LEPR_MACMU
ID LEPR_MACMU Reviewed; 1163 AA.
AC Q9MYL0; Q9MYK9; Q9MYL1; Q9MYL2;
DT 19-OCT-2002, integrated into UniProtKB/Swiss-Prot.
DT 19-OCT-2002, sequence version 2.
DT 25-MAY-2022, entry version 125.
DE RecName: Full=Leptin receptor;
DE Short=LEP-R;
DE AltName: Full=OB receptor;
DE Short=OB-R;
DE AltName: CD_antigen=CD295;
DE Flags: Precursor;
GN Name=LEPR; Synonyms=OBR;
OS Macaca mulatta (Rhesus macaque).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9544;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND B).
RC TISSUE=Adipose tissue;
RX PubMed=9738551; DOI=10.1002/j.1550-8528.1998.tb00363.x;
RA Hotta K., Gustafson T.A., Ortmeyer H.K., Bodkin N.L., Hansen B.C.;
RT "Monkey leptin receptor mRNA: sequence, tissue distribution, and mRNA
RT expression in the adipose tissue of normal, hyperinsulinemic, and type 2
RT diabetic rhesus monkeys.";
RL Obes. Res. 6:353-360(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND B).
RC TISSUE=Adipose tissue;
RA Hotta K., Gustafson T.A., Ortmeyer H.K., Bodkin N.L., Hansen B.C.;
RL Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Gustafson T.A., Ortmeyer H.K., Bodkin N.L., Hansen B.C.;
RL Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Receptor for hormone LEP/leptin (By similarity). On ligand
CC binding, mediates LEP central and peripheral effects through the
CC activation of different signaling pathways such as JAK2/STAT3 and MAPK
CC cascade/FOS. In the hypothalamus, LEP acts as an appetite-regulating
CC factor that induces a decrease in food intake and an increase in energy
CC consumption by inducing anorexinogenic factors and suppressing
CC orexigenic neuropeptides, also regulates bone mass and secretion of
CC hypothalamo-pituitary-adrenal hormones. In the periphery, increases
CC basal metabolism, influences reproductive function, regulates
CC pancreatic beta-cell function and insulin secretion, is pro-angiogenic
CC and affects innate and adaptive immunity (By similarity). Control of
CC energy homeostasis and melanocortin production (stimulation of POMC and
CC full repression of AgRP transcription) is mediated by STAT3 signaling,
CC whereas distinct signals regulate NPY and the control of fertility,
CC growth and glucose homeostasis. Involved in the regulation of counter-
CC regulatory response to hypoglycemia by inhibiting neurons of the
CC parabrachial nucleus. Has a specific effect on T lymphocyte responses,
CC differentially regulating the proliferation of naive and memory T-
CC cells. Leptin increases Th1 and suppresses Th2 cytokine production (By
CC similarity). {ECO:0000250|UniProtKB:P48356,
CC ECO:0000250|UniProtKB:P48357}.
CC -!- FUNCTION: [Isoform A]: May transport LEP across the blood-brain
CC barrier. Binds LEP and mediates LEP endocytosis. Does not induce
CC phosphorylation of and activate STAT3. {ECO:0000250|UniProtKB:P48356}.
CC -!- SUBUNIT: Present as a mixture of monomers and dimers. The
CC phosphorylated receptor binds a number of SH2 domain-containing
CC proteins such as JAK2, STAT3, PTPN11, and SOCS3 (By similarity).
CC Interaction with SOCS3 inhibits JAK/STAT signaling and MAPK cascade (By
CC similarity). {ECO:0000250|UniProtKB:P48356,
CC ECO:0000250|UniProtKB:P48357}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P48357};
CC Single-pass type I membrane protein {ECO:0000250|UniProtKB:P48357}.
CC Basolateral cell membrane {ECO:0000250|UniProtKB:P48357}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=B;
CC IsoId=Q9MYL0-1; Sequence=Displayed;
CC Name=A;
CC IsoId=Q9MYL0-2; Sequence=VSP_001695, VSP_001696;
CC -!- TISSUE SPECIFICITY: Widely expressed. High expression of isoform B in
CC liver, adipose tissue, hypothalamus and choroid plexus.
CC -!- DOMAIN: The cytoplasmic domain may be essential for intracellular
CC signal transduction by activation of JAK tyrosine kinase and STATs.
CC -!- DOMAIN: The WSXWS motif appears to be necessary for proper protein
CC folding and thereby efficient intracellular transport and cell-surface
CC receptor binding.
CC -!- DOMAIN: The box 1 motif is required for JAK interaction and/or
CC activation.
CC -!- PTM: On ligand binding, phosphorylated on two conserved C-terminal
CC tyrosine residues (isoform B only) by JAK2. Tyr-984 is required for
CC complete binding and activation of PTPN11, ERK/FOS activation and, for
CC interaction with SOCS3. Phosphorylation on Tyr-1139 is required for
CC STAT3 binding/activation (By similarity). {ECO:0000250}.
CC -!- PTM: On ligand binding, phosphorylated on two conserved C-terminal
CC tyrosine residues (isoform B only) by JAK2. Tyr-984 is required for
CC complete binding and activation of PTPN11, ERK/FOS activation,for
CC interaction with SOCS3 and SOCS3 mediated inhibition of leptin
CC signaling. Phosphorylation on Tyr-1139 is required for STAT3
CC binding/activation. Phosphorylation of Tyr-1077 has a more accessory
CC role. {ECO:0000250|UniProtKB:P48356}.
CC -!- SIMILARITY: Belongs to the type I cytokine receptor family. Type 2
CC subfamily. {ECO:0000305}.
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DR EMBL; AF225874; AAF35388.1; -; mRNA.
DR EMBL; AF225875; AAF35389.1; -; mRNA.
DR EMBL; AF225873; AAF35387.1; -; mRNA.
DR EMBL; AF222960; AAF34683.1; -; mRNA.
DR RefSeq; NP_001027991.1; NM_001032819.1.
DR AlphaFoldDB; Q9MYL0; -.
DR STRING; 9544.ENSMMUP00000040008; -.
DR GeneID; 574126; -.
DR KEGG; mcc:574126; -.
DR CTD; 3953; -.
DR eggNOG; ENOG502RK5B; Eukaryota.
DR InParanoid; Q9MYL0; -.
DR OrthoDB; 144839at2759; -.
DR Proteomes; UP000006718; Unplaced.
DR GO; GO:0016323; C:basolateral plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0019955; F:cytokine binding; IBA:GO_Central.
DR GO; GO:0004896; F:cytokine receptor activity; IBA:GO_Central.
DR GO; GO:0038021; F:leptin receptor activity; ISS:UniProtKB.
DR GO; GO:0017046; F:peptide hormone binding; IBA:GO_Central.
DR GO; GO:0001525; P:angiogenesis; ISS:UniProtKB.
DR GO; GO:0098868; P:bone growth; ISS:UniProtKB.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0097009; P:energy homeostasis; ISS:UniProtKB.
DR GO; GO:0042593; P:glucose homeostasis; ISS:UniProtKB.
DR GO; GO:0033210; P:leptin-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0010507; P:negative regulation of autophagy; ISS:UniProtKB.
DR GO; GO:0006909; P:phagocytosis; ISS:UniProtKB.
DR GO; GO:0046850; P:regulation of bone remodeling; ISS:UniProtKB.
DR GO; GO:0060259; P:regulation of feeding behavior; ISS:UniProtKB.
DR GO; GO:0044321; P:response to leptin; ISS:UniProtKB.
DR GO; GO:0019953; P:sexual reproduction; ISS:UniProtKB.
DR GO; GO:0030217; P:T cell differentiation; ISS:UniProtKB.
DR CDD; cd00063; FN3; 3.
DR Gene3D; 2.60.40.10; -; 7.
DR InterPro; IPR003961; FN3_dom.
DR InterPro; IPR036116; FN3_sf.
DR InterPro; IPR003529; Hematopoietin_rcpt_Gp130_CS.
DR InterPro; IPR003531; Hempt_rcpt_S_F1_CS.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR010457; IgC2-like_lig-bd.
DR InterPro; IPR041182; LEP-R_IGD.
DR InterPro; IPR015752; Lep_receptor.
DR PANTHER; PTHR23036:SF109; PTHR23036:SF109; 1.
DR Pfam; PF06328; Lep_receptor_Ig; 1.
DR Pfam; PF18589; ObR_Ig; 2.
DR SMART; SM00060; FN3; 4.
DR SUPFAM; SSF49265; SSF49265; 4.
DR PROSITE; PS50853; FN3; 3.
DR PROSITE; PS01353; HEMATOPO_REC_L_F2; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Cell membrane; Disulfide bond; Glycoprotein;
KW Membrane; Obesity; Phosphoprotein; Receptor; Reference proteome; Repeat;
KW Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..1163
FT /note="Leptin receptor"
FT /id="PRO_0000010905"
FT TOPO_DOM 22..837
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 838..860
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 861..1163
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 237..331
FT /note="Fibronectin type-III 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 537..632
FT /note="Fibronectin type-III 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 637..730
FT /note="Fibronectin type-III 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 738..831
FT /note="Fibronectin type-III 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT REGION 465..482
FT /note="Leptin-binding"
FT /evidence="ECO:0000250|UniProtKB:P48357"
FT REGION 891..896
FT /note="Required for JAK2 activation"
FT /evidence="ECO:0000250|UniProtKB:P48356"
FT REGION 896..904
FT /note="Required for STAT3 phosphorylation"
FT /evidence="ECO:0000250|UniProtKB:P48356"
FT MOTIF 620..624
FT /note="WSXWS motif"
FT MOTIF 869..877
FT /note="Box 1 motif"
FT MOD_RES 880
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P48357"
FT MOD_RES 984
FT /note="Phosphotyrosine; by JAK2"
FT /evidence="ECO:0000250|UniProtKB:P48356"
FT MOD_RES 1077
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P48356"
FT MOD_RES 1139
FT /note="Phosphotyrosine; by JAK2"
FT /evidence="ECO:0000250|UniProtKB:P48356"
FT CARBOHYD 23
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 41
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 56
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 71
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 79
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 96
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 114
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 185
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 204
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 274
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 345
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 395
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 431
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 622
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 657
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 668
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 686
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 695
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 726
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 748
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 37..88
FT /evidence="ECO:0000250|UniProtKB:P48357"
FT DISULFID 87..97
FT /evidence="ECO:0000250|UniProtKB:P48357"
FT DISULFID 129..140
FT /evidence="ECO:0000250|UniProtKB:P48357"
FT DISULFID 184..194
FT /evidence="ECO:0000250|UniProtKB:P48357"
FT DISULFID 350..410
FT /evidence="ECO:0000250|UniProtKB:P48357"
FT DISULFID 411..416
FT /evidence="ECO:0000250|UniProtKB:P48357"
FT DISULFID 434..445
FT /evidence="ECO:0000250|UniProtKB:P48357"
FT DISULFID 471..526
FT /evidence="ECO:0000250|UniProtKB:P48357"
FT DISULFID 486..496
FT /evidence="ECO:0000250|UniProtKB:P48357"
FT VAR_SEQ 890..894
FT /note="PETFE -> RTDIL (in isoform A)"
FT /evidence="ECO:0000303|PubMed:9738551, ECO:0000303|Ref.2"
FT /id="VSP_001695"
FT VAR_SEQ 895..1163
FT /note="Missing (in isoform A)"
FT /evidence="ECO:0000303|PubMed:9738551, ECO:0000303|Ref.2"
FT /id="VSP_001696"
FT CONFLICT 889
FT /note="K -> KIRGFVMLPRLVLNSQAQVIHPPRPPKVLELQ (in Ref. 2;
FT AAF35387/AAF34683)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1163 AA; 132296 MW; 6B7B89108F851895 CRC64;
MICQKFCVVL LHWEFICVIT AFNLSYPITP WRFKLSCMPP NSTYDYFLLP AGLSKNTSNL
NGHYETAVEF NSSDTHFSNL SKTTFHCCFR SEQDRNCSLC ADNIEGKTFV STVNSSVFQQ
MGANWNIQCW LKGDLKLFIC YVESLFKNPF KNYKHKVHLL YVLPEVLEDS PLVPQKGSFQ
MVHCNCSVHE RCECLVPVPT AKLNDTLLMC LKITSGGVIF QSPLMSVQPI NMVKPDPPLG
LRMEITDDGN LKISWSSPPL VPFPLQYEVK YSENSTTVIR EADKIVSATS LLVDGILPGS
SYEVQVRGKR LDGPGIWSDW STPHVFTTQD VIYFPPKILT SVGSNVSFHC IYKNENKIVS
SKKIVWWMNL AEKIPQSQYD VVSDHVSKVT FFNLNETKPR GKFTYDAVYC CNEHECHHRY
AELYVIDVNI NISCETDGHL TKMTCRWSTN TIQSLAGSTL QLRYRRSSLY CFDIPSIHPI
SKPKDCYLQS DGFYECVFQP IFLLSGYTMW IRINHPLGSL DSPPTCVLPD SVVKPLPPSS
VKAEIIKNIG LLKISWEKPV FPENNLQFQI RYGLSGKEIQ WKMYDVYDAK SKSVSLPVPD
FCAVYAVQVR CKRSDGLGLW SNWSNPAYTV VMDIKVPMRG PEFWRIINGD TMKKEKNVTL
LWKPLMKNES LCSVQRYVIN HHTSCNGTWS EDVGNHTKFT FLWTEQAHTV TVLAINSIGA
SVANFNLTFS WPMSKVNIVQ SLSAYPLNSS CVILSWILSP SDYKLMYFII EWKNLNEDGE
IKWLRISSSV KKYYIHDHFI PIEKYQFSLY PIFMEGVGKP KIINSFAQDN TEKHQNDAGL
YVIVPVIISS SILLLGTLLI LHQRMKKLFW EDVPNPKNCS WAQGLNFQKP ETFEHLFIKH
TASVTCGPLL LEPETISEDI SVDTSWKNKD EMVPTTVVSL LSTTDLEKGS VCISDQFNSV
NFSEAEGTEV TCEDESQRQP FVKYATLISN SKPSETDEEQ GLINSSVTKC FSSKNSPLKD
SFSNSSWEIE AQAFFILSDQ RPNIILPHLT FSEGLDELLR LEGNFPEENN DEKSIYYLGV
TSIKKRESGV LLTDKSRVLC PFPAPCLFTD IRVLQDSCSH FVENNFNLGT SSKKTFASYM
PQFQTCSTQT HKIMENKMCD LTV
