P80370 (DLK1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein delta homolog 1
Short name=DLK-1

Alternative name(s):
pG2

Cleaved into the following chain:

1. Fetal antigen 1
   Short name=FA1

Gene names

Name:	DLK1
Synonyms:	DLK

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	383 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	May have a role in neuroendocrine differentiation.
Subunit structure	Monomer.
Subcellular location	Membrane; Single-pass type I membrane protein.
Tissue specificity	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.
Post-translational modification	N- and O-glycosylated. Ref.6
Sequence similarities	Contains 6 EGF-like domains.
Sequence caution	The sequence CAA35582.1 differs from that shown. Reason: Frameshift at positions 22, 108 and 199.

Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	EGF-like domain Repeat Signal Transmembrane Transmembrane helix
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Cellular component	extracellular space Traceable author statement. Source: ProtInc integral to membrane Traceable author statement. Source: ProtInc soluble fraction Traceable author statement. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.

Isoform Long (identifier: P80370-1)

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.

Isoform Short (identifier: P80370-2)

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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 23	23	Ref.6 Ref.7 Ref.8
	Chain	24 – 383	360	Protein delta homolog 1		PRO_0000007518
	Chain	24 – 303	280	Fetal antigen 1		PRO_0000007519
Regions
	Topological domain	24 – 303	280	Extracellular Potential
	Transmembrane	304 – 327	24	Helical; Potential
	Topological domain	328 – 383	56	Cytoplasmic Potential
	Domain	24 – 55	32	EGF-like 1
	Domain	53 – 86	34	EGF-like 2
	Domain	88 – 125	38	EGF-like 3
	Domain	127 – 168	42	EGF-like 4
	Domain	170 – 206	37	EGF-like 5
	Domain	208 – 245	38	EGF-like 6
Amino acid modifications
	Glycosylation	94	1	O-linked (GalNAc...) Ref.6
	Glycosylation	100	1	N-linked (GlcNAc...) Ref.6
	Glycosylation	143	1	O-linked (GalNAc...) Ref.6
	Glycosylation	163	1	O-linked (GalNAc...); partial Ref.6
	Glycosylation	165	1	N-linked (GlcNAc...); partial; atypical Ref.6
	Glycosylation	172	1	N-linked (GlcNAc...); partial; atypical Ref.6
	Glycosylation	214	1	O-linked (GalNAc...) Ref.6
	Glycosylation	222	1	O-linked (GalNAc...); partial Ref.6
	Glycosylation	251	1	O-linked (GalNAc...); partial Ref.6
	Glycosylation	260	1	O-linked (GalNAc...); partial Ref.6
	Disulfide bond	26 ↔ 37		By similarity
	Disulfide bond	30 ↔ 43		By similarity
	Disulfide bond	45 ↔ 54		By similarity
	Disulfide bond	57 ↔ 68		By similarity
	Disulfide bond	63 ↔ 74		By similarity
	Disulfide bond	76 ↔ 85		By similarity
	Disulfide bond	92 ↔ 103		By similarity
	Disulfide bond	97 ↔ 113		By similarity
	Disulfide bond	115 ↔ 124		By similarity
	Disulfide bond	131 ↔ 144		By similarity
	Disulfide bond	138 ↔ 156		By similarity
	Disulfide bond	158 ↔ 167		By similarity
	Disulfide bond	174 ↔ 185		By similarity
	Disulfide bond	179 ↔ 194		By similarity
	Disulfide bond	196 ↔ 205		By similarity
	Disulfide bond	212 ↔ 223		By similarity
	Disulfide bond	217 ↔ 233		By similarity
	Disulfide bond	235 ↔ 244		By similarity
Natural variations
	Alternative sequence	229 – 301	73	Missing in isoform Short.		VSP_001377
	Natural variant	73	1	Q → L. Corresponds to variant rs34686110 [ dbSNP | Ensembl ].		VAR_055715
	Natural variant	101	1	R → G. Ref.1 Ref.2 Ref.3 Ref.5 Ref.6 Corresponds to variant rs6575799 [ dbSNP | Ensembl ].		VAR_060335
	Natural variant	104	1	V → M. Corresponds to variant rs2273607 [ dbSNP | Ensembl ].		VAR_055716
	Natural variant	108	1	D → G. Ref.1 Ref.2 Corresponds to variant rs1058006 [ dbSNP | Ensembl ].		VAR_060336
	Natural variant	260	1	S → N. Corresponds to variant rs1058009 [ dbSNP | Ensembl ].		VAR_055717
	Natural variant	347	1	Missing in clone HDLKAAG.		VAR_002274
Experimental info
	Sequence conflict	45 – 47	3	Missing in CAA35582. Ref.3
	Sequence conflict	46 – 47	2	QP → HV in CAA78163. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long [UniParc]. Last modified May 18, 2010. Version 3. Checksum: 9A2813B2801A98BD	FASTA	383	41,300
	10 20 30 40 50 60 MTATEALLRV LLLLLAFGHS TYGAECFPAC NPQNGFCEDD NVCRCQPGWQ GPLCDQCVTS 70 80 90 100 110 120 PGCLHGLCGE PGQCICTDGW DGELCDRDVR ACSSAPCANN RTCVSLDDGL YECSCAPGYS 130 140 150 160 170 180 GKDCQKKDGP CVINGSPCQH GGTCVDDEGR ASHASCLCPP GFSGNFCEIV ANSCTPNPCE 190 200 210 220 230 240 NDGVCTDIGG DFRCRCPAGF IDKTCSRPVT NCASSPCQNG GTCLQHTQVS YECLCKPEFT 250 260 270 280 290 300 GLTCVKKRAL SPQQVTRLPS GYGLAYRLTP GVHELPVQQP EHRILKVSMK ELNKKTPLLT 310 320 330 340 350 360 EGQAICFTIL GVLTSLVVLG TVGIVFLNKC ETWVSNLRYN HMLRKKKNLL LQYNSGEDLA 370 380 VNIIFPEKID MTTFSKEAGD EEI
	Isoform Short [UniParc]. Checksum: 938E477A8F5B4D86	FASTA	310	33,067
	10 20 30 40 50 60 MTATEALLRV LLLLLAFGHS TYGAECFPAC NPQNGFCEDD NVCRCQPGWQ GPLCDQCVTS 70 80 90 100 110 120 PGCLHGLCGE PGQCICTDGW DGELCDRDVR ACSSAPCANN RTCVSLDDGL YECSCAPGYS 130 140 150 160 170 180 GKDCQKKDGP CVINGSPCQH GGTCVDDEGR ASHASCLCPP GFSGNFCEIV ANSCTPNPCE 190 200 210 220 230 240 NDGVCTDIGG DFRCRCPAGF IDKTCSRPVT NCASSPCQNG GTCLQHTQGQ AICFTILGVL 250 260 270 280 290 300 TSLVVLGTVG IVFLNKCETW VSNLRYNHML RKKKNLLLQY NSGEDLAVNI IFPEKIDMTT 310 FSKEAGDEEI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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(1993) [PubMed: 8095043] [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(1995) [PubMed: 7711066] [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(1990) [PubMed: 2308864] [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(2003) [PubMed: 12508121] [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(2004) [PubMed: 15489334] [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(1994) [PubMed: 7925474] [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(1993) [PubMed: 8501199] [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(2004) [PubMed: 15340161] [Abstract] Cited for: PROTEIN SEQUENCE OF 24-38.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00160384. IPI00218210.
PIR	S53716. S71548.
RefSeq	NP_003827.3. NM_003836.5.
UniGene	Hs.533717.
3D structure databases
ProteinModelPortal	P80370.
SMR	P80370. Positions 21-247.
ModBase	Search...
Protein-protein interaction databases
STRING	P80370.
PTM databases
PhosphoSite	P80370.
Polymorphism databases
DMDM	296439371.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000341267; ENSP00000340292; ENSG00000185559.
GeneID	8788.
KEGG	hsa:8788.
UCSC	uc001yhu.2. human.
Organism-specific databases
CTD	8788.
GeneCards	GC14P101193.
HGNC	HGNC:2907. DLK1.
HPA	CAB005872.
MIM	176290. gene.
neXtProt	NX_P80370.
Orphanet	96184. Maternal uniparental disomy of chromosome 14. 96334. Paternal uniparental disomy of chromosome 14.
PharmGKB	PA27363.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	HBG717835.
HOVERGEN	HBG007065.
InParanoid	P80370.
OMA	INGSPCQ.
PhylomeDB	P80370.
Gene expression databases
ArrayExpress	P80370.
Bgee	P80370.
CleanEx	HS_DLK1.
Genevestigator	P80370.
GermOnline	ENSG00000185559. Homo sapiens.
Family and domain databases
InterPro	IPR006209. EGF. IPR006210. EGF-like. IPR013032. EGF-like_reg_CS. IPR000152. EGF-type_Asp/Asn_hydroxyl_site. IPR000742. EGF_3. [Graphical view]
Pfam	PF00008. EGF. 4 hits. [Graphical view]
SMART	SM00181. EGF. 6 hits. [Graphical view]
PROSITE	PS00010. ASX_HYDROXYL. 1 hit. PS00022. EGF_1. 5 hits. PS01186. EGF_2. 5 hits. PS50026. EGF_3. 5 hits. [Graphical view]
ProtoNet	Search...
Other
SOURCE	Search...

Entry information

Entry name

DLK1_HUMAN

Accession

Primary (citable) accession number: P80370
Secondary accession number(s): P15803, Q96DW5

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	May 18, 2010
Last modified:	January 25, 2012
This is version 126 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.