Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q9UPZ9 (ICK_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 127. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Serine/threonine-protein kinase ICK

EC=2.7.11.22
Alternative name(s):
Intestinal cell kinase
Short name=hICK
Laryngeal cancer kinase 2
Short name=LCK2
MAK-related kinase
Short name=MRK
Gene names
Name:ICK
Synonyms:KIAA0936
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length632 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

May play a key role in the development of multiple organ systems and particularly in cardiac development By similarity. Ref.1 Ref.10

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Cofactor

Magnesium. Ref.1

Subcellular location

Nucleus. Cytoplasmcytosol By similarity. Note: Nuclear localization has been observed with a GFP-tagged construct in transfected HeLa cells (Ref.2). Cytosolic localization was shown in rat embryonic cardiomyocytes by immunostaining (PubMed:8570168). Ref.2

Tissue specificity

Expressed in heart, brain, placenta, pancreas, thymus, prostate, testis, ovary, small intestine and colon, with highest levels in placenta and testis. Not detected in spleen. Also expressed in many cancer cell lines. Ref.1 Ref.2

Post-translational modification

Autophosphorylated on serine and threonine residues. May play a role in enzyme activation. Ref.1

Involvement in disease

Endocrine-cerebroosteodysplasia (ECO) [MIM:612651]: Previously unidentified neonatal lethal recessive disorder with multiple anomalies involving the endocrine, cerebral, and skeletal systems.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10

Sequence similarities

Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.

Contains 1 protein kinase domain.

Sequence caution

The sequence BAA76780.2 differs from that shown. Reason: Erroneous initiation.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

HSP90AB1P082382EBI-6381479,EBI-352572

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 Ref.1 (identifier: Q9UPZ9-1)

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.
Isoform 2 (identifier: Q9UPZ9-2)

The sequence of this isoform differs from the canonical sequence as follows:
     278-292: ALRYPYFQVGHPLGS → VFFHFLVITFISNSE
     293-632: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 632632Serine/threonine-protein kinase ICK
PRO_0000086007

Regions

Domain4 – 284281Protein kinase
Nucleotide binding10 – 189ATP By similarity UniProtKB P06493

Sites

Active site1251Proton acceptor By similarity UniProtKB P06493
Binding site331ATP Ref.1

Amino acid modifications

Modified residue1571Phosphothreonine Ref.1
Modified residue1591Phosphotyrosine Ref.1

Natural variations

Alternative sequence278 – 29215ALRYP…HPLGS → VFFHFLVITFISNSE in isoform 2.
VSP_050752
Alternative sequence293 – 632340Missing in isoform 2.
VSP_050753
Natural variant981P → L.
Corresponds to variant rs1493105 [ dbSNP | Ensembl ].
VAR_053931
Natural variant1151F → Y in a renal clear cell carcinoma sample; somatic mutation. Ref.9
VAR_042001
Natural variant2721R → Q in ECO; fails to localize at the nucleus and significantly impairs kinase activity. Ref.10
VAR_057994
Natural variant3201V → I. Ref.9
Corresponds to variant rs33936662 [ dbSNP | Ensembl ].
VAR_042002
Natural variant4711T → K. Ref.9
Corresponds to variant rs56164633 [ dbSNP | Ensembl ].
VAR_042003
Natural variant4761R → Q. Ref.9
Corresponds to variant rs55895113 [ dbSNP | Ensembl ].
VAR_042004
Natural variant6151A → T. Ref.9
Corresponds to variant rs55932059 [ dbSNP | Ensembl ].
VAR_042005

Experimental info

Mutagenesis331K → R: Loss of activity and autophosphorylation; when associated with R-34; R-36 and R-38. Ref.1
Mutagenesis341K → R: Loss of activity and autophosphorylation; when associated with R-33; R-36 and R-38. Ref.1
Mutagenesis361K → R: Loss of activity and autophosphorylation; when associated with R-33; R-34 and R-38. Ref.1
Mutagenesis381K → R: Loss of activity and autophosphorylation; when associated with R-33; R-34 and R-36. Ref.1
Mutagenesis1571T → A: Reduction of activity and loss of autophosphorylation. Loss of activity and autophosphorylation; when associated with F-159. Ref.1
Mutagenesis1591Y → F: Reduction of activity and loss of autophosphorylation. Loss of activity and autophosphorylation; when associated with A-157. Ref.1
Sequence conflict481L → Q in AAF37278. Ref.1
Sequence conflict1191H → L in AAF37278. Ref.1
Sequence conflict3101K → R in AAF37278. Ref.1
Sequence conflict598 – 5992FH → LD in AAF37278. Ref.1
Sequence conflict6291A → P in AAF37278. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 1, 2000. Version 1.
Checksum: F4C22C6CCD5878D2

FASTA63271,427
        10         20         30         40         50         60 
MNRYTTIRQL GDGTYGSVLL GRSIESGELI AIKKMKRKFY SWEECMNLRE VKSLKKLNHA 

        70         80         90        100        110        120 
NVVKLKEVIR ENDHLYFIFE YMKENLYQLI KERNKLFPES AIRNIMYQIL QGLAFIHKHG 

       130        140        150        160        170        180 
FFHRDLKPEN LLCMGPELVK IADFGLAREI RSKPPYTDYV STRWYRAPEV LLRSTNYSSP 

       190        200        210        220        230        240 
IDVWAVGCIM AEVYTLRPLF PGASEIDTIF KICQVLGTPK KTDWPEGYQL SSAMNFRWPQ 

       250        260        270        280        290        300 
CVPNNLKTLI PNASSEAVQL LRDMLQWDPK KRPTASQALR YPYFQVGHPL GSTTQNLQDS 

       310        320        330        340        350        360 
EKPQKGILEK AGPPPYIKPV PPAQPPAKPH TRISSRQHQA SQPPLHLTYP YKAEVSRTDH 

       370        380        390        400        410        420 
PSHLQEDKPS PLLFPSLHNK HPQSKITAGL EHKNGEIKPK SRRRWGLISR STKDSDDWAD 

       430        440        450        460        470        480 
LDDLDFSPSL SRIDLKNKKR QSDDTLCRFE SVLDLKPSEP VGTGNSAPTQ TSYQRRDTPT 

       490        500        510        520        530        540 
LRSAAKQHYL KHSRYLPGIS IRNGILSNPG KEFIPPNPWS SSGLSGKSSG TMSVISKVNS 

       550        560        570        580        590        600 
VGSSSTSSSG LTGNYVPSFL KKEIGSAMQR VHLAPIPDPS PGYSSLKAMR PHPGRPFFHT 

       610        620        630 
QPRSTPGLIP RPPAAQPVHG RTDWASKYAS RR 

« Hide

Isoform 2 [UniParc].

Checksum: AB4CA7370E16F983
Show »

FASTA29234,071

References

« Hide 'large scale' references
[1]"Intestinal cell kinase (ICK) localizes to the crypt region and requires a dual phosphorylation site found in map kinases."
Togawa K., Yan Y.-X., Inomoto T., Slaugenhaupt S.A., Rustgi A.K.
J. Cell. Physiol. 183:129-139(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, ENZYME REGULATION, TISSUE SPECIFICITY, MUTAGENESIS OF LYS-33; LYS-34; LYS-36; LYS-38; THR-157 AND TYR-159, PHOSPHORYLATION AT THR-157 AND TYR-159.
Tissue: Colon.
[2]"The identification and subcellular localization of human MRK."
Yang T., Jiang Y., Chen J.
Biomol. Eng. 19:1-4(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
Tissue: Cervix carcinoma.
[3]"Prediction of the coding sequences of unidentified human genes. XIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro."
Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
DNA Res. 6:63-70(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain.
[4]"The DNA sequence and analysis of human chromosome 6."
Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. expand/collapse author list , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"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] (ISOFORMS 1 AND 2).
Tissue: Brain.
[7]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[8]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[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. expand/collapse author list , 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] TYR-115; ILE-320; LYS-471; GLN-476 AND THR-615.
[10]"A multiplex human syndrome implicates a key role for intestinal cell kinase in development of central nervous, skeletal, and endocrine systems."
Lahiry P., Wang J., Robinson J.F., Turowec J.P., Litchfield D.W., Lanktree M.B., Gloor G.B., Puffenberger E.G., Strauss K.A., Martens M.B., Ramsay D.A., Rupar C.A., Siu V., Hegele R.A.
Am. J. Hum. Genet. 84:134-147(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ECO GLN-272, CHARACTERIZATION OF VARIANT ECO GLN-272, POSSIBLE FUNCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF225919 mRNA. Translation: AAF37278.1.
AF152469 mRNA. Translation: AAG43364.1.
AB023153 mRNA. Translation: BAA76780.2. Different initiation.
AL031178, AL162581 Genomic DNA. Translation: CAI20261.1.
AL162581, AL031178 Genomic DNA. Translation: CAI19518.1.
CH471081 Genomic DNA. Translation: EAX04400.1.
BC035807 mRNA. Translation: AAH35807.1.
BC136420 mRNA. Translation: AAI36421.1.
BC136421 mRNA. Translation: AAI36422.1.
BC152464 mRNA. Translation: AAI52465.1.
CCDSCCDS4949.1. [Q9UPZ9-1]
RefSeqNP_055735.1. NM_014920.3. [Q9UPZ9-1]
NP_057597.2. NM_016513.4. [Q9UPZ9-1]
UniGeneHs.417022.

3D structure databases

ProteinModelPortalQ9UPZ9.
SMRQ9UPZ9. Positions 1-353.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid116527. 18 interactions.
IntActQ9UPZ9. 8 interactions.
MINTMINT-1200416.
STRING9606.ENSP00000263043.

Chemistry

BindingDBQ9UPZ9.
ChEMBLCHEMBL1163126.
GuidetoPHARMACOLOGY2038.

PTM databases

PhosphoSiteQ9UPZ9.

Polymorphism databases

DMDM48428273.

Proteomic databases

PaxDbQ9UPZ9.
PRIDEQ9UPZ9.

Protocols and materials databases

DNASU22858.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000350082; ENSP00000263043; ENSG00000112144. [Q9UPZ9-1]
ENST00000356971; ENSP00000349458; ENSG00000112144. [Q9UPZ9-1]
GeneID22858.
KEGGhsa:22858.
UCSCuc003pbh.2. human. [Q9UPZ9-1]
uc003pbj.3. human. [Q9UPZ9-2]

Organism-specific databases

CTD22858.
GeneCardsGC06M052912.
HGNCHGNC:21219. ICK.
HPAHPA001113.
MIM612325. gene.
612651. phenotype.
neXtProtNX_Q9UPZ9.
Orphanet199332. Endocrine-cerebro-osteodysplasia syndrome.
PharmGKBPA134894544.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOVERGENHBG014652.
InParanoidQ9UPZ9.
KOK08828.
OMACIMAEVY.
OrthoDBEOG7NCV37.
PhylomeDBQ9UPZ9.
TreeFamTF328769.

Enzyme and pathway databases

SignaLinkQ9UPZ9.

Gene expression databases

BgeeQ9UPZ9.
CleanExHS_ICK.
GenevestigatorQ9UPZ9.

Family and domain databases

InterProIPR011009. 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]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiICK_(gene).
GenomeRNAi22858.
NextBio43345.
PROQ9UPZ9.
SOURCESearch...

Entry information

Entry nameICK_HUMAN
AccessionPrimary (citable) accession number: Q9UPZ9
Secondary accession number(s): A7MD41 expand/collapse secondary AC list , O75985, Q5THL2, Q8IYH8, Q9BX17, Q9NYX3
Entry history
Integrated into UniProtKB/Swiss-Prot: June 7, 2004
Last sequence update: May 1, 2000
Last modified: July 9, 2014
This is version 127 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

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

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 6

Human chromosome 6: entries, gene names and cross-references to MIM