DLK1_HUMAN
ID DLK1_HUMAN Reviewed; 383 AA.
AC P80370; P15803; Q96DW5;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 3.
DT 03-AUG-2022, entry version 210.
DE RecName: Full=Protein delta homolog 1;
DE Short=DLK-1;
DE AltName: Full=pG2;
DE Contains:
DE RecName: Full=Fetal antigen 1;
DE Short=FA1;
DE Flags: Precursor;
GN Name=DLK1; Synonyms=DLK;
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] (ISOFORM LONG), AND VARIANTS GLY-101 AND
RP GLY-108.
RC TISSUE=Adrenal gland;
RX PubMed=8095043; DOI=10.1016/s0021-9258(18)53544-4;
RA Laborda J., Sausville E.A., Hoffman T., Notario V.;
RT "dlk, a putative mammalian homeotic gene differentially expressed in small
RT cell lung carcinoma and neuroendocrine tumor cell line.";
RL J. Biol. Chem. 268:3817-3820(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG AND SHORT), AND VARIANTS GLY-101
RP AND GLY-108.
RC TISSUE=Adrenal gland, and Placenta;
RX PubMed=7711066; DOI=10.1016/0167-4781(95)00007-4;
RA Lee Y.L., Helman L., Hoffman T., Laborda J.;
RT "dlk, pG2 and Pref-1 mRNAs encode similar proteins belonging to the EGF-
RT like superfamily. Identification of polymorphic variants of this RNA.";
RL Biochim. Biophys. Acta 1261:223-232(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG), AND VARIANT GLY-101.
RC TISSUE=Adrenal gland;
RX PubMed=2308864; DOI=10.1093/nar/18.3.685;
RA Helman L.J., Sack N., Plon S., Israel M.A.;
RT "The sequence of an adrenal specific human cDNA, pG2.";
RL Nucleic Acids Res. 18:685-685(1990).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG), AND VARIANT GLY-101.
RC TISSUE=Adrenal gland;
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 PROTEIN SEQUENCE OF 24-383, GLYCOSYLATION AT SER-94; ASN-100; THR-143;
RP SER-163; ASN-165; ASN-172; SER-214; THR-222; SER-251 AND SER-260, AND
RP VARIANT GLY-101.
RC TISSUE=Amniotic fluid;
RX PubMed=7925474; DOI=10.1111/j.1432-1033.1994.00083.x;
RA Jensen C.H., Krogh T.N., Hoejrup P., Clausen P.P., Skjoedt K.,
RA Larsson L.-I., Enghild J.J., Teisner B.;
RT "Protein structure of fetal antigen 1 (FA1). A novel circulating human
RT epidermal-growth-factor-like protein expressed in neuroendocrine tumors and
RT its relation to the gene products of dlk and pG2.";
RL Eur. J. Biochem. 225:83-92(1994).
RN [7]
RP PROTEIN SEQUENCE OF 24-60.
RC TISSUE=Amniotic fluid;
RX PubMed=8501199; DOI=10.1093/oxfordjournals.humrep.a138110;
RA Jensen C.H., Teisner B., Hoejrup P., Rasmussen H.B., Madsen O.D.,
RA Nielsen B., Skjoedt K.;
RT "Studies on the isolation, structural analysis and tissue localization of
RT fetal antigen 1 and its relation to a human adrenal-specific cDNA, pG2.";
RL Hum. Reprod. 8:635-641(1993).
RN [8]
RP PROTEIN SEQUENCE OF 24-38.
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 [9]
RP GLYCOSYLATION AT THR-256, STRUCTURE OF CARBOHYDRATES, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RX PubMed=22171320; DOI=10.1074/mcp.m111.013649;
RA Halim A., Nilsson J., Ruetschi U., Hesse C., Larson G.;
RT "Human urinary glycoproteomics; attachment site specific analysis of N- and
RT O-linked glycosylations by CID and ECD.";
RL Mol. Cell. Proteomics 11:1-17(2012).
CC -!- FUNCTION: May have a role in neuroendocrine differentiation.
CC -!- SUBUNIT: Monomer. Interacts with SH3RF2 (By similarity).
CC {ECO:0000250|UniProtKB:O70534}.
CC -!- INTERACTION:
CC P80370; P28799-2: GRN; NbExp=3; IntAct=EBI-21555397, EBI-25860013;
CC P80370; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-21555397, EBI-5235340;
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
CC Cytoplasm {ECO:0000250|UniProtKB:O70534}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Comment=Additional isoforms seem to exist.;
CC Name=Long;
CC IsoId=P80370-1; Sequence=Displayed;
CC Name=Short;
CC IsoId=P80370-2; Sequence=VSP_001377;
CC -!- TISSUE SPECIFICITY: Found within the stromal cells in close contact to
CC the vascular structure of placental villi, yolk sac, fetal liver,
CC adrenal cortex and pancreas and in the beta cells of the islets of
CC Langerhans in the adult pancreas. Found also in some forms of
CC neuroendocrine lung tumor tissue.
CC -!- PTM: N- and O-glycosylated. O-glycosylated with core 1 or possibly core
CC 8 glycans. {ECO:0000269|PubMed:22171320, ECO:0000269|PubMed:7925474}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA35582.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; Z12172; CAA78163.1; -; mRNA.
DR EMBL; U15979; AAA75364.1; -; mRNA.
DR EMBL; U15981; AAA75365.1; -; mRNA.
DR EMBL; X17544; CAA35582.1; ALT_FRAME; mRNA.
DR EMBL; AL132711; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC013197; AAH13197.1; -; mRNA.
DR CCDS; CCDS81852.1; -. [P80370-2]
DR CCDS; CCDS9963.1; -. [P80370-1]
DR PIR; S53716; S53716.
DR PIR; S71548; S71548.
DR RefSeq; NP_001304101.1; NM_001317172.1. [P80370-2]
DR RefSeq; NP_003827.3; NM_003836.6. [P80370-1]
DR AlphaFoldDB; P80370; -.
DR SMR; P80370; -.
DR BioGRID; 114316; 103.
DR IntAct; P80370; 43.
DR STRING; 9606.ENSP00000340292; -.
DR BindingDB; P80370; -.
DR ChEMBL; CHEMBL5671; -.
DR DrugCentral; P80370; -.
DR GlyConnect; 745; 1 O-Linked glycan (1 site).
DR GlyGen; P80370; 12 sites, 2 O-linked glycans (2 sites).
DR iPTMnet; P80370; -.
DR PhosphoSitePlus; P80370; -.
DR SwissPalm; P80370; -.
DR BioMuta; DLK1; -.
DR DMDM; 296439371; -.
DR MassIVE; P80370; -.
DR PaxDb; P80370; -.
DR PeptideAtlas; P80370; -.
DR PRIDE; P80370; -.
DR ProteomicsDB; 57681; -. [P80370-1]
DR ProteomicsDB; 57682; -. [P80370-2]
DR ABCD; P80370; 9 sequenced antibodies.
DR Antibodypedia; 27564; 616 antibodies from 40 providers.
DR DNASU; 8788; -.
DR Ensembl; ENST00000331224.10; ENSP00000331081.6; ENSG00000185559.16. [P80370-2]
DR Ensembl; ENST00000341267.9; ENSP00000340292.4; ENSG00000185559.16. [P80370-1]
DR GeneID; 8788; -.
DR KEGG; hsa:8788; -.
DR MANE-Select; ENST00000341267.9; ENSP00000340292.4; NM_003836.7; NP_003827.4.
DR UCSC; uc001yhs.5; human. [P80370-1]
DR CTD; 8788; -.
DR DisGeNET; 8788; -.
DR GeneCards; DLK1; -.
DR HGNC; HGNC:2907; DLK1.
DR HPA; ENSG00000185559; Group enriched (adrenal gland, pituitary gland, placenta).
DR MalaCards; DLK1; -.
DR MIM; 176290; gene.
DR neXtProt; NX_P80370; -.
DR OpenTargets; ENSG00000185559; -.
DR Orphanet; 169615; Idiopathic central precocious puberty.
DR Orphanet; 254534; Kagami-Ogata syndrome due to maternal 14q32.2 hypermethylation.
DR Orphanet; 254528; Kagami-Ogata syndrome due to maternal 14q32.2 microdeletion.
DR Orphanet; 96334; Kagami-Ogata syndrome due to paternal uniparental disomy of chromosome 14.
DR Orphanet; 96184; Temple syndrome due to maternal uniparental disomy of chromosome 14.
DR Orphanet; 254531; Temple syndrome due to paternal 14q32.2 hypomethylation.
DR Orphanet; 254525; Temple syndrome due to paternal 14q32.2 microdeletion.
DR PharmGKB; PA27363; -.
DR VEuPathDB; HostDB:ENSG00000185559; -.
DR eggNOG; KOG1217; Eukaryota.
DR GeneTree; ENSGT00940000154225; -.
DR HOGENOM; CLU_039179_0_1_1; -.
DR InParanoid; P80370; -.
DR OMA; FNRCETW; -.
DR OrthoDB; 311898at2759; -.
DR PhylomeDB; P80370; -.
DR TreeFam; TF351835; -.
DR PathwayCommons; P80370; -.
DR Reactome; R-HSA-2122948; Activated NOTCH1 Transmits Signal to the Nucleus.
DR SignaLink; P80370; -.
DR SIGNOR; P80370; -.
DR BioGRID-ORCS; 8788; 16 hits in 1080 CRISPR screens.
DR ChiTaRS; DLK1; human.
DR GeneWiki; DLK1; -.
DR GenomeRNAi; 8788; -.
DR Pharos; P80370; Tchem.
DR PRO; PR:P80370; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; P80370; protein.
DR Bgee; ENSG00000185559; Expressed in right adrenal gland cortex and 139 other tissues.
DR ExpressionAtlas; P80370; baseline and differential.
DR Genevisible; P80370; HS.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005615; C:extracellular space; IDA:HGNC.
DR GO; GO:0016021; C:integral component of membrane; TAS:ProtInc.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0030154; P:cell differentiation; IEA:Ensembl.
DR GO; GO:0045746; P:negative regulation of Notch signaling pathway; IDA:HGNC.
DR InterPro; IPR001881; EGF-like_Ca-bd_dom.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site.
DR Pfam; PF00008; EGF; 4.
DR SMART; SM00181; EGF; 6.
DR SMART; SM00179; EGF_CA; 4.
DR PROSITE; PS00010; ASX_HYDROXYL; 1.
DR PROSITE; PS00022; EGF_1; 5.
DR PROSITE; PS01186; EGF_2; 5.
DR PROSITE; PS50026; EGF_3; 5.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Direct protein sequencing; Disulfide bond;
KW EGF-like domain; Glycoprotein; Membrane; Reference proteome; Repeat;
KW Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..23
FT /evidence="ECO:0000269|PubMed:15340161,
FT ECO:0000269|PubMed:7925474, ECO:0000269|PubMed:8501199"
FT CHAIN 24..383
FT /note="Protein delta homolog 1"
FT /id="PRO_0000007518"
FT CHAIN 24..303
FT /note="Fetal antigen 1"
FT /id="PRO_0000007519"
FT TOPO_DOM 24..303
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 304..327
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 328..383
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 24..55
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 53..86
FT /note="EGF-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 88..125
FT /note="EGF-like 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 127..168
FT /note="EGF-like 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 170..206
FT /note="EGF-like 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 208..245
FT /note="EGF-like 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT CARBOHYD 94
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000269|PubMed:7925474"
FT CARBOHYD 100
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:7925474"
FT CARBOHYD 143
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000269|PubMed:7925474"
FT CARBOHYD 163
FT /note="O-linked (GalNAc...) serine; partial"
FT /evidence="ECO:0000269|PubMed:7925474"
FT CARBOHYD 165
FT /note="N-linked (GlcNAc...) asparagine; atypical; partial"
FT /evidence="ECO:0000269|PubMed:7925474"
FT CARBOHYD 172
FT /note="N-linked (GlcNAc...) asparagine; atypical; partial"
FT /evidence="ECO:0000269|PubMed:7925474"
FT CARBOHYD 214
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000269|PubMed:7925474"
FT CARBOHYD 222
FT /note="O-linked (GalNAc...) threonine; partial"
FT /evidence="ECO:0000269|PubMed:7925474"
FT CARBOHYD 251
FT /note="O-linked (GalNAc...) serine; partial"
FT /evidence="ECO:0000269|PubMed:7925474"
FT CARBOHYD 256
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000269|PubMed:22171320"
FT CARBOHYD 260
FT /note="O-linked (GalNAc...) serine; partial"
FT /evidence="ECO:0000269|PubMed:7925474"
FT DISULFID 26..37
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 30..43
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 45..54
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 57..68
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 63..74
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 76..85
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 92..103
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 97..113
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 115..124
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 131..144
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 138..156
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 158..167
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 174..185
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 179..194
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 196..205
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 212..223
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 217..233
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 235..244
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT VAR_SEQ 229..301
FT /note="Missing (in isoform Short)"
FT /evidence="ECO:0000303|PubMed:7711066"
FT /id="VSP_001377"
FT VARIANT 73
FT /note="Q -> L (in dbSNP:rs34686110)"
FT /id="VAR_055715"
FT VARIANT 101
FT /note="R -> G (in dbSNP:rs6575799)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:2308864, ECO:0000269|PubMed:7711066,
FT ECO:0000269|PubMed:7925474, ECO:0000269|PubMed:8095043"
FT /id="VAR_060335"
FT VARIANT 104
FT /note="V -> M (in dbSNP:rs2273607)"
FT /id="VAR_055716"
FT VARIANT 108
FT /note="D -> G (in dbSNP:rs1058006)"
FT /evidence="ECO:0000269|PubMed:7711066,
FT ECO:0000269|PubMed:8095043"
FT /id="VAR_060336"
FT VARIANT 260
FT /note="S -> N (in dbSNP:rs1058009)"
FT /id="VAR_055717"
FT VARIANT 347
FT /note="Missing"
FT /id="VAR_002274"
FT CONFLICT 45..47
FT /note="Missing (in Ref. 3; CAA35582)"
FT /evidence="ECO:0000305"
FT CONFLICT 46..47
FT /note="QP -> HV (in Ref. 1; CAA78163)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 383 AA; 41300 MW; 9A2813B2801A98BD CRC64;
MTATEALLRV LLLLLAFGHS TYGAECFPAC NPQNGFCEDD NVCRCQPGWQ GPLCDQCVTS
PGCLHGLCGE PGQCICTDGW DGELCDRDVR ACSSAPCANN RTCVSLDDGL YECSCAPGYS
GKDCQKKDGP CVINGSPCQH GGTCVDDEGR ASHASCLCPP GFSGNFCEIV ANSCTPNPCE
NDGVCTDIGG DFRCRCPAGF IDKTCSRPVT NCASSPCQNG GTCLQHTQVS YECLCKPEFT
GLTCVKKRAL SPQQVTRLPS GYGLAYRLTP GVHELPVQQP EHRILKVSMK ELNKKTPLLT
EGQAICFTIL GVLTSLVVLG TVGIVFLNKC ETWVSNLRYN HMLRKKKNLL LQYNSGEDLA
VNIIFPEKID MTTFSKEAGD EEI
