Q9UPZ9 (ICK_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	632 AA.
Sequence status	Complete.
Protein existence	Evidence 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. Cytoplasm › cytosol 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 Ref.7 Ref.8
Involvement in disease	Defects in ICK are the cause of endocrine-cerebroosteodysplasia (ECO) [MIM:612651]. ECO is a previously unidentified neonatal lethal recessive disorder with multiple anomalies involving the endocrine, cerebral, and skeletal systems. 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.

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Developmental protein Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	intracellular protein kinase cascade Inferred from direct assay Ref.1. Source: UniProtKB multicellular organismal development Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytosol Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from direct assay Ref.1. Source: UniProtKB cyclin-dependent protein kinase activity Inferred from electronic annotation. Source: EC magnesium ion binding Inferred from direct assay Ref.1. Source: UniProtKB
Complete GO annotation...

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 632	632	Serine/threonine-protein kinase ICK		PRO_0000086007
Regions
	Domain	4 – 284	281	Protein kinase
	Nucleotide binding	10 – 18	9	ATP By similarity UniProtKB P06493
Sites
	Active site	125	1	Proton acceptor By similarity UniProtKB P06493
	Binding site	33	1	ATP Ref.1
Amino acid modifications
	Modified residue	14	1	Phosphothreonine By similarity UniProtKB P06493
	Modified residue	15	1	Phosphotyrosine By similarity UniProtKB P06493
	Modified residue	156	1	Phosphotyrosine Ref.7 Ref.8
	Modified residue	157	1	Phosphothreonine Ref.1 Ref.8
	Modified residue	159	1	Phosphotyrosine Ref.1 Ref.7 Ref.8
	Modified residue	583	1	Phosphotyrosine Ref.8
	Modified residue	584	1	Phosphoserine Ref.8
Natural variations
	Alternative sequence	278 – 292	15	ALRYP…HPLGS → VFFHFLVITFISNSE in isoform 2.		VSP_050752
	Alternative sequence	293 – 632	340	Missing in isoform 2.		VSP_050753
	Natural variant	98	1	P → L. Corresponds to variant rs1493105 [ dbSNP | Ensembl ].		VAR_053931
	Natural variant	115	1	F → Y in a renal clear cell carcinoma sample; somatic mutation. Ref.9		VAR_042001
	Natural variant	272	1	R → Q in ECO; fails to localize at the nucleus and significantly impairs kinase activity. Ref.10		VAR_057994
	Natural variant	320	1	V → I. Ref.9 Corresponds to variant rs33936662 [ dbSNP | Ensembl ].		VAR_042002
	Natural variant	471	1	T → K. Ref.9 Corresponds to variant rs56164633 [ dbSNP | Ensembl ].		VAR_042003
	Natural variant	476	1	R → Q. Ref.9 Corresponds to variant rs55895113 [ dbSNP | Ensembl ].		VAR_042004
	Natural variant	615	1	A → T. Ref.9 Corresponds to variant rs55932059 [ dbSNP | Ensembl ].		VAR_042005
Experimental info
	Mutagenesis	33	1	K → R: Loss of activity and autophosphorylation; when associated with R-34; R-36 and R-38. Ref.1
	Mutagenesis	34	1	K → R: Loss of activity and autophosphorylation; when associated with R-33; R-36 and R-38. Ref.1
	Mutagenesis	36	1	K → R: Loss of activity and autophosphorylation; when associated with R-33; R-34 and R-38. Ref.1
	Mutagenesis	38	1	K → R: Loss of activity and autophosphorylation; when associated with R-33; R-34 and R-36. Ref.1
	Mutagenesis	157	1	T → A: Reduction of activity and loss of autophosphorylation. Loss of activity and autophosphorylation; when associated with F-159. Ref.1
	Mutagenesis	159	1	Y → F: Reduction of activity and loss of autophosphorylation. Loss of activity and autophosphorylation; when associated with A-157. Ref.1
	Sequence conflict	48	1	L → Q in AAF37278. Ref.1
	Sequence conflict	119	1	H → L in AAF37278. Ref.1
	Sequence conflict	310	1	K → R in AAF37278. Ref.1
	Sequence conflict	598 – 599	2	FH → LD in AAF37278. Ref.1
	Sequence conflict	629	1	A → P in AAF37278. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: F4C22C6CCD5878D2	FASTA	632	71,427
	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
	Isoform 2 [UniParc]. Checksum: AB4CA7370E16F983	FASTA	292	34,071
	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 CVPNNLKTLI PNASSEAVQL LRDMLQWDPK KRPTASQVFF HFLVITFISN SE

References

	« Hide 'large scale' referencesShow '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: 10699974] [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: 12103360] [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: 10231032] [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. , 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: 14574404] [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. , 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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Brain.
[7]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-156 AND TYR-159, MASS SPECTROMETRY. Tissue: Lung 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: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-156; THR-157; TYR-159; TYR-583 AND SER-584, MASS SPECTROMETRY.
[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: 17344846] [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: 19185282] [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.
IPI	IPI00217776. IPI00414132.
RefSeq	NP_055735.1. NM_014920.3. NP_057597.2. NM_016513.4.
UniGene	Hs.417022.
3D structure databases
ProteinModelPortal	Q9UPZ9.
SMR	Q9UPZ9. Positions 1-287.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-1200416.
STRING	Q9UPZ9.
PTM databases
PhosphoSite	Q9UPZ9.
Polymorphism databases
DMDM	48428273.
Proteomic databases
PRIDE	Q9UPZ9.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000350082; ENSP00000263043; ENSG00000112144. ENST00000356971; ENSP00000349458; ENSG00000112144.
GeneID	22858.
KEGG	hsa:22858.
UCSC	uc003pbh.2. human. uc003pbj.1. human.
Organism-specific databases
CTD	22858.
GeneCards	GC06M052912.
H-InvDB	HIX0200827.
HGNC	HGNC:21219. ICK.
HPA	HPA001113.
MIM	612325. gene. 612651. phenotype.
neXtProt	NX_Q9UPZ9.
Orphanet	199332. Endocrine-cerebro-osteodysplasia syndrome.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG19551.
GeneTree	ENSGT00600000084046.
HOGENOM	HBG445725.
HOVERGEN	HBG014652.
InParanoid	Q9UPZ9.
OMA	CIMAEVY.
OrthoDB	EOG46DM2D.
PhylomeDB	Q9UPZ9.
Gene expression databases
ArrayExpress	Q9UPZ9.
Bgee	Q9UPZ9.
CleanEx	HS_ICK.
Genevestigator	Q9UPZ9.
GermOnline	ENSG00000112144. Homo sapiens.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_kinase-like_dom. IPR008271. Ser/Thr_kinase_AS. IPR002290. Ser/Thr_kinase_dom. [Graphical view]
KO	K08828.
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
SMART	SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	43345.
SOURCE	Search...

Entry information

Entry name

ICK_HUMAN

Accession

Primary (citable) accession number: Q9UPZ9
Secondary accession number(s): A7MD41 , O75985, Q5THL2, Q8IYH8, Q9BX17, Q9NYX3

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 7, 2004
Last sequence update:	May 1, 2000
Last modified:	January 25, 2012
This is version 101 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.