SRA1_HUMAN
ID SRA1_HUMAN Reviewed; 224 AA.
AC Q9HD15; Q6NVU9; Q8IXM1; Q9HD13; Q9HD14;
DT 16-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 23-FEB-2022, sequence version 2.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=Steroid receptor RNA activator 1 {ECO:0000305};
DE AltName: Full=Steroid receptor RNA activator protein;
DE Short=SRAP;
GN Name=SRA1 {ECO:0000312|HGNC:HGNC:11281}; ORFNames=PP7684;
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] {ECO:0000305, ECO:0000312|EMBL:AAG02114.1}
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Mammary gland {ECO:0000312|EMBL:AAG02114.1};
RX PubMed=12565891; DOI=10.1016/s0006-291x(02)03070-x;
RA Emberley E., Huang G.-J., Hamedani M.K., Czosnek A., Ali D., Grolla A.,
RA Lu B., Watson P.H., Murphy L.C., Leygue E.;
RT "Identification of new human coding steroid receptor RNA activator
RT isoforms.";
RL Biochem. Biophys. Res. Commun. 301:509-515(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15498874; DOI=10.1073/pnas.0404089101;
RA Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X.,
RA Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X.,
RA Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J.;
RT "Large-scale cDNA transfection screening for genes related to cancer
RT development and progression.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004).
RN [3] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 2-224, FUNCTION, IDENTIFICATION IN A
RP RIBONUCLEOPROTEIN COMPLEX WITH NCOA1, AND TISSUE SPECIFICITY.
RX PubMed=10199399; DOI=10.1016/s0092-8674(00)80711-4;
RA Lanz R.B., McKenna N.J., Onate S.A., Albrecht U., Wong J., Tsai S.Y.,
RA Tsai M.-J., O'Malley B.W.;
RT "A steroid receptor coactivator, SRA, functions as an RNA and is present in
RT an SRC-1 complex.";
RL Cell 97:17-27(1999).
RN [4] {ECO:0000305, ECO:0000312|EMBL:AAH40043.2}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 10-224.
RC TISSUE=Lymph {ECO:0000312|EMBL:AAH40043.2};
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 [5] {ECO:0000305}
RP FUNCTION.
RX PubMed=12943696; DOI=10.1016/s0960-0760(03)00225-5;
RA Deblois G., Giguere V.;
RT "Ligand-independent coactivation of ERalpha AF-1 by steroid receptor RNA
RT activator (SRA) via MAPK activation.";
RL J. Steroid Biochem. Mol. Biol. 85:123-131(2003).
RN [6] {ECO:0000305}
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=14517287; DOI=10.1128/mcb.23.20.7163-7176.2003;
RA Lanz R.B., Chua S.S., Barron N., Soder B.M., DeMayo F., O'Malley B.W.;
RT "Steroid receptor RNA activator stimulates proliferation as well as
RT apoptosis in vivo.";
RL Mol. Cell. Biol. 23:7163-7176(2003).
RN [7] {ECO:0000305}
RP FUNCTION.
RX PubMed=15351741; DOI=10.1016/j.bbrc.2004.08.090;
RA Coleman K.M., Lam V., Jaber B.M., Lanz R.B., Smith C.L.;
RT "SRA coactivation of estrogen receptor-alpha is phosphorylation-
RT independent, and enhances 4-hydroxytamoxifen agonist activity.";
RL Biochem. Biophys. Res. Commun. 323:332-338(2004).
RN [8] {ECO:0000305}
RP FUNCTION.
RX PubMed=15147866; DOI=10.1016/j.febslet.2004.03.104;
RA Chooniedass-Kothari S., Emberley E., Hamedani M.K., Troup S., Wang X.,
RA Czosnek A., Hube F., Mutawe M., Watson P.H., Leygue E.;
RT "The steroid receptor RNA activator is the first functional RNA encoding a
RT protein.";
RL FEBS Lett. 566:43-47(2004).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-48, AND IDENTIFICATION BY
RP 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 [10]
RP IDENTIFICATION BY 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 [11]
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 [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-57, AND IDENTIFICATION BY
RP 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 [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-75, 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).
CC -!- FUNCTION: Functional RNA which acts as a transcriptional coactivator
CC that selectively enhances steroid receptor-mediated transactivation
CC ligand-independently through a mechanism involving the modulating N-
CC terminal domain (AF-1) of steroid receptors. Also mediates
CC transcriptional coactivation of steroid receptors ligand-dependently
CC through the steroid-binding domain (AF-2). Enhances cellular
CC proliferation and differentiation and promotes apoptosis in vivo. May
CC play a role in tumorigenesis. {ECO:0000269|PubMed:10199399,
CC ECO:0000269|PubMed:12943696, ECO:0000269|PubMed:14517287,
CC ECO:0000269|PubMed:15147866, ECO:0000269|PubMed:15351741}.
CC -!- SUBUNIT: SRA1 RNA exists in a ribonucleoprotein complex containing
CC NCOA1. The RNA also forms a complex with PUS1 and RARG in the nucleus.
CC Interacts with AR. {ECO:0000250|UniProtKB:Q6QGW5,
CC ECO:0000250|UniProtKB:Q80VJ2, ECO:0000269|PubMed:10199399}.
CC -!- INTERACTION:
CC Q9HD15; Q92769: HDAC2; NbExp=2; IntAct=EBI-727136, EBI-301821;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12565891}. Cytoplasm
CC {ECO:0000269|PubMed:12565891}.
CC -!- TISSUE SPECIFICITY: Highly expressed in liver and skeletal muscle and
CC to a lesser extent in brain. Also expressed in both normal and
CC tumorigenic breast epithelial cell lines. Significantly up-regulated in
CC human tumors of the breast, ovary, and uterus.
CC {ECO:0000269|PubMed:10199399, ECO:0000269|PubMed:12565891,
CC ECO:0000269|PubMed:14517287}.
CC -!- MISCELLANEOUS: Appears to be the first example of a new class of
CC functional RNAs also able to encode a protein.
CC {ECO:0000269|PubMed:12565891, ECO:0000269|PubMed:15147866}.
CC -!- SIMILARITY: Belongs to the SRA1 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAG02114.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAG02115.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAG02116.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAH40043.2; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAL55868.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF293024; AAG02114.1; ALT_INIT; mRNA.
DR EMBL; AF293025; AAG02115.1; ALT_INIT; mRNA.
DR EMBL; AF293026; AAG02116.1; ALT_INIT; mRNA.
DR EMBL; AF318361; AAL55868.1; ALT_INIT; mRNA.
DR EMBL; AF092038; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC040043; AAH40043.2; ALT_FRAME; mRNA.
DR CCDS; CCDS34245.1; -.
DR RefSeq; NP_001030312.2; NM_001035235.3.
DR PDB; 2MGX; NMR; -; A=95-224.
DR PDB; 4NBO; X-ray; 2.81 A; A/B=94-203.
DR PDBsum; 2MGX; -.
DR PDBsum; 4NBO; -.
DR AlphaFoldDB; Q9HD15; -.
DR BMRB; Q9HD15; -.
DR BioGRID; 115329; 57.
DR CORUM; Q9HD15; -.
DR IntAct; Q9HD15; 12.
DR MINT; Q9HD15; -.
DR STRING; 9606.ENSP00000337513; -.
DR iPTMnet; Q9HD15; -.
DR PhosphoSitePlus; Q9HD15; -.
DR BioMuta; SRA1; -.
DR DMDM; 74718904; -.
DR EPD; Q9HD15; -.
DR jPOST; Q9HD15; -.
DR MassIVE; Q9HD15; -.
DR MaxQB; Q9HD15; -.
DR PaxDb; Q9HD15; -.
DR PeptideAtlas; Q9HD15; -.
DR PRIDE; Q9HD15; -.
DR ProteomicsDB; 81809; -.
DR Antibodypedia; 26969; 215 antibodies from 32 providers.
DR DNASU; 10011; -.
DR Ensembl; ENST00000336283.9; ENSP00000337513.6; ENSG00000213523.12.
DR GeneID; 10011; -.
DR KEGG; hsa:10011; -.
DR MANE-Select; ENST00000336283.9; ENSP00000337513.6; NM_001035235.4; NP_001030312.3.
DR UCSC; uc003lga.4; human.
DR CTD; 10011; -.
DR DisGeNET; 10011; -.
DR GeneCards; SRA1; -.
DR GeneReviews; SRA1; -.
DR HGNC; HGNC:11281; SRA1.
DR HPA; ENSG00000213523; Low tissue specificity.
DR MalaCards; SRA1; -.
DR MIM; 603819; gene.
DR neXtProt; NX_Q9HD15; -.
DR OpenTargets; ENSG00000213523; -.
DR PharmGKB; PA36110; -.
DR VEuPathDB; HostDB:ENSG00000213523; -.
DR eggNOG; ENOG502RZ38; Eukaryota.
DR GeneTree; ENSGT00390000001803; -.
DR HOGENOM; CLU_081395_0_0_1; -.
DR InParanoid; Q9HD15; -.
DR OMA; KDRGWND; -.
DR OrthoDB; 1577322at2759; -.
DR PhylomeDB; Q9HD15; -.
DR TreeFam; TF314789; -.
DR PathwayCommons; Q9HD15; -.
DR SignaLink; Q9HD15; -.
DR BioGRID-ORCS; 10011; 12 hits in 1077 CRISPR screens.
DR GeneWiki; SRA1; -.
DR GenomeRNAi; 10011; -.
DR Pharos; Q9HD15; Tbio.
DR PRO; PR:Q9HD15; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q9HD15; protein.
DR Bgee; ENSG00000213523; Expressed in pancreatic ductal cell and 178 other tissues.
DR ExpressionAtlas; Q9HD15; baseline and differential.
DR Genevisible; Q9HD15; HS.
DR GO; GO:0031252; C:cell leading edge; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0045171; C:intercellular bridge; IDA:HPA.
DR GO; GO:0015630; C:microtubule cytoskeleton; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:1990904; C:ribonucleoprotein complex; IDA:UniProtKB.
DR GO; GO:0031209; C:SCAR complex; IDA:UniProtKB.
DR GO; GO:0005667; C:transcription regulator complex; IEA:Ensembl.
DR GO; GO:0003677; F:DNA binding; IEA:Ensembl.
DR GO; GO:0030374; F:nuclear receptor coactivator activity; IBA:GO_Central.
DR GO; GO:0002153; F:steroid receptor RNA activator RNA binding; IDA:UniProtKB.
DR GO; GO:0003713; F:transcription coactivator activity; IDA:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0030154; P:cell differentiation; IDA:UniProtKB.
DR GO; GO:0071391; P:cellular response to estrogen stimulus; IMP:UniProtKB.
DR GO; GO:0045662; P:negative regulation of myoblast differentiation; IMP:UniProtKB.
DR GO; GO:0042981; P:regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:0007346; P:regulation of mitotic cell cycle; IDA:UniProtKB.
DR IDEAL; IID00683; -.
DR InterPro; IPR009917; SRA1/Sec31.
DR InterPro; IPR040243; Steroid_recept_RNA_1.
DR PANTHER; PTHR18834; PTHR18834; 1.
DR Pfam; PF07304; SRA1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Apoptosis; Cytoplasm; Nucleus; Phosphoprotein;
KW Receptor; Reference proteome; Ribonucleoprotein; Transcription;
KW Transcription regulation.
FT CHAIN 1..224
FT /note="Steroid receptor RNA activator 1"
FT /id="PRO_0000234105"
FT REGION 1..90
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 201..224
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 54..75
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 48
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 57
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 75
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT VARIANT 20
FT /note="Q -> E (in dbSNP:rs35610885)"
FT /id="VAR_052060"
FT CONFLICT 38
FT /note="T -> I (in Ref. 1; AAG02115)"
FT /evidence="ECO:0000305"
FT CONFLICT 98
FT /note="V -> RL (in Ref. 1; AAG02116 and 2; AAL55868)"
FT /evidence="ECO:0000305"
FT HELIX 99..112
FT /evidence="ECO:0007829|PDB:4NBO"
FT TURN 113..116
FT /evidence="ECO:0007829|PDB:4NBO"
FT HELIX 119..138
FT /evidence="ECO:0007829|PDB:4NBO"
FT HELIX 143..157
FT /evidence="ECO:0007829|PDB:4NBO"
FT HELIX 161..179
FT /evidence="ECO:0007829|PDB:4NBO"
FT TURN 180..182
FT /evidence="ECO:0007829|PDB:4NBO"
FT HELIX 183..197
FT /evidence="ECO:0007829|PDB:4NBO"
FT TURN 209..211
FT /evidence="ECO:0007829|PDB:2MGX"
FT STRAND 219..222
FT /evidence="ECO:0007829|PDB:2MGX"
SQ SEQUENCE 224 AA; 24400 MW; 000F380D23A9FE8F CRC64;
MAELYVKPGN KERGWNDPPQ FSYGLQTQAG GPRRSLLTKR VAAPQDGSPR VPASETSPGP
PPMGPPPPSS KAPRSPPVGS GPASGVEPTS FPVESEAVME DVLRPLEQAL EDCRGHTRKQ
VCDDISRRLA LLQEQWAGGK LSIPVKKRMA LLVQELSSHR WDAADDIHRS LMVDHVTEVS
QWMVGVKRLI AEKRSLFSEE AANEEKSAAT AEKNHTIPGF QQAS
