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Early placenta insulin-like peptide (EPIL) (Insulin-like peptide 4) (Placentin) [Cleaved into: Early placenta insulin-like peptide B chain; Early placenta insulin-like peptide A chain]

 INSL4_HUMAN             Reviewed;         139 AA.
Q14641; A8K678; Q5W127;
01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
01-NOV-1996, sequence version 1.
05-DEC-2018, entry version 144.
RecName: Full=Early placenta insulin-like peptide;
Short=EPIL;
AltName: Full=Insulin-like peptide 4;
AltName: Full=Placentin;
Contains:
RecName: Full=Early placenta insulin-like peptide B chain;
Contains:
RecName: Full=Early placenta insulin-like peptide A chain;
Flags: Precursor;
Name=INSL4;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA].
TISSUE=Placenta;
PubMed=8666396; DOI=10.1006/geno.1995.9980;
Chassin D., Laurent A., Janneau J.-L., Berger R., Bellet D.;
"Cloning of a new member of the insulin gene superfamily (INSL4)
expressed in human placenta.";
Genomics 29:465-470(1995).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Placenta;
PubMed=14702039; DOI=10.1038/ng1285;
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
"Complete sequencing and characterization of 21,243 full-length human
cDNAs.";
Nat. Genet. 36:40-45(2004).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=15164053; DOI=10.1038/nature02465;
Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E.,
Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C.,
Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S.,
Babbage A.K., Babbage S., Bagguley C.L., Bailey J., Banerjee R.,
Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P.,
Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W.,
Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G.,
Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M.,
Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W.,
Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A.,
Frankland J.A., French L., Fricker D.G., Garner P., Garnett J.,
Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
Kimberley A.M., King A., Knights A., Laird G.K., Langford C.,
Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M.,
Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S.,
McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J.,
Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R.,
Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M.,
Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M.,
Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A.,
Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P.,
Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W.,
Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S.,
Rogers J., Dunham I.;
"DNA sequence and analysis of human chromosome 9.";
Nature 429:369-374(2004).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
Venter J.C.;
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Placenta;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[6]
PROTEIN SEQUENCE OF 26-40.
PubMed=15340161; DOI=10.1110/ps.04682504;
Zhang Z., Henzel W.J.;
"Signal peptide prediction based on analysis of experimentally
verified cleavage sites.";
Protein Sci. 13:2819-2824(2004).
[7]
PROTEOLYTIC PROCESSING.
PubMed=9284764; DOI=10.1210/jcem.82.9.4359;
Bellet D., Lavaissiere L., Mock P., Laurent A., Sabourin J.-C.,
Bedossa P., Le Bouteiller P., Frydman R., Troalen F., Bidart J.-M.;
"Identification of pro-EPIL and EPIL peptides translated from insulin-
like 4 (INSL4) mRNA in human placenta.";
J. Clin. Endocrinol. Metab. 82:3169-3172(1997).
[8]
TISSUE SPECIFICITY.
PubMed=9740319;
DOI=10.1002/(SICI)1098-2795(199810)51:2<123::AID-MRD1>3.0.CO;2-S;
Laurent A., Rouillac C., Delezoide A.-L., Giovangrandi Y.,
Vekemans M., Bellet D., Abitbol M., Vidaud M.;
"Insulin-like 4 (INSL4) gene expression in human embryonic and
trophoblastic tissues.";
Mol. Reprod. Dev. 51:123-129(1998).
[9]
TISSUE SPECIFICITY, AND POSSIBLE INVOLVEMENT IN INVASION/MIGRATION OF
TROPHOBLAST CELLS.
PubMed=12414911; DOI=10.1210/jc.2002-021093;
Janneau J.-L., Maldonado-Estrada J., Tachdjian G., Miran I., Motte N.,
Saulnier P., Sabourin J.-C., Cote J.-F., Simon B., Frydman R.,
Chaouat G., Bellet D.;
"Transcriptional expression of genes involved in cell invasion and
migration by normal and tumoral trophoblast cells.";
J. Clin. Endocrinol. Metab. 87:5336-5339(2002).
-!- FUNCTION: May play an important role in trophoblast development
and in the regulation of bone formation.
-!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
-!- TISSUE SPECIFICITY: Expressed in placenta, uterus and in fetal
perichondrium. Expression levels were increased in both early
placentas and molar pregnancies and were reduced in
choriocarcinoma cells. {ECO:0000269|PubMed:12414911,
ECO:0000269|PubMed:9740319}.
-!- DEVELOPMENTAL STAGE: Highly expressed in the early placenta.
Expression of epil peptides in the villous cytotrophoblast is
different from that displayed by the syncytiotrophoblast. In fetal
tissues it was identified in the perichondrium of all four limbs,
vertebrae, and ribs. It was abundant in interbone ligaments.
-!- SIMILARITY: Belongs to the insulin family. {ECO:0000305}.
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EMBL; L34838; AAB08516.1; -; mRNA.
EMBL; AK291543; BAF84232.1; -; mRNA.
EMBL; AL133547; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; CH471071; EAW58772.1; -; Genomic_DNA.
EMBL; BC026254; AAH26254.1; -; mRNA.
CCDS; CCDS6459.1; -.
RefSeq; NP_002186.1; NM_002195.1.
UniGene; Hs.418506; -.
ProteinModelPortal; Q14641; -.
STRING; 9606.ENSP00000239316; -.
iPTMnet; Q14641; -.
PhosphoSitePlus; Q14641; -.
BioMuta; INSL4; -.
DMDM; 2497411; -.
MaxQB; Q14641; -.
PaxDb; Q14641; -.
PeptideAtlas; Q14641; -.
PRIDE; Q14641; -.
ProteomicsDB; 60079; -.
DNASU; 3641; -.
Ensembl; ENST00000239316; ENSP00000239316; ENSG00000120211.
GeneID; 3641; -.
KEGG; hsa:3641; -.
UCSC; uc003ziy.4; human.
CTD; 3641; -.
DisGeNET; 3641; -.
EuPathDB; HostDB:ENSG00000120211.4; -.
GeneCards; INSL4; -.
HGNC; HGNC:6087; INSL4.
MIM; 600910; gene.
neXtProt; NX_Q14641; -.
OpenTargets; ENSG00000120211; -.
PharmGKB; PA29894; -.
eggNOG; ENOG410KIDP; Eukaryota.
eggNOG; ENOG4110QC4; LUCA.
GeneTree; ENSGT00940000154434; -.
HOGENOM; HOG000236342; -.
HOVERGEN; HBG052134; -.
InParanoid; Q14641; -.
KO; K22006; -.
OMA; KKRNGHH; -.
OrthoDB; EOG091G0T3H; -.
PhylomeDB; Q14641; -.
TreeFam; TF333404; -.
GeneWiki; INSL4; -.
GenomeRNAi; 3641; -.
PRO; PR:Q14641; -.
Proteomes; UP000005640; Chromosome 9.
Bgee; ENSG00000120211; Expressed in 10 organ(s), highest expression level in chorionic villus.
CleanEx; HS_INSL4; -.
Genevisible; Q14641; HS.
GO; GO:0005615; C:extracellular space; TAS:ProtInc.
GO; GO:0005179; F:hormone activity; IEA:UniProtKB-KW.
GO; GO:0005159; F:insulin-like growth factor receptor binding; TAS:ProtInc.
GO; GO:0005102; F:signaling receptor binding; TAS:ProtInc.
GO; GO:0008283; P:cell proliferation; TAS:ProtInc.
GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
GO; GO:0007565; P:female pregnancy; TAS:ProtInc.
GO; GO:0007275; P:multicellular organism development; TAS:ProtInc.
GO; GO:0007165; P:signal transduction; TAS:ProtInc.
InterPro; IPR023258; Placentin.
InterPro; IPR022421; Relaxin.
PANTHER; PTHR12004:SF3; PTHR12004:SF3; 1.
PRINTS; PR02033; PLACENTIN.
PRINTS; PR02004; RELAXIN.
PROSITE; PS00262; INSULIN; 1.
1: Evidence at protein level;
Cleavage on pair of basic residues; Complete proteome;
Direct protein sequencing; Disulfide bond; Hormone;
Reference proteome; Secreted; Signal.
SIGNAL 1 25 {ECO:0000269|PubMed:15340161}.
CHAIN 26 139 Early placenta insulin-like peptide.
/FTId=PRO_0000016155.
PEPTIDE 26 58 Early placenta insulin-like peptide B
chain.
/FTId=PRO_0000016156.
PROPEP 59 114 C peptide.
/FTId=PRO_0000016157.
PEPTIDE 115 139 Early placenta insulin-like peptide A
chain.
/FTId=PRO_0000016158.
DISULFID 31 125 Interchain (between B and A chains).
{ECO:0000250}.
DISULFID 43 138 Interchain (between B and A chains).
{ECO:0000250}.
DISULFID 124 129 {ECO:0000250}.
SEQUENCE 139 AA; 15445 MW; 47FB61F6F86C1342 CRC64;
MASLFRSYLP AIWLLLSQLL RESLAAELRG CGPRFGKHLL SYCPMPEKTF TTTPGGWLLE
SGRPKEMVST SNNKDGQALG TTSEFIPNLS PELKKPLSEG QPSLKKIILS RKKRSGRHRF
DPFCCEVICD DGTSVKLCT


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