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Q9UPQ8 (DOLK_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 107. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length538 AA.
Sequence statusComplete.
Protein existenceEvidence 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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 538538Dolichol kinase
PRO_0000072595

Regions

Topological domain1 – 1313Lumenal Potential
Transmembrane14 – 3421Helical; Potential
Topological domain35 – 7440Cytoplasmic Potential
Transmembrane75 – 9521Helical; Potential
Topological domain96 – 11116Lumenal Potential
Transmembrane112 – 13221Helical; Potential
Topological domain133 – 1342Cytoplasmic Potential
Transmembrane135 – 15521Helical; Potential
Topological domain156 – 1638Lumenal Potential
Transmembrane164 – 18421Helical; Potential
Topological domain185 – 1884Cytoplasmic Potential
Transmembrane189 – 20921Helical; Potential
Topological domain210 – 22415Lumenal Potential
Transmembrane225 – 24521Helical; Potential
Topological domain246 – 2549Cytoplasmic Potential
Transmembrane255 – 27521Helical; Potential
Topological domain276 – 29722Lumenal Potential
Transmembrane298 – 31821Helical; Potential
Topological domain319 – 33719Cytoplasmic Potential
Transmembrane338 – 35417Helical; Potential
Topological domain355 – 3595Lumenal Potential
Transmembrane360 – 38021Helical; Potential
Topological domain381 – 40121Cytoplasmic Potential
Transmembrane402 – 42221Helical; Potential
Topological domain423 – 43614Lumenal Potential
Transmembrane437 – 45721Helical; Potential
Topological domain458 – 47215Cytoplasmic Potential
Transmembrane473 – 49321Helical; Potential
Topological domain494 – 4952Lumenal Potential
Transmembrane496 – 51621Helical; Potential
Topological domain517 – 53822Cytoplasmic Potential
Region459 – 47416CTP-binding

Natural variations

Natural variant991C → S in CDG1M; 2% residual activity; fails to complement the temperature-sensitive phenotype of DK1-deficient yeast cells. Ref.7
VAR_032851
Natural variant2241D → V.
Corresponds to variant rs17485436 [ dbSNP | Ensembl ].
VAR_049709
Natural variant4411Y → S in CDG1M; 4% residual activity; fails to complement the temperature-sensitive phenotype of DK1-deficient yeast cells. Ref.7
VAR_032852

Experimental info

Mutagenesis4431G → D: Abolishes kinase activity. Ref.6
Mutagenesis4511D → A: Reduces kinase activity. Ref.6
Mutagenesis4701K → A: Reduces kinase activity. Significant reduction in binding affinity for CTP; when associated with A-471. Ref.6
Mutagenesis4711K → A: Reduces kinase activity. Significant reduction in binding affinity for CTP. Ref.6
Mutagenesis4721T → A: Reduces kinase activity. Significant reduction in binding affinity for CTP. Ref.6
Mutagenesis4741E → A: No effect on kinase activity. Ref.6
Mutagenesis4751G → A: No effect on kinase activity. Ref.6

Sequences

Sequence LengthMass (Da)Tools
Q9UPQ8 [UniParc].

Last modified May 1, 2000. Version 1.
Checksum: EB7D1BABD45362AD

FASTA53859,268
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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.
CCDSCCDS6915.1.
RefSeqNP_055723.1. NM_014908.3.
UniGeneHs.531563.

3D structure databases

ProteinModelPortalQ9UPQ8.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid116517. 1 interaction.
IntActQ9UPQ8. 1 interaction.
MINTMINT-4724096.
STRING9606.ENSP00000361667.

PTM databases

PhosphoSiteQ9UPQ8.

Polymorphism databases

DMDM20140913.

Proteomic databases

MaxQBQ9UPQ8.
PaxDbQ9UPQ8.
PRIDEQ9UPQ8.

Protocols and materials databases

DNASU22845.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000372586; ENSP00000361667; ENSG00000175283.
GeneID22845.
KEGGhsa:22845.
UCSCuc004bwr.3. human.

Organism-specific databases

CTD22845.
GeneCardsGC09M131707.
GeneReviewsDOLK.
HGNCHGNC:23406. DOLK.
HPAHPA054813.
MIM610746. gene.
610768. phenotype.
neXtProtNX_Q9UPQ8.
Orphanet91131. DK1-CDG.
154. Familial isolated dilated cardiomyopathy.
PharmGKBPA162384054.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0170.
HOGENOMHOG000036052.
HOVERGENHBG054655.
InParanoidQ9UPQ8.
KOK00902.
OMARKYFHFI.
OrthoDBEOG7J9VPF.
PhylomeDBQ9UPQ8.
TreeFamTF323379.

Enzyme and pathway databases

ReactomeREACT_17015. Metabolism of proteins.

Gene expression databases

BgeeQ9UPQ8.
CleanExHS_DOLK.
GenevestigatorQ9UPQ8.

Family and domain databases

InterProIPR026566. DOLK.
[Graphical view]
PANTHERPTHR13205:SF14. PTHR13205:SF14. 1 hit.
ProtoNetSearch...

Other

GeneWikiDolichol_kinase.
GenomeRNAi22845.
NextBio43301.
PROQ9UPQ8.
SOURCESearch...

Entry information

Entry nameDOLK_HUMAN
AccessionPrimary (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: July 9, 2014
This is version 107 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 9

Human chromosome 9: entries, gene names and cross-references to MIM