Q9UPQ8 (DOLK_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Dolichol kinase
EC=2.7.1.108

Alternative name(s):
Transmembrane protein 15

Gene names

Name:	DOLK
Synonyms:	KIAA1094, TMEM15
ORF Names:	UNQ2422/PRO4980

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	538 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Involved in the synthesis of the sugar donor Dol-P-Man which is required in the synthesis of N-linked and O-linked oligosaccharides and for that of GPI anchors By similarity.
Catalytic activity	CTP + dolichol = CDP + dolichyl phosphate.
Subcellular location	Endoplasmic reticulum membrane; Multi-pass membrane protein Potential Ref.6.
Tissue specificity	Ubiquitous.
Involvement in disease	Congenital disorder of glycosylation 1M (CDG1M) [MIM:610768]: A multisystem disorder caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. CDG1M is a very severe disease with death occurring in early life. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7
Miscellaneous	Complements the defects in growth, dolichol kinase activity and protein N-glycosylation at the restrictive temperature in yeast sec59 mutant cells.
Sequence similarities	Belongs to the polyprenol kinase family.
Sequence caution	The sequence BAA83046.2 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Cellular component	Endoplasmic reticulum Membrane
Coding sequence diversity	Polymorphism
Disease	Congenital disorder of glycosylation Disease mutation
Domain	Transmembrane Transmembrane helix
Molecular function	Kinase Transferase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	dolichyl diphosphate biosynthetic process Traceable author statement. Source: Reactome dolichyl monophosphate biosynthetic process Inferred from direct assay Ref.1Ref.6. Source: UniProtKB post-translational protein modification Traceable author statement. Source: Reactome protein N-linked glycosylation via asparagine Traceable author statement. Source: Reactome
Cellular_component	integral to endoplasmic reticulum membrane Inferred from direct assay Ref.6. Source: UniProtKB
Molecular_function	dolichol kinase activity Inferred from direct assay Ref.1Ref.6. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 538	538	Dolichol kinase		PRO_0000072595
Regions
	Topological domain	1 – 13	13	Lumenal Potential
	Transmembrane	14 – 34	21	Helical; Potential
	Topological domain	35 – 74	40	Cytoplasmic Potential
	Transmembrane	75 – 95	21	Helical; Potential
	Topological domain	96 – 111	16	Lumenal Potential
	Transmembrane	112 – 132	21	Helical; Potential
	Topological domain	133 – 134	2	Cytoplasmic Potential
	Transmembrane	135 – 155	21	Helical; Potential
	Topological domain	156 – 163	8	Lumenal Potential
	Transmembrane	164 – 184	21	Helical; Potential
	Topological domain	185 – 188	4	Cytoplasmic Potential
	Transmembrane	189 – 209	21	Helical; Potential
	Topological domain	210 – 224	15	Lumenal Potential
	Transmembrane	225 – 245	21	Helical; Potential
	Topological domain	246 – 254	9	Cytoplasmic Potential
	Transmembrane	255 – 275	21	Helical; Potential
	Topological domain	276 – 297	22	Lumenal Potential
	Transmembrane	298 – 318	21	Helical; Potential
	Topological domain	319 – 337	19	Cytoplasmic Potential
	Transmembrane	338 – 354	17	Helical; Potential
	Topological domain	355 – 359	5	Lumenal Potential
	Transmembrane	360 – 380	21	Helical; Potential
	Topological domain	381 – 401	21	Cytoplasmic Potential
	Transmembrane	402 – 422	21	Helical; Potential
	Topological domain	423 – 436	14	Lumenal Potential
	Transmembrane	437 – 457	21	Helical; Potential
	Topological domain	458 – 472	15	Cytoplasmic Potential
	Transmembrane	473 – 493	21	Helical; Potential
	Topological domain	494 – 495	2	Lumenal Potential
	Transmembrane	496 – 516	21	Helical; Potential
	Topological domain	517 – 538	22	Cytoplasmic Potential
	Region	459 – 474	16	CTP-binding
Natural variations
	Natural variant	99	1	C → S in CDG1M; 2% residual activity; fails to complement the temperature-sensitive phenotype of DK1-deficient yeast cells. Ref.7		VAR_032851
	Natural variant	224	1	D → V. Corresponds to variant rs17485436 [ dbSNP | Ensembl ].		VAR_049709
	Natural variant	441	1	Y → S in CDG1M; 4% residual activity; fails to complement the temperature-sensitive phenotype of DK1-deficient yeast cells. Ref.7		VAR_032852
Experimental info
	Mutagenesis	443	1	G → D: Abolishes kinase activity. Ref.6
	Mutagenesis	451	1	D → A: Reduces kinase activity. Ref.6
	Mutagenesis	470	1	K → A: Reduces kinase activity. Significant reduction in binding affinity for CTP; when associated with A-471. Ref.6
	Mutagenesis	471	1	K → A: Reduces kinase activity. Significant reduction in binding affinity for CTP. Ref.6
	Mutagenesis	472	1	T → A: Reduces kinase activity. Significant reduction in binding affinity for CTP. Ref.6
	Mutagenesis	474	1	E → A: No effect on kinase activity. Ref.6
	Mutagenesis	475	1	G → A: No effect on kinase activity. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	Q9UPQ8 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: EB7D1BABD45362AD	FASTA	538	59,268
	10 20 30 40 50 60 MTRECPSPAP GPGAPLSGSV LAEAAVVFAV VLSIHATVWD RYSWCAVALA VQAFYVQYKW 70 80 90 100 110 120 DRLLQQGSAV FQFRMSANSG LLPASMVMPL LGLVMKERCQ TAGNPFFERF GIVVAATGMA 130 140 150 160 170 180 VALFSSVLAL GITRPVPTNT CVILGLAGGV IIYIMKHSLS VGEVIEVLEV LLIFVYLNMI 190 200 210 220 230 240 LLYLLPRCFT PGEALLVLGG ISFVLNQLIK RSLTLVESQG DPVDFFLLVV VVGMVLMGIF 250 260 270 280 290 300 FSTLFVFMDS GTWASSIFFH LMTCVLSLGV VLPWLHRLIR RNPLLWLLQF LFQTDTRIYL 310 320 330 340 350 360 LAYWSLLATL ACLVVLYQNA KRSSSESKKH QAPTIARKYF HLIVVATYIP GIIFDRPLLY 370 380 390 400 410 420 VAATVCLAVF IFLEYVRYFR IKPLGHTLRS FLSLFLDERD SGPLILTHIY LLLGMSLPIW 430 440 450 460 470 480 LIPRPCTQKG SLGGARALVP YAGVLAVGVG DTVASIFGST MGEIRWPGTK KTFEGTMTSI 490 500 510 520 530 FAQIISVALI LIFDSGVDLN YSYAWILGSI STVSLLEAYT TQIDNLLLPL YLLILLMA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Expression and characterization of a human cDNA that complements the temperature-sensitive defect in dolichol kinase activity in the yeast sec59-1 mutant: the enzymatic phosphorylation of dolichol and diacylglycerol are catalyzed by separate CTP-mediated kinase activities in Saccharomyces cerevisiae." Fernandez F., Shridas P., Jiang S., Aebi M., Waechter C.J. Glycobiology 12:555-562(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[2]	"Prediction of the coding sequences of unidentified human genes. XIV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro." Kikuno R., Nagase T., Ishikawa K., Hirosawa M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 6:197-205(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[3]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [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(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Pancreas and Spleen.
[6]	"Human dolichol kinase, a polytopic endoplasmic reticulum membrane protein with a cytoplasmically oriented CTP-binding site." Shridas P., Waechter C.J. J. Biol. Chem. 281:31696-31704(2006) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, TOPOLOGY, CTP-BINDING, MUTAGENESIS OF GLY-443; ASP-451; LYS-470; LYS-471; THR-472; GLU-474 AND GLY-475.
[7]	"A defect in dolichol phosphate biosynthesis causes a new inherited disorder with death in early infancy." Kranz C., Jungeblut C., Denecke J., Erlekotte A., Sohlbach C., Debus V., Kehl H.G., Harms E., Reith A., Reichel S., Groebe H., Hammersen G., Schwarzer U., Marquardt T. Am. J. Hum. Genet. 80:433-440(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CDG1M SER-99 AND SER-441, CHARACTERIZATION OF VARIANTS CDG1M SER-99 AND SER-441.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB029017 mRNA. Translation: BAA83046.2. Different initiation. AY358759 mRNA. Translation: AAQ89119.1. AL672142 Genomic DNA. Translation: CAI10844.1. BC035556 mRNA. Translation: AAH35556.1.
IPI	IPI00007165.
RefSeq	NP_055723.1. NM_014908.3.
UniGene	Hs.531563.
3D structure databases
ProteinModelPortal	Q9UPQ8.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-4724096.
STRING	9606.ENSP00000361667.
PTM databases
PhosphoSite	Q9UPQ8.
Polymorphism databases
DMDM	20140913.
Proteomic databases
PaxDb	Q9UPQ8.
PRIDE	Q9UPQ8.
Protocols and materials databases
DNASU	22845.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000372586; ENSP00000361667; ENSG00000175283.
GeneID	22845.
KEGG	hsa:22845.
UCSC	uc004bwr.3. human.
Organism-specific databases
CTD	22845.
GeneCards	GC09M131707.
HGNC	HGNC:23406. DOLK.
MIM	610746. gene. 610768. phenotype.
neXtProt	NX_Q9UPQ8.
Orphanet	91131. DK1-CDG syndrome. 154. Familial isolated dilated cardiomyopathy.
PharmGKB	PA162384054.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0170.
HOGENOM	HOG000036052.
HOVERGEN	HBG054655.
InParanoid	Q9UPQ8.
KO	K00902.
OMA	RKYFHFI.
OrthoDB	EOG4RV2R8.
PhylomeDB	Q9UPQ8.
Enzyme and pathway databases
Reactome	REACT_17015. Metabolism of proteins.
Gene expression databases
Bgee	Q9UPQ8.
CleanEx	HS_DOLK.
Genevestigator	Q9UPQ8.
GermOnline	ENSG00000175283. Homo sapiens.
Family and domain databases
InterPro	IPR026566. DOLK. [Graphical view]
PANTHER	PTHR13205:SF8. PTHR13205:SF8. 1 hit.
ProtoNet	Search...
Other
GenomeRNAi	22845.
NextBio	43301.
SOURCE	Search...

Entry information

Entry name

DOLK_HUMAN

Accession

Primary (citable) accession number: Q9UPQ8
Secondary accession number(s): Q5SRE6

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 31, 2002
Last sequence update:	May 1, 2000
Last modified:	May 29, 2013
This is version 96 of the entry and version 1 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.