ID APOM_HUMAN Reviewed; 188 AA. AC O95445; B0UX98; Q5SRP4; Q9P046; Q9UMP6; DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-2000, sequence version 2. DT 13-FEB-2019, entry version 166. DE RecName: Full=Apolipoprotein M; DE Short=Apo-M; DE Short=ApoM; DE AltName: Full=Protein G3a; GN Name=APOM; Synonyms=G3A, NG20; ORFNames=HSPC336; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND PROTEIN SEQUENCE OF 1-15. RC TISSUE=Liver; RX PubMed=10531326; DOI=10.1074/jbc.274.44.31286; RA Xu N., Dahlbaeck B.; RT "A novel human apolipoprotein (apoM)."; RL J. Biol. Chem. 274:31286-31290(1999). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RA Thomson W., Campbell R.D.; RT "Characterisation of the novel gene G3a located in the class III RT region of the human major histocompatibility complex."; RL Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Umbilical cord blood; RA Ye M., Zhang Q.-H., Zhou J., Shen Y., Wu X.-Y., Guan Z.Q., Wang L., RA Fan H.-Y., Mao Y.-F., Dai M., Huang Q.-H., Chen S.-J., Chen Z.; RT "Human partial CDS from CD34+ stem cells."; RL Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Shiina S., Tamiya G., Oka A., Inoko H.; RT "Homo sapiens 2,229,817bp genomic DNA of 6p21.3 HLA class I region."; RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=14656967; DOI=10.1101/gr.1736803; RA Xie T., Rowen L., Aguado B., Ahearn M.E., Madan A., Qin S., RA Campbell R.D., Hood L.; RT "Analysis of the gene-dense major histocompatibility complex class III RT region and its comparison to mouse."; RL Genome Res. 13:2621-2636(2003). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Embryonic stem cell; RX PubMed=15146197; DOI=10.1038/nbt971; RA Brandenberger R., Wei H., Zhang S., Lei S., Murage J., Fisk G.J., RA Li Y., Xu C., Fang R., Guegler K., Rao M.S., Mandalam R., RA Lebkowski J., Stanton L.W.; RT "Transcriptome characterization elucidates signaling networks that RT control human ES cell growth and differentiation."; RL Nat. Biotechnol. 22:707-716(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=14574404; DOI=10.1038/nature02055; RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., RA Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., RA Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S., RA Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., RA Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., RA Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., RA Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., RA Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., RA Frankland J., French L., Garner P., Garnett J., Ghori M.J., RA Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., RA Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., RA Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., RA Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., RA Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., RA Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., RA Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., RA McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., RA Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., RA Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., RA Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., RA Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., RA Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., RA Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., RA Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., RA Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., RA Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., RA Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.; RT "The DNA sequence and analysis of human chromosome 6."; RL Nature 425:805-811(2003). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Liver; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [10] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-135. RC TISSUE=Plasma; RX PubMed=16335952; DOI=10.1021/pr0502065; RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., RA Moore R.J., Smith R.D.; RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction, RT hydrazide chemistry, and mass spectrometry."; RL J. Proteome Res. 4:2070-2080(2005). RN [11] RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF GLN-22. RX PubMed=17525477; DOI=10.1194/jlr.M700103-JLR200; RA Ahnstrom J., Faber K., Axler O., Dahlback B.; RT "Hydrophobic ligand binding properties of the human lipocalin RT apolipoprotein M."; RL J. Lipid Res. 48:1754-1762(2007). RN [12] RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF GLN-22. RX PubMed=18279674; DOI=10.1016/j.febslet.2008.02.007; RA Axler O., Ahnstrom J., Dahlback B.; RT "Apolipoprotein M associates to lipoproteins through its retained RT signal peptide."; RL FEBS Lett. 582:826-828(2008). RN [13] RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF GLN-22. RX PubMed=18460466; DOI=10.1074/jbc.M800695200; RA Christoffersen C., Ahnstrom J., Axler O., Christensen E.I., RA Dahlback B., Nielsen L.B.; RT "The signal peptide anchors apolipoprotein M in plasma lipoproteins RT and prevents rapid clearance of apolipoprotein M from plasma."; RL J. Biol. Chem. 283:18765-18772(2008). RN [14] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-135. RC TISSUE=Liver; RX PubMed=19159218; DOI=10.1021/pr8008012; RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.; RT "Glycoproteomics analysis of human liver tissue by combination of RT multiple enzyme digestion and hydrazide chemistry."; RL J. Proteome Res. 8:651-661(2009). RN [15] 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., RA Buerckstuemmer T., 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 [16] RP 3D-STRUCTURE MODELING, AND MUTAGENESIS. RX PubMed=11418126; DOI=10.1016/S0014-5793(01)02544-3; RA Duan J., Dahlbaeck B., Villoutreix B.O.; RT "Proposed lipocalin fold for apolipoprotein M based on bioinformatics RT and site-directed mutagenesis."; RL FEBS Lett. 499:127-132(2001). RN [17] RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 22-188 IN COMPLEX WITH FATTY RP ACIDS, DISULFIDE BONDS, AND FUNCTION. RX PubMed=19733574; DOI=10.1016/j.jmb.2009.08.071; RA Sevvana M., Ahnstrom J., Egerer-Sieber C., Lange H.A., Dahlback B., RA Muller Y.A.; RT "Serendipitous fatty acid binding reveals the structural determinants RT for ligand recognition in apolipoprotein M."; RL J. Mol. Biol. 393:920-936(2009). CC -!- FUNCTION: Probably involved in lipid transport. Can bind CC sphingosine-1-phosphate, myristic acid, palmitic acid and stearic CC acid, retinol, all-trans-retinoic acid and 9-cis-retinoic acid. CC {ECO:0000269|PubMed:17525477, ECO:0000269|PubMed:19733574}. CC -!- SUBUNIT: Interacts with LRP2; LRP2 mediates APOM renal uptake and CC subsequent lysosomal degradation. {ECO:0000250|UniProtKB:Q9Z1R3}. CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:17525477, CC ECO:0000269|PubMed:18279674, ECO:0000269|PubMed:18460466}. CC Note=Present in high density lipoprotein (HDL) and to a lesser CC extent in triglyceride-rich lipoproteins (TGRLP) and low density CC lipoproteins (LDL). CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O95445-1; Sequence=Displayed; CC Name=2; CC IsoId=O95445-2; Sequence=VSP_045586; CC Note=No experimental confirmation available.; CC -!- TISSUE SPECIFICITY: Plasma protein. Expressed in liver and kidney. CC -!- SIMILARITY: Belongs to the calycin superfamily. Lipocalin family. CC Highly divergent. {ECO:0000305}. 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; AF118393; AAD11443.2; -; mRNA. DR EMBL; AJ245434; CAB51604.1; -; mRNA. DR EMBL; AF161454; AAF29014.1; -; mRNA. DR EMBL; AF129756; AAD18084.1; -; Genomic_DNA. DR EMBL; CN428415; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; BA000025; BAB63389.1; -; Genomic_DNA. DR EMBL; AL662801; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL670886; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL805934; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BX511262; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CR753842; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CR354443; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CR759761; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471081; EAX03461.1; -; Genomic_DNA. DR EMBL; CH471081; EAX03463.1; -; Genomic_DNA. DR EMBL; BC020683; AAH20683.1; -; mRNA. DR CCDS; CCDS4710.1; -. [O95445-1] DR CCDS; CCDS59004.1; -. [O95445-2] DR RefSeq; NP_001243098.1; NM_001256169.1. [O95445-2] DR RefSeq; NP_061974.2; NM_019101.2. [O95445-1] DR UniGene; Hs.534468; -. DR PDB; 2WEW; X-ray; 1.95 A; A=22-188. DR PDB; 2WEX; X-ray; 2.00 A; A=22-188. DR PDB; 2YG2; X-ray; 1.70 A; A/B=22-188. DR PDBsum; 2WEW; -. DR PDBsum; 2WEX; -. DR PDBsum; 2YG2; -. DR ProteinModelPortal; O95445; -. DR SMR; O95445; -. DR BioGrid; 121006; 7. DR IntAct; O95445; 2. DR STRING; 9606.ENSP00000365081; -. DR DrugBank; DB08231; MYRISTIC ACID. DR GlyConnect; 1015; -. DR iPTMnet; O95445; -. DR PhosphoSitePlus; O95445; -. DR BioMuta; APOM; -. DR jPOST; O95445; -. DR MaxQB; O95445; -. DR PaxDb; O95445; -. DR PeptideAtlas; O95445; -. DR PRIDE; O95445; -. DR ProteomicsDB; 50881; -. DR DNASU; 55937; -. DR Ensembl; ENST00000375916; ENSP00000365081; ENSG00000204444. [O95445-1] DR Ensembl; ENST00000375920; ENSP00000365085; ENSG00000204444. [O95445-2] DR Ensembl; ENST00000383438; ENSP00000372930; ENSG00000206409. [O95445-1] DR Ensembl; ENST00000400157; ENSP00000383021; ENSG00000206409. [O95445-2] DR Ensembl; ENST00000416324; ENSP00000393581; ENSG00000224290. [O95445-2] DR Ensembl; ENST00000422771; ENSP00000392021; ENSG00000226215. [O95445-2] DR Ensembl; ENST00000425177; ENSP00000403062; ENSG00000235754. [O95445-2] DR Ensembl; ENST00000426800; ENSP00000405730; ENSG00000227567. [O95445-1] DR Ensembl; ENST00000430282; ENSP00000401684; ENSG00000224290. [O95445-1] DR Ensembl; ENST00000432598; ENSP00000389591; ENSG00000235754. [O95445-1] DR Ensembl; ENST00000436931; ENSP00000394610; ENSG00000231974. [O95445-1] DR Ensembl; ENST00000439902; ENSP00000413446; ENSG00000227567. [O95445-2] DR Ensembl; ENST00000441436; ENSP00000398944; ENSG00000226215. [O95445-1] DR Ensembl; ENST00000443975; ENSP00000416335; ENSG00000231974. [O95445-2] DR GeneID; 55937; -. DR KEGG; hsa:55937; -. DR UCSC; uc003nvk.5; human. [O95445-1] DR CTD; 55937; -. DR DisGeNET; 55937; -. DR EuPathDB; HostDB:ENSG00000204444.10; -. DR GeneCards; APOM; -. DR HGNC; HGNC:13916; APOM. DR HPA; CAB034086; -. DR HPA; HPA051006; -. DR MIM; 606907; gene. DR neXtProt; NX_O95445; -. DR OpenTargets; ENSG00000204444; -. DR PharmGKB; PA38370; -. DR eggNOG; ENOG410IG6S; Eukaryota. DR eggNOG; ENOG4111Z0U; LUCA. DR GeneTree; ENSGT00390000001026; -. DR HOGENOM; HOG000034009; -. DR HOVERGEN; HBG057947; -. DR InParanoid; O95445; -. DR OMA; FPEPHLG; -. DR OrthoDB; 1302737at2759; -. DR PhylomeDB; O95445; -. DR TreeFam; TF330771; -. DR Reactome; R-HSA-975634; Retinoid metabolism and transport. DR ChiTaRS; APOM; human. DR EvolutionaryTrace; O95445; -. DR GeneWiki; APOM; -. DR GenomeRNAi; 55937; -. DR PRO; PR:O95445; -. DR Proteomes; UP000005640; Chromosome 6. DR Bgee; ENSG00000204444; Expressed in 159 organ(s), highest expression level in liver. DR ExpressionAtlas; O95445; baseline and differential. DR Genevisible; O95445; HS. DR GO; GO:0034365; C:discoidal high-density lipoprotein particle; IDA:BHF-UCL. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0034364; C:high-density lipoprotein particle; IDA:BHF-UCL. DR GO; GO:0034362; C:low-density lipoprotein particle; IDA:BHF-UCL. DR GO; GO:0034366; C:spherical high-density lipoprotein particle; IDA:BHF-UCL. DR GO; GO:0034361; C:very-low-density lipoprotein particle; IDA:BHF-UCL. DR GO; GO:0016209; F:antioxidant activity; IDA:BHF-UCL. DR GO; GO:0005319; F:lipid transporter activity; IDA:BHF-UCL. DR GO; GO:0005543; F:phospholipid binding; IDA:BHF-UCL. DR GO; GO:0033344; P:cholesterol efflux; IDA:BHF-UCL. DR GO; GO:0042632; P:cholesterol homeostasis; IC:BHF-UCL. DR GO; GO:0034380; P:high-density lipoprotein particle assembly; ISS:BHF-UCL. DR GO; GO:0034384; P:high-density lipoprotein particle clearance; ISS:BHF-UCL. DR GO; GO:0034375; P:high-density lipoprotein particle remodeling; IMP:BHF-UCL. DR GO; GO:0042157; P:lipoprotein metabolic process; IEA:Ensembl. DR GO; GO:0034445; P:negative regulation of plasma lipoprotein oxidation; IDA:BHF-UCL. DR GO; GO:0009749; P:response to glucose; IEA:Ensembl. DR GO; GO:0001523; P:retinoid metabolic process; TAS:Reactome. DR GO; GO:0043691; P:reverse cholesterol transport; ISS:BHF-UCL. DR Gene3D; 2.40.128.20; -; 1. DR InterPro; IPR022734; ApoM. DR InterPro; IPR012674; Calycin. DR PANTHER; PTHR32028; PTHR32028; 1. DR Pfam; PF11032; ApoM; 1. DR SUPFAM; SSF50814; SSF50814; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Complete proteome; KW Direct protein sequencing; Disulfide bond; Glycoprotein; HDL; KW Lipid transport; Reference proteome; Secreted; Signal; Transport. FT CHAIN 1 188 Apolipoprotein M. FT /FTId=PRO_0000223278. FT SIGNAL 1 ?22 Not cleaved. FT BINDING 136 136 Fatty acid. FT BINDING 143 143 Fatty acid. FT CARBOHYD 135 135 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:16335952, FT ECO:0000269|PubMed:19159218}. FT DISULFID 23 167 {ECO:0000269|PubMed:19733574}. FT DISULFID 95 183 {ECO:0000269|PubMed:19733574}. FT DISULFID 128 157 {ECO:0000269|PubMed:19733574}. FT VAR_SEQ 1 72 Missing (in isoform 2). FT {ECO:0000303|PubMed:15146197}. FT /FTId=VSP_045586. FT MUTAGEN 22 22 Q->A: Introduces a signal cleavage site. FT Abolishes interaction with lipoprotein FT particles. Leads to rapid elimination FT from plasma. FT {ECO:0000269|PubMed:17525477, FT ECO:0000269|PubMed:18279674, FT ECO:0000269|PubMed:18460466}. FT MUTAGEN 135 135 N->Q: Loss of glycosylation. FT {ECO:0000269|PubMed:11418126}. FT MUTAGEN 148 148 N->Q: No loss of glycosylation. FT {ECO:0000269|PubMed:11418126}. FT CONFLICT 1 38 MFHQIWAALLYFYGIILNSIYQCPEHSQLTTLGVDGKE -> FT RFPDSIWGSRSDTSGSPQVPKLYFCGARRESPQPQT (in FT Ref. 3; AAF29014). {ECO:0000305}. FT CONFLICT 175 188 LTPRNQEACELSNN -> VDS (in Ref. 2; FT CAB51604). {ECO:0000305}. FT HELIX 36 38 {ECO:0000244|PDB:2WEW}. FT HELIX 39 42 {ECO:0000244|PDB:2YG2}. FT STRAND 45 56 {ECO:0000244|PDB:2YG2}. FT HELIX 57 63 {ECO:0000244|PDB:2YG2}. FT STRAND 66 75 {ECO:0000244|PDB:2YG2}. FT STRAND 81 90 {ECO:0000244|PDB:2YG2}. FT STRAND 95 104 {ECO:0000244|PDB:2YG2}. FT STRAND 111 113 {ECO:0000244|PDB:2YG2}. FT STRAND 116 124 {ECO:0000244|PDB:2YG2}. FT STRAND 131 138 {ECO:0000244|PDB:2YG2}. FT STRAND 141 152 {ECO:0000244|PDB:2YG2}. FT HELIX 155 167 {ECO:0000244|PDB:2YG2}. FT STRAND 172 175 {ECO:0000244|PDB:2YG2}. SQ SEQUENCE 188 AA; 21253 MW; E4C35FEC32B7CB86 CRC64; MFHQIWAALL YFYGIILNSI YQCPEHSQLT TLGVDGKEFP EVHLGQWYFI AGAAPTKEEL ATFDPVDNIV FNMAAGSAPM QLHLRATIRM KDGLCVPRKW IYHLTEGSTD LRTEGRPDMK TELFSSSCPG GIMLNETGQG YQRFLLYNRS PHPPEKCVEE FKSLTSCLDS KAFLLTPRNQ EACELSNN //