ESP1_MOUSE
ID ESP1_MOUSE Reviewed; 102 AA.
AC Q3LHH8;
DT 11-DEC-2013, integrated into UniProtKB/Swiss-Prot.
DT 08-NOV-2005, sequence version 1.
DT 03-AUG-2022, entry version 88.
DE RecName: Full=Exocrine gland-secreted peptide 1;
DE Flags: Precursor;
GN Name=Esp1 {ECO:0000312|EMBL:BAE46402.1};
GN Synonyms=Gm6084 {ECO:0000312|MGI:MGI:3645915};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1] {ECO:0000305, ECO:0000312|EMBL:BAE46402.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, DEVELOPMENTAL STAGE, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=BALB/cJ {ECO:0000312|EMBL:BAE46402.1};
RC TISSUE=Lacrimal gland {ECO:0000312|EMBL:BAE46402.1};
RX PubMed=16208374; DOI=10.1038/nature04033;
RA Kimoto H., Haga S., Sato K., Touhara K.;
RT "Sex-specific peptides from exocrine glands stimulate mouse vomeronasal
RT sensory neurons.";
RL Nature 437:898-901(2005).
RN [2] {ECO:0000312|Ensembl:ENSMUSP00000123886}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J {ECO:0000312|Ensembl:ENSMUSP00000123886};
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3] {ECO:0000305}
RP PROTEIN SEQUENCE OF 36-55, FUNCTION, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC STRAIN=BALB/cJ {ECO:0000269|Ref.3};
RC TISSUE=Lacrimal gland {ECO:0000269|Ref.3};
RX DOI=10.1351/pac200779040775;
RA Haga S., Kimoto H., Touhara K.;
RT "Molecular characterization of vomeronasal sensory neurons responding to a
RT male-specific peptide in tear fluid: sexual communication in mice.";
RL Pure Appl. Chem. 79:775-783(2007).
RN [4] {ECO:0000305}
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=17935991; DOI=10.1016/j.cub.2007.09.042;
RA Kimoto H., Sato K., Nodari F., Haga S., Holy T.E., Touhara K.;
RT "Sex- and strain-specific expression and vomeronasal activity of mouse ESP
RT family peptides.";
RL Curr. Biol. 17:1879-1884(2007).
RN [5] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, AND POLYMORPHISM.
RX PubMed=20596023; DOI=10.1038/nature09142;
RA Haga S., Hattori T., Sato T., Sato K., Matsuda S., Kobayakawa R.,
RA Sakano H., Yoshihara Y., Kikusui T., Touhara K.;
RT "The male mouse pheromone ESP1 enhances female sexual receptive behaviour
RT through a specific vomeronasal receptor.";
RL Nature 466:118-122(2010).
RN [6] {ECO:0000305, ECO:0000312|PDB:2LMK}
RP STRUCTURE BY NMR OF 48-102, SUBUNIT, INTERACTION WITH VMN2R116, DISULFIDE
RP BOND, AND MUTAGENESIS OF ARG-56; ARG-60; CYS-63; GLU-67; ASP-69; LYS-70;
RP ASP-88; ARG-92; CYS-95 AND ARG-96.
RC STRAIN=BALB/cJ {ECO:0000269|PubMed:23576433};
RX PubMed=23576433; DOI=10.1074/jbc.m112.436782;
RA Yoshinaga S., Sato T., Hirakane M., Esaki K., Hamaguchi T.,
RA Haga-Yamanaka S., Tsunoda M., Kimoto H., Shimada I., Touhara K.,
RA Terasawa H.;
RT "Structure of the mouse sex peptide pheromone ESP1 reveals a molecular
RT basis for specific binding to the class C G-protein-coupled vomeronasal
RT receptor.";
RL J. Biol. Chem. 288:16064-16072(2013).
CC -!- FUNCTION: Male-specific phermone which is recognized by the
CC Vmn2r116/V2rp5 receptor in the vomeronasal organ (VNO) and enhances
CC female sexual receptive behavior (lordosis) upon male mounting,
CC resulting in successful copulation. {ECO:0000269|PubMed:16208374,
CC ECO:0000269|PubMed:17935991, ECO:0000269|PubMed:20596023,
CC ECO:0000269|PubMed:23576433, ECO:0000269|Ref.3}.
CC -!- SUBUNIT: Monomer. {ECO:0000303|PubMed:23576433, ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16208374,
CC ECO:0000269|PubMed:20596023}. Note=Secreted by the extraorbital
CC lacrimal gland into tears. {ECO:0000269|PubMed:16208374,
CC ECO:0000269|PubMed:20596023}.
CC -!- TISSUE SPECIFICITY: Expressed in the extraorbital lacrimal gland from
CC where it is secreted into tears. {ECO:0000269|PubMed:16208374}.
CC -!- DEVELOPMENTAL STAGE: Expression is observed after 4 weeks of age in
CC males only. Not expressed in females or in males castrated at 3 weeks
CC of age whereas expression is not down-regulated in castrated adult
CC males. {ECO:0000269|PubMed:16208374, ECO:0000269|PubMed:17935991}.
CC -!- POLYMORPHISM: Expressed at very low levels in most inbred strains with
CC high levels detected only in strains BALB/c and DBA/2. Expressed at
CC high levels in a number of wild mouse-derived strains.
CC {ECO:0000269|PubMed:20596023}.
CC -!- SIMILARITY: Belongs to the exocrine gland-secreted peptide family.
CC {ECO:0000305}.
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DR EMBL; AB194091; BAE46402.1; -; mRNA.
DR EMBL; AC135084; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS28785.1; -.
DR RefSeq; NP_001033589.1; NM_001038500.2.
DR PDB; 2LMK; NMR; -; A=48-102.
DR PDBsum; 2LMK; -.
DR AlphaFoldDB; Q3LHH8; -.
DR SMR; Q3LHH8; -.
DR IntAct; Q3LHH8; 1.
DR STRING; 10090.ENSMUSP00000123886; -.
DR PaxDb; Q3LHH8; -.
DR PRIDE; Q3LHH8; -.
DR DNASU; 619517; -.
DR Ensembl; ENSMUST00000161110; ENSMUSP00000123886; ENSMUSG00000073396.
DR GeneID; 619517; -.
DR KEGG; mmu:619517; -.
DR UCSC; uc008coi.1; mouse.
DR CTD; 619517; -.
DR MGI; MGI:3645915; Esp1.
DR VEuPathDB; HostDB:ENSMUSG00000073396; -.
DR GeneTree; ENSGT00840000130532; -.
DR HOGENOM; CLU_146128_0_0_1; -.
DR PhylomeDB; Q3LHH8; -.
DR BioGRID-ORCS; 619517; 1 hit in 71 CRISPR screens.
DR ChiTaRS; Espl1; mouse.
DR PRO; PR:Q3LHH8; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; Q3LHH8; protein.
DR ExpressionAtlas; Q3LHH8; differential.
DR GO; GO:0005615; C:extracellular space; IDA:MGI.
DR GO; GO:0005186; F:pheromone activity; IDA:MGI.
DR GO; GO:0045925; P:positive regulation of female receptivity; IDA:MGI.
DR Gene3D; 1.20.50.60; -; 1.
DR InterPro; IPR032253; Esp1/Esp22.
DR InterPro; IPR043126; Esp1_core.
DR Pfam; PF16590; ESP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Behavior; Direct protein sequencing; Disulfide bond;
KW Pheromone; Reference proteome; Secreted; Signal.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..102
FT /note="Exocrine gland-secreted peptide 1"
FT /id="PRO_0000424697"
FT SITE 67
FT /note="Required for activity"
FT /evidence="ECO:0000269|PubMed:23576433"
FT DISULFID 63..95
FT /evidence="ECO:0000269|PubMed:23576433"
FT MUTAGEN 56
FT /note="R->E: Reduced neuron activity in the VNO."
FT /evidence="ECO:0000269|PubMed:23576433"
FT MUTAGEN 60
FT /note="R->E: Reduced neuron activity in the VNO."
FT /evidence="ECO:0000269|PubMed:23576433"
FT MUTAGEN 63
FT /note="C->S: No neuron activity in the VNO."
FT /evidence="ECO:0000269|PubMed:23576433"
FT MUTAGEN 67
FT /note="E->R,Q: No neuron activity in the VNO and marked
FT reduction in the accessory olfactory bulb."
FT /evidence="ECO:0000269|PubMed:23576433"
FT MUTAGEN 69
FT /note="D->R: Reduced neuron activity in the VNO."
FT /evidence="ECO:0000269|PubMed:23576433"
FT MUTAGEN 70
FT /note="K->E: Reduced neuron activity in the VNO."
FT /evidence="ECO:0000269|PubMed:23576433"
FT MUTAGEN 88
FT /note="D->R: Reduced neuron activity in the VNO."
FT /evidence="ECO:0000269|PubMed:23576433"
FT MUTAGEN 92
FT /note="R->E: Reduced neuron activity in the VNO."
FT /evidence="ECO:0000269|PubMed:23576433"
FT MUTAGEN 95
FT /note="C->S: No neuron activity in the VNO."
FT /evidence="ECO:0000269|PubMed:23576433"
FT MUTAGEN 96
FT /note="R->E: Reduced neuron activity in the VNO."
FT /evidence="ECO:0000269|PubMed:23576433"
FT HELIX 53..58
FT /evidence="ECO:0007829|PDB:2LMK"
FT HELIX 61..64
FT /evidence="ECO:0007829|PDB:2LMK"
FT STRAND 65..67
FT /evidence="ECO:0007829|PDB:2LMK"
FT HELIX 69..76
FT /evidence="ECO:0007829|PDB:2LMK"
FT HELIX 88..91
FT /evidence="ECO:0007829|PDB:2LMK"
SQ SEQUENCE 102 AA; 11346 MW; 1A149532653E91C5 CRC64;
MTSLPVLLFL IILLLPSMIT EGRVLTQTGK EATIFADQKT NHEADLKNPD PQEVQRALAR
ILCALGELDK LVKDQANAGQ QEFKLPKDFT GRSKCRSLGR IK
