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Protein

Protein delta homolog 1

Gene

DLK1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

May have a role in neuroendocrine differentiation.

GO - Biological processi

  1. cell differentiation Source: Ensembl
  2. embryonic skeletal system development Source: Ensembl
  3. multicellular organismal development Source: ProtInc
  4. negative regulation of Notch signaling pathway Source: Ensembl
  5. Notch signaling pathway Source: Reactome
  6. post-embryonic development Source: Ensembl
  7. regulation of gene expression Source: Ensembl
Complete GO annotation...

Enzyme and pathway databases

ReactomeiREACT_118614. Activated NOTCH1 Transmits Signal to the Nucleus.
SignaLinkiP80370.

Names & Taxonomyi

Protein namesi
Recommended name:
Protein delta homolog 1
Short name:
DLK-1
Alternative name(s):
pG2
Cleaved into the following chain:
Fetal antigen 1
Short name:
FA1
Gene namesi
Name:DLK1
Synonyms:DLK
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 14

Organism-specific databases

HGNCiHGNC:2907. DLK1.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini24 – 303280ExtracellularSequence AnalysisAdd
BLAST
Transmembranei304 – 32724HelicalSequence AnalysisAdd
BLAST
Topological domaini328 – 38356CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. external side of plasma membrane Source: Ensembl
  2. extracellular space Source: ProtInc
  3. integral component of membrane Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

Orphaneti96184. Maternal uniparental disomy of chromosome 14.
96334. Paternal uniparental disomy of chromosome 14.
PharmGKBiPA27363.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 23233 PublicationsAdd
BLAST
Chaini24 – 383360Protein delta homolog 1PRO_0000007518Add
BLAST
Chaini24 – 303280Fetal antigen 1PRO_0000007519Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi26 ↔ 37PROSITE-ProRule annotation
Disulfide bondi30 ↔ 43PROSITE-ProRule annotation
Disulfide bondi45 ↔ 54PROSITE-ProRule annotation
Disulfide bondi57 ↔ 68PROSITE-ProRule annotation
Disulfide bondi63 ↔ 74PROSITE-ProRule annotation
Disulfide bondi76 ↔ 85PROSITE-ProRule annotation
Disulfide bondi92 ↔ 103PROSITE-ProRule annotation
Glycosylationi94 – 941O-linked (GalNAc...)1 Publication
Disulfide bondi97 ↔ 113PROSITE-ProRule annotation
Glycosylationi100 – 1001N-linked (GlcNAc...)1 Publication
Disulfide bondi115 ↔ 124PROSITE-ProRule annotation
Disulfide bondi131 ↔ 144PROSITE-ProRule annotation
Disulfide bondi138 ↔ 156PROSITE-ProRule annotation
Glycosylationi143 – 1431O-linked (GalNAc...)1 Publication
Disulfide bondi158 ↔ 167PROSITE-ProRule annotation
Glycosylationi163 – 1631O-linked (GalNAc...); partial1 Publication
Glycosylationi165 – 1651N-linked (GlcNAc...); partial; atypical1 Publication
Glycosylationi172 – 1721N-linked (GlcNAc...); partial; atypical1 Publication
Disulfide bondi174 ↔ 185PROSITE-ProRule annotation
Disulfide bondi179 ↔ 194PROSITE-ProRule annotation
Disulfide bondi196 ↔ 205PROSITE-ProRule annotation
Disulfide bondi212 ↔ 223PROSITE-ProRule annotation
Glycosylationi214 – 2141O-linked (GalNAc...)1 Publication
Disulfide bondi217 ↔ 233PROSITE-ProRule annotation
Glycosylationi222 – 2221O-linked (GalNAc...); partial1 Publication
Disulfide bondi235 ↔ 244PROSITE-ProRule annotation
Glycosylationi251 – 2511O-linked (GalNAc...); partial1 Publication
Glycosylationi256 – 2561O-linked (GalNAc...)1 Publication
Glycosylationi260 – 2601O-linked (GalNAc...); partial1 Publication

Post-translational modificationi

N- and O-glycosylated. O-glycosylated with core 1 or possibly core 8 glycans.2 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP80370.
PRIDEiP80370.

PTM databases

PhosphoSiteiP80370.

Expressioni

Tissue specificityi

Found within the stromal cells in close contact to the vascular structure of placental villi, yolk sac, fetal liver, adrenal cortex and pancreas and in the beta cells of the islets of Langerhans in the adult pancreas. Found also in some forms of neuroendocrine lung tumor tissue.

Gene expression databases

BgeeiP80370.
CleanExiHS_DLK1.
ExpressionAtlasiP80370. baseline and differential.
GenevestigatoriP80370.

Organism-specific databases

HPAiCAB005872.
HPA053879.
HPA062262.

Interactioni

Subunit structurei

Monomer.

Protein-protein interaction databases

BioGridi114316. 66 interactions.
STRINGi9606.ENSP00000340292.

Structurei

3D structure databases

ProteinModelPortaliP80370.
SMRiP80370. Positions 24-247.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini24 – 5532EGF-like 1PROSITE-ProRule annotationAdd
BLAST
Domaini53 – 8634EGF-like 2PROSITE-ProRule annotationAdd
BLAST
Domaini88 – 12538EGF-like 3PROSITE-ProRule annotationAdd
BLAST
Domaini127 – 16842EGF-like 4PROSITE-ProRule annotationAdd
BLAST
Domaini170 – 20637EGF-like 5PROSITE-ProRule annotationAdd
BLAST
Domaini208 – 24538EGF-like 6PROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 6 EGF-like domains.PROSITE-ProRule annotation

Keywords - Domaini

EGF-like domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG306005.
GeneTreeiENSGT00760000118786.
HOGENOMiHOG000072581.
HOVERGENiHBG007065.
InParanoidiP80370.
OMAiECLCKPE.
PhylomeDBiP80370.
TreeFamiTF351835.

Family and domain databases

InterProiIPR000742. EG-like_dom.
IPR013032. EGF-like_CS.
IPR000152. EGF-type_Asp/Asn_hydroxyl_site.
[Graphical view]
PfamiPF00008. EGF. 4 hits.
PF12661. hEGF. 1 hit.
[Graphical view]
SMARTiSM00181. EGF. 6 hits.
[Graphical view]
PROSITEiPS00010. ASX_HYDROXYL. 1 hit.
PS00022. EGF_1. 5 hits.
PS01186. EGF_2. 5 hits.
PS50026. EGF_3. 5 hits.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist.

Isoform Long (identifier: P80370-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MTATEALLRV LLLLLAFGHS TYGAECFPAC NPQNGFCEDD NVCRCQPGWQ
60 70 80 90 100
GPLCDQCVTS PGCLHGLCGE PGQCICTDGW DGELCDRDVR ACSSAPCANN
110 120 130 140 150
RTCVSLDDGL YECSCAPGYS GKDCQKKDGP CVINGSPCQH GGTCVDDEGR
160 170 180 190 200
ASHASCLCPP GFSGNFCEIV ANSCTPNPCE NDGVCTDIGG DFRCRCPAGF
210 220 230 240 250
IDKTCSRPVT NCASSPCQNG GTCLQHTQVS YECLCKPEFT GLTCVKKRAL
260 270 280 290 300
SPQQVTRLPS GYGLAYRLTP GVHELPVQQP EHRILKVSMK ELNKKTPLLT
310 320 330 340 350
EGQAICFTIL GVLTSLVVLG TVGIVFLNKC ETWVSNLRYN HMLRKKKNLL
360 370 380
LQYNSGEDLA VNIIFPEKID MTTFSKEAGD EEI
Length:383
Mass (Da):41,300
Last modified:May 17, 2010 - v3
Checksum:i9A2813B2801A98BD
GO
Isoform Short (identifier: P80370-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     229-301: Missing.

Show »
Length:310
Mass (Da):33,067
Checksum:i938E477A8F5B4D86
GO

Sequence cautioni

The sequence CAA35582.1 differs from that shown. Reason: Frameshift at positions 22, 108 and 199. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti45 – 473Missing in CAA35582 (PubMed:2308864).Curated
Sequence conflicti46 – 472QP → HV in CAA78163 (PubMed:8095043).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti73 – 731Q → L.
Corresponds to variant rs34686110 [ dbSNP | Ensembl ].
VAR_055715
Natural varianti101 – 1011R → G.5 Publications
Corresponds to variant rs6575799 [ dbSNP | Ensembl ].
VAR_060335
Natural varianti104 – 1041V → M.
Corresponds to variant rs2273607 [ dbSNP | Ensembl ].
VAR_055716
Natural varianti108 – 1081D → G.2 Publications
Corresponds to variant rs1058006 [ dbSNP | Ensembl ].
VAR_060336
Natural varianti260 – 2601S → N.
Corresponds to variant rs1058009 [ dbSNP | Ensembl ].
VAR_055717
Natural varianti347 – 3471Missing in clone HDLKAAG.
VAR_002274

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei229 – 30173Missing in isoform Short. 1 PublicationVSP_001377Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z12172 mRNA. Translation: CAA78163.1.
U15979 mRNA. Translation: AAA75364.1.
U15981 mRNA. Translation: AAA75365.1.
X17544 mRNA. Translation: CAA35582.1. Frameshift.
AL132711 Genomic DNA. No translation available.
BC013197 mRNA. Translation: AAH13197.1.
CCDSiCCDS9963.1. [P80370-1]
PIRiS53716.
S71548.
RefSeqiNP_003827.3. NM_003836.5.
UniGeneiHs.533717.

Genome annotation databases

EnsembliENST00000331224; ENSP00000331081; ENSG00000185559. [P80370-2]
ENST00000341267; ENSP00000340292; ENSG00000185559. [P80370-1]
GeneIDi8788.
KEGGihsa:8788.
UCSCiuc001yhs.4. human. [P80370-1]
uc001yhu.4. human. [P80370-2]

Polymorphism databases

DMDMi296439371.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z12172 mRNA. Translation: CAA78163.1.
U15979 mRNA. Translation: AAA75364.1.
U15981 mRNA. Translation: AAA75365.1.
X17544 mRNA. Translation: CAA35582.1. Frameshift.
AL132711 Genomic DNA. No translation available.
BC013197 mRNA. Translation: AAH13197.1.
CCDSiCCDS9963.1. [P80370-1]
PIRiS53716.
S71548.
RefSeqiNP_003827.3. NM_003836.5.
UniGeneiHs.533717.

3D structure databases

ProteinModelPortaliP80370.
SMRiP80370. Positions 24-247.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114316. 66 interactions.
STRINGi9606.ENSP00000340292.

Chemistry

BindingDBiP80370.
ChEMBLiCHEMBL5671.

PTM databases

PhosphoSiteiP80370.

Polymorphism databases

DMDMi296439371.

Proteomic databases

PaxDbiP80370.
PRIDEiP80370.

Protocols and materials databases

DNASUi8788.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000331224; ENSP00000331081; ENSG00000185559. [P80370-2]
ENST00000341267; ENSP00000340292; ENSG00000185559. [P80370-1]
GeneIDi8788.
KEGGihsa:8788.
UCSCiuc001yhs.4. human. [P80370-1]
uc001yhu.4. human. [P80370-2]

Organism-specific databases

CTDi8788.
GeneCardsiGC14P101197.
H-InvDBHIX0131238.
HGNCiHGNC:2907. DLK1.
HPAiCAB005872.
HPA053879.
HPA062262.
MIMi176290. gene.
neXtProtiNX_P80370.
Orphaneti96184. Maternal uniparental disomy of chromosome 14.
96334. Paternal uniparental disomy of chromosome 14.
PharmGKBiPA27363.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG306005.
GeneTreeiENSGT00760000118786.
HOGENOMiHOG000072581.
HOVERGENiHBG007065.
InParanoidiP80370.
OMAiECLCKPE.
PhylomeDBiP80370.
TreeFamiTF351835.

Enzyme and pathway databases

ReactomeiREACT_118614. Activated NOTCH1 Transmits Signal to the Nucleus.
SignaLinkiP80370.

Miscellaneous databases

ChiTaRSiDLK1. human.
GeneWikiiDLK1.
GenomeRNAii8788.
NextBioi32960.
PROiP80370.
SOURCEiSearch...

Gene expression databases

BgeeiP80370.
CleanExiHS_DLK1.
ExpressionAtlasiP80370. baseline and differential.
GenevestigatoriP80370.

Family and domain databases

InterProiIPR000742. EG-like_dom.
IPR013032. EGF-like_CS.
IPR000152. EGF-type_Asp/Asn_hydroxyl_site.
[Graphical view]
PfamiPF00008. EGF. 4 hits.
PF12661. hEGF. 1 hit.
[Graphical view]
SMARTiSM00181. EGF. 6 hits.
[Graphical view]
PROSITEiPS00010. ASX_HYDROXYL. 1 hit.
PS00022. EGF_1. 5 hits.
PS01186. EGF_2. 5 hits.
PS50026. EGF_3. 5 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "dlk, a putative mammalian homeotic gene differentially expressed in small cell lung carcinoma and neuroendocrine tumor cell line."
    Laborda J., Sausville E.A., Hoffman T., Notario V.
    J. Biol. Chem. 268:3817-3820(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG), VARIANTS GLY-101 AND GLY-108.
    Tissue: Adrenal gland.
  2. "dlk, pG2 and Pref-1 mRNAs encode similar proteins belonging to the EGF-like superfamily. Identification of polymorphic variants of this RNA."
    Lee Y.L., Helman L., Hoffman T., Laborda J.
    Biochim. Biophys. Acta 1261:223-232(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG AND SHORT), VARIANTS GLY-101 AND GLY-108.
    Tissue: Adrenal gland and Placenta.
  3. "The sequence of an adrenal specific human cDNA, pG2."
    Helman L.J., Sack N., Plon S., Israel M.A.
    Nucleic Acids Res. 18:685-685(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG), VARIANT GLY-101.
    Tissue: Adrenal gland.
  4. "The DNA sequence and analysis of human chromosome 14."
    Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H.
    , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J.
    Nature 421:601-607(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG), VARIANT GLY-101.
    Tissue: Adrenal gland.
  6. "Protein structure of fetal antigen 1 (FA1). A novel circulating human epidermal-growth-factor-like protein expressed in neuroendocrine tumors and its relation to the gene products of dlk and pG2."
    Jensen C.H., Krogh T.N., Hoejrup P., Clausen P.P., Skjoedt K., Larsson L.-I., Enghild J.J., Teisner B.
    Eur. J. Biochem. 225:83-92(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 24-383, GLYCOSYLATION AT SER-94; ASN-100; THR-143; SER-163; ASN-165; ASN-172; SER-214; THR-222; SER-251 AND SER-260, VARIANT GLY-101.
    Tissue: Amniotic fluid.
  7. "Studies on the isolation, structural analysis and tissue localization of fetal antigen 1 and its relation to a human adrenal-specific cDNA, pG2."
    Jensen C.H., Teisner B., Hoejrup P., Rasmussen H.B., Madsen O.D., Nielsen B., Skjoedt K.
    Hum. Reprod. 8:635-641(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 24-60.
    Tissue: Amniotic fluid.
  8. "Signal peptide prediction based on analysis of experimentally verified cleavage sites."
    Zhang Z., Henzel W.J.
    Protein Sci. 13:2819-2824(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 24-38.
  9. "Human urinary glycoproteomics; attachment site specific analysis of N-and O-linked glycosylations by CID and ECD."
    Halim A., Nilsson J., Ruetschi U., Hesse C., Larson G.
    Mol. Cell. Proteomics 0:0-0(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCOSYLATION AT THR-256, STRUCTURE OF CARBOHYDRATES, IDENTIFICATION BY MASS SPECTROMETRY.

Entry informationi

Entry nameiDLK1_HUMAN
AccessioniPrimary (citable) accession number: P80370
Secondary accession number(s): P15803, Q96DW5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 31, 1995
Last sequence update: May 17, 2010
Last modified: March 3, 2015
This is version 157 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.