DLK2_HUMAN
ID DLK2_HUMAN Reviewed; 383 AA.
AC Q6UY11; B3KNZ7; Q5T3T8; Q9BQ54;
DT 25-OCT-2004, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Protein delta homolog 2;
DE Short=DLK-2;
DE AltName: Full=Epidermal growth factor-like protein 9;
DE Short=EGF-like protein 9;
DE Flags: Precursor;
GN Name=DLK2; Synonyms=EGFL9; ORFNames=UNQ2903/PRO28633;
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 [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Eye;
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).
CC -!- FUNCTION: Regulates adipogenesis. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass type I
CC membrane protein {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6UY11-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6UY11-2; Sequence=VSP_011767;
CC -!- MISCELLANEOUS: [Isoform 2]: Splicing acceptor site not canonical.
CC {ECO:0000305}.
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DR EMBL; AY358126; AAQ88493.1; -; mRNA.
DR EMBL; AK055380; BAG51509.1; -; mRNA.
DR EMBL; AL359813; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471081; EAX04186.1; -; Genomic_DNA.
DR EMBL; BC000230; AAH00230.1; -; mRNA.
DR EMBL; BC006425; AAH06425.1; -; mRNA.
DR EMBL; BC110320; AAI10321.1; -; mRNA.
DR CCDS; CCDS4897.1; -. [Q6UY11-1]
DR RefSeq; NP_001273584.1; NM_001286655.1.
DR RefSeq; NP_001273585.1; NM_001286656.1.
DR RefSeq; NP_076421.2; NM_023932.3. [Q6UY11-1]
DR RefSeq; NP_996262.1; NM_206539.2. [Q6UY11-1]
DR AlphaFoldDB; Q6UY11; -.
DR SMR; Q6UY11; -.
DR BioGRID; 122438; 35.
DR IntAct; Q6UY11; 31.
DR MINT; Q6UY11; -.
DR STRING; 9606.ENSP00000349893; -.
DR GlyGen; Q6UY11; 1 site.
DR PhosphoSitePlus; Q6UY11; -.
DR BioMuta; DLK2; -.
DR DMDM; 55976806; -.
DR EPD; Q6UY11; -.
DR jPOST; Q6UY11; -.
DR MassIVE; Q6UY11; -.
DR PaxDb; Q6UY11; -.
DR PeptideAtlas; Q6UY11; -.
DR PRIDE; Q6UY11; -.
DR ProteomicsDB; 67690; -. [Q6UY11-1]
DR Antibodypedia; 30417; 122 antibodies from 24 providers.
DR DNASU; 65989; -.
DR Ensembl; ENST00000357338.3; ENSP00000349893.3; ENSG00000171462.15. [Q6UY11-1]
DR Ensembl; ENST00000372488.8; ENSP00000361566.3; ENSG00000171462.15. [Q6UY11-1]
DR GeneID; 65989; -.
DR KEGG; hsa:65989; -.
DR MANE-Select; ENST00000372488.8; ENSP00000361566.3; NM_023932.4; NP_076421.2.
DR UCSC; uc003ova.5; human. [Q6UY11-1]
DR CTD; 65989; -.
DR DisGeNET; 65989; -.
DR GeneCards; DLK2; -.
DR HGNC; HGNC:21113; DLK2.
DR HPA; ENSG00000171462; Tissue enhanced (esophagus, prostate, skin).
DR neXtProt; NX_Q6UY11; -.
DR OpenTargets; ENSG00000171462; -.
DR PharmGKB; PA162383762; -.
DR VEuPathDB; HostDB:ENSG00000171462; -.
DR eggNOG; KOG1217; Eukaryota.
DR GeneTree; ENSGT00940000160761; -.
DR InParanoid; Q6UY11; -.
DR OMA; QECQVGM; -.
DR OrthoDB; 880666at2759; -.
DR PhylomeDB; Q6UY11; -.
DR TreeFam; TF351835; -.
DR PathwayCommons; Q6UY11; -.
DR SignaLink; Q6UY11; -.
DR SIGNOR; Q6UY11; -.
DR BioGRID-ORCS; 65989; 8 hits in 1068 CRISPR screens.
DR GenomeRNAi; 65989; -.
DR Pharos; Q6UY11; Tbio.
DR PRO; PR:Q6UY11; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q6UY11; protein.
DR Bgee; ENSG00000171462; Expressed in lower esophagus mucosa and 124 other tissues.
DR ExpressionAtlas; Q6UY11; baseline and differential.
DR Genevisible; Q6UY11; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0005112; F:Notch binding; IBA:GO_Central.
DR GO; GO:0045746; P:negative regulation of Notch signaling pathway; IDA:HGNC.
DR GO; GO:0045598; P:regulation of fat cell differentiation; IEA:Ensembl.
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 InterPro; IPR018097; EGF_Ca-bd_CS.
DR Pfam; PF00008; EGF; 3.
DR Pfam; PF12661; hEGF; 1.
DR SMART; SM00181; EGF; 6.
DR SMART; SM00179; EGF_CA; 4.
DR PROSITE; PS00010; ASX_HYDROXYL; 2.
DR PROSITE; PS00022; EGF_1; 6.
DR PROSITE; PS01186; EGF_2; 6.
DR PROSITE; PS50026; EGF_3; 6.
DR PROSITE; PS01187; EGF_CA; 2.
PE 2: Evidence at transcript level;
KW Alternative splicing; Calcium; Disulfide bond; EGF-like domain;
KW Glycoprotein; Membrane; Reference proteome; Repeat; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..26
FT /evidence="ECO:0000255"
FT CHAIN 27..383
FT /note="Protein delta homolog 2"
FT /id="PRO_0000007534"
FT TOPO_DOM 27..306
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 307..327
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 328..383
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 27..58
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 62..89
FT /note="EGF-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 91..129
FT /note="EGF-like 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 131..172
FT /note="EGF-like 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 174..210
FT /note="EGF-like 5; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 212..248
FT /note="EGF-like 6; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT CARBOHYD 157
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 29..40
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 33..46
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 48..57
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 66..71
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 79..88
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 95..107
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 101..117
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 119..128
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 135..148
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 142..160
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 162..171
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 178..189
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 183..198
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 200..209
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 216..227
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 221..236
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 238..247
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT VAR_SEQ 1..179
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_011767"
FT VARIANT 301
FT /note="G -> R (in dbSNP:rs35192247)"
FT /id="VAR_048977"
SQ SEQUENCE 383 AA; 40548 MW; 701AC6B043863EA7 CRC64;
MPSGCRCLHL VCLLCILGAP GQPVRADDCS SHCDLAHGCC APDGSCRCDP GWEGLHCERC
VRMPGCQHGT CHQPWQCICH SGWAGKFCDK DEHICTTQSP CQNGGQCMYD GGGEYHCVCL
PGFHGRDCER KAGPCEQAGS PCRNGGQCQD DQGFALNFTC RCLVGFVGAR CEVNVDDCLM
RPCANGATCL DGINRFSCLC PEGFAGRFCT INLDDCASRP CQRGARCRDR VHDFDCLCPS
GYGGKTCELV LPVPDPPTTV DTPLGPTSAV VVPATGPAPH SAGAGLLRIS VKEVVRRQEA
GLGEPSLVAL VVFGALTAAL VLATVLLTLR AWRRGVCPPG PCCYPAPHYA PACQDQECQV
SMLPAGLPLP RDLPPEPGKT TAL
