Reviewed, UniProtKB/Swiss-Prot O15084 (ANR28_HUMAN)

Names and origin

Protein names

Recommended name:
    Serine/threonine-protein phosphatase 6 regulatory ankyrin repeat subunit A
      Short name=Serine/threonine-protein phosphatase 6 regulatory subunit ARS-A
      Short name=PP6-ARS-A
Alternative name(s):
    Ankyrin repeat domain-containing protein 28
    Phosphatase interactor targeting protein hnRNP K
      Short name=PITK

Gene names

Name:	ANKRD28
Synonyms:	KIAA0379

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	1086 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Putative regulatory subunit of protein phospatase 6 (PP6) that may be involved in the recognition of phosphoprotein substrates. Involved in the PP6-mediated dephosphorylation of NFKBIE opposing its degradation in response to TNF-alpha. Selectively inhibits the phosphatase activity of PPP1C. Targets PPP1C to modulate HNRPK phosphorylation. Ref.5 Ref.6
Subunit structure	Protein phospatase 6 (PP6) holoenzyme is proposed to be a heterotrimeric complex formed by the catalytic subunit, a SAPS domain-containing subunit (PP6R) and an ankyrin repeat-domain containing regulatory subunit (ARS). Interacts with PPP1C and HNRPK. Interacts with PPP6C, SAPS1 and SAPS3. Ref.5 Ref.6
Subcellular location	Nucleus › nucleoplasm. Note= Seems to be excluded from nucleoli. Ref.5
Sequence similarities	Contains 27 ANK repeats.

Ontologies

Keywords
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Domain	ANK repeat Repeat
PTM	Phosphoprotein
Gene Ontology (GO)
Cellular component	nucleus Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
NCL	P19338	1	EBI-359567,EBI-352553

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O15084-1)

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: O15084-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-566: Missing.

Notes: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1086	1086	Serine/threonine-protein phosphatase 6 regulatory ankyrin repeat subunit A		PRO_0000066919
Regions
	Repeat	73 – 102	30	ANK 1
	Repeat	106 – 135	30	ANK 2
	Repeat	139 – 168	30	ANK 3
	Repeat	172 – 201	30	ANK 4
	Repeat	205 – 234	30	ANK 5
	Repeat	238 – 267	30	ANK 6
	Repeat	271 – 300	30	ANK 7
	Repeat	304 – 334	31	ANK 8
	Repeat	338 – 367	30	ANK 9
	Repeat	371 – 400	30	ANK 10
	Repeat	404 – 433	30	ANK 11
	Repeat	437 – 466	30	ANK 12
	Repeat	470 – 499	30	ANK 13
	Repeat	503 – 533	31	ANK 14
	Repeat	537 – 567	31	ANK 15
	Repeat	582 – 611	30	ANK 16
	Repeat	615 – 644	30	ANK 17
	Repeat	649 – 678	30	ANK 18
	Repeat	685 – 714	30	ANK 19
	Repeat	718 – 747	30	ANK 20
	Repeat	751 – 780	30	ANK 21
	Repeat	788 – 817	30	ANK 22
	Repeat	820 – 850	31	ANK 23
	Repeat	855 – 884	30	ANK 24
	Repeat	888 – 918	31	ANK 25
	Repeat	922 – 951	30	ANK 26
	Repeat	958 – 987	30	ANK 27
Amino acid modifications
	Modified residue	117	1	Phosphoserine By similarity
	Modified residue	1040	1	Phosphoserine Ref.5
	Modified residue	1044	1	Phosphoserine Ref.5
Natural variations
	Alternative sequence	1 – 566	566	Missing in isoform 2.		VSP_012433
Experimental info
	Mutagenesis	1040 – 1044	5	SKTVS → AKTVA: Marked decrease in phosphorylation. Increased PPP1C-binding. No effect on HNRPK-binding Ref.5
	Sequence conflict	28 – 42	15	KSLHS…VLVRY → GAEATAMAFLKLRDQ in BAA20833. Ref.3
	Sequence conflict	533	1	I → V in AAQ72374. Ref.1
	Sequence conflict	533	1	I → V in BAC86737. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified April 17, 2007. Version 4. Checksum: 47A3F97E5C72F0E8	FASTA	1,086	116,543
	10 20 30 40 50 60 MSRVCIVVLE EVEDESPAFI SKLPQENKSL HSPPSGNVLV RYPSLVQAIF NGDPDEVRAL 70 80 90 100 110 120 IFKKEDVNFQ DNEKRTPLHA AAYLGDAEII ELLILSGARV NAKDSKWLTP LHRAVASCSE 130 140 150 160 170 180 EAVQVLLKHS ADVNARDKNW QTPLHIAAAN KAVKCAEALV PLLSNVNVSD RAGRTALHHA 190 200 210 220 230 240 AFSGHGEMVK LLLSRGANIN AFDKKDRRAI HWAAYMGHIE VVKLLVSHGA EVTCKDKKSY 250 260 270 280 290 300 TPLHAAASSG MISVVKYLLD LGVDMNEPNA YGNTPLHVAC YNGQDVVVNE LIDCGAIVNQ 310 320 330 340 350 360 KNEKGFTPLH FAAASTHGAL CLELLVGNGA DVNMKSKDGK TPLHMTALHG RFSRSQTIIQ 370 380 390 400 410 420 SGAVIDCEDK NGNTPLHIAA RYGHELLINT LITSGADTAK RGIHGMFPLH LAALSGFSDC 430 440 450 460 470 480 CRKLLSSGFD IDTPDDFGRT CLHAAAAGGN LECLNLLLNT GADFNKKDKF GRSPLHYAAA 490 500 510 520 530 540 NCNYQCLFAL VGSGASVNDL DERGCTPLHY AATSDTDGKC LEYLLRNDAN PGIRDKQGYN 550 560 570 580 590 600 AVHYSAAYGH RLCLQLIASE TPLDVLMETS GTDMLSDSDN RATISPLHLA AYHGHHQALE 610 620 630 640 650 660 VLVQSLLDLD VRNSSGRTPL DLAAFKGHVE CVDVLINQGA SILVKDYILK RTPIHAAATN 670 680 690 700 710 720 GHSECLRLLI GNAEPQNAVD IQDGNGQTPL MLSVLNGHTD CVYSLLNKGA NVDAKDKWGR 730 740 750 760 770 780 TALHRGAVTG HEECVDALLQ HGAKCLLRDS RGRTPIHLSA ACGHIGVLGA LLQSAASMDA 790 800 810 820 830 840 NPATADNHGY TALHWACYNG HETCVELLLE QEVFQKTEGN AFSPLHCAVI NDNEGAAEML 850 860 870 880 890 900 IDTLGASIVN ATDSKGRTPL HAAAFTDHVE CLQLLLSHNA QVNSVDSTGK TPLMMAAENG 910 920 930 940 950 960 QTNTVEMLVS SASAELTLQD NSKNTALHLA CSKGHETSAL LILEKITDRN LINATNAALQ 970 980 990 1000 1010 1020 TPLHVAARNG LTMVVQELLG KGASVLAVDE NGYTPALACA PNKDVADCLA LILATMMPVS 1030 1040 1050 1060 1070 1080 SSSPLSSLTF NAINRYTNTS KTVSFEALPI MRNEPSSYCS FNNIGGEQEY LYTDVDELND SDSETY
	Isoform 2. Checksum: F4FCB772B2027B87		520	55,422
	10 20 30 40 50 60 METSGTDMLS DSDNRATISP LHLAAYHGHH QALEVLVQSL LDLDVRNSSG RTPLDLAAFK 70 80 90 100 110 120 GHVECVDVLI NQGASILVKD YILKRTPIHA AATNGHSECL RLLIGNAEPQ NAVDIQDGNG 130 140 150 160 170 180 QTPLMLSVLN GHTDCVYSLL NKGANVDAKD KWGRTALHRG AVTGHEECVD ALLQHGAKCL 190 200 210 220 230 240 LRDSRGRTPI HLSAACGHIG VLGALLQSAA SMDANPATAD NHGYTALHWA CYNGHETCVE 250 260 270 280 290 300 LLLEQEVFQK TEGNAFSPLH CAVINDNEGA AEMLIDTLGA SIVNATDSKG RTPLHAAAFT 310 320 330 340 350 360 DHVECLQLLL SHNAQVNSVD STGKTPLMMA AENGQTNTVE MLVSSASAEL TLQDNSKNTA 370 380 390 400 410 420 LHLACSKGHE TSALLILEKI TDRNLINATN AALQTPLHVA ARNGLTMVVQ ELLGKGASVL 430 440 450 460 470 480 AVDENGYTPA LACAPNKDVA DCLALILATM MPVSSSSPLS SLTFNAINRY TNTSKTVSFE 490 500 510 520 ALPIMRNEPS SYCSFNNIGG EQEYLYTDVD ELNDSDSETY

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning a new transcript of KIAA0379 protein in testis." Lu L., Huang X.Y., Yin L.L., Xu M., Li J.M., Zhou Z.M., Sha J.H. Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Testis.
[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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-687. Tissue: Amygdala.
[3]	"Prediction of the coding sequences of unidentified human genes. VII. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro." Nagase T., Ishikawa K., Nakajima D., Ohira M., Seki N., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 4:141-150(1997) [PubMed: 9205841] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 28-1086. Tissue: Brain.
[4]	"Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones." Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T. DNA Res. 9:99-106(2002) [PubMed: 12168954] [Abstract] Cited for: SEQUENCE REVISION.
[5]	"PITK, a PP1 targeting subunit that modulates the phosphorylation of the transcriptional regulator hnRNP K." Kwiek N.C., Thacker D.F., Datto M.B., Megosh H.B., Haystead T.A.J. Cell. Signal. 18:1769-1778(2006) [PubMed: 16564677] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PPP1C AND HNRPK, PHOSPHORYLATION AT SER-1040 AND SER-1044, MUTAGENESIS OF 1040-SER--SER-1044.
[6]	"Protein phosphatase 6 regulatory subunits composed of ankyrin repeat domains." Stefansson B., Ohama T., Daugherty A.E., Brautigan D.L. Biochemistry 47:1442-1451(2008) [PubMed: 18186651] [Abstract] Cited for: FUNCTION, INTERACTION WITH PPP6C; SAPS1 AND SAPS3.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AY367056 mRNA. Translation: AAQ72374.1. AK126888 mRNA. Translation: BAC86737.1. AB002377 mRNA. Translation: BAA20833.2.
RefSeq	NP_056014.2.
UniGene	Hs.335239
3D structure databases
HSSP	HSSP built from PDB template 2MYO based on UniProtKB P80144.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP:27583N.
IntAct	O15084. 7 interactions.
PTM databases
PhosphoSite	O15084.
Proteomic databases
PRIDE	O15084.
Genome annotation databases
Ensembl	ENSG00000206560. Homo sapiens. [Contig view]
GeneID	23243.
KEGG	hsa:23243.
Organism-specific databases
GeneCards	GC03M015700.
H-InvDB	HIX0003106.
HGNC	HGNC:29024. ANKRD28.
MIM	611122. gene.
PharmGKB	PA134880251.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
HOGENOM	O15084.
HOVERGEN	O15084.
Gene expression databases
ArrayExpress	O15084.
CleanEx	HS_ANKRD28.
GermOnline	ENSG00000206560. Homo sapiens.
Family and domain databases
InterPro	IPR002110. ANK. [Graphical view]
Gene3D	G3DSA:1.25.40.20. ANK. 4 hits.
Pfam	PF00023. Ank. 28 hits. [Graphical view]
PRINTS	PR01415. ANKYRIN.
SMART	SM00248. ANK. 28 hits. [Graphical view]
PROSITE	PS50297. ANK_REP_REGION. 1 hit. PS50088. ANK_REPEAT. 24 hits. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	44912.
SOURCE	Search...

Entry information

Entry name

ANR28_HUMAN

Accession

Primary (citable) accession number: O15084
Secondary accession number(s): Q6ULS0, Q6ZT57

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 20, 2001
Last sequence update:	April 17, 2007
Last modified:	December 16, 2008
This is version 69 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)