GenomeNet

Database: UniProt
Entry: P80370
LinkDB: P80370
Original site: P80370 
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   12-AUG-2020, entry version 201.
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;
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   -!- 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};
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   SMR; P80370; -.
DR   BioGRID; 114316; 72.
DR   IntAct; P80370; 41.
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, 1 O-linked glycan (2 sites).
DR   iPTMnet; P80370; -.
DR   PhosphoSitePlus; P80370; -.
DR   UniCarbKB; 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; 599 antibodies.
DR   DNASU; 8788; -.
DR   Ensembl; ENST00000331224; ENSP00000331081; ENSG00000185559. [P80370-2]
DR   Ensembl; ENST00000341267; ENSP00000340292; ENSG00000185559. [P80370-1]
DR   GeneID; 8788; -.
DR   KEGG; hsa:8788; -.
DR   UCSC; uc001yhs.5; human. [P80370-1]
DR   CTD; 8788; -.
DR   DisGeNET; 8788; -.
DR   EuPathDB; HostDB:ENSG00000185559.13; -.
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   eggNOG; KOG1217; Eukaryota.
DR   GeneTree; ENSGT00940000154225; -.
DR   HOGENOM; CLU_039179_0_1_1; -.
DR   InParanoid; P80370; -.
DR   OMA; NFCEIDR; -.
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; 7 hits in 873 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 metanephros and 171 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; IPR013032; EGF-like_CS.
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; Polymorphism; Reference proteome;
KW   Repeat; 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
//
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