O14975 (S27A2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Very long-chain acyl-CoA synthetase
Short name=VLACS
Short name=VLCS
EC=6.2.1.-

Alternative name(s):
Fatty acid transport protein 2
Short name=FATP-2
Fatty-acid-coenzyme A ligase, very long-chain 1
Long-chain-fatty-acid--CoA ligase
EC=6.2.1.3
Solute carrier family 27 member 2
THCA-CoA ligase
Very long-chain-fatty-acid-CoA ligase

Gene names

Name:	SLC27A2
Synonyms:	ACSVL1, FACVL1, FATP2, VLACS

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	620 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Acyl-CoA synthetase probably involved in bile acid metabolism. Proposed to activate C27 precurors of bile acids to their CoA thioesters derivatives before side chain cleavage via peroxisomal beta-oxidation occurs. In vitro, activates 3-alpha,7-alpha,12-alpha-trihydroxy-5-beta-cholestanate (THCA), the C27 precursor of cholic acid deriving from the de novo synthesis from cholesterol. Does not utilize C24 bile acids as substrates. In vitro, also activates long- and branched-chain fatty acids and may have additional roles in fatty acid metabolism. May be involved in translocation of long-chain fatty acids (LFCA) across membranes By similarity. Ref.7
Catalytic activity	ATP + a long-chain carboxylic acid + CoA = AMP + diphosphate + an acyl-CoA. Ref.7 ATP + a very-long-chain carboxylic acid + CoA = AMP + diphosphate + an acyl-CoA. Ref.7
Subcellular location	Endoplasmic reticulum membrane; Multi-pass membrane protein. Peroxisome membrane; Multi-pass membrane protein. Note: Peripheral membrane associated with the lumenal side of peroxisomes. Ref.2 Ref.7
Tissue specificity	Expressed in liver, kidney, placenta and pancreas. Ref.2
Sequence similarities	Belongs to the ATP-dependent AMP-binding enzyme family.

Ontologies

Keywords
Biological process	Fatty acid metabolism Lipid metabolism
Cellular component	Endoplasmic reticulum Membrane Peroxisome
Coding sequence diversity	Polymorphism
Domain	Transmembrane Transmembrane helix
Ligand	ATP-binding Nucleotide-binding
Molecular function	Ligase
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	bile acid biosynthetic process Traceable author statement. Source: Reactome fatty acid alpha-oxidation Traceable author statement. Source: Reactome
Cellular component	endoplasmic reticulum membrane Traceable author statement. Source: Reactome integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW peroxisomal matrix Traceable author statement. Source: ProtInc peroxisomal membrane Traceable author statement. Source: Reactome
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW long-chain fatty acid-CoA ligase activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 620	620	Very long-chain acyl-CoA synthetase		PRO_0000193204
Regions
	Topological domain	1 – 4	4	Lumenal Probable
	Transmembrane	5 – 27	23	Helical; Potential
	Topological domain	28 – 106	79	Cytoplasmic Potential
	Transmembrane	107 – 127	21	Helical; Potential
	Topological domain	128 – 261	134	Lumenal Potential
	Transmembrane	262 – 282	21	Helical; Potential
	Topological domain	283 – 620	338	Cytoplasmic Potential
	Nucleotide binding	222 – 233	12	AMP Potential
Amino acid modifications
	Modified residue	291	1	N6-acetyllysine By similarity
	Modified residue	325	1	N6-acetyllysine By similarity
	Modified residue	577	1	Phosphothreonine Ref.8
Natural variations
	Natural variant	48	1	K → Q. Ref.1 Ref.2 Ref.3 Ref.6 Corresponds to variant rs1648348 [ dbSNP | Ensembl ].		VAR_046533

Sequences

	Sequence		Length	Mass (Da)
	O14975 [UniParc]. Last modified October 5, 2010. Version 2. Checksum: 752E2FFBB2E47C26	FASTA	620	70,312
	10 20 30 40 50 60 MLSAIYTVLA GLLFLPLLVN LCCPYFFQDI GYFLKVAAVG RRVRSYGKRR PARTILRAFL 70 80 90 100 110 120 EKARQTPHKP FLLFRDETLT YAQVDRRSNQ VARALHDHLG LRQGDCVALL MGNEPAYVWL 130 140 150 160 170 180 WLGLVKLGCA MACLNYNIRA KSLLHCFQCC GAKVLLVSPE LQAAVEEILP SLKKDDVSIY 190 200 210 220 230 240 YVSRTSNTDG IDSFLDKVDE VSTEPIPESW RSEVTFSTPA LYIYTSGTTG LPKAAMITHQ 250 260 270 280 290 300 RIWYGTGLTF VSGLKADDVI YITLPFYHSA ALLIGIHGCI VAGATLALRT KFSASQFWDD 310 320 330 340 350 360 CRKYNVTVIQ YIGELLRYLC NSPQKPNDRD HKVRLALGNG LRGDVWRQFV KRFGDICIYE 370 380 390 400 410 420 FYAATEGNIG FMNYARKVGA VGRVNYLQKK IITYDLIKYD VEKDEPVRDE NGYCVRVPKG 430 440 450 460 470 480 EVGLLVCKIT QLTPFNGYAG AKAQTEKKKL RDVFKKGDLY FNSGDLLMVD HENFIYFHDR 490 500 510 520 530 540 VGDTFRWKGE NVATTEVADT VGLVDFVQEV NVYGVHVPDH EGRIGMASIK MKENHEFDGK 550 560 570 580 590 600 KLFQHIADYL PSYARPRFLR IQDTIEITGT FKHRKMTLVE EGFNPAVIKD ALYFLDDTAK 610 620 MYVPMTEDIY NAISAKTLKL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of a possible human homolog of the rat very-long-chain acyl-CoA synthetase cDNA and its chromosomal localization." Uchiyama A., Aoyama T., Kamijo K., Wakui K., Fukushima Y., Shimozawa N., Suzuki Y., Kondo N., Orii T., Hashimoto T. Submitted (DEC-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT GLN-48. Tissue: Liver.
[2]	"Human very-long-chain acyl-CoA synthetase: cloning, topography, and relevance to branched-chain fatty acid metabolism." Steinberg S.J., Wang S.J., Kim D.G., Mihalik S.J., Watkins P.A. Biochem. Biophys. Res. Commun. 257:615-621(1999) [PubMed: 10198260] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, SUBCELLULAR LOCATION, VARIANT GLN-48.
[3]	"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], VARIANT GLN-48. Tissue: Colon.
[4]	Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Kidney.
[5]	"Analysis of the DNA sequence and duplication history of human chromosome 15." Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A. , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C. Nature 440:671-675(2006) [PubMed: 16572171] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	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 (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT GLN-48.
[7]	"Participation of two members of the very long-chain acyl-CoA synthetase family in bile acid synthesis and recycling." Mihalik S.J., Steinberg S.J., Pei Z., Park J., Kim do G., Heinzer A.K., Dacremont G., Wanders R.J., Cuebas D.A., Smith K.D., Watkins P.A. J. Biol. Chem. 277:24771-24779(2002) [PubMed: 11980911] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, TOPOLOGY.
[8]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-577, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[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].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	D88308 mRNA. Translation: BAA23644.1. AF096290 mRNA. Translation: AAC64973.1. AK223145 mRNA. Translation: BAD96865.1. AK290262 mRNA. Translation: BAF82951.1. AC009753 Genomic DNA. No translation available. CH471082 Genomic DNA. Translation: EAW77386.1.
IPI	IPI00024787.
RefSeq	NP_001153101.1. NM_001159629.1. NP_003636.2. NM_003645.3.
UniGene	Hs.11729.
3D structure databases
ProteinModelPortal	O14975.
ModBase	Search...
Protein-protein interaction databases
IntAct	O14975. 1 interaction.
MINT	MINT-2998454.
STRING	O14975.
Protein family/group databases
TCDB	4.C.1.1.5. proposed fatty acid transporter (FAT) family.
PTM databases
PhosphoSite	O14975.
Proteomic databases
PRIDE	O14975.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000267842; ENSP00000267842; ENSG00000140284.
GeneID	11001.
KEGG	hsa:11001.
UCSC	uc001zxw.1. human.
Organism-specific databases
CTD	11001.
GeneCards	GC15P050474.
H-InvDB	HIX0026779.
HGNC	HGNC:10996. SLC27A2.
HPA	HPA026089.
MIM	603247. gene.
neXtProt	NX_O14975.
PharmGKB	PA27971.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG12818.
HOGENOM	HBG712034.
HOVERGEN	HBG005642.
InParanoid	O14975.
OMA	FSTPALY.
OrthoDB	EOG41ZF9B.
PhylomeDB	O14975.
Enzyme and pathway databases
Reactome	REACT_22258. Metabolism of lipids and lipoproteins.
Gene expression databases
ArrayExpress	O14975.
Bgee	O14975.
CleanEx	HS_SLC27A2.
Genevestigator	O14975.
GermOnline	ENSG00000140284. Homo sapiens.
Family and domain databases
InterPro	IPR020845. AMP-binding_CS. IPR000873. AMP-dep_Synth/Lig. [Graphical view]
KO	K08746.
Pfam	PF00501. AMP-binding. 1 hit. [Graphical view]
PROSITE	PS00455. AMP_BINDING. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	41795.
SOURCE	Search...

Entry information

Entry name

S27A2_HUMAN

Accession

Primary (citable) accession number: O14975
Secondary accession number(s): A8K2J7, Q53FY6

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	October 5, 2010
Last modified:	January 25, 2012
This is version 95 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.