Reviewed, UniProtKB/Swiss-Prot P41159 (LEP_HUMAN)

Names and origin

Protein names

Recommended name:
    Leptin
Alternative name(s):
    Obesity factor
    Obese protein

Gene names

Name:	LEP
Synonyms:	OB, OBS

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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	Defects in LEP may be a cause of autosomal recessive obesity [MIM:601665].
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
Gene Ontology (GO)
Biological process	adult feeding behavior Inferred from sequence or structural similarity. Source: HGNC energy reserve metabolic process Traceable author statement. Source: ProtInc negative regulation of appetite Inferred from sequence or structural similarity. Source: HGNC signal transduction Inferred from electronic annotation. Source: InterPro
Cellular component	extracellular space Inferred from sequence or structural similarity. Source: HGNC
Molecular function	hormone activity Inferred from electronic annotation. Source: InterPro
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: dbSNP rs17151919. Ref.9 Ref.15

VAR_004197

Natural variant

105

1

R → W in morbid obesity and hypogonadism. Ref.16

VAR_008094

Natural variant

110

1

V → M: dbSNP rs1800564.

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)
	P41159-1 [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: 7984236] [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: 7789654] [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: 8626726] [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: 7499240] [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: 8621021] [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: 15489334] [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: 10428856] [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: 9166907] [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: 9144295] [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: 9500540] [Abstract] Cited for: VARIANT MORBID OBESITY TRP-105.
+	Additional computationally mapped references.

Web resources

R&D Systems' cytokine mini-reviews: Leptin

Wikipedia

Leptin entry

SeattleSNPs

Cross-references

Sequence databases

EMBLGenBankDDBJ

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.

UniGene

Hs.194236

3D structure databases

PDBPDBe

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

SMR

P41159. Positions 24-167.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:6116N.

Proteomic databases

PeptideAtlas

P41159.

PRIDE

P41159.

Genome annotation databases

Ensembl

ENSG00000174697. Homo sapiens. [Contig view]

GeneID

3952.

KEGG

hsa:3952.

UCSC

uc003vml.2. human.

Organism-specific databases

GeneCards

GC07P127668.

H-InvDB

HIX0033518.

HGNC

HGNC:6553. LEP.

HPA

CAB010490.
CAB016730.

MIM

164160. gene.
601665. phenotype.

Orphanet

66628. Obesity due to congenital leptin deficiency.

PharmGKB

PA228.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P41159.

HOVERGEN

P41159.

OMA

P41159. GLDFIPG.

Enzyme and pathway databases

Pathway_Interaction_DB

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

Gene expression databases

ArrayExpress

P41159.

Bgee

P41159.

CleanEx

HS_LEP.

GermOnline

ENSG00000174697. Homo sapiens.

Family and domain databases

InterPro

IPR012351. 4_helix_cytokine_core.
IPR000065. Leptin.
[Graphical view]

Gene3D

G3DSA:1.20.1250.10. 4_helix_cytokine_core. 1 hit.

PANTHER

PTHR11724. Leptin. 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]

ProtoNet

Search...

Other Resources

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:	July 7, 2009
This is version 101 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)