P41159 (LEP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Leptin

Alternative name(s):
Obese protein
Obesity factor

Gene names

Name:	LEP
Synonyms:	OB, OBS

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

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 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 component	Secreted
Coding sequence diversity	Polymorphism
Disease	Diabetes mellitus Disease mutation Obesity
Domain	Signal
PTM	Disulfide bond
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	adipose tissue development Inferred from electronic annotation. Source: Compara adult feeding behavior Inferred from sequence or structural similarity. Source: HGNC bile acid metabolic process Inferred from electronic annotation. Source: Compara bone mineralization involved in bone maturation Inferred from electronic annotation. Source: Compara cellular response to L-ascorbic acid Inferred from electronic annotation. Source: Compara cellular response to retinoic acid Inferred from electronic annotation. Source: Compara central nervous system neuron development Inferred from electronic annotation. Source: Compara cholesterol metabolic process Inferred from electronic annotation. Source: Compara circadian rhythm Inferred from electronic annotation. Source: Compara eating behavior Inferred from electronic annotation. Source: Compara energy reserve metabolic process Traceable author statement PubMed 9537324. Source: ProtInc fatty acid catabolic process Inferred from electronic annotation. Source: Compara female pregnancy Inferred from electronic annotation. Source: Compara glucose metabolic process Inferred from electronic annotation. Source: Compara glycerol biosynthetic process Inferred from electronic annotation. Source: Compara hormone metabolic process Inferred from electronic annotation. Source: Compara insulin secretion Inferred from electronic annotation. Source: Compara leptin-mediated signaling pathway Inferred from electronic annotation. Source: Compara leukocyte tethering or rolling Inferred from electronic annotation. Source: Compara negative regulation of apoptotic process Inferred from electronic annotation. Source: Compara negative regulation of appetite Inferred from sequence or structural similarity. Source: HGNC negative regulation of cartilage development Inferred from electronic annotation. Source: Compara negative regulation of glucagon secretion Inferred from electronic annotation. Source: Compara negative regulation of glutamine transport Inferred from electronic annotation. Source: Compara negative regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara negative regulation of vasoconstriction Inferred from electronic annotation. Source: Compara ovulation from ovarian follicle Inferred from electronic annotation. Source: Compara placenta development Inferred from direct assay PubMed 17957153. Source: DFLAT positive regulation of MAPK cascade Inferred from electronic annotation. Source: Compara positive regulation of STAT protein import into nucleus Inferred from electronic annotation. Source: Compara positive regulation of cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of cytokine production Inferred from electronic annotation. Source: Compara 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: Compara positive regulation of hepatic stellate cell activation Inferred from electronic annotation. Source: Compara positive regulation of insulin receptor signaling pathway Inferred from electronic annotation. Source: Compara positive regulation of ion transport Inferred from electronic annotation. Source: Compara positive regulation of luteinizing hormone secretion Inferred from electronic annotation. Source: Compara positive regulation of myeloid cell differentiation Inferred from electronic annotation. Source: Compara positive regulation of tyrosine phosphorylation of Stat3 protein Inferred from electronic annotation. Source: Compara regulation of blood pressure Inferred from electronic annotation. Source: Compara 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 electronic annotation. Source: Compara regulation of steroid biosynthetic process Inferred from electronic annotation. Source: Compara response to dietary excess Inferred from electronic annotation. Source: Compara response to hypoxia Inferred from electronic annotation. Source: Compara response to insulin stimulus Inferred from electronic annotation. Source: Compara response to vitamin E Inferred from electronic annotation. Source: Compara tyrosine phosphorylation of STAT protein Inferred from electronic annotation. Source: Compara
Cellular_component	extracellular space Inferred from sequence or structural similarity. Source: HGNC
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_0000017685

Amino acid modifications

Disulfide bond

117 ↔ 167

Natural variations

Natural variant

49

1

Missing in 30% the clones.

VAR_004196

Natural variant

94

1

V → M. Ref.9 Ref.15
Corresponds to variant rs17151919 [ dbSNP | Ensembl ].

VAR_004197

Natural variant

105

1

R → W in LEPD. Ref.16
Corresponds to variant rs104894023 [ dbSNP | Ensembl ].

VAR_008094

Natural variant

110

1

V → M.
Corresponds to variant rs1800564 [ dbSNP | Ensembl ].

VAR_011955

Experimental info

Sequence conflict

96

1

Q → R in AAB63507. Ref.8

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

167

Helix Strand Turn

Details...

Helix

25 – 44

20

Helix

72 – 87

16

Helix

92 – 114

23

Helix

128 – 131

4

Helix

132 – 135

4

Helix

142 – 160

19

Helix

161 – 163

3

Sequences

	Sequence		Length	Mass (Da)
	P41159 [UniParc]. Last modified February 1, 1995. Version 1. Checksum: C91A121E92D37B69	FASTA	167	18,641
	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

References

	« Hide 'large scale' referencesShow '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.

Web resources

R&D Systems' cytokine mini-reviews: Leptin

Wikipedia

Leptin entry

SeattleSNPs

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.

IPI

IPI00012760.

PIR

LTHU. A38952.
I53166.

RefSeq

NP_000221.1. NM_000230.2.

UniGene

Hs.194236.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1AX8	X-ray	2.40	A	22-167	[»]

ProteinModelPortal

P41159.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-6116N.

STRING

9606.ENSP00000312652.

PTM databases

PhosphoSite

P41159.

Polymorphism databases

DMDM

730218.

Proteomic databases

PaxDb

P41159.

PeptideAtlas

P41159.

PRIDE

P41159.

Protocols and materials databases

DNASU

3952.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000308868; ENSP00000312652; ENSG00000174697.

GeneID

3952.

KEGG

hsa:3952.

UCSC

uc003vml.2. human.

Organism-specific databases

CTD

3952.

GeneCards

GC07P127881.

HGNC

HGNC:6553. LEP.

HPA

CAB010490.
CAB016730.

MIM

164160. gene.
614962. phenotype.

neXtProt

NX_P41159.

Orphanet

66628. Obesity due to congenital leptin deficiency.

PharmGKB

PA228.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG45133.

HOGENOM

HOG000252923.

HOVERGEN

HBG007860.

InParanoid

P41159.

KO

K05424.

OMA

KTIVTRI.

OrthoDB

EOG4QNMXC.

PhylomeDB

P41159.

Enzyme and pathway databases

Pathway_Interaction_DB

hif1_tfpathway. HIF-1-alpha transcription factor network.
ptp1bpathway. Signaling events mediated by PTP1B.

Reactome

REACT_111045. Developmental Biology.

SignaLink

P41159.

Gene expression databases

ArrayExpress

P41159.

Bgee

P41159.

CleanEx

HS_LEP.

Genevestigator

P41159.

GermOnline

ENSG00000174697. Homo sapiens.

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

EvolutionaryTrace

P41159.

GenomeRNAi

3952.

NextBio

15501.

SOURCE

Search...

Entry information

Entry name

LEP_HUMAN

Accession

Primary (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:	May 29, 2013
This is version 137 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.