ACATN_HUMAN
ID ACATN_HUMAN Reviewed; 549 AA.
AC O00400; B2R5Q2; D3DNK4;
DT 20-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=Acetyl-coenzyme A transporter 1;
DE Short=AT-1;
DE Short=Acetyl-CoA transporter 1;
DE AltName: Full=Solute carrier family 33 member 1;
GN Name=SLC33A1; Synonyms=ACATN, AT1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, AND SUBCELLULAR
RP LOCATION.
RC TISSUE=Melanoma;
RX PubMed=9096318; DOI=10.1073/pnas.94.7.2897;
RA Kanamori A., Nakayama J., Fukuda M.N., Stallcup W.B., Sasaki K., Fukuda M.,
RA Hirabayashi Y.;
RT "Expression cloning and characterization of a cDNA encoding a novel
RT membrane protein required for the formation of O-acetylated gangliosides: a
RT putative acetyl CoA transporter.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:2897-2902(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
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 [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-22, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [6]
RP FUNCTION, VARIANT SPG42 ARG-113, AND CHARACTERIZATION OF VARIANT SPG42
RP ARG-113.
RX PubMed=25402622; DOI=10.1002/humu.22732;
RA Mao F., Li Z., Zhao B., Lin P., Liu P., Zhai M., Liu Q., Shao C., Sun W.,
RA Gong Y.;
RT "Identification and Functional Analysis of a SLC33A1: c.339T>G
RT (p.Ser113Arg) Variant in the Original SPG42 Family.";
RL Hum. Mutat. 36:240-249(2015).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [8]
RP VARIANT [LARGE SCALE ANALYSIS] ALA-400.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [9]
RP VARIANT SPG42 ARG-113.
RX PubMed=19061983; DOI=10.1016/j.ajhg.2008.11.003;
RA Lin P., Li J., Liu Q., Mao F., Li J., Qiu R., Hu H., Song Y., Yang Y.,
RA Gao G., Yan C., Yang W., Shao C., Gong Y.;
RT "A missense mutation in SLC33A1, which encodes the acetyl-CoA transporter,
RT causes autosomal-dominant spastic paraplegia (SPG42).";
RL Am. J. Hum. Genet. 83:752-759(2008).
RN [10]
RP VARIANT CCHLND PRO-110, AND CHARACTERIZATION OF VARIANT CCHLND PRO-110.
RX PubMed=22243965; DOI=10.1016/j.ajhg.2011.11.030;
RA Huppke P., Brendel C., Kalscheuer V., Korenke G.C., Marquardt I.,
RA Freisinger P., Christodoulou J., Hillebrand M., Pitelet G., Wilson C.,
RA Gruber-Sedlmayr U., Ullmann R., Haas S., Elpeleg O., Nurnberg G.,
RA Nurnberg P., Dad S., Moller L.B., Kaler S.G., Gartner J.;
RT "Mutations in SLC33A1 cause a lethal autosomal-recessive disorder with
RT congenital cataracts, hearing loss, and low serum copper and
RT ceruloplasmin.";
RL Am. J. Hum. Genet. 90:61-68(2012).
RN [11]
RP ERRATUM OF PUBMED:22243965.
RA Huppke P., Brendel C., Kalscheuer V., Korenke G.C., Marquardt I.,
RA Freisinger P., Christodoulou J., Hillebrand M., Pitelet G., Wilson C.,
RA Gruber-Sedlmayr U., Ullmann R., Haas S., Elpeleg O., Nurnberg G.,
RA Nurnberg P., Dad S., Moller L.B., Kaler S.G., Gartner J.;
RL Am. J. Hum. Genet. 90:378-378(2012).
CC -!- FUNCTION: Probable acetyl-CoA transporter necessary for O-acetylation
CC of gangliosides (PubMed:9096318). Negatively regulates BMP signaling
CC (PubMed:25402622). {ECO:0000269|PubMed:25402622,
CC ECO:0000269|PubMed:9096318}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000305|PubMed:9096318}; Multi-pass membrane protein
CC {ECO:0000305|PubMed:9096318}.
CC -!- TISSUE SPECIFICITY: Ubiquitous. Detected in heart, brain, placenta,
CC lung, liver, skeletal muscle, kidney and pancreas. With strongest
CC signals in pancreas. {ECO:0000269|PubMed:9096318}.
CC -!- DISEASE: Spastic paraplegia 42, autosomal dominant (SPG42)
CC [MIM:612539]: A form of spastic paraplegia, a neurodegenerative
CC disorder characterized by a slow, gradual, progressive weakness and
CC spasticity of the lower limbs. Rate of progression and the severity of
CC symptoms are quite variable. Initial symptoms may include difficulty
CC with balance, weakness and stiffness in the legs, muscle spasms, and
CC dragging the toes when walking. In some forms of the disorder, bladder
CC symptoms (such as incontinence) may appear, or the weakness and
CC stiffness may spread to other parts of the body.
CC {ECO:0000269|PubMed:19061983, ECO:0000269|PubMed:25402622}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Congenital cataracts, hearing loss, and neurodegeneration
CC (CCHLND) [MIM:614482]: An autosomal recessive disorder characterized by
CC congenital cataracts, severe psychomotor retardation, and hearing loss
CC associated with decreased serum ceruloplasmin and copper. Brain MRI
CC shows cerebral and cerebellar atrophy and hypomyelination.
CC {ECO:0000269|PubMed:22243965}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the SLC33A transporter family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Mendelian genes solute carrier family 33 (acetyl-CoA
CC transporter), member 1 (SLC33A1); Note=Leiden Open Variation Database
CC (LOVD);
CC URL="https://databases.lovd.nl/shared/genes/SLC33A1";
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DR EMBL; D88152; BAA20072.1; -; mRNA.
DR EMBL; AK312268; BAG35199.1; -; mRNA.
DR EMBL; CH471052; EAW78743.1; -; Genomic_DNA.
DR EMBL; CH471052; EAW78744.1; -; Genomic_DNA.
DR EMBL; BC014416; AAH14416.1; -; mRNA.
DR CCDS; CCDS3173.1; -.
DR RefSeq; NP_001177921.1; NM_001190992.1.
DR RefSeq; NP_004724.1; NM_004733.3.
DR AlphaFoldDB; O00400; -.
DR BioGRID; 114632; 189.
DR IntAct; O00400; 67.
DR MINT; O00400; -.
DR STRING; 9606.ENSP00000376587; -.
DR BindingDB; O00400; -.
DR ChEMBL; CHEMBL3638338; -.
DR TCDB; 2.A.1.25.1; the major facilitator superfamily (mfs).
DR GlyConnect; 2835; 1 N-Linked glycan (1 site).
DR GlyGen; O00400; 1 site.
DR iPTMnet; O00400; -.
DR PhosphoSitePlus; O00400; -.
DR SwissPalm; O00400; -.
DR BioMuta; SLC33A1; -.
DR EPD; O00400; -.
DR jPOST; O00400; -.
DR MassIVE; O00400; -.
DR MaxQB; O00400; -.
DR PaxDb; O00400; -.
DR PeptideAtlas; O00400; -.
DR PRIDE; O00400; -.
DR ProteomicsDB; 47866; -.
DR Antibodypedia; 33630; 178 antibodies from 25 providers.
DR DNASU; 9197; -.
DR Ensembl; ENST00000359479.7; ENSP00000352456.3; ENSG00000169359.16.
DR Ensembl; ENST00000643144.2; ENSP00000496241.1; ENSG00000169359.16.
DR GeneID; 9197; -.
DR KEGG; hsa:9197; -.
DR MANE-Select; ENST00000643144.2; ENSP00000496241.1; NM_004733.4; NP_004724.1.
DR UCSC; uc003fan.6; human.
DR CTD; 9197; -.
DR DisGeNET; 9197; -.
DR GeneCards; SLC33A1; -.
DR GeneReviews; SLC33A1; -.
DR HGNC; HGNC:95; SLC33A1.
DR HPA; ENSG00000169359; Low tissue specificity.
DR MalaCards; SLC33A1; -.
DR MIM; 603690; gene.
DR MIM; 612539; phenotype.
DR MIM; 614482; phenotype.
DR neXtProt; NX_O00400; -.
DR OpenTargets; ENSG00000169359; -.
DR Orphanet; 171863; Autosomal dominant spastic paraplegia type 42.
DR Orphanet; 300313; Congenital cataract-hearing loss-severe developmental delay syndrome.
DR PharmGKB; PA24432; -.
DR VEuPathDB; HostDB:ENSG00000169359; -.
DR eggNOG; KOG3574; Eukaryota.
DR GeneTree; ENSGT00940000154019; -.
DR HOGENOM; CLU_020502_1_0_1; -.
DR InParanoid; O00400; -.
DR OMA; LWFWGIT; -.
DR OrthoDB; 1300300at2759; -.
DR PhylomeDB; O00400; -.
DR TreeFam; TF300008; -.
DR PathwayCommons; O00400; -.
DR Reactome; R-HSA-425397; Transport of vitamins, nucleosides, and related molecules.
DR Reactome; R-HSA-5619061; Defective SLC33A1 causes spastic paraplegia 42 (SPG42).
DR SignaLink; O00400; -.
DR BioGRID-ORCS; 9197; 88 hits in 1089 CRISPR screens.
DR ChiTaRS; SLC33A1; human.
DR GenomeRNAi; 9197; -.
DR Pharos; O00400; Tchem.
DR PRO; PR:O00400; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; O00400; protein.
DR Bgee; ENSG00000169359; Expressed in corpus epididymis and 196 other tissues.
DR ExpressionAtlas; O00400; baseline and differential.
DR Genevisible; O00400; HS.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:ProtInc.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0008521; F:acetyl-CoA transmembrane transporter activity; TAS:Reactome.
DR GO; GO:0015295; F:solute:proton symporter activity; IBA:GO_Central.
DR GO; GO:0030509; P:BMP signaling pathway; IDA:UniProtKB.
DR GO; GO:0060395; P:SMAD protein signal transduction; IDA:UniProtKB.
DR GO; GO:0055085; P:transmembrane transport; TAS:Reactome.
DR Gene3D; 1.20.1250.20; -; 1.
DR InterPro; IPR024371; AcetylCoA_trans_1-like.
DR InterPro; IPR004752; AmpG_permease/AT-1.
DR InterPro; IPR036259; MFS_trans_sf.
DR PANTHER; PTHR12778; PTHR12778; 1.
DR Pfam; PF13000; Acatn; 2.
DR SUPFAM; SSF103473; SSF103473; 1.
PE 1: Evidence at protein level;
KW Cataract; Deafness; Disease variant; Endoplasmic reticulum; Glycoprotein;
KW Hereditary spastic paraplegia; Membrane; Neurodegeneration; Phosphoprotein;
KW Reference proteome; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..549
FT /note="Acetyl-coenzyme A transporter 1"
FT /id="PRO_0000076165"
FT TOPO_DOM 1..74
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 75..95
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 96..113
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 114..134
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 135..141
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 142..162
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 163..175
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 176..196
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 197..217
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 218..238
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 239..256
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 257..277
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 278..299
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 300..320
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 321..343
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 344..364
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 365..378
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 379..398
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 399..404
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 405..425
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 426..508
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 509..529
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 530..549
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT REGION 1..46
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 22
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 42
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99J27"
FT CARBOHYD 103
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 110
FT /note="A -> P (in CCHLND; the mutant protein is present at
FT normal levels in patient fibroblasts; the mutant protein
FT fails to localize normally to the Golgi apparatus and
FT instead shows punctate staining in the cytoplasm;
FT dbSNP:rs281875283)"
FT /evidence="ECO:0000269|PubMed:22243965"
FT /id="VAR_067915"
FT VARIANT 113
FT /note="S -> R (in SPG42; significant increase in the amount
FT of nuclear phosphorylated SMAD1-SMAD5-SMAD8 protein
FT complex; marked increase of the BMPR1A protein level; no
FT change for BMPR2 protein level; decrease of BMPR1A
FT degradation; dbSNP:rs121909484)"
FT /evidence="ECO:0000269|PubMed:19061983,
FT ECO:0000269|PubMed:25402622"
FT /id="VAR_054850"
FT VARIANT 171
FT /note="D -> G (in dbSNP:rs3804769)"
FT /id="VAR_050631"
FT VARIANT 400
FT /note="V -> A (in a colorectal cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035776"
SQ SEQUENCE 549 AA; 60909 MW; ABDE59DEDEBAA9A5 CRC64;
MSPTISHKDS SRQRRPGNFS HSLDMKSGPL PPGGWDDSHL DSAGREGDRE ALLGDTGTGD
FLKAPQSFRA ELSSILLLLF LYVLQGIPLG LAGSIPLILQ SKNVSYTDQA FFSFVFWPFS
LKLLWAPLVD AVYVKNFGRR KSWLVPTQYI LGLFMIYLST QVDRLLGNTD DRTPDVIALT
VAFFLFEFLA ATQDIAVDGW ALTMLSRENV GYASTCNSVG QTAGYFLGNV LFLALESADF
CNKYLRFQPQ PRGIVTLSDF LFFWGTVFLI TTTLVALLKK ENEVSVVKEE TQGITDTYKL
LFAIIKMPAV LTFCLLILTA KIGFSAADAV TGLKLVEEGV PKEHLALLAV PMVPLQIILP
LIISKYTAGP QPLNTFYKAM PYRLLLGLEY ALLVWWTPKV EHQGGFPIYY YIVVLLSYAL
HQVTVYSMYV SIMAFNAKVS DPLIGGTYMT LLNTVSNLGG NWPSTVALWL VDPLTVKECV
GASNQNCRTP DAVELCKKLG GSCVTALDGY YVESIICVFI GFGWWFFLGP KFKKLQDEGS
SSWKCKRNN
