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Q9NR20

- DYRK4_HUMAN

UniProt

Q9NR20 - DYRK4_HUMAN

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Protein

Dual specificity tyrosine-phosphorylation-regulated kinase 4

Gene

DYRK4

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

Functioni

Possible non-essential role in spermiogenesis.By similarity

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Mg2+By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei133 – 1331ATP
Active sitei230 – 2301Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi110 – 1189ATPPROSITE-ProRule annotation
Nucleotide bindingi183 – 1864ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. metal ion binding Source: UniProtKB-KW
  3. protein serine/threonine/tyrosine kinase activity Source: UniProtKB-EC
  4. protein serine/threonine kinase activity Source: UniProtKB-KW
  5. protein tyrosine kinase activity Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase, Tyrosine-protein kinase

Keywords - Ligandi

ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

SignaLinkiQ9NR20.

Names & Taxonomyi

Protein namesi
Recommended name:
Dual specificity tyrosine-phosphorylation-regulated kinase 4 (EC:2.7.12.1)
Gene namesi
Name:DYRK4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 12

Organism-specific databases

HGNCiHGNC:3095. DYRK4.

Subcellular locationi

Isoform 1 : Cytoplasm 1 Publication
Isoform 4 : Cytoplasm 1 Publication. Nucleus 1 Publication

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB-KW
  2. intracellular membrane-bounded organelle Source: HPA
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi133 – 1331K → R: Loss of kinase activity. 1 Publication
Mutagenesisi264 – 2641Y → F: Abolishes kinase activity. 1 Publication

Organism-specific databases

PharmGKBiPA27552.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 520520Dual specificity tyrosine-phosphorylation-regulated kinase 4PRO_0000085940Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei264 – 2641Phosphotyrosine; by autocatalysis1 Publication

Post-translational modificationi

Autophosphorylation on Tyr-264 in the activation loop is required for kinase activity.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ9NR20.
PaxDbiQ9NR20.
PRIDEiQ9NR20.

PTM databases

PhosphoSiteiQ9NR20.

Expressioni

Gene expression databases

BgeeiQ9NR20.
CleanExiHS_DYRK4.
ExpressionAtlasiQ9NR20. baseline and differential.
GenevestigatoriQ9NR20.

Organism-specific databases

HPAiHPA028065.
HPA056073.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
DYRK2Q926303EBI-3914009,EBI-749432

Protein-protein interaction databases

BioGridi114326. 15 interactions.
IntActiQ9NR20. 12 interactions.
STRINGi9606.ENSP00000010132.

Structurei

3D structure databases

ProteinModelPortaliQ9NR20.
SMRiQ9NR20. Positions 30-400.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini104 – 400297Protein kinasePROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00760000119032.
HOGENOMiHOG000220863.
HOVERGENiHBG051426.
InParanoidiQ9NR20.
KOiK08825.
OMAiQHSGDQQ.
PhylomeDBiQ9NR20.
TreeFamiTF314624.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequences (5)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: Q9NR20-1) [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
MPASELKASE IPFHPSIKTQ DPKAEEKSPK KQKVTLTAAE ALKLFKNQLS
60 70 80 90 100
PYEQSEILGY AELWFLGLEA KKLDTAPEKF SKTSFDDEHG FYLKVLHDHI
110 120 130 140 150
AYRYEVLETI GKGSFGQVAK CLDHKNNELV ALKIIRNKKR FHQQALMELK
160 170 180 190 200
ILEALRKKDK DNTYNVVHMK DFFYFRNHFC ITFELLGINL YELMKNNNFQ
210 220 230 240 250
GFSLSIVRRF TLSVLKCLQM LSVEKIIHCD LKPENIVLYQ KGQASVKVID
260 270 280 290 300
FGSSCYEHQK VYTYIQSRFY RSPEVILGHP YDVAIDMWSL GCITAELYTG
310 320 330 340 350
YPLFPGENEV EQLACIMEVL GLPPAGFIQT ASRRQTFFDS KGFPKNITNN
360 370 380 390 400
RGKKRYPDSK DLTMVLKTYD TSFLDFLRRC LVWEPSLRMT PDQALKHAWI
410 420 430 440 450
HQSRNLKPQP RPQTLRKSNS FFPSETRKDK VQGCHHSSRK ADEITKETTE
460 470 480 490 500
KTKDSPTKHV QHSGDQQDCL QHGADTVQLP QLVDAPKKSE AAVGAEVSMT
510 520
SPGQSKNFSL KNTNVLPPIV

Note: May be due to a competing acceptor splice site. No experimental confirmation available.

Length:520
Mass (Da):59,608
Last modified:May 10, 2005 - v2
Checksum:i33FECD8249DDB223
GO
Isoform 2 (identifier: Q9NR20-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     441-441: Missing.

Show »
Length:519
Mass (Da):59,537
Checksum:i2ACD1BC87AA1591B
GO
Isoform 3 (identifier: Q9NR20-3) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MQLLPPPIRT...YQENQAHNQM

Note: No experimental confirmation available.

Show »
Length:635
Mass (Da):72,577
Checksum:i42F432C350F65F2D
GO
Isoform 4 (identifier: Q9NR20-4) [UniParc]FASTAAdd to Basket

Also known as: DYRK4-L

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MQLLPPPIRT...YQENQAHNQM

Note: Contains a bipartite nuclear localization signal at positions 19-37.1 Publication

Show »
Length:644
Mass (Da):73,569
Checksum:i688041E86A28626C
GO
Isoform 5 (identifier: Q9NR20-5) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     380-382: Missing.

Note: Due to an alternative splicing donor site in exon 19. Markedly reduced enzymatic activity.1 Publication

Show »
Length:517
Mass (Da):59,293
Checksum:i0C076681A026AC27
GO

Sequence cautioni

The sequence AAF91393.1 differs from that shown. Reason: Erroneous initiation. Curated
The sequence AK308260 differs from that shown. Reason: Frameshift at position 470. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti165 – 1651N → I in BAF85011. (PubMed:14702039)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti61 – 611A → T.
Corresponds to variant rs12306130 [ dbSNP | Ensembl ].
VAR_033900
Natural varianti70 – 701A → S.1 Publication
VAR_040465
Natural varianti95 – 951V → I.1 Publication
VAR_010721
Natural varianti189 – 1891N → S.1 Publication
Corresponds to variant rs3741927 [ dbSNP | Ensembl ].
VAR_010722
Natural varianti454 – 4541D → V.
Corresponds to variant rs1801016 [ dbSNP | Ensembl ].
VAR_014948

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 11M → MQLLPPPIRTGTKTQMDAKK PRKCDLTPFLVLKARKKQKF TSAKVGSKLSVQIQKPPSNI KNSRMTQVFHKNTSVTSLPF VDTKGKKNTVSFPHISKKVL LKSSLLYQENQAHNQM in isoform 3. 1 PublicationVSP_057132
Alternative sequencei1 – 11M → MQLLPPPIRTGTKTQMDAKK PRKCDLTPFLVLKARKKQKF TSAKGPTLSEIYMVGSKLSV QIQKPPSNIKNSRMTQVFHK NTSVTSLPFVDTKGKKNTVS FPHISKKVLLKSSLLYQENQ AHNQM in isoform 4. 1 PublicationVSP_057133
Alternative sequencei380 – 3823Missing in isoform 5. 1 PublicationVSP_057134
Alternative sequencei441 – 4411Missing in isoform 2. 2 PublicationsVSP_013745

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF263541 mRNA. Translation: AAF91393.1. Different initiation.
AK292322 mRNA. Translation: BAF85011.1.
AK308260 mRNA. No translation available.
BC031244 mRNA. Translation: AAH31244.1.
Y09305 mRNA. Translation: CAA70488.1.
CCDSiCCDS8530.1. [Q9NR20-1]
RefSeqiNP_003836.1. NM_003845.2. [Q9NR20-1]
UniGeneiHs.439530.

Genome annotation databases

EnsembliENST00000010132; ENSP00000010132; ENSG00000010219. [Q9NR20-1]
ENST00000540757; ENSP00000441755; ENSG00000010219. [Q9NR20-1]
GeneIDi8798.
KEGGihsa:8798.
UCSCiuc001qmx.3. human. [Q9NR20-1]
uc001qmy.2. human. [Q9NR20-2]

Polymorphism databases

DMDMi68566308.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF263541 mRNA. Translation: AAF91393.1 . Different initiation.
AK292322 mRNA. Translation: BAF85011.1 .
AK308260 mRNA. No translation available.
BC031244 mRNA. Translation: AAH31244.1 .
Y09305 mRNA. Translation: CAA70488.1 .
CCDSi CCDS8530.1. [Q9NR20-1 ]
RefSeqi NP_003836.1. NM_003845.2. [Q9NR20-1 ]
UniGenei Hs.439530.

3D structure databases

ProteinModelPortali Q9NR20.
SMRi Q9NR20. Positions 30-400.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 114326. 15 interactions.
IntActi Q9NR20. 12 interactions.
STRINGi 9606.ENSP00000010132.

Chemistry

BindingDBi Q9NR20.
ChEMBLi CHEMBL1075115.
GuidetoPHARMACOLOGYi 2013.

PTM databases

PhosphoSitei Q9NR20.

Polymorphism databases

DMDMi 68566308.

Proteomic databases

MaxQBi Q9NR20.
PaxDbi Q9NR20.
PRIDEi Q9NR20.

Protocols and materials databases

DNASUi 8798.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000010132 ; ENSP00000010132 ; ENSG00000010219 . [Q9NR20-1 ]
ENST00000540757 ; ENSP00000441755 ; ENSG00000010219 . [Q9NR20-1 ]
GeneIDi 8798.
KEGGi hsa:8798.
UCSCi uc001qmx.3. human. [Q9NR20-1 ]
uc001qmy.2. human. [Q9NR20-2 ]

Organism-specific databases

CTDi 8798.
GeneCardsi GC12P004671.
HGNCi HGNC:3095. DYRK4.
HPAi HPA028065.
HPA056073.
MIMi 609181. gene.
neXtProti NX_Q9NR20.
PharmGKBi PA27552.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0515.
GeneTreei ENSGT00760000119032.
HOGENOMi HOG000220863.
HOVERGENi HBG051426.
InParanoidi Q9NR20.
KOi K08825.
OMAi QHSGDQQ.
PhylomeDBi Q9NR20.
TreeFami TF314624.

Enzyme and pathway databases

SignaLinki Q9NR20.

Miscellaneous databases

GenomeRNAii 8798.
NextBioi 33000.
PROi Q9NR20.
SOURCEi Search...

Gene expression databases

Bgeei Q9NR20.
CleanExi HS_DYRK4.
ExpressionAtlasi Q9NR20. baseline and differential.
Genevestigatori Q9NR20.

Family and domain databases

InterProi IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view ]
Pfami PF00069. Pkinase. 1 hit.
[Graphical view ]
SMARTi SM00220. S_TKc. 1 hit.
[Graphical view ]
SUPFAMi SSF56112. SSF56112. 1 hit.
PROSITEi PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23."
    White K.E., Evans W.E., O'Riordan J.L.H., Speer M.C., Econs M.J., Lorenz-Depiereux B., Grabowski M., Meitinger T., Strom T.M.
    Nat. Genet. 26:345-348(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANTS ILE-95 AND SER-189.
    Tissue: Brain and Kidney.
  2. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-430 (ISOFORM 3).
    Tissue: Testis.
  3. "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] (ISOFORM 1).
    Tissue: Testis.
  4. "Sequence characteristics, subcellular localization, and substrate specificity of DYRK-related kinases, a novel family of dual specificity protein kinases."
    Becker W., Weber Y., Wetzel K., Eirmbter K., Tejedor F.J., Joost H.-G.
    J. Biol. Chem. 273:25893-25902(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 280-520 (ISOFORM 2).
    Tissue: Lung.
  5. "The expression of the testis-specific Dyrk4 kinase is highly restricted to step 8 spermatids but is not required for male fertility in mice."
    Sacher F., Moeller C., Bone W., Gottwald U., Fritsch M.
    Mol. Cell. Endocrinol. 267:80-88(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-133.
  6. "Splice variants of the dual specificity tyrosine phosphorylation-regulated kinase 4 (DYRK4) differ in their subcellular localization and catalytic activity."
    Papadopoulos C., Arato K., Lilienthal E., Zerweck J., Schutkowski M., Chatain N., Muller-Newen G., Becker W., de la Luna S.
    J. Biol. Chem. 286:5494-5505(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: ALTERNATIVE SPLICING (ISOFORMS 4 AND 5), SUBCELLULAR LOCATION (ISOFORM 4), MUTAGENESIS OF TYR-264, PHOSPHORYLATION AT TYR-264.
  7. "Patterns of somatic mutation in human cancer genomes."
    Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.
    , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
    Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT [LARGE SCALE ANALYSIS] SER-70.

Entry informationi

Entry nameiDYRK4_HUMAN
AccessioniPrimary (citable) accession number: Q9NR20
Secondary accession number(s): A8K8F7, Q8NEF2, Q92631
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: May 10, 2005
Last modified: November 26, 2014
This is version 139 of the entry and version 2 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, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: 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. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3