GDF1_HUMAN
ID GDF1_HUMAN Reviewed; 372 AA.
AC P27539; O43344;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 2.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=Embryonic growth/differentiation factor 1;
DE Short=GDF-1;
DE Flags: Precursor;
GN Name=GDF1;
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], AND VARIANT VAL-118.
RX PubMed=2034669; DOI=10.1073/pnas.88.10.4250;
RA Lee S.-J.;
RT "Expression of growth/differentiation factor 1 in the nervous system:
RT conservation of a bicistronic structure.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:4250-4254(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [3]
RP INVOLVEMENT IN RAI, AND VARIANT RAI 227-CYS--ARG-372 DEL.
RX PubMed=20413652; DOI=10.1093/hmg/ddq164;
RA Kaasinen E., Aittomaki K., Eronen M., Vahteristo P., Karhu A.,
RA Mecklin J.P., Kajantie E., Aaltonen L.A., Lehtonen R.;
RT "Recessively inherited right atrial isomerism caused by mutations in
RT growth/differentiation factor 1 (GDF1).";
RL Hum. Mol. Genet. 19:2747-2753(2010).
RN [4]
RP INVOLVEMENT IN CHTD6, VARIANTS CHTD6 227-CYS--ARG-372 DEL AND THR-318,
RP VARIANTS TOF ASP-162; PRO-309 AND THR-312, VARIANT CTHM TYR-267, AND
RP VARIANTS HIS-68 AND SER-262.
RX PubMed=17924340; DOI=10.1086/522890;
RA Karkera J.D., Lee J.S., Roessler E., Banerjee-Basu S., Ouspenskaia M.V.,
RA Mez J., Goldmuntz E., Bowers P., Towbin J., Belmont J.W., Baxevanis A.D.,
RA Schier A.F., Muenke M.;
RT "Loss-of-function mutations in growth differentiation factor-1 (GDF1) are
RT associated with congenital heart defects in humans.";
RL Am. J. Hum. Genet. 81:987-994(2007).
RN [5]
RP INVOLVEMENT IN CHTD6, VARIANT CHTD6 THR-364, AND VARIANTS RAI
RP 227-CYS--ARG-372 DEL AND MET-364 DEL.
RX PubMed=28991257; DOI=10.1038/ng.3970;
RA Jin S.C., Homsy J., Zaidi S., Lu Q., Morton S., DePalma S.R., Zeng X.,
RA Qi H., Chang W., Sierant M.C., Hung W.C., Haider S., Zhang J., Knight J.,
RA Bjornson R.D., Castaldi C., Tikhonoa I.R., Bilguvar K., Mane S.M.,
RA Sanders S.J., Mital S., Russell M.W., Gaynor J.W., Deanfield J.,
RA Giardini A., Porter G.A. Jr., Srivastava D., Lo C.W., Shen Y.,
RA Watkins W.S., Yandell M., Yost H.J., Tristani-Firouzi M., Newburger J.W.,
RA Roberts A.E., Kim R., Zhao H., Kaltman J.R., Goldmuntz E., Chung W.K.,
RA Seidman J.G., Gelb B.D., Seidman C.E., Lifton R.P., Brueckner M.;
RT "Contribution of rare inherited and de novo variants in 2,871 congenital
RT heart disease probands.";
RL Nat. Genet. 49:1593-1601(2017).
CC -!- FUNCTION: May mediate cell differentiation events during embryonic
CC development.
CC -!- SUBUNIT: Homodimer; disulfide-linked. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Expressed in the brain.
CC -!- DISEASE: Conotruncal heart malformations (CTHM) [MIM:217095]: A group
CC of congenital heart defects involving the outflow tracts. Examples
CC include truncus arteriosus communis, double-outlet right ventricle and
CC transposition of great arteries. Truncus arteriosus communis is
CC characterized by a single outflow tract instead of a separate aorta and
CC pulmonary artery. In transposition of the great arteries, the aorta
CC arises from the right ventricle and the pulmonary artery from the left
CC ventricle. In double outlet of the right ventricle, both the pulmonary
CC artery and aorta arise from the right ventricle.
CC {ECO:0000269|PubMed:17924340}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Congenital heart defects, multiple types, 6 (CHTD6)
CC [MIM:613854]: An autosomal dominant disorder characterized by
CC congenital developmental abnormalities involving structures of the
CC heart. Common defects include tetralogy of Fallot, transposition of the
CC great arteries, double-outlet right ventricle, total anomalous
CC pulmonary venous return, pulmonary stenosis or atresia,
CC atrioventricular canal, ventricular septal defect, and hypoplastic left
CC or right ventricle. {ECO:0000269|PubMed:17924340,
CC ECO:0000269|PubMed:28991257}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Tetralogy of Fallot (TOF) [MIM:187500]: A congenital heart
CC anomaly which consists of pulmonary stenosis, ventricular septal
CC defect, dextroposition of the aorta (aorta is on the right side instead
CC of the left) and hypertrophy of the right ventricle. In this condition,
CC blood from both ventricles (oxygen-rich and oxygen-poor) is pumped into
CC the body often causing cyanosis. {ECO:0000269|PubMed:17924340}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- DISEASE: Right atrial isomerism (RAI) [MIM:208530]: A severe complex
CC congenital heart defect resulting from embryonic disruption of proper
CC left-right axis determination. RAI is usually characterized by complete
CC atrioventricular septal defect with a common atrium and univentricular
CC AV connection, total anomalous pulmonary drainage, and transposition or
CC malposition of the great arteries. Affected individuals present at
CC birth with severe cardiac failure. Other associated abnormalities
CC include bilateral trilobed lungs, midline liver, and asplenia, as well
CC as situs inversus affecting other organs. {ECO:0000269|PubMed:20413652,
CC ECO:0000269|PubMed:28991257}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: This protein is produced by a bicistronic gene which
CC also produces the CERS1 protein from a non-overlapping reading frame.
CC -!- SIMILARITY: Belongs to the TGF-beta family. {ECO:0000305}.
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DR EMBL; M62302; AAA58501.1; -; mRNA.
DR EMBL; AC003972; AAB94786.1; -; Genomic_DNA.
DR CCDS; CCDS42526.1; -.
DR PIR; C39364; C39364.
DR RefSeq; NP_001483.3; NM_001492.5.
DR AlphaFoldDB; P27539; -.
DR SMR; P27539; -.
DR BioGRID; 108927; 1.
DR IntAct; P27539; 1.
DR MINT; P27539; -.
DR STRING; 9606.ENSP00000247005; -.
DR GlyGen; P27539; 1 site.
DR iPTMnet; P27539; -.
DR PhosphoSitePlus; P27539; -.
DR BioMuta; GDF1; -.
DR DMDM; 116242492; -.
DR EPD; P27539; -.
DR PaxDb; P27539; -.
DR PeptideAtlas; P27539; -.
DR PRIDE; P27539; -.
DR Antibodypedia; 28214; 116 antibodies from 24 providers.
DR DNASU; 2657; -.
DR Ensembl; ENST00000247005.8; ENSP00000247005.5; ENSG00000130283.9.
DR GeneID; 2657; -.
DR KEGG; hsa:2657; -.
DR MANE-Select; ENST00000247005.8; ENSP00000247005.5; NM_001492.6; NP_001483.3.
DR UCSC; uc060vuk.1; human.
DR CTD; 2657; -.
DR DisGeNET; 2657; -.
DR GeneCards; GDF1; -.
DR HGNC; HGNC:4214; GDF1.
DR HPA; ENSG00000130283; Group enriched (brain, pituitary gland, skeletal muscle, testis).
DR MalaCards; GDF1; -.
DR MIM; 187500; phenotype.
DR MIM; 208530; phenotype.
DR MIM; 217095; phenotype.
DR MIM; 602880; gene.
DR MIM; 613854; phenotype.
DR neXtProt; NX_P27539; -.
DR OpenTargets; ENSG00000130283; -.
DR Orphanet; 216718; Isolated congenitally uncorrected transposition of the great arteries.
DR Orphanet; 97548; Right sided atrial isomerism.
DR Orphanet; 3303; Tetralogy of Fallot.
DR PharmGKB; PA28629; -.
DR VEuPathDB; HostDB:ENSG00000130283; -.
DR eggNOG; KOG3900; Eukaryota.
DR GeneTree; ENSGT00940000162926; -.
DR HOGENOM; CLU_020515_4_0_1; -.
DR InParanoid; P27539; -.
DR OMA; LMWRLFR; -.
DR OrthoDB; 1106226at2759; -.
DR PhylomeDB; P27539; -.
DR TreeFam; TF351789; -.
DR PathwayCommons; P27539; -.
DR Reactome; R-HSA-1181150; Signaling by NODAL.
DR SignaLink; P27539; -.
DR BioGRID-ORCS; 2657; 17 hits in 1042 CRISPR screens.
DR GeneWiki; GDF1; -.
DR GenomeRNAi; 2657; -.
DR Pharos; P27539; Tbio.
DR PRO; PR:P27539; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; P27539; protein.
DR Bgee; ENSG00000130283; Expressed in primary visual cortex and 31 other tissues.
DR ExpressionAtlas; P27539; baseline.
DR Genevisible; P27539; HS.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0005125; F:cytokine activity; IBA:GO_Central.
DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR GO; GO:0030509; P:BMP signaling pathway; IBA:GO_Central.
DR GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; IBA:GO_Central.
DR GO; GO:0060395; P:SMAD protein signal transduction; IBA:GO_Central.
DR Gene3D; 2.10.90.10; -; 1.
DR InterPro; IPR029034; Cystine-knot_cytokine.
DR InterPro; IPR001839; TGF-b_C.
DR InterPro; IPR015615; TGF-beta-rel.
DR InterPro; IPR017948; TGFb_CS.
DR PANTHER; PTHR11848; PTHR11848; 1.
DR Pfam; PF00019; TGF_beta; 1.
DR SMART; SM00204; TGFB; 1.
DR SUPFAM; SSF57501; SSF57501; 1.
DR PROSITE; PS00250; TGF_BETA_1; 1.
DR PROSITE; PS51362; TGF_BETA_2; 1.
PE 1: Evidence at protein level;
KW Cleavage on pair of basic residues; Cytokine; Disease variant;
KW Disulfide bond; Glycoprotein; Growth factor; Reference proteome; Secreted;
KW Signal.
FT SIGNAL 1..29
FT /evidence="ECO:0000255"
FT PROPEP 30..253
FT /evidence="ECO:0000255"
FT /id="PRO_0000033898"
FT CHAIN 254..372
FT /note="Embryonic growth/differentiation factor 1"
FT /id="PRO_0000033899"
FT REGION 67..86
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 206
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 267..337
FT /evidence="ECO:0000250"
FT DISULFID 296..369
FT /evidence="ECO:0000250"
FT DISULFID 300..371
FT /evidence="ECO:0000250"
FT DISULFID 336
FT /note="Interchain"
FT /evidence="ECO:0000250"
FT VARIANT 68
FT /note="R -> H (found in a patient with atrioventricular
FT canal-cleft mitral valve; unknown pathological
FT significance; dbSNP:rs763822282)"
FT /evidence="ECO:0000269|PubMed:17924340"
FT /id="VAR_065332"
FT VARIANT 118
FT /note="A -> V (in dbSNP:rs4808863)"
FT /evidence="ECO:0000269|PubMed:2034669"
FT /id="VAR_028274"
FT VARIANT 162
FT /note="G -> D (in TOF; dbSNP:rs121434424)"
FT /evidence="ECO:0000269|PubMed:17924340"
FT /id="VAR_065333"
FT VARIANT 227..372
FT /note="Missing (in CHTD6 and RAI)"
FT /evidence="ECO:0000269|PubMed:17924340,
FT ECO:0000269|PubMed:20413652, ECO:0000269|PubMed:28991257"
FT /id="VAR_080779"
FT VARIANT 262
FT /note="G -> S (in a patient with Rastelli type
FT atrioventricular canal)"
FT /evidence="ECO:0000269|PubMed:17924340"
FT /id="VAR_065334"
FT VARIANT 267
FT /note="C -> Y (in CTHM; double-outlet right ventricle;
FT dbSNP:rs121434423)"
FT /evidence="ECO:0000269|PubMed:17924340"
FT /id="VAR_065335"
FT VARIANT 309
FT /note="S -> P (in TOF; dbSNP:rs864622513)"
FT /evidence="ECO:0000269|PubMed:17924340"
FT /id="VAR_065336"
FT VARIANT 312
FT /note="P -> T (in TOF)"
FT /evidence="ECO:0000269|PubMed:17924340"
FT /id="VAR_065337"
FT VARIANT 318
FT /note="A -> T (in CHTD6; dbSNP:rs1064793138)"
FT /evidence="ECO:0000269|PubMed:17924340"
FT /id="VAR_065338"
FT VARIANT 364
FT /note="M -> T (in CHTD6; dbSNP:rs374016704)"
FT /evidence="ECO:0000269|PubMed:28991257"
FT /id="VAR_080780"
FT VARIANT 364
FT /note="Missing (in RAI; dbSNP:rs753643819)"
FT /evidence="ECO:0000269|PubMed:28991257"
FT /id="VAR_080781"
SQ SEQUENCE 372 AA; 39475 MW; 10A4893F063047B9 CRC64;
MPPPQQGPCG HHLLLLLALL LPSLPLTRAP VPPGPAAALL QALGLRDEPQ GAPRLRPVPP
VMWRLFRRRD PQETRSGSRR TSPGVTLQPC HVEELGVAGN IVRHIPDRGA PTRASEPASA
AGHCPEWTVV FDLSAVEPAE RPSRARLELR FAAAAAAAPE GGWELSVAQA GQGAGADPGP
VLLRQLVPAL GPPVRAELLG AAWARNASWP RSLRLALALR PRAPAACARL AEASLLLVTL
DPRLCHPLAR PRRDAEPVLG GGPGGACRAR RLYVSFREVG WHRWVIAPRG FLANYCQGQC
ALPVALSGSG GPPALNHAVL RALMHAAAPG AADLPCCVPA RLSPISVLFF DNSDNVVLRQ
YEDMVVDECG CR
