Reviewed, UniProtKB/Swiss-Prot O43681 (ASNA_HUMAN)

Names and origin

Protein names

Recommended name:
    ATPase ASNA1
    EC=3.6.3.16
Alternative name(s):
    Arsenite-stimulated ATPase
      Short name=hARSA-I
      Short name=hASNA-I
    Arsenical pump-driving ATPase
    Transmembrane domain recognition complex 40 kDa ATPase subunit

Gene names

Name:	ASNA1
Synonyms:	ARSA, TRC40

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	348 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	ATPase required for the post-translational delivery of tail-anchored (TA) proteins to the endoplasmic reticulum. Recognizes and selectively binds the transmembrane domain of TA proteins in the cytosol. This complex then targets to the endoplasmic reticulum by membrane-bound receptors, where the tail-anchored protein is released for insertion. This process is regulated by ATP binding and hydrolysis. ATP binding drives the homodimer towards the closed dimer state, facilitating recognition of newly synthesized TA membrane proteins. ATP hydolysis is required for insertion. Subsequently, the homodimer reverts towards the open dimer state, lowering its affinity for the membrane-bound receptor, and returning it to the cytosol to initiate a new round of targeting By similarity. May be involved in insulin signaling.
Catalytic activity	ATP + H2O + arsenite(In) = ADP + phosphate + arsenite(Out).
Subunit structure	Homodimer By similarity. Component of a transmembrane domain recognition complex (TRC) By similarity. Interacts with SERP1 and SEC61B By similarity.
Subcellular location	Cytoplasm. Endoplasmic reticulum. Nucleus › nucleolus.
Tissue specificity	Expressed in the epithelial cells of the liver, kidney, and stomach wall, in the adrenal medulla, in the islet cells of the pancreas, in the red pulp of the spleen, and in cardiac and skeletal muscle. Ref.11
Sequence similarities	Belongs to the arsA ATPase family.
Biophysicochemical properties	Kinetic parameters: KM=0.22 mM for ATP Vmax=16.6 nmol/min/mg enzyme for ATP
Sequence caution	The sequence AAC50731.1 differs from that shown. Reason: Frameshift at position 19.

Ontologies

Keywords
Biological process	Transport
Cellular component	Cytoplasm Endoplasmic reticulum Nucleus
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Metal-binding Nucleotide-binding Zinc
Molecular function	Hydrolase
PTM	Acetylation
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	cellular metal ion homeostasis Inferred from electronic annotation. Source: InterPro response to arsenic Inferred from electronic annotation. Source: UniProtKB-KW transport Ref.10 Traceable author statement. Source: ProtInc
Cellular component	cytoplasm Ref.10 Traceable author statement. Source: ProtInc nucleolus Ref.10 Traceable author statement. Source: ProtInc soluble fraction Ref.10 Traceable author statement. Source: ProtInc
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW arsenite transmembrane-transporting ATPase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed
	Chain	2 – 348	347	ATPase ASNA1		PRO_0000152253
Regions
	Nucleotide binding	45 – 52	8	ATP By similarity
Sites
	Active site	74	1	By similarity
	Metal binding	289	1	Zinc; shared with dimeric partner By similarity
	Metal binding	292	1	Zinc; shared with dimeric partner By similarity
	Binding site	251	1	ATP By similarity
	Binding site	278	1	ATP By similarity
Amino acid modifications
	Modified residue	2	1	N-acetylalanine
Natural variations
	Natural variant	332	1	N → S: dbSNP rs8177499. Ref.4		VAR_018844
Experimental info
	Mutagenesis	49	1	G → R: Abolishes ATPase activity, dominantely inhibits the TA protein insertion pathway. Ref.12
	Sequence conflict	113 – 114	2	EL → DV in AAC50731. Ref.8
	Sequence conflict	205	1	C → F in AAC03551. Ref.1
	Sequence conflict	303	1	L → P in BAD97083. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	O43681-1 [UniParc]. Last modified May 30, 2000. Version 2. Checksum: DA52C4ACC35C7A36	FASTA	348	38,793
	10 20 30 40 50 60 MAAGVAGWGV EAEEFEDAPD VEPLEPTLSN IIEQRSLKWI FVGGKGGVGK TTCSCSLAVQ 70 80 90 100 110 120 LSKGRESVLI ISTDPAHNIS DAFDQKFSKV PTKVKGYDNL FAMEIDPSLG VAELPDEFFE 130 140 150 160 170 180 EDNMLSMGKK MMQEAMSAFP GIDEAMSYAE VMRLVKGMNF SVVVFDTAPT GHTLRLLNFP 190 200 210 220 230 240 TIVERGLGRL MQIKNQISPF ISQMCNMLGL GDMNADQLAS KLEETLPVIR SVSEQFKDPE 250 260 270 280 290 300 QTTFICVCIA EFLSLYETER LIQELAKCKI DTHNIIVNQL VFPDPEKPCK MCEARHKIQA 310 320 330 340 KYLDQMEDLY EDFHIVKLPL LPHEVRGADK VNTFSALLLE PYKPPSAQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human homolog of bacterial and mouse arsenite translocating ATPase gene, ArsA." Hu G. Submitted (FEB-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"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]. Tissue: Salivary gland.
[3]	Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Cerebellum.
[4]	NIEHS SNPs program Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT SER-332.
[5]	"The DNA sequence and biology of human chromosome 19." Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M. Nature 428:529-535(2004) [PubMed: 15057824] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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]. Tissue: Uterus.
[8]	"Isolation of the ATP-binding human homolog of the arsA component of the bacterial arsenite transporter." Kurdi-Haidar B., Aebi S., Heath D., Enns R.E., Naredi P., Hom D.K., Howell S.B. Genomics 36:486-491(1996) [PubMed: 8884272] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 18-348.
[9]	"Biochemical characterization of the human arsenite-stimulated ATPase (hASNA-I)." Kurdi-Haidar B., Heath D., Aebi S., Howell S.B. J. Biol. Chem. 273:22173-22176(1998) [PubMed: 9712828] [Abstract] Cited for: BIOPHYSICOCHEMICAL PROPERTIES.
[10]	"Dual cytoplasmic and nuclear distribution of the novel arsenite-stimulated human ATPase (hASNA-I)." Kurdi-Haidar B., Hom D.K., Flittner D.E., Heath D., Fink L., Naredi P., Howell S.B. J. Cell. Biochem. 71:1-10(1998) [PubMed: 9736449] [Abstract] Cited for: SUBCELLULAR LOCATION.
[11]	"Immunohistochemical analysis of the distribution of the human ATPase (hASNA-I) in normal tissues and its overexpression in breast adenomas and carcinomas." Kurdi-Haidar B., Heath D., Naredi P., Varki N., Howell S.B. J. Histochem. Cytochem. 46:1243-1248(1998) [PubMed: 9774623] [Abstract] Cited for: TISSUE SPECIFICITY.
[12]	"Identification of a targeting factor for posttranslational membrane protein insertion into the ER." Stefanovic S., Hegde R.S. Cell 128:1147-1159(2007) [PubMed: 17382883] [Abstract] Cited for: FUNCTION, IDENTIFICATION IN TRC COMPLEX, MUTAGENESIS OF GLY-49, SUBCELLULAR LOCATION, INTERACTION WITH SEC61B.
[13]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[14]	"Distinct targeting pathways for the membrane insertion of tail-anchored (TA) proteins." Favaloro V., Spasic M., Schwappach B., Dobberstein B. J. Cell Sci. 121:1832-1840(2008) [PubMed: 18477612] [Abstract] Cited for: FUNCTION, INTERACTION WITH SERP1 AND SEC61B.
[15]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF047469 mRNA. Translation: AAC03551.1. AK291855 mRNA. Translation: BAF84544.1. AK223363 mRNA. Translation: BAD97083.1. AY304483 Genomic DNA. Translation: AAP45050.1. AC018761 Genomic DNA. No translation available. CH471106 Genomic DNA. Translation: EAW84303.1. BC002651 mRNA. Translation: AAH02651.1. U60276 mRNA. Translation: AAC50731.1. Frameshift.
IPI	IPI00013466.
RefSeq	NP_004308.2.
UniGene	Hs.465985
3D structure databases
ModBase	Search...
Protein-protein interaction databases
STRING	O43681.
Protein family/group databases
TCDB	3.A.19.1.1. TMS recognition/insertion complex (TRC) family.
PTM databases
PhosphoSite	O43681.
2-D gel databases
OGP	O43681.
Proteomic databases
PRIDE	O43681.
Genome annotation databases
Ensembl	ENST00000357332; ENSP00000349887; ENSG00000198356; Homo sapiens. [Genome view]
GeneID	439.
KEGG	hsa:439.
UCSC	uc002muv.1. human.
Organism-specific databases
CTD	439.
GeneCards	GC19P012709.
H-InvDB	HIX0014802.
HGNC	HGNC:752. ASNA1.
MIM	601913. gene.
PharmGKB	PA25051.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	O43681.
OMA	RAQRNIT
OrthoDB	EOG9323J6
Enzyme and pathway databases
BRENDA	3.6.3.16. 247.
Gene expression databases
ArrayExpress	O43681.
Bgee	O43681.
CleanEx	HS_ARSA. HS_ASNA1.
Genevestigator	O43681.
GermOnline	ENSG00000198356. Homo sapiens.
Family and domain databases
InterPro	IPR003348. ATPase_anion-transp. [Graphical view]
Pfam	PF02374. ArsA_ATPase. 1 hit. [Graphical view]
TIGRFAMs	TIGR00345. arsA. 1 hit.
ProtoNet	Search...
Other Resources
DrugBank	DB00171. Adenosine triphosphate.
NextBio	1839.
SOURCE	Search...

Entry information

Entry name

ASNA_HUMAN

Accession

Primary (citable) accession number: O43681
Secondary accession number(s): A6NHP8 , A8K740, Q53FC6, Q92849

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	May 30, 2000
Last modified:	November 24, 2009
This is version 84 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.