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P41159 (LEP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 146. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Leptin
Alternative name(s):
Obese protein
Obesity factor
Gene names
Name:LEP
Synonyms:OB, OBS
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length167 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein 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.

Subunit structure

Interacts with SIGLEC6. Ref.11

Subcellular location

Secreted.

Involvement in disease

Leptin deficiency (LEPD) [MIM:614962]: A rare disease characterized by low levels of serum leptin, severe hyperphagia and intractable obesity from an early age.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.16

Sequence similarities

Belongs to the leptin family.

Ontologies

Keywords
   Cellular componentSecreted
   Coding sequence diversityPolymorphism
   DiseaseDiabetes mellitus
Disease mutation
Obesity
   DomainSignal
   PTMDisulfide bond
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processadipose tissue development

Inferred from electronic annotation. Source: Ensembl

adult feeding behavior

Inferred from sequence or structural similarity. Source: HGNC

bile acid metabolic process

Inferred from electronic annotation. Source: Ensembl

bone mineralization involved in bone maturation

Inferred from electronic annotation. Source: Ensembl

cellular response to L-ascorbic acid

Inferred from electronic annotation. Source: Ensembl

cellular response to retinoic acid

Inferred from electronic annotation. Source: Ensembl

central nervous system neuron development

Inferred from electronic annotation. Source: Ensembl

cholesterol metabolic process

Inferred from electronic annotation. Source: Ensembl

circadian rhythm

Inferred from electronic annotation. Source: Ensembl

eating behavior

Inferred from electronic annotation. Source: Ensembl

energy reserve metabolic process

Traceable author statement PubMed 9537324. Source: ProtInc

fatty acid catabolic process

Inferred from electronic annotation. Source: Ensembl

female pregnancy

Inferred from electronic annotation. Source: Ensembl

glucose metabolic process

Inferred from electronic annotation. Source: Ensembl

glycerol biosynthetic process

Inferred from electronic annotation. Source: Ensembl

hormone metabolic process

Inferred from electronic annotation. Source: Ensembl

insulin secretion

Inferred from electronic annotation. Source: Ensembl

leptin-mediated signaling pathway

Inferred from electronic annotation. Source: Ensembl

leukocyte tethering or rolling

Inferred from electronic annotation. Source: Ensembl

negative regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of appetite

Inferred from sequence or structural similarity. Source: HGNC

negative regulation of cartilage development

Inferred from electronic annotation. Source: Ensembl

negative regulation of glucagon secretion

Inferred from electronic annotation. Source: Ensembl

negative regulation of glutamine transport

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

negative regulation of vasoconstriction

Inferred from electronic annotation. Source: Ensembl

ovulation from ovarian follicle

Inferred from electronic annotation. Source: Ensembl

placenta development

Inferred from direct assay PubMed 17957153. Source: DFLAT

positive regulation of MAPK cascade

Inferred from electronic annotation. Source: Ensembl

positive regulation of STAT protein import into nucleus

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of cytokine production

Inferred from electronic annotation. Source: Ensembl

positive regulation of developmental growth

Inferred from direct assay PubMed 17957153. Source: DFLAT

positive regulation of follicle-stimulating hormone secretion

Inferred from electronic annotation. Source: Ensembl

positive regulation of hepatic stellate cell activation

Inferred from electronic annotation. Source: Ensembl

positive regulation of insulin receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

positive regulation of ion transport

Inferred from electronic annotation. Source: Ensembl

positive regulation of luteinizing hormone secretion

Inferred from electronic annotation. Source: Ensembl

positive regulation of myeloid cell differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of tyrosine phosphorylation of Stat3 protein

Inferred from electronic annotation. Source: Ensembl

regulation of blood pressure

Inferred from electronic annotation. Source: Ensembl

regulation of fat cell differentiation

Inferred from electronic annotation. Source: Ensembl

regulation of gluconeogenesis

Inferred from electronic annotation. Source: Ensembl

regulation of insulin secretion

Inferred from electronic annotation. Source: Ensembl

regulation of intestinal cholesterol absorption

Inferred from electronic annotation. Source: Ensembl

regulation of lipoprotein lipid oxidation

Inferred from electronic annotation. Source: Ensembl

regulation of steroid biosynthetic process

Inferred from electronic annotation. Source: Ensembl

response to dietary excess

Inferred from electronic annotation. Source: Ensembl

response to hypoxia

Inferred from electronic annotation. Source: Ensembl

response to insulin

Inferred from electronic annotation. Source: Ensembl

response to vitamin E

Inferred from electronic annotation. Source: Ensembl

tyrosine phosphorylation of STAT protein

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: Ensembl

extracellular region

Traceable author statement. Source: Reactome

extracellular space

Inferred from sequence or structural similarity. Source: HGNC

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2121 Potential
Chain22 – 167146Leptin
PRO_0000017685

Amino acid modifications

Disulfide bond117 ↔ 167

Natural variations

Natural variant491Missing in 30% the clones.
VAR_004196
Natural variant941V → M. Ref.9 Ref.15
Corresponds to variant rs17151919 [ dbSNP | Ensembl ].
VAR_004197
Natural variant1051R → W in LEPD. Ref.16
Corresponds to variant rs104894023 [ dbSNP | Ensembl ].
VAR_008094
Natural variant1101V → M.
Corresponds to variant rs1800564 [ dbSNP | Ensembl ].
VAR_011955

Experimental info

Sequence conflict961Q → R in AAB63507. Ref.8

Secondary structure

............. 167
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P41159 [UniParc].

Last modified February 1, 1995. Version 1.
Checksum: C91A121E92D37B69

FASTA16718,641
        10         20         30         40         50         60 
MHWGTLCGFL WLWPYLFYVQ AVPIQKVQDD TKTLIKTIVT RINDISHTQS VSSKQKVTGL 

        70         80         90        100        110        120 
DFIPGLHPIL TLSKMDQTLA VYQQILTSMP SRNVIQISND LENLRDLLHV LAFSKSCHLP 

       130        140        150        160 
WASGLETLDS LGGVLEASGY STEVVALSRL QGSLQDMLWQ LDLSPGC 

« Hide

References

« Hide 'large scale' references
[1]"Positional cloning of the mouse obese gene and its human homologue."
Zhang Y., Proenca P., Maffei M., Barone M., Leopold L., Friedman J.M.
Nature 372:425-432(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]Erratum
Zhang Y., Proenca P., Maffei M., Barone M., Leopold L., Friedman J.M.
Nature 374:479-479(1995)
[3]"Human obese gene expression. Adipocyte-specific expression and regional differences in the adipose tissue."
Masuzaki H., Ogawa Y., Isse N., Satoh N., Okazaki T., Shigemoto M., Mori K., Tamura N., Hosoda K., Yoshimasa Y., Jingami H., Kawada T., Nakao K.
Diabetes 44:855-858(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]"Genomic structure and promoter analysis of the human obese gene."
Gong D.W., Bi S., Pratley R.E., Weintraub B.D.
J. Biol. Chem. 271:3971-3974(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]Chehab F.F., Lim M.E.
Submitted (DEC-1995) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]"Structural organization and chromosomal assignment of the human obese gene."
Isse N., Ogawa Y., Tamura N., Masuzaki H., Mori K., Okazaki T., Satoh N., Shigemoto M., Yoshimasa Y., Nishi S., Hosada K., Inazawa J., Nakao K.
J. Biol. Chem. 270:27728-27733(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[7]"Human obese gene: molecular screening in Japanese and Asian Indian NIDDM patients associated with obesity."
Niki T., Mori H., Tamori Y., Kishimoto-Hashiramoto M., Ueno H., Araki S., Masugi J., Sawant N., Majithia H.R., Rais N., Hashiramoto M., Taniguchi H., Kasuga M.
Diabetes 45:675-678(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[8]Lu L., Fu Z., Xu M., Fu Y., Hu Z.
Submitted (JUN-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[9]SeattleSNPs variation discovery resource
Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT MET-94.
[10]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Placenta.
[11]"OB-BP1/Siglec-6. A leptin- and sialic acid-binding protein of the immunoglobulin superfamily."
Patel N., Brinkman-Van der Linden E.C.M., Altmann S.W., Gish K.C., Balasubramanian S., Timans J.C., Peterson D., Bell M.P., Bazan J.F., Varki A., Kastelein R.A.
J. Biol. Chem. 274:22729-22738(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SIGLEC6.
[12]Erratum
Patel N., Brinkman-Van der Linden E.C.M., Altmann S.W., Gish K.C., Balasubramanian S., Timans J.C., Peterson D., Bell M.P., Bazan J.F., Varki A., Kastelein R.A.
J. Biol. Chem. 274:28058-28058(1999)
[13]"Leptin is a four-helix bundle: secondary structure by NMR."
Kline A.D., Becker G.W., Churgay L.M., Landen B.E., Martin D.K., Muth W.L., Rathnachalam R., Richardson J.M., Schoner B., Ulmer M., Hale J.E.
FEBS Lett. 407:239-242(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR.
[14]"Crystal structure of the obese protein leptin-E100."
Zhang F., Basinski M.B., Beals J.M., Briggs S.L., Churgay L.M., Clawson D.K., Dimarchi R.D., Furman T.C., Hale J.E., Hsiung H.M., Schoner B.E., Smith D.P., Zhang X.Y., Wery J.P., Schevitz R.W.
Nature 387:206-209(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS).
[15]"A novel polymorphism in the leptin gene."
Bartholomew D.W., McClellan J.M.
Hum. Mutat. 12:220-220(1998)
Cited for: VARIANT MET-94.
[16]"A leptin missense mutation associated with hypogonadism and morbid obesity."
Strobel A., Issad T., Camoin L., Ozata M., Strosberg A.D.
Nat. Genet. 18:213-215(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT LEPD TRP-105.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U18915 mRNA. Translation: AAA60470.1.
D49487 mRNA. Translation: BAA08448.1.
U43653 mRNA. Translation: AAC50400.1.
U43415 Genomic DNA. Translation: AAC31660.1.
D63710 Genomic DNA. Translation: BAA09839.1.
D63519 Genomic DNA. Translation: BAA09787.1.
AF008123 mRNA. Translation: AAB63507.1.
AY996373 Genomic DNA. Translation: AAX81413.1.
BC060830 mRNA. Translation: AAH60830.1.
BC069452 mRNA. Translation: AAH69452.1.
BC069527 mRNA. Translation: AAH69527.1.
CCDSCCDS5800.1.
PIRLTHU. A38952.
I53166.
RefSeqNP_000221.1. NM_000230.2.
XP_005250397.1. XM_005250340.2.
UniGeneHs.194236.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1AX8X-ray2.40A22-167[»]
ProteinModelPortalP41159.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110143. 4 interactions.
DIPDIP-6116N.
STRING9606.ENSP00000312652.

PTM databases

PhosphoSiteP41159.

Proteomic databases

PaxDbP41159.
PeptideAtlasP41159.
PRIDEP41159.

Protocols and materials databases

DNASU3952.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000308868; ENSP00000312652; ENSG00000174697.
GeneID3952.
KEGGhsa:3952.
UCSCuc003vml.2. human.

Organism-specific databases

CTD3952.
GeneCardsGC07P127881.
HGNCHGNC:6553. LEP.
HPACAB010490.
CAB016730.
HPA030721.
MIM164160. gene.
614962. phenotype.
neXtProtNX_P41159.
Orphanet66628. Obesity due to congenital leptin deficiency.
PharmGKBPA228.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG45133.
HOGENOMHOG000252923.
HOVERGENHBG007860.
InParanoidP41159.
KOK05424.
OMATIVTRIN.
OrthoDBEOG77Q4Z3.
PhylomeDBP41159.
TreeFamTF105086.

Enzyme and pathway databases

ReactomeREACT_111045. Developmental Biology.
REACT_111102. Signal Transduction.
SignaLinkP41159.

Gene expression databases

ArrayExpressP41159.
BgeeP41159.
CleanExHS_LEP.
GenevestigatorP41159.

Family and domain databases

Gene3D1.20.1250.10. 1 hit.
InterProIPR009079. 4_helix_cytokine-like_core.
IPR012351. 4_helix_cytokine_core.
IPR000065. Leptin.
[Graphical view]
PANTHERPTHR11724. PTHR11724. 1 hit.
PfamPF02024. Leptin. 1 hit.
[Graphical view]
PIRSFPIRSF001837. Leptin. 1 hit.
PRINTSPR00495. LEPTIN.
ProDomPD005698. Leptin. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SUPFAMSSF47266. SSF47266. 1 hit.
ProtoNetSearch...

Other

EvolutionaryTraceP41159.
GeneWikiLeptin.
GenomeRNAi3952.
NextBio15501.
PROP41159.
SOURCESearch...

Entry information

Entry nameLEP_HUMAN
AccessionPrimary (citable) accession number: P41159
Secondary accession number(s): O15158, Q56A88
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: July 9, 2014
This is version 146 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM