SAMD1_HUMAN
ID SAMD1_HUMAN Reviewed; 538 AA.
AC Q6SPF0; Q6P0R3; Q6PIS7; Q96IM4;
DT 06-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 25-MAY-2022, entry version 119.
DE RecName: Full=Sterile alpha motif domain-containing protein 1;
DE Short=SAM domain-containing protein 1;
DE AltName: Full=Atherin;
GN Name=SAMD1 {ECO:0000312|HGNC:HGNC:17958};
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], TISSUE SPECIFICITY, FUNCTION, AND SUBCELLULAR
RP LOCATION.
RC TISSUE=Aorta;
RX PubMed=16159594; DOI=10.1016/j.atherosclerosis.2005.01.041;
RA Lees A.M., Deconinck A.E., Campbell B.D., Lees R.S.;
RT "Atherin: a newly identified, lesion-specific, LDL-binding protein in human
RT atherosclerosis.";
RL Atherosclerosis 182:219-230(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 244-538.
RC TISSUE=Lung, Lymph, and Ovary;
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 [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-161, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-161, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-161 AND SER-261, AND
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 [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-161, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-161, 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 [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-107 AND SER-161, AND
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 [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-161, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [12]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=34006929; DOI=10.1038/s41598-021-89981-z;
RA Tian S., Cao Y., Wang J., Bi Y., Zhong J., Meng X., Sun W., Yang R.,
RA Gan L., Wang X., Li H., Wang R.;
RT "The miR-378c-Samd1 circuit promotes phenotypic modulation of vascular
RT smooth muscle cells and foam cells formation in atherosclerosis lesions.";
RL Sci. Rep. 11:10548-10548(2021).
RN [13] {ECO:0007744|PDB:6LUI, ECO:0007744|PDB:6LUJ, ECO:0007744|PDB:6LUK}
RP X-RAY CRYSTALLOGRAPHY (1.12 ANGSTROMS) OF 27-105 AND 459-526, DOMAIN,
RP MUTAGENESIS OF ARG-43; 45-ARG-LYS-46; ARG-48; 87-TYR-LYS-88; ARG-94 AND
RP 498-ARG--LYS-514, AND INTERACTION WITH KDM1A AND L3MBTL3.
RX PubMed=33980486; DOI=10.1126/sciadv.abf2229;
RA Stielow B., Zhou Y., Cao Y., Simon C., Pogoda H.M., Jiang J., Ren Y.,
RA Phanor S.K., Rohner I., Nist A., Stiewe T., Hammerschmidt M., Shi Y.,
RA Bulyk M.L., Wang Z., Liefke R.;
RT "The SAM domain-containing protein 1 (SAMD1) acts as a repressive chromatin
RT regulator at unmethylated CpG islands.";
RL Sci. Adv. 7:0-0(2021).
CC -!- FUNCTION: Unmethylated CpG islands (CGIs)-binding protein which
CC localizes to H3K4me3-decorated CGIs, where it acts as a transcriptional
CC repressor (PubMed:33980486). Tethers L3MBTL3 to chromatin and interacts
CC with the KDM1A histone demethylase complex to modulate H3K4me2 and
CC H3K4me3 levels at CGIs (PubMed:33980486). Plays a role in atherogenesis
CC by binding with LDL on cell surface and promoting LDL oxidation which
CC leads to the formation of foam cell (PubMed:16159594, PubMed:34006929).
CC {ECO:0000269|PubMed:16159594, ECO:0000269|PubMed:33980486,
CC ECO:0000269|PubMed:34006929}.
CC -!- SUBUNIT: Homopolymerize into a closed pentameric ring
CC (PubMed:33980486). Interacts (via SAM domain) with L3MBTL3 (via SAM
CC domain); the interaction mediates L3MBTL3 binding to chromatin
CC (PubMed:33980486). Interacts (via WH domain) with KDM1A; the
CC interaction modulates KDM1A function (PubMed:33980486).
CC {ECO:0000269|PubMed:33980486}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:34006929}. Chromosome
CC {ECO:0000269|PubMed:34006929}. Secreted {ECO:0000269|PubMed:16159594,
CC ECO:0000269|PubMed:34006929}. Note=In atherosclerotic lesions, it is
CC found in the extracellular compartment and in foam cells cytoplasm.
CC {ECO:0000269|PubMed:16159594, ECO:0000269|PubMed:34006929}.
CC -!- TISSUE SPECIFICITY: Expressed in atherosclerotic lesions, not in normal
CC intima. Expressed in foam cells. {ECO:0000269|PubMed:16159594}.
CC -!- INDUCTION: Expression is inhibited by miRNA MIR378C.
CC {ECO:0000269|PubMed:34006929}.
CC -!- DOMAIN: Winged-helix (WH) domain directly recognizes and binds
CC unmethylated CpG-containing DNA via simultaneous interactions with both
CC the major and the minor groove of DNA. {ECO:0000269|PubMed:34006929}.
CC -!- CAUTION: Due to its high GC content it turned out to be difficult to
CC sequence the 5' end of the gene encoding the N-terminal proline-rich
CC region of the protein and to unambiguously determine which sequence is
CC correct. We display the sequence described in PubMed:16159594. This
CC sequence fits better with orthologous sequences but is not consistent
CC with the human reference genome sequence. {ECO:0000305}.
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DR EMBL; AY453840; AAR24087.1; -; mRNA.
DR EMBL; AC022098; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC007384; AAH07384.2; -; mRNA.
DR EMBL; BC030129; AAH30129.1; -; mRNA.
DR EMBL; BC065477; AAH65477.1; -; mRNA.
DR EMBL; BC080588; AAH80588.1; -; mRNA.
DR RefSeq; NP_612361.1; NM_138352.2.
DR PDB; 6LUI; X-ray; 1.78 A; A=27-105.
DR PDB; 6LUJ; X-ray; 1.12 A; A/B/C/D/E=459-523.
DR PDB; 6LUK; X-ray; 2.05 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T=459-526.
DR PDBsum; 6LUI; -.
DR PDBsum; 6LUJ; -.
DR PDBsum; 6LUK; -.
DR AlphaFoldDB; Q6SPF0; -.
DR SMR; Q6SPF0; -.
DR BioGRID; 124704; 165.
DR IntAct; Q6SPF0; 56.
DR MINT; Q6SPF0; -.
DR iPTMnet; Q6SPF0; -.
DR PhosphoSitePlus; Q6SPF0; -.
DR BioMuta; SAMD1; -.
DR DMDM; 74749329; -.
DR EPD; Q6SPF0; -.
DR jPOST; Q6SPF0; -.
DR MassIVE; Q6SPF0; -.
DR MaxQB; Q6SPF0; -.
DR PaxDb; Q6SPF0; -.
DR PeptideAtlas; Q6SPF0; -.
DR PRIDE; Q6SPF0; -.
DR ProteomicsDB; 67359; -.
DR DNASU; 90378; -.
DR GeneID; 90378; -.
DR KEGG; hsa:90378; -.
DR CTD; 90378; -.
DR DisGeNET; 90378; -.
DR GeneCards; SAMD1; -.
DR HGNC; HGNC:17958; SAMD1.
DR neXtProt; NX_Q6SPF0; -.
DR PharmGKB; PA34937; -.
DR eggNOG; KOG2747; Eukaryota.
DR InParanoid; Q6SPF0; -.
DR OrthoDB; 619766at2759; -.
DR PathwayCommons; Q6SPF0; -.
DR SignaLink; Q6SPF0; -.
DR BioGRID-ORCS; 90378; 30 hits in 255 CRISPR screens.
DR ChiTaRS; SAMD1; human.
DR GenomeRNAi; 90378; -.
DR Pharos; Q6SPF0; Tdark.
DR PRO; PR:Q6SPF0; -.
DR Proteomes; UP000005640; Unplaced.
DR RNAct; Q6SPF0; protein.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB.
DR GO; GO:0042393; F:histone binding; IBA:GO_Central.
DR GO; GO:0030169; F:low-density lipoprotein particle binding; ISS:UniProtKB.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0090077; P:foam cell differentiation; ISS:UniProtKB.
DR GO; GO:0034439; P:lipoprotein lipid oxidation; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IBA:GO_Central.
DR GO; GO:0051260; P:protein homooligomerization; IDA:UniProtKB.
DR GO; GO:0090308; P:regulation of DNA methylation-dependent heterochromatin assembly; IDA:UniProtKB.
DR Gene3D; 1.10.150.50; -; 1.
DR InterPro; IPR001660; SAM.
DR InterPro; IPR013761; SAM/pointed_sf.
DR Pfam; PF00536; SAM_1; 1.
DR SMART; SM00454; SAM; 1.
DR SUPFAM; SSF47769; SSF47769; 1.
DR PROSITE; PS50105; SAM_DOMAIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Chromatin regulator; Chromosome; Nucleus; Phosphoprotein;
KW Reference proteome; Secreted.
FT CHAIN 1..538
FT /note="Sterile alpha motif domain-containing protein 1"
FT /id="PRO_0000279494"
FT DOMAIN 462..530
FT /note="SAM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00184"
FT REGION 1..30
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 28..98
FT /note="Winged-helix domain"
FT /evidence="ECO:0000303|PubMed:33980486"
FT REGION 92..247
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 282..458
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 104..143
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 160..236
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 327..348
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 425..439
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 107
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 161
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 261
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT VARIANT 340
FT /note="E -> D (in dbSNP:rs8062)"
FT /id="VAR_061701"
FT MUTAGEN 43
FT /note="R->A: Slightly decreases binding to unmethylated CpG
FT islands."
FT /evidence="ECO:0000269|PubMed:33980486"
FT MUTAGEN 45..46
FT /note="RK->AA: Strongly decreases binding to unmethylated
FT CpG islands. Abolishes interaction with KDM1A."
FT /evidence="ECO:0000269|PubMed:33980486"
FT MUTAGEN 48
FT /note="R->A: Decreases binding to unmethylated CpG
FT islands."
FT /evidence="ECO:0000269|PubMed:33980486"
FT MUTAGEN 87..88
FT /note="YK->AA: Decreases binding to unmethylated CpG
FT islands."
FT /evidence="ECO:0000269|PubMed:33980486"
FT MUTAGEN 94
FT /note="R->A: Decreases binding to unmethylated CpG
FT islands."
FT /evidence="ECO:0000269|PubMed:33980486"
FT MUTAGEN 498..514
FT /note="RTDVLTGLSIRLGPALK->ATDVLTGLSIRLGPALA: Abolishes
FT interaction with L3MBTL3."
FT /evidence="ECO:0000269|PubMed:33980486"
FT CONFLICT 111..216
FT /note="Missing (in Ref. 2; AC022098)"
FT /evidence="ECO:0000305"
FT HELIX 31..44
FT /evidence="ECO:0007829|PDB:6LUI"
FT HELIX 51..62
FT /evidence="ECO:0007829|PDB:6LUI"
FT HELIX 66..78
FT /evidence="ECO:0007829|PDB:6LUI"
FT STRAND 81..87
FT /evidence="ECO:0007829|PDB:6LUI"
FT STRAND 90..95
FT /evidence="ECO:0007829|PDB:6LUI"
FT HELIX 459..461
FT /evidence="ECO:0007829|PDB:6LUJ"
FT HELIX 464..473
FT /evidence="ECO:0007829|PDB:6LUJ"
FT HELIX 477..485
FT /evidence="ECO:0007829|PDB:6LUJ"
FT HELIX 490..493
FT /evidence="ECO:0007829|PDB:6LUJ"
FT HELIX 498..502
FT /evidence="ECO:0007829|PDB:6LUJ"
FT HELIX 509..518
FT /evidence="ECO:0007829|PDB:6LUJ"
FT TURN 519..522
FT /evidence="ECO:0007829|PDB:6LUJ"
SQ SEQUENCE 538 AA; 56052 MW; 083A170790654F2F CRC64;
MAGPPALPPP ETAAAATTAA AASSSAASPH YQEWILDTID SLRSRKARPD LERICRMVRR
RHGPEPERTR AELEKLIQQR AVLRVSYKGS ISYRNAARVQ PPRRGATPPA PPRAPRGAPA
AAAAAAPPPT PAPPPPPAPV AAAAPARAPR AAAAAATAPP SPGPAQPGPR AQRAAPLAAP
PPAPAAPPAV APPAGPRRAP PPAVAAREPP LPPPPQPPAP PQQQQPPPPQ PQPPPEGGAV
RAGGAARPVS LREVVRYLGG SGGAGGRLTR GRVQGLLEEE AAARGRLERT RLGALALPRG
DRPGRAPPAA SARPSRSKRG GEERVLEKEE EEDDDEDEDE EDDVSEGSEV PESDRPAGAQ
HHQLNGERGP QSAKERVKEW TPCGPHQGQD EGRGPAPGSG TRQVFSMAAM NKEGGTASVA
TGPDSPSPVP LPPGKPALPG ADGTPFGCPP GRKEKPSDPV EWTVMDVVEY FTEAGFPEQA
TAFQEQEIDG KSLLLMQRTD VLTGLSIRLG PALKIYEHHI KVLQQGHFED DDPDGFLG
