INSL5_HUMAN
ID INSL5_HUMAN Reviewed; 135 AA.
AC Q9Y5Q6; Q3MIY4; Q5VYD8;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 02-SEP-2008, sequence version 2.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=Insulin-like peptide INSL5;
DE Short=Insulin-like peptide 5;
DE Contains:
DE RecName: Full=Insulin-like peptide INSL5 B chain;
DE Contains:
DE RecName: Full=Insulin-like peptide INSL5 A chain;
DE Flags: Precursor;
GN Name=INSL5; ORFNames=UNQ156/PRO182;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND VARIANT LEU-50.
RC TISSUE=Colon;
RX PubMed=10458910; DOI=10.1006/geno.1999.5899;
RA Conklin D., Lofton-Day C.E., Haldeman B.A., Ching A., Whitmore T.E.,
RA Lok S., Jaspers S.;
RT "Identification of INSL5, a new member of the insulin superfamily.";
RL Genomics 60:50-56(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT LEU-50.
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT LEU-50.
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP PROTEIN SEQUENCE OF 23-37.
RX PubMed=15340161; DOI=10.1110/ps.04682504;
RA Zhang Z., Henzel W.J.;
RT "Signal peptide prediction based on analysis of experimentally verified
RT cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
RN [6]
RP BINDING TO RXFP4.
RX PubMed=15525639; DOI=10.1074/jbc.m409916200;
RA Liu C., Kuei C., Sutton S., Chen J., Bonaventure P., Wu J., Nepomuceno D.,
RA Kamme F., Tran D.T., Zhu J., Wilkinson T., Bathgate R., Eriste E.,
RA Sillard R., Lovenberg T.W.;
RT "INSL5 is a high affinity specific agonist for GPCR142 (GPR100).";
RL J. Biol. Chem. 280:292-300(2005).
RN [7]
RP SYNTHESIS OF 23-46 AND 115-135, DISULFIDE BONDS, AND PYROGLUTAMATE
RP FORMATION AT GLN-115.
RX PubMed=18576448; DOI=10.1002/cbic.200800113;
RA Akhter Hossain M., Bathgate R.A.D., Kong C.K., Shabanpoor F., Zhang S.,
RA Haugaard-Joensson L.M., Rosengren K.J., Tregear G.W., Wade J.D.;
RT "Synthesis, conformation, and activity of human insulin-like peptide 5
RT (INSL5).";
RL ChemBioChem 9:1816-1822(2008).
RN [8]
RP STRUCTURE BY NMR OF 23-46 AND 115-135.
RX PubMed=19178384; DOI=10.1042/bj20082353;
RA Haugaard-Joensson L.M., Hossain M.A., Daly N.L., Craik D.J., Wade J.D.,
RA Rosengren K.J.;
RT "Structure of human insulin-like peptide 5 and characterization of
RT conserved hydrogen bonds and electrostatic interactions within the relaxin
RT framework.";
RL Biochem. J. 419:619-627(2009).
CC -!- FUNCTION: May have a role in gut contractility or in thymic development
CC and regulation. Activates RXFP4 with high potency and appears to be the
CC endogenous ligand for this receptor.
CC -!- SUBUNIT: Heterodimer of a B chain and an A chain linked by two
CC disulfide bonds.
CC -!- INTERACTION:
CC Q9Y5Q6; Q12797-6: ASPH; NbExp=3; IntAct=EBI-21626318, EBI-12092171;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Highly expressed in rectum with lower levels in
CC uterus and ascending and descending colon.
CC {ECO:0000269|PubMed:10458910}.
CC -!- SIMILARITY: Belongs to the insulin family. {ECO:0000305}.
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DR EMBL; AF133816; AAD29686.1; -; mRNA.
DR EMBL; AY359030; AAQ89389.1; -; mRNA.
DR EMBL; AL354978; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC101646; AAI01647.1; -; mRNA.
DR EMBL; BC101648; AAI01649.1; -; mRNA.
DR CCDS; CCDS634.1; -.
DR RefSeq; NP_005469.2; NM_005478.4.
DR PDB; 2K1V; NMR; -; A=116-135.
DR PDB; 2KBC; NMR; -; A=116-135, B=23-46.
DR PDBsum; 2K1V; -.
DR PDBsum; 2KBC; -.
DR AlphaFoldDB; Q9Y5Q6; -.
DR SMR; Q9Y5Q6; -.
DR BioGRID; 115339; 71.
DR IntAct; Q9Y5Q6; 53.
DR STRING; 9606.ENSP00000302724; -.
DR BioMuta; INSL5; -.
DR DMDM; 205371762; -.
DR MassIVE; Q9Y5Q6; -.
DR PaxDb; Q9Y5Q6; -.
DR PeptideAtlas; Q9Y5Q6; -.
DR PRIDE; Q9Y5Q6; -.
DR ProteomicsDB; 86474; -.
DR Antibodypedia; 33391; 69 antibodies from 20 providers.
DR DNASU; 10022; -.
DR Ensembl; ENST00000304526.3; ENSP00000302724.2; ENSG00000172410.5.
DR GeneID; 10022; -.
DR KEGG; hsa:10022; -.
DR MANE-Select; ENST00000304526.3; ENSP00000302724.2; NM_005478.6; NP_005469.2.
DR UCSC; uc001dcw.4; human.
DR CTD; 10022; -.
DR DisGeNET; 10022; -.
DR GeneCards; INSL5; -.
DR HGNC; HGNC:6088; INSL5.
DR HPA; ENSG00000172410; Tissue enriched (intestine).
DR MIM; 606413; gene.
DR neXtProt; NX_Q9Y5Q6; -.
DR OpenTargets; ENSG00000172410; -.
DR PharmGKB; PA29895; -.
DR VEuPathDB; HostDB:ENSG00000172410; -.
DR eggNOG; ENOG502S9UT; Eukaryota.
DR GeneTree; ENSGT00940000154396; -.
DR HOGENOM; CLU_120043_1_0_1; -.
DR InParanoid; Q9Y5Q6; -.
DR OMA; YVRTVVY; -.
DR OrthoDB; 1578838at2759; -.
DR PhylomeDB; Q9Y5Q6; -.
DR TreeFam; TF333404; -.
DR PathwayCommons; Q9Y5Q6; -.
DR Reactome; R-HSA-418594; G alpha (i) signalling events.
DR Reactome; R-HSA-444821; Relaxin receptors.
DR SignaLink; Q9Y5Q6; -.
DR BioGRID-ORCS; 10022; 8 hits in 1058 CRISPR screens.
DR EvolutionaryTrace; Q9Y5Q6; -.
DR GeneWiki; INSL5; -.
DR GenomeRNAi; 10022; -.
DR Pharos; Q9Y5Q6; Tbio.
DR PRO; PR:Q9Y5Q6; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9Y5Q6; protein.
DR Bgee; ENSG00000172410; Expressed in rectum and 62 other tissues.
DR Genevisible; Q9Y5Q6; HS.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0001664; F:G protein-coupled receptor binding; IBA:GO_Central.
DR GO; GO:0005179; F:hormone activity; IEA:UniProtKB-KW.
DR GO; GO:2000253; P:positive regulation of feeding behavior; IBA:GO_Central.
DR InterPro; IPR016179; Insulin-like.
DR InterPro; IPR036438; Insulin-like_sf.
DR InterPro; IPR022353; Insulin_CS.
DR Pfam; PF00049; Insulin; 1.
DR SMART; SM00078; IlGF; 1.
DR SUPFAM; SSF56994; SSF56994; 1.
DR PROSITE; PS00262; INSULIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cleavage on pair of basic residues;
KW Direct protein sequencing; Disulfide bond; Hormone;
KW Pyrrolidone carboxylic acid; Reference proteome; Secreted; Signal.
FT SIGNAL 1..22
FT /evidence="ECO:0000269|PubMed:15340161"
FT PEPTIDE 23..46
FT /note="Insulin-like peptide INSL5 B chain"
FT /id="PRO_0000016163"
FT PROPEP 49..114
FT /note="Connecting peptide"
FT /evidence="ECO:0000255"
FT /id="PRO_0000016164"
FT PEPTIDE 115..135
FT /note="Insulin-like peptide INSL5 A chain"
FT /id="PRO_0000016165"
FT MOD_RES 115
FT /note="Pyrrolidone carboxylic acid"
FT /evidence="ECO:0000269|PubMed:18576448"
FT DISULFID 29..122
FT /note="Interchain (between B and A chains)"
FT /evidence="ECO:0000269|PubMed:18576448"
FT DISULFID 41..135
FT /note="Interchain (between B and A chains)"
FT /evidence="ECO:0000269|PubMed:18576448"
FT DISULFID 121..126
FT /evidence="ECO:0000269|PubMed:18576448"
FT VARIANT 50
FT /note="Q -> L (in dbSNP:rs549148)"
FT /evidence="ECO:0000269|PubMed:10458910,
FT ECO:0000269|PubMed:12975309, ECO:0000269|PubMed:15489334"
FT /id="VAR_046099"
FT HELIX 31..45
FT /evidence="ECO:0007829|PDB:2KBC"
FT TURN 116..118
FT /evidence="ECO:0007829|PDB:2K1V"
FT HELIX 119..123
FT /evidence="ECO:0007829|PDB:2K1V"
FT HELIX 128..131
FT /evidence="ECO:0007829|PDB:2K1V"
FT TURN 132..134
FT /evidence="ECO:0007829|PDB:2K1V"
SQ SEQUENCE 135 AA; 15333 MW; A932D7EDE9D173F5 CRC64;
MKGSIFTLFL FSVLFAISEV RSKESVRLCG LEYIRTVIYI CASSRWRRHQ EGIPQAQQAE
TGNSFQLPHK REFSEENPAQ NLPKVDASGE DRLWGGQMPT EELWKSKKHS VMSRQDLQTL
CCTDGCSMTD LSALC
