Q9NUB1 (ACS2L_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Acetyl-coenzyme A synthetase 2-like, mitochondrial
EC=6.2.1.1

Alternative name(s):
Acetate--CoA ligase 2
Acetyl-CoA synthetase 2
Short name=AceCS2
Acyl-CoA synthetase short-chain family member 1

Gene names

Name:	ACSS1
Synonyms:	ACAS2L, KIAA1846

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	689 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Important for maintaining normal body temperature during fasting and for energy homeostasis. Essential for energy expenditure under ketogenic conditions By similarity. Converts acetate to acetyl-CoA so that it can be used for oxidation through the tricarboxylic cycle to produce ATP and CO2. Ref.7
Catalytic activity	ATP + acetate + CoA = AMP + diphosphate + acetyl-CoA.
Enzyme regulation	Inhibited by acetylation at Lys-642 and activated by deacetylation. Ref.7
Subunit structure	Interacts with SIRT3.
Subcellular location	Mitochondrion matrix Ref.7.
Post-translational modification	Reversibly acetylated on Lys-642. The acetyl-CoA synthase activity is inhibited by acetylation and activated by deacetylation.
Sequence similarities	Belongs to the ATP-dependent AMP-binding enzyme family.
Sequence caution	The sequence BAB55390.1 differs from that shown. Reason: Erroneous initiation. The sequence BAC03853.1 differs from that shown. Reason: Frameshift at position 250. The sequence BAC03853.1 differs from that shown. Reason: Sequencing errors.

Ontologies

Keywords
Cellular component	Mitochondrion
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transit peptide
Ligand	ATP-binding Nucleotide-binding
Molecular function	Ligase
PTM	Acetylation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	acetyl-CoA biosynthetic process Inferred from direct assay Ref.7. Source: UniProtKB ethanol oxidation Traceable author statement. Source: Reactome xenobiotic metabolic process Traceable author statement. Source: Reactome
Cellular component	mitochondrial matrix Inferred from direct assay Ref.7. Source: UniProtKB
Molecular function	AMP binding Inferred from electronic annotation. Source: InterPro ATP binding Inferred from electronic annotation. Source: UniProtKB-KW acetate-CoA ligase activity Inferred from direct assay Ref.7. Source: UniProtKB protein binding Inferred from physical interaction Ref.7Ref.10. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9NUB1-1)

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: Q9NUB1-2)

The sequence of this isoform differs from the canonical sequence as follows:
     446-447: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 37

37

Mitochondrion

Chain

38 – 689

652

Acetyl-coenzyme A synthetase 2-like, mitochondrial

PRO_0000000596

Regions

Compositional bias

45 – 53

9

Poly-Ala

Amino acid modifications

Modified residue

396

1

N6-acetyllysine Ref.8

Modified residue

642

1

N6-acetyllysine Ref.7

Natural variations

Alternative sequence

446 – 447

2

Missing in isoform 2.

VSP_007249

Natural variant

488

1

V → M. Ref.3
Corresponds to variant rs6050249 [ dbSNP | Ensembl ].

VAR_048184

Experimental info

Mutagenesis

642

1

K → Q: Loss of activity. Ref.7

Sequence conflict

277

1

V → M in AAH39261. Ref.3

Secondary structure

1

.

.

.

689

Helix Strand Turn

Details...

Beta strand

643 – 645

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified April 23, 2003. Version 2. Checksum: 66E84E39302AD08B	FASTA	689	74,857
	10 20 30 40 50 60 MAARTLGRGV GRLLGSLRGL SGQPARPPCG VSAPRRAASG PSGSAPAVAA AAAQPGSYPA 70 80 90 100 110 120 LSAQAAREPA AFWGPLARDT LVWDTPYHTV WDCDFSTGKI GWFLGGQLNV SVNCLDQHVR 130 140 150 160 170 180 KSPESVALIW ERDEPGTEVR ITYRELLETT CRLANTLKRH GVHRGDRVAI YMPVSPLAVA 190 200 210 220 230 240 AMLACARIGA VHTVIFAGFS AESLAGRIND AKCKVVITFN QGLRGGRVVE LKKIVDEAVK 250 260 270 280 290 300 HCPTVQHVLV AHRTDNKVHM GDLDVPLEQE MAKEDPVCAP ESMGSEDMLF MLYTSGSTGM 310 320 330 340 350 360 PKGIVHTQAG YLLYAALTHK LVFDHQPGDI FGCVADIGWI TGHSYVVYGP LCNGATSVLF 370 380 390 400 410 420 ESTPVYPNAG RYWETVERLK INQFYGAPTA VRLLLKYGDA WVKKYDRSSL RTLGSVGEPI 430 440 450 460 470 480 NCEAWEWLHR VVGDSRCTLV DTWWQTETGG ICIAPRPSEE GAEILPAMAM RPFFGIVPVL 490 500 510 520 530 540 MDEKGSVVEG SNVSGALCIS QAWPGMARTI YGDHQRFVDA YFKAYPGYYF TGDGAYRTEG 550 560 570 580 590 600 GYYQITGRMD DVINISGHRL GTAEIEDAIA DHPAVPESAV IGYPHDIKGE AAFAFIVVKD 610 620 630 640 650 660 SAGDSDVVVQ ELKSMVATKI AKYAVPDEIL VVKRLPKTRS GKVMRRLLRK IITSEAQELG 670 680 DTTTLEDPSI IAEILSVYQK CKDKQAAAK
	Isoform 2 [UniParc]. Checksum: 99888770D7E10BA4	FASTA	687	74,627
	10 20 30 40 50 60 MAARTLGRGV GRLLGSLRGL SGQPARPPCG VSAPRRAASG PSGSAPAVAA AAAQPGSYPA 70 80 90 100 110 120 LSAQAAREPA AFWGPLARDT LVWDTPYHTV WDCDFSTGKI GWFLGGQLNV SVNCLDQHVR 130 140 150 160 170 180 KSPESVALIW ERDEPGTEVR ITYRELLETT CRLANTLKRH GVHRGDRVAI YMPVSPLAVA 190 200 210 220 230 240 AMLACARIGA VHTVIFAGFS AESLAGRIND AKCKVVITFN QGLRGGRVVE LKKIVDEAVK 250 260 270 280 290 300 HCPTVQHVLV AHRTDNKVHM GDLDVPLEQE MAKEDPVCAP ESMGSEDMLF MLYTSGSTGM 310 320 330 340 350 360 PKGIVHTQAG YLLYAALTHK LVFDHQPGDI FGCVADIGWI TGHSYVVYGP LCNGATSVLF 370 380 390 400 410 420 ESTPVYPNAG RYWETVERLK INQFYGAPTA VRLLLKYGDA WVKKYDRSSL RTLGSVGEPI 430 440 450 460 470 480 NCEAWEWLHR VVGDSRCTLV DTWWQTGGIC IAPRPSEEGA EILPAMAMRP FFGIVPVLMD 490 500 510 520 530 540 EKGSVVEGSN VSGALCISQA WPGMARTIYG DHQRFVDAYF KAYPGYYFTG DGAYRTEGGY 550 560 570 580 590 600 YQITGRMDDV INISGHRLGT AEIEDAIADH PAVPESAVIG YPHDIKGEAA FAFIVVKDSA 610 620 630 640 650 660 GDSDVVVQEL KSMVATKIAK YAVPDEILVV KRLPKTRSGK VMRRLLRKII TSEAQELGDT 670 680 TTLEDPSIIA EILSVYQKCK DKQAAAK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The DNA sequence and comparative analysis of human chromosome 20." Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J. Nature 414:865-871(2001) [PubMed: 11780052] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[2]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANT MET-488. Tissue: Brain and Testis.
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 169-689 (ISOFORM 1). Tissue: Placenta and Tongue.
[5]	"Prediction of the coding sequences of unidentified human genes. XX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Nakayama M., Nakajima D., Kikuno R., Ohara O. DNA Res. 8:85-95(2001) [PubMed: 11347906] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 336-689 (ISOFORM 1). Tissue: Brain.
[6]	"Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones." Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T. DNA Res. 9:99-106(2002) [PubMed: 12168954] [Abstract] Cited for: SEQUENCE REVISION.
[7]	"Reversible lysine acetylation controls the activity of the mitochondrial enzyme acetyl-CoA synthetase 2." Schwer B., Bunkenborg J., Verdin R.O., Andersen J.S., Verdin E. Proc. Natl. Acad. Sci. U.S.A. 103:10224-10229(2006) [PubMed: 16788062] [Abstract] Cited for: ACETYLATION AT LYS-642, MUTAGENESIS OF LYS-642, FUNCTION, ENZYME REGULATION, PROTEIN SEQUENCE OF N-TERMINUS, MASS SPECTROMETRY, SUBCELLULAR LOCATION.
[8]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-396, MASS SPECTROMETRY.
[9]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]	"Crystal structures of human SIRT3 displaying substrate-induced conformational changes." Jin L., Wei W., Jiang Y., Peng H., Cai J., Mao C., Dai H., Choy W., Bemis J.E., Jirousek M.R., Milne J.C., Westphal C.H., Perni R.B. J. Biol. Chem. 284:24394-24405(2009) [PubMed: 19535340] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 638-649 IN COMPLEX WITH SIRT3.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AL035661, AL080312 Genomic DNA. Translation: CAI21828.1.
AL080312, AL035661 Genomic DNA. Translation: CAI18917.1.
CH471133 Genomic DNA. Translation: EAX10106.1.
CH471133 Genomic DNA. Translation: EAX10109.1.
BC039261 mRNA. Translation: AAH39261.1.
BC044588 mRNA. Translation: AAH44588.1.
AK027817 mRNA. Translation: BAB55390.1. Different initiation.
AK092295 mRNA. Translation: BAC03853.1. Sequence problems.
AB058749 mRNA. Translation: BAB47475.1.

IPI

IPI00216932.
IPI00248961.

RefSeq

NP_115890.2. NM_032501.2.

UniGene

Hs.529353.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3GLR	X-ray	1.80	B	638-649	[»]
3GLT	X-ray	2.10	B	638-649	[»]
3GLU	X-ray	2.50	B	638-649	[»]

ProteinModelPortal

Q9NUB1.

SMR

Q9NUB1. Positions 49-679.

ModBase

Search...

Protein-protein interaction databases

STRING

Q9NUB1.

PTM databases

PhosphoSite

Q9NUB1.

Polymorphism databases

DMDM

30172968.

Proteomic databases

PRIDE

Q9NUB1.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000323482; ENSP00000316924; ENSG00000154930.

GeneID

84532.

KEGG

hsa:84532.

NMPDR

fig|9606.3.peg.19997.

UCSC

uc002wub.1. human.
uc002wuc.1. human.

Organism-specific databases

CTD

84532.

GeneCards

GC20M024986.

H-InvDB

HIX0015699.

HGNC

HGNC:16091. ACSS1.

MIM

614355. gene.

neXtProt

NX_Q9NUB1.

PharmGKB

PA24430.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

GeneTree

ENSGT00550000074278.

HOVERGEN

HBG014401.

InParanoid

Q9NUB1.

OMA

LDQHVQK.

OrthoDB

EOG4RFKS6.

PhylomeDB

Q9NUB1.

Enzyme and pathway databases

BRENDA

6.2.1.1. 2681.

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

Q9NUB1.

Bgee

Q9NUB1.

CleanEx

HS_ACSS1.

Genevestigator

Q9NUB1.

GermOnline

ENSG00000154930. Homo sapiens.

Family and domain databases

InterPro

IPR011904. Ac_CoA_lig.
IPR024597. Acyl-CoA_synth_DUF3448.
IPR020845. AMP-binding_CS.
IPR000873. AMP-dep_Synth/Lig.
[Graphical view]

KO

K01895.

PANTHER

PTHR24095:SF42. PTHR24095:SF42. 1 hit.

Pfam

PF00501. AMP-binding. 1 hit.
PF11930. DUF3448. 1 hit.
[Graphical view]

TIGRFAMs

TIGR02188. Ac_CoA_lig_AcsA. 1 hit.

PROSITE

PS00455. AMP_BINDING. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

DrugBank

DB00131. Adenosine monophosphate.
DB00171. Adenosine triphosphate.

NextBio

74375.

SOURCE

Search...

Entry information

Entry name

ACS2L_HUMAN

Accession

Primary (citable) accession number: Q9NUB1
Secondary accession number(s): D3DW48 , Q5TF42, Q8IV99, Q8N234, Q96JI1, Q96JX6, Q9NU28

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 23, 2003
Last sequence update:	April 23, 2003
Last modified:	January 25, 2012
This is version 93 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.