ID   DLK1_MOUSE              Reviewed;         385 AA.
AC   Q09163; Q07645; Q62208;
DT   01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1995, sequence version 1.
DT   27-MAR-2024, entry version 185.
DE   RecName: Full=Protein delta homolog 1;
DE            Short=DLK-1;
DE   AltName: Full=Adipocyte differentiation inhibitor protein;
DE   AltName: Full=Preadipocyte factor 1;
DE            Short=Pref-1;
DE   Contains:
DE     RecName: Full=Fetal antigen 1;
DE              Short=FA1;
DE   Flags: Precursor;
GN   Name=Dlk1; Synonyms=Dlk, Pref1, Scp-1;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RC   STRAIN=SWR/J; TISSUE=Fibroblast;
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], AND FUNCTION.
RX   PubMed=8500166; DOI=10.1016/0092-8674(93)90252-l;
RA   Smas C.M., Sul H.S.;
RT   "Pref-1, a protein containing EGF-like repeats, inhibits adipocyte
RT   differentiation.";
RL   Cell 73:725-734(1993).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT LYS-347 DEL.
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   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RA   Maruyama K., Nishijima S., Kuromitsu S., Ichikawa A., Masuda E.,
RA   Takemoto T., Kodama H., Kawashima H.;
RL   Submitted (AUG-1993) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-8, AND ALTERNATIVE SPLICING.
RX   PubMed=7519443; DOI=10.1021/bi00197a029;
RA   Smas C.M., Green D., Sul H.S.;
RT   "Structural characterization and alternate splicing of the gene encoding
RT   the preadipocyte EGF-like protein pref-1.";
RL   Biochemistry 33:9257-9265(1994).
RN   [6]
RP   GLYCOSYLATION AT SER-94; ASN-100; ASN-165; ASN-174; SER-216; THR-224;
RP   THR-258; THR-267 AND THR-271, AND STRUCTURE OF CARBOHYDRATE.
RX   PubMed=9118998; DOI=10.1111/j.1432-1033.1997.00334.x;
RA   Krogh T.N., Bachmann E., Teisner B., Skjoedt K., Hoejrup P.;
RT   "Glycosylation analysis and protein structure determination of murine fetal
RT   antigen 1 (mFA1) -- the circulating gene product of the delta-like protein
RT   (dlk), preadipocyte factor 1 (Pref-1) and stromal-cell-derived protein 1
RT   (SCP-1) cDNAs.";
RL   Eur. J. Biochem. 244:334-342(1997).
RN   [7]
RP   TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX   PubMed=17320102; DOI=10.1016/j.jmb.2006.10.020;
RA   Nueda M.L., Baladron V., Garcia-Ramirez J.J., Sanchez-Solana B.,
RA   Ruvira M.D., Rivero S., Ballesteros M.A., Monsalve E.M., Diaz-Guerra M.J.,
RA   Ruiz-Hidalgo M.J., Laborda J.;
RT   "The novel gene EGFL9/Dlk2, highly homologous to Dlk1, functions as a
RT   modulator of adipogenesis.";
RL   J. Mol. Biol. 367:1270-1280(2007).
CC   -!- FUNCTION: May have a role in neuroendocrine differentiation. Inhibits
CC       adipocyte differentiation. {ECO:0000269|PubMed:8095043,
CC       ECO:0000269|PubMed:8500166}.
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=6;
CC         Comment=Additional isoforms seem to exist.;
CC       Name=A;
CC         IsoId=Q09163-1; Sequence=Displayed;
CC       Name=B;
CC         IsoId=Q09163-2; Sequence=VSP_001380;
CC       Name=C;
CC         IsoId=Q09163-3; Sequence=VSP_001381;
CC       Name=C2;
CC         IsoId=Q09163-4; Sequence=VSP_001382;
CC       Name=D;
CC         IsoId=Q09163-5; Sequence=VSP_001378;
CC       Name=D2;
CC         IsoId=Q09163-6; Sequence=VSP_001379;
CC   -!- TISSUE SPECIFICITY: Highly expressed in fetal liver, placenta, adult
CC       adrenal gland, brain, testis and ovary and, to a lesser degree, in
CC       adult kidney, muscle, thymus and heart. {ECO:0000269|PubMed:17320102}.
CC   -!- DEVELOPMENTAL STAGE: Expression is elevated in liver after birth but
CC       starts to decline around postnatal day 16.
CC       {ECO:0000269|PubMed:17320102}.
CC   -!- PTM: N- and O-glycosylated. {ECO:0000269|PubMed:9118998}.
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DR   EMBL; Z12171; CAA78162.1; -; mRNA.
DR   EMBL; U15980; AAB60495.1; -; mRNA.
DR   EMBL; L12721; AAA37175.1; -; mRNA.
DR   EMBL; S71340; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; D16847; BAA04121.1; -; mRNA.
DR   CCDS; CCDS26168.1; -. [Q09163-1]
DR   CCDS; CCDS49173.1; -. [Q09163-6]
DR   CCDS; CCDS49174.1; -. [Q09163-2]
DR   CCDS; CCDS56863.1; -. [Q09163-3]
DR   PIR; A54785; A54785.
DR   PIR; S53718; S53718.
DR   RefSeq; NP_034182.2; NM_010052.5.
DR   AlphaFoldDB; Q09163; -.
DR   SMR; Q09163; -.
DR   BioGRID; 199231; 4.
DR   DIP; DIP-6010N; -.
DR   IntAct; Q09163; 1.
DR   STRING; 10090.ENSMUSP00000063104; -.
DR   GlyConnect; 153; 9 N-Linked glycans (1 site), 1 O-Fuc glycan (1 site), 1 O-Glc glycan (2 sites), 2 O-Linked glycans.
DR   GlyCosmos; Q09163; 10 sites, 24 glycans.
DR   GlyGen; Q09163; 11 sites, 18 N-linked glycans (3 sites), 6 O-linked glycans (7 sites).
DR   iPTMnet; Q09163; -.
DR   PhosphoSitePlus; Q09163; -.
DR   jPOST; Q09163; -.
DR   PaxDb; 10090-ENSMUSP00000105470; -.
DR   ProteomicsDB; 279427; -. [Q09163-1]
DR   ProteomicsDB; 279428; -. [Q09163-2]
DR   ProteomicsDB; 279429; -. [Q09163-3]
DR   ProteomicsDB; 279430; -. [Q09163-4]
DR   ProteomicsDB; 279431; -. [Q09163-5]
DR   ProteomicsDB; 279432; -. [Q09163-6]
DR   Pumba; Q09163; -.
DR   DNASU; 13386; -.
DR   GeneID; 13386; -.
DR   KEGG; mmu:13386; -.
DR   AGR; MGI:94900; -.
DR   CTD; 8788; -.
DR   MGI; MGI:94900; Dlk1.
DR   eggNOG; KOG1217; Eukaryota.
DR   InParanoid; Q09163; -.
DR   OrthoDB; 5475408at2759; -.
DR   PhylomeDB; Q09163; -.
DR   BioGRID-ORCS; 13386; 1 hit in 78 CRISPR screens.
DR   ChiTaRS; Dlk1; mouse.
DR   PRO; PR:Q09163; -.
DR   Proteomes; UP000000589; Unplaced.
DR   RNAct; Q09163; Protein.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0009897; C:external side of plasma membrane; IDA:MGI.
DR   GO; GO:0005615; C:extracellular space; ISO:MGI.
DR   GO; GO:0016020; C:membrane; IBA:GO_Central.
DR   GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR   GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR   GO; GO:0030282; P:bone mineralization; IMP:MGI.
DR   GO; GO:0030154; P:cell differentiation; ISO:MGI.
DR   GO; GO:0048706; P:embryonic skeletal system development; IDA:MGI.
DR   GO; GO:0035264; P:multicellular organism growth; IMP:MGI.
DR   GO; GO:0045599; P:negative regulation of fat cell differentiation; IDA:HGNC.
DR   GO; GO:0045746; P:negative regulation of Notch signaling pathway; IGI:MGI.
DR   GO; GO:0030279; P:negative regulation of ossification; ISO:MGI.
DR   GO; GO:0045668; P:negative regulation of osteoblast differentiation; ISO:MGI.
DR   GO; GO:1905563; P:negative regulation of vascular endothelial cell proliferation; IDA:BHF-UCL.
DR   GO; GO:0001503; P:ossification; IMP:MGI.
DR   GO; GO:0001649; P:osteoblast differentiation; IMP:MGI.
DR   GO; GO:0045780; P:positive regulation of bone resorption; IMP:MGI.
DR   GO; GO:0001819; P:positive regulation of cytokine production; IDA:MGI.
DR   GO; GO:0045672; P:positive regulation of osteoclast differentiation; ISO:MGI.
DR   GO; GO:0009791; P:post-embryonic development; IDA:MGI.
DR   GO; GO:0046850; P:regulation of bone remodeling; ISO:MGI.
DR   GO; GO:0010468; P:regulation of gene expression; IMP:MGI.
DR   CDD; cd00054; EGF_CA; 4.
DR   Gene3D; 2.10.25.10; Laminin; 6.
DR   InterPro; IPR001881; EGF-like_Ca-bd_dom.
DR   InterPro; IPR000742; EGF-like_dom.
DR   InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site.
DR   PANTHER; PTHR24052; DELTA-RELATED; 1.
DR   PANTHER; PTHR24052:SF8; NIMROD A, ISOFORM E; 1.
DR   Pfam; PF21700; DL-JAG_EGF-like; 1.
DR   Pfam; PF00008; EGF; 4.
DR   PRINTS; PR00010; EGFBLOOD.
DR   SMART; SM00181; EGF; 6.
DR   SMART; SM00179; EGF_CA; 4.
DR   SUPFAM; SSF57196; EGF/Laminin; 4.
DR   PROSITE; PS00010; ASX_HYDROXYL; 1.
DR   PROSITE; PS00022; EGF_1; 5.
DR   PROSITE; PS01186; EGF_2; 6.
DR   PROSITE; PS50026; EGF_3; 6.
PE   1: Evidence at protein level;
KW   Alternative splicing; Cytoplasm; Disulfide bond; EGF-like domain;
KW   Glycoprotein; Membrane; Reference proteome; Repeat; Signal; Transmembrane;
KW   Transmembrane helix.
FT   SIGNAL          1..23
FT                   /evidence="ECO:0000255"
FT   CHAIN           24..385
FT                   /note="Protein delta homolog 1"
FT                   /id="PRO_0000007520"
FT   CHAIN           24..305
FT                   /note="Fetal antigen 1"
FT                   /id="PRO_0000007521"
FT   TOPO_DOM        24..305
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        306..329
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        330..385
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          172..208
FT                   /note="EGF-like 5"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DOMAIN          210..247
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:9118998"
FT                   /id="CAR_000160"
FT   CARBOHYD        100
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:9118998"
FT                   /id="CAR_000183"
FT   CARBOHYD        165
FT                   /note="N-linked (GlcNAc...) asparagine; atypical; partial"
FT                   /evidence="ECO:0000269|PubMed:9118998"
FT   CARBOHYD        174
FT                   /note="N-linked (GlcNAc...) asparagine; atypical"
FT                   /evidence="ECO:0000269|PubMed:9118998"
FT   CARBOHYD        216
FT                   /note="O-linked (GalNAc...) serine"
FT                   /evidence="ECO:0000269|PubMed:9118998"
FT                   /id="CAR_000161"
FT   CARBOHYD        224
FT                   /note="O-linked (GalNAc...) threonine"
FT                   /evidence="ECO:0000269|PubMed:9118998"
FT                   /id="CAR_000162"
FT   CARBOHYD        258
FT                   /note="O-linked (GalNAc...) threonine"
FT                   /evidence="ECO:0000269|PubMed:9118998"
FT   CARBOHYD        267
FT                   /note="O-linked (GalNAc...) threonine; partial"
FT                   /evidence="ECO:0000269|PubMed:9118998"
FT   CARBOHYD        271
FT                   /note="O-linked (GalNAc...) threonine"
FT                   /evidence="ECO:0000269|PubMed:9118998"
FT   CARBOHYD        295
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
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        176..187
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        181..196
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        198..207
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        214..225
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        219..235
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        237..246
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   VAR_SEQ         211..305
FT                   /note="Missing (in isoform D2)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_001379"
FT   VAR_SEQ         211..303
FT                   /note="Missing (in isoform D)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_001378"
FT   VAR_SEQ         231..305
FT                   /note="Missing (in isoform C2)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_001382"
FT   VAR_SEQ         231..303
FT                   /note="Missing (in isoform C)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_001381"
FT   VAR_SEQ         231..281
FT                   /note="Missing (in isoform B)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_001380"
FT   VARIANT         347
FT                   /note="Missing"
FT                   /evidence="ECO:0000269|PubMed:7711066"
FT   CONFLICT        250
FT                   /note="R -> P (in Ref. 2; AAA37175)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        320..385
FT                   /note="VLGTVAIVFLNKCETWVSNLRYNHTFRKKKNLLLQYNSGEELAVNIIFPEKI
FT                   DMTTFNKEAGDEEI -> CWAPWPSSFSTSAKPGCPTCATTTCFARRRTSCCSITAARS
FT                   WRSISSSPRRLT (in Ref. 2; AAA37175)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        344..345
FT                   /note="TF -> ML (in Ref. 4; BAA04121)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   385 AA;  41320 MW;  E79864FEA5AF4FF1 CRC64;
     MIATGALLRV LLLLLAFGHS TYGAECDPPC DPQYGFCEAD NVCRCHVGWE GPLCDKCVTA
     PGCVNGVCKE PWQCICKDGW DGKFCEIDVR ACTSTPCANN GTCVDLEKGQ YECSCTPGFS
     GKDCQHKAGP CVINGSPCQH GGACVDDEGQ ASHASCLCPP GFSGNFCEIV AATNSCTPNP
     CENDGVCTDI GGDFRCRCPA GFVDKTCSRP VSNCASGPCQ NGGTCLQHTQ VSFECLCKPP
     FMGPTCAKKR GASPVQVTHL PSGYGLTYRL TPGVHELPVQ QPEQHILKVS MKELNKSTPL
     LTEGQAICFT ILGVLTSLVV LGTVAIVFLN KCETWVSNLR YNHTFRKKKN LLLQYNSGEE
     LAVNIIFPEK IDMTTFNKEA GDEEI
//