RBCC Red Blood Cell Collection

ATE1 [Confidence: low (only semi-automatic identification from reviews)]
Arginyl-tRNA--protein transferase 1; Arginyltransferase 1; R-transferase 1; 2.3.2.8 (Arginine-tRNA--protein transferase 1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)

UniProt O95260
ID ATE1_HUMAN Reviewed; 518 AA.
AC O95260; O95261; Q5SQQ3; Q8WW04;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
read moreDT 26-JUL-2002, sequence version 2.
DT 22-JAN-2014, entry version 104.
DE RecName: Full=Arginyl-tRNA--protein transferase 1;
DE Short=Arginyltransferase 1;
DE Short=R-transferase 1;
DE EC=2.3.2.8;
DE AltName: Full=Arginine-tRNA--protein transferase 1;
GN Name=ATE1;
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 [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D.,
RA Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L.,
RA Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S.,
RA Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L.,
RA Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J.,
RA Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M.,
RA Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S.,
RA Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M.,
RA Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A.,
RA Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T.,
RA Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I.,
RA Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T.,
RA Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W.,
RA Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H.,
RA Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L.,
RA Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K.,
RA Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T.,
RA Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [2]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ATE1-2).
RC TISSUE=Testis;
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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 5-518 (ISOFORMS ATE1-1 AND ATE1-2).
RC TISSUE=Embryonic kidney;
RX PubMed=9858543;
RA Kwon Y.T., Kashina A.S., Varshavsky A.;
RT "Alternative splicing results in differential expression, activity,
RT and localization of the two forms of arginyl-tRNA-protein transferase,
RT a component of the N-end rule pathway.";
RL Mol. Cell. Biol. 19:182-193(1999).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-169, AND MASS
RP SPECTROMETRY.
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III,
RA Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N.,
RA Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [6]
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).
CC -!- FUNCTION: Involved in the post-translational conjugation of
CC arginine to the N-terminal aspartate or glutamate of a protein.
CC This arginylation is required for degradation of the protein via
CC the ubiquitin pathway. Does not arginylate cysteine residues (By
CC similarity).
CC -!- CATALYTIC ACTIVITY: L-arginyl-tRNA(Arg) + [protein] = tRNA(Arg) +
CC L-arginyl-[protein].
CC -!- SUBUNIT: Monomer (Potential).
CC -!- INTERACTION:
CC O43463:SUV39H1; NbExp=2; IntAct=EBI-1043378, EBI-349968;
CC -!- SUBCELLULAR LOCATION: Isoform ATE1-1: Nucleus (By similarity).
CC Cytoplasm (By similarity).
CC -!- SUBCELLULAR LOCATION: Isoform ATE1-2: Cytoplasm (By similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=ATE1-1;
CC IsoId=O95260-1; Sequence=Displayed;
CC Name=ATE1-2;
CC IsoId=O95260-2; Sequence=VSP_000336;
CC -!- SIMILARITY: Belongs to the R-transferase family.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-37 is the initiator.
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DR EMBL; AL731542; CAI12918.1; -; Genomic_DNA.
DR EMBL; AC025947; CAI12918.1; JOINED; Genomic_DNA.
DR EMBL; AL731566; CAI12918.1; JOINED; Genomic_DNA.
DR EMBL; AL731566; CAI14813.1; -; Genomic_DNA.
DR EMBL; AC025947; CAI14813.1; JOINED; Genomic_DNA.
DR EMBL; AL731542; CAI14813.1; JOINED; Genomic_DNA.
DR EMBL; CH471066; EAW49334.1; -; Genomic_DNA.
DR EMBL; BC022026; AAH22026.2; -; mRNA.
DR EMBL; AF079098; AAD12366.1; -; mRNA.
DR EMBL; AF079099; AAD12367.1; -; mRNA.
DR RefSeq; NP_001001976.1; NM_001001976.1.
DR RefSeq; NP_008972.2; NM_007041.2.
DR UniGene; Hs.632080; -.
DR ProteinModelPortal; O95260; -.
DR IntAct; O95260; 3.
DR MINT; MINT-4527548; -.
DR STRING; 9606.ENSP00000224652; -.
DR PhosphoSite; O95260; -.
DR PaxDb; O95260; -.
DR PRIDE; O95260; -.
DR DNASU; 11101; -.
DR Ensembl; ENST00000224652; ENSP00000224652; ENSG00000107669.
DR Ensembl; ENST00000369043; ENSP00000358039; ENSG00000107669.
DR GeneID; 11101; -.
DR KEGG; hsa:11101; -.
DR UCSC; uc001lfq.3; human.
DR CTD; 11101; -.
DR GeneCards; GC10M123492; -.
DR HGNC; HGNC:782; ATE1.
DR HPA; HPA038444; -.
DR MIM; 607103; gene.
DR neXtProt; NX_O95260; -.
DR PharmGKB; PA25082; -.
DR eggNOG; COG2935; -.
DR HOGENOM; HOG000007968; -.
DR HOVERGEN; HBG004299; -.
DR KO; K00685; -.
DR OMA; FHKKAIM; -.
DR OrthoDB; EOG7Q5HDG; -.
DR PhylomeDB; O95260; -.
DR ChiTaRS; ATE1; human.
DR GenomeRNAi; 11101; -.
DR NextBio; 42204; -.
DR PRO; PR:O95260; -.
DR ArrayExpress; O95260; -.
DR Bgee; O95260; -.
DR CleanEx; HS_ATE1; -.
DR Genevestigator; O95260; -.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0004057; F:arginyltransferase activity; TAS:UniProtKB.
DR GO; GO:0016598; P:protein arginylation; NAS:UniProtKB.
DR InterPro; IPR016181; Acyl_CoA_acyltransferase.
DR InterPro; IPR017137; Arg-tRNA-P_Trfase_1_euk.
DR InterPro; IPR007472; Arg-tRNA-P_Trfase_C.
DR InterPro; IPR007471; Arg_tRNA_PTrfase_N.
DR Pfam; PF04377; ATE_C; 1.
DR Pfam; PF04376; ATE_N; 1.
DR PIRSF; PIRSF037207; ATE1_euk; 1.
DR SUPFAM; SSF55729; SSF55729; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Alternative splicing; Complete proteome; Cytoplasm;
KW Nucleus; Phosphoprotein; Reference proteome; Transferase;
KW Ubl conjugation pathway.
FT CHAIN 1 518 Arginyl-tRNA--protein transferase 1.
FT /FTId=PRO_0000195088.
FT MOD_RES 169 169 Phosphoserine.
FT VAR_SEQ 274 314 VVRSSPPSSQFKATLLESYQVYKRYQMVIHKNPPDTPTESQ
FT -> LVPVSFEDPEFKSSFSQSFSLYVKYQVAIHQDPPDECG
FT KTE (in isoform ATE1-2).
FT /FTId=VSP_000336.
FT CONFLICT 5 11 AGGSPSV -> GGGFAAS (in Ref. 4; AAD12366).
SQ SEQUENCE 518 AA; 59090 MW; BFD1CF8925CF5820 CRC64;
MAFWAGGSPS VVDYFPSEDF YRCGYCKNES GSRSNGMWAH SMTVQDYQDL IDRGWRRSGK
YVYKPVMNQT CCPQYTIRCR PLQFQPSKSH KKVLKKMLKF LAKGEVPKGS CEDEPMDSTM
DDAVAGDFAL INKLDIQCDL KTLSDDIKES LESEGKNSKK EEPQELLQSQ DFVGEKLGSG
EPSHSVKVHT VPKPGKGADL SKPPCRKAKE IRKERKRLKL MQQNPAGELE GFQAQGHPPS
LFPPKAKSNQ PKSLEDLIFE SLPENASHKL EVRVVRSSPP SSQFKATLLE SYQVYKRYQM
VIHKNPPDTP TESQFTRFLC SSPLEAETPP NGPDCGYGSF HQQYWLDGKI IAVGVIDILP
NCVSSVYLYY DPDYSFLSLG VYSALREIAF TRQLHEKTSQ LSYYYMGFYI HSCPKMKYKG
QYRPSDLLCP ETYVWVPIEQ CLPSLENSKY CRFNQDPEAV DEDRSTEPDR LQVFHKRAIM
PYGVYKKQQK DPSEEAAVLQ YASLVGQKCS ERMLLFRN
//

MIM 607103
*RECORD*
*FIELD* NO
607103
*FIELD* TI
*607103 ARGINYLTRANSFERASE 1; ATE1
*FIELD* TX

DESCRIPTION

The N-end rule relates the in vivo half-life of a protein to the
read moreidentity of its N-terminal residue. N-terminal arginine is a primary
destabilizing residue for ubiquitin-dependent degradation, while
N-terminal aspartate and glutamate are secondary destabilizing residues
due to their role as substrates for arginylation by ATE1.

CLONING

Based on sequence similarity to mouse Ate1, Kwon et al. (1999)
identified human ATE1 within an EST clone and subsequently cloned 2
forms of ATE1 cDNA from human embryonic kidney cells. They determined
that the 2 variants of ATE1, which they termed ATE1-1 and ATE1-2, are
found in both human and mouse and result from the use of alternate
second exons. In mouse, both variants encode deduced 516-amino acid
proteins with calculated molecular masses of about 59 kD. The 43-residue
sequences encoded by the alternate exons are 31% identical. Northern
blot analysis of mouse tissues revealed a 5-kb transcript in all tissues
tested except testis, where the major transcript was 2 kb. Restriction
digests of the transcripts suggested that the ratio of Ate1-1 to Ate1-2
varies between tissues. Transfection of fluorescence-tagged Ate1-1 into
mouse fibroblasts resulted in both nuclear and cytosolic localization,
whereas Ate1-2 localization was exclusively cytosolic.

ANIMAL MODEL

Kwon et al. (2002) generated mice lacking ATE1. Ate1 -/- embryos died
with defects in heart development and in angiogenic remodeling of the
early vascular plexus. Through biochemical analyses, Kwon et al. (2002)
demonstrated that the N-terminal cysteine, in contrast to N-terminal
aspartate and glutamate, is oxidized before its arginylation by
R-transferase, suggesting that the arginylation branch of the N-end rule
pathway functions as an oxygen sensor. Ate1 +/- mice were apparently
normal, but Ate1 knockout embryos were pale and had thinner blood
vessels and frequent skin edema in embryonic days 9.5 to 12.5.
Hemorrhages were a consistent feature of homozygous mutant embryos and
were the likely proximal cause of death. Of 22 Ate1 -/- hearts examined
at embryonic days 13.5 to 15.5, about 85% had an atrial septal defect.
The atria were thin-walled with sparse trabeculae and a large atrial
septal defect. About 90% of examined Ate1-knockout embryonic hearts
exhibited hypoplasia of both the right and left ventricular myocardium.
The compact zone of the left ventricular myocardium was 2 or 3 cells
thick, in contrast to 7 to 10 cells in wildtype embryos. About 70% of
knockout Ate1 knockout mice had persistent truncus arteriosus, with the
common root of the aorta and pulmonary artery straddling a large ventral
septal defect. Vasculogenesis was normal at embryonic day 9.5, but
angiogenic remodeling was suppressed. Kwon et al. (2002) identified a
physiologic function for the posttranslational conjugation of arginine
to N-termini of proteins, a reaction first described by Kaji et al.
(1963). Kwon et al. (2002) also showed that the N-terminal cysteine
undergoes 2 covalent modifications, oxidation and arginylation, by the
N-end rule pathway. Methionine-aminopeptidases cleave off the N-terminal
methionine of the newly formed protein if a second residue is small
enough. Among the arginylatable residues, only cysteine satisfies this
condition.

In immunoprecipitation studies of embryonic fibroblasts from wildtype
and knockout mice deficient in the arginylation enzyme Ate1, Karakozova
et al. (2006) found that approximately 40% of intracellular beta-actin
(102630) is arginylated in vivo. In both wildtype and Ate1-null cells
beta-actin was stable, suggesting that arginylation does not induce
beta-actin degradation. Karakozova et al. (2006) found that arginylation
of beta-actin regulates cell motility. The majority of Ate1-null cells
appeared smaller than wildtype cells and were apparently unable to form
lamellae during movement along the substrate. Ate-null cells failed to
form normal lamellae during motility, resulting in their inability to
cover the same distance or occupy the same area of th substrate as the
control cells. In addition, Ate1-null cells exhibited apparent defects
in ruffling activity and cortical flow. Karakozova et al. (2006)
concluded that arginylation of beta-actin apparently represents a
critical step in the actin N-terminal processing needed for actin
functioning in vivo.

GENE FUNCTION

By stabilization assays and N-terminal sequencing of beta-galactosidase
substrate proteins, Kwon et al. (1999) found that both mouse Ate1-1 and
Ate1-2 conferred instability on asp-beta-galactosidase through
arginylation of the N-terminal asp. Cys-beta-galactosidase was a
less-efficient substrate.

The conjugation of arginine to proteins is a part of the N-end rule
pathway of protein degradation. Three N-terminal residues--aspartate,
glutamate, and cysteine--are arginylated by ATE1-encoded
arginyl-transferases. Hu et al. (2005) reported that oxidation of
N-terminal cysteine is essential for its arginylation. They showed that
the in vivo oxidation of N-terminal cysteine, before its arginylation,
requires nitric oxide, and reconstituted this process in vitro as well.
The levels of regulatory proteins bearing N-terminal cysteine, such as
RGS4 (602516), RGS5 (603276), and RGS16 (602514), were greatly increased
in mouse Ate1-null embryos, which lack arginylation. Stabilization of
these proteins, the first physiologic substrates of mammalian N-end rule
pathway, may underlie cardiovascular defects in Ate1-null embryos. Hu et
al. (2005) concluded that their findings identify the N-end rule pathway
as a new nitric oxide sensor that functions through its ability to
destroy specific regulatory proteins bearing N-terminal cysteine, at
rates controlled by nitric oxide and apparently by oxygen as well.

GENE STRUCTURE

Kwon et al. (1999) determined that the mouse Ate1 gene contains 3 exons.
Two alternate 129-bp regions, which are separated by 0.8 kb, are used as
exon 2.

*FIELD* RF
1. Hu, R.-G.; Sheng, J.; Qi, X.; Xu, Z.; Takahashi, T. T.; Varshavsky,
A.: The N-end rule pathway as a nitric oxide sensor controlling the
levels of multiple regulators. Nature 437: 981-986, 2005.

2. Kaji, H.; Novelli, G. D.; Kaji, A.: A soluble amino acid-incorporating
system from rat liver. Biochim. Biophys. Acta 76: 474-477, 1963.

3. Karakozova, M.; Kozak, M.; Wong, C. C. L.; Bailey, A. O.; Yates,
J. R, III; Mogilner, A.; Zebroski, H.; Kashina, A.: Arginylation
of beta-actin regulates actin cytoskeleton and cell motility. Science 313:
192-196, 2006.

4. Kwon, Y. T.; Kashina, A. S.; Davydov, I. V.; Hu, R.-G.; An, J.
Y.; Seo, J. W.; Du, F.; Varshavsky, A.: An essential role of N-terminal
arginylation in cardiovascular development. Science 297: 96-99,
2002.

5. Kwon, Y. T.; Kashina, A. S.; Varshavsky, A.: Alternative splicing
results in differential expression, activity, and localization of
the two forms of arginyl-tRNA-protein transferase, a component of
the N-end rule pathway. Molec. Cell. Biol. 19: 182-193, 1999.

*FIELD* CN
Ada Hamosh - updated: 8/7/2006
Ada Hamosh - updated: 11/21/2005
Ada Hamosh - updated: 7/25/2002

*FIELD* CD
Patricia A. Hartz: 7/10/2002

*FIELD* ED
alopez: 04/11/2012
alopez: 8/9/2006
terry: 8/7/2006
terry: 12/21/2005
alopez: 11/21/2005
terry: 11/21/2005
terry: 1/2/2003
alopez: 7/26/2002
terry: 7/25/2002
mgross: 7/10/2002