Q9H0C8 (ILKAP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Integrin-linked kinase-associated serine/threonine phosphatase 2C
Short name=ILKAP
EC=3.1.3.16

Gene names

Name:

ILKAP

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	392 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Protein phosphatase that may play a role in regulation of cell cycle progression via dephosphorylation of its substrates whose appropriate phosphorylation states might be crucial for cell proliferation. Selectively associates with integrin linked kinase (ILK), to modulate cell adhesion and growth factor signaling. Inhibits the ILK-GSK3B signaling axis and may play an important role in inhibiting oncogenic transformation. Ref.1 Ref.7
Catalytic activity	A phosphoprotein + H2O = a protein + phosphate.
Cofactor	Binds 2 magnesium or manganese ions per subunit By similarity. Ref.1
Enzyme regulation	Inhibited rather than stimulated by magnesium.
Subunit structure	Interacts with ILK. Specific association with ILK is independent of the catalytic activity of either partner. Ref.1 Ref.7
Subcellular location	Cytoplasm Ref.1.
Tissue specificity	Widely expressed. Highest levels expressed in striated muscle. Much lower levels evident in various smooth muscle tissues. Ref.1
Sequence similarities	Belongs to the PP2C family. Contains 1 PP2C-like domain.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Ligand	Magnesium Manganese Metal-binding
Molecular function	Hydrolase Protein phosphatase
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	negative regulation of cell cycle Inferred from electronic annotation. Source: Compara protein dephosphorylation Inferred from electronic annotation. Source: Compara regulation of S phase of mitotic cell cycle Inferred from electronic annotation. Source: Compara
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein serine/threonine phosphatase activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ILK	Q13418	3	EBI-2620298,EBI-747644

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 392	392	Integrin-linked kinase-associated serine/threonine phosphatase 2C		PRO_0000272271
Regions
	Domain	123 – 390	268	PP2C-like
Sites
	Metal binding	152	1	Manganese 1 By similarity
	Metal binding	152	1	Manganese 2 By similarity
	Metal binding	153	1	Manganese 1; via carbonyl oxygen By similarity
	Metal binding	326	1	Manganese 2 By similarity
	Metal binding	381	1	Manganese 2 By similarity
Amino acid modifications
	Modified residue	1	1	N-acetylmethionine Ref.10 Ref.12
	Modified residue	13	1	Phosphoserine Ref.8 Ref.10 Ref.12
	Modified residue	210	1	N6-acetyllysine Ref.9
Natural variations
	Natural variant	66	1	I → M. Ref.4 Corresponds to variant rs34371548 [ dbSNP | Ensembl ].		VAR_061542
Experimental info
	Mutagenesis	152	1	D → A: Loss of >90% of activity. Ref.1
	Mutagenesis	154	1	H → D: Loss of >90% of activity. Ref.1
	Mutagenesis	154	1	H → L: Loss of >90% of activity. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q9H0C8 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: AF6ACC98508CBEA3	FASTA	392	42,907
	10 20 30 40 50 60 MDLFGDLPEP ERSPRPAAGK EAQKGPLLFD DLPPASSTDS GSGGPLLFDD LPPASSGDSG 70 80 90 100 110 120 SLATSISQMV KTEGKGAKRK TSEEEKNGSE ELVEKKVCKA SSVIFGLKGY VAERKGEREE 130 140 150 160 170 180 MQDAHVILND ITEECRPPSS LITRVSYFAV FDGHGGIRAS KFAAQNLHQN LIRKFPKGDV 190 200 210 220 230 240 ISVEKTVKRC LLDTFKHTDE EFLKQASSQK PAWKDGSTAT CVLAVDNILY IANLGDSRAI 250 260 270 280 290 300 LCRYNEESQK HAALSLSKEH NPTQYEERMR IQKAGGNVRD GRVLGVLEVS RSIGDGQYKR 310 320 330 340 350 360 CGVTSVPDIR RCQLTPNDRF ILLACDGLFK VFTPEEAVNF ILSCLEDEKI QTREGKSAAD 370 380 390 ARYEAACNRL ANKAVQRGSA DNVTVMVVRI GH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Modulation of integrin signal transduction by ILKAP, a protein phosphatase 2C associating with the integrin-linked kinase, ILK1." Leung-Hagesteijn C., Mahendra A., Naruszewicz I., Hannigan G.E. EMBO J. 20:2160-2170(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], COFACTOR, INTERACTION WITH ILK, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INDUCTION, MUTAGENESIS OF ASP-152 AND HIS-154, POSSIBLE FUNCTION.
[2]	"Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs." Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., Ottenwaelder B., Obermaier B. , Tampe J., Heubner D., Wambutt R., Korn B., Klein M., Poustka A. Genome Res. 11:422-435(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Testis.
[3]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	"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], VARIANT MET-66. Tissue: Embryo.
[5]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] 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]. Tissue: Uterus.
[7]	"ILKAP regulates ILK signaling and inhibits anchorage-independent growth." Kumar A.S., Naruszewicz I., Wang P., Leung-Hagesteijn C., Hannigan G.E. Oncogene 23:3454-3461(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ILK, ROLE IN ONCOGENIC TRANSFORMATION, POSSIBLE FUNCTION.
[8]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-13, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[9]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-210, MASS SPECTROMETRY.
[10]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-13, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[11]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-13, MASS SPECTROMETRY.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY024365 mRNA. Translation: AAK07736.1. AL136850 mRNA. Translation: CAB66784.1. CR533533 mRNA. Translation: CAG38564.1. AK001043 mRNA. Translation: BAG50851.1. AC016757 Genomic DNA. Translation: AAY24336.1. BC006576 mRNA. Translation: AAH06576.1.
IPI	IPI00006164.
RefSeq	NP_110395.1. NM_030768.2.
UniGene	Hs.92033.
3D structure databases
HSSP	HSSP built from PDB template 1A6Q based on UniProtKB P35813.
ProteinModelPortal	Q9H0C8.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9H0C8. 1 interaction.
STRING	9606.ENSP00000254654.
PTM databases
PhosphoSite	Q9H0C8.
Polymorphism databases
DMDM	74752560.
Proteomic databases
PaxDb	Q9H0C8.
PeptideAtlas	Q9H0C8.
PRIDE	Q9H0C8.
Protocols and materials databases
DNASU	80895.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000254654; ENSP00000254654; ENSG00000132323.
GeneID	80895.
KEGG	hsa:80895.
UCSC	uc002vxv.3. human.
Organism-specific databases
CTD	80895.
GeneCards	GC02M239079.
HGNC	HGNC:15566. ILKAP.
HPA	HPA004752.
neXtProt	NX_Q9H0C8.
PharmGKB	PA29856.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0631.
HOGENOM	HOG000233896.
HOVERGEN	HBG054286.
InParanoid	Q9H0C8.
OMA	DIKRCQL.
OrthoDB	EOG4R503N.
PhylomeDB	Q9H0C8.
Gene expression databases
ArrayExpress	Q9H0C8.
Bgee	Q9H0C8.
CleanEx	HS_ILKAP.
Genevestigator	Q9H0C8.
Family and domain databases
Gene3D	3.60.40.10. 1 hit.
InterPro	IPR001932. PP2C-like. IPR000222. PP2C_Mn2_Asp60_BS. IPR015655. Protein_Pase_2C. [Graphical view]
PANTHER	PTHR13832. PTHR13832. 1 hit.
Pfam	PF00481. PP2C. 1 hit. [Graphical view]
SMART	SM00331. PP2C_SIG. 1 hit. SM00332. PP2Cc. 1 hit. [Graphical view]
SUPFAM	SSF81606. PP2C-related. 1 hit.
PROSITE	PS01032. PP2C. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChEMBL	CHEMBL2290.
GenomeRNAi	80895.
NextBio	71332.

Entry information

Entry name

ILKAP_HUMAN

Accession

Primary (citable) accession number: Q9H0C8
Secondary accession number(s): B3KM39

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 23, 2007
Last sequence update:	March 1, 2001
Last modified:	May 1, 2013
This is version 96 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.