ID   GALA_HUMAN              Reviewed;         123 AA.
AC   P22466; Q14413;
DT   01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1997, sequence version 3.
DT   27-MAR-2024, entry version 198.
DE   RecName: Full=Galanin peptides;
DE   Contains:
DE     RecName: Full=Galanin;
DE   Contains:
DE     RecName: Full=Galanin message-associated peptide;
DE              Short=GMAP;
DE   Flags: Precursor;
GN   Name=GAL; Synonyms=GAL1, GALN, GLNN;
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] OF 1-45.
RC   TISSUE=Blood;
RX   PubMed=7508413; DOI=10.1016/s0888-7543(11)80002-9;
RA   Evans H., Baumgartner M., Shine J., Herzog H.;
RT   "Genomic organization and localization of the gene encoding human
RT   preprogalanin.";
RL   Genomics 18:473-477(1993).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 16-123, FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=1370155; DOI=10.2337/diab.41.1.82;
RA   McKnight G.L., Karlsen A.E., Kowalyk S., Mathewes S.L., Sheppard P.O.,
RA   O'Hara P.J., Taborsky G.L.;
RT   "Sequence of human galanin and its inhibition of glucose-stimulated insulin
RT   secretion from RIN cells.";
RL   Diabetes 41:82-87(1992).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Cervix;
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   [4]
RP   PROTEIN SEQUENCE OF 33-62.
RX   PubMed=1710578; DOI=10.1016/0014-5793(91)80585-q;
RA   Bersani M., Johnsen A.H., Hoejrup P., Dunning B.E., Andreasen J.J.,
RA   Holst J.J.;
RT   "Human galanin: primary structure and identification of two molecular
RT   forms.";
RL   FEBS Lett. 283:189-194(1991).
RN   [5]
RP   PROTEIN SEQUENCE OF 33-62, SYNTHESIS, FUNCTION, AND SUBCELLULAR LOCATION.
RC   TISSUE=Pituitary;
RX   PubMed=1722333; DOI=10.1073/pnas.88.24.11435;
RA   Schmidt W.E., Kratzin H., Eckart K., Drevs D., Mundkowski G., Clemens A.,
RA   Katsoulis S., Schaefer H., Gallwitz B., Creutzfeldt W.;
RT   "Isolation and primary structure of pituitary human galanin, a 30-residue
RT   nonamidated neuropeptide.";
RL   Proc. Natl. Acad. Sci. U.S.A. 88:11435-11439(1991).
RN   [6]
RP   PHOSPHORYLATION AT SER-117.
RC   TISSUE=Pituitary;
RX   PubMed=14997482; DOI=10.1002/pmic.200300584;
RA   Giorgianni F., Beranova-Giorgianni S., Desiderio D.M.;
RT   "Identification and characterization of phosphorylated proteins in the
RT   human pituitary.";
RL   Proteomics 4:587-598(2004).
RN   [7]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Pituitary;
RX   PubMed=16807684; DOI=10.1007/s11102-006-8916-x;
RA   Beranova-Giorgianni S., Zhao Y., Desiderio D.M., Giorgianni F.;
RT   "Phosphoproteomic analysis of the human pituitary.";
RL   Pituitary 9:109-120(2006).
RN   [8]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA   Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA   Elledge S.J., Gygi S.P.;
RT   "A quantitative atlas of mitotic phosphorylation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN   [9]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-117, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA   Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA   Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT   "System-wide temporal characterization of the proteome and phosphoproteome
RT   of human embryonic stem cell differentiation.";
RL   Sci. Signal. 4:RS3-RS3(2011).
RN   [10]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-116, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=23186163; DOI=10.1021/pr300630k;
RA   Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA   Mohammed S.;
RT   "Toward a comprehensive characterization of a human cancer cell
RT   phosphoproteome.";
RL   J. Proteome Res. 12:260-271(2013).
RN   [11]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA   Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT   phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
RN   [12]
RP   FUNCTION, INVOLVEMENT IN ETL8, VARIANT ETL8 GLU-39, AND CHARACTERIZATION OF
RP   VARIANT ETL8 GLU-39.
RX   PubMed=25691535; DOI=10.1093/hmg/ddv060;
RA   Guipponi M., Chentouf A., Webling K.E., Freimann K., Crespel A., Nobile C.,
RA   Lemke J.R., Hansen J., Dorn T., Lesca G., Ryvlin P., Hirsch E., Rudolf G.,
RA   Rosenberg D.S., Weber Y., Becker F., Helbig I., Muhle H., Salzmann A.,
RA   Chaouch M., Oubaiche M.L., Ziglio S., Gehrig C., Santoni F., Pizzato M.,
RA   Langel U., Antonarakis S.E.;
RT   "Galanin pathogenic mutations in temporal lobe epilepsy.";
RL   Hum. Mol. Genet. 24:3082-3091(2015).
CC   -!- FUNCTION: Endocrine hormone of the central and peripheral nervous
CC       systems that binds and activates the G protein-coupled receptors GALR1,
CC       GALR2, and GALR3. This small neuropeptide may regulate diverse
CC       physiologic functions including contraction of smooth muscle of the
CC       gastrointestinal and genitourinary tract, growth hormone and insulin
CC       release and adrenal secretion. {ECO:0000269|PubMed:1370155,
CC       ECO:0000269|PubMed:1722333, ECO:0000269|PubMed:25691535}.
CC   -!- INTERACTION:
CC       P22466; P31749: AKT1; NbExp=3; IntAct=EBI-6624768, EBI-296087;
CC       P22466; Q12797-6: ASPH; NbExp=3; IntAct=EBI-6624768, EBI-12092171;
CC       P22466; P23560-2: BDNF; NbExp=3; IntAct=EBI-6624768, EBI-12275524;
CC       P22466; P35520: CBS; NbExp=3; IntAct=EBI-6624768, EBI-740135;
CC       P22466; O43765: SGTA; NbExp=6; IntAct=EBI-6624768, EBI-347996;
CC       P22466; Q9UNE7: STUB1; NbExp=3; IntAct=EBI-6624768, EBI-357085;
CC       P22466; Q9UMX0: UBQLN1; NbExp=3; IntAct=EBI-6624768, EBI-741480;
CC       P22466; Q9UHD9: UBQLN2; NbExp=3; IntAct=EBI-6624768, EBI-947187;
CC       PRO_0000010449; P47211: GALR1; NbExp=2; IntAct=EBI-6624800, EBI-6624741;
CC       PRO_0000010449; O43603: GALR2; NbExp=2; IntAct=EBI-6624800, EBI-6624855;
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:1370155,
CC       ECO:0000269|PubMed:1722333}.
CC   -!- DISEASE: Epilepsy, familial temporal lobe, 8 (ETL8) [MIM:616461]: A
CC       focal form of epilepsy characterized by recurrent seizures that arise
CC       from foci within the temporal lobe. Seizures are usually accompanied by
CC       sensory symptoms, most often auditory in nature.
CC       {ECO:0000269|PubMed:25691535}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the galanin family. {ECO:0000305}.
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DR   EMBL; L11144; AAA18248.1; -; Genomic_DNA.
DR   EMBL; M77140; AAA60178.1; -; mRNA.
DR   EMBL; BC030241; AAH30241.1; -; mRNA.
DR   CCDS; CCDS8183.1; -.
DR   PIR; A49353; RHHUN.
DR   RefSeq; NP_057057.2; NM_015973.4.
DR   PDB; 7S3O; NMR; -; A=34-46.
DR   PDB; 7S3Q; NMR; -; A=33-46.
DR   PDB; 7S3R; NMR; -; A=33-50.
DR   PDB; 7WQ3; EM; 2.70 A; L=33-62.
DR   PDB; 7WQ4; EM; 2.60 A; L=33-62.
DR   PDB; 7XBD; EM; 3.11 A; F=33-62.
DR   PDB; 7XJJ; EM; 3.30 A; C=33-62.
DR   PDB; 7XJK; EM; 3.30 A; A=33-62.
DR   PDB; 8DHZ; NMR; -; A=49-62.
DR   PDB; 8DJ4; NMR; -; A=33-62.
DR   PDBsum; 7S3O; -.
DR   PDBsum; 7S3Q; -.
DR   PDBsum; 7S3R; -.
DR   PDBsum; 7WQ3; -.
DR   PDBsum; 7WQ4; -.
DR   PDBsum; 7XBD; -.
DR   PDBsum; 7XJJ; -.
DR   PDBsum; 7XJK; -.
DR   PDBsum; 8DHZ; -.
DR   PDBsum; 8DJ4; -.
DR   AlphaFoldDB; P22466; -.
DR   EMDB; EMD-32698; -.
DR   EMDB; EMD-33229; -.
DR   SMR; P22466; -.
DR   BioGRID; 119273; 25.
DR   IntAct; P22466; 16.
DR   MINT; P22466; -.
DR   STRING; 9606.ENSP00000265643; -.
DR   BindingDB; P22466; -.
DR   GlyGen; P22466; 2 sites, 1 O-linked glycan (2 sites).
DR   iPTMnet; P22466; -.
DR   PhosphoSitePlus; P22466; -.
DR   BioMuta; GAL; -.
DR   DMDM; 2506449; -.
DR   EPD; P22466; -.
DR   jPOST; P22466; -.
DR   MassIVE; P22466; -.
DR   MaxQB; P22466; -.
DR   PaxDb; 9606-ENSP00000265643; -.
DR   PeptideAtlas; P22466; -.
DR   ProteomicsDB; 53995; -.
DR   Pumba; P22466; -.
DR   ABCD; P22466; 16 sequenced antibodies.
DR   Antibodypedia; 30599; 426 antibodies from 37 providers.
DR   DNASU; 51083; -.
DR   Ensembl; ENST00000265643.4; ENSP00000265643.3; ENSG00000069482.7.
DR   GeneID; 51083; -.
DR   KEGG; hsa:51083; -.
DR   MANE-Select; ENST00000265643.4; ENSP00000265643.3; NM_015973.5; NP_057057.2.
DR   UCSC; uc001oob.4; human.
DR   AGR; HGNC:4114; -.
DR   DisGeNET; 51083; -.
DR   GeneCards; GAL; -.
DR   HGNC; HGNC:4114; GAL.
DR   HPA; ENSG00000069482; Tissue enriched (pituitary).
DR   MalaCards; GAL; -.
DR   MIM; 137035; gene.
DR   MIM; 616461; phenotype.
DR   neXtProt; NX_P22466; -.
DR   OpenTargets; ENSG00000069482; -.
DR   PharmGKB; PA28529; -.
DR   VEuPathDB; HostDB:ENSG00000069482; -.
DR   eggNOG; ENOG502RZ1E; Eukaryota.
DR   GeneTree; ENSGT00390000009663; -.
DR   HOGENOM; CLU_166244_0_0_1; -.
DR   InParanoid; P22466; -.
DR   OMA; PHAVDSH; -.
DR   OrthoDB; 4119714at2759; -.
DR   PhylomeDB; P22466; -.
DR   TreeFam; TF335850; -.
DR   PathwayCommons; P22466; -.
DR   Reactome; R-HSA-375276; Peptide ligand-binding receptors.
DR   Reactome; R-HSA-418594; G alpha (i) signalling events.
DR   SignaLink; P22466; -.
DR   SIGNOR; P22466; -.
DR   BioGRID-ORCS; 51083; 22 hits in 1154 CRISPR screens.
DR   ChiTaRS; GAL; human.
DR   GeneWiki; Galanin; -.
DR   GenomeRNAi; 51083; -.
DR   Pharos; P22466; Tbio.
DR   PRO; PR:P22466; -.
DR   Proteomes; UP000005640; Chromosome 11.
DR   RNAct; P22466; Protein.
DR   Bgee; ENSG00000069482; Expressed in adenohypophysis and 105 other cell types or tissues.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR   GO; GO:0043025; C:neuronal cell body; IDA:UniProtKB.
DR   GO; GO:0030141; C:secretory granule; IBA:GO_Central.
DR   GO; GO:0004966; F:galanin receptor activity; IMP:UniProtKB.
DR   GO; GO:0031763; F:galanin receptor binding; IBA:GO_Central.
DR   GO; GO:0005184; F:neuropeptide hormone activity; IDA:UniProtKB.
DR   GO; GO:0031764; F:type 1 galanin receptor binding; IDA:UniProtKB.
DR   GO; GO:0031765; F:type 2 galanin receptor binding; IDA:UniProtKB.
DR   GO; GO:0031766; F:type 3 galanin receptor binding; IDA:UniProtKB.
DR   GO; GO:0019933; P:cAMP-mediated signaling; IDA:UniProtKB.
DR   GO; GO:0007631; P:feeding behavior; IEA:Ensembl.
DR   GO; GO:0030073; P:insulin secretion; NAS:UniProtKB.
DR   GO; GO:0050672; P:negative regulation of lymphocyte proliferation; IEA:Ensembl.
DR   GO; GO:0007218; P:neuropeptide signaling pathway; IBA:GO_Central.
DR   GO; GO:0043065; P:positive regulation of apoptotic process; IEA:Ensembl.
DR   GO; GO:0051464; P:positive regulation of cortisol secretion; IDA:UniProtKB.
DR   GO; GO:1902608; P:positive regulation of large conductance calcium-activated potassium channel activity; IDA:UniProtKB.
DR   GO; GO:0051795; P:positive regulation of timing of catagen; IDA:UniProtKB.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR   GO; GO:0010737; P:protein kinase A signaling; IDA:UniProtKB.
DR   GO; GO:0031943; P:regulation of glucocorticoid metabolic process; IEA:Ensembl.
DR   GO; GO:0043627; P:response to estrogen; IEA:Ensembl.
DR   GO; GO:0035902; P:response to immobilization stress; IEA:Ensembl.
DR   GO; GO:0032868; P:response to insulin; IEA:Ensembl.
DR   GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR   InterPro; IPR008174; Galanin.
DR   InterPro; IPR008175; Galanin_pre.
DR   InterPro; IPR013068; GMAP.
DR   PANTHER; PTHR16839; GALANIN; 1.
DR   PANTHER; PTHR16839:SF1; GALANIN PEPTIDES; 1.
DR   Pfam; PF01296; Galanin; 1.
DR   Pfam; PF06540; GMAP; 1.
DR   PRINTS; PR00273; GALANIN.
DR   SMART; SM00071; Galanin; 1.
DR   PROSITE; PS00861; GALANIN; 1.
DR   Genevisible; P22466; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Cleavage on pair of basic residues;
KW   Direct protein sequencing; Disease variant; Epilepsy; Hormone;
KW   Neuropeptide; Phosphoprotein; Reference proteome; Secreted; Signal.
FT   SIGNAL          1..19
FT                   /evidence="ECO:0000255"
FT   PROPEP          20..30
FT                   /id="PRO_0000010448"
FT   PEPTIDE         33..62
FT                   /note="Galanin"
FT                   /id="PRO_0000010449"
FT   PEPTIDE         65..123
FT                   /note="Galanin message-associated peptide"
FT                   /id="PRO_0000010450"
FT   REGION          46..80
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        57..77
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         116
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         117
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:14997482,
FT                   ECO:0007744|PubMed:21406692"
FT   VARIANT         16
FT                   /note="A -> V (in dbSNP:rs34725707)"
FT                   /id="VAR_049121"
FT   VARIANT         39
FT                   /note="A -> E (in ETL8; decreased affinity for GALR2; but
FT                   no effect on affinity for GALR1 and GALR3; decreased
FT                   activity in GALR2-mediated signaling; dominant-negative
FT                   that inhibits GALR1-mediated signaling;
FT                   dbSNP:rs1057517661)"
FT                   /evidence="ECO:0000269|PubMed:25691535"
FT                   /id="VAR_074671"
FT   HELIX           36..43
FT                   /evidence="ECO:0007829|PDB:7WQ4"
FT   HELIX           45..48
FT                   /evidence="ECO:0007829|PDB:7XJJ"
SQ   SEQUENCE   123 AA;  13302 MW;  48D2170AF1248E6D CRC64;
     MARGSALLLA SLLLAAALSA SAGLWSPAKE KRGWTLNSAG YLLGPHAVGN HRSFSDKNGL
     TSKRELRPED DMKPGSFDRS IPENNIMRTI IEFLSFLHLK EAGALDRLLD LPAAASSEDI
     ERS
//