ACSF4_MOUSE
ID ACSF4_MOUSE Reviewed; 1100 AA.
AC Q80WC9; Q3V3L2; Q505K4; Q8BRP4;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=Beta-alanine-activating enzyme {ECO:0000303|PubMed:24467666};
DE EC=6.2.1.- {ECO:0000305|PubMed:24467666};
DE AltName: Full=Acyl-CoA synthetase family member 4;
DE AltName: Full=Protein LYS2 homolog;
GN Name=Aasdh; Synonyms=Acsf4, U26;
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 [MRNA] (ISOFORM 1), AND INDUCTION.
RX PubMed=12712191; DOI=10.1038/422832a;
RA Kasahara T., Kato T.;
RT "Nutritional biochemistry: a new redox-cofactor vitamin for mammals.";
RL Nature 422:832-832(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 1-645 (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Brain cortex, and Hypothalamus;
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] (ISOFORMS 1 AND 2).
RC TISSUE=Olfactory epithelium;
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 COMMENT ON PUBMED:12712191 RESULTS.
RX PubMed=15689995; DOI=10.1038/nature03322;
RA Felton L.M., Anthony C.;
RT "Biochemistry: role of PQQ as a mammalian enzyme cofactor?";
RL Nature 433:E10-E10(2005).
RN [5]
RP COMMENT ON PUBMED:12712191 RESULTS.
RX PubMed=15689994; DOI=10.1038/nature03323;
RA Rucker R., Storms D., Sheets A., Tchaparian E., Fascetti A.;
RT "Biochemistry: is pyrroloquinoline quinone a vitamin?";
RL Nature 433:E10-E11(2005).
RN [6]
RP INDUCTION.
RX PubMed=17029795; DOI=10.1016/j.bbagen.2006.07.009;
RA Bauerly K.A., Storms D.H., Harris C.B., Hajizadeh S., Sun M.Y.,
RA Cheung C.P., Satre M.A., Fascetti A.J., Tchaparian E., Rucker R.B.;
RT "Pyrroloquinoline quinone nutritional status alters lysine metabolism and
RT modulates mitochondrial DNA content in the mouse and rat.";
RL Biochim. Biophys. Acta 1760:1741-1748(2006).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF SER-591.
RX PubMed=24467666; DOI=10.1111/febs.12725;
RA Drozak J., Veiga-da-Cunha M., Kadziolka B., Van Schaftingen E.;
RT "Vertebrate acyl CoA synthetase family member 4 (ACSF4-U26) is a beta-
RT alanine-activating enzyme homologous to bacterial non-ribosomal peptide
RT synthetase.";
RL FEBS J. 281:1585-1597(2014).
CC -!- FUNCTION: Covalently binds beta-alanine in an ATP-dependent manner to
CC form a thioester bond with its phosphopantetheine group and transfers
CC it to an as yet unknown acceptor via an amide bond. May be required for
CC a post-translational protein modification or for post-transcriptional
CC modification of an RNA. {ECO:0000269|PubMed:24467666,
CC ECO:0000303|PubMed:24467666}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q80WC9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q80WC9-2; Sequence=VSP_030715;
CC Name=3;
CC IsoId=Q80WC9-3; Sequence=VSP_030714;
CC -!- INDUCTION: Has been shown to be up-regulated by a lysine-rich diet
CC (PubMed:12712191). However, levels of expression have also been shown
CC not to be significantly changed even when diets differ markedly in PQQ
CC and lysine content (PubMed:17029795). {ECO:0000269|PubMed:12712191,
CC ECO:0000269|PubMed:17029795}.
CC -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC {ECO:0000305}.
CC -!- CAUTION: Was suggested to bind pyrroloquinoline quinone (PQQ) based on
CC prediction tools and indirect results (PubMed:12712191). However, this
CC has not been confirmed in other publications (PubMed:15689995,
CC PubMed:15689994). {ECO:0000305|PubMed:12712191,
CC ECO:0000305|PubMed:15689994, ECO:0000305|PubMed:15689995}.
CC -!- CAUTION: In invertebrates, the aminoadipate-semialdehyde dehydrogenase
CC reaction is a key step of the L-lysine biosynthesis pathway which is
CC not fully conserved in vertebrates and it has been suggested that this
CC protein participates in the reverse reaction i.e. in lysine catabolism
CC (PubMed:12712191). However, this is unlikely to be the case as no
CC dehydrogenase activity has been detected and the authentic mammalian 2-
CC aminoadipate semialdehyde dehydrogenase has been identified as ALDH7A1
CC (PubMed:24467666). {ECO:0000305|PubMed:12712191,
CC ECO:0000305|PubMed:24467666}.
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DR EMBL; AB095954; BAC75954.1; -; mRNA.
DR EMBL; AK038779; BAE43303.1; -; mRNA.
DR EMBL; AK043807; BAC31660.1; -; mRNA.
DR EMBL; BC094507; AAH94507.1; -; mRNA.
DR EMBL; BC128330; AAI28331.1; -; mRNA.
DR CCDS; CCDS19366.1; -. [Q80WC9-1]
DR RefSeq; NP_776126.1; NM_173765.3. [Q80WC9-1]
DR RefSeq; XP_006534916.1; XM_006534853.2. [Q80WC9-1]
DR RefSeq; XP_011247723.1; XM_011249421.1.
DR RefSeq; XP_011247724.1; XM_011249422.1. [Q80WC9-1]
DR AlphaFoldDB; Q80WC9; -.
DR SMR; Q80WC9; -.
DR BioGRID; 231109; 1.
DR STRING; 10090.ENSMUSP00000113792; -.
DR iPTMnet; Q80WC9; -.
DR PhosphoSitePlus; Q80WC9; -.
DR EPD; Q80WC9; -.
DR PaxDb; Q80WC9; -.
DR PRIDE; Q80WC9; -.
DR ProteomicsDB; 285942; -. [Q80WC9-1]
DR ProteomicsDB; 285943; -. [Q80WC9-2]
DR Antibodypedia; 24007; 57 antibodies from 16 providers.
DR DNASU; 231326; -.
DR Ensembl; ENSMUST00000069709; ENSMUSP00000069279; ENSMUSG00000055923. [Q80WC9-1]
DR Ensembl; ENSMUST00000120963; ENSMUSP00000113792; ENSMUSG00000055923. [Q80WC9-1]
DR GeneID; 231326; -.
DR KEGG; mmu:231326; -.
DR UCSC; uc008xvi.2; mouse. [Q80WC9-1]
DR UCSC; uc008xvk.2; mouse. [Q80WC9-3]
DR CTD; 132949; -.
DR MGI; MGI:2442517; Aasdh.
DR VEuPathDB; HostDB:ENSMUSG00000055923; -.
DR eggNOG; KOG1178; Eukaryota.
DR eggNOG; KOG4649; Eukaryota.
DR GeneTree; ENSGT00440000033811; -.
DR HOGENOM; CLU_010423_0_0_1; -.
DR InParanoid; Q80WC9; -.
DR OMA; GEKPIFA; -.
DR OrthoDB; 881306at2759; -.
DR PhylomeDB; Q80WC9; -.
DR TreeFam; TF314245; -.
DR BioGRID-ORCS; 231326; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Aasdh; mouse.
DR PRO; PR:Q80WC9; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q80WC9; protein.
DR Bgee; ENSMUSG00000055923; Expressed in indifferent gonad and 221 other tissues.
DR ExpressionAtlas; Q80WC9; baseline and differential.
DR Genevisible; Q80WC9; MM.
DR GO; GO:0016878; F:acid-thiol ligase activity; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0043041; P:amino acid activation for nonribosomal peptide biosynthetic process; IDA:MGI.
DR GO; GO:0019482; P:beta-alanine metabolic process; IDA:MGI.
DR GO; GO:0006631; P:fatty acid metabolic process; ISS:UniProtKB.
DR Gene3D; 2.130.10.10; -; 1.
DR Gene3D; 3.30.300.30; -; 1.
DR Gene3D; 3.40.50.12780; -; 1.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR045851; AMP-bd_C_sf.
DR InterPro; IPR020845; AMP-binding_CS.
DR InterPro; IPR000873; AMP-dep_Synth/Lig.
DR InterPro; IPR042099; ANL_N_sf.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR InterPro; IPR025666; PQQ-like_dom.
DR InterPro; IPR018391; PQQ_beta_propeller_repeat.
DR InterPro; IPR002372; PQQ_repeat.
DR InterPro; IPR011047; Quinoprotein_ADH-like_supfam.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR Pfam; PF00501; AMP-binding; 1.
DR Pfam; PF00550; PP-binding; 1.
DR Pfam; PF13360; PQQ_2; 1.
DR Pfam; PF13570; PQQ_3; 1.
DR SMART; SM00564; PQQ; 6.
DR SUPFAM; SSF47336; SSF47336; 1.
DR SUPFAM; SSF50998; SSF50998; 1.
DR PROSITE; PS00455; AMP_BINDING; 1.
DR PROSITE; PS50075; CARRIER; 1.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Fatty acid metabolism; Ligase;
KW Lipid metabolism; NAD; Nucleotide-binding; Phosphopantetheine;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1..1100
FT /note="Beta-alanine-activating enzyme"
FT /id="PRO_0000315804"
FT DOMAIN 552..632
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 162..181
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 643..671
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 643..661
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 197..205
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 427
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 441
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 526
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT MOD_RES 591
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 651
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q4L235"
FT VAR_SEQ 223..1100
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_030714"
FT VAR_SEQ 368..1100
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_030715"
FT MUTAGEN 591
FT /note="S->A: Abolishes incorporation of beta-alanine."
FT /evidence="ECO:0000269|PubMed:24467666"
SQ SEQUENCE 1100 AA; 121569 MW; 86B303CFF07B234C CRC64;
MTLQELVLRT ASVYMDRTAV CFDEGNNQPP VCYSYKALLS AASELSHFLI AHCDFGGIRE
IGLYCQPGIN LPSWILGILQ VPAAYAPIDP DSPPSLSTYF MKKCDLKYVL VEKQQLSKFK
SSHETVLNYD TVSVEHKDLA LFRLHWEDGR VSTVLGDRAD QHKVTDREDR VSAESRTPEK
EHMDMRHDGC LAYVLHTSGT TGTPKIVRVP HACILPNIQH FRSLFDITQE DILFLASPLT
FDPSVVEIFV SLSSGACLLI VPTSVKVLPS KLADILFSRH RVTVLQATPT LLRRFGSELI
KSTVLSAHTS LRVLALGGEA FPSLTILKSW RGKGNRTQIF NIYGITEVSS WATFYRIPEE
ILNSAVKHES PVQLGSPLLG TVIEVRDQNG SPVLEGTGQV FLGGKNRVCF LDDEMTVPLG
TMRATGDFVT VKDGEIFFLG RKDSQIKRHG KRLNIALVQQ VAEELRQVES CAVTWYNQER
LILFIVSKVD LVKDCIFKEL QKHLPAHALP DDMVLIDTLP FTCHGKVDVS ELNKIYLDYI
SSQPRNELHG KEELWGKLQY LWKSILCLPE DPEDTLKVPA NSVFLDSGGD SLKSMRLLSE
IERLTGTAIP GLLEVILSSS LLDVYNHIVQ AVFTPEDRKA NRSYTTKRKF SDADPEEASG
KPARLESAWP SNHAGETNSV IALSRGSQVL SLGAGRLLTQ LGLCLPVCSL DLIPQTNTQI
LKSLSPPAPD ENLEKPPLFQ QGSPVVGAMA MALRERWRSD TGKCVDASPL LVRAAVQDKP
STTVYIGSHS HTVKAVDLSS GETRWEQLLG DRIESSACVS KCGNFIVVGC YNGLVYVLKS
NSGEKYWTFT TEDAVKSSPA VDPTTGLIYV GSHDQHAYAL DIYEKKCVWK LNCEGALFSS
PCVSLSPHHL YCATLGGLLL ALNPASGSTV WKRSCGKPLF SSPRCYQQYI CIGCVDGSLL
CFTHSGEQVW RFAAGGPIFS SPCVSAAEQE IFFGSHDCFI YCCSKEGHLR WKFETTARVY
ATPFAFSNHP RSDDALLAAA STDGKLWVLE SRSGELRSVY ELPGEVFSSP VVWESMLVIG
CRNNYIYCLD LLCGDKNNQV
