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Protein

Leptin

Gene

LEP

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in the activation of several major signaling pathways (By similarity). In the hypothalamus, acts as an appetite-regulating factor that induces a decrease in food intake and an increase in energy consumption by inducing anorexinogenic factors and suppressing orexigenic neuropeptides, also regulates bone mass and secretion of hypothalamo-pituitary-adrenal hormones. In the periphery, increases basal metabolism, influences reproductive function, regulates pancreatic beta-cell function and insulin secretion, is pro-angiogenic for endothelial cell and affects innate and adaptive immunity (By similarity). In the arcuate nucleus of the hypothalamus, activates by depolarization POMC neurons inducing FOS and SOCS3 expression to release anorexigenic peptides and inhibits by hyperpolarization NPY neurons inducing SOCS3 with a consequent reduction on release of orexigenic peptides (By similarity). In addition to its known satiety inducing effect, has a modulatory role in nutrient absorption. In the intestine, reduces glucose absorption by enterocytes by activating PKC and leading to a sequential activation of p38, PI3K and ERK signaling pathways which exerts an inhibitory effect on glucose absorption (By similarity). Acts as a growth factor on certain tissues, through the activation of different signaling pathways increases expression of genes involved in cell cycle regulation such as CCND1, via JAK2-STAT3 pathway, or VEGFA, via MAPK1/3 and PI3K-AKT1 pathways (By similarity). May also play an apoptotic role via JAK2-STAT3 pathway and up-regulation of BIRC5 expression. Pro-angiogenic, has mitogenic activity on vascular endothelial cells and plays a role in matrix remodeling by regulating the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). In innate immunity, modulates the activity and function of neutrophils by increasing chemotaxis and the secretion of oxygen radicals. Increases phagocytosis by macrophages and enhances secretion of pro-inflammatory mediators. Increases cytotoxic ability of NK cells. Plays a pro-inflammatory role, in synergy with IL1B, by inducing NOS2 wich promotes the production of IL6, IL8 and Prostaglandin E2, through a signaling pathway that involves JAK2, PI3K, MAP2K1/MEK1 and MAPK14/p38 (By similarity). In adaptive immunity, promotes the switch of memory T-cells towards T helper-1 cell immune responses (By similarity). Increases CD4+CD25- T-cell proliferation and reduces autophagy during TCR (T-cell receptor) stimulation, through MTOR signaling pathway activation and BCL2 up-regulation (By similarity).By similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Names & Taxonomyi

Protein namesi
Recommended name:
Leptin
Alternative name(s):
Obesity factor
Gene namesi
Name:LEP
Synonyms:OB, OBS
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Unplaced

Subcellular locationi

  • Secreted By similarity

GO - Cellular componenti

  • extracellular space Source: AgBase
  • intracellular Source: GOC
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Keywords - Diseasei

Obesity

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2121Sequence analysisAdd
BLAST
Chaini22 – 167146LeptinPRO_0000017679Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi117 ↔ 167By similarity

Keywords - PTMi

Disulfide bond

Proteomic databases

PaxDbiP50595.
PRIDEiP50595.

Interactioni

GO - Molecular functioni

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000019853.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2A16model-A1-167[»]
ProteinModelPortaliP50595.
SMRiP50595. Positions 24-167.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the leptin family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IVT0. Eukaryota.
ENOG410Y7NT. LUCA.
HOGENOMiHOG000252923.
HOVERGENiHBG007860.
InParanoidiP50595.
KOiK05424.

Family and domain databases

Gene3Di1.20.1250.10. 1 hit.
InterProiIPR009079. 4_helix_cytokine-like_core.
IPR012351. 4_helix_cytokine_core.
IPR000065. Leptin.
[Graphical view]
PANTHERiPTHR11724. PTHR11724. 1 hit.
PfamiPF02024. Leptin. 1 hit.
[Graphical view]
PIRSFiPIRSF001837. Leptin. 1 hit.
PRINTSiPR00495. LEPTIN.
ProDomiPD005698. Leptin. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SUPFAMiSSF47266. SSF47266. 1 hit.

Sequencei

Sequence statusi: Complete.

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

P50595-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRCGPLYRFL WLWPYLSYVE AVPIRKVQDD TKTLIKTIVT RINDISHTQS
60 70 80 90 100
VSSKQRVTGL DFIPGLHPLL SLSKMDQTLA IYQQILTSLP SRNVVQISND
110 120 130 140 150
LENLRDLLHL LAASKSCPLP QVRALESLES LGVVLEASLY STEVVALSRL
160
QGSLQDMLRQ LDLSPGC
Length:167
Mass (Da):18,716
Last modified:October 1, 1996 - v1
Checksum:i94C666B3069E50B7
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti25 – 251R → Q in AAB06579 (Ref. 6) Curated
Sequence conflicti166 – 1661G → E in AAB06579 (Ref. 6) Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti25 – 251R → C.3 Publications
Natural varianti80 – 801A → V.2 Publications

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U43943 mRNA. Translation: AAA85906.1.
U50365 Genomic DNA. Translation: AAB61244.1.
AJ236854 Genomic DNA. Translation: CAB38018.1.
AJ132764 Genomic DNA. Translation: CAB64255.1.
AJ512638, AJ512639 Genomic DNA. Translation: CAD54745.1.
AF120500 Genomic DNA. Translation: AAD23567.1.
BT020625 mRNA. Translation: AAX08642.1.
U65793 mRNA. Translation: AAB06579.1.
AB003143 mRNA. Translation: BAA19750.1.
Y11369 Genomic DNA. Translation: CAA72197.1.
U43833 Genomic DNA. Translation: AAB18762.1.
RefSeqiNP_776353.2. NM_173928.2.
UniGeneiBt.1939.

Genome annotation databases

GeneIDi280836.
KEGGibta:280836.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U43943 mRNA. Translation: AAA85906.1.
U50365 Genomic DNA. Translation: AAB61244.1.
AJ236854 Genomic DNA. Translation: CAB38018.1.
AJ132764 Genomic DNA. Translation: CAB64255.1.
AJ512638, AJ512639 Genomic DNA. Translation: CAD54745.1.
AF120500 Genomic DNA. Translation: AAD23567.1.
BT020625 mRNA. Translation: AAX08642.1.
U65793 mRNA. Translation: AAB06579.1.
AB003143 mRNA. Translation: BAA19750.1.
Y11369 Genomic DNA. Translation: CAA72197.1.
U43833 Genomic DNA. Translation: AAB18762.1.
RefSeqiNP_776353.2. NM_173928.2.
UniGeneiBt.1939.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2A16model-A1-167[»]
ProteinModelPortaliP50595.
SMRiP50595. Positions 24-167.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000019853.

Proteomic databases

PaxDbiP50595.
PRIDEiP50595.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi280836.
KEGGibta:280836.

Organism-specific databases

CTDi3952.

Phylogenomic databases

eggNOGiENOG410IVT0. Eukaryota.
ENOG410Y7NT. LUCA.
HOGENOMiHOG000252923.
HOVERGENiHBG007860.
InParanoidiP50595.
KOiK05424.

Family and domain databases

Gene3Di1.20.1250.10. 1 hit.
InterProiIPR009079. 4_helix_cytokine-like_core.
IPR012351. 4_helix_cytokine_core.
IPR000065. Leptin.
[Graphical view]
PANTHERiPTHR11724. PTHR11724. 1 hit.
PfamiPF02024. Leptin. 1 hit.
[Graphical view]
PIRSFiPIRSF001837. Leptin. 1 hit.
PRINTSiPR00495. LEPTIN.
ProDomiPD005698. Leptin. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SUPFAMiSSF47266. SSF47266. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Tellam R.L., Briscoe S., Vuocolo A.
    Submitted (JUN-1997) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
    Tissue: Liver.
  2. "Resequencing of DNA from a diverse panel of cattle reveals a high level of polymorphism in both intron and exon."
    Konfortov B.A., Licence V.E., Miller J.R.
    Mamm. Genome 10:1142-1145(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS CYS-25 AND VAL-80.
    Strain: Jersey.
  3. "Association of leptin gene polymorphisms with serum leptin concentration in dairy cows."
    Liefers S.C., te Pas M.F.W., Veerkamp R.F., Chilliard Y., Delavaud C., Gerritsen R., van der Lende T.
    Mamm. Genome 14:657-663(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS CYS-25 AND VAL-80.
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT CYS-25.
  5. "Exon two of the bovine obese, leptin, gene."
    Fitzsimmons C.J., Schmutz S.M.
    Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-48.
  6. "Partial cloning of bovine obesity gene."
    Ji S., Spurlock M.E.
    Submitted (AUG-1996) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 22-167.
  7. Kawakita Y., Abe H., Miyashige T.
    Submitted (APR-1997) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 22-167.
    Tissue: White adipose tissue.
  8. "Two novel polymorphisms in the bovine obesity gene (OBS)."
    Lien S., Sundvold H., Klungland H., Vaege D.I.
    Anim. Genet. 28:245-245(1997)
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 46-145.
  9. "Chromosomal localization of the bovine obesity (OBS) gene."
    Pfister-Genskow M.A., Hayes H., Eggen A., Bishop M.D.
    Mamm. Genome 7:398-399(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 60-146.

Entry informationi

Entry nameiLEP_BOVIN
AccessioniPrimary (citable) accession number: P50595
Secondary accession number(s): O97918
, Q5EAE4, Q95133, Q9TSZ9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: June 8, 2016
This is version 100 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.