ID SERF1_HUMAN Reviewed; 110 AA. AC O75920; B7ZKM2; O75919; Q52LK5; DT 19-SEP-2002, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1998, sequence version 1. DT 27-MAR-2024, entry version 164. DE RecName: Full=Small EDRK-rich factor 1; DE AltName: Full=Protein 4F5; DE Short=h4F5; DE AltName: Full=SMA modifier 1; GN Name=SERF1A; Synonyms=FAM2A, SERF1, SMAM1; GN and GN Name=SERF1B; Synonyms=FAM2B, SERF1, SMAM1; 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] (ISOFORMS LONG AND SHORT), AND TISSUE RP SPECIFICITY. RX PubMed=9731538; DOI=10.1038/1753; RA Scharf J.M., Endrizzi M.G., Wetter A., Huang S., Thompson T.G., Zerres K., RA Dietrich W.F., Wirth B., Kunkel L.M.; RT "Identification of a candidate modifying gene for spinal muscular atrophy RT by comparative genomics."; RL Nat. Genet. 20:83-86(1998). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS SHORT AND LONG). RC TISSUE=Brain, and 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. RX PubMed=20723760; DOI=10.1016/j.cell.2010.07.020; RA van Ham T.J., Holmberg M.A., van der Goot A.T., Teuling E., RA Garcia-Arencibia M., Kim H.E., Du D., Thijssen K.L., Wiersma M., RA Burggraaff R., van Bergeijk P., van Rheenen J., Jerre van Veluw G., RA Hofstra R.M., Rubinsztein D.C., Nollen E.A.; RT "Identification of MOAG-4/SERF as a regulator of age-related RT proteotoxicity."; RL Cell 142:601-612(2010). RN [4] RP FUNCTION, AND INTERACTION WITH SNCA. RX PubMed=22854022; DOI=10.1016/j.celrep.2012.06.012; RA Falsone S.F., Meyer N.H., Schrank E., Leitinger G., Pham C.L., RA Fodero-Tavoletti M.T., Holmberg M., Dulle M., Scicluna B., Gesslbauer B., RA Rueckert H.M., Wagner G.E., Merle D.A., Nollen E.A., Kungl A.J., Hill A.F., RA Cappai R., Zangger K.; RT "SERF protein is a direct modifier of amyloid fiber assembly."; RL Cell Rep. 2:358-371(2012). RN [5] RP FUNCTION, INTERACTION WITH SNCA, SUBCELLULAR LOCATION, AND MUTAGENESIS OF RP ARG-11; GLN-12; LYS-13; ASN-14; LYS-16; LYS-17 AND THR-18. RX PubMed=31034892; DOI=10.1016/j.jmb.2019.04.031; RA Merle D.A., Witternigg A., Tam-Amersdorfer C., Hartlmueller C., RA Spreitzer E., Schrank E., Wagner-Lichtenegger S., Werzer O., Zangger K., RA Kungl A.J., Madl T., Meyer N.H., Falsone S.F.; RT "Increased Aggregation Tendency of Alpha-Synuclein in a Fully Disordered RT Protein Complex."; RL J. Mol. Biol. 431:2581-2598(2019). CC -!- FUNCTION: Positive regulator of amyloid protein aggregation and CC proteotoxicity (PubMed:20723760, PubMed:22854022, PubMed:31034892). CC Induces conformational changes in amyloid proteins, such as APP, HTT, CC and SNCA, driving them into compact formations preceding the formation CC of aggregates (PubMed:20723760, PubMed:22854022, PubMed:31034892). CC {ECO:0000269|PubMed:20723760, ECO:0000269|PubMed:22854022, CC ECO:0000269|PubMed:31034892}. CC -!- SUBUNIT: Interacts with SNCA; this interaction promotes the aggregation CC of SNCA. {ECO:0000269|PubMed:22854022, ECO:0000269|PubMed:31034892}. CC -!- INTERACTION: CC O75920; O95870: ABHD16A; NbExp=3; IntAct=EBI-2115181, EBI-348517; CC O75920; Q13520: AQP6; NbExp=3; IntAct=EBI-2115181, EBI-13059134; CC O75920; Q9HA82: CERS4; NbExp=3; IntAct=EBI-2115181, EBI-2622997; CC O75920; Q9BUF7-2: CRB3; NbExp=3; IntAct=EBI-2115181, EBI-17233035; CC O75920; Q9GZR5: ELOVL4; NbExp=3; IntAct=EBI-2115181, EBI-18535450; CC O75920; A1L3X0: ELOVL7; NbExp=3; IntAct=EBI-2115181, EBI-10285373; CC O75920; Q8TDT2: GPR152; NbExp=3; IntAct=EBI-2115181, EBI-13345167; CC O75920; Q9H6H4: REEP4; NbExp=3; IntAct=EBI-2115181, EBI-7545592; CC O75920; Q6P5S7: RNASEK; NbExp=3; IntAct=EBI-2115181, EBI-18397230; CC O75920; Q9NPL8: TIMMDC1; NbExp=3; IntAct=EBI-2115181, EBI-6268651; CC O75920; Q9NUH8: TMEM14B; NbExp=3; IntAct=EBI-2115181, EBI-8638294; CC O75920; Q9Y320: TMX2; NbExp=3; IntAct=EBI-2115181, EBI-6447886; CC O75920-2; P37840: SNCA; NbExp=4; IntAct=EBI-21283682, EBI-985879; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:31034892}. CC Nucleus {ECO:0000269|PubMed:31034892}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=Long; CC IsoId=O75920-1; Sequence=Displayed; CC Name=Short; CC IsoId=O75920-2; Sequence=VSP_006057; CC -!- TISSUE SPECIFICITY: Isoform Long is predominantly expressed in heart, CC brain and skeletal muscle. Isoform Short and Isoform Long are expressed CC throughout the central nervous system, including spinal cord. CC {ECO:0000269|PubMed:9731538}. CC -!- SIMILARITY: Belongs to the SERF family. {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; AF073518; AAC63517.1; -; mRNA. DR EMBL; AF073519; AAC63518.1; -; mRNA. DR EMBL; BC021174; AAH21174.1; -; mRNA. DR EMBL; BC035932; AAH35932.1; -; mRNA. DR EMBL; BC093880; AAH93880.1; -; mRNA. DR EMBL; BC093882; AAH93882.1; -; mRNA. DR EMBL; BC101970; AAI01971.1; -; mRNA. DR EMBL; BC104738; AAI04739.1; -; mRNA. DR EMBL; BC103687; AAI03688.1; -; mRNA. DR EMBL; BC143255; AAI43256.1; -; mRNA. DR EMBL; BC143260; AAI43261.1; -; mRNA. DR EMBL; BC171749; AAI71749.1; -; mRNA. DR CCDS; CCDS43326.1; -. [O75920-1] DR CCDS; CCDS47228.1; -. [O75920-1] DR CCDS; CCDS47229.1; -. [O75920-2] DR CCDS; CCDS54866.1; -. [O75920-2] DR RefSeq; NP_001171558.1; NM_001178087.1. [O75920-2] DR RefSeq; NP_068802.1; NM_021967.2. [O75920-1] DR RefSeq; NP_075257.1; NM_022968.1. [O75920-2] DR RefSeq; NP_075267.1; NM_022978.2. [O75920-1] DR AlphaFoldDB; O75920; -. DR BioGRID; 113898; 27. DR BioGRID; 608917; 12. DR IntAct; O75920; 21. DR MINT; O75920; -. DR STRING; 9606.ENSP00000346892; -. DR GlyGen; O75920; 3 sites, 1 O-linked glycan (3 sites). DR iPTMnet; O75920; -. DR PhosphoSitePlus; O75920; -. DR BioMuta; SERF1A; -. DR EPD; O75920; -. DR jPOST; O75920; -. DR MassIVE; O75920; -. DR MaxQB; O75920; -. DR PaxDb; 9606-ENSP00000346892; -. DR PeptideAtlas; O75920; -. DR ProteomicsDB; 50276; -. [O75920-1] DR ProteomicsDB; 50277; -. [O75920-2] DR Pumba; O75920; -. DR TopDownProteomics; O75920-2; -. [O75920-2] DR Antibodypedia; 24018; 24 antibodies from 6 providers. DR Antibodypedia; 67412; 127 antibodies from 10 providers. DR DNASU; 8293; -. DR Ensembl; ENST00000317633.14; ENSP00000321791.8; ENSG00000172058.16. [O75920-2] DR Ensembl; ENST00000354833.7; ENSP00000346892.3; ENSG00000172058.16. [O75920-1] DR Ensembl; ENST00000380750.8; ENSP00000370126.4; ENSG00000205572.11. [O75920-1] DR Ensembl; ENST00000380751.10; ENSP00000370127.5; ENSG00000205572.11. [O75920-2] DR Ensembl; ENST00000611616.4; ENSP00000482392.1; ENSG00000278839.4. [O75920-2] DR Ensembl; ENST00000613172.4; ENSP00000484795.1; ENSG00000277429.4. [O75920-1] DR Ensembl; ENST00000614527.4; ENSP00000479724.1; ENSG00000275581.4. [O75920-1] DR Ensembl; ENST00000621283.3; ENSP00000481118.1; ENSG00000277429.4. [O75920-2] DR Ensembl; ENST00000622553.4; ENSP00000480543.1; ENSG00000278839.4. [O75920-1] DR Ensembl; ENST00000627372.2; ENSP00000487374.1; ENSG00000275581.4. [O75920-2] DR Ensembl; ENST00000630567.1; ENSP00000487531.1; ENSG00000275581.4. [O75920-1] DR GeneID; 728492; -. DR GeneID; 8293; -. DR KEGG; hsa:728492; -. DR KEGG; hsa:8293; -. DR MANE-Select; ENST00000317633.14; ENSP00000321791.8; NM_022968.2; NP_075257.1. [O75920-2] DR MANE-Select; ENST00000380750.8; ENSP00000370126.4; NM_022978.3; NP_075267.1. DR UCSC; uc003jxz.4; human. [O75920-1] DR AGR; HGNC:10755; -. DR AGR; HGNC:10756; -. DR CTD; 728492; -. DR CTD; 8293; -. DR DisGeNET; 728492; -. DR DisGeNET; 8293; -. DR GeneCards; SERF1A; -. DR GeneCards; SERF1B; -. DR HGNC; HGNC:10755; SERF1A. DR HGNC; HGNC:10756; SERF1B. DR HPA; ENSG00000172058; Tissue enhanced (retina, testis). DR HPA; ENSG00000205572; Tissue enhanced (testis). DR MIM; 603011; gene. DR neXtProt; NX_O75920; -. DR OpenTargets; ENSG00000172058; -. DR OpenTargets; ENSG00000205572; -. DR PharmGKB; PA35675; -. DR VEuPathDB; HostDB:ENSG00000172058; -. DR VEuPathDB; HostDB:ENSG00000205572; -. DR eggNOG; KOG4488; Eukaryota. DR GeneTree; ENSGT00940000161793; -. DR HOGENOM; CLU_165034_1_1_1; -. DR InParanoid; O75920; -. DR OMA; GQSINQK; -. DR OrthoDB; 1442097at2759; -. DR PhylomeDB; O75920; -. DR PathwayCommons; O75920; -. DR SignaLink; O75920; -. DR BioGRID-ORCS; 728492; 7 hits in 131 CRISPR screens. DR BioGRID-ORCS; 8293; 14 hits in 662 CRISPR screens. DR ChiTaRS; SERF1B; human. DR Pharos; O75920; Tdark. DR PRO; PR:O75920; -. DR Proteomes; UP000005640; Chromosome 5. DR RNAct; O75920; Protein. DR Bgee; ENSG00000172058; Expressed in left testis and 98 other cell types or tissues. DR ExpressionAtlas; O75920; baseline and differential. DR GO; GO:0005829; C:cytosol; IMP:UniProtKB. DR GO; GO:0005634; C:nucleus; IMP:UniProtKB. DR GO; GO:0032991; C:protein-containing complex; IMP:UniProtKB. DR GO; GO:1990000; P:amyloid fibril formation; IMP:UniProtKB. DR GO; GO:0007399; P:nervous system development; TAS:ProtInc. DR GO; GO:0031648; P:protein destabilization; IMP:UniProtKB. DR InterPro; IPR007513; SERF-like_N. DR InterPro; IPR040211; SERF1/2-like. DR PANTHER; PTHR13596; SMALL EDRK-RICH FACTOR 1; 1. DR PANTHER; PTHR13596:SF1; SMALL EDRK-RICH FACTOR 1; 1. DR Pfam; PF04419; SERF-like_N; 1. DR Genevisible; O75920; HS. PE 1: Evidence at protein level; KW Alternative splicing; Cytoplasm; Nucleus; Reference proteome. FT CHAIN 1..110 FT /note="Small EDRK-rich factor 1" FT /id="PRO_0000050710" FT REGION 1..61 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 11..17 FT /note="Required for SNCA binding" FT /evidence="ECO:0000269|PubMed:31034892" FT COMPBIAS 9..33 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT VAR_SEQ 39..110 FT /note="SSGGQKSESKMSAGPHLPLKAPRENPCFPLPAAGGSRYYLAYGSITPISAFV FT FVVFFSVFFPSFYEDFCCWI -> RDSEIMQEKQKAANEKKSMQTREK (in FT isoform Short)" FT /evidence="ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:9731538" FT /id="VSP_006057" FT MUTAGEN 11 FT /note="R->A: No effect on SNCA binding." FT /evidence="ECO:0000269|PubMed:31034892" FT MUTAGEN 11 FT /note="R->E: Decreases SNCA binding." FT /evidence="ECO:0000269|PubMed:31034892" FT MUTAGEN 12 FT /note="Q->A: Slightly decreases SNCA binding." FT /evidence="ECO:0000269|PubMed:31034892" FT MUTAGEN 13 FT /note="K->A: Decreases SNCA binding." FT /evidence="ECO:0000269|PubMed:31034892" FT MUTAGEN 13 FT /note="K->E: Inhibits SNCA binding." FT /evidence="ECO:0000269|PubMed:31034892" FT MUTAGEN 14 FT /note="N->A: Decreases SNCA binding." FT /evidence="ECO:0000269|PubMed:31034892" FT MUTAGEN 16 FT /note="K->A: Drastically decreases SNCA binding." FT /evidence="ECO:0000269|PubMed:31034892" FT MUTAGEN 16 FT /note="K->E: Inhibits SNCA binding." FT /evidence="ECO:0000269|PubMed:31034892" FT MUTAGEN 17 FT /note="K->A: Drastically decreases SNCA binding." FT /evidence="ECO:0000269|PubMed:31034892" FT MUTAGEN 17 FT /note="K->E: Inhibits SNCA binding." FT /evidence="ECO:0000269|PubMed:31034892" FT MUTAGEN 18 FT /note="T->A: No effect on SNCA binding." FT /evidence="ECO:0000269|PubMed:31034892" SQ SEQUENCE 110 AA; 12349 MW; ED9143455DB925AB CRC64; MARGNQRELA RQKNMKKTQE ISKGKRKEDS LTASQRKQSS GGQKSESKMS AGPHLPLKAP RENPCFPLPA AGGSRYYLAY GSITPISAFV FVVFFSVFFP SFYEDFCCWI //