SERF1_HUMAN
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 03-AUG-2022, entry version 156.
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}.
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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; 26.
DR BioGRID; 608917; 12.
DR IntAct; O75920; 21.
DR MINT; O75920; -.
DR STRING; 9606.ENSP00000346892; -.
DR iPTMnet; O75920; -.
DR PhosphoSitePlus; O75920; -.
DR BioMuta; SERF1A; -.
DR EPD; O75920; -.
DR jPOST; O75920; -.
DR MassIVE; O75920; -.
DR MaxQB; O75920; -.
DR PaxDb; O75920; -.
DR PeptideAtlas; O75920; -.
DR PRIDE; O75920; -.
DR ProteomicsDB; 50276; -. [O75920-1]
DR ProteomicsDB; 50277; -. [O75920-2]
DR TopDownProteomics; O75920-2; -. [O75920-2]
DR Antibodypedia; 24018; 20 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; ENSG00000205572.10. [O75920-1]
DR Ensembl; ENST00000380751.9; ENSP00000370127.5; ENSG00000205572.10. [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 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; KKDGDPK; -.
DR OrthoDB; 1559007at2759; -.
DR PhylomeDB; O75920; -.
DR PathwayCommons; O75920; -.
DR SignaLink; O75920; -.
DR BioGRID-ORCS; 728492; 7 hits in 122 CRISPR screens.
DR BioGRID-ORCS; 8293; 14 hits in 611 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 96 other tissues.
DR ExpressionAtlas; O75920; baseline and differential.
DR Genevisible; O75920; HS.
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; IPR040211; SERF1/2.
DR InterPro; IPR007513; Uncharacterised_SERF_N.
DR PANTHER; PTHR13596; PTHR13596; 1.
DR Pfam; PF04419; 4F5; 1.
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
