ID   CORT_HUMAN              Reviewed;         105 AA.
AC   O00230; Q5T6G0; Q6UX11;
DT   15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT   01-JUL-1997, sequence version 1.
DT   03-AUG-2022, entry version 146.
DE   RecName: Full=Cortistatin;
DE   Contains:
DE     RecName: Full=Cortistatin-29;
DE   Contains:
DE     RecName: Full=Cortistatin-17;
DE   Flags: Precursor;
GN   Name=CORT; ORFNames=UNQ307/PRO350;
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].
RC   TISSUE=Brain;
RX   PubMed=9125122; DOI=10.1006/bbrc.1997.6252;
RA   Fukusumi S., Kitada C., Takekawa S., Kizawa H., Sakamoto J., Miyamoto M.,
RA   Hinuma S., Kitano K., Fujino M.;
RT   "Identification and characterization of a novel human cortistatin-like
RT   peptide.";
RL   Biochem. Biophys. Res. Commun. 232:157-163(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=9205124; DOI=10.1006/geno.1997.4763;
RA   de Lecea L., Ruiz-Lozano P., Danielson P.E., Peelle-Kirley J., Foye P.E.,
RA   Frankel W.N., Sutcliffe J.G.;
RT   "Cloning, mRNA expression, and chromosomal mapping of mouse and human
RT   preprocortistatin.";
RL   Genomics 42:499-506(1997).
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 GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-104.
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).
CC   -!- FUNCTION: Binds to all human somatostatin receptor (SSTR) subtypes. It
CC       also inhibits cAMP production induced by forskolin through SSTRs.
CC   -!- INTERACTION:
CC       PRO_0000033156; PRO_0000000092 [P05067]: APP; NbExp=4; IntAct=EBI-20824092, EBI-821758;
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- TISSUE SPECIFICITY: Expressed in a subset of GABAergic cells in the
CC       cortex and hippocampus.
CC   -!- SIMILARITY: Belongs to the somatostatin family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAI19725.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC       Sequence=AAI19726.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC       Sequence=AAQ89950.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC       Sequence=EAW71650.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR   EMBL; AB000263; BAA19770.1; -; mRNA.
DR   EMBL; AF013252; AAB66895.1; -; mRNA.
DR   EMBL; AL354956; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471130; EAW71650.1; ALT_INIT; Genomic_DNA.
DR   EMBL; BC119724; AAI19725.1; ALT_INIT; mRNA.
DR   EMBL; BC119725; AAI19726.1; ALT_INIT; mRNA.
DR   EMBL; AY358561; AAQ89950.1; ALT_INIT; mRNA.
DR   CCDS; CCDS117.2; -.
DR   PIR; JC5414; JC5414.
DR   RefSeq; NP_001293.3; NM_001302.4.
DR   PDB; 7VDL; EM; 3.22 A; L=92-105.
DR   PDB; 7VV4; EM; 2.97 A; L=92-105.
DR   PDBsum; 7VDL; -.
DR   PDBsum; 7VV4; -.
DR   AlphaFoldDB; O00230; -.
DR   SMR; O00230; -.
DR   BioGRID; 107718; 20.
DR   IntAct; O00230; 3.
DR   STRING; 9606.ENSP00000366248; -.
DR   iPTMnet; O00230; -.
DR   PhosphoSitePlus; O00230; -.
DR   BioMuta; CORT; -.
DR   MassIVE; O00230; -.
DR   PaxDb; O00230; -.
DR   PeptideAtlas; O00230; -.
DR   PRIDE; O00230; -.
DR   ProteomicsDB; 47795; -.
DR   Antibodypedia; 57276; 52 antibodies from 12 providers.
DR   DNASU; 1325; -.
DR   Ensembl; ENST00000377049.4; ENSP00000366248.4; ENSG00000241563.4.
DR   GeneID; 1325; -.
DR   KEGG; hsa:1325; -.
DR   MANE-Select; ENST00000377049.4; ENSP00000366248.4; NM_001302.5; NP_001293.3.
DR   UCSC; uc001ari.5; human.
DR   CTD; 1325; -.
DR   DisGeNET; 1325; -.
DR   GeneCards; CORT; -.
DR   HGNC; HGNC:2257; CORT.
DR   HPA; ENSG00000241563; Tissue enriched (brain).
DR   MIM; 602784; gene.
DR   neXtProt; NX_O00230; -.
DR   OpenTargets; ENSG00000241563; -.
DR   PharmGKB; PA26773; -.
DR   VEuPathDB; HostDB:ENSG00000241563; -.
DR   eggNOG; ENOG502S1NT; Eukaryota.
DR   GeneTree; ENSGT00730000111752; -.
DR   HOGENOM; CLU_124515_0_0_1; -.
DR   InParanoid; O00230; -.
DR   OMA; SGHMQEV; -.
DR   OrthoDB; 1614009at2759; -.
DR   PhylomeDB; O00230; -.
DR   PathwayCommons; O00230; -.
DR   Reactome; R-HSA-375276; Peptide ligand-binding receptors.
DR   Reactome; R-HSA-418594; G alpha (i) signalling events.
DR   SignaLink; O00230; -.
DR   SIGNOR; O00230; -.
DR   BioGRID-ORCS; 1325; 29 hits in 1032 CRISPR screens.
DR   ChiTaRS; CORT; human.
DR   GeneWiki; Cortistatin_(neuropeptide); -.
DR   GenomeRNAi; 1325; -.
DR   Pharos; O00230; Tbio.
DR   PRO; PR:O00230; -.
DR   Proteomes; UP000005640; Chromosome 1.
DR   RNAct; O00230; protein.
DR   Bgee; ENSG00000241563; Expressed in putamen and 92 other tissues.
DR   Genevisible; O00230; HS.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005615; C:extracellular space; NAS:UniProtKB.
DR   GO; GO:0071821; C:FANCM-MHF complex; IBA:GO_Central.
DR   GO; GO:0043240; C:Fanconi anaemia nuclear complex; IBA:GO_Central.
DR   GO; GO:0045202; C:synapse; IEA:GOC.
DR   GO; GO:0003682; F:chromatin binding; IBA:GO_Central.
DR   GO; GO:0001664; F:G protein-coupled receptor binding; IPI:UniProtKB.
DR   GO; GO:0005184; F:neuropeptide hormone activity; IDA:UniProtKB.
DR   GO; GO:0007193; P:adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway; IDA:UniProtKB.
DR   GO; GO:0007268; P:chemical synaptic transmission; NAS:UniProtKB.
DR   GO; GO:0031297; P:replication fork processing; IBA:GO_Central.
DR   GO; GO:0000712; P:resolution of meiotic recombination intermediates; IBA:GO_Central.
DR   InterPro; IPR004250; Somatostatin.
DR   InterPro; IPR018142; Somatostatin/Cortistatin_C.
DR   Pfam; PF03002; Somatostatin; 1.
DR   PIRSF; PIRSF001814; Somatostatin; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Cleavage on pair of basic residues; Disulfide bond; Hormone;
KW   Reference proteome; Secreted; Signal.
FT   SIGNAL          1..18
FT                   /evidence="ECO:0000255"
FT   PROPEP          19..74
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000033154"
FT   PEPTIDE         77..105
FT                   /note="Cortistatin-29"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000033155"
FT   PEPTIDE         89..105
FT                   /note="Cortistatin-17"
FT                   /id="PRO_0000033156"
FT   DISULFID        93..104
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   105 AA;  11532 MW;  09578F4520201551 CRC64;
     MPLSPGLLLL LLSGATATAA LPLEGGPTGR DSEHMQEAAG IRKSSLLTFL AWWFEWTSQA
     SAGPLIGEEA REVARRQEGA PPQQSARRDR MPCRNFFWKT FSSCK