P48357 (LEPR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Leptin receptor
Short name=LEP-R

Alternative name(s):
HuB219
OB receptor
Short name=OB-R
CD_antigen=CD295

Gene names

Name:	LEPR
Synonyms:	DB, OBR

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	1165 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	Receptor for obesity factor (leptin). On ligand binding, mediates signaling through JAK2/STAT3. Involved in the regulation of fat metabolism and, in a hematopoietic pathway, required for normal lymphopoiesis. May play a role in reproduction. Can also mediate the ERK/FOS signaling pathway By similarity.
Subunit structure	On leptin stimulation, homodimerizes. The phosphorylated receptor binds a number of SH2 domain-containing proteins such as STAT3, PTPN11, and SOCS3 By similarity. Interaction with SOCS3 inhibits LRb signaling By similarity.
Subcellular location	Cell membrane; Single-pass type I membrane protein. Isoform E: Secreted Probable.
Tissue specificity	Isoform A is expressed in fetal liver and in hematopoietic tissues and choroid plexus. In adults highest expression in heart, liver, small intestine, prostate and ovary. Low level in lung and kidney. Isoform B is highly expressed in hypothalamus.
Domain	The cytoplasmic domain may be essential for intracellular signal transduction by activation of JAK tyrosine kinase and STATs. The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding. The box 1 motif is required for JAK interaction and/or activation.
Post-translational modification	On ligand binding, phosphorylated on two conserved C-terminal tyrosine residues (isoform B only) by JAK2. Tyr-986 is required for complete binding and activation of PTPN11, ERK/FOS activation and, for interaction with SOCS3 By similarity. Phosphorylation on Tyr-1141 is required for STAT3 binding/activation.
Sequence similarities	Belongs to the type I cytokine receptor family. Type 2 subfamily. Contains 4 fibronectin type-III domains. Contains 1 Ig-like (immunoglobulin-like) domain.

Ontologies

Keywords
Cellular component	Cell membrane Membrane Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Obesity
Domain	Immunoglobulin domain Repeat Signal Transmembrane Transmembrane helix
Molecular function	Receptor
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cholesterol metabolic process Inferred from electronic annotation. Source: Compara cytokine-mediated signaling pathway Inferred from electronic annotation. Source: GOC energy reserve metabolic process Traceable author statement PubMed 9537324. Source: ProtInc multicellular organismal development Traceable author statement PubMed 9537324. Source: ProtInc negative regulation of hydrolase activity Inferred from electronic annotation. Source: Compara
Cellular_component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	cytokine receptor activity Inferred from electronic annotation. Source: InterPro transmembrane signaling receptor activity Traceable author statement PubMed 9537324. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
GRB2	P62993	3	EBI-518596,EBI-401755

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Isoform B (identifier: P48357-1)

Also known as: 13.2; OBRb;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform A (identifier: P48357-2)

Also known as: 6.4; HuB219.3;

The sequence of this isoform differs from the canonical sequence as follows:
     892-896: PETFE → RTDIL
     897-1165: Missing.

Isoform C (identifier: P48357-3)

Also known as: 12.1; OBRa;

The sequence of this isoform differs from the canonical sequence as follows:
     892-958: PETFEHLFIK...EKGSVCISDQ → MLEGSMFVKS...KSPSVRNTQE
     959-1165: Missing.

Isoform D (identifier: P48357-4)

Also known as: HuB219.2;

The sequence of this isoform differs from the canonical sequence as follows:
     892-906: PETFEHLFIKHTASV → KMPGTKELLGGGWLT
     907-1165: Missing.

Isoform E (identifier: P48357-5)

The sequence of this isoform differs from the canonical sequence as follows:
     840-1165: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 21

21

Chain

22 – 1165

1144

Leptin receptor

PRO_0000010904

Regions

Topological domain

22 – 839

818

Extracellular Potential

Transmembrane

840 – 862

23

Helical; Potential

Topological domain

863 – 1165

303

Cytoplasmic Potential

Domain

237 – 330

94

Fibronectin type-III 1

Domain

331 – 429

99

Ig-like

Domain

537 – 631

95

Fibronectin type-III 2

Domain

639 – 732

94

Fibronectin type-III 3

Domain

734 – 829

96

Fibronectin type-III 4

Region

467 – 484

18

Leptin-binding Probable

Region

893 – 898

6

Required for JAK2 activation By similarity

Motif

622 – 626

5

WSXWS motif

Motif

871 – 879

9

Box 1 motif

Amino acid modifications

Modified residue

986

1

Phosphotyrosine; by JAK2 By similarity

Modified residue

1079

1

Phosphotyrosine By similarity

Modified residue

1141

1

Phosphotyrosine; by JAK2 By similarity

Glycosylation

23

1

N-linked (GlcNAc...) Ref.8

Glycosylation

41

1

N-linked (GlcNAc...) Ref.8

Glycosylation

56

1

N-linked (GlcNAc...) Ref.8

Glycosylation

73

1

N-linked (GlcNAc...) Ref.8

Glycosylation

81

1

N-linked (GlcNAc...) Ref.8

Glycosylation

98

1

N-linked (GlcNAc...) Ref.8

Glycosylation

187

1

N-linked (GlcNAc...) Ref.8

Glycosylation

206

1

N-linked (GlcNAc...) Ref.8

Glycosylation

276

1

N-linked (GlcNAc...) Ref.8 Ref.9 Ref.10

Glycosylation

347

1

N-linked (GlcNAc...) Ref.8

Glycosylation

397

1

N-linked (GlcNAc...) Ref.8 Ref.10

Glycosylation

516

1

N-linked (GlcNAc...) Ref.8 Ref.9

Glycosylation

624

1

N-linked (GlcNAc...) Ref.8

Glycosylation

659

1

N-linked (GlcNAc...) Ref.8

Glycosylation

688

1

N-linked (GlcNAc...) Ref.8

Glycosylation

697

1

N-linked (GlcNAc...) Ref.8

Glycosylation

728

1

N-linked (GlcNAc...) Ref.8

Glycosylation

750

1

N-linked (GlcNAc...) Ref.8

Disulfide bond

37 ↔ 90

Ref.8 Ref.11

Disulfide bond

89 ↔ 99

Ref.8 Ref.11

Disulfide bond

131 ↔ 142

Ref.8 Ref.11

Disulfide bond

186 ↔ 196

Ref.8 Ref.11

Disulfide bond

188 ↔ 193

Ref.8 Ref.11

Disulfide bond

352 ↔ 412

Ref.8 Ref.11

Disulfide bond

413 ↔ 418

Ref.8 Ref.11

Disulfide bond

436 ↔ 447

Ref.8 Ref.11

Disulfide bond

473 ↔ 528

Ref.8 Ref.11

Disulfide bond

488 ↔ 498

Ref.8 Ref.11

Natural variations

Alternative sequence

840 – 1165

326

Missing in isoform E.

VSP_001688

Alternative sequence

892 – 958

67

PETFE…CISDQ → MLEGSMFVKSHHHSLISSTQ GHKHCGRPQGPLHRKTRDLC SLVYLLTLPPLLSYDPAKSP SVRNTQE in isoform C.

VSP_001691

Alternative sequence

892 – 906

15

PETFE…HTASV → KMPGTKELLGGGWLT in isoform D.

VSP_001693

Alternative sequence

892 – 896

5

PETFE → RTDIL in isoform A.

VSP_001689

Alternative sequence

897 – 1165

269

Missing in isoform A.

VSP_001690

Alternative sequence

907 – 1165

259

Missing in isoform D.

VSP_001694

Alternative sequence

959 – 1165

207

Missing in isoform C.

VSP_001692

Natural variant

109

1

K → R. Ref.3 Ref.4 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17
Corresponds to variant rs1137100 [ dbSNP | Ensembl ].

VAR_002703

Natural variant

124

1

D → G.
Corresponds to variant rs35573508 [ dbSNP | Ensembl ].

VAR_049167

Natural variant

204

1

K → R. Ref.13

VAR_002704

Natural variant

223

1

Q → R. Ref.3 Ref.4 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17
Corresponds to variant rs1137101 [ dbSNP | Ensembl ].

VAR_002705

Natural variant

503

1

I → V.
Corresponds to variant rs13306526 [ dbSNP | Ensembl ].

VAR_028201

Natural variant

656

1

K → N. Ref.13 Ref.14 Ref.15 Ref.16
Corresponds to variant rs8179183 [ dbSNP | Ensembl ].

VAR_002706

Natural variant

675

1

S → T. Ref.16

VAR_002707

Natural variant

699

1

T → M.
Corresponds to variant rs34499590 [ dbSNP | Ensembl ].

VAR_049168

Experimental info

Mutagenesis

986

1

Y → F: Greatly reduced PTPN11 binding; no PTPN11 phosphorylation; no effect on STAT3 phosphorylation. Ref.7

Mutagenesis

1078 – 1079

2

YY → FF: No effect on PTPN11 nor STAT3 phosphorylation.

Mutagenesis

1141

1

Y → F: No effect on PTPN11 phosphorylation; no STAT3 phosphorylation. Ref.7

Sequence conflict

85

1

T → A in AAC50509. Ref.3

Sequence conflict

85

1

T → A in AAC50510. Ref.3

Sequence conflict

85

1

T → A in AAC50511. Ref.3

Sequence conflict

976

1

D → A in AAA93015. Ref.1

Sequence conflict

976

1

D → A in AAB09673. Ref.4

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

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.

.

.

.

.

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.

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.

.

.

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.

1165

Helix Strand Turn

Details...

Beta strand

435 – 438

4

Beta strand

445 – 449

5

Beta strand

461 – 468

8

Beta strand

484 – 486

3

Beta strand

488 – 490

3

Beta strand

496 – 500

5

Beta strand

509 – 516

8

Beta strand

527 – 529

3

Helix

531 – 534

4

Beta strand

544 – 548

5

Turn

549 – 552

4

Beta strand

553 – 557

5

Beta strand

568 – 580

13

Beta strand

584 – 588

5

Beta strand

595 – 598

4

Beta strand

607 – 615

9

Sequences

	Sequence		Length	Mass (Da)
	Isoform B (13.2) (OBRb) [UniParc]. Last modified October 17, 2006. Version 2. Checksum: CAA03BEAF2602D0A	FASTA	1,165	132,494
	10 20 30 40 50 60 MICQKFCVVL LHWEFIYVIT AFNLSYPITP WRFKLSCMPP NSTYDYFLLP AGLSKNTSNS 70 80 90 100 110 120 NGHYETAVEP KFNSSGTHFS NLSKTTFHCC FRSEQDRNCS LCADNIEGKT FVSTVNSLVF 130 140 150 160 170 180 QQIDANWNIQ CWLKGDLKLF ICYVESLFKN LFRNYNYKVH LLYVLPEVLE DSPLVPQKGS 190 200 210 220 230 240 FQMVHCNCSV HECCECLVPV PTAKLNDTLL MCLKITSGGV IFQSPLMSVQ PINMVKPDPP 250 260 270 280 290 300 LGLHMEITDD GNLKISWSSP PLVPFPLQYQ VKYSENSTTV IREADKIVSA TSLLVDSILP 310 320 330 340 350 360 GSSYEVQVRG KRLDGPGIWS DWSTPRVFTT QDVIYFPPKI LTSVGSNVSF HCIYKKENKI 370 380 390 400 410 420 VPSKEIVWWM NLAEKIPQSQ YDVVSDHVSK VTFFNLNETK PRGKFTYDAV YCCNEHECHH 430 440 450 460 470 480 RYAELYVIDV NINISCETDG YLTKMTCRWS TSTIQSLAES TLQLRYHRSS LYCSDIPSIH 490 500 510 520 530 540 PISEPKDCYL QSDGFYECIF QPIFLLSGYT MWIRINHSLG SLDSPPTCVL PDSVVKPLPP 550 560 570 580 590 600 SSVKAEITIN IGLLKISWEK PVFPENNLQF QIRYGLSGKE VQWKMYEVYD AKSKSVSLPV 610 620 630 640 650 660 PDLCAVYAVQ VRCKRLDGLG YWSNWSNPAY TVVMDIKVPM RGPEFWRIIN GDTMKKEKNV 670 680 690 700 710 720 TLLWKPLMKN DSLCSVQRYV INHHTSCNGT WSEDVGNHTK FTFLWTEQAH TVTVLAINSI 730 740 750 760 770 780 GASVANFNLT FSWPMSKVNI VQSLSAYPLN SSCVIVSWIL SPSDYKLMYF IIEWKNLNED 790 800 810 820 830 840 GEIKWLRISS SVKKYYIHDH FIPIEKYQFS LYPIFMEGVG KPKIINSFTQ DDIEKHQSDA 850 860 870 880 890 900 GLYVIVPVII SSSILLLGTL LISHQRMKKL FWEDVPNPKN CSWAQGLNFQ KPETFEHLFI 910 920 930 940 950 960 KHTASVTCGP LLLEPETISE DISVDTSWKN KDEMMPTTVV SLLSTTDLEK GSVCISDQFN 970 980 990 1000 1010 1020 SVNFSEAEGT EVTYEDESQR QPFVKYATLI SNSKPSETGE EQGLINSSVT KCFSSKNSPL 1030 1040 1050 1060 1070 1080 KDSFSNSSWE IEAQAFFILS DQHPNIISPH LTFSEGLDEL LKLEGNFPEE NNDKKSIYYL 1090 1100 1110 1120 1130 1140 GVTSIKKRES GVLLTDKSRV SCPFPAPCLF TDIRVLQDSC SHFVENNINL GTSSKKTFAS 1150 1160 YMPQFQTCST QTHKIMENKM CDLTV
	Isoform A (6.4) (HuB219.3) [UniParc]. Checksum: D371C7A4186DEEF3	FASTA	896	102,490
	10 20 30 40 50 60 MICQKFCVVL LHWEFIYVIT AFNLSYPITP WRFKLSCMPP NSTYDYFLLP AGLSKNTSNS 70 80 90 100 110 120 NGHYETAVEP KFNSSGTHFS NLSKTTFHCC FRSEQDRNCS LCADNIEGKT FVSTVNSLVF 130 140 150 160 170 180 QQIDANWNIQ CWLKGDLKLF ICYVESLFKN LFRNYNYKVH LLYVLPEVLE DSPLVPQKGS 190 200 210 220 230 240 FQMVHCNCSV HECCECLVPV PTAKLNDTLL MCLKITSGGV IFQSPLMSVQ PINMVKPDPP 250 260 270 280 290 300 LGLHMEITDD GNLKISWSSP PLVPFPLQYQ VKYSENSTTV IREADKIVSA TSLLVDSILP 310 320 330 340 350 360 GSSYEVQVRG KRLDGPGIWS DWSTPRVFTT QDVIYFPPKI LTSVGSNVSF HCIYKKENKI 370 380 390 400 410 420 VPSKEIVWWM NLAEKIPQSQ YDVVSDHVSK VTFFNLNETK PRGKFTYDAV YCCNEHECHH 430 440 450 460 470 480 RYAELYVIDV NINISCETDG YLTKMTCRWS TSTIQSLAES TLQLRYHRSS LYCSDIPSIH 490 500 510 520 530 540 PISEPKDCYL QSDGFYECIF QPIFLLSGYT MWIRINHSLG SLDSPPTCVL PDSVVKPLPP 550 560 570 580 590 600 SSVKAEITIN IGLLKISWEK PVFPENNLQF QIRYGLSGKE VQWKMYEVYD AKSKSVSLPV 610 620 630 640 650 660 PDLCAVYAVQ VRCKRLDGLG YWSNWSNPAY TVVMDIKVPM RGPEFWRIIN GDTMKKEKNV 670 680 690 700 710 720 TLLWKPLMKN DSLCSVQRYV INHHTSCNGT WSEDVGNHTK FTFLWTEQAH TVTVLAINSI 730 740 750 760 770 780 GASVANFNLT FSWPMSKVNI VQSLSAYPLN SSCVIVSWIL SPSDYKLMYF IIEWKNLNED 790 800 810 820 830 840 GEIKWLRISS SVKKYYIHDH FIPIEKYQFS LYPIFMEGVG KPKIINSFTQ DDIEKHQSDA 850 860 870 880 890 GLYVIVPVII SSSILLLGTL LISHQRMKKL FWEDVPNPKN CSWAQGLNFQ KRTDIL
	Isoform C (12.1) (OBRa) [UniParc]. Checksum: 3F65BC5A187E803A	FASTA	958	109,393
	10 20 30 40 50 60 MICQKFCVVL LHWEFIYVIT AFNLSYPITP WRFKLSCMPP NSTYDYFLLP AGLSKNTSNS 70 80 90 100 110 120 NGHYETAVEP KFNSSGTHFS NLSKTTFHCC FRSEQDRNCS LCADNIEGKT FVSTVNSLVF 130 140 150 160 170 180 QQIDANWNIQ CWLKGDLKLF ICYVESLFKN LFRNYNYKVH LLYVLPEVLE DSPLVPQKGS 190 200 210 220 230 240 FQMVHCNCSV HECCECLVPV PTAKLNDTLL MCLKITSGGV IFQSPLMSVQ PINMVKPDPP 250 260 270 280 290 300 LGLHMEITDD GNLKISWSSP PLVPFPLQYQ VKYSENSTTV IREADKIVSA TSLLVDSILP 310 320 330 340 350 360 GSSYEVQVRG KRLDGPGIWS DWSTPRVFTT QDVIYFPPKI LTSVGSNVSF HCIYKKENKI 370 380 390 400 410 420 VPSKEIVWWM NLAEKIPQSQ YDVVSDHVSK VTFFNLNETK PRGKFTYDAV YCCNEHECHH 430 440 450 460 470 480 RYAELYVIDV NINISCETDG YLTKMTCRWS TSTIQSLAES TLQLRYHRSS LYCSDIPSIH 490 500 510 520 530 540 PISEPKDCYL QSDGFYECIF QPIFLLSGYT MWIRINHSLG SLDSPPTCVL PDSVVKPLPP 550 560 570 580 590 600 SSVKAEITIN IGLLKISWEK PVFPENNLQF QIRYGLSGKE VQWKMYEVYD AKSKSVSLPV 610 620 630 640 650 660 PDLCAVYAVQ VRCKRLDGLG YWSNWSNPAY TVVMDIKVPM RGPEFWRIIN GDTMKKEKNV 670 680 690 700 710 720 TLLWKPLMKN DSLCSVQRYV INHHTSCNGT WSEDVGNHTK FTFLWTEQAH TVTVLAINSI 730 740 750 760 770 780 GASVANFNLT FSWPMSKVNI VQSLSAYPLN SSCVIVSWIL SPSDYKLMYF IIEWKNLNED 790 800 810 820 830 840 GEIKWLRISS SVKKYYIHDH FIPIEKYQFS LYPIFMEGVG KPKIINSFTQ DDIEKHQSDA 850 860 870 880 890 900 GLYVIVPVII SSSILLLGTL LISHQRMKKL FWEDVPNPKN CSWAQGLNFQ KMLEGSMFVK 910 920 930 940 950 SHHHSLISST QGHKHCGRPQ GPLHRKTRDL CSLVYLLTLP PLLSYDPAKS PSVRNTQE
	Isoform D (HuB219.2) [UniParc]. Checksum: 07F4D89DDFDB83CA	FASTA	906	103,461
	10 20 30 40 50 60 MICQKFCVVL LHWEFIYVIT AFNLSYPITP WRFKLSCMPP NSTYDYFLLP AGLSKNTSNS 70 80 90 100 110 120 NGHYETAVEP KFNSSGTHFS NLSKTTFHCC FRSEQDRNCS LCADNIEGKT FVSTVNSLVF 130 140 150 160 170 180 QQIDANWNIQ CWLKGDLKLF ICYVESLFKN LFRNYNYKVH LLYVLPEVLE DSPLVPQKGS 190 200 210 220 230 240 FQMVHCNCSV HECCECLVPV PTAKLNDTLL MCLKITSGGV IFQSPLMSVQ PINMVKPDPP 250 260 270 280 290 300 LGLHMEITDD GNLKISWSSP PLVPFPLQYQ VKYSENSTTV IREADKIVSA TSLLVDSILP 310 320 330 340 350 360 GSSYEVQVRG KRLDGPGIWS DWSTPRVFTT QDVIYFPPKI LTSVGSNVSF HCIYKKENKI 370 380 390 400 410 420 VPSKEIVWWM NLAEKIPQSQ YDVVSDHVSK VTFFNLNETK PRGKFTYDAV YCCNEHECHH 430 440 450 460 470 480 RYAELYVIDV NINISCETDG YLTKMTCRWS TSTIQSLAES TLQLRYHRSS LYCSDIPSIH 490 500 510 520 530 540 PISEPKDCYL QSDGFYECIF QPIFLLSGYT MWIRINHSLG SLDSPPTCVL PDSVVKPLPP 550 560 570 580 590 600 SSVKAEITIN IGLLKISWEK PVFPENNLQF QIRYGLSGKE VQWKMYEVYD AKSKSVSLPV 610 620 630 640 650 660 PDLCAVYAVQ VRCKRLDGLG YWSNWSNPAY TVVMDIKVPM RGPEFWRIIN GDTMKKEKNV 670 680 690 700 710 720 TLLWKPLMKN DSLCSVQRYV INHHTSCNGT WSEDVGNHTK FTFLWTEQAH TVTVLAINSI 730 740 750 760 770 780 GASVANFNLT FSWPMSKVNI VQSLSAYPLN SSCVIVSWIL SPSDYKLMYF IIEWKNLNED 790 800 810 820 830 840 GEIKWLRISS SVKKYYIHDH FIPIEKYQFS LYPIFMEGVG KPKIINSFTQ DDIEKHQSDA 850 860 870 880 890 900 GLYVIVPVII SSSILLLGTL LISHQRMKKL FWEDVPNPKN CSWAQGLNFQ KKMPGTKELL GGGWLT
	Isoform E [UniParc]. Checksum: 96CA923928EE36FA	FASTA	839	96,042
	10 20 30 40 50 60 MICQKFCVVL LHWEFIYVIT AFNLSYPITP WRFKLSCMPP NSTYDYFLLP AGLSKNTSNS 70 80 90 100 110 120 NGHYETAVEP KFNSSGTHFS NLSKTTFHCC FRSEQDRNCS LCADNIEGKT FVSTVNSLVF 130 140 150 160 170 180 QQIDANWNIQ CWLKGDLKLF ICYVESLFKN LFRNYNYKVH LLYVLPEVLE DSPLVPQKGS 190 200 210 220 230 240 FQMVHCNCSV HECCECLVPV PTAKLNDTLL MCLKITSGGV IFQSPLMSVQ PINMVKPDPP 250 260 270 280 290 300 LGLHMEITDD GNLKISWSSP PLVPFPLQYQ VKYSENSTTV IREADKIVSA TSLLVDSILP 310 320 330 340 350 360 GSSYEVQVRG KRLDGPGIWS DWSTPRVFTT QDVIYFPPKI LTSVGSNVSF HCIYKKENKI 370 380 390 400 410 420 VPSKEIVWWM NLAEKIPQSQ YDVVSDHVSK VTFFNLNETK PRGKFTYDAV YCCNEHECHH 430 440 450 460 470 480 RYAELYVIDV NINISCETDG YLTKMTCRWS TSTIQSLAES TLQLRYHRSS LYCSDIPSIH 490 500 510 520 530 540 PISEPKDCYL QSDGFYECIF QPIFLLSGYT MWIRINHSLG SLDSPPTCVL PDSVVKPLPP 550 560 570 580 590 600 SSVKAEITIN IGLLKISWEK PVFPENNLQF QIRYGLSGKE VQWKMYEVYD AKSKSVSLPV 610 620 630 640 650 660 PDLCAVYAVQ VRCKRLDGLG YWSNWSNPAY TVVMDIKVPM RGPEFWRIIN GDTMKKEKNV 670 680 690 700 710 720 TLLWKPLMKN DSLCSVQRYV INHHTSCNGT WSEDVGNHTK FTFLWTEQAH TVTVLAINSI 730 740 750 760 770 780 GASVANFNLT FSWPMSKVNI VQSLSAYPLN SSCVIVSWIL SPSDYKLMYF IIEWKNLNED 790 800 810 820 830 GEIKWLRISS SVKKYYIHDH FIPIEKYQFS LYPIFMEGVG KPKIINSFTQ DDIEKHQSD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification and expression cloning of a leptin receptor, OB-R." Tartaglia L.A., Dembski M., Weng X., Deng N., Culpepper J., Devos R., Richards G.J., Campfield L.A., Clark F.T., Deeds J., Muir C., Sanker S., Moriarty A., Moore K.J., Smutko J.S., Mays G.G., Woolf E.A., Monroe C.A., Tepper R.I. Cell 83:1263-1271(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS B AND E). Tissue: Brain.
[2]	"A role for leptin and its cognate receptor in hematopoiesis." Bennett B.D., Solar G.P., Yuan J.Q., Mathias J., Thomas G.R., Matthews W. Curr. Biol. 6:1170-1180(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A; B AND C). Tissue: Fetal liver.
[3]	"Novel B219/OB receptor isoforms: possible role of leptin in hematopoiesis and reproduction." Cioffi J.A., Shafer A.W., Zupancic T.J., Smith-Gbur J., Mikhail A., Platika D., Snodgrass H.R. Nat. Med. 2:585-589(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A; C AND D), VARIANTS ARG-109 AND ARG-223. Tissue: Fetal liver.
[4]	"Structure and sequence variation at the human leptin receptor gene in lean and obese Pima Indians." Thompson D.B., Ravussin E., Bennett P.H., Bogardus C. Hum. Mol. Genet. 6:675-679(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM B), VARIANTS ARG-109 AND ARG-223.
[5]	"Cloning and characterization of a human leptin receptor using a biologically active leptin immunoadhesin." Luoh S.-M., Di Marco F., Levin N., Armanini M., Xie M.H., Nelson C., Bennett G.L., Williams M., Spencer S.A., Gurney A., de Sauvage F.J. J. Mol. Endocrinol. 18:77-85(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
[6]	"The long terminal repeat of an endogenous retrovirus induces alternative splicing and encodes an additional carboxy-terminal sequence in the human leptin receptor." Kapitonov V.V., Jurka J. J. Mol. Evol. 48:248-251(1999) [PubMed] [Europe PMC] [Abstract] Cited for: ALTERNATIVE SPLICING DUE TO AN ENDOGENOUS RETROVIRUS.
[7]	"Enhancing leptin response by preventing SH2-containing phosphatase 2 interaction with Ob receptor." Carpenter L.R., Farruggella T.J., Symes A., Karow M.L., Yancopoulos G.D., Stahl N. Proc. Natl. Acad. Sci. U.S.A. 95:6061-6066(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PTPN11, MUTAGENESIS OF TYR-986; 1078-TYR-TYR-1079 AND TYR-1141.
[8]	"Human leptin receptor. Determination of disulfide structure and N-glycosylation sites of the extracellular domain." Haniu M., Arakawa T., Bures E.J., Young Y., Hui J.O., Rohde M.F., Welcher A.A., Horan T. J. Biol. Chem. 273:28691-28699(1998) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION AT ASN-23; ASN-41; ASN-56; ASN-73; ASN-81; ASN-98; ASN-187; ASN-206; ASN-276; ASN-347; ASN-397; ASN-516; ASN-624; ASN-659; ASN-688; ASN-697; ASN-728 AND ASN-750, DISULFIDE BONDS, PARTIAL PROTEIN SEQUENCE.
[9]	"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry." Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D. J. Proteome Res. 4:2070-2080(2005) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-276 AND ASN-516, MASS SPECTROMETRY. Tissue: Plasma.
[10]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-276 AND ASN-397, MASS SPECTROMETRY. Tissue: Liver.
[11]	"Structure of the human obesity receptor leptin-binding domain reveals the mechanism of leptin antagonism by a monoclonal antibody." Carpenter B., Hemsworth G.R., Wu Z., Maamra M., Strasburger C.J., Ross R.J., Artymiuk P.J. Structure 20:487-497(2012) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 428-633 IN COMPLEX WITH ANTIBODY, LEPTIN-BINDING REGION, DISULFIDE BONDS.
[12]	"The hypothalamic leptin receptor in humans: identification of incidental sequence polymorphisms and absence of the db/db mouse and fa/fa rat mutations." Considine R.V., Considine E.L., Williams C.J., Hyde T.M., Caro J.F. Diabetes 45:992-994(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ARG-223.
[13]	"Amino acid variants in the human leptin receptor: lack of association to juvenile onset obesity." Echwald S.M., Soerensen T.D., Soerensen T.I., Tybjaerg-Hansen A., Andersen T., Chung W.K., Leibel R.L., Pedersen O. Biochem. Biophys. Res. Commun. 233:248-252(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ARG-109; ARG-204; ARG-223 AND ASN-656.
[14]	"Exonic and intronic sequence variation in the human leptin receptor gene (LEPR)." Chung W.K., Power-Kehoe L., Chua M., Chu F., Aronne L., Huma Z., Sothern M., Udall J.N., Kahle B., Leibel R.L. Diabetes 46:1509-1511(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ARG-109; ARG-223 AND ASN-656.
[15]	"Leptin receptor gene variation and obesity: lack of association in a white British male population." Gotoda T., Manning B.S., Goldstone A.P., Imrie H., Evans A.L., Strosberg A.D., McKeigue P.M., Scott J., Aitman T.J. Hum. Mol. Genet. 6:869-876(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ARG-109; ARG-223 AND ASN-656.
[16]	"Transmission disequilibrium and sequence variants at the leptin receptor gene in extremely obese German children and adolescents." Roth H., Korn T., Rosenkranz K., Hinney A., Ziegler A., Kunz J., Siegfried W., Mayer H., Hebebrand J., Grzeschik K.-H. Hum. Genet. 103:540-546(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ARG-109; ARG-223; ASN-656 AND THR-675.
[17]	"DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome." Ley T.J., Mardis E.R., Ding L., Fulton B., McLellan M.D., Chen K., Dooling D., Dunford-Shore B.H., McGrath S., Hickenbotham M., Cook L., Abbott R., Larson D.E., Koboldt D.C., Pohl C., Smith S., Hawkins A., Abbott S. , Locke D., Hillier L.W., Miner T., Fulton L., Magrini V., Wylie T., Glasscock J., Conyers J., Sander N., Shi X., Osborne J.R., Minx P., Gordon D., Chinwalla A., Zhao Y., Ries R.E., Payton J.E., Westervelt P., Tomasson M.H., Watson M., Baty J., Ivanovich J., Heath S., Shannon W.D., Nagarajan R., Walter M.J., Link D.C., Graubert T.A., DiPersio J.F., Wilson R.K. Nature 456:66-72(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] ARG-109 AND ARG-223.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U43168 mRNA. Translation: AAA93015.1.
U66495 mRNA. Translation: AAB07495.1.
U66496 mRNA. Translation: AAB07496.1.
U66497 mRNA. Translation: AAB07497.1.
U52912 mRNA. Translation: AAC50509.1.
U52913 mRNA. Translation: AAC50510.1.
U52914 mRNA. Translation: AAC50511.1.
U59263 , U59248, U59249, U59250, U59252, U59253, U59254, U59255, U59256, U59257, U59258, U59259, U59260, U59261, U59262 Genomic DNA. Translation: AAB09673.1.
U50748 mRNA. Translation: AAC23650.1.

IPI

IPI00009243.
IPI00219708.
IPI00219709.
IPI00219710.
IPI00219711.

RefSeq

NP_001003679.1. NM_001003679.3.
NP_001003680.1. NM_001003680.3.
NP_001185616.1. NM_001198687.1.
NP_001185617.1. NM_001198688.1.
NP_001185618.1. NM_001198689.1.
NP_002294.2. NM_002303.5.

UniGene

Hs.23581.
Hs.723178.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3V6O	X-ray	1.95	A/B	428-633	[»]

ProteinModelPortal

P48357.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-6117N.

IntAct

P48357. 6 interactions.

MINT

MINT-1387953.

STRING

9606.ENSP00000330393.

PTM databases

PhosphoSite

P48357.

Polymorphism databases

DMDM

116242617.

Proteomic databases

PaxDb

P48357.

PRIDE

P48357.

Protocols and materials databases

DNASU

3953.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000344610; ENSP00000340884; ENSG00000116678.
ENST00000349533; ENSP00000330393; ENSG00000116678.
ENST00000371058; ENSP00000360097; ENSG00000116678.
ENST00000371059; ENSP00000360098; ENSG00000116678.
ENST00000371060; ENSP00000360099; ENSG00000116678.

GeneID

3953.

KEGG

hsa:3953.

UCSC

uc001dcg.3. human.
uc001dch.3. human.
uc001dci.3. human.
uc021ool.1. human.

Organism-specific databases

CTD

3953.

GeneCards

GC01P065886.

HGNC

HGNC:6554. LEPR.

HPA

HPA030899.

MIM

601007. gene.

neXtProt

NX_P48357.

Orphanet

179494. Obesity due to leptin receptor gene deficiency.

PharmGKB

PA229.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG29456.

HOVERGEN

HBG000140.

InParanoid

P48357.

KO

K05062.

OMA

LKLFICY.

OrthoDB

EOG469QT5.

PhylomeDB

P48357.

Enzyme and pathway databases

Pathway_Interaction_DB

ptp1bpathway. Signaling events mediated by PTP1B.

Gene expression databases

ArrayExpress

P48357.

Bgee

P48357.

CleanEx

HS_LEPR.

Genevestigator

P48357.

GermOnline

ENSG00000116678. Homo sapiens.

Family and domain databases

Gene3D

2.60.40.10. 4 hits.

InterPro

IPR003961. Fibronectin_type3.
IPR003529. Hematopoietin_rcpt_Gp130_CS.
IPR003531. Hempt_rcpt_S_F1_CS.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR010457. IgC2-like_lig-bd.
IPR015752. Lep_receptor.
[Graphical view]

PANTHER

PTHR23036:SF11. PTHR23036:SF11. 1 hit.

Pfam

PF06328. Lep_receptor_Ig. 1 hit.
[Graphical view]

SMART

SM00060. FN3. 4 hits.
[Graphical view]

SUPFAM

SSF49265. FN_III-like. 4 hits.

PROSITE

PS50853. FN3. 4 hits.
PS01353. HEMATOPO_REC_L_F2. 1 hit.
PS50835. IG_LIKE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChEMBL

CHEMBL5913.

GenomeRNAi

3953.

NextBio

15505.

SOURCE

Search...

Entry information

Entry name

LEPR_HUMAN

Accession

Primary (citable) accession number: P48357
Secondary accession number(s): Q13592 , Q13593, Q13594, Q92919, Q92920, Q92921

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	October 17, 2006
Last modified:	May 1, 2013
This is version 146 of the entry and version 2 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.