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Q9H422

- HIPK3_HUMAN

UniProt

Q9H422 - HIPK3_HUMAN

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Protein
Homeodomain-interacting protein kinase 3
Gene
HIPK3, DYRK6, FIST3, PKY
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

Serine/threonine-protein kinase involved in transcription regulation, apoptosis and steroidogenic gene expression. Phosphorylates JUN and RUNX2. Seems to negatively regulate apoptosis by promoting FADD phosphorylation. Enhances androgen receptor-mediated transcription. May act as a transcriptional corepressor for NK homeodomain transcription factors. The phosphorylation of NR5A1 activates SF1 leading to increased steroidogenic gene expression upon cAMP signaling pathway stimulation. In osteoblasts, supports transcription activation: phosphorylates RUNX2 that synergizes with SPEN/MINT to enhance FGFR2-mediated activation of the osteocalcin FGF-responsive element (OCFRE).2 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei226 – 2261ATP By similarity
Active sitei322 – 3221Proton acceptor By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi203 – 2119ATP By similarity

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. protein kinase activity Source: UniProtKB
  3. protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

  1. apoptotic process Source: UniProtKB-KW
  2. mRNA transcription Source: UniProtKB
  3. negative regulation of JUN kinase activity Source: UniProtKB
  4. negative regulation of apoptotic process Source: UniProtKB
  5. peptidyl-serine phosphorylation Source: UniProtKB
  6. peptidyl-threonine phosphorylation Source: UniProtKB
  7. protein phosphorylation Source: UniProtKB
  8. regulation of transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Apoptosis, Transcription, Transcription regulation

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

SignaLinkiQ9H422.

Names & Taxonomyi

Protein namesi
Recommended name:
Homeodomain-interacting protein kinase 3 (EC:2.7.11.1)
Alternative name(s):
Androgen receptor-interacting nuclear protein kinase
Short name:
ANPK
Fas-interacting serine/threonine-protein kinase
Short name:
FIST
Homolog of protein kinase YAK1
Gene namesi
Name:HIPK3
Synonyms:DYRK6, FIST3, PKY
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 11

Organism-specific databases

HGNCiHGNC:4915. HIPK3.

Subcellular locationi

Cytoplasm. Nucleus 1 Publication

GO - Cellular componenti

  1. PML body Source: Ensembl
  2. cytoplasm Source: HPA
  3. nucleus Source: HPA
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi226 – 2261K → R: Loss of kinase activity and impaired activation of SF1. 1 Publication

Organism-specific databases

PharmGKBiPA29292.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 12151215Homeodomain-interacting protein kinase 3
PRO_0000085998Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Cross-linki27 – 27Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity
Modified residuei359 – 3591Phosphotyrosine By similarity
Cross-linki1208 – 1208Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity

Post-translational modificationi

Autophosphorylated, but autophosphorylation is not required for catalytic activity By similarity.
May be sumoylated By similarity.

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ9H422.
PRIDEiQ9H422.

PTM databases

PhosphoSiteiQ9H422.

Expressioni

Tissue specificityi

Overexpressed in multidrug resistant cells. Highly expressed in heart and skeletal muscle, and at lower levels in placenta, pancreas, brain, spleen, prostate, thymus, testis, small intestine, colon and leukocytes. Not found in liver and lung.3 Publications

Gene expression databases

ArrayExpressiQ9H422.
BgeeiQ9H422.
CleanExiHS_HIPK3.
GenevestigatoriQ9H422.

Organism-specific databases

HPAiHPA028069.

Interactioni

Subunit structurei

Interacts with Nkx1-2. Interacts with FAS and DAXX. Probably part of a complex consisting of HIPK3, FAS and FADD. Interacts with and stabilizes ligand-bound androgen receptor (AR) By similarity. Interacts with UBL1/SUMO-1. Binds to NR5A1/SF1, SPEN/MINT and RUNX2.2 Publications

Protein-protein interaction databases

BioGridi115420. 32 interactions.
IntActiQ9H422. 22 interactions.
MINTiMINT-1183373.
STRINGi9606.ENSP00000304226.

Structurei

3D structure databases

ProteinModelPortaliQ9H422.
SMRiQ9H422. Positions 189-557.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini197 – 525329Protein kinase
Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni767 – 944178Interaction with AR By similarity
Add
BLAST
Regioni796 – 89196Interaction with FAS By similarity
Add
BLAST
Regioni855 – 1011157Required for localization to nuclear speckles By similarity
Add
BLAST
Regioni866 – 91853SUMO interaction motifs (SIM); required for nuclear localization and kinase activity By similarity
Add
BLAST
Regioni870 – 88011Interaction with UBL1 Inferred
Add
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi910 – 96253Ser-rich
Add
BLAST

Sequence similaritiesi

Phylogenomic databases

eggNOGiCOG0515.
HOGENOMiHOG000231785.
HOVERGENiHBG051908.
InParanoidiQ9H422.
KOiK08826.
OMAiPAMLQTN.
OrthoDBiEOG7034GK.
PhylomeDBiQ9H422.
TreeFamiTF105417.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 2 hits.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: Q9H422-1) [UniParc]FASTAAdd to Basket

Also known as: HIPK3

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

MASQVLVYPP YVYQTQSSAF CSVKKLKVEP SSCVFQERNY PRTYVNGRNF     50
GNSHPPTKGS AFQTKIPFNR PRGHNFSLQT SAVVLKNTAG ATKVIAAQAQ 100
QAHVQAPQIG AWRNRLHFLE GPQRCGLKRK SEELDNHSSA MQIVDELSIL 150
PAMLQTNMGN PVTVVTATTG SKQNCTTGEG DYQLVQHEVL CSMKNTYEVL 200
DFLGRGTFGQ VVKCWKRGTN EIVAIKILKN HPSYARQGQI EVSILARLST 250
ENADEYNFVR AYECFQHRNH TCLVFEMLEQ NLYDFLKQNK FSPLPLKVIR 300
PILQQVATAL KKLKSLGLIH ADLKPENIML VDPVRQPYRV KVIDFGSASH 350
VSKTVCSTYL QSRYYRAPEI ILGLPFCEAI DMWSLGCVIA ELFLGWPLYP 400
GALEYDQIRY ISQTQGLPGE QLLNVGTKST RFFCKETDMS HSGWRLKTLE 450
EHEAETGMKS KEARKYIFNS LDDVAHVNTV MDLEGSDLLA EKADRREFVS 500
LLKKMLLIDA DLRITPAETL NHPFVNMKHL LDFPHSNHVK SCFHIMDICK 550
SHLNSCDTNN HNKTSLLRPV ASSSTATLTA NFTKIGTLRS QALTTSAHSV 600
VHHGIPLQAG TAQFGCGDAF QQTLIICPPA IQGIPATHGK PTSYSIRVDN 650
TVPLVTQAPA VQPLQIRPGV LSQTWSGRTQ QMLVPAWQQV TPLAPATTTL 700
TSESVAGSHR LGDWGKMISC SNHYNSVMPQ PLLTNQITLS APQPVSVGIA 750
HVVWPQPATT KKNKQCQNRG ILVKLMEWEP GREEINAFSW SNSLQNTNIP 800
HSAFISPKII NGKDVEEVSC IETQDNQNSE GEARNCCETS IRQDSDSSVS 850
DKQRQTIIIA DSPSPAVSVI TISSDTDEEE TSQRHSLREC KGSLDCEACQ 900
STLNIDRMCS LSSPDSTLST SSSGQSSPSP CKRPNSMSDE EQESSCDTVD 950
GSPTSDSSGH DSPFAESTFV EDTHENTELV SSADTETKPA VCSVVVPPVE 1000
LENGLNADEH MANTDSICQP LIKGRSAPGR LNQPSAVGTR QQKLTSAFQQ 1050
QHLNFSQVQH FGSGHQEWNG NFGHRRQQAY IPTSVTSNPF TLSHGSPNHT 1100
AVHAHLAGNT HLGGQPTLLP YPSSATLSSA APVAHLLASP CTSRPMLQHP 1150
TYNISHPSGI VHQVPVGLNP RLLPSPTIHQ TQYKPIFPPH SYIAASPAYT 1200
GFPLSPTKLS QYPYM 1215
Length:1,215
Mass (Da):133,743
Last modified:March 1, 2001 - v1
Checksum:iE952D04786955721
GO
Isoform 2 (identifier: Q9H422-2) [UniParc]FASTAAdd to Basket

Also known as: FIST

The sequence of this isoform differs from the canonical sequence as follows:
     770-790: Missing.

Show »
Length:1,194
Mass (Da):131,256
Checksum:i9F7C34FB1110F10B
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti142 – 1421Q → R.1 Publication
Corresponds to variant rs34193811 [ dbSNP | Ensembl ].
VAR_040549
Natural varianti170 – 1701G → E.1 Publication
Corresponds to variant rs34698015 [ dbSNP | Ensembl ].
VAR_040550
Natural varianti191 – 1911C → R.1 Publication
Corresponds to variant rs35689361 [ dbSNP | Ensembl ].
VAR_040551
Natural varianti474 – 4741V → I.
Corresponds to variant rs266472 [ dbSNP | Ensembl ].
VAR_051627
Natural varianti500 – 5001S → N.1 Publication
Corresponds to variant rs11032229 [ dbSNP | Ensembl ].
VAR_040552
Natural varianti729 – 7291P → L.1 Publication
Corresponds to variant rs55807239 [ dbSNP | Ensembl ].
VAR_040553

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei770 – 79021Missing in isoform 2.
VSP_013140Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti69 – 691N → K in AAG25990. 1 Publication
Sequence conflicti111 – 1111A → V in AAC64294. 1 Publication
Sequence conflicti1148 – 11481Q → K in AAG25990. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF004849 mRNA. Translation: AAC64294.1.
AF305239 mRNA. Translation: AAG25990.1.
AL122015 Genomic DNA. Translation: CAC13164.1.
AL122015 Genomic DNA. Translation: CAJ55828.1.
Y09306 mRNA. Translation: CAA70489.1. Different termination.
CCDSiCCDS41634.1. [Q9H422-2]
CCDS7884.1. [Q9H422-1]
RefSeqiNP_001041665.1. NM_001048200.2. [Q9H422-2]
NP_001265092.1. NM_001278163.1. [Q9H422-2]
NP_005725.3. NM_005734.4. [Q9H422-1]
XP_005252786.1. XM_005252729.2. [Q9H422-1]
XP_006718183.1. XM_006718120.1. [Q9H422-1]
UniGeneiHs.201918.
Hs.709696.

Genome annotation databases

EnsembliENST00000303296; ENSP00000304226; ENSG00000110422. [Q9H422-1]
ENST00000379016; ENSP00000368301; ENSG00000110422. [Q9H422-2]
ENST00000456517; ENSP00000398241; ENSG00000110422. [Q9H422-2]
ENST00000525975; ENSP00000431710; ENSG00000110422. [Q9H422-2]
GeneIDi10114.
KEGGihsa:10114.
UCSCiuc001mul.2. human. [Q9H422-1]
uc001mum.2. human. [Q9H422-2]

Polymorphism databases

DMDMi61213741.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF004849 mRNA. Translation: AAC64294.1 .
AF305239 mRNA. Translation: AAG25990.1 .
AL122015 Genomic DNA. Translation: CAC13164.1 .
AL122015 Genomic DNA. Translation: CAJ55828.1 .
Y09306 mRNA. Translation: CAA70489.1 . Different termination.
CCDSi CCDS41634.1. [Q9H422-2 ]
CCDS7884.1. [Q9H422-1 ]
RefSeqi NP_001041665.1. NM_001048200.2. [Q9H422-2 ]
NP_001265092.1. NM_001278163.1. [Q9H422-2 ]
NP_005725.3. NM_005734.4. [Q9H422-1 ]
XP_005252786.1. XM_005252729.2. [Q9H422-1 ]
XP_006718183.1. XM_006718120.1. [Q9H422-1 ]
UniGenei Hs.201918.
Hs.709696.

3D structure databases

ProteinModelPortali Q9H422.
SMRi Q9H422. Positions 189-557.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 115420. 32 interactions.
IntActi Q9H422. 22 interactions.
MINTi MINT-1183373.
STRINGi 9606.ENSP00000304226.

Chemistry

BindingDBi Q9H422.
ChEMBLi CHEMBL4577.
GuidetoPHARMACOLOGYi 2035.

PTM databases

PhosphoSitei Q9H422.

Polymorphism databases

DMDMi 61213741.

Proteomic databases

PaxDbi Q9H422.
PRIDEi Q9H422.

Protocols and materials databases

DNASUi 10114.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000303296 ; ENSP00000304226 ; ENSG00000110422 . [Q9H422-1 ]
ENST00000379016 ; ENSP00000368301 ; ENSG00000110422 . [Q9H422-2 ]
ENST00000456517 ; ENSP00000398241 ; ENSG00000110422 . [Q9H422-2 ]
ENST00000525975 ; ENSP00000431710 ; ENSG00000110422 . [Q9H422-2 ]
GeneIDi 10114.
KEGGi hsa:10114.
UCSCi uc001mul.2. human. [Q9H422-1 ]
uc001mum.2. human. [Q9H422-2 ]

Organism-specific databases

CTDi 10114.
GeneCardsi GC11P033235.
HGNCi HGNC:4915. HIPK3.
HPAi HPA028069.
MIMi 604424. gene.
neXtProti NX_Q9H422.
PharmGKBi PA29292.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0515.
HOGENOMi HOG000231785.
HOVERGENi HBG051908.
InParanoidi Q9H422.
KOi K08826.
OMAi PAMLQTN.
OrthoDBi EOG7034GK.
PhylomeDBi Q9H422.
TreeFami TF105417.

Enzyme and pathway databases

SignaLinki Q9H422.

Miscellaneous databases

ChiTaRSi HIPK3. human.
GeneWikii HIPK3.
GenomeRNAii 10114.
NextBioi 38263.
PROi Q9H422.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q9H422.
Bgeei Q9H422.
CleanExi HS_HIPK3.
Genevestigatori Q9H422.

Family and domain databases

InterProi IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
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. 2 hits.
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. "Identification and sequence of human PKY, a putative kinase with increased expression in multidrug-resistant cells, with homology to yeast protein kinase Yak1."
    Begley D.A., Berkenpas M.B., Sampson K.E., Abraham I.
    Gene 200:35-43(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
  2. "FIST/HIPK3: a Fas/FADD-interacting serine/threonine kinase that induces FADD phosphorylation and inhibits Fas-mediated Jun NH2-terminal kinase activation."
    Rochat-Steiner V., Becker K., Micheau O., Schneider P., Burns K., Tschopp J.
    J. Exp. Med. 192:1165-1174(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. Becker W., Joost H.G.
    Submitted (NOV-1996) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-295 (ISOFORMS 1/2).
  5. "Activation of androgen receptor function by a novel nuclear protein kinase."
    Moilanen A.-M., Karvonen U., Poukka H., Jaenne O.A., Palvimo J.J.
    Mol. Biol. Cell 9:2527-2543(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  6. "Covalent modification of p73alpha by SUMO-1. Two-hybrid screening with p73 identifies novel SUMO-1-interacting proteins and a SUMO-1 interaction motif."
    Minty A., Dumont X., Kaghad M., Caput D.
    J. Biol. Chem. 275:36316-36323(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH UBL1.
  7. "JNK regulates HIPK3 expression and promotes resistance to Fas-mediated apoptosis in DU 145 prostate carcinoma cells."
    Curtin J.F., Cotter T.G.
    J. Biol. Chem. 279:17090-17100(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  8. "Cyclic AMP stimulates SF-1-dependent CYP11A1 expression through homeodomain-interacting protein kinase 3-mediated Jun N-terminal kinase and c-Jun phosphorylation."
    Lan H.-C., Li H.-J., Lin G., Lai P.-Y., Chung B.-C.
    Mol. Cell. Biol. 27:2027-2036(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION AS KINASE AND IN CAMP SIGNALING PATHWAY, INTERACTION WITH NR5A1/SF1, MUTAGENESIS OF LYS-226.
  9. "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: VARIANTS [LARGE SCALE ANALYSIS] ARG-142; GLU-170; ARG-191; ASN-500 AND LEU-729.

Entry informationi

Entry nameiHIPK3_HUMAN
AccessioniPrimary (citable) accession number: Q9H422
Secondary accession number(s): O14632
, Q2PBG4, Q2PBG5, Q92632, Q9HAS2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 15, 2005
Last sequence update: March 1, 2001
Last modified: July 9, 2014
This is version 123 of the entry and version 1 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 11
    Human chromosome 11: 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

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