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Protein

Sterol regulatory element-binding protein 1

Gene

Srebf1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Transcriptional activator required for lipid homeostasis. Regulates transcription of the LDL receptor gene as well as the fatty acid and to a lesser degree the cholesterol synthesis pathway (By similarity). Binds to the sterol regulatory element 1 (SRE-1) (5'-ATCACCCCAC-3') (PubMed:7739539). Has dual sequence specificity binding to both an E-box motif (5'-ATCACGTGA-3') and to SRE-1 (5'-ATCACCCCAC-3').By similarity1 Publication

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionActivator, DNA-binding
Biological processCholesterol metabolism, Lipid metabolism, Steroid metabolism, Sterol metabolism, Transcription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-RNO-1655829 Regulation of cholesterol biosynthesis by SREBP (SREBF)

Names & Taxonomyi

Protein namesi
Recommended name:
Sterol regulatory element-binding protein 1
Short name:
SREBP-1
Alternative name(s):
Adipocyte determination- and differentiation-dependent factor 1
Short name:
ADD1
Sterol regulatory element-binding transcription factor 1
Cleaved into the following chain:
Gene namesi
Name:Srebf1
Synonyms:Srebp1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 10

Organism-specific databases

RGDi69423 Srebf1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 481CytoplasmicSequence analysisAdd BLAST481
Transmembranei482 – 502HelicalSequence analysisAdd BLAST21
Topological domaini503 – 536LumenalSequence analysisAdd BLAST34
Transmembranei537 – 557HelicalSequence analysisAdd BLAST21
Topological domaini558 – 1134CytoplasmicSequence analysisAdd BLAST577

Keywords - Cellular componenti

Cytoplasmic vesicle, Endoplasmic reticulum, Golgi apparatus, Membrane, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001274501 – 1134Sterol regulatory element-binding protein 1Add BLAST1134
ChainiPRO_00003140311 – 480Processed sterol regulatory element-binding protein 1Add BLAST480

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei97PhosphoserineCombined sources1
Modified residuei116PhosphoserineBy similarity1
Modified residuei331Phosphoserine; by SIK1By similarity1
Modified residuei332Phosphoserine; by SIK1By similarity1
Modified residuei389Phosphoserine; by AMPKBy similarity1
Modified residuei395Phosphoserine; by SIK1By similarity1
Modified residuei448PhosphoserineCombined sources1
Modified residuei1047PhosphoserineBy similarity1

Post-translational modificationi

At low cholesterol the SCAP/SREBP complex is recruited into COPII vesicles for export from the ER. In the Golgi complex SREBPs are cleaved sequentially by site-1 and site-2 protease. The first cleavage by site-1 protease occurs within the luminal loop, the second cleavage by site-2 protease occurs within the first transmembrane domain and releases the transcription factor from the Golgi membrane. Apoptosis triggers cleavage by the cysteine proteases caspase-3 and caspase-7 (By similarity).By similarity
Phosphorylated by AMPK, leading to suppress protein processing and nuclear translocation, and repress target gene expression. Phosphorylation at Ser-395 by SIK1 represses activity possibly by inhibiting DNA-binding (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei451 – 452Cleavage; by caspase-3 and caspase-7By similarity2
Sitei480 – 481Cleavage; by S2PBy similarity2
Sitei519 – 520Cleavage; by S1PBy similarity2

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiP56720
PRIDEiP56720

PTM databases

iPTMnetiP56720
PhosphoSitePlusiP56720

Expressioni

Tissue specificityi

Expressed predominantly in brown adipose tissue.

Gene expression databases

BgeeiENSRNOG00000003463 Expressed in 10 organ(s), highest expression level in liver
GenevisibleiP56720 RN

Interactioni

Subunit structurei

Forms a tight complex with SCAP in the ER membrane. Efficient DNA binding of the soluble transcription factor fragment requires dimerization with another bHLH protein. Interacts with LMNA. Interacts with CEBPA, the interaction produces a transcriptional synergy (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi249376, 8 interactors
STRINGi10116.ENSRNOP00000050057

Structurei

3D structure databases

ProteinModelPortaliP56720
SMRiP56720
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini317 – 367bHLHPROSITE-ProRule annotationAdd BLAST51

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 60Transcriptional activation (acidic)By similarityAdd BLAST60
Regioni227 – 487Interaction with LMNABy similarityAdd BLAST261
Regioni367 – 388Leucine-zipperAdd BLAST22

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi61 – 176Pro/Ser-richAdd BLAST116
Compositional biasi420 – 453Gly/Pro/Ser-richAdd BLAST34

Sequence similaritiesi

Belongs to the SREBP family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG2588 Eukaryota
ENOG410XSVP LUCA
GeneTreeiENSGT00390000017651
HOGENOMiHOG000007091
HOVERGENiHBG061592
InParanoidiP56720
KOiK07197
OMAiLHQLHMT
OrthoDBiEOG091G01RE
PhylomeDBiP56720
TreeFamiTF313894

Family and domain databases

CDDicd00083 HLH, 1 hit
Gene3Di4.10.280.10, 1 hit
InterProiView protein in InterPro
IPR011598 bHLH_dom
IPR024097 bHLH_ZIP_TF
IPR036638 HLH_DNA-bd_sf
PANTHERiPTHR12565 PTHR12565, 1 hit
PfamiView protein in Pfam
PF00010 HLH, 1 hit
SMARTiView protein in SMART
SM00353 HLH, 1 hit
SUPFAMiSSF47459 SSF47459, 1 hit
PROSITEiView protein in PROSITE
PS50888 BHLH, 1 hit

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket
Isoform SREBP-1A (identifier: P56720-2) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MDELPFGEAA LEQALAEVCE MDAALLTDIE DMLQLINNQD SDFPGLFDAP
60 70 80 90 100
YAGGETGDTG PSSPGASSPE SFSSPASLGS SLEAFLGGPK VTPAPLSPPP
110 120 130 140 150
SAPTAVKMYP SVPPFSPGPG IKEEPVPLTI LQPPAPQPSP GTLLPPSFPP
160 170 180 190 200
PPVQLSPAPV LGYSSLPSGF SGTLPGNTQQ TPSSLPLGST PGISPTPLHT
210 220 230 240 250
QVQSSAAQQP PPASAAPRMS TVASQIQQVP VVLQPHFIKA DSLLLTAVKT
260 270 280 290 300
DTGATMKTAG INTLAPGTAV QAGPLQTLVS GGTILATVPL VVDTDKLPIH
310 320 330 340 350
RLAAGGKALG SAQSRGEKRT AHNAIEKRYR SSINDKIVEL KDLVVGTEAK
360 370 380 390 400
LNKSAVLRKA IDYIRFLQHS NQKLKQENLT LRSAHKSKSL KDLVSACGSG
410 420 430 440 450
GGTDVSMEGM KPEVVETLTP PPSDAGSPSQ SSPLSLGSRG SSSGGSDSEP
460 470 480 490 500
DSPAFEDNQV KAQRLPSHSR GMLDRSRLAL CVLVFLCLTC NPLASLFGWG
510 520 530 540 550
ILTPSDASGV HRSSGRSMLE AESRDGSNWT QWLLPPLVWL ANGLLVLACL
560 570 580 590 600
ALLFVYGEPV TRPHSGPAVH FWRHRKQADL DLARGDFAQA AQQLWLALQA
610 620 630 640 650
LGRPLPTSNL DLACSLLWNL VRHLLQRLWV GRWLAGQAGG LQRDYRLRKD
660 670 680 690 700
ARASARDAAV VYHKLHQLHA MGKYTGGHLV ASNLALSALN LAECAGDAIS
710 720 730 740 750
MATLAEIYVA AALRVKTSLP RALHFLTRFF LSSARQACLA QSGAVPLAMQ
760 770 780 790 800
WLCHPVGHRF FVDGDWAVHG APQESLYSVA GNPVDPLAQV TRLFCEHLLE
810 820 830 840 850
RALNCIAQPS PGAADGDREF SDALGYLQLL NSCSDAVGAP ACSFSVSSSM
860 870 880 890 900
ATTTGTDPVA KWWASLTAVV IHWLRRDEEA AERLYPLVEH IPQVLQETER
910 920 930 940 950
PLPRAALYSF KAARALLDHR KVESSPASLA ICEKASGYLR DSLASTSTAS
960 970 980 990 1000
SIDKAMQLLL CDLLLVARTS LWRRQQSAAS AQGAHGTSNG PQASALELRG
1010 1020 1030 1040 1050
FQHDLSSLRR LAQSFRPAMR RVFLHEATAR LMAGASPART HQLLDRSLRR
1060 1070 1080 1090 1100
RAGSSGKGGA AAELEPRPTW REHTEALLLA SCYLPPAFLS APGQRVSMLA
1110 1120 1130
EAARTVEKLG DHRLLLDCQQ MLLRLGGGTT VTSS
Length:1,134
Mass (Da):120,521
Last modified:February 5, 2008 - v3
Checksum:i1D31A9AD3C36AB29
GO
Isoform SREBP-1C (identifier: P56720-1) [UniParc]FASTAAdd to basket
Also known as: ADD1

The sequence of this isoform differs from the canonical sequence as follows:
     1-29: MDELPFGEAALEQALAEVCEMDAALLTDI → MDCTF

Show »
Length:1,110
Mass (Da):118,027
Checksum:iC7CDAE780EA056D3
GO

Sequence cautioni

The sequence L16995 differs from that shown. Reason: Frameshift at positions 902, 939, 956, 972 and 1016.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti267G → A in L16995 (PubMed:15057822).Curated1
Sequence conflicti475R → P in L16995 (PubMed:15057822).Curated1
Sequence conflicti817D → H in L16995 (PubMed:15057822).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti779V → M in spontaneously hypertensive rats. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0308601 – 29MDELP…LLTDI → MDCTF in isoform SREBP-1C. 2 PublicationsAdd BLAST29

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AABR03073826 Genomic DNA No translation available.
AABR03076830 Genomic DNA No translation available.
L16995 mRNA No translation available.
AF286469 mRNA Translation: AAG28733.2
AF286470 mRNA Translation: AAG28734.2 Different termination.
RefSeqiNP_001263636.1, NM_001276707.1 [P56720-2]
NP_001263637.1, NM_001276708.1 [P56720-1]
UniGeneiRn.198857

Genome annotation databases

EnsembliENSRNOT00000004753; ENSRNOP00000004753; ENSRNOG00000003463 [P56720-1]
ENSRNOT00000047053; ENSRNOP00000050057; ENSRNOG00000003463 [P56720-2]
GeneIDi78968
KEGGirno:78968
UCSCiRGD:69423 rat [P56720-2]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AABR03073826 Genomic DNA No translation available.
AABR03076830 Genomic DNA No translation available.
L16995 mRNA No translation available.
AF286469 mRNA Translation: AAG28733.2
AF286470 mRNA Translation: AAG28734.2 Different termination.
RefSeqiNP_001263636.1, NM_001276707.1 [P56720-2]
NP_001263637.1, NM_001276708.1 [P56720-1]
UniGeneiRn.198857

3D structure databases

ProteinModelPortaliP56720
SMRiP56720
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi249376, 8 interactors
STRINGi10116.ENSRNOP00000050057

PTM databases

iPTMnetiP56720
PhosphoSitePlusiP56720

Proteomic databases

PaxDbiP56720
PRIDEiP56720

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000004753; ENSRNOP00000004753; ENSRNOG00000003463 [P56720-1]
ENSRNOT00000047053; ENSRNOP00000050057; ENSRNOG00000003463 [P56720-2]
GeneIDi78968
KEGGirno:78968
UCSCiRGD:69423 rat [P56720-2]

Organism-specific databases

CTDi6720
RGDi69423 Srebf1

Phylogenomic databases

eggNOGiKOG2588 Eukaryota
ENOG410XSVP LUCA
GeneTreeiENSGT00390000017651
HOGENOMiHOG000007091
HOVERGENiHBG061592
InParanoidiP56720
KOiK07197
OMAiLHQLHMT
OrthoDBiEOG091G01RE
PhylomeDBiP56720
TreeFamiTF313894

Enzyme and pathway databases

ReactomeiR-RNO-1655829 Regulation of cholesterol biosynthesis by SREBP (SREBF)

Miscellaneous databases

PROiPR:P56720

Gene expression databases

BgeeiENSRNOG00000003463 Expressed in 10 organ(s), highest expression level in liver
GenevisibleiP56720 RN

Family and domain databases

CDDicd00083 HLH, 1 hit
Gene3Di4.10.280.10, 1 hit
InterProiView protein in InterPro
IPR011598 bHLH_dom
IPR024097 bHLH_ZIP_TF
IPR036638 HLH_DNA-bd_sf
PANTHERiPTHR12565 PTHR12565, 1 hit
PfamiView protein in Pfam
PF00010 HLH, 1 hit
SMARTiView protein in SMART
SM00353 HLH, 1 hit
SUPFAMiSSF47459 SSF47459, 1 hit
PROSITEiView protein in PROSITE
PS50888 BHLH, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiSRBP1_RAT
AccessioniPrimary (citable) accession number: P56720
Secondary accession number(s): Q99PI6, Q99PI7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: February 5, 2008
Last modified: November 7, 2018
This is version 169 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
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Main funding by: National Institutes of Health

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