1; -; mRNA.
DR EMBL; AY304483; AAP45050.1; -; Genomic_DNA.
DR EMBL; AC018761; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471106; EAW84303.1; -; Genomic_DNA.
DR EMBL; BC002651; AAH02651.1; -; mRNA.
DR EMBL; U60276; AAC50731.1; ALT_FRAME; mRNA.
DR RefSeq; NP_004308.2; NM_004317.2.
DR UniGene; Hs.465985; -.
DR ProteinModelPortal; O43681; -.
DR SMR; O43681; 27-342.
DR IntAct; O43681; 8.
DR MINT; MINT-4656878; -.
DR STRING; 9606.ENSP00000349887; -.
DR DrugBank; DB00171; Adenosine triphosphate.
DR TCDB; 3.A.19.1.1; the tms recognition/insertion complex (trc) family.
DR PhosphoSite; O43681; -.
DR OGP; O43681; -.
DR PaxDb; O43681; -.
DR PRIDE; O43681; -.
DR DNASU; 439; -.
DR Ensembl; ENST00000357332; ENSP00000349887; ENSG00000198356.
DR Ensembl; ENST00000591090; ENSP00000466379; ENSG00000198356.
DR GeneID; 439; -.
DR KEGG; hsa:439; -.
DR UCSC; uc002muv.3; human.
DR CTD; 439; -.
DR GeneCards; GC19P012848; -.
DR HGNC; HGNC:752; ASNA1.
DR HPA; HPA045951; -.
DR MIM; 601913; gene.
DR neXtProt; NX_O43681; -.
DR PharmGKB; PA25051; -.
DR eggNOG; COG0003; -.
DR HOGENOM; HOG000197637; -.
DR InParanoid; O43681; -.
DR KO; K01551; -.
DR OMA; IPEEMSI; -.
DR OrthoDB; EOG79W95W; -.
DR ChiTaRS; ASNA1; human.
DR GeneWiki; ASNA1; -.
DR GenomeRNAi; 439; -.
DR NextBio; 1839; -.
DR PRO; PR:O43681; -.
DR ArrayExpress; O43681; -.
DR Bgee; O43681; -.
DR CleanEx; HS_ARSA; -.
DR CleanEx; HS_ASNA1; -.
DR Genevestigator; O43681; -.
DR GO; GO:0005737; C:cytoplasm; TAS:ProtInc.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0005730; C:nucleolus; TAS:ProtInc.
DR GO; GO:0015105; F:arsenite transmembrane transporter activity; TAS:ProtInc.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-HAMAP.
DR GO; GO:0016887; F:ATPase activity; IEA:InterPro.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006200; P:ATP catabolic process; IEA:GOC.
DR GO; GO:0045048; P:protein insertion into ER membrane; IEA:UniProtKB-HAMAP.
DR HAMAP; MF_03112; Asna1_Get3; 1; -.
DR InterPro; IPR025723; Anion-transp_ATPase-like_dom.
DR InterPro; IPR016300; ATPase_ArsA/GET3.
DR InterPro; IPR027542; ATPase_ArsA/GET3_euk.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR10803; PTHR10803; 1.
DR Pfam; PF02374; ArsA_ATPase; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00345; GET3_arsA_TRC40; 1.
PE 1: Evidence at protein level;
KW Acetylation; ATP-binding; Complete proteome; Cytoplasm;
KW Endoplasmic reticulum; Hydrolase; Metal-binding; Nucleotide-binding;
KW Nucleus; Polymorphism; Reference proteome; Transport; Zinc.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 348 ATPase ASNA1.
FT /FTId=PRO_0000152253.
FT NP_BIND 45 52 ATP (By similarity).
FT ACT_SITE 74 74 By similarity.
FT METAL 289 289 Zinc; shared with dimeric partner (By
FT similarity).
FT METAL 292 292 Zinc; shared with dimeric partner (By
FT similarity).
FT BINDING 251 251 ATP (By similarity).
FT BINDING 278 278 ATP (By similarity).
FT MOD_RES 2 2 N-acetylalanine.
FT VARIANT 332 332 N -> S (in dbSNP:rs8177499).
FT /FTId=VAR_018844.
FT MUTAGEN 46 46 G->R: Abolishes ATPase activity,
FT dominantly inhibits the TA protein
FT insertion pathway.
FT CONFLICT 113 114 EL -> DV (in Ref. 8; AAC50731).
FT CONFLICT 205 205 C -> F (in Ref. 1; AAC03551).
FT CONFLICT 303 303 L -> P (in Ref. 3; BAD97083).
SQ SEQUENCE 348 AA; 38793 MW; DA52C4ACC35C7A36 CRC64;
MAAGVAGWGV EAEEFEDAPD VEPLEPTLSN IIEQRSLKWI FVGGKGGVGK TTCSCSLAVQ
LSKGRESVLI ISTDPAHNIS DAFDQKFSKV PTKVKGYDNL FAMEIDPSLG VAELPDEFFE
EDNMLSMGKK MMQEAMSAFP GIDEAMSYAE VMRLVKGMNF SVVVFDTAPT GHTLRLLNFP
TIVERGLGRL MQIKNQISPF ISQMCNMLGL GDMNADQLAS KLEETLPVIR SVSEQFKDPE
QTTFICVCIA EFLSLYETER LIQELAKCKI DTHNIIVNQL VFPDPEKPCK MCEARHKIQA
KYLDQMEDLY EDFHIVKLPL LPHEVRGADK VNTFSALLLE PYKPPSAQ
//
ID ASNA_HUMAN Reviewed; 348 AA.
AC O43681; A6NHP8; A8K740; Q53FC6; Q92849;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
read moreDT 30-MAY-2000, sequence version 2.
DT 22-JAN-2014, entry version 127.
DE RecName: Full=ATPase ASNA1;
DE EC=3.6.-.-;
DE AltName: Full=Arsenical pump-driving ATPase;
DE AltName: Full=Arsenite-stimulated ATPase;
DE AltName: Full=Transmembrane domain recognition complex 40 kDa ATPase subunit;
DE AltName: Full=hARSA-I;
DE AltName: Full=hASNA-I;
GN Name=ASNA1; Synonyms=ARSA, TRC40;
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 [MRNA].
RA Hu G.;
RT "Human homolog of bacterial and mouse arsenite translocating ATPase
RT gene, ArsA.";
RL Submitted (FEB-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Salivary gland;
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cerebellum;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT SER-332.
RG NIEHS SNPs program;
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J.,
RA Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M.,
RA Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E.,
RA Caenepeel S., Carrano A.V., Caoile C., Chan Y.M., Christensen M.,
RA Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C.,
RA Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M.,
RA Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H.,
RA Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S.,
RA Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J.,
RA Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M.,
RA Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J.,
RA Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D.,
RA Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A.,
RA Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I.,
RA Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Uterus;
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 [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 18-348.
RX PubMed=8884272; DOI=10.1006/geno.1996.0494;
RA Kurdi-Haidar B., Aebi S., Heath D., Enns R.E., Naredi P., Hom D.K.,
RA Howell S.B.;
RT "Isolation of the ATP-binding human homolog of the arsA component of
RT the bacterial arsenite transporter.";
RL Genomics 36:486-491(1996).
RN [9]
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=9712828; DOI=10.1074/jbc.273.35.22173;
RA Kurdi-Haidar B., Heath D., Aebi S., Howell S.B.;
RT "Biochemical characterization of the human arsenite-stimulated ATPase
RT (hASNA-I).";
RL J. Biol. Chem. 273:22173-22176(1998).
RN [10]
RP SUBCELLULAR LOCATION.
RX PubMed=9736449;
RX DOI=10.1002/(SICI)1097-4644(19981001)71:1<1::AID-JCB1>3.3.CO;2-R;
RA Kurdi-Haidar B., Hom D.K., Flittner D.E., Heath D., Fink L.,
RA Naredi P., Howell S.B.;
RT "Dual cytoplasmic and nuclear distribution of the novel arsenite-
RT stimulated human ATPase (hASNA-I).";
RL J. Cell. Biochem. 71:1-10(1998).
RN [11]
RP TISSUE SPECIFICITY.
RX PubMed=9774623;
RA Kurdi-Haidar B., Heath D., Naredi P., Varki N., Howell S.B.;
RT "Immunohistochemical analysis of the distribution of the human ATPase
RT (hASNA-I) in normal tissues and its overexpression in breast adenomas
RT and carcinomas.";
RL J. Histochem. Cytochem. 46:1243-1248(1998).
RN [12]
RP FUNCTION, IDENTIFICATION IN THE TRC COMPLEX, MUTAGENESIS OF GLY-46,
RP SUBCELLULAR LOCATION, AND INTERACTION WITH SEC61B.
RX PubMed=17382883; DOI=10.1016/j.cell.2007.01.036;
RA Stefanovic S., Hegde R.S.;
RT "Identification of a targeting factor for posttranslational membrane
RT protein insertion into the ER.";
RL Cell 128:1147-1159(2007).
RN [13]
RP FUNCTION, AND INTERACTION WITH SERP1 AND SEC61B.
RX PubMed=18477612; DOI=10.1242/jcs.020321;
RA Favaloro V., Spasic M., Schwappach B., Dobberstein B.;
RT "Distinct targeting pathways for the membrane insertion of tail-
RT anchored (TA) proteins.";
RL J. Cell Sci. 121:1832-1840(2008).
RN [14]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
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 [15]
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 [16]
RP INTERACTION WITH WRB, AND SUBCELLULAR LOCATION.
RX PubMed=21444755; DOI=10.1242/jcs.084277;
RA Vilardi F., Lorenz H., Dobberstein B.;
RT "WRB is the receptor for TRC40/Asna1-mediated insertion of tail-
RT anchored proteins into the ER membrane.";
RL J. Cell Sci. 124:1301-1307(2011).
CC -!- FUNCTION: ATPase required for the post-translational delivery of
CC tail-anchored (TA) proteins to the endoplasmic reticulum.
CC Recognizes and selectively binds the transmembrane domain of TA
CC proteins in the cytosol. This complex then targets to the
CC endoplasmic reticulum by membrane-bound receptors, where the tail-
CC anchored protein is released for insertion. This process is
CC regulated by ATP binding and hydrolysis. ATP binding drives the
CC homodimer towards the closed dimer state, facilitating recognition
CC of newly synthesized TA membrane proteins. ATP hydrolysis is
CC required for insertion. Subsequently, the homodimer reverts
CC towards the open dimer state, lowering its affinity for the
CC membrane-bound receptor, and returning it to the cytosol to
CC initiate a new round of targeting (By similarity). May be involved
CC in insulin signaling.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.22 mM for ATP;
CC Vmax=16.6 nmol/min/mg enzyme for ATP;
CC -!- SUBUNIT: Homodimer (By similarity). Component of a transmembrane
CC domain recognition complex (TRC) (By similarity). Interacts with
CC SERP1 and SEC61B (By similarity). Interacts with WRB.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Endoplasmic reticulum. Nucleus,
CC nucleolus.
CC -!- TISSUE SPECIFICITY: Expressed in the epithelial cells of the
CC liver, kidney, and stomach wall, in the adrenal medulla, in the
CC islet cells of the pancreas, in the red pulp of the spleen, and in
CC cardiac and skeletal muscle.
CC -!- SIMILARITY: Belongs to the arsA ATPase family.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC50731.1; Type=Frameshift; Positions=19;
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/asna1/";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AF047469; AAC03551.1; -; mRNA.
DR EMBL; AK291855; BAF84544.1; -; mRNA.
DR EMBL; AK223363; BAD97083.1; -; mRNA.
DR EMBL; AY304483; AAP45050.1; -; Genomic_DNA.
DR EMBL; AC018761; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471106; EAW84303.1; -; Genomic_DNA.
DR EMBL; BC002651; AAH02651.1; -; mRNA.
DR EMBL; U60276; AAC50731.1; ALT_FRAME; mRNA.
DR RefSeq; NP_004308.2; NM_004317.2.
DR UniGene; Hs.465985; -.
DR ProteinModelPortal; O43681; -.
DR SMR; O43681; 27-342.
DR IntAct; O43681; 8.
DR MINT; MINT-4656878; -.
DR STRING; 9606.ENSP00000349887; -.
DR DrugBank; DB00171; Adenosine triphosphate.
DR TCDB; 3.A.19.1.1; the tms recognition/insertion complex (trc) family.
DR PhosphoSite; O43681; -.
DR OGP; O43681; -.
DR PaxDb; O43681; -.
DR PRIDE; O43681; -.
DR DNASU; 439; -.
DR Ensembl; ENST00000357332; ENSP00000349887; ENSG00000198356.
DR Ensembl; ENST00000591090; ENSP00000466379; ENSG00000198356.
DR GeneID; 439; -.
DR KEGG; hsa:439; -.
DR UCSC; uc002muv.3; human.
DR CTD; 439; -.
DR GeneCards; GC19P012848; -.
DR HGNC; HGNC:752; ASNA1.
DR HPA; HPA045951; -.
DR MIM; 601913; gene.
DR neXtProt; NX_O43681; -.
DR PharmGKB; PA25051; -.
DR eggNOG; COG0003; -.
DR HOGENOM; HOG000197637; -.
DR InParanoid; O43681; -.
DR KO; K01551; -.
DR OMA; IPEEMSI; -.
DR OrthoDB; EOG79W95W; -.
DR ChiTaRS; ASNA1; human.
DR GeneWiki; ASNA1; -.
DR GenomeRNAi; 439; -.
DR NextBio; 1839; -.
DR PRO; PR:O43681; -.
DR ArrayExpress; O43681; -.
DR Bgee; O43681; -.
DR CleanEx; HS_ARSA; -.
DR CleanEx; HS_ASNA1; -.
DR Genevestigator; O43681; -.
DR GO; GO:0005737; C:cytoplasm; TAS:ProtInc.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0005730; C:nucleolus; TAS:ProtInc.
DR GO; GO:0015105; F:arsenite transmembrane transporter activity; TAS:ProtInc.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-HAMAP.
DR GO; GO:0016887; F:ATPase activity; IEA:InterPro.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006200; P:ATP catabolic process; IEA:GOC.
DR GO; GO:0045048; P:protein insertion into ER membrane; IEA:UniProtKB-HAMAP.
DR HAMAP; MF_03112; Asna1_Get3; 1; -.
DR InterPro; IPR025723; Anion-transp_ATPase-like_dom.
DR InterPro; IPR016300; ATPase_ArsA/GET3.
DR InterPro; IPR027542; ATPase_ArsA/GET3_euk.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR10803; PTHR10803; 1.
DR Pfam; PF02374; ArsA_ATPase; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00345; GET3_arsA_TRC40; 1.
PE 1: Evidence at protein level;
KW Acetylation; ATP-binding; Complete proteome; Cytoplasm;
KW Endoplasmic reticulum; Hydrolase; Metal-binding; Nucleotide-binding;
KW Nucleus; Polymorphism; Reference proteome; Transport; Zinc.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 348 ATPase ASNA1.
FT /FTId=PRO_0000152253.
FT NP_BIND 45 52 ATP (By similarity).
FT ACT_SITE 74 74 By similarity.
FT METAL 289 289 Zinc; shared with dimeric partner (By
FT similarity).
FT METAL 292 292 Zinc; shared with dimeric partner (By
FT similarity).
FT BINDING 251 251 ATP (By similarity).
FT BINDING 278 278 ATP (By similarity).
FT MOD_RES 2 2 N-acetylalanine.
FT VARIANT 332 332 N -> S (in dbSNP:rs8177499).
FT /FTId=VAR_018844.
FT MUTAGEN 46 46 G->R: Abolishes ATPase activity,
FT dominantly inhibits the TA protein
FT insertion pathway.
FT CONFLICT 113 114 EL -> DV (in Ref. 8; AAC50731).
FT CONFLICT 205 205 C -> F (in Ref. 1; AAC03551).
FT CONFLICT 303 303 L -> P (in Ref. 3; BAD97083).
SQ SEQUENCE 348 AA; 38793 MW; DA52C4ACC35C7A36 CRC64;
MAAGVAGWGV EAEEFEDAPD VEPLEPTLSN IIEQRSLKWI FVGGKGGVGK TTCSCSLAVQ
LSKGRESVLI ISTDPAHNIS DAFDQKFSKV PTKVKGYDNL FAMEIDPSLG VAELPDEFFE
EDNMLSMGKK MMQEAMSAFP GIDEAMSYAE VMRLVKGMNF SVVVFDTAPT GHTLRLLNFP
TIVERGLGRL MQIKNQISPF ISQMCNMLGL GDMNADQLAS KLEETLPVIR SVSEQFKDPE
QTTFICVCIA EFLSLYETER LIQELAKCKI DTHNIIVNQL VFPDPEKPCK MCEARHKIQA
KYLDQMEDLY EDFHIVKLPL LPHEVRGADK VNTFSALLLE PYKPPSAQ
//
MIM
601913
*RECORD*
*FIELD* NO
601913
*FIELD* TI
*601913 arsA ARSENITE TRANSPORTER, ATP-BINDING, E. COLI, HOMOLOG OF, 1; ASNA1
;;ARSA1;;
read moreTRANSMEMBRANE DOMAIN RECOGNITION COMPLEX, 40-KD; TRC40
*FIELD* TX
DESCRIPTION
ASNA1 is the human homolog of the bacterial arsA gene. In E. coli, ArsA
ATPase is the catalytic component of a multisubunit oxyanion pump that
is responsible for resistance to arsenicals and antimonials.
CLONING
Kurdi-Haidar et al. (1996) used degenerate PCR to clone a human homolog
of the bacterial arsA gene. The human ARSA1 cDNA was isolated from a
human ovarian carcinoma library and found to encode a 332-amino acid
polypeptide having an N-terminal ATP-binding cassette (ABC) domain and a
C-terminal domain of unknown function. The protein sequence is highly
homologous throughout both domains to hypothetical arsA proteins of C.
elegans and yeast. Northern blot analysis revealed that the ARSA1 gene
is ubiquitously expressed. Southern blot analysis indicated the
existence of 2 closely related ARSA genes in the human genome. The
existence of a second human ARSA protein was further supported by
Western blot analysis, which demonstrated that anti-ARSA1 antibodies
identify 2 proteins of 37 and 42 kD. Kurdi-Haidar et al. (1996)
expressed ARSA1 and found that the resulting 37-kD protein had ATPase
activity.
Kurdi-Haidar et al. (1998) found that ASNA1 shows a cytoplasmic,
perinuclear, and nucleolar distribution. By cell fractionation and
extensive use of double-label immunolocalizations, they demonstrated
that the cytoplasmic protein was soluble, the perinuclear protein was
associated with invaginations of the nuclear membranes rather than with
the endoplasmic reticulum, and that the nucleolar signal colocalized
with known nucleolar markers. Bhattacharjee et al. (2001) cloned mouse
Asna1 which encodes a 348-amino acid protein sharing 27% and 99%
identity with the E. coli and human proteins, respectively. Northern
blot analysis detected a 1.3-kb transcript in mouse at highest levels in
kidney and testis, moderate levels in brain, liver, lung, and skin, low
levels in heart, small intestine, spleen, stomach, and thymus, and
negligible levels in skeletal muscle.
GENE FUNCTION
Kurdi-Haidar et al. (1998) characterized purified recombinant ASNA1.
They determined that the ATPase activity increases in the presence of
sodium arsenite and that Vmax rather than ATP affinity is enhanced.
Unlike the E. coli homolog in which arsenite or antimonite
allosterically activates arsA ATPase activity, potassium antimonite had
no effect on the ATPase activity of human ASNA1. Through chemical
crosslinking of recombinant protein and by nonreducing PAGE analysis of
ASNA1 overexpressed in human kidney cells, they found that the active
species is likely a dimer or tetramer.
Mariappan et al. (2010) identified a conserved 3-protein complex
composed of BAT3 (142590), TRC35 (612056), and UBL4A (312070) that
facilitates tail-anchored protein capture by TRC40. This BAT3 complex is
recruited to ribosomes synthesizing membrane proteins, interacts with
the transmembrane domains of newly released tail-anchored proteins, and
transfers them to TRC40 for targeting. Depletion of the BAT3 complex
allows non-TRC40 factors to compete for tail-anchored proteins,
explaining their mislocalization in the analogous yeast deletion
strains. Thus, the BAT3 complex acts as a transmembrane domain-selective
chaperone that effectively channels tail-anchored proteins to the TRC40
insertion pathway.
GENE STRUCTURE
Kurdi-Haidar et al. (1998) determined that the ASNA1 gene contains 4
exons and spans 6 kb. Bhattacharjee et al. (2001) determined that the
mouse Asna1 gene consists of 7 exons spanning over 7 kb.
MAPPING
By somatic-cell hybrid PCR mapping and identification of a cosmid
containing the full-length sequence, Kurdi-Haidar et al. (1998) mapped
the ASNA1 gene to chromosome 19q13.3. Bhattacharjee et al. (2001) mapped
the mouse Asna1 gene to the C3-D1 region of chromosome 8.
*FIELD* RF
1. Bhattacharjee, H.; Ho, Y.-S.; Rosen, B. P.: Genomic organization
and chromosomal localization of the Asna1 gene, a mouse homologue
of a bacterial arsenic-translocating ATPase gene. Gene 272: 291-299,
2001.
2. Kurdi-Haidar, B.; Aebi, S.; Heath, D.; Enns, R. E.; Naredi, P.;
Hom, D. K.; Howell, S. B.: Isolation of the ATP-binding human homolog
of the arsA component of the bacterial arsenite transporter. Genomics 36:
486-491, 1996.
3. Kurdi-Haidar, B.; Heath, D.; Aebi, S.; Howell, S. B.: Biochemical
characterization of the human arsenite-stimulated ATPase (hASNA-I). J.
Biol. Chem. 273: 22173-22176, 1998.
4. Kurdi-Haidar, B.; Heath, D.; Lennon, G.; Howell, S. B.: Chromosomal
localization and genomic structure of the human arsenite-stimulated
ATPase (hASNA-I). Somat. Cell Molec. Genet. 24: 307-311, 1998.
5. Kurdi-Haidar, B.; Hom, D. K.; Flittner, D. E.; Heath, D.; Fink,
L.; Naredi, P.; Howell, S. B.: Dual cytoplasmic and nuclear distribution
of the novel arsenite-stimulated human ATPase (hASNA-I). J. Cell.
Biochem. 71: 1-10, 1998.
6. Mariappan, M.; Li, X.; Stefanovic, S.; Sharma, A.; Mateja, A.;
Keenan, R. J.; Hegde, R. S.: A ribosome-associating factor chaperones
tail-anchored membrane proteins. Nature 466: 1120-1124, 2010.
*FIELD* CN
Ada Hamosh - updated: 9/14/2010
Patricia A. Hartz - updated: 5/24/2002
*FIELD* CD
Jennifer P. Macke: 4/24/1997
*FIELD* ED
alopez: 09/15/2010
terry: 9/14/2010
carol: 5/30/2002
terry: 5/24/2002
alopez: 11/23/1998
alopez: 7/14/1997
*RECORD*
*FIELD* NO
601913
*FIELD* TI
*601913 arsA ARSENITE TRANSPORTER, ATP-BINDING, E. COLI, HOMOLOG OF, 1; ASNA1
;;ARSA1;;
read moreTRANSMEMBRANE DOMAIN RECOGNITION COMPLEX, 40-KD; TRC40
*FIELD* TX
DESCRIPTION
ASNA1 is the human homolog of the bacterial arsA gene. In E. coli, ArsA
ATPase is the catalytic component of a multisubunit oxyanion pump that
is responsible for resistance to arsenicals and antimonials.
CLONING
Kurdi-Haidar et al. (1996) used degenerate PCR to clone a human homolog
of the bacterial arsA gene. The human ARSA1 cDNA was isolated from a
human ovarian carcinoma library and found to encode a 332-amino acid
polypeptide having an N-terminal ATP-binding cassette (ABC) domain and a
C-terminal domain of unknown function. The protein sequence is highly
homologous throughout both domains to hypothetical arsA proteins of C.
elegans and yeast. Northern blot analysis revealed that the ARSA1 gene
is ubiquitously expressed. Southern blot analysis indicated the
existence of 2 closely related ARSA genes in the human genome. The
existence of a second human ARSA protein was further supported by
Western blot analysis, which demonstrated that anti-ARSA1 antibodies
identify 2 proteins of 37 and 42 kD. Kurdi-Haidar et al. (1996)
expressed ARSA1 and found that the resulting 37-kD protein had ATPase
activity.
Kurdi-Haidar et al. (1998) found that ASNA1 shows a cytoplasmic,
perinuclear, and nucleolar distribution. By cell fractionation and
extensive use of double-label immunolocalizations, they demonstrated
that the cytoplasmic protein was soluble, the perinuclear protein was
associated with invaginations of the nuclear membranes rather than with
the endoplasmic reticulum, and that the nucleolar signal colocalized
with known nucleolar markers. Bhattacharjee et al. (2001) cloned mouse
Asna1 which encodes a 348-amino acid protein sharing 27% and 99%
identity with the E. coli and human proteins, respectively. Northern
blot analysis detected a 1.3-kb transcript in mouse at highest levels in
kidney and testis, moderate levels in brain, liver, lung, and skin, low
levels in heart, small intestine, spleen, stomach, and thymus, and
negligible levels in skeletal muscle.
GENE FUNCTION
Kurdi-Haidar et al. (1998) characterized purified recombinant ASNA1.
They determined that the ATPase activity increases in the presence of
sodium arsenite and that Vmax rather than ATP affinity is enhanced.
Unlike the E. coli homolog in which arsenite or antimonite
allosterically activates arsA ATPase activity, potassium antimonite had
no effect on the ATPase activity of human ASNA1. Through chemical
crosslinking of recombinant protein and by nonreducing PAGE analysis of
ASNA1 overexpressed in human kidney cells, they found that the active
species is likely a dimer or tetramer.
Mariappan et al. (2010) identified a conserved 3-protein complex
composed of BAT3 (142590), TRC35 (612056), and UBL4A (312070) that
facilitates tail-anchored protein capture by TRC40. This BAT3 complex is
recruited to ribosomes synthesizing membrane proteins, interacts with
the transmembrane domains of newly released tail-anchored proteins, and
transfers them to TRC40 for targeting. Depletion of the BAT3 complex
allows non-TRC40 factors to compete for tail-anchored proteins,
explaining their mislocalization in the analogous yeast deletion
strains. Thus, the BAT3 complex acts as a transmembrane domain-selective
chaperone that effectively channels tail-anchored proteins to the TRC40
insertion pathway.
GENE STRUCTURE
Kurdi-Haidar et al. (1998) determined that the ASNA1 gene contains 4
exons and spans 6 kb. Bhattacharjee et al. (2001) determined that the
mouse Asna1 gene consists of 7 exons spanning over 7 kb.
MAPPING
By somatic-cell hybrid PCR mapping and identification of a cosmid
containing the full-length sequence, Kurdi-Haidar et al. (1998) mapped
the ASNA1 gene to chromosome 19q13.3. Bhattacharjee et al. (2001) mapped
the mouse Asna1 gene to the C3-D1 region of chromosome 8.
*FIELD* RF
1. Bhattacharjee, H.; Ho, Y.-S.; Rosen, B. P.: Genomic organization
and chromosomal localization of the Asna1 gene, a mouse homologue
of a bacterial arsenic-translocating ATPase gene. Gene 272: 291-299,
2001.
2. Kurdi-Haidar, B.; Aebi, S.; Heath, D.; Enns, R. E.; Naredi, P.;
Hom, D. K.; Howell, S. B.: Isolation of the ATP-binding human homolog
of the arsA component of the bacterial arsenite transporter. Genomics 36:
486-491, 1996.
3. Kurdi-Haidar, B.; Heath, D.; Aebi, S.; Howell, S. B.: Biochemical
characterization of the human arsenite-stimulated ATPase (hASNA-I). J.
Biol. Chem. 273: 22173-22176, 1998.
4. Kurdi-Haidar, B.; Heath, D.; Lennon, G.; Howell, S. B.: Chromosomal
localization and genomic structure of the human arsenite-stimulated
ATPase (hASNA-I). Somat. Cell Molec. Genet. 24: 307-311, 1998.
5. Kurdi-Haidar, B.; Hom, D. K.; Flittner, D. E.; Heath, D.; Fink,
L.; Naredi, P.; Howell, S. B.: Dual cytoplasmic and nuclear distribution
of the novel arsenite-stimulated human ATPase (hASNA-I). J. Cell.
Biochem. 71: 1-10, 1998.
6. Mariappan, M.; Li, X.; Stefanovic, S.; Sharma, A.; Mateja, A.;
Keenan, R. J.; Hegde, R. S.: A ribosome-associating factor chaperones
tail-anchored membrane proteins. Nature 466: 1120-1124, 2010.
*FIELD* CN
Ada Hamosh - updated: 9/14/2010
Patricia A. Hartz - updated: 5/24/2002
*FIELD* CD
Jennifer P. Macke: 4/24/1997
*FIELD* ED
alopez: 09/15/2010
terry: 9/14/2010
carol: 5/30/2002
terry: 5/24/2002
alopez: 11/23/1998
alopez: 7/14/1997