ID ACBD6_HUMAN Reviewed; 282 AA. AC Q9BR61; DT 18-APR-2006, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-2001, sequence version 1. DT 28-JAN-2026, entry version 182. DE RecName: Full=Acyl-CoA-binding domain-containing protein 6; GN Name=ACBD6; 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 [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Lung; 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 [3] RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=18268358; DOI=10.1194/jlr.m800007-jlr200; RA Soupene E., Serikov V., Kuypers F.A.; RT "Characterization of an acyl-coenzyme A binding protein predominantly RT expressed in human primitive progenitor cells."; RL J. Lipid Res. 49:1103-1112(2008). RN [4] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [5] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-106, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [6] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [7] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and 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 [8] RP INVOLVEMENT IN NEDPM. RX PubMed=36457943; DOI=10.1212/nxg.0000000000200046; RA Yeetong P., Tanpowpong N., Rakwongkhachon S., Suphapeetiporn K., RA Shotelersuk V.; RT "Neurodevelopmental Disorder, Obesity, Pancytopenia, Diabetes Mellitus, RT Cirrhosis, and Renal Failure in ACBD6-Associated Syndrome: A Case Report."; RL Neurol. Genet. 9:e200046-e200046(2023). RN [9] RP STRUCTURE BY NMR OF 42-137. RG RIKEN structural genomics initiative (RSGI); RT "Solution structure of RSGI RUH-040, an ACBP domain from human cDNA."; RL Submitted (NOV-2005) to the PDB data bank. RN [10] RP VARIANTS NEDPM 54-GLN--ALA-282 DEL; 63-GLU--ALA-282 DEL; 72-TYR--ALA-282 RP DEL; 73-LYS--ALA-282 DEL; 94-GLN--ALA-282 DEL; 180-SER--ALA-282 DEL; RP 198-TRP--ALA-282 DEL; GLY-201; ASN-219 INS AND 254-ARG--ALA-282 DEL, RP INVOLVEMENT IN NEDPM, SUBCELLULAR LOCATION, AND FUNCTION. RX PubMed=37951597; DOI=10.1093/brain/awad380; RA Kaiyrzhanov R., Rad A., Lin S.J., Bertoli-Avella A., Kallemeijn W.W., RA Godwin A., Zaki M.S., Huang K., Lau T., Petree C., Efthymiou S., RA Karimiani E.G., Hempel M., Normand E.A., Rudnik-Schoeneborn S., RA Schatz U.A., Baggelaar M.P., Ilyas M., Sultan T., Alvi J.R., Ganieva M., RA Fowler B., Aanicai R., Tayfun G.A., Al Saman A., Alswaid A., Amiri N., RA Asilova N., Shotelersuk V., Yeetong P., Azam M., Babaei M., Monajemi G.B., RA Mohammadi P., Samie S., Banu S.H., Pinto Basto J., Kortuem F., Bauer M., RA Bauer P., Beetz C., Garshasbi M., Issa A.H., Eyaid W., Ahmed H., RA Hashemi N., Hassanpour K., Herman I., Ibrohimov S., Abdul-Majeed B.A., RA Imdad M., Isrofilov M., Kaiyal Q., Khan S., Kirmse B., Koster J., RA Lourenco C.M., Mitani T., Moldovan O., Murphy D., Najafi M., Pehlivan D., RA Rocha M.E., Salpietro V., Schmidts M., Shalata A., Mahroum M., RA Talbeya J.K., Taylor R.W., Vazquez D., Vetro A., Waterham H.R., Zaman M., RA Schrader T.A., Chung W.K., Guerrini R., Lupski J.R., Gleeson J., Suri M., RA Jamshidi Y., Bhatia K.P., Vona B., Schrader M., Severino M., Guille M., RA Tate E.W., Varshney G.K., Houlden H., Maroofian R.; RT "Bi-allelic ACBD6 variants lead to a neurodevelopmental syndrome with RT progressive and complex movement disorders."; RL Brain 147:1436-1456(2024). CC -!- FUNCTION: Binds long-chain acyl-coenzyme A molecules with a strong CC preference for unsaturated C18:1-CoA, lower affinity for unsaturated CC C20:4-CoA, and very weak affinity for saturated C16:0-CoA. Does not CC bind fatty acids. Plays a role in protein N-myristoylation CC (PubMed:37951597). {ECO:0000269|PubMed:18268358, CC ECO:0000269|PubMed:37951597}. CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:18268358}. CC -!- INTERACTION: CC Q9BR61; P30419: NMT1; NbExp=7; IntAct=EBI-2848793, EBI-5280164; CC Q9BR61; O60551: NMT2; NbExp=18; IntAct=EBI-2848793, EBI-3920273; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:18268358, CC ECO:0000269|PubMed:37951597}. Nucleus {ECO:0000269|PubMed:37951597}. CC -!- TISSUE SPECIFICITY: Detected in placenta and spleen (at protein level). CC Detected in placenta, umbilical cord blood, CD34-positive hematopoietic CC progenitor cells and bone marrow. {ECO:0000269|PubMed:18268358}. CC -!- DISEASE: Neurodevelopmental disorder with progressive movement CC abnormalities (NEDPM) [MIM:620785]: An autosomal recessive, progressive CC disorder characterized by global developmental delay, intellectual CC disability, significant expressive language impairment, behavioral CC abnormalities, and movement disorders including dystonia, spasticity CC and cerebellar ataxia associated with gait impairment. Additional CC features include facial dysmorphism, oculomotor anomalies, CC microcephaly, seizures and brain imaging abnormalities. Parkinsonism CC may develop in older patients. {ECO:0000269|PubMed:36457943, CC ECO:0000269|PubMed:37951597}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AL445469; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL139141; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL358354; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC006505; AAH06505.1; -; mRNA. DR CCDS; CCDS1339.1; -. DR RefSeq; NP_115736.1; NM_032360.4. DR RefSeq; XP_047288036.1; XM_047432080.1. DR RefSeq; XP_047288037.1; XM_047432081.1. DR RefSeq; XP_047288038.1; XM_047432082.1. DR RefSeq; XP_047288039.1; XM_047432083.1. DR RefSeq; XP_047288040.1; XM_047432084.1. DR RefSeq; XP_047288041.1; XM_047432085.1. DR RefSeq; XP_054195160.1; XM_054339185.1. DR RefSeq; XP_054195161.1; XM_054339186.1. DR RefSeq; XP_054195162.1; XM_054339187.1. DR RefSeq; XP_054195163.1; XM_054339188.1. DR RefSeq; XP_054195164.1; XM_054339189.1. DR RefSeq; XP_054195165.1; XM_054339190.1. DR PDB; 2COP; NMR; -; A=42-137. DR PDBsum; 2COP; -. DR AlphaFoldDB; Q9BR61; -. DR SMR; Q9BR61; -. DR BioGRID; 124046; 20. DR FunCoup; Q9BR61; 1398. DR IntAct; Q9BR61; 20. DR STRING; 9606.ENSP00000495710; -. DR iPTMnet; Q9BR61; -. DR MetOSite; Q9BR61; -. DR PhosphoSitePlus; Q9BR61; -. DR BioMuta; ACBD6; -. DR DMDM; 74762703; -. DR jPOST; Q9BR61; -. DR MassIVE; Q9BR61; -. DR PaxDb; 9606-ENSP00000356567; -. DR PeptideAtlas; Q9BR61; -. DR ProteomicsDB; 78745; -. DR Pumba; Q9BR61; -. DR Antibodypedia; 72484; 198 antibodies from 28 providers. DR DNASU; 84320; -. DR Ensembl; ENST00000367595.4; ENSP00000356567.3; ENSG00000230124.9. DR Ensembl; ENST00000642319.1; ENSP00000495710.1; ENSG00000230124.9. DR GeneID; 84320; -. DR KEGG; hsa:84320; -. DR MANE-Select; ENST00000367595.4; ENSP00000356567.3; NM_032360.4; NP_115736.1. DR UCSC; uc001gog.4; human. DR AGR; HGNC:23339; -. DR ClinPGx; PA134925459; -. DR CTD; 84320; -. DR DisGeNET; 84320; -. DR GeneCards; ACBD6; -. DR HGNC; HGNC:23339; ACBD6. DR HPA; ENSG00000230124; Low tissue specificity. DR MalaCards; ACBD6; -. DR MIM; 616352; gene. DR MIM; 620785; phenotype. DR OpenTargets; ENSG00000230124; -. DR VEuPathDB; HostDB:ENSG00000230124; -. DR eggNOG; KOG0817; Eukaryota. DR GeneTree; ENSGT00940000157458; -. DR HOGENOM; CLU_050309_1_0_1; -. DR InParanoid; Q9BR61; -. DR OMA; ARSKWQA; -. DR OrthoDB; 10254927at2759; -. DR PAN-GO; Q9BR61; 1 GO annotation based on evolutionary models. DR PhylomeDB; Q9BR61; -. DR PathwayCommons; Q9BR61; -. DR Reactome; R-HSA-77289; Mitochondrial Fatty Acid Beta-Oxidation. DR SignaLink; Q9BR61; -. DR Agora; ENSG00000230124; -. DR BioGRID-ORCS; 84320; 15 hits in 1158 CRISPR screens. DR ChiTaRS; ACBD6; human. DR EvolutionaryTrace; Q9BR61; -. DR GenomeRNAi; 84320; -. DR Pharos; Q9BR61; Tbio. DR PRO; PR:Q9BR61; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q9BR61; protein. DR Bgee; ENSG00000230124; Expressed in cortical plate and 162 other cell types or tissues. DR ExpressionAtlas; Q9BR61; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0000062; F:fatty-acyl-CoA binding; IMP:UniProtKB. DR GO; GO:0008289; F:lipid binding; IMP:UniProtKB. DR FunFam; 1.20.80.10:FF:000022; acyl-CoA-binding domain-containing protein 6 isoform X1; 1. DR FunFam; 1.25.40.20:FF:000252; acyl-CoA-binding domain-containing protein 6 isoform X2; 1. DR Gene3D; 1.20.80.10; -; 1. DR Gene3D; 1.25.40.20; Ankyrin repeat-containing domain; 2. DR InterPro; IPR000582; Acyl-CoA-binding_protein. DR InterPro; IPR035984; Acyl-CoA-binding_sf. DR InterPro; IPR002110; Ankyrin_rpt. DR InterPro; IPR036770; Ankyrin_rpt-contain_sf. DR InterPro; IPR014352; FERM/acyl-CoA-bd_prot_sf. DR PANTHER; PTHR24119; ACYL-COA-BINDING DOMAIN-CONTAINING PROTEIN 6; 1. DR PANTHER; PTHR24119:SF0; ACYL-COA-BINDING DOMAIN-CONTAINING PROTEIN 6; 1. DR Pfam; PF00887; ACBP; 1. DR Pfam; PF12796; Ank_2; 1. DR PRINTS; PR00689; ACOABINDINGP. DR PRINTS; PR01415; ANKYRIN. DR SMART; SM00248; ANK; 2. DR SUPFAM; SSF47027; Acyl-CoA binding protein; 1. DR SUPFAM; SSF48403; Ankyrin repeat; 1. DR PROSITE; PS51228; ACB_2; 1. DR PROSITE; PS50297; ANK_REP_REGION; 1. DR PROSITE; PS50088; ANK_REPEAT; 2. PE 1: Evidence at protein level; KW 3D-structure; ANK repeat; Autism spectrum disorder; Cytoplasm; KW Disease variant; Dystonia; Intellectual disability; Lipid-binding; Nucleus; KW Parkinsonism; Phosphoprotein; Proteomics identification; KW Reference proteome; Repeat. FT CHAIN 1..282 FT /note="Acyl-CoA-binding domain-containing protein 6" FT /id="PRO_0000232879" FT DOMAIN 42..127 FT /note="ACB" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00573" FT REPEAT 191..220 FT /note="ANK 1" FT REPEAT 224..253 FT /note="ANK 2" FT REGION 1..31 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 69..73 FT /ligand="an acyl-CoA" FT /ligand_id="ChEBI:CHEBI:58342" FT /evidence="ECO:0000250" FT BINDING 95 FT /ligand="an acyl-CoA" FT /ligand_id="ChEBI:CHEBI:58342" FT /evidence="ECO:0000250" FT BINDING 114 FT /ligand="an acyl-CoA" FT /ligand_id="ChEBI:CHEBI:58342" FT /evidence="ECO:0000250" FT MOD_RES 106 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231" FT VARIANT 54..282 FT /note="Missing (in NEDPM; pathogenic)" FT /evidence="ECO:0000269|PubMed:37951597" FT /id="VAR_089637" FT VARIANT 63..282 FT /note="Missing (in NEDPM; pathogenic)" FT /evidence="ECO:0000269|PubMed:37951597" FT /id="VAR_089638" FT VARIANT 72..282 FT /note="Missing (in NEDPM; pathogenic)" FT /evidence="ECO:0000269|PubMed:37951597" FT /id="VAR_089639" FT VARIANT 73..282 FT /note="Missing (in NEDPM; pathogenic)" FT /evidence="ECO:0000269|PubMed:37951597" FT /id="VAR_089640" FT VARIANT 94..282 FT /note="Missing (in NEDPM; pathogenic)" FT /evidence="ECO:0000269|PubMed:37951597" FT /id="VAR_089641" FT VARIANT 180..282 FT /note="Missing (in NEDPM; likely pathogenic)" FT /evidence="ECO:0000269|PubMed:37951597" FT /id="VAR_089642" FT VARIANT 198..282 FT /note="Missing (in NEDPM; likely pathogenic)" FT /evidence="ECO:0000269|PubMed:37951597" FT /id="VAR_089643" FT VARIANT 201 FT /note="D -> G (in NEDPM; uncertain significance)" FT /evidence="ECO:0000269|PubMed:37951597" FT /id="VAR_089644" FT VARIANT 219 FT /note="N -> NN (in NEDPM; uncertain significance)" FT /evidence="ECO:0000269|PubMed:37951597" FT /id="VAR_089645" FT VARIANT 254..282 FT /note="Missing (in NEDPM; uncertain significance)" FT /evidence="ECO:0000269|PubMed:37951597" FT /id="VAR_089646" FT HELIX 43..53 FT /evidence="ECO:0007829|PDB:2COP" FT TURN 57..59 FT /evidence="ECO:0007829|PDB:2COP" FT HELIX 62..76 FT /evidence="ECO:0007829|PDB:2COP" FT HELIX 90..100 FT /evidence="ECO:0007829|PDB:2COP" FT HELIX 107..121 FT /evidence="ECO:0007829|PDB:2COP" SQ SEQUENCE 282 AA; 31151 MW; 0EA01CFDB5C5ECB2 CRC64; MASSFLPAGA ITGDSGGELS SGDDSGEVEF PHSPEIEETS CLAELFEKAA AHLQGLIQVA SREQLLYLYA RYKQVKVGNC NTPKPSFFDF EGKQKWEAWK ALGDSSPSQA MQEYIAVVKK LDPGWNPQIP EKKGKEANTG FGGPVISSLY HEETIREEDK NIFDYCRENN IDHITKAIKS KNVDVNVKDE EGRALLHWAC DRGHKELVTV LLQHRADINC QDNEGQTALH YASACEFLDI VELLLQSGAD PTLRDQDGCL PEEVTGCKTV SLVLQRHTTG KA //