ID   DOLK_HUMAN              Reviewed;         538 AA.
AC   Q9UPQ8; Q5SRE6;
DT   31-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-2000, sequence version 1.
DT   22-APR-2020, entry version 150.
DE   RecName: Full=Dolichol kinase;
DE            EC=2.7.1.108;
DE   AltName: Full=Transmembrane protein 15;
GN   Name=DOLK; Synonyms=KIAA1094, TMEM15; ORFNames=UNQ2422/PRO4980;
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 [MRNA].
RC   TISSUE=Brain;
RX   PubMed=12213788; DOI=10.1093/glycob/cwf068;
RA   Fernandez F., Shridas P., Jiang S., Aebi M., Waechter C.J.;
RT   "Expression and characterization of a human cDNA that complements the
RT   temperature-sensitive defect in dolichol kinase activity in the yeast
RT   sec59-1 mutant: the enzymatic phosphorylation of dolichol and
RT   diacylglycerol are catalyzed by separate CTP-mediated kinase activities in
RT   Saccharomyces cerevisiae.";
RL   Glycobiology 12:555-562(2002).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain;
RX   PubMed=10470851; DOI=10.1093/dnares/6.3.197;
RA   Kikuno R., Nagase T., Ishikawa K., Hirosawa M., Miyajima N., Tanaka A.,
RA   Kotani H., Nomura N., Ohara O.;
RT   "Prediction of the coding sequences of unidentified human genes. XIV. The
RT   complete sequences of 100 new cDNA clones from brain which code for large
RT   proteins in vitro.";
RL   DNA Res. 6:197-205(1999).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15164053; DOI=10.1038/nature02465;
RA   Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA   Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA   Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA   Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA   Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA   Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA   Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA   Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA   Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA   Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA   Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA   Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA   Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA   Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA   Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA   Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA   Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA   Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA   McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA   Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA   Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA   Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA   Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA   West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA   Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA   Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA   Dunham I.;
RT   "DNA sequence and analysis of human chromosome 9.";
RL   Nature 429:369-374(2004).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Pancreas, and Spleen;
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).
RN   [6]
RP   SUBCELLULAR LOCATION, TOPOLOGY, CTP-BINDING, AND MUTAGENESIS OF GLY-443;
RP   ASP-451; LYS-470; LYS-471; THR-472; GLU-474 AND GLY-475.
RX   PubMed=16923818; DOI=10.1074/jbc.m604087200;
RA   Shridas P., Waechter C.J.;
RT   "Human dolichol kinase, a polytopic endoplasmic reticulum membrane protein
RT   with a cytoplasmically oriented CTP-binding site.";
RL   J. Biol. Chem. 281:31696-31704(2006).
RN   [7]
RP   VARIANTS CDG1M SER-99 AND SER-441, AND CHARACTERIZATION OF VARIANTS CDG1M
RP   SER-99 AND SER-441.
RX   PubMed=17273964; DOI=10.1086/512130;
RA   Kranz C., Jungeblut C., Denecke J., Erlekotte A., Sohlbach C., Debus V.,
RA   Kehl H.G., Harms E., Reith A., Reichel S., Groebe H., Hammersen G.,
RA   Schwarzer U., Marquardt T.;
RT   "A defect in dolichol phosphate biosynthesis causes a new inherited
RT   disorder with death in early infancy.";
RL   Am. J. Hum. Genet. 80:433-440(2007).
CC   -!- FUNCTION: Involved in the synthesis of the sugar donor Dol-P-Man which
CC       is required in the synthesis of N-linked and O-linked oligosaccharides
CC       and for that of GPI anchors. {ECO:0000250}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=CTP + di-trans,poly-cis-dolichol = CDP + dolichyl phosphate +
CC         H(+); Xref=Rhea:RHEA:13133, Rhea:RHEA-COMP:9517, Rhea:RHEA-COMP:9521,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:16091, ChEBI:CHEBI:37563,
CC         ChEBI:CHEBI:57683, ChEBI:CHEBI:58069; EC=2.7.1.108;
CC   -!- INTERACTION:
CC       Q9UPQ8; Q92624: APPBP2; NbExp=3; IntAct=EBI-8645574, EBI-743771;
CC       Q9UPQ8; P11912: CD79A; NbExp=3; IntAct=EBI-8645574, EBI-7797864;
CC       Q9UPQ8; Q9H9P2: CHODL; NbExp=3; IntAct=EBI-8645574, EBI-17447707;
CC       Q9UPQ8; Q96BA8: CREB3L1; NbExp=3; IntAct=EBI-8645574, EBI-6942903;
CC       Q9UPQ8; Q92838: EDA; NbExp=6; IntAct=EBI-8645574, EBI-529425;
CC       Q9UPQ8; Q5JX71: FAM209A; NbExp=3; IntAct=EBI-8645574, EBI-18304435;
CC       Q9UPQ8; Q8TBE3: FNDC9; NbExp=3; IntAct=EBI-8645574, EBI-12142257;
CC       Q9UPQ8; P48165: GJA8; NbExp=3; IntAct=EBI-8645574, EBI-17458373;
CC       Q9UPQ8; Q8TED1: GPX8; NbExp=3; IntAct=EBI-8645574, EBI-11721746;
CC       Q9UPQ8; Q09470: KCNA1; NbExp=7; IntAct=EBI-8645574, EBI-8286599;
CC       Q9UPQ8; Q16322: KCNA10; NbExp=5; IntAct=EBI-8645574, EBI-12265328;
CC       Q9UPQ8; P22001: KCNA3; NbExp=6; IntAct=EBI-8645574, EBI-8627664;
CC       Q9UPQ8; P17658: KCNA6; NbExp=4; IntAct=EBI-8645574, EBI-6426142;
CC       Q9UPQ8; Q9HCJ2: LRRC4C; NbExp=4; IntAct=EBI-8645574, EBI-3925442;
CC       Q9UPQ8; Q92536: SLC7A6; NbExp=3; IntAct=EBI-8645574, EBI-2880595;
CC       Q9UPQ8; Q8TBG9: SYNPR; NbExp=3; IntAct=EBI-8645574, EBI-10273251;
CC       Q9UPQ8; Q96B21: TMEM45B; NbExp=3; IntAct=EBI-8645574, EBI-3923061;
CC       Q9UPQ8; Q96HE8: TMEM80; NbExp=3; IntAct=EBI-8645574, EBI-11742770;
CC       Q9UPQ8; Q9H7M9: VSIR; NbExp=3; IntAct=EBI-8645574, EBI-744988;
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000305};
CC       Multi-pass membrane protein {ECO:0000305}.
CC   -!- TISSUE SPECIFICITY: Ubiquitous.
CC   -!- DISEASE: Congenital disorder of glycosylation 1M (CDG1M) [MIM:610768]:
CC       A form of congenital disorder of glycosylation, a multisystem disorder
CC       caused by a defect in glycoprotein biosynthesis and characterized by
CC       under-glycosylated serum glycoproteins. Congenital disorders of
CC       glycosylation result in a wide variety of clinical features, such as
CC       defects in the nervous system development, psychomotor retardation,
CC       dysmorphic features, hypotonia, coagulation disorders, and
CC       immunodeficiency. The broad spectrum of features reflects the critical
CC       role of N-glycoproteins during embryonic development, differentiation,
CC       and maintenance of cell functions. CDG1M is a very severe disease with
CC       death occurring in early life. {ECO:0000269|PubMed:17273964}. Note=The
CC       disease is caused by mutations affecting the gene represented in this
CC       entry.
CC   -!- MISCELLANEOUS: Complements the defects in growth, dolichol kinase
CC       activity and protein N-glycosylation at the restrictive temperature in
CC       yeast sec59 mutant cells.
CC   -!- SIMILARITY: Belongs to the polyprenol kinase family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAA83046.2; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR   EMBL; AB029017; BAA83046.2; ALT_INIT; mRNA.
DR   EMBL; AY358759; AAQ89119.1; -; mRNA.
DR   EMBL; AL672142; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC035556; AAH35556.1; -; mRNA.
DR   CCDS; CCDS6915.1; -.
DR   RefSeq; NP_055723.1; NM_014908.3.
DR   BioGrid; 116517; 20.
DR   IntAct; Q9UPQ8; 30.
DR   MINT; Q9UPQ8; -.
DR   STRING; 9606.ENSP00000361667; -.
DR   iPTMnet; Q9UPQ8; -.
DR   PhosphoSitePlus; Q9UPQ8; -.
DR   BioMuta; DOLK; -.
DR   DMDM; 20140913; -.
DR   EPD; Q9UPQ8; -.
DR   jPOST; Q9UPQ8; -.
DR   MassIVE; Q9UPQ8; -.
DR   MaxQB; Q9UPQ8; -.
DR   PaxDb; Q9UPQ8; -.
DR   PeptideAtlas; Q9UPQ8; -.
DR   PRIDE; Q9UPQ8; -.
DR   ProteomicsDB; 85419; -.
DR   Antibodypedia; 53680; 70 antibodies.
DR   DNASU; 22845; -.
DR   Ensembl; ENST00000372586; ENSP00000361667; ENSG00000175283.
DR   GeneID; 22845; -.
DR   KEGG; hsa:22845; -.
DR   UCSC; uc004bwr.4; human.
DR   CTD; 22845; -.
DR   DisGeNET; 22845; -.
DR   GeneCards; DOLK; -.
DR   GeneReviews; DOLK; -.
DR   HGNC; HGNC:23406; DOLK.
DR   HPA; ENSG00000175283; Low tissue specificity.
DR   MalaCards; DOLK; -.
DR   MIM; 610746; gene.
DR   MIM; 610768; phenotype.
DR   neXtProt; NX_Q9UPQ8; -.
DR   OpenTargets; ENSG00000175283; -.
DR   Orphanet; 91131; DK1-CDG.
DR   Orphanet; 154; Familial isolated dilated cardiomyopathy.
DR   PharmGKB; PA162384054; -.
DR   eggNOG; KOG2468; Eukaryota.
DR   eggNOG; COG0170; LUCA.
DR   GeneTree; ENSGT00390000004067; -.
DR   HOGENOM; CLU_027611_2_1_1; -.
DR   InParanoid; Q9UPQ8; -.
DR   KO; K00902; -.
DR   OMA; RKYFHFI; -.
DR   OrthoDB; 1533260at2759; -.
DR   PhylomeDB; Q9UPQ8; -.
DR   TreeFam; TF323379; -.
DR   Reactome; R-HSA-446199; Synthesis of Dolichyl-phosphate.
DR   Reactome; R-HSA-4755583; Defective DOLK causes DOLK-CDG (CDG-1m).
DR   GeneWiki; Dolichol_kinase; -.
DR   GenomeRNAi; 22845; -.
DR   Pharos; Q9UPQ8; Tbio.
DR   PRO; PR:Q9UPQ8; -.
DR   Proteomes; UP000005640; Chromosome 9.
DR   RNAct; Q9UPQ8; protein.
DR   Bgee; ENSG00000175283; Expressed in right adrenal gland and 198 other tissues.
DR   ExpressionAtlas; Q9UPQ8; baseline and differential.
DR   Genevisible; Q9UPQ8; HS.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR   GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; IDA:UniProtKB.
DR   GO; GO:0004168; F:dolichol kinase activity; IDA:UniProtKB.
DR   GO; GO:0006489; P:dolichyl diphosphate biosynthetic process; TAS:Reactome.
DR   GO; GO:0043048; P:dolichyl monophosphate biosynthetic process; IDA:UniProtKB.
DR   InterPro; IPR026566; DOLK.
DR   InterPro; IPR032974; Polypren_kinase.
DR   PANTHER; PTHR13205; PTHR13205; 1.
DR   PANTHER; PTHR13205:SF15; PTHR13205:SF15; 1.
PE   1: Evidence at protein level;
KW   Congenital disorder of glycosylation; Disease mutation;
KW   Endoplasmic reticulum; Kinase; Membrane; Polymorphism; Reference proteome;
KW   Transferase; Transmembrane; Transmembrane helix.
FT   CHAIN           1..538
FT                   /note="Dolichol kinase"
FT                   /id="PRO_0000072595"
FT   TOPO_DOM        1..13
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        14..34
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        35..74
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        75..95
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        96..111
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        112..132
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        133..134
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        135..155
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        156..163
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        164..184
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        185..188
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        189..209
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        210..224
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        225..245
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        246..254
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        255..275
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        276..297
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        298..318
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        319..337
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        338..354
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        355..359
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        360..380
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        381..401
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        402..422
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        423..436
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        437..457
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        458..472
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        473..493
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        494..495
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        496..516
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        517..538
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   REGION          459..474
FT                   /note="CTP-binding"
FT   VARIANT         99
FT                   /note="C -> S (in CDG1M; 2% residual activity; fails to
FT                   complement the temperature-sensitive phenotype of DK1-
FT                   deficient yeast cells; dbSNP:rs137853109)"
FT                   /evidence="ECO:0000269|PubMed:17273964"
FT                   /id="VAR_032851"
FT   VARIANT         224
FT                   /note="D -> V (in dbSNP:rs17485436)"
FT                   /id="VAR_049709"
FT   VARIANT         441
FT                   /note="Y -> S (in CDG1M; 4% residual activity; fails to
FT                   complement the temperature-sensitive phenotype of DK1-
FT                   deficient yeast cells; dbSNP:rs137853110)"
FT                   /evidence="ECO:0000269|PubMed:17273964"
FT                   /id="VAR_032852"
FT   MUTAGEN         443
FT                   /note="G->D: Abolishes kinase activity."
FT                   /evidence="ECO:0000269|PubMed:16923818"
FT   MUTAGEN         451
FT                   /note="D->A: Reduces kinase activity."
FT                   /evidence="ECO:0000269|PubMed:16923818"
FT   MUTAGEN         470
FT                   /note="K->A: Reduces kinase activity. Significant reduction
FT                   in binding affinity for CTP; when associated with A-471."
FT                   /evidence="ECO:0000269|PubMed:16923818"
FT   MUTAGEN         471
FT                   /note="K->A: Reduces kinase activity. Significant reduction
FT                   in binding affinity for CTP."
FT                   /evidence="ECO:0000269|PubMed:16923818"
FT   MUTAGEN         472
FT                   /note="T->A: Reduces kinase activity. Significant reduction
FT                   in binding affinity for CTP."
FT                   /evidence="ECO:0000269|PubMed:16923818"
FT   MUTAGEN         474
FT                   /note="E->A: No effect on kinase activity."
FT                   /evidence="ECO:0000269|PubMed:16923818"
FT   MUTAGEN         475
FT                   /note="G->A: No effect on kinase activity."
FT                   /evidence="ECO:0000269|PubMed:16923818"
SQ   SEQUENCE   538 AA;  59268 MW;  EB7D1BABD45362AD CRC64;
     MTRECPSPAP GPGAPLSGSV LAEAAVVFAV VLSIHATVWD RYSWCAVALA VQAFYVQYKW
     DRLLQQGSAV FQFRMSANSG LLPASMVMPL LGLVMKERCQ TAGNPFFERF GIVVAATGMA
     VALFSSVLAL GITRPVPTNT CVILGLAGGV IIYIMKHSLS VGEVIEVLEV LLIFVYLNMI
     LLYLLPRCFT PGEALLVLGG ISFVLNQLIK RSLTLVESQG DPVDFFLLVV VVGMVLMGIF
     FSTLFVFMDS GTWASSIFFH LMTCVLSLGV VLPWLHRLIR RNPLLWLLQF LFQTDTRIYL
     LAYWSLLATL ACLVVLYQNA KRSSSESKKH QAPTIARKYF HLIVVATYIP GIIFDRPLLY
     VAATVCLAVF IFLEYVRYFR IKPLGHTLRS FLSLFLDERD SGPLILTHIY LLLGMSLPIW
     LIPRPCTQKG SLGGARALVP YAGVLAVGVG DTVASIFGST MGEIRWPGTK KTFEGTMTSI
     FAQIISVALI LIFDSGVDLN YSYAWILGSI STVSLLEAYT TQIDNLLLPL YLLILLMA
//