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Protein

Leptin

Gene

LEP

Organism
Homo sapiens (Human)
Status
Unreviewed-Annotation score: Annotation score: 5 out of 5-Protein inferred from homologyi

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. 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. 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. 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. 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. 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. In adaptive immunity, promotes the switch of memory T-cells towards T helper-1 cell immune responses. Increases CD4+CD25- T-cell proliferation and reduces autophagy during TCR (T-cell receptor) stimulation, through MTOR signaling pathway activation and BCL2 up-regulation.UniRule annotation

GO - Biological processi

Complete GO annotation...

Names & Taxonomyi

Protein namesi
Recommended name:
LeptinUniRule annotation
Alternative name(s):
Obesity factorUniRule annotation
Gene namesi
Name:LEPImported
ORF Names:hCG_33000Imported, tcag7.84Imported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Subcellular locationi

  • Secreted UniRule annotation

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

SecretedUniRule annotation

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA228.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2121Sequence analysisAdd
BLAST
Chaini22 – 167146LeptinSequence analysisPRO_5007306102Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi117 ↔ 167UniRule annotation

Keywords - PTMi

Disulfide bondUniRule annotation

Interactioni

Protein-protein interaction databases

STRINGi9606.ENSP00000312652.

Family & Domainsi

Sequence similaritiesi

Belongs to the leptin family.UniRule annotation

Keywords - Domaini

SignalSequence analysis

Phylogenomic databases

eggNOGiENOG410IVT0. Eukaryota.
ENOG410Y7NT. LUCA.
HOVERGENiHBG007860.
KOiK05424.
OMAiINDISHT.

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.

A4D0Y8-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MHWGTLCGFL WLWPYLFYVQ AVPIQKVQDD TKTLIKTIVT RINDISHTQS
60 70 80 90 100
VSSKQKVTGL DFIPGLHPIL TLSKMDQTLA VYQQILTSMP SRNVIQISND
110 120 130 140 150
LENLRDLLHV LAFSKSCHLP WASGLETLDS LGGVLEASGY STEVVALSRL
160
QGSLQDMLWQ LDLSPGC
Length:167
Mass (Da):18,641
Last modified:April 3, 2007 - v1
Checksum:iC91A121E92D37B69
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
CH236947 Genomic DNA. Translation: EAL24315.1.
CH471070 Genomic DNA. Translation: EAW83640.1.
RefSeqiNP_000221.1. NM_000230.2.
UniGeneiHs.194236.

Genome annotation databases

GeneIDi3952.
KEGGihsa:3952.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
CH236947 Genomic DNA. Translation: EAL24315.1.
CH471070 Genomic DNA. Translation: EAW83640.1.
RefSeqiNP_000221.1. NM_000230.2.
UniGeneiHs.194236.

3D structure databases

ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000312652.

Protocols and materials databases

DNASUi3952.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi3952.
KEGGihsa:3952.

Organism-specific databases

CTDi3952.
PharmGKBiPA228.

Phylogenomic databases

eggNOGiENOG410IVT0. Eukaryota.
ENOG410Y7NT. LUCA.
HOVERGENiHBG007860.
KOiK05424.
OMAiINDISHT.

Miscellaneous databases

GenomeRNAii3952.

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. "The sequence of the human genome."
    Venter J.C., Adams M.D., Myers E.W., Li P.W., Mural R.J., Sutton G.G., Smith H.O., Yandell M., Evans C.A., Holt R.A., Gocayne J.D., Amanatides P., Ballew R.M., Huson D.H., Wortman J.R., Zhang Q., Kodira C.D., Zheng X.H.
    , Chen L., Skupski M., Subramanian G., Thomas P.D., Zhang J., Gabor Miklos G.L., Nelson C., Broder S., Clark A.G., Nadeau J., McKusick V.A., Zinder N., Levine A.J., Roberts R.J., Simon M., Slayman C., Hunkapiller M., Bolanos R., Delcher A., Dew I., Fasulo D., Flanigan M., Florea L., Halpern A., Hannenhalli S., Kravitz S., Levy S., Mobarry C., Reinert K., Remington K., Abu-Threideh J., Beasley E., Biddick K., Bonazzi V., Brandon R., Cargill M., Chandramouliswaran I., Charlab R., Chaturvedi K., Deng Z., Di Francesco V., Dunn P., Eilbeck K., Evangelista C., Gabrielian A.E., Gan W., Ge W., Gong F., Gu Z., Guan P., Heiman T.J., Higgins M.E., Ji R.R., Ke Z., Ketchum K.A., Lai Z., Lei Y., Li Z., Li J., Liang Y., Lin X., Lu F., Merkulov G.V., Milshina N., Moore H.M., Naik A.K., Narayan V.A., Neelam B., Nusskern D., Rusch D.B., Salzberg S., Shao W., Shue B., Sun J., Wang Z., Wang A., Wang X., Wang J., Wei M., Wides R., Xiao C., Yan C., Yao A., Ye J., Zhan M., Zhang W., Zhang H., Zhao Q., Zheng L., Zhong F., Zhong W., Zhu S., Zhao S., Gilbert D., Baumhueter S., Spier G., Carter C., Cravchik A., Woodage T., Ali F., An H., Awe A., Baldwin D., Baden H., Barnstead M., Barrow I., Beeson K., Busam D., Carver A., Center A., Cheng M.L., Curry L., Danaher S., Davenport L., Desilets R., Dietz S., Dodson K., Doup L., Ferriera S., Garg N., Gluecksmann A., Hart B., Haynes J., Haynes C., Heiner C., Hladun S., Hostin D., Houck J., Howland T., Ibegwam C., Johnson J., Kalush F., Kline L., Koduru S., Love A., Mann F., May D., McCawley S., McIntosh T., McMullen I., Moy M., Moy L., Murphy B., Nelson K., Pfannkoch C., Pratts E., Puri V., Qureshi H., Reardon M., Rodriguez R., Rogers Y.H., Romblad D., Ruhfel B., Scott R., Sitter C., Smallwood M., Stewart E., Strong R., Suh E., Thomas R., Tint N.N., Tse S., Vech C., Wang G., Wetter J., Williams S., Williams M., Windsor S., Winn-Deen E., Wolfe K., Zaveri J., Zaveri K., Abril J.F., Guigo R., Campbell M.J., Sjolander K.V., Karlak B., Kejariwal A., Mi H., Lazareva B., Hatton T., Narechania A., Diemer K., Muruganujan A., Guo N., Sato S., Bafna V., Istrail S., Lippert R., Schwartz R., Walenz B., Yooseph S., Allen D., Basu A., Baxendale J., Blick L., Caminha M., Carnes-Stine J., Caulk P., Chiang Y.H., Coyne M., Dahlke C., Mays A., Dombroski M., Donnelly M., Ely D., Esparham S., Fosler C., Gire H., Glanowski S., Glasser K., Glodek A., Gorokhov M., Graham K., Gropman B., Harris M., Heil J., Henderson S., Hoover J., Jennings D., Jordan C., Jordan J., Kasha J., Kagan L., Kraft C., Levitsky A., Lewis M., Liu X., Lopez J., Ma D., Majoros W., McDaniel J., Murphy S., Newman M., Nguyen T., Nguyen N., Nodell M., Pan S., Peck J., Peterson M., Rowe W., Sanders R., Scott J., Simpson M., Smith T., Sprague A., Stockwell T., Turner R., Venter E., Wang M., Wen M., Wu D., Wu M., Xia A., Zandieh A., Zhu X.
    Science 291:1304-1351(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE.
  2. "Human chromosome 7: DNA sequence and biology."
    Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S.
    , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J., Grzeschik K.H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Dohner H., Dohner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.C.
    Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S.
    , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Nusskern D., Zhang Q., Gu Z., Lu F., Zeesman S., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P., Lococo F., Belloni E., Shaffer L.G., Morton C.C., Pober B., Gusella J., Bruns G., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.Angel., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C.
    Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE.
  4. Cited for: NUCLEOTIDE SEQUENCE.

Entry informationi

Entry nameiA4D0Y8_HUMAN
AccessioniPrimary (citable) accession number: A4D0Y8
Entry historyi
Integrated into UniProtKB/TrEMBL: April 3, 2007
Last sequence update: April 3, 2007
Last modified: June 8, 2016
This is version 82 of the entry and version 1 of the sequence. [Complete history]
Entry statusiUnreviewed (UniProtKB/TrEMBL)
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

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.