Full text data of UBA6
UBA6
(MOP4, UBE1L2)
[Confidence: low (only semi-automatic identification from reviews)]
Ubiquitin-like modifier-activating enzyme 6; Ubiquitin-activating enzyme 6 (Monocyte protein 4; MOP-4; Ubiquitin-activating enzyme E1-like protein 2; E1-L2)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Ubiquitin-like modifier-activating enzyme 6; Ubiquitin-activating enzyme 6 (Monocyte protein 4; MOP-4; Ubiquitin-activating enzyme E1-like protein 2; E1-L2)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
A0AVT1
ID UBA6_HUMAN Reviewed; 1052 AA.
AC A0AVT1; A6N8M7; B2RAV3; Q4W5K0; Q6UV21; Q86T78; Q86TC7; Q8N5T3;
read moreAC Q8N9E4; Q9H3T7; Q9NVC9;
DT 20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 28-NOV-2006, sequence version 1.
DT 22-JAN-2014, entry version 77.
DE RecName: Full=Ubiquitin-like modifier-activating enzyme 6;
DE Short=Ubiquitin-activating enzyme 6;
DE AltName: Full=Monocyte protein 4;
DE Short=MOP-4;
DE AltName: Full=Ubiquitin-activating enzyme E1-like protein 2;
DE Short=E1-L2;
GN Name=UBA6; Synonyms=MOP4, UBE1L2;
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] (ISOFORM 2), TISSUE SPECIFICITY, AND
RP FUNCTION.
RX PubMed=15202508; DOI=10.1093/abbs/36.3.227;
RA Zhu H., Zhou Z.-M., Huo R., Huang X.-Y., Lu L., Lin M., Wang L.-R.,
RA Zhou Y.-D., Li J.-M., Sha J.-H.;
RT "Identification and characteristics of a novel E1 like gene nUBE1L in
RT human testis.";
RL Acta Biochim. Biophys. Sin. 36:227-234(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT THR-224, FUNCTION,
RP TISSUE SPECIFICITY, AND MUTAGENESIS OF CYS-625.
RX PubMed=17597759; DOI=10.1038/nature05902;
RA Jin J., Li X., Gygi S.P., Harper J.W.;
RT "Dual E1 activation systems for ubiquitin differentially regulate E2
RT enzyme charging.";
RL Nature 447:1135-1138(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Blood;
RA Takayama K., Fujii Y., Ukai Y., Yoshimoto M.;
RT "Molecular and biological characterization of a new ubiquitin-
RT activating enzyme E1 like protein, MOP-4 which is highly expressed in
RT human monocytes.";
RL Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 4), AND VARIANT
RP THR-224.
RC TISSUE=Hippocampus;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT
RP THR-224.
RC TISSUE=Skeletal muscle;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
RA Waterston R.H., Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2
RT and 4.";
RL Nature 434:724-731(2005).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Brain;
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 FUNCTION, INTERACTION WITH UBD, THIOESTER FORMATION, AND MUTAGENESIS
RP OF CYS-625.
RX PubMed=17889673; DOI=10.1016/j.molcel.2007.08.020;
RA Chiu Y.-H., Sun Q., Chen Z.J.;
RT "E1-L2 activates both ubiquitin and FAT10.";
RL Mol. Cell 27:1014-1023(2007).
RN [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
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 [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-544, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [11]
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: Activates ubiquitin by first adenylating its C-terminal
CC glycine residue with ATP, and thereafter linking this residue to
CC the side chain of a cysteine residue in E1, yielding an ubiquitin-
CC E1 thioester and free AMP. Specific for ubiquitin, does not
CC activate ubiquitin-like peptides. Differs from UBE1 in its
CC specificity for substrate E2 charging. Does not charge cell cycle
CC E2s, such as CDC34. Essential for embryonic development. Required
CC for UBD/FAT10 conjugation. Isoform 2 may play a key role in
CC ubiquitin system and may influence spermatogenesis and male
CC fertility.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Forms a thioester with UBD in cells stimulated with tumor
CC necrosis factor-alpha (TNFa) and interferon-gamma (IFNg).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Comment=Named isoforms=3;
CC Name=1;
CC IsoId=A0AVT1-1; Sequence=Displayed;
CC Name=2; Synonyms=nUBE1L;
CC IsoId=A0AVT1-2; Sequence=VSP_023083;
CC Name=3;
CC IsoId=A0AVT1-3; Sequence=VSP_023086, VSP_023087;
CC Name=4;
CC IsoId=A0AVT1-4; Sequence=VSP_023084, VSP_023085;
CC -!- TISSUE SPECIFICITY: Widely expressed. Isoform 2 is predominantly
CC expressed in testis with higher expression in adult testis than in
CC fetal testis.
CC -!- SIMILARITY: Belongs to the ubiquitin-activating E1 family.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA91824.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
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DR EMBL; AY359880; AAQ63403.1; -; mRNA.
DR EMBL; EF623993; ABR25253.1; -; mRNA.
DR EMBL; AB014773; BAB19785.1; -; mRNA.
DR EMBL; AK001670; BAA91824.1; ALT_INIT; mRNA.
DR EMBL; AK094969; BAC04463.1; -; mRNA.
DR EMBL; AK314371; BAG37000.1; -; mRNA.
DR EMBL; AL832015; CAD89908.1; -; mRNA.
DR EMBL; AL832458; CAD89959.1; -; mRNA.
DR EMBL; AC079880; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC096720; AAY40999.1; -; Genomic_DNA.
DR EMBL; BC031637; AAH31637.1; -; mRNA.
DR EMBL; BC126484; AAI26485.1; -; mRNA.
DR EMBL; BC126486; AAI26487.1; -; mRNA.
DR RefSeq; NP_060697.4; NM_018227.5.
DR UniGene; Hs.212774; -.
DR ProteinModelPortal; A0AVT1; -.
DR SMR; A0AVT1; 38-1019.
DR IntAct; A0AVT1; 1.
DR MINT; MINT-1195700; -.
DR ChEMBL; CHEMBL2321622; -.
DR PhosphoSite; A0AVT1; -.
DR PaxDb; A0AVT1; -.
DR PRIDE; A0AVT1; -.
DR DNASU; 55236; -.
DR Ensembl; ENST00000322244; ENSP00000313454; ENSG00000033178.
DR Ensembl; ENST00000420827; ENSP00000399234; ENSG00000033178.
DR GeneID; 55236; -.
DR KEGG; hsa:55236; -.
DR UCSC; uc003hdg.4; human.
DR CTD; 55236; -.
DR GeneCards; GC04M068481; -.
DR H-InvDB; HIX0031574; -.
DR H-InvDB; HIX0120163; -.
DR HGNC; HGNC:25581; UBA6.
DR HPA; HPA037001; -.
DR MIM; 611361; gene.
DR neXtProt; NX_A0AVT1; -.
DR PharmGKB; PA162407690; -.
DR eggNOG; COG0476; -.
DR HOVERGEN; HBG054199; -.
DR InParanoid; A0AVT1; -.
DR KO; K10699; -.
DR OMA; QKPKSYT; -.
DR OrthoDB; EOG74R1PV; -.
DR PhylomeDB; A0AVT1; -.
DR Reactome; REACT_6900; Immune System.
DR UniPathway; UPA00143; -.
DR ChiTaRS; UBA6; human.
DR GeneWiki; UBE1L2; -.
DR GenomeRNAi; 55236; -.
DR NextBio; 59255; -.
DR PRO; PR:A0AVT1; -.
DR ArrayExpress; A0AVT1; -.
DR Bgee; A0AVT1; -.
DR Genevestigator; A0AVT1; -.
DR GO; GO:0005737; C:cytoplasm; IDA:LIFEdb.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0019780; F:FAT10 activating enzyme activity; IMP:UniProtKB.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR GO; GO:0016567; P:protein ubiquitination; IMP:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR Gene3D; 1.10.3240.10; -; 2.
DR Gene3D; 3.40.50.720; -; 4.
DR InterPro; IPR009036; Molybdenum_cofac_synth_MoeB.
DR InterPro; IPR016040; NAD(P)-bd_dom.
DR InterPro; IPR000594; ThiF_NAD_FAD-bd.
DR InterPro; IPR018965; Ub-activating_enz_e1_C.
DR InterPro; IPR023280; Ub-like_act_enz_cat_cys_dom.
DR InterPro; IPR000127; UBact_repeat.
DR InterPro; IPR019572; Ubiquitin-activating_enzyme.
DR InterPro; IPR018075; UBQ-activ_enz_E1.
DR InterPro; IPR000011; UBQ/SUMO-activ_enz_E1-like.
DR Pfam; PF00899; ThiF; 2.
DR Pfam; PF09358; UBA_e1_C; 1.
DR Pfam; PF10585; UBA_e1_thiolCys; 1.
DR Pfam; PF02134; UBACT; 1.
DR PRINTS; PR01849; UBIQUITINACT.
DR SMART; SM00985; UBA_e1_C; 1.
DR SUPFAM; SSF69572; SSF69572; 2.
DR TIGRFAMs; TIGR01408; Ube1; 1.
DR PROSITE; PS00536; UBIQUITIN_ACTIVAT_1; FALSE_NEG.
DR PROSITE; PS00865; UBIQUITIN_ACTIVAT_2; FALSE_NEG.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; ATP-binding; Complete proteome;
KW Ligase; Nucleotide-binding; Polymorphism; Reference proteome;
KW Ubl conjugation pathway.
FT CHAIN 1 1052 Ubiquitin-like modifier-activating enzyme
FT 6.
FT /FTId=PRO_0000277797.
FT NP_BIND 470 500 ATP (By similarity).
FT ACT_SITE 625 625 Glycyl thioester intermediate (By
FT similarity).
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 544 544 N6-acetyllysine.
FT VAR_SEQ 1 474 Missing (in isoform 2).
FT /FTId=VSP_023083.
FT VAR_SEQ 321 340 APLEIHTAMLALDQFQEKYS -> VNKHFAGLREAAESEMR
FT ISE (in isoform 4).
FT /FTId=VSP_023084.
FT VAR_SEQ 341 1052 Missing (in isoform 4).
FT /FTId=VSP_023085.
FT VAR_SEQ 369 389 PDVNADIVHWLSWTAQGFLSP -> VTIEIYGCPNICLLIH
FT KCSVY (in isoform 3).
FT /FTId=VSP_023086.
FT VAR_SEQ 390 1052 Missing (in isoform 3).
FT /FTId=VSP_023087.
FT VARIANT 224 224 A -> T (in dbSNP:rs10010188).
FT /FTId=VAR_030594.
FT MUTAGEN 625 625 C->A,S: Impairs ubiquitin activation.
FT CONFLICT 14 14 E -> K (in Ref. 5; CAD89908).
FT CONFLICT 140 140 V -> A (in Ref. 5; CAD89908).
FT CONFLICT 197 197 C -> Y (in Ref. 4; BAC04463).
FT CONFLICT 234 234 N -> D (in Ref. 5; CAD89959).
FT CONFLICT 297 297 V -> A (in Ref. 4; BAC04463).
FT CONFLICT 645 645 F -> V (in Ref. 1; AAQ63403).
FT CONFLICT 803 803 Q -> H (in Ref. 4; BAA91824).
FT CONFLICT 821 821 E -> G (in Ref. 5; CAD89959).
FT CONFLICT 868 868 L -> P (in Ref. 5; CAD89908).
FT CONFLICT 905 905 V -> G (in Ref. 1; AAQ63403).
FT CONFLICT 909 909 M -> K (in Ref. 5; CAD89959).
FT CONFLICT 920 920 A -> V (in Ref. 3; BAB19785).
SQ SEQUENCE 1052 AA; 117970 MW; 9F9C70EABA750A71 CRC64;
MEGSEPVAAH QGEEASCSSW GTGSTNKNLP IMSTASVEID DALYSRQRYV LGDTAMQKMA
KSHVFLSGMG GLGLEIAKNL VLAGIKAVTI HDTEKCQAWD LGTNFFLSED DVVNKRNRAE
AVLKHIAELN PYVHVTSSSV PFNETTDLSF LDKYQCVVLT EMKLPLQKKI NDFCRSQCPP
IKFISADVHG IWSRLFCDFG DEFEVLDTTG EEPKEIFISN ITQANPGIVT CLENHPHKLE
TGQFLTFREI NGMTGLNGSI QQITVISPFS FSIGDTTELE PYLHGGIAVQ VKTPKTVFFE
SLERQLKHPK CLIVDFSNPE APLEIHTAML ALDQFQEKYS RKPNVGCQQD SEELLKLATS
ISETLEEKPD VNADIVHWLS WTAQGFLSPL AAAVGGVASQ EVLKAVTGKF SPLCQWLYLE
AADIVESLGK PECEEFLPRG DRYDALRACI GDTLCQKLQN LNIFLVGCGA IGCEMLKNFA
LLGVGTSKEK GMITVTDPDL IEKSNLNRQF LFRPHHIQKP KSYTAADATL KINSQIKIDA
HLNKVCPTTE TIYNDEFYTK QDVIITALDN VEARRYVDSR CLANLRPLLD SGTMGTKGHT
EVIVPHLTES YNSHRDPPEE EIPFCTLKSF PAAIEHTIQW ARDKFESSFS HKPSLFNKFW
QTYSSAEEVL QKIQSGHSLE GCFQVIKLLS RRPRNWSQCV ELARLKFEKY FNHKALQLLH
CFPLDIRLKD GSLFWQSPKR PPSPIKFDLN EPLHLSFLQN AAKLYATVYC IPFAEEDLSA
DALLNILSEV KIQEFKPSNK VVQTDETARK PDHVPISSED ERNAIFQLEK AILSNEATKS
DLQMAVLSFE KDDDHNGHID FITAASNLRA KMYSIEPADR FKTKRIAGKI IPAIATTTAT
VSGLVALEMI KVTGGYPFEA YKNCFLNLAI PIVVFTETTE VRKTKIRNGI SFTIWDRWTV
HGKEDFTLLD FINAVKEKYG IEPTMVVQGV KMLYVPVMPG HAKRLKLTMH KLVKPTTEKK
YVDLTVSFAP DIDGDEDLPG PPVRYYFSHD TD
//
ID UBA6_HUMAN Reviewed; 1052 AA.
AC A0AVT1; A6N8M7; B2RAV3; Q4W5K0; Q6UV21; Q86T78; Q86TC7; Q8N5T3;
read moreAC Q8N9E4; Q9H3T7; Q9NVC9;
DT 20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 28-NOV-2006, sequence version 1.
DT 22-JAN-2014, entry version 77.
DE RecName: Full=Ubiquitin-like modifier-activating enzyme 6;
DE Short=Ubiquitin-activating enzyme 6;
DE AltName: Full=Monocyte protein 4;
DE Short=MOP-4;
DE AltName: Full=Ubiquitin-activating enzyme E1-like protein 2;
DE Short=E1-L2;
GN Name=UBA6; Synonyms=MOP4, UBE1L2;
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] (ISOFORM 2), TISSUE SPECIFICITY, AND
RP FUNCTION.
RX PubMed=15202508; DOI=10.1093/abbs/36.3.227;
RA Zhu H., Zhou Z.-M., Huo R., Huang X.-Y., Lu L., Lin M., Wang L.-R.,
RA Zhou Y.-D., Li J.-M., Sha J.-H.;
RT "Identification and characteristics of a novel E1 like gene nUBE1L in
RT human testis.";
RL Acta Biochim. Biophys. Sin. 36:227-234(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT THR-224, FUNCTION,
RP TISSUE SPECIFICITY, AND MUTAGENESIS OF CYS-625.
RX PubMed=17597759; DOI=10.1038/nature05902;
RA Jin J., Li X., Gygi S.P., Harper J.W.;
RT "Dual E1 activation systems for ubiquitin differentially regulate E2
RT enzyme charging.";
RL Nature 447:1135-1138(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Blood;
RA Takayama K., Fujii Y., Ukai Y., Yoshimoto M.;
RT "Molecular and biological characterization of a new ubiquitin-
RT activating enzyme E1 like protein, MOP-4 which is highly expressed in
RT human monocytes.";
RL Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 4), AND VARIANT
RP THR-224.
RC TISSUE=Hippocampus;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT
RP THR-224.
RC TISSUE=Skeletal muscle;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
RA Waterston R.H., Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2
RT and 4.";
RL Nature 434:724-731(2005).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Brain;
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 FUNCTION, INTERACTION WITH UBD, THIOESTER FORMATION, AND MUTAGENESIS
RP OF CYS-625.
RX PubMed=17889673; DOI=10.1016/j.molcel.2007.08.020;
RA Chiu Y.-H., Sun Q., Chen Z.J.;
RT "E1-L2 activates both ubiquitin and FAT10.";
RL Mol. Cell 27:1014-1023(2007).
RN [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
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 [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-544, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [11]
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: Activates ubiquitin by first adenylating its C-terminal
CC glycine residue with ATP, and thereafter linking this residue to
CC the side chain of a cysteine residue in E1, yielding an ubiquitin-
CC E1 thioester and free AMP. Specific for ubiquitin, does not
CC activate ubiquitin-like peptides. Differs from UBE1 in its
CC specificity for substrate E2 charging. Does not charge cell cycle
CC E2s, such as CDC34. Essential for embryonic development. Required
CC for UBD/FAT10 conjugation. Isoform 2 may play a key role in
CC ubiquitin system and may influence spermatogenesis and male
CC fertility.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Forms a thioester with UBD in cells stimulated with tumor
CC necrosis factor-alpha (TNFa) and interferon-gamma (IFNg).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Comment=Named isoforms=3;
CC Name=1;
CC IsoId=A0AVT1-1; Sequence=Displayed;
CC Name=2; Synonyms=nUBE1L;
CC IsoId=A0AVT1-2; Sequence=VSP_023083;
CC Name=3;
CC IsoId=A0AVT1-3; Sequence=VSP_023086, VSP_023087;
CC Name=4;
CC IsoId=A0AVT1-4; Sequence=VSP_023084, VSP_023085;
CC -!- TISSUE SPECIFICITY: Widely expressed. Isoform 2 is predominantly
CC expressed in testis with higher expression in adult testis than in
CC fetal testis.
CC -!- SIMILARITY: Belongs to the ubiquitin-activating E1 family.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA91824.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC -----------------------------------------------------------------------
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DR EMBL; AY359880; AAQ63403.1; -; mRNA.
DR EMBL; EF623993; ABR25253.1; -; mRNA.
DR EMBL; AB014773; BAB19785.1; -; mRNA.
DR EMBL; AK001670; BAA91824.1; ALT_INIT; mRNA.
DR EMBL; AK094969; BAC04463.1; -; mRNA.
DR EMBL; AK314371; BAG37000.1; -; mRNA.
DR EMBL; AL832015; CAD89908.1; -; mRNA.
DR EMBL; AL832458; CAD89959.1; -; mRNA.
DR EMBL; AC079880; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC096720; AAY40999.1; -; Genomic_DNA.
DR EMBL; BC031637; AAH31637.1; -; mRNA.
DR EMBL; BC126484; AAI26485.1; -; mRNA.
DR EMBL; BC126486; AAI26487.1; -; mRNA.
DR RefSeq; NP_060697.4; NM_018227.5.
DR UniGene; Hs.212774; -.
DR ProteinModelPortal; A0AVT1; -.
DR SMR; A0AVT1; 38-1019.
DR IntAct; A0AVT1; 1.
DR MINT; MINT-1195700; -.
DR ChEMBL; CHEMBL2321622; -.
DR PhosphoSite; A0AVT1; -.
DR PaxDb; A0AVT1; -.
DR PRIDE; A0AVT1; -.
DR DNASU; 55236; -.
DR Ensembl; ENST00000322244; ENSP00000313454; ENSG00000033178.
DR Ensembl; ENST00000420827; ENSP00000399234; ENSG00000033178.
DR GeneID; 55236; -.
DR KEGG; hsa:55236; -.
DR UCSC; uc003hdg.4; human.
DR CTD; 55236; -.
DR GeneCards; GC04M068481; -.
DR H-InvDB; HIX0031574; -.
DR H-InvDB; HIX0120163; -.
DR HGNC; HGNC:25581; UBA6.
DR HPA; HPA037001; -.
DR MIM; 611361; gene.
DR neXtProt; NX_A0AVT1; -.
DR PharmGKB; PA162407690; -.
DR eggNOG; COG0476; -.
DR HOVERGEN; HBG054199; -.
DR InParanoid; A0AVT1; -.
DR KO; K10699; -.
DR OMA; QKPKSYT; -.
DR OrthoDB; EOG74R1PV; -.
DR PhylomeDB; A0AVT1; -.
DR Reactome; REACT_6900; Immune System.
DR UniPathway; UPA00143; -.
DR ChiTaRS; UBA6; human.
DR GeneWiki; UBE1L2; -.
DR GenomeRNAi; 55236; -.
DR NextBio; 59255; -.
DR PRO; PR:A0AVT1; -.
DR ArrayExpress; A0AVT1; -.
DR Bgee; A0AVT1; -.
DR Genevestigator; A0AVT1; -.
DR GO; GO:0005737; C:cytoplasm; IDA:LIFEdb.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0019780; F:FAT10 activating enzyme activity; IMP:UniProtKB.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR GO; GO:0016567; P:protein ubiquitination; IMP:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR Gene3D; 1.10.3240.10; -; 2.
DR Gene3D; 3.40.50.720; -; 4.
DR InterPro; IPR009036; Molybdenum_cofac_synth_MoeB.
DR InterPro; IPR016040; NAD(P)-bd_dom.
DR InterPro; IPR000594; ThiF_NAD_FAD-bd.
DR InterPro; IPR018965; Ub-activating_enz_e1_C.
DR InterPro; IPR023280; Ub-like_act_enz_cat_cys_dom.
DR InterPro; IPR000127; UBact_repeat.
DR InterPro; IPR019572; Ubiquitin-activating_enzyme.
DR InterPro; IPR018075; UBQ-activ_enz_E1.
DR InterPro; IPR000011; UBQ/SUMO-activ_enz_E1-like.
DR Pfam; PF00899; ThiF; 2.
DR Pfam; PF09358; UBA_e1_C; 1.
DR Pfam; PF10585; UBA_e1_thiolCys; 1.
DR Pfam; PF02134; UBACT; 1.
DR PRINTS; PR01849; UBIQUITINACT.
DR SMART; SM00985; UBA_e1_C; 1.
DR SUPFAM; SSF69572; SSF69572; 2.
DR TIGRFAMs; TIGR01408; Ube1; 1.
DR PROSITE; PS00536; UBIQUITIN_ACTIVAT_1; FALSE_NEG.
DR PROSITE; PS00865; UBIQUITIN_ACTIVAT_2; FALSE_NEG.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; ATP-binding; Complete proteome;
KW Ligase; Nucleotide-binding; Polymorphism; Reference proteome;
KW Ubl conjugation pathway.
FT CHAIN 1 1052 Ubiquitin-like modifier-activating enzyme
FT 6.
FT /FTId=PRO_0000277797.
FT NP_BIND 470 500 ATP (By similarity).
FT ACT_SITE 625 625 Glycyl thioester intermediate (By
FT similarity).
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 544 544 N6-acetyllysine.
FT VAR_SEQ 1 474 Missing (in isoform 2).
FT /FTId=VSP_023083.
FT VAR_SEQ 321 340 APLEIHTAMLALDQFQEKYS -> VNKHFAGLREAAESEMR
FT ISE (in isoform 4).
FT /FTId=VSP_023084.
FT VAR_SEQ 341 1052 Missing (in isoform 4).
FT /FTId=VSP_023085.
FT VAR_SEQ 369 389 PDVNADIVHWLSWTAQGFLSP -> VTIEIYGCPNICLLIH
FT KCSVY (in isoform 3).
FT /FTId=VSP_023086.
FT VAR_SEQ 390 1052 Missing (in isoform 3).
FT /FTId=VSP_023087.
FT VARIANT 224 224 A -> T (in dbSNP:rs10010188).
FT /FTId=VAR_030594.
FT MUTAGEN 625 625 C->A,S: Impairs ubiquitin activation.
FT CONFLICT 14 14 E -> K (in Ref. 5; CAD89908).
FT CONFLICT 140 140 V -> A (in Ref. 5; CAD89908).
FT CONFLICT 197 197 C -> Y (in Ref. 4; BAC04463).
FT CONFLICT 234 234 N -> D (in Ref. 5; CAD89959).
FT CONFLICT 297 297 V -> A (in Ref. 4; BAC04463).
FT CONFLICT 645 645 F -> V (in Ref. 1; AAQ63403).
FT CONFLICT 803 803 Q -> H (in Ref. 4; BAA91824).
FT CONFLICT 821 821 E -> G (in Ref. 5; CAD89959).
FT CONFLICT 868 868 L -> P (in Ref. 5; CAD89908).
FT CONFLICT 905 905 V -> G (in Ref. 1; AAQ63403).
FT CONFLICT 909 909 M -> K (in Ref. 5; CAD89959).
FT CONFLICT 920 920 A -> V (in Ref. 3; BAB19785).
SQ SEQUENCE 1052 AA; 117970 MW; 9F9C70EABA750A71 CRC64;
MEGSEPVAAH QGEEASCSSW GTGSTNKNLP IMSTASVEID DALYSRQRYV LGDTAMQKMA
KSHVFLSGMG GLGLEIAKNL VLAGIKAVTI HDTEKCQAWD LGTNFFLSED DVVNKRNRAE
AVLKHIAELN PYVHVTSSSV PFNETTDLSF LDKYQCVVLT EMKLPLQKKI NDFCRSQCPP
IKFISADVHG IWSRLFCDFG DEFEVLDTTG EEPKEIFISN ITQANPGIVT CLENHPHKLE
TGQFLTFREI NGMTGLNGSI QQITVISPFS FSIGDTTELE PYLHGGIAVQ VKTPKTVFFE
SLERQLKHPK CLIVDFSNPE APLEIHTAML ALDQFQEKYS RKPNVGCQQD SEELLKLATS
ISETLEEKPD VNADIVHWLS WTAQGFLSPL AAAVGGVASQ EVLKAVTGKF SPLCQWLYLE
AADIVESLGK PECEEFLPRG DRYDALRACI GDTLCQKLQN LNIFLVGCGA IGCEMLKNFA
LLGVGTSKEK GMITVTDPDL IEKSNLNRQF LFRPHHIQKP KSYTAADATL KINSQIKIDA
HLNKVCPTTE TIYNDEFYTK QDVIITALDN VEARRYVDSR CLANLRPLLD SGTMGTKGHT
EVIVPHLTES YNSHRDPPEE EIPFCTLKSF PAAIEHTIQW ARDKFESSFS HKPSLFNKFW
QTYSSAEEVL QKIQSGHSLE GCFQVIKLLS RRPRNWSQCV ELARLKFEKY FNHKALQLLH
CFPLDIRLKD GSLFWQSPKR PPSPIKFDLN EPLHLSFLQN AAKLYATVYC IPFAEEDLSA
DALLNILSEV KIQEFKPSNK VVQTDETARK PDHVPISSED ERNAIFQLEK AILSNEATKS
DLQMAVLSFE KDDDHNGHID FITAASNLRA KMYSIEPADR FKTKRIAGKI IPAIATTTAT
VSGLVALEMI KVTGGYPFEA YKNCFLNLAI PIVVFTETTE VRKTKIRNGI SFTIWDRWTV
HGKEDFTLLD FINAVKEKYG IEPTMVVQGV KMLYVPVMPG HAKRLKLTMH KLVKPTTEKK
YVDLTVSFAP DIDGDEDLPG PPVRYYFSHD TD
//
MIM
611361
*RECORD*
*FIELD* NO
611361
*FIELD* TI
*611361 UBIQUITIN-ACTIVATING ENZYME E1-LIKE 2; UBE1L2
;;UBIQUITIN-ACTIVATING ENZYME 6; UBA6
read more*FIELD* TX
DESCRIPTION
Modification of proteins with ubiquitin (UBB; 191339) or ubiquitin-like
proteins controls many signaling networks and requires a
ubiquitin-activating enzyme (E1), a ubiquitin conjugating enzyme (E2),
and a ubiquitin protein ligase (E3). UBE1L2 is an E1 enzyme that
initiates the activation and conjugation of ubiquitin-like proteins (Jin
et al., 2007).
CLONING
Using the ThiF-homology motif of E1 enzymes as query, Jin et al. (2007)
identified UBE1L2, which they called UBA6. The deduced 1,052-amino acid
protein contains an N-terminal adenylation domain with 2 ThiF-homology
regions, a catalytic cysteine domain, and a C-terminal ubiquitin-fold
domain that functions to recruit E2s. UBE1L2 shares approximately 40%
overall sequence identity with UBE1 (314370). Database analysis revealed
wide expression of UBE1L2 in human tissues and cell lines. Jin et al.
(2007) found orthologs of UBE1L2 in vertebrates and the echinoderm sea
urchin, but not in insects, worms, fungi, or plants.
GENE FUNCTION
Jin et al. (2007) showed that UBE1L2 activated ubiquitin but not other
ubiquitin-like proteins in vitro and in vivo. UBE1L2 charged a number of
E2 substrates with ubiquitin, but its substrate specificity was
different from that of UBE1. UBA6 specifically charged USE1 (611362),
but it did not charge the cell cycle E2s CDC34A and CDC34B (see 116948),
which were good substrates for UBE1. The difference in substrate
specificity between UBA6 and UBE1 was due to their distinct C-terminal
ubiquitin-fold domains.
Chiu et al. (2007) showed that E1L2 could activate ubiquitin and
transfer ubiquitin to a subset of ubiquitin E2s. E1L2 could also
activate FAT10 (UBD; 606050) by forming a thioester between the
active-site cysteine of E1L2 and the C-terminal diglycine motif of
FAT10. Endogenous E1L2 and FAT10 also formed a thioester in human cells
stimulated with TNF-alpha (TNF; 191160) and interferon-gamma (IFNG;
147570). Knockdown of E1L2 by RNA interference significantly reduced
FAT10 conjugation in cells.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the UBE1L2
gene to chromosome 4 (TMAP SHGC-52778).
ANIMAL MODEL
Chiu et al. (2007) found that homozygous deletion of E1l2 in mice was
embryonic lethal. Heterozygous mice were fertile and developed normally.
*FIELD* RF
1. Chiu, Y.-H.; Sun, Q.; Chen, Z. J.: E1-L2 activates both ubiquitin
and FAT10. Molec. Cell 27: 1014-1023, 2007.
2. Jin, J.; Li, X.; Gygi, S. P.; Harper, J. W.: Dual E1 activation
systems for ubiquitin differentially regulate E2 enzyme charging. Nature 447:
1135-1138, 2007.
*FIELD* CN
Matthew B. Gross - updated: 10/23/2007
Patricia A. Hartz - updated: 10/18/2007
*FIELD* CD
Patricia A. Hartz: 8/20/2007
*FIELD* ED
alopez: 10/26/2007
mgross: 10/23/2007
terry: 10/18/2007
carol: 8/20/2007
*RECORD*
*FIELD* NO
611361
*FIELD* TI
*611361 UBIQUITIN-ACTIVATING ENZYME E1-LIKE 2; UBE1L2
;;UBIQUITIN-ACTIVATING ENZYME 6; UBA6
read more*FIELD* TX
DESCRIPTION
Modification of proteins with ubiquitin (UBB; 191339) or ubiquitin-like
proteins controls many signaling networks and requires a
ubiquitin-activating enzyme (E1), a ubiquitin conjugating enzyme (E2),
and a ubiquitin protein ligase (E3). UBE1L2 is an E1 enzyme that
initiates the activation and conjugation of ubiquitin-like proteins (Jin
et al., 2007).
CLONING
Using the ThiF-homology motif of E1 enzymes as query, Jin et al. (2007)
identified UBE1L2, which they called UBA6. The deduced 1,052-amino acid
protein contains an N-terminal adenylation domain with 2 ThiF-homology
regions, a catalytic cysteine domain, and a C-terminal ubiquitin-fold
domain that functions to recruit E2s. UBE1L2 shares approximately 40%
overall sequence identity with UBE1 (314370). Database analysis revealed
wide expression of UBE1L2 in human tissues and cell lines. Jin et al.
(2007) found orthologs of UBE1L2 in vertebrates and the echinoderm sea
urchin, but not in insects, worms, fungi, or plants.
GENE FUNCTION
Jin et al. (2007) showed that UBE1L2 activated ubiquitin but not other
ubiquitin-like proteins in vitro and in vivo. UBE1L2 charged a number of
E2 substrates with ubiquitin, but its substrate specificity was
different from that of UBE1. UBA6 specifically charged USE1 (611362),
but it did not charge the cell cycle E2s CDC34A and CDC34B (see 116948),
which were good substrates for UBE1. The difference in substrate
specificity between UBA6 and UBE1 was due to their distinct C-terminal
ubiquitin-fold domains.
Chiu et al. (2007) showed that E1L2 could activate ubiquitin and
transfer ubiquitin to a subset of ubiquitin E2s. E1L2 could also
activate FAT10 (UBD; 606050) by forming a thioester between the
active-site cysteine of E1L2 and the C-terminal diglycine motif of
FAT10. Endogenous E1L2 and FAT10 also formed a thioester in human cells
stimulated with TNF-alpha (TNF; 191160) and interferon-gamma (IFNG;
147570). Knockdown of E1L2 by RNA interference significantly reduced
FAT10 conjugation in cells.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the UBE1L2
gene to chromosome 4 (TMAP SHGC-52778).
ANIMAL MODEL
Chiu et al. (2007) found that homozygous deletion of E1l2 in mice was
embryonic lethal. Heterozygous mice were fertile and developed normally.
*FIELD* RF
1. Chiu, Y.-H.; Sun, Q.; Chen, Z. J.: E1-L2 activates both ubiquitin
and FAT10. Molec. Cell 27: 1014-1023, 2007.
2. Jin, J.; Li, X.; Gygi, S. P.; Harper, J. W.: Dual E1 activation
systems for ubiquitin differentially regulate E2 enzyme charging. Nature 447:
1135-1138, 2007.
*FIELD* CN
Matthew B. Gross - updated: 10/23/2007
Patricia A. Hartz - updated: 10/18/2007
*FIELD* CD
Patricia A. Hartz: 8/20/2007
*FIELD* ED
alopez: 10/26/2007
mgross: 10/23/2007
terry: 10/18/2007
carol: 8/20/2007