CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-012050
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Steroidogenic factor 1 
Protein Synonyms/Alias
 SF-1; STF-1; Adrenal 4-binding protein; Fushi tarazu factor homolog 1; Nuclear receptor subfamily 5 group A member 1; Steroid hormone receptor Ad4BP 
Gene Name
 NR5A1 
Gene Synonyms/Alias
 AD4BP; FTZF1; SF1 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
34LLTCESCKGFFKRTVacetylation[1]
38ESCKGFFKRTVQNNKacetylation[1, 2]
72CPFCRFQKCLTVGMRacetylation[1]
119QIRANGFKLETGPPMsumoylation[3, 4, 5, 6, 7]
194AFPGRAIKSEYPEPYsumoylation[3, 4, 5, 7, 8]
Reference
 [1] Acetylation of steroidogenic factor 1 protein regulates its transcriptional activity and recruits the coactivator GCN5.
 Jacob AL, Lund J, Martinez P, Hedin L.
 J Biol Chem. 2001 Oct 5;276(40):37659-64. [PMID: 11479297]
 [2] Regulation of cellular metabolism by protein lysine acetylation.
 Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, Yao J, Zhou L, Zeng Y, Li H, Li Y, Shi J, An W, Hancock SM, He F, Qin L, Chin J, Yang P, Chen X, Lei Q, Xiong Y, Guan KL.
 Science. 2010 Feb 19;327(5968):1000-4. [PMID: 20167786]
 [3] Small ubiquitin-like modifier 1 (SUMO-1) modification of the synergy control motif of Ad4 binding protein/steroidogenic factor 1 (Ad4BP/SF-1) regulates synergistic transcription between Ad4BP/SF-1 and Sox9.
 Komatsu T, Mizusaki H, Mukai T, Ogawa H, Baba D, Shirakawa M, Hatakeyama S, Nakayama KI, Yamamoto H, Kikuchi A, Morohashi K.
 Mol Endocrinol. 2004 Oct;18(10):2451-62. [PMID: 15192080]
 [4] SUMO modification of repression domains modulates function of nuclear receptor 5A1 (steroidogenic factor-1).
 Chen WY, Lee WC, Hsu NC, Huang F, Chung BC.
 J Biol Chem. 2004 Sep 10;279(37):38730-5. [PMID: 15192092]
 [5] The DEAD-box protein DP103 (Ddx20 or Gemin-3) represses orphan nuclear receptor activity via SUMO modification.
 Lee MB, Lebedeva LA, Suzawa M, Wadekar SA, Desclozeaux M, Ingraham HA.
 Mol Cell Biol. 2005 Mar;25(5):1879-90. [PMID: 15713642]
 [6] Pin1 facilitates the phosphorylation-dependent ubiquitination of SF-1 to regulate gonadotropin beta-subunit gene transcription.
 Luo Z, Wijeweera A, Oh Y, Liou YC, Melamed P.
 Mol Cell Biol. 2010 Feb;30(3):745-63. [PMID: 19995909]
 [7] Eliminating SF-1 (NR5A1) sumoylation in vivo results in ectopic hedgehog signaling and disruption of endocrine development.
 Lee FY, Faivre EJ, Suzawa M, Lontok E, Ebert D, Cai F, Belsham DD, Ingraham HA.
 Dev Cell. 2011 Aug 16;21(2):315-27. [PMID: 21820362]
 [8] SUMOylation inhibits SF-1 activity by reducing CDK7-mediated serine 203 phosphorylation.
 Yang WH, Heaton JH, Brevig H, Mukherjee S, Iñiguez-Lluhí JA, Hammer GD.
 Mol Cell Biol. 2009 Feb;29(3):613-25. [PMID: 19015234] 
Functional Description
 Transcriptional activator. Seems to be essential for sexual differentiation and formation of the primary steroidogenic tissues. Binds to the Ad4 site found in the promoter region of steroidogenic P450 genes such as CYP11A, CYP11B and CYP21B. Also regulates the AMH/Muellerian inhibiting substance gene as well as the AHCH and STAR genes. 5'-YCAAGGYC-3' and 5'-RRAGGTCA-3' are the consensus sequences for the recognition by NR5A1. The SFPQ-NONO- NR5A1 complex binds to the CYP17 promoter and regulates basal and cAMP-dependent transcriptional avtivity. Binds phosphatidylcholine (By similarity). Binds phospholipids with a phosphatidylinositol (PI) headgroup, in particular PI(3,4)P2 and PI(3,4,5)P3. Activated by the phosphorylation of NR5A1 by HIPK3 leading to increased steroidogenic gene expression upon cAMP signaling pathway stimulation. 
Sequence Annotation
 DNA_BIND 10 85 Nuclear receptor.
 ZN_FING 13 33 NR C4-type.
 ZN_FING 49 73 NR C4-type.
 REGION 230 461 Important for dimerization.
 REGION 260 347 Ligand-binding.
 BINDING 341 341 Lipid headgroup; via amide nitrogen.
 BINDING 436 436 Lipid headgroup.
 BINDING 440 440 Lipid headgroup.
 MOD_RES 34 34 N6-acetyllysine (Probable).
 MOD_RES 38 38 N6-acetyllysine (Probable).
 MOD_RES 72 72 N6-acetyllysine (Probable).
 MOD_RES 203 203 Phosphoserine; by CDK7.
 CROSSLNK 119 119 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 194 194 Glycyl lysine isopeptide (Lys-Gly)  
Keyword
 3D-structure; Acetylation; Activator; Complete proteome; Disease mutation; DNA-binding; Isopeptide bond; Lipid-binding; Metal-binding; Nucleus; Phosphoprotein; Polymorphism; Premature ovarian failure; Receptor; Reference proteome; Transcription; Transcription regulation; Ubl conjugation; Zinc; Zinc-finger. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 461 AA 
Protein Sequence
MDYSYDEDLD ELCPVCGDKV SGYHYGLLTC ESCKGFFKRT VQNNKHYTCT ESQSCKIDKT 60
QRKRCPFCRF QKCLTVGMRL EAVRADRMRG GRNKFGPMYK RDRALKQQKK AQIRANGFKL 120
ETGPPMGVPP PPPPAPDYVL PPSLHGPEPK GLAAGPPAGP LGDFGAPALP MAVPGAHGPL 180
AGYLYPAFPG RAIKSEYPEP YASPPQPGLP YGYPEPFSGG PNVPELILQL LQLEPDEDQV 240
RARILGCLQE PTKSRPDQPA AFGLLCRMAD QTFISIVDWA RRCMVFKELE VADQMTLLQN 300
CWSELLVFDH IYRQVQHGKE GSILLVTGQE VELTTVATQA GSLLHSLVLR AQELVLQLLA 360
LQLDRQEFVC LKFIILFSLD LKFLNNHILV KDAQEKANAA LLDYTLCHYP HCGDKFQQLL 420
LCLVEVRALS MQAKEYLYHK HLGNEMPRNN LLIEMLQAKQ T 461 
Gene Ontology
 GO:0005654; C:nucleoplasm; TAS:Reactome.
 GO:0003682; F:chromatin binding; IEA:Compara.
 GO:0003677; F:DNA binding; IDA:UniProtKB.
 GO:0003690; F:double-stranded DNA binding; IEA:Compara.
 GO:0004879; F:ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity; TAS:ProtInc.
 GO:0005543; F:phospholipid binding; IDA:UniProtKB.
 GO:0003705; F:RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity; IDA:UniProtKB.
 GO:0043565; F:sequence-specific DNA binding; IEA:Compara.
 GO:0003707; F:steroid hormone receptor activity; IEA:InterPro.
 GO:0003713; F:transcription coactivator activity; TAS:ProtInc.
 GO:0008270; F:zinc ion binding; IEA:InterPro.
 GO:0030325; P:adrenal gland development; IEA:Compara.
 GO:0030154; P:cell differentiation; IEA:Compara.
 GO:0007267; P:cell-cell signaling; TAS:ProtInc.
 GO:0042445; P:hormone metabolic process; IEA:Compara.
 GO:0001553; P:luteinization; IEA:Compara.
 GO:0051457; P:maintenance of protein location in nucleus; IEA:Compara.
 GO:0008584; P:male gonad development; TAS:ProtInc.
 GO:0010259; P:multicellular organismal aging; IEA:Compara.
 GO:2000195; P:negative regulation of female gonad development; IEA:Compara.
 GO:2000020; P:positive regulation of male gonad development; IDA:UniProtKB.
 GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IMP:UniProtKB.
 GO:0007538; P:primary sex determination; TAS:ProtInc.
 GO:0050810; P:regulation of steroid biosynthetic process; TAS:UniProtKB.
 GO:0009888; P:tissue development; IEA:Compara.
 GO:0006367; P:transcription initiation from RNA polymerase II promoter; TAS:Reactome. 
Interpro
 IPR008946; Nucl_hormone_rcpt_ligand-bd.
 IPR000536; Nucl_hrmn_rcpt_lig-bd_core.
 IPR016355; Steroidogenic_factor_1.
 IPR001723; Str_hrmn_rcpt.
 IPR001628; Znf_hrmn_rcpt.
 IPR013088; Znf_NHR/GATA. 
Pfam
 PF00104; Hormone_recep
 PF00105; zf-C4 
SMART
 SM00430; HOLI
 SM00399; ZnF_C4 
PROSITE
 PS00031; NUCLEAR_REC_DBD_1
 PS51030; NUCLEAR_REC_DBD_2 
PRINTS
 PR00398; STRDHORMONER.
 PR00047; STROIDFINGER.