Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

O14975 (S27A2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 122. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length620 AA.
Sequence statusComplete.
Protein existenceEvidence 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.8

Catalytic activity

ATP + a long-chain fatty acid + CoA = AMP + diphosphate + an acyl-CoA. Ref.8

ATP + a very-long-chain carboxylic acid + CoA = AMP + diphosphate + an acyl-CoA. Ref.8

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.8

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 processFatty acid metabolism
Lipid metabolism
   Cellular componentEndoplasmic reticulum
Membrane
Peroxisome
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainTransmembrane
Transmembrane helix
   LigandATP-binding
Nucleotide-binding
   Molecular functionLigase
   PTMAcetylation
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processbile acid biosynthetic process

Inferred from direct assay Ref.8. Source: UniProtKB

bile acid metabolic process

Traceable author statement. Source: Reactome

cellular lipid metabolic process

Traceable author statement. Source: Reactome

fatty acid alpha-oxidation

Inferred from direct assay Ref.2. Source: UniProtKB

fatty acid beta-oxidation

Inferred from direct assay Ref.2. Source: UniProtKB

long-chain fatty acid import

Inferred from direct assay PubMed 22022213. Source: UniProtKB

long-chain fatty acid metabolic process

Inferred from direct assay PubMed 22022213. Source: UniProtKB

methyl-branched fatty acid metabolic process

Inferred from direct assay Ref.2. Source: UniProtKB

small molecule metabolic process

Traceable author statement. Source: Reactome

very long-chain fatty acid catabolic process

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentendoplasmic reticulum lumen

Inferred from direct assay Ref.2. Source: UniProtKB

endoplasmic reticulum membrane

Inferred from direct assay PubMed 22022213. Source: UniProtKB

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867PubMed 23376485. Source: UniProt

integral component of endoplasmic reticulum membrane

Inferred from direct assay Ref.8. Source: UniProtKB

integral component of peroxisomal membrane

Inferred from direct assay Ref.2. Source: UniProtKB

mitochondrion

Inferred from electronic annotation. Source: Ensembl

peroxisomal membrane

Inferred from direct assay PubMed 10640429. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

enzyme binding

Inferred from physical interaction PubMed 16781659. Source: UniProtKB

fatty acid transporter activity

Inferred from electronic annotation. Source: Ensembl

long-chain fatty acid-CoA ligase activity

Inferred from direct assay Ref.2PubMed 22022213. Source: UniProtKB

phytanate-CoA ligase activity

Inferred from direct assay Ref.2. Source: UniProtKB

pristanate-CoA ligase activity

Inferred from direct assay Ref.2. Source: UniProtKB

receptor binding

Inferred from physical interaction PubMed 20178365. Source: UniProtKB

very long-chain fatty acid-CoA ligase activity

Inferred from direct assay Ref.2Ref.8. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O14975-1)

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: O14975-2)

The sequence of this isoform differs from the canonical sequence as follows:
     230-282: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 620620Very long-chain acyl-CoA synthetase
PRO_0000193204

Regions

Topological domain1 – 44Lumenal Probable
Transmembrane5 – 2723Helical; Potential
Topological domain28 – 10679Cytoplasmic Potential
Transmembrane107 – 12721Helical; Potential
Topological domain128 – 261134Lumenal Potential
Transmembrane262 – 28221Helical; Potential
Topological domain283 – 620338Cytoplasmic Potential
Nucleotide binding222 – 23312AMP Potential

Amino acid modifications

Modified residue2911N6-acetyllysine By similarity
Modified residue5771Phosphothreonine Ref.10

Natural variations

Alternative sequence230 – 28253Missing in isoform 2.
VSP_042726
Natural variant481K → Q. Ref.1 Ref.2 Ref.3 Ref.6
Corresponds to variant rs1648348 [ dbSNP | Ensembl ].
VAR_046533

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 5, 2010. Version 2.
Checksum: 752E2FFBB2E47C26

FASTA62070,312
        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 

« Hide

Isoform 2 [UniParc].

Checksum: FF3A2B0FD68177B0
Show »

FASTA56764,616

References

« Hide '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] (ISOFORM 1), 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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), 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. expand/collapse author list , 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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), 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] (ISOFORM 1).
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. expand/collapse author list , 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] [Europe PMC] [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. expand/collapse author list , 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]"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] (ISOFORM 2).
Tissue: Placenta.
[8]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, TOPOLOGY.
[9]"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] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[10]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-577, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[11]"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] [Europe PMC] [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.
BC057770 mRNA. Translation: AAH57770.1.
CCDSCCDS10133.1. [O14975-1]
CCDS53943.1. [O14975-2]
RefSeqNP_001153101.1. NM_001159629.1. [O14975-2]
NP_003636.2. NM_003645.3. [O14975-1]
UniGeneHs.11729.

3D structure databases

ProteinModelPortalO14975.
SMRO14975. Positions 60-555.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid116194. 8 interactions.
IntActO14975. 2 interactions.
MINTMINT-2998454.
STRING9606.ENSP00000267842.

Chemistry

ChEMBLCHEMBL4326.

Protein family/group databases

TCDB4.C.1.1.5. the proposed fatty acid transporter (fat) family.

PTM databases

PhosphoSiteO14975.

Proteomic databases

MaxQBO14975.
PaxDbO14975.
PRIDEO14975.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000267842; ENSP00000267842; ENSG00000140284. [O14975-1]
ENST00000380902; ENSP00000370289; ENSG00000140284. [O14975-2]
GeneID11001.
KEGGhsa:11001.
UCSCuc001zxw.3. human. [O14975-1]
uc010bes.3. human. [O14975-2]

Organism-specific databases

CTD11001.
GeneCardsGC15P050474.
HGNCHGNC:10996. SLC27A2.
HPAHPA026089.
MIM603247. gene.
neXtProtNX_O14975.
PharmGKBPA27971.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0318.
HOGENOMHOG000044189.
HOVERGENHBG005642.
InParanoidO14975.
KOK08746.
OMAIPMTEDI.
OrthoDBEOG7W6WKB.
PhylomeDBO14975.
TreeFamTF313430.

Enzyme and pathway databases

BioCycMetaCyc:HS06695-MONOMER.
ReactomeREACT_111217. Metabolism.

Gene expression databases

ArrayExpressO14975.
BgeeO14975.
CleanExHS_SLC27A2.
GenevestigatorO14975.

Family and domain databases

InterProIPR025110. AMP-bd_C.
IPR020845. AMP-binding_CS.
IPR000873. AMP-dep_Synth/Lig.
[Graphical view]
PfamPF00501. AMP-binding. 1 hit.
PF13193. AMP-binding_C. 1 hit.
[Graphical view]
PROSITEPS00455. AMP_BINDING. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSSLC27A2. human.
GeneWikiSLC27A2.
GenomeRNAi11001.
NextBio41795.
PROO14975.
SOURCESearch...

Entry information

Entry nameS27A2_HUMAN
AccessionPrimary (citable) accession number: O14975
Secondary accession number(s): A8K2J7, Q53FY6, Q6PF09
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: October 5, 2010
Last modified: July 9, 2014
This is version 122 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 15

Human chromosome 15: entries, gene names and cross-references to MIM