LEPR_PIG
ID LEPR_PIG Reviewed; 1165 AA.
AC O02671; Q95257; Q9MZS2; Q9N1F9; Q9XSN9;
DT 19-OCT-2002, integrated into UniProtKB/Swiss-Prot.
DT 19-OCT-2002, sequence version 3.
DT 25-MAY-2022, entry version 128.
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 Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=10911396;
RX DOI=10.1002/1098-2795(200008)56:4<465::aid-mrd4>3.0.co;2-q;
RA Ruiz-Cortes Z.T., Men T., Palin M.-F., Downey B.R., Lacroix D.A.,
RA Murphy B.D.;
RT "Porcine leptin receptor: molecular structure and expression in the
RT ovary.";
RL Mol. Reprod. Dev. 56:465-474(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-123.
RC STRAIN=Yorkshire X Meishan;
RA Lacroix D.A., Gevry N.Y., Ruiz-Cortes Z.T., Murphy B.D.;
RT "Porcine leptin receptor intron 3, partial.";
RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 7-854.
RC TISSUE=Liver;
RA Hu X., Dai R., Li N., Wu C.;
RT "Expression, detection, and partial cloning of porcine leptin receptor
RT (OBR) gene.";
RL Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 13-159 AND 916-1088.
RC TISSUE=Hypothalamus;
RA Matteri R.L., Carroll J.A.;
RT "Partial cDNA sequence of the porcine leptin receptor.";
RL Submitted (DEC-1997) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 109-123.
RX PubMed=9800339;
RA Stratil A., Kopecny M., Moser G., Schroffel J. Jr., Cepica S.;
RT "HpaII and RsaI PCR-RFLPs within an intron of the porcine leptin receptor
RT gene (LEPR) and its linkage mapping.";
RL Anim. Genet. 29:405-406(1998).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 408-470.
RX PubMed=9069130; DOI=10.1007/s003359900397;
RA Ernst C.W., Kapke P.A., Yerle M., Rothschild M.F.;
RT "The leptin receptor gene (LEPR) maps to porcine chromosome 6.";
RL Mamm. Genome 8:226-226(1997).
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 -!- 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 -!- TISSUE SPECIFICITY: Kidney, liver, spleen, lung, brain, testis, uterus,
CC ovary, corpus luteum, theca and granulosa cells.
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 by JAK2. Tyr-986 is required for complete binding and
CC activation of PTPN11, ERK/FOS activation,for interaction with SOCS3 and
CC SOCS3 mediated inhibition of leptin signaling. Phosphorylation on Tyr-
CC 1141 is required for STAT3 binding/activation. Phosphorylation of Tyr-
CC 1079 has a more accessory 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; AF092422; AAC61766.1; -; mRNA.
DR EMBL; AH009271; AAF66822.1; -; Genomic_DNA.
DR EMBL; AF167719; AAF89633.1; -; mRNA.
DR EMBL; AF036908; AAB88825.1; -; mRNA.
DR EMBL; U67739; AAB07892.1; -; mRNA.
DR EMBL; AJ223162; CAA11142.1; -; Genomic_DNA.
DR EMBL; AJ223163; CAA11143.1; -; Genomic_DNA.
DR EMBL; U72070; AAC48707.1; -; Genomic_DNA.
DR RefSeq; NP_001019758.1; NM_001024587.1.
DR AlphaFoldDB; O02671; -.
DR SMR; O02671; -.
DR STRING; 9823.ENSSSCP00000022838; -.
DR PaxDb; O02671; -.
DR PRIDE; O02671; -.
DR GeneID; 396836; -.
DR KEGG; ssc:396836; -.
DR CTD; 3953; -.
DR eggNOG; ENOG502RK5B; Eukaryota.
DR InParanoid; O02671; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; 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; 1.
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; 4.
DR PROSITE; PS01353; HEMATOPO_REC_L_F2; 1.
PE 2: Evidence at transcript level;
KW Cell membrane; Disulfide bond; Glycoprotein; Membrane; Obesity;
KW Phosphoprotein; Receptor; Reference proteome; Repeat; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..1165
FT /note="Leptin receptor"
FT /id="PRO_0000010907"
FT TOPO_DOM 22..838
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 839..861
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 862..1165
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 239..332
FT /note="Fibronectin type-III 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 539..634
FT /note="Fibronectin type-III 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 642..736
FT /note="Fibronectin type-III 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 740..834
FT /note="Fibronectin type-III 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT REGION 467..484
FT /note="Leptin-binding"
FT /evidence="ECO:0000250|UniProtKB:P48357"
FT REGION 892..897
FT /note="Required for JAK2 activation"
FT /evidence="ECO:0000250|UniProtKB:P48356"
FT REGION 897..905
FT /note="Required for STAT3 phosphorylation"
FT /evidence="ECO:0000250|UniProtKB:P48356"
FT MOTIF 622..626
FT /note="WSXWS motif"
FT MOTIF 870..878
FT /note="Box 1 motif"
FT MOD_RES 881
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P48357"
FT MOD_RES 986
FT /note="Phosphotyrosine; by JAK2"
FT /evidence="ECO:0000250|UniProtKB:P48356"
FT MOD_RES 1079
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P48356"
FT MOD_RES 1141
FT /note="Phosphotyrosine; by JAK2"
FT /evidence="ECO:0000250|UniProtKB:P48356"
FT CARBOHYD 41
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 55
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 72
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 80
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 98
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 187
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 206
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 276
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 347
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 397
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 433
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 624
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 659
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 670
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 697
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 728
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 750
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 37..90
FT /evidence="ECO:0000250|UniProtKB:P48357"
FT DISULFID 89..99
FT /evidence="ECO:0000250|UniProtKB:P48357"
FT DISULFID 131..142
FT /evidence="ECO:0000250|UniProtKB:P48357"
FT DISULFID 186..196
FT /evidence="ECO:0000250|UniProtKB:P48357"
FT DISULFID 188..193
FT /evidence="ECO:0000250|UniProtKB:P48357"
FT DISULFID 352..412
FT /evidence="ECO:0000250|UniProtKB:P48357"
FT DISULFID 413..418
FT /evidence="ECO:0000250|UniProtKB:P48357"
FT DISULFID 436..447
FT /evidence="ECO:0000250|UniProtKB:P48357"
FT DISULFID 473..528
FT /evidence="ECO:0000250|UniProtKB:P48357"
FT DISULFID 488..498
FT /evidence="ECO:0000250|UniProtKB:P48357"
FT CONFLICT 7..9
FT /note="SVA -> CVV (in Ref. 3; AAF89633)"
FT /evidence="ECO:0000305"
FT CONFLICT 69
FT /note="T -> M (in Ref. 3; AAF89633 and 4; AAB07892)"
FT /evidence="ECO:0000305"
FT CONFLICT 73
FT /note="S -> I (in Ref. 1; AAC61766)"
FT /evidence="ECO:0000305"
FT CONFLICT 283
FT /note="E -> K (in Ref. 3; AAF89633)"
FT /evidence="ECO:0000305"
FT CONFLICT 350
FT /note="F -> L (in Ref. 3; AAF89633)"
FT /evidence="ECO:0000305"
FT CONFLICT 362
FT /note="S -> P (in Ref. 3; AAF89633)"
FT /evidence="ECO:0000305"
FT CONFLICT 365
FT /note="K -> E (in Ref. 3; AAF89633)"
FT /evidence="ECO:0000305"
FT CONFLICT 385
FT /note="G -> S (in Ref. 3; AAF89633)"
FT /evidence="ECO:0000305"
FT CONFLICT 974
FT /note="R -> C (in Ref. 4; AAB88825)"
FT /evidence="ECO:0000305"
FT CONFLICT 1047
FT /note="T -> I (in Ref. 4; AAB88825)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1165 AA; 132523 MW; 9F02EADDEDC26D21 CRC64;
MTCPKFSVAL LHWEFIYVIT AFDLAYPITP WKFKLSCMPP NTTYDFLLPA GISKNTSTLN
GHDEAVVETE LNSSGTYLSN LSSKTTFHCC FWSEEDKNCS VHADNIAGKA FVSAVNSLVF
QQTGANWNIQ CWMKEDLKLF ICYMESLFKN PFKNYDLKVH LLYVLLEVLE GSPLLPQKGS
FQSVQCNCSA RECCECHVPV SAAKLNYTLL MYLKITSGGA VFHSPLMSVQ PINVVKPDPP
LGLHMEITDT GNLKISWSSP TLVPFQLQYQ VKYSENSTTN MREADEIVSD TSLLVDSVLP
GSSYEVQVRG KRLDGPGIWS DWSTPFTFTT QDVIYFPPKI LTSVGSNISF HCIYKNENKI
VSSKKIVWWM NLAEKIPQSQ YDVVGDHVSK VTFPNMNATK PRGKFTYDAV YCCNEHECHH
RYAELYVIDV NINISCETDG YLTKMTCRWS TNAIQSLVGS TLQLRYHRSS LYCSDVPSVH
PISEPKDCQL QRDGFYECIF QPIFLLSGYT MWIRINHPLG SLDSPPTCVI PDSVVKPLPP
SSVKAEITAK IGLLKISWEK PVFPENNLQF QIRYGLSGKE VQWKIYEVYD TKLKSTSLPV
PDLCAVYAVQ VRCKRLDGLG YWSNWSTPAY TVVTDVKVPI RGPEFWRIIN EDATKKERNI
TLLWKPLMKN DSLCSVRSYV VKHHTSRHGT WSEDVGNHTK LTFLWTEQAH SVTVLAVNSI
GASSANFNLT FSWPMSKVNI VQSLSAYPLN SSCVGLSWLL SPSDYNLMYF ILEWKILNED
HEIKWLRIPS SVKKYYIHDH FIPIEKYQFS LYPIFMEGVG KPKIINSFTQ DGEKHRNDAG
LYVIVPIIIS SSILLLGTLL MSHQRMKKLF WEDVPNPKNC SWAQGLNFQK PETFEHLFIK
HTESVTFGPL LLEPETISED ISVDTSWKNK DEMVPPTTVS LLLTTPDLEK SSICISDQRS
SAHFSEAESM EITREDENRR QPSIKYATLL SSPKSGETEQ EQELVSSLVS RCFSSSNSLP
KESFSNSSWE IETQAFFILS DQHPNMTSPH LSFSEGLDEL MKFEGNFPKE HNDERSVYYL
GVTSIKKRES DVFLTDESRV RCPFPAHCLF ADIKILQESC SHLVENNFNL GTSGQKTFVS
YMPQFQTCST QTQKIMENKM YDLTV
