CSH2_HUMAN
ID CSH2_HUMAN Reviewed; 217 AA.
AC P0DML3; P01243; Q0VDB1; Q14407;
DT 09-JUL-2014, integrated into UniProtKB/Swiss-Prot.
DT 09-JUL-2014, sequence version 1.
DT 03-AUG-2022, entry version 48.
DE RecName: Full=Chorionic somatomammotropin hormone 2;
DE Short=Choriomammotropin;
DE AltName: Full=Lactogen;
DE AltName: Full=Placental lactogen;
DE Short=PL;
DE Flags: Precursor;
GN Name=CSH2;
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].
RX PubMed=3030680; DOI=10.1089/dna.1987.6.59;
RA Hirt H., Kimelman J., Birnbaum M.J., Chen E.Y., Seeburg P.H.,
RA Eberhardt N.L., Barta A.;
RT "The human growth hormone gene locus: structure, evolution, and allelic
RT variations.";
RL DNA 6:59-70(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
RX PubMed=6300056; DOI=10.1016/s0021-9258(18)32734-0;
RA Barrera-Saldana H.A., Seeburg P.H., Saunders G.F.;
RT "Two structurally different genes produce the same secreted human placental
RT lactogen hormone.";
RL J. Biol. Chem. 258:3787-3793(1983).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2744760; DOI=10.1016/0888-7543(89)90271-1;
RA Chen E.Y., Liao Y.C., Smith D.H., Barrera-Saldana H.A., Gelinas R.E.,
RA Seeburg P.H.;
RT "The human growth hormone locus: nucleotide sequence, biology, and
RT evolution.";
RL Genomics 4:479-497(1989).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
RX PubMed=7169009; DOI=10.1089/dna.1.1982.1.239;
RA Seeburg P.H.;
RT "The human growth hormone gene family: nucleotide sequences show recent
RT divergence and predict a new polypeptide hormone.";
RL DNA 1:239-249(1982).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=18473352; DOI=10.1002/humu.20767;
RA Sedman L., Padhukasahasram B., Kelgo P., Laan M.;
RT "Complex signatures of locus-specific selective pressures and gene
RT conversion on human growth hormone/chorionic somatomammotropin genes.";
RL Hum. Mutat. 29:1181-1193(2008).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta, and Uterus;
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 [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 50-217 (ISOFORM 1).
RX PubMed=593368; DOI=10.1038/270494a0;
RA Shine J., Seeburg P.H., Martial J.A., Baxter J.D., Goodman H.M.;
RT "Construction and analysis of recombinant DNA for human chorionic
RT somatomammotropin.";
RL Nature 270:494-499(1977).
RN [9]
RP PROTEIN SEQUENCE OF 27-217.
RX PubMed=4712450; DOI=10.1016/s0003-9861(73)80012-8;
RA Li C.H., Dixon J.S., Chung D.;
RT "Amino acid sequence of human chorionic somatomammotropin.";
RL Arch. Biochem. Biophys. 155:95-110(1973).
RN [10]
RP PROTEIN SEQUENCE OF 27-217.
RX PubMed=5286363; DOI=10.1038/newbio233059a0;
RA Sherwood L.M., Handwerger S., McLaurin W.D., Lanner M.;
RT "Amino-acid sequence of human placental lactogen.";
RL Nature New Biol. 233:59-61(1971).
RN [11]
RP ERRATUM OF PUBMED:5286363.
RA Sherwood L.M., Handwerger S., McLaurin W.D., Lanner M.;
RL Nature New Biol. 235:64-64(1972).
RN [12]
RP INTERCHAIN DISULFIDE BONDS, AND SUBUNIT.
RX PubMed=438159; DOI=10.1016/s0021-9258(18)50655-4;
RA Schneider A.B., Kowalski K., Russell J., Sherwood L.M.;
RT "Identification of the interchain disulfide bonds of dimeric human
RT placental lactogen.";
RL J. Biol. Chem. 254:3782-3787(1979).
RN [13]
RP FUNCTION, ZINC-BINDING SITES, AND DISULFIDE BONDS.
RX PubMed=16546209; DOI=10.1016/j.jmb.2006.02.038;
RA Walsh S.T., Kossiakoff A.A.;
RT "Crystal structure and site 1 binding energetics of human placental
RT lactogen.";
RL J. Mol. Biol. 358:773-784(2006).
CC -!- FUNCTION: Produced only during pregnancy and is involved in stimulating
CC lactation, fetal growth and metabolism. Does not interact with GHR but
CC only activates PRLR through zinc-induced dimerization.
CC {ECO:0000269|PubMed:16546209}.
CC -!- SUBUNIT: Can be found in a monomeric as well as dimeric form.
CC {ECO:0000269|PubMed:438159}.
CC -!- INTERACTION:
CC P0DML3; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-12167441, EBI-16439278;
CC P0DML3; Q96EQ0: SGTB; NbExp=3; IntAct=EBI-12167441, EBI-744081;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage; Named isoforms=3;
CC Name=1;
CC IsoId=P0DML3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P0DML3-2; Sequence=VSP_055245;
CC Name=3;
CC IsoId=P0DML3-3; Sequence=VSP_055244;
CC -!- MISCELLANEOUS: CSH2 sequence only differs from CSH1 sequence in 1 aa.
CC -!- SIMILARITY: Belongs to the somatotropin/prolactin family.
CC {ECO:0000305}.
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DR EMBL; V00573; CAA23836.1; -; mRNA.
DR EMBL; J00289; AAA98747.1; -; Genomic_DNA.
DR EMBL; K02401; AAA52115.1; -; Genomic_DNA.
DR EMBL; M15894; AAA52116.1; -; Genomic_DNA.
DR EMBL; J03071; AAA52553.1; -; Genomic_DNA.
DR EMBL; EU421716; ABZ88723.1; -; Genomic_DNA.
DR EMBL; BC022044; AAH22044.1; -; mRNA.
DR EMBL; BC035965; AAH35965.1; -; mRNA.
DR EMBL; BC119748; AAI19749.1; -; mRNA.
DR CCDS; CCDS11646.1; -. [P0DML3-2]
DR CCDS; CCDS42368.1; -. [P0DML3-3]
DR CCDS; CCDS42369.1; -. [P0DML3-1]
DR PIR; A26449; A26449.
DR PIR; E32435; E32435.
DR RefSeq; NP_001308.1; NM_001317.5.
DR RefSeq; NP_066271.1; NM_020991.3. [P0DML3-1]
DR AlphaFoldDB; P0DML3; -.
DR SMR; P0DML3; -.
DR BioGRID; 107829; 14.
DR BioGRID; 107830; 15.
DR IntAct; P0DML3; 5.
DR STRING; 9606.ENSP00000376623; -.
DR iPTMnet; P0DML3; -.
DR BioMuta; CSH2; -.
DR MassIVE; P0DML3; -.
DR PaxDb; P0DML3; -.
DR PeptideAtlas; P0DML3; -.
DR Antibodypedia; 31377; 121 antibodies from 21 providers.
DR DNASU; 1442; -.
DR Ensembl; ENST00000336844.9; ENSP00000338816.5; ENSG00000213218.11. [P0DML3-2]
DR Ensembl; ENST00000345366.8; ENSP00000308396.10; ENSG00000213218.11. [P0DML3-3]
DR Ensembl; ENST00000392886.7; ENSP00000376623.2; ENSG00000213218.11. [P0DML3-1]
DR GeneID; 1442; -.
DR GeneID; 1443; -.
DR KEGG; hsa:1442; -.
DR KEGG; hsa:1443; -.
DR MANE-Select; ENST00000392886.7; ENSP00000376623.2; NM_020991.4; NP_066271.1.
DR UCSC; uc002jcg.3; human. [P0DML3-1]
DR CTD; 1442; -.
DR CTD; 1443; -.
DR DisGeNET; 1442; -.
DR DisGeNET; 1443; -.
DR GeneCards; CSH2; -.
DR HGNC; HGNC:2441; CSH2.
DR HPA; ENSG00000213218; Tissue enriched (placenta).
DR MIM; 118820; gene.
DR neXtProt; NX_P0DML3; -.
DR OpenTargets; ENSG00000213218; -.
DR VEuPathDB; HostDB:ENSG00000213218; -.
DR eggNOG; ENOG502R5GJ; Eukaryota.
DR GeneTree; ENSGT00950000182818; -.
DR HOGENOM; CLU_088274_2_1_1; -.
DR OMA; VHRTSDS; -.
DR OrthoDB; 1190548at2759; -.
DR PhylomeDB; P0DML3; -.
DR PathwayCommons; P0DML3; -.
DR SignaLink; P0DML3; -.
DR BioGRID-ORCS; 1442; 13 hits in 969 CRISPR screens.
DR BioGRID-ORCS; 1443; 82 hits in 985 CRISPR screens.
DR ChiTaRS; CSH2; human.
DR Pharos; P0DML3; Tbio.
DR PRO; PR:P0DML3; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; P0DML3; protein.
DR Bgee; ENSG00000213218; Expressed in placenta and 44 other tissues.
DR ExpressionAtlas; P0DML3; baseline and differential.
DR Genevisible; P0DML3; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:AgBase.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0031982; C:vesicle; IDA:AgBase.
DR GO; GO:0008083; F:growth factor activity; IBA:GO_Central.
DR GO; GO:0005131; F:growth hormone receptor binding; IBA:GO_Central.
DR GO; GO:0005179; F:hormone activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0048513; P:animal organ development; IBA:GO_Central.
DR GO; GO:0060396; P:growth hormone receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0045927; P:positive regulation of growth; IBA:GO_Central.
DR GO; GO:0046427; P:positive regulation of receptor signaling pathway via JAK-STAT; IBA:GO_Central.
DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; IBA:GO_Central.
DR GO; GO:0031667; P:response to nutrient levels; IBA:GO_Central.
DR Gene3D; 1.20.1250.10; -; 1.
DR InterPro; IPR009079; 4_helix_cytokine-like_core.
DR InterPro; IPR001400; Somatotropin/Prolactin.
DR InterPro; IPR018116; Somatotropin_CS.
DR PANTHER; PTHR11417; PTHR11417; 1.
DR Pfam; PF00103; Hormone_1; 1.
DR PRINTS; PR00836; SOMATOTROPIN.
DR SUPFAM; SSF47266; SSF47266; 1.
DR PROSITE; PS00266; SOMATOTROPIN_1; 1.
DR PROSITE; PS00338; SOMATOTROPIN_2; 1.
PE 1: Evidence at protein level;
KW Alternative promoter usage; Direct protein sequencing; Disulfide bond;
KW Hormone; Metal-binding; Reference proteome; Secreted; Signal; Zinc.
FT SIGNAL 1..26
FT /evidence="ECO:0000269|PubMed:4712450,
FT ECO:0000269|PubMed:5286363"
FT CHAIN 27..217
FT /note="Chorionic somatomammotropin hormone 2"
FT /id="PRO_0000429797"
FT BINDING 44
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT BINDING 200
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT DISULFID 79..191
FT /evidence="ECO:0000269|PubMed:16546209"
FT DISULFID 208..215
FT /note="In monomeric form"
FT /evidence="ECO:0000269|PubMed:16546209"
FT DISULFID 208
FT /note="Interchain (with C-215); in dimeric form"
FT /evidence="ECO:0000269|PubMed:16546209"
FT DISULFID 215
FT /note="Interchain (with C-208); in dimeric form"
FT /evidence="ECO:0000269|PubMed:16546209"
FT VAR_SEQ 58..152
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_055244"
FT VAR_SEQ 153..217
FT /note="RLEDGSRRTGQILKQTYSKFDTNSHNHDALLKNYGLLYCFRKDMDKVETFLR
FT MVQCRSVEGSCGF -> VRVAPGVANPGTPLA (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_055245"
FT VARIANT 104..105
FT /note="IS -> L"
FT /id="VAR_007167"
FT CONFLICT 84
FT /note="I -> T (in Ref. 10; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 95
FT /note="Missing (in Ref. 10; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 116
FT /note="Missing (in Ref. 10; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 134..136
FT /note="SDD -> BBS (in Ref. 10; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 217 AA; 24994 MW; 39FAACDDB6B2E951 CRC64;
MAAGSRTSLL LAFALLCLPW LQEAGAVQTV PLSRLFDHAM LQAHRAHQLA IDTYQEFEET
YIPKDQKYSF LHDSQTSFCF SDSIPTPSNM EETQQKSNLE LLRISLLLIE SWLEPVRFLR
SMFANNLVYD TSDSDDYHLL KDLEEGIQTL MGRLEDGSRR TGQILKQTYS KFDTNSHNHD
ALLKNYGLLY CFRKDMDKVE TFLRMVQCRS VEGSCGF
