CCKN_HUMAN
ID CCKN_HUMAN Reviewed; 115 AA.
AC P06307;
DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1988, sequence version 1.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=Cholecystokinin;
DE Short=CCK;
DE Contains:
DE RecName: Full=Cholecystokinin-58;
DE Short=CCK58;
DE Contains:
DE RecName: Full=Cholecystokinin-58 desnonopeptide;
DE AltName: Full=(1-49)-CCK58;
DE Contains:
DE RecName: Full=Cholecystokinin-39;
DE Short=CCK39;
DE Contains:
DE RecName: Full=Cholecystokinin-33;
DE Short=CCK33;
DE Contains:
DE RecName: Full=Cholecystokinin-25;
DE Short=CCK25;
DE Contains:
DE RecName: Full=Cholecystokinin-18;
DE Short=CCK18;
DE Contains:
DE RecName: Full=Cholecystokinin-12;
DE Short=CCK12;
DE Contains:
DE RecName: Full=Cholecystokinin-8;
DE Short=CCK8;
DE Contains:
DE RecName: Full=Cholecystokinin-7;
DE Short=CCK7;
DE Contains:
DE RecName: Full=Cholecystokinin-5;
DE Short=CCK5;
DE Flags: Precursor;
GN Name=CCK;
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].
RA Kato K., Takahashi Y., Matsubara K.;
RT "Molecular cloning of the human cholecystokinin gene.";
RL Ann. N. Y. Acad. Sci. 448:613-615(1985).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND AMIDATION AT PHE-103.
RX PubMed=3856870; DOI=10.1073/pnas.82.7.1931;
RA Takahashi Y., Kato K., Hayashizaki Y., Wakabayashi T., Ohtsuka E.,
RA Matsuki S., Ikehara M., Matsubara K.;
RT "Molecular cloning of the human cholecystokinin gene by use of a synthetic
RT probe containing deoxyinosine.";
RL Proc. Natl. Acad. Sci. U.S.A. 82:1931-1935(1985).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLU-32.
RG NIEHS SNPs program;
RL Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Pancreas;
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 PROTEOLYTIC CLEAVAGE (CHOLECYSTOKININ-5).
RX PubMed=9371719; DOI=10.1042/bj3280587;
RA Isaac R.E., Williams T.A., Sajid M., Corvol P., Coates D.;
RT "Cleavage of arginyl-arginine and lysyl-arginine from the C-terminus of
RT pro-hormone peptides by human germinal angiotensin I-converting enzyme
RT (ACE) and the C-domain of human somatic ACE.";
RL Biochem. J. 328:587-591(1997).
RN [7]
RP PROTEOLYTIC CLEAVAGE (CHOLECYSTOKININ-5).
RX PubMed=10336644; DOI=10.1046/j.1432-1327.1999.00419.x;
RA Isaac R.E., Michaud A., Keen J.N., Williams T.A., Coates D., Wetsel W.C.,
RA Corvol P.;
RT "Hydrolysis by somatic angiotensin-I converting enzyme of basic dipeptides
RT from a cholecystokinin/gastrin and a LH-RH peptide extended at the C-
RT terminus with gly-Arg/Lys-arg, but not from diarginyl insulin.";
RL Eur. J. Biochem. 262:569-574(1999).
RN [8]
RP MUTAGENESIS OF TYR-97, AND SULFATION AT TYR-97.
RX PubMed=11076522; DOI=10.1021/bi0011072;
RA Vishnuvardhan D., Beinfeld M.C.;
RT "Role of tyrosine sulfation and serine phosphorylation in the processing of
RT procholecystokinin to amidated cholecystokinin and its secretion in
RT transfected AtT-20 cells.";
RL Biochemistry 39:13825-13830(2000).
CC -!- FUNCTION: This peptide hormone induces gall bladder contraction and the
CC release of pancreatic enzymes in the gut. Its function in the brain is
CC not clear. Binding to CCK-A receptors stimulates amylase release from
CC the pancreas, binding to CCK-B receptors stimulates gastric acid
CC secretion. {ECO:0000250|UniProtKB:Q9TS44}.
CC -!- SUBUNIT: Binds to CCK-A receptors in the pancreas and CCK-B receptors
CC in the brain. {ECO:0000250|UniProtKB:Q9TS44}.
CC -!- INTERACTION:
CC P06307; Q6DHV7-2: ADAL; NbExp=3; IntAct=EBI-6624398, EBI-18899653;
CC P06307; Q6UY14-3: ADAMTSL4; NbExp=3; IntAct=EBI-6624398, EBI-10173507;
CC P06307; Q9NU02: ANKEF1; NbExp=3; IntAct=EBI-6624398, EBI-8464238;
CC P06307; Q66PJ3-4: ARL6IP4; NbExp=3; IntAct=EBI-6624398, EBI-5280499;
CC P06307; Q6XD76: ASCL4; NbExp=3; IntAct=EBI-6624398, EBI-10254793;
CC P06307; C1IDX9: ATG12; NbExp=3; IntAct=EBI-6624398, EBI-25836940;
CC P06307; Q9NSI6-4: BRWD1; NbExp=3; IntAct=EBI-6624398, EBI-10693038;
CC P06307; O00257-3: CBX4; NbExp=3; IntAct=EBI-6624398, EBI-4392727;
CC P06307; Q494V2-2: CFAP100; NbExp=3; IntAct=EBI-6624398, EBI-11953200;
CC P06307; Q8WUX9: CHMP7; NbExp=3; IntAct=EBI-6624398, EBI-749253;
CC P06307; Q9Y3D0: CIAO2B; NbExp=3; IntAct=EBI-6624398, EBI-744045;
CC P06307; Q99966: CITED1; NbExp=3; IntAct=EBI-6624398, EBI-2624951;
CC P06307; O95278-6: EPM2A; NbExp=3; IntAct=EBI-6624398, EBI-25836908;
CC P06307; Q6NXG1-3: ESRP1; NbExp=3; IntAct=EBI-6624398, EBI-21567429;
CC P06307; P06241: FYN; NbExp=3; IntAct=EBI-6624398, EBI-515315;
CC P06307; Q06547-3: GABPB1; NbExp=3; IntAct=EBI-6624398, EBI-9088619;
CC P06307; O75409: H2AP; NbExp=3; IntAct=EBI-6624398, EBI-6447217;
CC P06307; Q6NXT2: H3-5; NbExp=3; IntAct=EBI-6624398, EBI-2868501;
CC P06307; P53701: HCCS; NbExp=3; IntAct=EBI-6624398, EBI-10763431;
CC P06307; Q9NRZ9-6: HELLS; NbExp=3; IntAct=EBI-6624398, EBI-12003732;
CC P06307; Q9UK76: JPT1; NbExp=3; IntAct=EBI-6624398, EBI-720411;
CC P06307; Q8N1A0: KRT222; NbExp=3; IntAct=EBI-6624398, EBI-8473062;
CC P06307; Q6DKI2: LGALS9C; NbExp=3; IntAct=EBI-6624398, EBI-9088829;
CC P06307; Q9H2C1: LHX5; NbExp=3; IntAct=EBI-6624398, EBI-25835523;
CC P06307; Q16609: LPAL2; NbExp=3; IntAct=EBI-6624398, EBI-10238012;
CC P06307; Q8NI22: MCFD2; NbExp=3; IntAct=EBI-6624398, EBI-2689785;
CC P06307; P01106: MYC; NbExp=3; IntAct=EBI-6624398, EBI-447544;
CC P06307; Q9UJ70-2: NAGK; NbExp=3; IntAct=EBI-6624398, EBI-11526455;
CC P06307; P25208: NFYB; NbExp=3; IntAct=EBI-6624398, EBI-389728;
CC P06307; Q8NFH3: NUP43; NbExp=3; IntAct=EBI-6624398, EBI-1059321;
CC P06307; Q7Z3B4: NUP54; NbExp=3; IntAct=EBI-6624398, EBI-741048;
CC P06307; Q07869: PPARA; NbExp=3; IntAct=EBI-6624398, EBI-78615;
CC P06307; P02775: PPBP; NbExp=3; IntAct=EBI-6624398, EBI-718973;
CC P06307; Q6ZMI0-5: PPP1R21; NbExp=3; IntAct=EBI-6624398, EBI-25835994;
CC P06307; P23942: PRPH2; NbExp=3; IntAct=EBI-6624398, EBI-25836834;
CC P06307; P29074: PTPN4; NbExp=3; IntAct=EBI-6624398, EBI-710431;
CC P06307; Q96HR9-2: REEP6; NbExp=3; IntAct=EBI-6624398, EBI-14065960;
CC P06307; Q04206: RELA; NbExp=3; IntAct=EBI-6624398, EBI-73886;
CC P06307; P47804-3: RGR; NbExp=3; IntAct=EBI-6624398, EBI-25834767;
CC P06307; Q15382: RHEB; NbExp=3; IntAct=EBI-6624398, EBI-1055287;
CC P06307; P62701: RPS4X; NbExp=3; IntAct=EBI-6624398, EBI-354303;
CC P06307; Q66K80: RUSC1-AS1; NbExp=3; IntAct=EBI-6624398, EBI-10248967;
CC P06307; Q7L8J4: SH3BP5L; NbExp=3; IntAct=EBI-6624398, EBI-747389;
CC P06307; Q8IYM2: SLFN12; NbExp=3; IntAct=EBI-6624398, EBI-2822550;
CC P06307; Q9C004: SPRY4; NbExp=3; IntAct=EBI-6624398, EBI-354861;
CC P06307; Q5W111-2: SPRYD7; NbExp=3; IntAct=EBI-6624398, EBI-12408727;
CC P06307; Q96BD6: SPSB1; NbExp=3; IntAct=EBI-6624398, EBI-2659201;
CC P06307; Q92797-2: SYMPK; NbExp=3; IntAct=EBI-6624398, EBI-21560407;
CC P06307; P62253: UBE2G1; NbExp=3; IntAct=EBI-6624398, EBI-2340619;
CC P06307; Q9UHD9: UBQLN2; NbExp=3; IntAct=EBI-6624398, EBI-947187;
CC P06307; Q9P1Q0-4: VPS54; NbExp=3; IntAct=EBI-6624398, EBI-25835297;
CC P06307; Q9NX94: WBP1L; NbExp=3; IntAct=EBI-6624398, EBI-10316321;
CC P06307; Q8IWT0-2: ZBTB8OS; NbExp=3; IntAct=EBI-6624398, EBI-12956041;
CC P06307; Q53FD0-2: ZC2HC1C; NbExp=3; IntAct=EBI-6624398, EBI-14104088;
CC P06307; Q96JL9-2: ZNF333; NbExp=3; IntAct=EBI-6624398, EBI-25835852;
CC PRO_0000010542; P32239: CCKBR; NbExp=2; IntAct=EBI-6624436, EBI-1753137;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P09240}.
CC -!- PTM: The precursor is cleaved by proteases to produce a number of
CC active cholecystokinins.
CC -!- PTM: [Cholecystokinin-5]: The precursor is cleaved by ACE, which
CC removes the Gly-Arg-Arg peptide at the C-terminus, leading to mature
CC hormone. {ECO:0000269|PubMed:10336644, ECO:0000269|PubMed:9371719}.
CC -!- SIMILARITY: Belongs to the gastrin/cholecystokinin family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/cck/";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Cholecystokinin entry;
CC URL="https://en.wikipedia.org/wiki/Cholecystokinin";
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DR EMBL; L00354; AAA53094.1; -; Genomic_DNA.
DR EMBL; BT006991; AAP35637.1; -; mRNA.
DR EMBL; AY514491; AAR89908.1; -; Genomic_DNA.
DR EMBL; BC008283; AAH08283.1; -; mRNA.
DR CCDS; CCDS2696.1; -.
DR PIR; A01623; GMHUCP.
DR RefSeq; NP_000720.1; NM_000729.5.
DR RefSeq; NP_001167609.1; NM_001174138.2.
DR PDB; 7EZH; EM; 3.20 A; P=96-103.
DR PDB; 7EZK; EM; 3.10 A; P=96-103.
DR PDB; 7EZM; EM; 2.90 A; P=96-103.
DR PDB; 7MBX; EM; 1.95 A; P=96-103.
DR PDB; 7MBY; EM; 2.44 A; P=96-103.
DR PDBsum; 7EZH; -.
DR PDBsum; 7EZK; -.
DR PDBsum; 7EZM; -.
DR PDBsum; 7MBX; -.
DR PDBsum; 7MBY; -.
DR AlphaFoldDB; P06307; -.
DR SMR; P06307; -.
DR BioGRID; 107327; 13.
DR IntAct; P06307; 56.
DR STRING; 9606.ENSP00000379472; -.
DR BindingDB; P06307; -.
DR ChEMBL; CHEMBL1649050; -.
DR DrugBank; DB13729; Camostat.
DR iPTMnet; P06307; -.
DR PhosphoSitePlus; P06307; -.
DR BioMuta; CCK; -.
DR DMDM; 115945; -.
DR MassIVE; P06307; -.
DR PaxDb; P06307; -.
DR PeptideAtlas; P06307; -.
DR PRIDE; P06307; -.
DR ProteomicsDB; 51882; -.
DR Antibodypedia; 29187; 272 antibodies from 34 providers.
DR DNASU; 885; -.
DR Ensembl; ENST00000334681.9; ENSP00000335657.5; ENSG00000187094.12.
DR Ensembl; ENST00000396169.7; ENSP00000379472.2; ENSG00000187094.12.
DR Ensembl; ENST00000434608.1; ENSP00000409124.1; ENSG00000187094.12.
DR GeneID; 885; -.
DR KEGG; hsa:885; -.
DR MANE-Select; ENST00000396169.7; ENSP00000379472.2; NM_000729.6; NP_000720.1.
DR CTD; 885; -.
DR DisGeNET; 885; -.
DR GeneCards; CCK; -.
DR HGNC; HGNC:1569; CCK.
DR HPA; ENSG00000187094; Group enriched (brain, choroid plexus, intestine).
DR MIM; 118440; gene.
DR neXtProt; NX_P06307; -.
DR OpenTargets; ENSG00000187094; -.
DR PharmGKB; PA26141; -.
DR VEuPathDB; HostDB:ENSG00000187094; -.
DR eggNOG; ENOG502S472; Eukaryota.
DR GeneTree; ENSGT00390000003571; -.
DR HOGENOM; CLU_169783_0_0_1; -.
DR InParanoid; P06307; -.
DR OMA; YSGLCIC; -.
DR OrthoDB; 1524113at2759; -.
DR PhylomeDB; P06307; -.
DR TreeFam; TF333419; -.
DR PathwayCommons; P06307; -.
DR Reactome; R-HSA-375276; Peptide ligand-binding receptors.
DR Reactome; R-HSA-416476; G alpha (q) signalling events.
DR SignaLink; P06307; -.
DR SIGNOR; P06307; -.
DR BioGRID-ORCS; 885; 15 hits in 1068 CRISPR screens.
DR ChiTaRS; CCK; human.
DR GeneWiki; Cholecystokinin; -.
DR GenomeRNAi; 885; -.
DR Pharos; P06307; Tbio.
DR PRO; PR:P06307; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; P06307; protein.
DR Bgee; ENSG00000187094; Expressed in frontal pole and 123 other tissues.
DR ExpressionAtlas; P06307; baseline and differential.
DR Genevisible; P06307; HS.
DR GO; GO:0030424; C:axon; ISS:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0005179; F:hormone activity; TAS:ProtInc.
DR GO; GO:0005184; F:neuropeptide hormone activity; ISS:UniProtKB.
DR GO; GO:0051428; F:peptide hormone receptor binding; IPI:GO_Central.
DR GO; GO:0007409; P:axonogenesis; ISS:UniProtKB.
DR GO; GO:0007586; P:digestion; IBA:GO_Central.
DR GO; GO:0042755; P:eating behavior; ISS:UniProtKB.
DR GO; GO:0001764; P:neuron migration; ISS:UniProtKB.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR InterPro; IPR015499; CCK-like.
DR InterPro; IPR001651; Gastrin/CCK.
DR InterPro; IPR013152; Gastrin/cholecystokinin_CS.
DR PANTHER; PTHR10786; PTHR10786; 1.
DR Pfam; PF00918; Gastrin; 1.
DR PROSITE; PS00259; GASTRIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Amidation; Cleavage on pair of basic residues; Hormone;
KW Reference proteome; Secreted; Signal; Sulfation.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..115
FT /note="Cholecystokinin"
FT /id="PRO_0000010536"
FT PROPEP 21..44
FT /evidence="ECO:0000250|UniProtKB:Q9TS44"
FT /id="PRO_0000010537"
FT PEPTIDE 46..103
FT /note="Cholecystokinin-58"
FT /evidence="ECO:0000250|UniProtKB:Q9TS44"
FT /id="PRO_0000010538"
FT PEPTIDE 46..94
FT /note="Cholecystokinin-58 desnonopeptide"
FT /evidence="ECO:0000250|UniProtKB:Q9TS44"
FT /id="PRO_0000306304"
FT PEPTIDE 65..103
FT /note="Cholecystokinin-39"
FT /evidence="ECO:0000250|UniProtKB:Q9TS44"
FT /id="PRO_0000010539"
FT PEPTIDE 71..103
FT /note="Cholecystokinin-33"
FT /evidence="ECO:0000250|UniProtKB:Q9TS44"
FT /id="PRO_0000010540"
FT PEPTIDE 79..103
FT /note="Cholecystokinin-25"
FT /evidence="ECO:0000250|UniProtKB:Q9TS44"
FT /id="PRO_0000306305"
FT PEPTIDE 86..103
FT /note="Cholecystokinin-18"
FT /evidence="ECO:0000250|UniProtKB:Q9TS44"
FT /id="PRO_0000306306"
FT PEPTIDE 92..103
FT /note="Cholecystokinin-12"
FT /evidence="ECO:0000250|UniProtKB:P01356"
FT /id="PRO_0000010541"
FT PEPTIDE 96..103
FT /note="Cholecystokinin-8"
FT /evidence="ECO:0000250|UniProtKB:Q9TS44"
FT /id="PRO_0000010542"
FT PEPTIDE 97..103
FT /note="Cholecystokinin-7"
FT /evidence="ECO:0000250|UniProtKB:Q9TS44"
FT /id="PRO_0000306307"
FT PEPTIDE 99..103
FT /note="Cholecystokinin-5"
FT /evidence="ECO:0000250|UniProtKB:Q9TS44"
FT /id="PRO_0000306308"
FT PROPEP 107..115
FT /id="PRO_0000010543"
FT REGION 22..52
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 38..52
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 97
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000269|PubMed:11076522"
FT MOD_RES 103
FT /note="Phenylalanine amide"
FT /evidence="ECO:0000269|PubMed:3856870"
FT MOD_RES 111
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9TS44"
FT MOD_RES 113
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9TS44"
FT VARIANT 32
FT /note="G -> E (in dbSNP:rs11571848)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_018818"
FT VARIANT 95
FT /note="R -> W (in dbSNP:rs3774395)"
FT /id="VAR_024452"
FT MUTAGEN 97
FT /note="Y->F: Reduces the quantity of secreted CCK8 by 50%."
FT /evidence="ECO:0000269|PubMed:11076522"
SQ SEQUENCE 115 AA; 12669 MW; 8A3EE6442FAEAF4B CRC64;
MNSGVCLCVL MAVLAAGALT QPVPPADPAG SGLQRAEEAP RRQLRVSQRT DGESRAHLGA
LLARYIQQAR KAPSGRMSIV KNLQNLDPSH RISDRDYMGW MDFGRRSAEE YEYPS
