P56720 (SRBP1_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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:

1. Processed sterol regulatory element-binding protein 1

Gene names

Name:	Srebf1
Synonyms:	Srebp1

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	1134 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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'). Has dual sequence specificity binding to both an E-box motif (5'-ATCACGTGA-3') and to SRE-1 (5'-ATCACCCCAC-3').
Subunit structure	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.
Subcellular location	Endoplasmic reticulum membrane; Multi-pass membrane protein. Golgi apparatus membrane; Multi-pass membrane protein. Cytoplasmic vesicle › COPII-coated vesicle membrane; Multi-pass membrane protein. Note: Moves from the endoplasmic reticulum to the Golgi in the absence of sterols. Processed sterol regulatory element-binding protein 1: Nucleus.
Tissue specificity	Expressed predominantly in brown adipose tissue.
Post-translational modification	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. 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.
Sequence similarities	Belongs to the SREBP family. Contains 1 bHLH (basic helix-loop-helix) domain.
Sequence caution	The sequence L16995 differs from that shown. Reason: Frameshift at positions 902, 939, 956, 972 and 1016.

Ontologies

Keywords
Biological process	Cholesterol metabolism Lipid metabolism Steroid metabolism Sterol metabolism Transcription Transcription regulation
Cellular component	Cytoplasmic vesicle Endoplasmic reticulum Golgi apparatus Membrane Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transmembrane Transmembrane helix
Ligand	DNA-binding
Molecular function	Activator
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	SREBP signaling pathway Inferred from electronic annotation. Source: Compara aging Inferred from expression pattern PubMed 16741953. Source: RGD cellular response to insulin stimulus Inferred from expression pattern PubMed 10207099PubMed 19158095. Source: RGD cellular response to starvation Inferred from direct assay PubMed 16407292. Source: HGNC cholesterol metabolic process Inferred from mutant phenotype PubMed 18071061. Source: RGD insulin receptor signaling pathway Inferred from electronic annotation. Source: Compara lipid biosynthetic process Inferred from sequence or structural similarity. Source: UniProtKB lung development Inferred from expression pattern PubMed 12896875. Source: RGD negative regulation of insulin secretion Inferred from electronic annotation. Source: Compara negative regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara positive regulation of cholesterol biosynthetic process Inferred from electronic annotation. Source: Compara positive regulation of histone deacetylation Inferred from electronic annotation. Source: Compara positive regulation of transcription, DNA-dependent Inferred from mutant phenotype PubMed 10207099. Source: RGD positive regulation of triglyceride biosynthetic process Inferred from sequence or structural similarity. Source: UniProtKB regulation of fatty acid metabolic process Inferred from electronic annotation. Source: Compara regulation of heart rate by chemical signal Inferred from electronic annotation. Source: Compara response to cAMP Inferred from expression pattern PubMed 10207099. Source: RGD response to drug Inferred from expression pattern PubMed 17526932PubMed 18171911. Source: RGD response to fatty acid Inferred from expression pattern PubMed 16222032. Source: RGD response to food Inferred from expression pattern PubMed 19357831. Source: RGD response to glucagon stimulus Inferred from expression pattern PubMed 10207099. Source: RGD response to glucose stimulus Inferred from electronic annotation. Source: Compara response to progesterone stimulus Inferred from expression pattern PubMed 11278421. Source: RGD response to retinoic acid Inferred from expression pattern PubMed 9121491. Source: RGD transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	ER to Golgi transport vesicle membrane Inferred from electronic annotation. Source: UniProtKB-SubCell Golgi membrane Inferred from electronic annotation. Source: UniProtKB-SubCell cytoplasmic part Inferred from sequence or structural similarity. Source: UniProtKB endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW nucleus Inferred from direct assay PubMed 15944339. Source: RGD protein complex Inferred from direct assay PubMed 19158095. Source: RGD
Molecular_function	chromatin binding Inferred from electronic annotation. Source: Compara sequence-specific DNA binding Inferred from direct assay PubMed 9786926. Source: RGD sequence-specific DNA binding transcription factor activity Inferred from sequence or structural similarity PubMed 16407292. Source: HGNC sterol response element binding Inferred from sequence or structural similarity PubMed 16407292. Source: HGNC
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform SREBP-1A (identifier: P56720-2)

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.

Isoform SREBP-1C (identifier: P56720-1)

Also known as: ADD1;

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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1134	1134	Sterol regulatory element-binding protein 1		PRO_0000127450
	Chain	1 – 480	480	Processed sterol regulatory element-binding protein 1		PRO_0000314031
Regions
	Topological domain	1 – 481	481	Cytoplasmic Potential
	Transmembrane	482 – 502	21	Helical; Potential
	Topological domain	503 – 536	34	Lumenal Potential
	Transmembrane	537 – 557	21	Helical; Potential
	Topological domain	558 – 1134	577	Cytoplasmic Potential
	Domain	317 – 367	51	bHLH
	Region	1 – 60	60	Transcriptional activation (acidic) By similarity
	Region	227 – 487	261	Interaction with LMNA By similarity
	Region	367 – 388	22	Leucine-zipper
	Compositional bias	61 – 176	116	Pro/Ser-rich
	Compositional bias	420 – 453	34	Gly/Pro/Ser-rich
Sites
	Site	451 – 452	2	Cleavage; by caspase-3 and caspase-7 By similarity
	Site	480 – 481	2	Cleavage; by S2P By similarity
	Site	519 – 520	2	Cleavage; by S1P By similarity
Amino acid modifications
	Modified residue	109	1	Phosphotyrosine By similarity
	Modified residue	116	1	Phosphoserine By similarity
	Modified residue	331	1	Phosphoserine; by SIK1 By similarity
	Modified residue	332	1	Phosphoserine; by SIK1 By similarity
	Modified residue	389	1	Phosphoserine; by AMPK By similarity
	Modified residue	395	1	Phosphoserine; by SIK1 By similarity
Natural variations
	Alternative sequence	1 – 29	29	MDELP…LLTDI → MDCTF in isoform SREBP-1C.		VSP_030860
	Natural variant	779	1	V → M in spontaneously hypertensive rats. Ref.3
Experimental info
	Sequence conflict	267	1	G → A in L16995. Ref.1
	Sequence conflict	475	1	R → P in L16995. Ref.1
	Sequence conflict	817	1	D → H in L16995. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform SREBP-1A [UniParc]. Last modified February 5, 2008. Version 3. Checksum: 1D31A9AD3C36AB29	FASTA	1,134	120,521
	10 20 30 40 50 60 MDELPFGEAA LEQALAEVCE MDAALLTDIE DMLQLINNQD SDFPGLFDAP YAGGETGDTG 70 80 90 100 110 120 PSSPGASSPE SFSSPASLGS SLEAFLGGPK VTPAPLSPPP SAPTAVKMYP SVPPFSPGPG 130 140 150 160 170 180 IKEEPVPLTI LQPPAPQPSP GTLLPPSFPP PPVQLSPAPV LGYSSLPSGF SGTLPGNTQQ 190 200 210 220 230 240 TPSSLPLGST PGISPTPLHT QVQSSAAQQP PPASAAPRMS TVASQIQQVP VVLQPHFIKA 250 260 270 280 290 300 DSLLLTAVKT DTGATMKTAG INTLAPGTAV QAGPLQTLVS GGTILATVPL VVDTDKLPIH 310 320 330 340 350 360 RLAAGGKALG SAQSRGEKRT AHNAIEKRYR SSINDKIVEL KDLVVGTEAK LNKSAVLRKA 370 380 390 400 410 420 IDYIRFLQHS NQKLKQENLT LRSAHKSKSL KDLVSACGSG GGTDVSMEGM KPEVVETLTP 430 440 450 460 470 480 PPSDAGSPSQ SSPLSLGSRG SSSGGSDSEP DSPAFEDNQV KAQRLPSHSR GMLDRSRLAL 490 500 510 520 530 540 CVLVFLCLTC NPLASLFGWG ILTPSDASGV HRSSGRSMLE AESRDGSNWT QWLLPPLVWL 550 560 570 580 590 600 ANGLLVLACL ALLFVYGEPV TRPHSGPAVH FWRHRKQADL DLARGDFAQA AQQLWLALQA 610 620 630 640 650 660 LGRPLPTSNL DLACSLLWNL VRHLLQRLWV GRWLAGQAGG LQRDYRLRKD ARASARDAAV 670 680 690 700 710 720 VYHKLHQLHA MGKYTGGHLV ASNLALSALN LAECAGDAIS MATLAEIYVA AALRVKTSLP 730 740 750 760 770 780 RALHFLTRFF LSSARQACLA QSGAVPLAMQ WLCHPVGHRF FVDGDWAVHG APQESLYSVA 790 800 810 820 830 840 GNPVDPLAQV TRLFCEHLLE RALNCIAQPS PGAADGDREF SDALGYLQLL NSCSDAVGAP 850 860 870 880 890 900 ACSFSVSSSM ATTTGTDPVA KWWASLTAVV IHWLRRDEEA AERLYPLVEH IPQVLQETER 910 920 930 940 950 960 PLPRAALYSF KAARALLDHR KVESSPASLA ICEKASGYLR DSLASTSTAS SIDKAMQLLL 970 980 990 1000 1010 1020 CDLLLVARTS LWRRQQSAAS AQGAHGTSNG PQASALELRG FQHDLSSLRR LAQSFRPAMR 1030 1040 1050 1060 1070 1080 RVFLHEATAR LMAGASPART HQLLDRSLRR RAGSSGKGGA AAELEPRPTW REHTEALLLA 1090 1100 1110 1120 1130 SCYLPPAFLS APGQRVSMLA EAARTVEKLG DHRLLLDCQQ MLLRLGGGTT VTSS
	Isoform SREBP-1C (ADD1) [UniParc]. Checksum: C7CDAE780EA056D3	FASTA	1,110	118,027
	10 20 30 40 50 60 MDCTFEDMLQ LINNQDSDFP GLFDAPYAGG ETGDTGPSSP GASSPESFSS PASLGSSLEA 70 80 90 100 110 120 FLGGPKVTPA PLSPPPSAPT AVKMYPSVPP FSPGPGIKEE PVPLTILQPP APQPSPGTLL 130 140 150 160 170 180 PPSFPPPPVQ LSPAPVLGYS SLPSGFSGTL PGNTQQTPSS LPLGSTPGIS PTPLHTQVQS 190 200 210 220 230 240 SAAQQPPPAS AAPRMSTVAS QIQQVPVVLQ PHFIKADSLL LTAVKTDTGA TMKTAGINTL 250 260 270 280 290 300 APGTAVQAGP LQTLVSGGTI LATVPLVVDT DKLPIHRLAA GGKALGSAQS RGEKRTAHNA 310 320 330 340 350 360 IEKRYRSSIN DKIVELKDLV VGTEAKLNKS AVLRKAIDYI RFLQHSNQKL KQENLTLRSA 370 380 390 400 410 420 HKSKSLKDLV SACGSGGGTD VSMEGMKPEV VETLTPPPSD AGSPSQSSPL SLGSRGSSSG 430 440 450 460 470 480 GSDSEPDSPA FEDNQVKAQR LPSHSRGMLD RSRLALCVLV FLCLTCNPLA SLFGWGILTP 490 500 510 520 530 540 SDASGVHRSS GRSMLEAESR DGSNWTQWLL PPLVWLANGL LVLACLALLF VYGEPVTRPH 550 560 570 580 590 600 SGPAVHFWRH RKQADLDLAR GDFAQAAQQL WLALQALGRP LPTSNLDLAC SLLWNLVRHL 610 620 630 640 650 660 LQRLWVGRWL AGQAGGLQRD YRLRKDARAS ARDAAVVYHK LHQLHAMGKY TGGHLVASNL 670 680 690 700 710 720 ALSALNLAEC AGDAISMATL AEIYVAAALR VKTSLPRALH FLTRFFLSSA RQACLAQSGA 730 740 750 760 770 780 VPLAMQWLCH PVGHRFFVDG DWAVHGAPQE SLYSVAGNPV DPLAQVTRLF CEHLLERALN 790 800 810 820 830 840 CIAQPSPGAA DGDREFSDAL GYLQLLNSCS DAVGAPACSF SVSSSMATTT GTDPVAKWWA 850 860 870 880 890 900 SLTAVVIHWL RRDEEAAERL YPLVEHIPQV LQETERPLPR AALYSFKAAR ALLDHRKVES 910 920 930 940 950 960 SPASLAICEK ASGYLRDSLA STSTASSIDK AMQLLLCDLL LVARTSLWRR QQSAASAQGA 970 980 990 1000 1010 1020 HGTSNGPQAS ALELRGFQHD LSSLRRLAQS FRPAMRRVFL HEATARLMAG ASPARTHQLL 1030 1040 1050 1060 1070 1080 DRSLRRRAGS SGKGGAAAEL EPRPTWREHT EALLLASCYL PPAFLSAPGQ RVSMLAEAAR 1090 1100 1110 TVEKLGDHRL LLDCQQMLLR LGGGTTVTSS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Genome sequence of the Brown Norway rat yields insights into mammalian evolution." Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J., Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G., Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G., Morgan M. , Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G., Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S., Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T., Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D., Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L., Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D., Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M., Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C., Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J., Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H., Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X., Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q., Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P., Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A., Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C., Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J., Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J., Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F., Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A., Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A., Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J., Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M., Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C., Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L., Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W., Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y., Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V., Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M., Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S., Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B., Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., Mockrin S., Collins F.S. Nature 428:493-521(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Brown Norway.
[2]	"ADD1: a novel helix-loop-helix transcription factor associated with adipocyte determination and differentiation." Tontonoz P., Kim J.B., Graves R.A., Spiegelman B.M. Mol. Cell. Biol. 13:4753-4759(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-1046 (ISOFORM SREBP-1C). Tissue: Adipocyte.
[3]	"Identification of a mutation in ADD1/SREBP-1 in the spontaneously hypertensive rat." Pravenec M., Jansa P., Kostka V., Zidek V., Kren V., Forejt J., Kurtz T.W. Mamm. Genome 12:295-298(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-1012 (ISOFORM SREBP-1C), VARIANT MET-779. Strain: BN-Lx/Cub and SHR/Ola.
[4]	"Dual DNA binding specificity of ADD1/SREBP1 controlled by a single amino acid in the basic helix-loop-helix domain." Kim J.B., Spotts G.D., Halvorsen Y.D., Shih H.M., Ellenberger T., Towle H.C., Spiegelman B.M. Mol. Cell. Biol. 15:2582-2588(1995) [PubMed] [Europe PMC] [Abstract] Cited for: DNA-BINDING.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00560536. IPI00562316.
RefSeq	NP_001263636.1. NM_001276707.1. NP_001263637.1. NM_001276708.1. XP_001075680.2. XM_001075680.3. XP_213329.5. XM_213329.6.
UniGene	Rn.198857.
3D structure databases
ProteinModelPortal	P56720.
SMR	P56720. Positions 313-393.
ModBase	Search...
PTM databases
PhosphoSite	P56720.
Proteomic databases
PRIDE	P56720.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000047053; ENSRNOP00000050057; ENSRNOG00000003463.
GeneID	78968.
KEGG	rno:78968.
UCSC	RGD:69423. rat.
Organism-specific databases
CTD	6720.
RGD	69423. Srebf1.
Phylogenomic databases
eggNOG	NOG242942.
GeneTree	ENSGT00390000017651.
HOGENOM	HOG000007091.
HOVERGEN	HBG061592.
InParanoid	P56720.
KO	K07197.
OMA	FLQHSNQ.
OrthoDB	EOG4K9BBH.
Gene expression databases
ArrayExpress	P56720.
Genevestigator	P56720.
GermOnline	ENSRNOG00000003463. Rattus norvegicus.
Family and domain databases
Gene3D	4.10.280.10. 1 hit.
InterPro	IPR011598. bHLH_dom. [Graphical view]
Pfam	PF00010. HLH. 1 hit. [Graphical view]
SMART	SM00353. HLH. 1 hit. [Graphical view]
SUPFAM	SSF47459. HLH_basic. 1 hit.
PROSITE	PS50888. BHLH. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	614418.

Entry information

Entry name

SRBP1_RAT

Accession

Primary (citable) accession number: P56720
Secondary accession number(s): Q99PI6, Q99PI7

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	February 5, 2008
Last modified:	May 1, 2013
This is version 116 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program