P50596 (LEP_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Leptin

Alternative name(s):
Obesity factor

Gene names

Name:	Lep
Synonyms:	Ob

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

General annotation (Comments)

Function	May function as part of a signaling pathway that acts to regulate the size of the body fat depot. An increase in the level of Lep may act directly or indirectly on the CNS to inhibit food intake and/or regulate energy expenditure as part of a homeostatic mechanism to maintain constancy of the adipose mass.
Subcellular location	Secreted Probable.
Sequence similarities	Belongs to the leptin family.

Ontologies

Keywords
Cellular component	Secreted
Disease	Obesity
Domain	Signal
PTM	Disulfide bond
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	JAK-STAT cascade Traceable author statement PubMed 12101402. Source: RGD adipose tissue development Inferred from electronic annotation. Source: Compara adult feeding behavior Inferred from sequence or structural similarity PubMed 9590691. Source: HGNC bile acid metabolic process Inferred from electronic annotation. Source: Compara bone mineralization involved in bone maturation Inferred from direct assay PubMed 21353474. Source: RGD cAMP-mediated signaling Traceable author statement PubMed 12101402. Source: RGD cellular response to L-ascorbic acid Inferred from expression pattern PubMed 20400526. Source: RGD cellular response to retinoic acid Inferred from expression pattern PubMed 19212007. Source: RGD central nervous system neuron development Inferred from electronic annotation. Source: Compara cholesterol metabolic process Inferred from electronic annotation. Source: Compara circadian rhythm Inferred from expression pattern PubMed 21164040. Source: RGD eating behavior Inferred from electronic annotation. Source: Compara energy reserve metabolic process Inferred from direct assay PubMed 12058043. Source: RGD fatty acid catabolic process Inferred from direct assay PubMed 12058043. Source: RGD female pregnancy Inferred from expression pattern PubMed 21303957. Source: RGD glucose metabolic process Inferred from electronic annotation. Source: Compara glycerol biosynthetic process Inferred from direct assay PubMed 21068181. Source: RGD hormone metabolic process Inferred from electronic annotation. Source: Compara insulin secretion Inferred from electronic annotation. Source: Compara leptin-mediated signaling pathway Inferred from direct assay PubMed 9070213PubMed 9618284. Source: RGD leukocyte tethering or rolling Inferred from direct assay PubMed 20150963. Source: RGD negative regulation of apoptotic process Inferred from direct assay PubMed 19730157. Source: RGD negative regulation of appetite Inferred from sequence or structural similarity PubMed 9590691. Source: HGNC negative regulation of cartilage development Inferred from direct assay PubMed 19876764. Source: RGD negative regulation of glucagon secretion Inferred from electronic annotation. Source: Compara negative regulation of glutamine transport Inferred from mutant phenotype PubMed 20448142. Source: RGD negative regulation of metabolic process Inferred from direct assay PubMed 12130569. Source: RGD negative regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara negative regulation of vasoconstriction Inferred from direct assay PubMed 20978518. Source: RGD ovulation from ovarian follicle Inferred from direct assay PubMed 17071778. Source: RGD placenta development Inferred from electronic annotation. Source: Compara positive regulation of MAPK cascade Inferred from direct assay PubMed 9618284. Source: RGD positive regulation of STAT protein import into nucleus Inferred from electronic annotation. Source: Compara positive regulation of cell proliferation Inferred from direct assay PubMed 18978578. Source: RGD positive regulation of cytokine production Inferred from expression pattern PubMed 19922787. Source: RGD positive regulation of developmental growth Inferred from electronic annotation. Source: Compara positive regulation of follicle-stimulating hormone secretion Inferred from expression pattern PubMed 19112389. Source: RGD positive regulation of hepatic stellate cell activation Inferred from direct assay PubMed 19299451. Source: RGD positive regulation of insulin receptor signaling pathway Inferred from direct assay PubMed 20977462. Source: RGD positive regulation of ion transport Inferred from direct assay PubMed 20203064. Source: RGD positive regulation of luteinizing hormone secretion Inferred from expression pattern PubMed 19112389. Source: RGD positive regulation of myeloid cell differentiation Inferred from electronic annotation. Source: Compara positive regulation of tyrosine phosphorylation of Stat3 protein Inferred from mutant phenotype PubMed 19726711. Source: RGD regulation of blood pressure Inferred from direct assay PubMed 20059648. Source: RGD regulation of gluconeogenesis Inferred from electronic annotation. Source: Compara regulation of insulin secretion Inferred from electronic annotation. Source: Compara regulation of intestinal cholesterol absorption Inferred from electronic annotation. Source: Compara regulation of lipoprotein lipid oxidation Inferred from direct assay PubMed 21068181. Source: RGD regulation of steroid biosynthetic process Inferred from electronic annotation. Source: Compara response to dietary excess Inferred from mutant phenotype PubMed 19726711. Source: RGD response to hypoxia Inferred from expression pattern PubMed 15284063. Source: RGD response to insulin stimulus Inferred from electronic annotation. Source: Compara response to vitamin E Inferred from expression pattern PubMed 20404018. Source: RGD tyrosine phosphorylation of STAT protein Inferred from electronic annotation. Source: Compara
Cellular_component	extracellular space Inferred from direct assay PubMed 9590691. Source: HGNC
Molecular_function	cytokine activity Traceable author statement PubMed 11829746. Source: RGD hormone activity Inferred from direct assay PubMed 9070213. Source: RGD peptide hormone receptor binding Inferred from direct assay PubMed 9070213. Source: RGD
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 21	21	Potential
	Chain	22 – 167	146	Leptin		PRO_0000017690
Amino acid modifications
	Disulfide bond	117 ↔ 167		By similarity
Experimental info
	Sequence conflict	32	1	K → T Ref.2
	Sequence conflict	163	1	L → V in AAC52514. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	P50596 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: 3B5B563DA42EC84E	FASTA	167	18,866
	10 20 30 40 50 60 MCWRPLCRFL WLWSYLSYVQ AVPIHKVQDD TKTLIKTIVT RINDISHTQS VSARQRVTGL 70 80 90 100 110 120 DFIPGLHPIL SLSKMDQTLA VYQQILTSLP SQNVLQIAHD LENLRDLLHL LAFSKSCSLP 130 140 150 160 QTRGLQKPES LDGVLEASLY STEVVALSRL QGSLQDILQQ LDLSPEC

References

[1]	"Molecular cloning of rat obese cDNA and augmented gene expression in genetically obese Zucker fatty (fa/fa) rats." Ogawa Y., Masuzaki H., Isse N., Okazaki T., Mori K., Shigemoto M., Satoh N., Tamura N., Hosoda K., Yoshimasa Y., Jingami H., Kawada T., Nakao K. J. Clin. Invest. 96:1647-1652(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Testis.
[2]	"Enhanced expression of rat obese (ob) gene in adipose tissues of ventromedial hypothalamus (VMH)-lesioned rats." Funahashi T., Shimomura I., Hiraoka H., Arai T., Takahashi M., Nakamura T., Nozaki S., Yamashita S., Takemura K., Tokunaga K. Biochem. Biophys. Res. Commun. 211:469-475(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Sprague-Dawley. Tissue: Adipose tissue.
[3]	"Cloning of rat obese cDNA and its expression in obese rats." Murakami T., Shima K. Biochem. Biophys. Res. Commun. 209:944-952(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Leto, OLETF and Zucker. Tissue: Adipose tissue.
[4]	Donohoue P.A., Sivitz W.I., Bailey H.L. Submitted (FEB-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 14-167. Strain: Sprague-Dawley. Tissue: Adipose tissue.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	D45862 mRNA. Translation: BAA08296.1. S78586 mRNA. Translation: AAB34657.2. D49653 mRNA. Translation: BAA08529.1. U48849 mRNA. Translation: AAC52514.1.
IPI	IPI00199521.
PIR	LTRT. PC4034.
RefSeq	NP_037208.1. NM_013076.3.
UniGene	Rn.44444.
3D structure databases
ProteinModelPortal	P50596.
SMR	P50596. Positions 24-167.
ModBase	Search...
Protein-protein interaction databases
STRING	10116.ENSRNOP00000008020.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000071926; ENSRNOP00000066184; ENSRNOG00000045797.
GeneID	25608.
KEGG	rno:25608.
UCSC	RGD:3000. rat.
Organism-specific databases
CTD	3952.
RGD	3000. Lep.
Phylogenomic databases
eggNOG	NOG45133.
GeneTree	ENSGT00390000011772.
HOGENOM	HOG000252923.
HOVERGEN	HBG007860.
InParanoid	P50596.
KO	K05424.
OMA	KTIVTRI.
OrthoDB	EOG4QNMXC.
Gene expression databases
Genevestigator	P50596.
GermOnline	ENSRNOG00000006059. Rattus norvegicus.
Family and domain databases
Gene3D	1.20.1250.10. 1 hit.
InterPro	IPR009079. 4_helix_cytokine-like_core. IPR012351. 4_helix_cytokine_core. IPR000065. Leptin. [Graphical view]
PANTHER	PTHR11724. PTHR11724. 1 hit.
Pfam	PF02024. Leptin. 1 hit. [Graphical view]
PIRSF	PIRSF001837. Leptin. 1 hit.
PRINTS	PR00495. LEPTIN.
ProDom	PD005698. Leptin. 1 hit. [Graphical view] [Entries sharing at least one domain]
SUPFAM	SSF47266. 4_helix_cytokine. 1 hit.
ProtoNet	Search...
Other
NextBio	607339.

Entry information

Entry name

LEP_RAT

Accession

Primary (citable) accession number: P50596

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	April 3, 2013
This is version 96 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program