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Protein

Leptin

Gene

LEP

Organism
Sus scrofa (Pig)
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...

Enzyme and pathway databases

ReactomeiR-SSC-2586552. Signaling by Leptin.
R-SSC-381771. Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1).
R-SSC-422085. Synthesis, secretion, and deacylation of Ghrelin.

Names & Taxonomyi

Protein namesi
Recommended name:
Leptin
Alternative name(s):
Obesity factor
Gene namesi
Name:LEP
Synonyms:OB, OBS
OrganismiSus scrofa (Pig)
Taxonomic identifieri9823 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaSuinaSuidaeSus
Proteomesi
  • UP000008227 Componenti: Chromosome 18

Subcellular locationi

  • Secreted By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Keywords - Diseasei

Obesity

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 21Sequence analysisAdd BLAST21
ChainiPRO_000001768922 – 167LeptinAdd BLAST146

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi117 ↔ 167By similarity

Keywords - PTMi

Disulfide bond

Proteomic databases

PaxDbiQ29406.
PRIDEiQ29406.

Interactioni

GO - Molecular functioni

Protein-protein interaction databases

STRINGi9823.ENSSSCP00000017572.

Structurei

3D structure databases

ProteinModelPortaliQ29406.
SMRiQ29406.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the leptin family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IVT0. Eukaryota.
ENOG410Y7NT. LUCA.
GeneTreeiENSGT00390000011772.
HOGENOMiHOG000252923.
HOVERGENiHBG007860.
InParanoidiQ29406.
KOiK05424.
OMAiINDISHT.
OrthoDBiEOG091G0Y82.
TreeFamiTF105086.

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.

Q29406-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRCGPLCRFL WLWPYLSYVE AVPIWRVQDD TKTLIKTIVT RISDISHMQS
60 70 80 90 100
VSSKQRVTGL DFIPGLHPVL SLSKMDQTLA IYQQILTSLP SRNVIQISND
110 120 130 140 150
LENLRDLLHL LASSKSCPLP QARALETLES LGGVLEASLY STEVVALSRL
160
QGALQDMLRQ LDLSPGC
Length:167
Mass (Da):18,661
Last modified:November 1, 1997 - v1
Checksum:i27550E1E0E63814E
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti21 – 22AV → GP in AAC48641 (PubMed:8856925).Curated2
Sequence conflicti97I → L in AAC48641 (PubMed:8856925).Curated1
Sequence conflicti122A → R in AAB97308 (Ref. 3) Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U63540 mRNA. Translation: AAB05923.1.
AF026976 mRNA. Translation: AAB82724.1.
U66254 Genomic DNA. Translation: AAB97308.1.
U59894 mRNA. Translation: AAB03458.1.
AF052691 mRNA. Translation: AAC06303.1.
AF102856 mRNA. Translation: AAC78147.1.
AF477387, AF477386 Genomic DNA. Translation: AAL84792.1.
U40812 mRNA. Translation: AAC48641.1.
RefSeqiNP_999005.1. NM_213840.1.
UniGeneiSsc.265.

Genome annotation databases

EnsembliENSSSCT00000018060; ENSSSCP00000017572; ENSSSCG00000016588.
GeneIDi396832.
KEGGissc:396832.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U63540 mRNA. Translation: AAB05923.1.
AF026976 mRNA. Translation: AAB82724.1.
U66254 Genomic DNA. Translation: AAB97308.1.
U59894 mRNA. Translation: AAB03458.1.
AF052691 mRNA. Translation: AAC06303.1.
AF102856 mRNA. Translation: AAC78147.1.
AF477387, AF477386 Genomic DNA. Translation: AAL84792.1.
U40812 mRNA. Translation: AAC48641.1.
RefSeqiNP_999005.1. NM_213840.1.
UniGeneiSsc.265.

3D structure databases

ProteinModelPortaliQ29406.
SMRiQ29406.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9823.ENSSSCP00000017572.

Proteomic databases

PaxDbiQ29406.
PRIDEiQ29406.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSSSCT00000018060; ENSSSCP00000017572; ENSSSCG00000016588.
GeneIDi396832.
KEGGissc:396832.

Organism-specific databases

CTDi3952.

Phylogenomic databases

eggNOGiENOG410IVT0. Eukaryota.
ENOG410Y7NT. LUCA.
GeneTreeiENSGT00390000011772.
HOGENOMiHOG000252923.
HOVERGENiHBG007860.
InParanoidiQ29406.
KOiK05424.
OMAiINDISHT.
OrthoDBiEOG091G0Y82.
TreeFamiTF105086.

Enzyme and pathway databases

ReactomeiR-SSC-2586552. Signaling by Leptin.
R-SSC-381771. Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1).
R-SSC-422085. Synthesis, secretion, and deacylation of Ghrelin.

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...

Entry informationi

Entry nameiLEP_PIG
AccessioniPrimary (citable) accession number: Q29406
Secondary accession number(s): O19095, Q95251
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: November 2, 2016
This is version 98 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

Complete proteome, Reference proteome

Documents

  1. 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.