AREL1_MOUSE
ID AREL1_MOUSE Reviewed; 823 AA.
AC Q8CHG5; Q6P9Q1; Q80YC4; Q8C5W5;
DT 29-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 29-MAR-2005, sequence version 2.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Apoptosis-resistant E3 ubiquitin protein ligase 1;
DE EC=2.3.2.26 {ECO:0000250|UniProtKB:O15033};
DE AltName: Full=Apoptosis-resistant HECT-type E3 ubiquitin transferase 1;
GN Name=Arel1; Synonyms=Kiaa0317;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=12465718; DOI=10.1093/dnares/9.5.179;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Hara Y., Nagase T., Ohara O.,
RA Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: I.
RT The complete nucleotide sequences of 100 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 9:179-188(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Testis;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain, and Eye;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP INTERACTION WITH SEPTIN4; HTRA2 AND DIABLO, AND TISSUE SPECIFICITY.
RX PubMed=23479728; DOI=10.1074/jbc.m112.436113;
RA Kim J.B., Kim S.Y., Kim B.M., Lee H., Kim I., Yun J., Jo Y., Oh T., Jo Y.,
RA Chae H.D., Shin D.Y.;
RT "Identification of a novel anti-apoptotic E3 ubiquitin ligase that
RT ubiquitinates antagonists of inhibitor of apoptosis proteins SMAC, HtrA2,
RT and ARTS.";
RL J. Biol. Chem. 288:12014-12021(2013).
RN [5]
RP FUNCTION, DISRUPTION PHENOTYPE, AND INTERACTION WITH SOCS2.
RX PubMed=31578312; DOI=10.1172/jci.insight.129110;
RA Lear T.B., McKelvey A.C., Evankovich J.W., Rajbhandari S., Coon T.A.,
RA Dunn S.R., Londino J.D., McVerry B.J., Zhang Y., Valenzi E., Burton C.L.,
RA Gordon R., Gingras S., Lockwood K.C., Jurczak M.J., Lafyatis R.,
RA Shlomchik M.J., Liu Y., Chen B.B.;
RT "KIAA0317 regulates pulmonary inflammation through SOCS2 degradation.";
RL JCI Insight 4:0-0(2019).
CC -!- FUNCTION: E3 ubiquitin-protein ligase that catalyzes 'Lys-11'- or 'Lys-
CC 33'-linked polyubiquitin chains, with some preference for 'Lys-33'
CC linkages (By similarity). E3 ubiquitin-protein ligases accept ubiquitin
CC from an E2 ubiquitin-conjugating enzyme in the form of a thioester and
CC then directly transfers the ubiquitin to targeted substrates (By
CC similarity). Ubiquitinates SEPTIN4, DIABLO/SMAC and HTRA2 in vitro (By
CC similarity). Modulates pulmonary inflammation by targeting SOCS2 for
CC ubiquitination and subsequent degradation by the proteasome
CC (PubMed:31578312). {ECO:0000250|UniProtKB:O15033,
CC ECO:0000269|PubMed:31578312}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.26; Evidence={ECO:0000250|UniProtKB:O15033};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000250|UniProtKB:O15033}.
CC -!- SUBUNIT: Interacts with SOCS2 (PubMed:31578312). Interacts (via HECT
CC domain) with HTRA2, DIABLO/SMAC and SEPTIN4; in the cytoplasm following
CC induction of apoptosis (PubMed:23479728). {ECO:0000269|PubMed:23479728,
CC ECO:0000269|PubMed:31578312}.
CC -!- TISSUE SPECIFICITY: Detected in brain, testis, heart, liver, lung and
CC kidney with very low levels in skeletal muscle and spleen.
CC {ECO:0000269|PubMed:23479728}.
CC -!- PTM: Autoubiquitinated in vitro in the presence of E2 enzyme
CC UBE2D1/UBCH5A. {ECO:0000250|UniProtKB:O15033}.
CC -!- DISRUPTION PHENOTYPE: Mice show significant and stepwise decreases in
CC indicators of inflammatory injury, such as bronchoalveolar lavage fluid
CC protein concentration and cell count, as well as decreases in pro-
CC inflammatory cytokine release. {ECO:0000269|PubMed:31578312}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC41414.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB093230; BAC41414.1; ALT_INIT; mRNA.
DR EMBL; AK077015; BAC36566.1; -; mRNA.
DR EMBL; BC049900; AAH49900.1; -; mRNA.
DR EMBL; BC060658; AAH60658.1; -; mRNA.
DR CCDS; CCDS26051.1; -.
DR RefSeq; NP_835166.3; NM_178065.4.
DR RefSeq; XP_006516252.1; XM_006516189.3.
DR RefSeq; XP_006516253.1; XM_006516190.2.
DR AlphaFoldDB; Q8CHG5; -.
DR SMR; Q8CHG5; -.
DR BioGRID; 212887; 1.
DR STRING; 10090.ENSMUSP00000048780; -.
DR iPTMnet; Q8CHG5; -.
DR PhosphoSitePlus; Q8CHG5; -.
DR jPOST; Q8CHG5; -.
DR MaxQB; Q8CHG5; -.
DR PaxDb; Q8CHG5; -.
DR PRIDE; Q8CHG5; -.
DR ProteomicsDB; 273919; -.
DR Antibodypedia; 25651; 59 antibodies from 17 providers.
DR DNASU; 68497; -.
DR Ensembl; ENSMUST00000043169; ENSMUSP00000048780; ENSMUSG00000042350.
DR GeneID; 68497; -.
DR KEGG; mmu:68497; -.
DR UCSC; uc007ofy.1; mouse.
DR CTD; 9870; -.
DR MGI; MGI:1915747; Arel1.
DR VEuPathDB; HostDB:ENSMUSG00000042350; -.
DR eggNOG; KOG0939; Eukaryota.
DR GeneTree; ENSGT00940000156723; -.
DR HOGENOM; CLU_014403_0_0_1; -.
DR InParanoid; Q8CHG5; -.
DR OMA; HLPPMHT; -.
DR OrthoDB; 266565at2759; -.
DR PhylomeDB; Q8CHG5; -.
DR TreeFam; TF323417; -.
DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 68497; 3 hits in 74 CRISPR screens.
DR ChiTaRS; Arel1; mouse.
DR PRO; PR:Q8CHG5; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; Q8CHG5; protein.
DR Bgee; ENSMUSG00000042350; Expressed in olfactory tubercle and 223 other tissues.
DR ExpressionAtlas; Q8CHG5; baseline and differential.
DR Genevisible; Q8CHG5; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; ISS:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR GO; GO:0070979; P:protein K11-linked ubiquitination; ISS:UniProtKB.
DR GO; GO:1990390; P:protein K33-linked ubiquitination; ISS:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; IBA:GO_Central.
DR GO; GO:0016567; P:protein ubiquitination; IMP:UniProtKB.
DR GO; GO:0050727; P:regulation of inflammatory response; IMP:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IDA:CACAO.
DR CDD; cd00078; HECTc; 1.
DR Gene3D; 2.60.40.10; -; 1.
DR InterPro; IPR017868; Filamin/ABP280_repeat-like.
DR InterPro; IPR000569; HECT_dom.
DR InterPro; IPR035983; Hect_E3_ubiquitin_ligase.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR014756; Ig_E-set.
DR Pfam; PF00630; Filamin; 1.
DR Pfam; PF00632; HECT; 1.
DR SMART; SM00119; HECTc; 1.
DR SUPFAM; SSF56204; SSF56204; 1.
DR SUPFAM; SSF81296; SSF81296; 1.
DR PROSITE; PS50194; FILAMIN_REPEAT; 1.
DR PROSITE; PS50237; HECT; 1.
PE 1: Evidence at protein level;
KW Apoptosis; Reference proteome; Transferase; Ubl conjugation;
KW Ubl conjugation pathway.
FT CHAIN 1..823
FT /note="Apoptosis-resistant E3 ubiquitin protein ligase 1"
FT /id="PRO_0000120350"
FT REPEAT 64..158
FT /note="Filamin"
FT DOMAIN 483..823
FT /note="HECT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00104"
FT REGION 315..345
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 483..789
FT /note="Interaction with SOCS2"
FT /evidence="ECO:0000250|UniProtKB:O15033"
FT ACT_SITE 790
FT /note="Glycyl thioester intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00104"
FT CONFLICT 424
FT /note="T -> I (in Ref. 3; AAH60658)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 823 AA; 94199 MW; E74AAE76555A20D4 CRC64;
MFYVIGGIIV SVVAFFFTIK FLFELAARVV SFLQNEDRER RGDRTIYDYV RGNYLDPRSC
KVSWDWKDPY EVGHSMAFRV HLFYKNGQPF PAHRPVGLRV HISHVELAVD IPVTQEVLQE
PNSNVVKVAF TVRKAGRYEI TVKLGGLNVA YSPYYKIFQP GMVVPSKTKI VCHFSTLVLT
CGQPHTLQIV PRDEYDNPTN NSMSLRDEHS YSLAIHELGP QEEENNEVSF EKSVTSNRQT
CQVFLRLTLH SRGCFHACIS YQNQPINNGE FDIIVLSENE KNIVERNVST SGVSIYFEAY
LYNANNCTST PWHLPPMHMS SSQRRPSTAI EEDDEDSPSE CHTPEKVKKP KKVYCYVSPK
QFSVKEFYLK IIPWRLYTFR VCPGTKFSYL GPDPVHKLLT LVVDDGIQPP VELSCKERNI
LAATFIRSLH KNIGGSETFQ DKVNFFQREL RQVHMKRPHS KVTLKVSRHA LLESSLKATR
NFSISDWSKN FEVVFQDEEA LDWGGPRREW FELICKALFD TTSQLFARFT DSNQALVHPN
PNRPAHLRLK MYEFAGRLVG KCLYESSLGG AYKQLVRARF TRSFLAQIIG LRMHYKYFET
DDPEFYKSKV CFILNNDMSE MELVFAEEKY NKSGQLDKIV ELMTGGAQTP VTNANKIFYL
NLLAQYRLAS QVKEEVEHFL KGLNELVPEN LLAIFDENEL ELLMCGTGDI NVSDFKAHAV
VVGGSWHFRE KVMRWFWAVV SSLTQEELAR LLQFTTGSSQ LPPGGFAALC PSFQIIAAPT
HSTLPTAHTC FNQLCLPTYD SYEEVHRMLQ LAISEGCEGF GML
