Q80WC9 (ACSF4_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Acyl-CoA synthetase family member 4
EC=6.2.1.-

Alternative name(s):
2-aminoadipic 6-semialdehyde dehydrogenase
Protein LYS2 homolog
Putative aminoadipate-semialdehyde dehydrogenase
EC=1.2.1.31

Gene names

Name:	Aasdh
Synonyms:	Acsf4, U26

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	1100 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Acyl-CoA synthases catalyze the initial reaction in fatty acid metabolism, by forming a thioester with CoA By similarity. Putative 2-aminoadipic 6-semialdehyde dehydrogenase, which may be involved in lysine catabolism. Ref.1
Catalytic activity	(S)-2-amino-6-oxohexanoate + NAD(P)+ + H2O = L-2-aminoadipate + NAD(P)H.
Induction	According to Ref.1, it is up-regulated by lysine-rich diet, while according to Ref.6 levels of expression are not significantly changed even when diets differed markedly in PQQ and lysine content. Ref.1 Ref.6
Sequence similarities	Belongs to the ATP-dependent AMP-binding enzyme family. Contains 1 acyl carrier domain.
Caution	According to Ref.1, it may bind pyrroloquinoline quinone (PQQ) cofactor. However, their conclusions are based on prediction tools and indirect results and are not confirmed by Ref.4 and Ref.5. The relevance of PQQ-binding is therefore unclear in vivo. In invertebrates, aminoadipate-semialdehyde dehydrogenase reaction is a key step of the L-lysine biosynthesis pathway, which is not fully conserved in vertebrates. It has been suggested by Ref.1 that this protein participates in the reverse reaction (i.e. in lysine catabolism), however the relevance of this catalytic activity in vivo remains unclear.

Ontologies

Keywords
Biological process	Fatty acid metabolism Lipid metabolism
Coding sequence diversity	Alternative splicing
Ligand	ATP-binding NAD Nucleotide-binding Phosphopantetheine
Molecular function	Ligase Oxidoreductase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	fatty acid metabolic process Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW L-aminoadipate-semialdehyde dehydrogenase activity Inferred from electronic annotation. Source: EC acid-thiol ligase activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q80WC9-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q80WC9-2)

The sequence of this isoform differs from the canonical sequence as follows:
     368-1100: Missing.

Note: No experimental confirmation available.

Isoform 3 (identifier: Q80WC9-3)

The sequence of this isoform differs from the canonical sequence as follows:
     223-1100: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1100	1100	Acyl-CoA synthetase family member 4		PRO_0000315804
Regions
	Domain	554 – 628	75	Acyl carrier
	Nucleotide binding	197 – 205	9	ATP By similarity
Sites
	Binding site	427	1	ATP By similarity
	Binding site	441	1	ATP By similarity
	Binding site	526	1	ATP By similarity
Amino acid modifications
	Modified residue	591	1	O-(pantetheine 4'-phosphoryl)serine By similarity
	Modified residue	651	1	Phosphoserine By similarity
Natural variations
	Alternative sequence	223 – 1100	878	Missing in isoform 3.		VSP_030714
	Alternative sequence	368 – 1100	733	Missing in isoform 2.		VSP_030715

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 1, 2003. Version 1. Checksum: 86B303CFF07B234C	FASTA	1,100	121,569
	10 20 30 40 50 60 MTLQELVLRT ASVYMDRTAV CFDEGNNQPP VCYSYKALLS AASELSHFLI AHCDFGGIRE 70 80 90 100 110 120 IGLYCQPGIN LPSWILGILQ VPAAYAPIDP DSPPSLSTYF MKKCDLKYVL VEKQQLSKFK 130 140 150 160 170 180 SSHETVLNYD TVSVEHKDLA LFRLHWEDGR VSTVLGDRAD QHKVTDREDR VSAESRTPEK 190 200 210 220 230 240 EHMDMRHDGC LAYVLHTSGT TGTPKIVRVP HACILPNIQH FRSLFDITQE DILFLASPLT 250 260 270 280 290 300 FDPSVVEIFV SLSSGACLLI VPTSVKVLPS KLADILFSRH RVTVLQATPT LLRRFGSELI 310 320 330 340 350 360 KSTVLSAHTS LRVLALGGEA FPSLTILKSW RGKGNRTQIF NIYGITEVSS WATFYRIPEE 370 380 390 400 410 420 ILNSAVKHES PVQLGSPLLG TVIEVRDQNG SPVLEGTGQV FLGGKNRVCF LDDEMTVPLG 430 440 450 460 470 480 TMRATGDFVT VKDGEIFFLG RKDSQIKRHG KRLNIALVQQ VAEELRQVES CAVTWYNQER 490 500 510 520 530 540 LILFIVSKVD LVKDCIFKEL QKHLPAHALP DDMVLIDTLP FTCHGKVDVS ELNKIYLDYI 550 560 570 580 590 600 SSQPRNELHG KEELWGKLQY LWKSILCLPE DPEDTLKVPA NSVFLDSGGD SLKSMRLLSE 610 620 630 640 650 660 IERLTGTAIP GLLEVILSSS LLDVYNHIVQ AVFTPEDRKA NRSYTTKRKF SDADPEEASG 670 680 690 700 710 720 KPARLESAWP SNHAGETNSV IALSRGSQVL SLGAGRLLTQ LGLCLPVCSL DLIPQTNTQI 730 740 750 760 770 780 LKSLSPPAPD ENLEKPPLFQ QGSPVVGAMA MALRERWRSD TGKCVDASPL LVRAAVQDKP 790 800 810 820 830 840 STTVYIGSHS HTVKAVDLSS GETRWEQLLG DRIESSACVS KCGNFIVVGC YNGLVYVLKS 850 860 870 880 890 900 NSGEKYWTFT TEDAVKSSPA VDPTTGLIYV GSHDQHAYAL DIYEKKCVWK LNCEGALFSS 910 920 930 940 950 960 PCVSLSPHHL YCATLGGLLL ALNPASGSTV WKRSCGKPLF SSPRCYQQYI CIGCVDGSLL 970 980 990 1000 1010 1020 CFTHSGEQVW RFAAGGPIFS SPCVSAAEQE IFFGSHDCFI YCCSKEGHLR WKFETTARVY 1030 1040 1050 1060 1070 1080 ATPFAFSNHP RSDDALLAAA STDGKLWVLE SRSGELRSVY ELPGEVFSSP VVWESMLVIG 1090 1100 CRNNYIYCLD LLCGDKNNQV
	Isoform 2 [UniParc]. Checksum: 19368BB77FDDF580	FASTA	367	40,964
	10 20 30 40 50 60 MTLQELVLRT ASVYMDRTAV CFDEGNNQPP VCYSYKALLS AASELSHFLI AHCDFGGIRE 70 80 90 100 110 120 IGLYCQPGIN LPSWILGILQ VPAAYAPIDP DSPPSLSTYF MKKCDLKYVL VEKQQLSKFK 130 140 150 160 170 180 SSHETVLNYD TVSVEHKDLA LFRLHWEDGR VSTVLGDRAD QHKVTDREDR VSAESRTPEK 190 200 210 220 230 240 EHMDMRHDGC LAYVLHTSGT TGTPKIVRVP HACILPNIQH FRSLFDITQE DILFLASPLT 250 260 270 280 290 300 FDPSVVEIFV SLSSGACLLI VPTSVKVLPS KLADILFSRH RVTVLQATPT LLRRFGSELI 310 320 330 340 350 360 KSTVLSAHTS LRVLALGGEA FPSLTILKSW RGKGNRTQIF NIYGITEVSS WATFYRIPEE ILNSAVK
	Isoform 3 [UniParc]. Checksum: 2850F469893CD77F	FASTA	222	25,031
	10 20 30 40 50 60 MTLQELVLRT ASVYMDRTAV CFDEGNNQPP VCYSYKALLS AASELSHFLI AHCDFGGIRE 70 80 90 100 110 120 IGLYCQPGIN LPSWILGILQ VPAAYAPIDP DSPPSLSTYF MKKCDLKYVL VEKQQLSKFK 130 140 150 160 170 180 SSHETVLNYD TVSVEHKDLA LFRLHWEDGR VSTVLGDRAD QHKVTDREDR VSAESRTPEK 190 200 210 220 EHMDMRHDGC LAYVLHTSGT TGTPKIVRVP HACILPNIQH FR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Nutritional biochemistry: a new redox-cofactor vitamin for mammals." Kasahara T., Kato T. Nature 422:832-832(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), POSSIBLE FUNCTION, INDUCTION.
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-645 (ISOFORM 1). Strain: C57BL/6J. Tissue: Brain cortex and Hypothalamus.
[3]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Olfactory epithelium.
[4]	"Biochemistry: role of PQQ as a mammalian enzyme cofactor?" Felton L.M., Anthony C. Nature 433:E10-E10(2005) [PubMed] [Europe PMC] [Abstract] Cited for: COMMENT ON PUBMED:12712191 RESULTS.
[5]	"Biochemistry: is pyrroloquinoline quinone a vitamin?" Rucker R., Storms D., Sheets A., Tchaparian E., Fascetti A. Nature 433:E10-E11(2005) [PubMed] [Europe PMC] [Abstract] Cited for: COMMENT ON PUBMED:12712191 RESULTS.
[6]	"Pyrroloquinoline quinone nutritional status alters lysine metabolism and modulates mitochondrial DNA content in the mouse and rat." Bauerly K.A., Storms D.H., Harris C.B., Hajizadeh S., Sun M.Y., Cheung C.P., Satre M.A., Fascetti A.J., Tchaparian E., Rucker R.B. Biochim. Biophys. Acta 1760:1741-1748(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB095954 mRNA. Translation: BAC75954.1. AK038779 mRNA. Translation: BAE43303.1. AK043807 mRNA. Translation: BAC31660.1. BC094507 mRNA. Translation: AAH94507.1. BC128330 mRNA. Translation: AAI28331.1.
IPI	IPI00265000. IPI00880667. IPI00880979.
RefSeq	NP_776126.1. NM_173765.3.
UniGene	Mm.39271.
3D structure databases
ProteinModelPortal	Q80WC9.
SMR	Q80WC9. Positions 150-606, 754-1091.
ModBase	Search...
Protein-protein interaction databases
STRING	10090.ENSMUSP00000113792.
PTM databases
PhosphoSite	Q80WC9.
Proteomic databases
PRIDE	Q80WC9.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000069709; ENSMUSP00000069279; ENSMUSG00000055923. ENSMUST00000120963; ENSMUSP00000113792; ENSMUSG00000055923. ENSMUST00000146570; ENSMUSP00000117639; ENSMUSG00000055923.
GeneID	231326.
KEGG	mmu:231326.
UCSC	uc008xvi.2. mouse. uc008xvk.2. mouse.
Organism-specific databases
CTD	132949.
MGI	MGI:2442517. Aasdh.
Phylogenomic databases
eggNOG	COG1520.
GeneTree	ENSGT00440000033811.
HOGENOM	HOG000033793.
HOVERGEN	HBG057704.
InParanoid	Q80WC9.
KO	K00142.
OMA	TMRATGD.
OrthoDB	EOG415GCV.
Gene expression databases
ArrayExpress	Q80WC9.
Bgee	Q80WC9.
CleanEx	MM_AASDH.
Genevestigator	Q80WC9.
Family and domain databases
Gene3D	1.10.1200.10. 1 hit. 2.140.10.10. 1 hit.
InterPro	IPR026897. ACSF4. IPR009081. Acyl_carrier_prot-like. IPR020845. AMP-binding_CS. IPR000873. AMP-dep_Synth/Lig. IPR006162. PPantetheine_attach_site. IPR018391. PQQ_beta_propeller_repeat. IPR027295. Quinonprotein_ADH-like_fam. IPR011047. Quinonprotein_ADH-like_supfam. [Graphical view]
PANTHER	PTHR24095:SF18. PTHR24095:SF18. 1 hit.
Pfam	PF00501. AMP-binding. 1 hit. PF00550. PP-binding. 1 hit. [Graphical view]
SMART	SM00564. PQQ. 6 hits. [Graphical view]
SUPFAM	SSF50998. Quin_alc_DH_like. 1 hit.
PROSITE	PS50075. ACP_DOMAIN. 1 hit. PS00455. AMP_BINDING. 1 hit. PS00012. PHOSPHOPANTETHEINE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	AASDH. mouse.
NextBio	380501.
SOURCE	Search...

Entry information

Entry name

ACSF4_MOUSE

Accession

Primary (citable) accession number: Q80WC9
Secondary accession number(s): Q3V3L2, Q505K4, Q8BRP4

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 15, 2008
Last sequence update:	June 1, 2003
Last modified:	May 29, 2013
This is version 85 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program