CART_HUMAN
ID CART_HUMAN Reviewed; 116 AA.
AC Q16568; Q6FG92;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=Cocaine- and amphetamine-regulated transcript protein;
DE Contains:
DE RecName: Full=CART(1-39);
DE Contains:
DE RecName: Full=CART(42-89);
DE Flags: Precursor;
GN Name=CARTPT; Synonyms=CART;
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 [GENOMIC DNA / MRNA].
RX PubMed=8647455; DOI=10.1016/0378-1119(96)88651-3;
RA Douglass J.O., Daoud S.;
RT "Characterization of the human cDNA and genomic DNA encoding CART: a
RT cocaine- and amphetamine-regulated transcript.";
RL Gene 169:241-245(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 28-42.
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 FUNCTION.
RX PubMed=9590691; DOI=10.1038/29993;
RA Kristensen P., Judge M.E., Thim L., Ribel U., Christjansen K.N.,
RA Wulff B.S., Clausen J.T., Jensen P.B., Madsen O.D., Vrang N., Larsen P.J.,
RA Hastrup S.;
RT "Hypothalamic CART is a new anorectic peptide regulated by leptin.";
RL Nature 393:72-76(1998).
RN [7]
RP STRUCTURE BY NMR OF 75-116.
RX PubMed=11478874; DOI=10.1021/bi010433u;
RA Ludvigsen S., Thim L., Blom A.M., Wulff B.S.;
RT "Solution structure of the satiety factor, CART, reveals new functionality
RT of a well-known fold.";
RL Biochemistry 40:9082-9088(2001).
RN [8]
RP VARIANT THR-66.
RX PubMed=10905499; DOI=10.2337/diabetes.49.5.872;
RA Challis B.G., Yeo G.S.H., Farooqi I.S., Luan J., Aminian S., Halsall D.J.,
RA Keogh J.M., Wareham N.J., O'Rahilly S.;
RT "The CART gene and human obesity: mutational analysis and population
RT genetics.";
RL Diabetes 49:872-875(2000).
RN [9]
RP VARIANT PHE-61.
RX PubMed=11522684; DOI=10.2337/diabetes.50.9.2157;
RA del Giudice E.M., Santoro N., Cirillo G., D'Urso L., Di Toro R.,
RA Perrone L.;
RT "Mutational screening of the CART gene in obese children: identifying a
RT mutation (Leu34Phe) associated with reduced resting energy expenditure and
RT cosegregating with obesity phenotype in a large family.";
RL Diabetes 50:2157-2160(2001).
CC -!- FUNCTION: Satiety factor closely associated with the actions of leptin
CC and neuropeptide Y; this anorectic peptide inhibits both normal and
CC starvation-induced feeding and completely blocks the feeding response
CC induced by neuropeptide Y and regulated by leptin in the hypothalamus.
CC It promotes neuronal development and survival in vitro.
CC {ECO:0000269|PubMed:9590691}.
CC -!- INTERACTION:
CC Q16568; P13688: CEACAM1; NbExp=3; IntAct=EBI-4314526, EBI-4314481;
CC Q16568; P40199: CEACAM6; NbExp=3; IntAct=EBI-4314526, EBI-4314501;
CC Q16568; O14770-4: MEIS2; NbExp=3; IntAct=EBI-4314526, EBI-8025850;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Hypothalamus. Found in neurons of the ventrolateral
CC part of the arcuate nucleus, in the external zone of the median
CC eminence, and also found in terminals in the periventricular part of
CC the paraventricular nucleus.
CC -!- INDUCTION: By leptin.
CC -!- SIMILARITY: Belongs to the CART family. {ECO:0000305}.
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DR EMBL; U16826; AAB08010.1; -; mRNA.
DR EMBL; U20325; AAB08011.1; -; Genomic_DNA.
DR EMBL; CR542216; CAG47012.1; -; mRNA.
DR EMBL; CH471084; EAW95694.1; -; Genomic_DNA.
DR EMBL; BC029882; AAH29882.1; -; mRNA.
DR CCDS; CCDS4011.1; -.
DR PIR; JC4669; JC4669.
DR RefSeq; NP_004282.1; NM_004291.3.
DR PDB; 1HY9; NMR; -; A=76-116.
DR PDBsum; 1HY9; -.
DR AlphaFoldDB; Q16568; -.
DR SMR; Q16568; -.
DR BioGRID; 114970; 47.
DR IntAct; Q16568; 4.
DR STRING; 9606.ENSP00000296777; -.
DR DrugBank; DB00182; Amphetamine.
DR DrugCentral; Q16568; -.
DR iPTMnet; Q16568; -.
DR PhosphoSitePlus; Q16568; -.
DR BioMuta; CARTPT; -.
DR DMDM; 2833274; -.
DR jPOST; Q16568; -.
DR MassIVE; Q16568; -.
DR PaxDb; Q16568; -.
DR PeptideAtlas; Q16568; -.
DR PRIDE; Q16568; -.
DR ProteomicsDB; 60922; -.
DR Antibodypedia; 24184; 226 antibodies from 30 providers.
DR DNASU; 9607; -.
DR Ensembl; ENST00000296777.5; ENSP00000296777.4; ENSG00000164326.5.
DR GeneID; 9607; -.
DR KEGG; hsa:9607; -.
DR MANE-Select; ENST00000296777.5; ENSP00000296777.4; NM_004291.4; NP_004282.1.
DR UCSC; uc003kbv.2; human.
DR CTD; 9607; -.
DR DisGeNET; 9607; -.
DR GeneCards; CARTPT; -.
DR HGNC; HGNC:24323; CARTPT.
DR HPA; ENSG00000164326; Group enriched (adrenal gland, brain).
DR MalaCards; CARTPT; -.
DR MIM; 602606; gene.
DR neXtProt; NX_Q16568; -.
DR OpenTargets; ENSG00000164326; -.
DR PharmGKB; PA162381084; -.
DR VEuPathDB; HostDB:ENSG00000164326; -.
DR eggNOG; ENOG502S2YU; Eukaryota.
DR GeneTree; ENSGT00390000018319; -.
DR HOGENOM; CLU_157363_1_0_1; -.
DR InParanoid; Q16568; -.
DR OMA; PRTGTMQ; -.
DR OrthoDB; 1562917at2759; -.
DR PhylomeDB; Q16568; -.
DR TreeFam; TF332948; -.
DR PathwayCommons; Q16568; -.
DR SignaLink; Q16568; -.
DR SIGNOR; Q16568; -.
DR BioGRID-ORCS; 9607; 12 hits in 1073 CRISPR screens.
DR EvolutionaryTrace; Q16568; -.
DR GenomeRNAi; 9607; -.
DR Pharos; Q16568; Tbio.
DR PRO; PR:Q16568; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q16568; protein.
DR Bgee; ENSG00000164326; Expressed in hypothalamus and 123 other tissues.
DR Genevisible; Q16568; HS.
DR GO; GO:0005615; C:extracellular space; IDA:HGNC-UCL.
DR GO; GO:0030141; C:secretory granule; IDA:UniProtKB.
DR GO; GO:0045202; C:synapse; IEA:GOC.
DR GO; GO:0005184; F:neuropeptide hormone activity; IEA:InterPro.
DR GO; GO:0008343; P:adult feeding behavior; ISS:HGNC-UCL.
DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
DR GO; GO:0001678; P:cellular glucose homeostasis; IDA:HGNC-UCL.
DR GO; GO:0009267; P:cellular response to starvation; ISS:HGNC-UCL.
DR GO; GO:0007268; P:chemical synaptic transmission; IEA:UniProtKB-KW.
DR GO; GO:0032922; P:circadian regulation of gene expression; ISS:HGNC-UCL.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; ISS:HGNC-UCL.
DR GO; GO:0032099; P:negative regulation of appetite; ISS:HGNC-UCL.
DR GO; GO:0045779; P:negative regulation of bone resorption; IMP:HGNC-UCL.
DR GO; GO:0070093; P:negative regulation of glucagon secretion; IEA:Ensembl.
DR GO; GO:0045671; P:negative regulation of osteoclast differentiation; TAS:HGNC-UCL.
DR GO; GO:0007218; P:neuropeptide signaling pathway; IEA:UniProtKB-KW.
DR GO; GO:0045777; P:positive regulation of blood pressure; IDA:HGNC-UCL.
DR GO; GO:0032812; P:positive regulation of epinephrine secretion; IDA:HGNC-UCL.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISS:HGNC-UCL.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; ISS:HGNC-UCL.
DR GO; GO:0051971; P:positive regulation of transmission of nerve impulse; IDA:HGNC-UCL.
DR GO; GO:0050796; P:regulation of insulin secretion; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0070253; P:somatostatin secretion; IEA:Ensembl.
DR Gene3D; 4.10.40.30; -; 1.
DR InterPro; IPR009106; CART.
DR InterPro; IPR036722; CART_C_sf.
DR PANTHER; PTHR16655; PTHR16655; 1.
DR Pfam; PF06373; CART; 1.
DR SUPFAM; SSF64546; SSF64546; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cleavage on pair of basic residues;
KW Direct protein sequencing; Disulfide bond; Neuropeptide; Neurotransmitter;
KW Obesity; Phosphoprotein; Reference proteome; Secreted; Signal.
FT SIGNAL 1..27
FT /evidence="ECO:0000269|PubMed:15340161"
FT CHAIN 28..116
FT /note="Cocaine- and amphetamine-regulated transcript
FT protein"
FT /id="PRO_0000004433"
FT PEPTIDE 28..66
FT /note="CART(1-39)"
FT /id="PRO_0000004434"
FT PEPTIDE 69..116
FT /note="CART(42-89)"
FT /id="PRO_0000004435"
FT MOD_RES 41
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P49192"
FT MOD_RES 48
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P56388"
FT DISULFID 82..100
FT /evidence="ECO:0007744|PDB:1HY9"
FT DISULFID 88..108
FT /evidence="ECO:0007744|PDB:1HY9"
FT DISULFID 102..115
FT /evidence="ECO:0007744|PDB:1HY9"
FT VARIANT 61
FT /note="L -> F (cosegregates with obesity phenotype in a
FT large family; dbSNP:rs121909065)"
FT /evidence="ECO:0000269|PubMed:11522684"
FT /id="VAR_012199"
FT VARIANT 66
FT /note="S -> T (in dbSNP:rs78242624)"
FT /evidence="ECO:0000269|PubMed:10905499"
FT /id="VAR_012200"
FT VARIANT 113
FT /note="L -> M (in dbSNP:rs12517689)"
FT /id="VAR_053022"
FT STRAND 84..86
FT /evidence="ECO:0007829|PDB:1HY9"
FT STRAND 88..91
FT /evidence="ECO:0007829|PDB:1HY9"
FT STRAND 93..98
FT /evidence="ECO:0007829|PDB:1HY9"
FT TURN 110..112
FT /evidence="ECO:0007829|PDB:1HY9"
SQ SEQUENCE 116 AA; 12829 MW; FC396CA2C032AA83 CRC64;
MESSRVRLLP LLGAALLLML PLLGTRAQED AELQPRALDI YSAVDDASHE KELIEALQEV
LKKLKSKRVP IYEKKYGQVP MCDAGEQCAV RKGARIGKLC DCPRGTSCNS FLLKCL
