LEPR_HUMAN » Leptin receptor

LEPR_HUMAN » Leptin receptor
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Topology in Plasma membrane
Topologyextracellular side
cytoplasmic side
LEPR_HUMAN » Leptin receptor » LEP-R; HuB219;OB receptor;OB-R;
Hydrophobic Thickness 35.2 ± 0.6 Å
Tilt Angle 0 ± 0°
ΔGtransfer -44.3 kcal/mol
ΔGfold -13.8 kcal/mol
Links UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC
Topology Out
TM Segments 841-865 (832-868)
Pathways

Adipocytokine signaling pathway (KEGG)

Cytokine-cytokine receptor interaction (KEGG)

Jak-STAT signaling pathway (KEGG)

Neuroactive ligand-receptor interaction (KEGG)

PDB 3v6o (A/B=428-633)
OPM none
Complexes

LEPR:LEPR_HUMAN

Interactions

ERBB2, Complex: LEPR:ERBB2, PubMed

IGF1R, Complex: IGF1R:LEPR, PubMed

ITB5, Complex: LEPR:ITB5, PubMed

LEPR, Complex: Homodimer of leptin receptor, PDBID: 3V6O

PTPRC, Complex: PTPRC:LEPR, PubMed

PTPRJ, Complex: PTPRJ:LEPR, PubMed

Domains

AA: 330-420, PDBID: 1I1R, Subunit A, Seq Identity:19%, Ig-like C2-type domain

UniProt annotation for LEPR_HUMAN » Leptin receptor
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: 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).

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.

DOMAIN: The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell- surface receptor binding.

DOMAIN: The box 1 motif is required for JAK interaction and/or activation.

DISEASE: Leptin receptor deficiency (LEPRD) OMIM: A rare disease characterized by normal levels of serum leptin, hyperphagia and severe obesity from an early age. Additional features include alterations in immune function, and delayed puberty due to hypogonadotropic hypogonadism. mutations affecting the gene represented in this entry.

UniProt features for LEPR_HUMAN » Leptin receptor
SIGNAL 1 21
CHAIN 22 1165 Leptin receptor.
DOMAIN 237 330 Fibronectin type-III 1.
DOMAIN 331 429 Ig-like.
DOMAIN 537 631 Fibronectin type-III 2.
DOMAIN 639 732 Fibronectin type-III 3.
DOMAIN 734 829 Fibronectin type-III 4.
REGION 467 484 Leptin-binding (Probable).
REGION 893 898 Required for JAK2 activation (By similarity).
MOTIF 622 626 WSXWS motif.
MOTIF 871 879 Box 1 motif.
DISULFID 37 90
DISULFID 89 99
DISULFID 131 142
DISULFID 186 196
DISULFID 188 193
DISULFID 352 412
DISULFID 413 418
DISULFID 436 447
DISULFID 473 528
DISULFID 488 498
Amino Acid Sequence for LEPR_HUMAN » Leptin receptor
MICQKFCVVL LHWEFIYVIT AFNLSYPITP WRFKLSCMPP NSTYDYFLLP AGLSKNTSNS NGHYETAVEP KFNSSGTHFS NLSKTTFHCC FRSEQDRNCS LCADNIEGKT FVSTVNSLVF QQIDANWNIQ CWLKGDLKLF ICYVESLFKN LFRNYNYKVH LLYVLPEVLE DSPLVPQKGS FQMVHCNCSV HECCECLVPV PTAKLNDTLL MCLKITSGGV IFQSPLMSVQ PINMVKPDPP LGLHMEITDD GNLKISWSSP PLVPFPLQYQ VKYSENSTTV IREADKIVSA TSLLVDSILP GSSYEVQVRG KRLDGPGIWS DWSTPRVFTT QDVIYFPPKI LTSVGSNVSF HCIYKKENKI VPSKEIVWWM NLAEKIPQSQ YDVVSDHVSK VTFFNLNETK PRGKFTYDAV YCCNEHECHH RYAELYVIDV NINISCETDG YLTKMTCRWS TSTIQSLAES TLQLRYHRSS LYCSDIPSIH PISEPKDCYL QSDGFYECIF QPIFLLSGYT MWIRINHSLG SLDSPPTCVL PDSVVKPLPP SSVKAEITIN IGLLKISWEK PVFPENNLQF QIRYGLSGKE VQWKMYEVYD AKSKSVSLPV PDLCAVYAVQ VRCKRLDGLG YWSNWSNPAY TVVMDIKVPM RGPEFWRIIN GDTMKKEKNV TLLWKPLMKN DSLCSVQRYV INHHTSCNGT WSEDVGNHTK FTFLWTEQAH TVTVLAINSI GASVANFNLT FSWPMSKVNI VQSLSAYPLN SSCVIVSWIL SPSDYKLMYF IIEWKNLNED GEIKWLRISS SVKKYYIHDH FIPIEKYQFS LYPIFMEGVG KPKIINSFTQ DDIEKHQSDA GLYVIVPVII SSSILLLGTL LISHQRMKKL FWEDVPNPKN CSWAQGLNFQ KPETFEHLFI KHTASVTCGP LLLEPETISE DISVDTSWKN KDEMMPTTVV SLLSTTDLEK GSVCISDQFN SVNFSEAEGT EVTYEDESQR QPFVKYATLI SNSKPSETGE EQGLINSSVT KCFSSKNSPL KDSFSNSSWE IEAQAFFILS DQHPNIISPH LTFSEGLDEL LKLEGNFPEE NNDKKSIYYL GVTSIKKRES GVLLTDKSRV SCPFPAPCLF TDIRVLQDSC SHFVENNINL GTSSKKTFAS YMPQFQTCST QTHKIMENKM CDLTV