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Q63ZY3 (KANK2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 99. 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:
KN motif and ankyrin repeat domain-containing protein 2
Alternative name(s):
Ankyrin repeat domain-containing protein 25
Matrix-remodeling-associated protein 3
SRC-1-interacting protein
Short name=SIP
Short name=SRC-interacting protein
Short name=SRC1-interacting protein
Gene names
Name:KANK2
Synonyms:ANKRD25, KIAA1518, MXRA3, SIP
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length851 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Involved in transcription regulation by sequestering nuclear receptor coactivators, such as NCOA1, NCOA2 and NCOA3, in the cytoplasm; the function is deregulated by phosphorylation. May be involved in the control of cytoskeleton formation by regulating actin polymerization. Involved in regulation of caspase-independent apoptosis; proposed to sequester AIFM1 in mitochondria and apoptotic stimuli lead to its proteasomal degradation allowing the release of AIFM1 to the nucleus. May be involved in promotion of cell proliferation. Ref.1 Ref.9 Ref.14

Subunit structure

Interacts (phosphorylated) with NCOA1; NCOA2 AND NCOA3. Interacts with AIFM1. Ref.1 Ref.14

Subcellular location

Cytoplasm. Mitochondrion Ref.1 Ref.9.

Tissue specificity

Strongly expressed in cervix, colon, heart, kidney and lung. Expressed in kidney glomerular podocytes and mesangial cells (at protein level). Ref.9 Ref.13

Post-translational modification

Phosphorylated by CaMK2 upon estrogen stimulation. Ref.1

Sequence similarities

Contains 5 ANK repeats.

Sequence caution

The sequence BAA92081.1 differs from that shown. Reason: Erroneous initiation.

The sequence BAA96042.2 differs from that shown. Reason: Erroneous initiation.

The sequence BAB14531.1 differs from that shown. Reason: Erroneous initiation.

Binary interactions

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q63ZY3-1)

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: Q63ZY3-2)

The sequence of this isoform differs from the canonical sequence as follows:
     472-472: T → TAPPLSSPP
Note: No experimental confirmation available.
Isoform 3 (identifier: Q63ZY3-3)

The sequence of this isoform differs from the canonical sequence as follows:
     835-841: FAPMSDD → VSLNPAG
     842-851: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 851851KN motif and ankyrin repeat domain-containing protein 2
PRO_0000240840

Regions

Repeat666 – 69631ANK 1
Repeat700 – 73334ANK 2
Repeat738 – 76730ANK 3
Repeat771 – 80131ANK 4
Repeat805 – 83531ANK 5
Region1 – 7272Interaction with AIFM1
Region669 – 835167Interaction with NCOA1
Coiled coil183 – 23452 Potential
Coiled coil282 – 31231 Potential
Compositional bias425 – 4284Poly-Ser

Amino acid modifications

Modified residue191Phosphoserine Ref.7
Modified residue3561Phosphoserine Ref.10
Modified residue3751Phosphoserine Ref.7 Ref.11 Ref.12
Modified residue4721Phosphothreonine Ref.10

Natural variations

Alternative sequence4721T → TAPPLSSPP in isoform 2.
VSP_019427
Alternative sequence835 – 8417FAPMSDD → VSLNPAG in isoform 3.
VSP_019428
Alternative sequence842 – 85110Missing in isoform 3.
VSP_019429
Natural variant1181G → S.
Corresponds to variant rs755237 [ dbSNP | Ensembl ].
VAR_048304
Natural variant4011M → T.
Corresponds to variant rs17616661 [ dbSNP | Ensembl ].
VAR_048305

Experimental info

Mutagenesis510 – 5123SSS → AAA: Impairs phosphorylation; when associated with A-515. Ref.1
Mutagenesis5151S → A: Impairs phosphorylation; when associated with 510-A--A-512. Ref.1
Sequence conflict5251D → N in BAA96042. Ref.3

Secondary structure

................................ 851
Helix Strand Turn

Details...

Sequences

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

Last modified October 25, 2004. Version 1.
Checksum: C14CD8B937A7B6E8

FASTA85191,174
        10         20         30         40         50         60 
MAQVLHVPAP FPGTPGPASP PAFPAKDPDP PYSVETPYGY RLDLDFLKYV DDIEKGHTLR 

        70         80         90        100        110        120 
RVAVQRRPRL SSLPRGPGSW WTSTESLCSN ASGDSRHSAY SYCGRGFYPQ YGALETRGGF 

       130        140        150        160        170        180 
NPRVERTLLD ARRRLEDQAA TPTGLGSLTP SAAGSTASLV GVGLPPPTPR SSGLSTPVPP 

       190        200        210        220        230        240 
SAGHLAHVRE QMAGALRKLR QLEEQVKLIP VLQVKLSVLQ EEKRQLTVQL KSQKFLGHPT 

       250        260        270        280        290        300 
AGRGRSELCL DLPDPPEDPV ALETRSVGTW VRERDLGMPD GEAALAAKVA VLETQLKKAL 

       310        320        330        340        350        360 
QELQAAQARQ ADPQPQAWPP PDSPVRVDTV RVVEGPREVE VVASTAAGAP AQRAQSLEPY 

       370        380        390        400        410        420 
GTGLRALAMP GRPESPPVFR SQEVVETMCP VPAAATSNVH MVKKISITER SCDGAAGLPE 

       430        440        450        460        470        480 
VPAESSSSPP GSEVASLTQP EKSTGRVPTQ EPTHREPTRQ AASQESEEAG GTGGPPAGVR 

       490        500        510        520        530        540 
SIMKRKEEVA DPTAHRRSLQ FVGVNGGYES SSEDSSTAEN ISDNDSTENE APEPRERVPS 

       550        560        570        580        590        600 
VAEAPQLRPA GTAAAKTSRQ ECQLSRESQH IPTAEGASGS NTEEEIRMEL SPDLISACLA 

       610        620        630        640        650        660 
LEKYLDNPNA LTERELKVAY TTVLQEWLRL ACRSDAHPEL VRRHLVTFRA MSARLLDYVV 

       670        680        690        700        710        720 
NIADSNGNTA LHYSVSHANF PVVQQLLDSG VCKVDKQNRA GYSPIMLTAL ATLKTQDDIE 

       730        740        750        760        770        780 
TVLQLFRLGN INAKASQAGQ TALMLAVSHG RVDVVKALLA CEADVNVQDD DGSTALMCAC 

       790        800        810        820        830        840 
EHGHKEIAGL LLAVPSCDIS LTDRDGSTAL MVALDAGQSE IASMLYSRMN IKCSFAPMSD 

       850 
DESPTSSSAE E 

« Hide

Isoform 2 [UniParc].

Checksum: 0629BE4E0E29FCEE
Show »

FASTA85991,921
Isoform 3 [UniParc].

Checksum: D82155CD26E514F1
Show »

FASTA84190,044

References

« Hide 'large scale' references
[1]"SIP, a novel ankyrin repeat containing protein, sequesters steroid receptor coactivators in the cytoplasm."
Zhang Y., Zhang H., Liang J., Yu W., Shang Y.
EMBO J. 26:2645-2657(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, INTERACTION WITH NCOA1; NCOA2 AND NCOA3, SUBCELLULAR LOCATION, PHOSPHORYLATION, MUTAGENESIS OF 510-SER--SER-512 AND SER-515.
[2]Zhu Y., Kakinuma N., Wang Y., Kiyama R.
Submitted (NOV-2006) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]"Prediction of the coding sequences of unidentified human genes. XVII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro."
Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.
DNA Res. 7:143-150(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Spleen.
[4]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].
[5]"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] (ISOFORM 1).
Tissue: Cervix and Lung.
[6]"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. expand/collapse author list , 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] OF 386-841 (ISOFORM 3).
Tissue: Ovary and Placenta.
[7]"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-19 AND SER-375, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[8]"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage."
Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.
Science 316:1160-1166(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic kidney.
[9]"Kank proteins: a new family of ankyrin-repeat domain-containing proteins."
Zhu Y., Kakinuma N., Wang Y., Kiyama R.
Biochim. Biophys. Acta 1780:128-133(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: POSSIBLE FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[10]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-356 AND THR-472, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[11]"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: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-375, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"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: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-375, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[13]"Expression of novel podocyte-associated proteins sult1b1 and ankrd25."
Xu X., Patrakka J., Sistani L., Uhlen M., Jalanko H., Betsholtz C., Tryggvason K.
Nephron Exp. Nephrol. 117:E39-E46(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[14]"Steroid receptor coactivator-interacting protein (SIP) inhibits caspase-independent apoptosis by preventing apoptosis-inducing factor (AIF) from being released from mitochondria."
Wang D., Liang J., Zhang Y., Gui B., Wang F., Yi X., Sun L., Yao Z., Shang Y.
J. Biol. Chem. 287:12612-12621(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH AIFM1.
[15]"Crystal structure of KANK2 ankyrin repeats."
Structural genomics consortium (SGC)
Submitted (DEC-2012) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (1.72 ANGSTROMS) OF 578-832.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY639929 mRNA. Translation: AAT57879.1.
AB284125 mRNA. Translation: BAG06864.1.
AB040951 mRNA. Translation: BAA96042.2. Different initiation.
CH471106 Genomic DNA. Translation: EAW84177.1.
BC082762 mRNA. Translation: AAH82762.1.
BC098105 mRNA. Translation: AAH98105.1.
BC098286 mRNA. Translation: AAH98286.1.
BC098312 mRNA. Translation: AAH98312.1.
BC105989 mRNA. Translation: AAI05990.1.
AK002094 mRNA. Translation: BAA92081.1. Different initiation.
AK023332 mRNA. Translation: BAB14531.1. Different initiation.
CCDSCCDS12255.1. [Q63ZY3-1]
CCDS54219.1. [Q63ZY3-2]
RefSeqNP_001129663.1. NM_001136191.2. [Q63ZY3-1]
NP_056308.3. NM_015493.6. [Q63ZY3-2]
UniGeneHs.284208.
Hs.723365.
Hs.744940.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4HBDX-ray1.72A578-832[»]
ProteinModelPortalQ63ZY3.
SMRQ63ZY3. Positions 588-832.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid117449. 11 interactions.
IntActQ63ZY3. 15 interactions.
MINTMINT-4540700.
STRING9606.ENSP00000347276.

PTM databases

PhosphoSiteQ63ZY3.

Polymorphism databases

DMDM74757262.

Proteomic databases

MaxQBQ63ZY3.
PaxDbQ63ZY3.
PRIDEQ63ZY3.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000355150; ENSP00000347276; ENSG00000197256. [Q63ZY3-1]
ENST00000432929; ENSP00000395650; ENSG00000197256. [Q63ZY3-2]
ENST00000586659; ENSP00000465650; ENSG00000197256. [Q63ZY3-1]
ENST00000589359; ENSP00000468002; ENSG00000197256. [Q63ZY3-2]
ENST00000589894; ENSP00000467029; ENSG00000197256. [Q63ZY3-3]
GeneID25959.
KEGGhsa:25959.
UCSCuc002mqm.3. human. [Q63ZY3-2]
uc002mqo.4. human. [Q63ZY3-1]
uc002mqp.1. human. [Q63ZY3-3]

Organism-specific databases

CTD25959.
GeneCardsGC19M011274.
HGNCHGNC:29300. KANK2.
HPAHPA015643.
MIM614610. gene.
neXtProtNX_Q63ZY3.
PharmGKBPA162392581.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0666.
HOVERGENHBG062256.
InParanoidQ63ZY3.
OMASVGTWVR.
OrthoDBEOG7NW687.
PhylomeDBQ63ZY3.
TreeFamTF324499.

Gene expression databases

ArrayExpressQ63ZY3.
BgeeQ63ZY3.
CleanExHS_KANK2.
GenevestigatorQ63ZY3.

Family and domain databases

Gene3D1.25.40.20. 1 hit.
InterProIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR021939. KN_motif.
[Graphical view]
PfamPF00023. Ank. 1 hit.
PF12796. Ank_2. 1 hit.
PF12075. KN_motif. 1 hit.
[Graphical view]
SMARTSM00248. ANK. 5 hits.
[Graphical view]
SUPFAMSSF48403. SSF48403. 1 hit.
PROSITEPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiANKRD25.
GenomeRNAi25959.
NextBio47574.
PROQ63ZY3.
SOURCESearch...

Entry information

Entry nameKANK2_HUMAN
AccessionPrimary (citable) accession number: Q63ZY3
Secondary accession number(s): B0I1P4 expand/collapse secondary AC list , Q3KQZ3, Q6GUF5, Q9H8S4, Q9NUP0, Q9P210
Entry history
Integrated into UniProtKB/Swiss-Prot: June 27, 2006
Last sequence update: October 25, 2004
Last modified: July 9, 2014
This is version 99 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

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 19

Human chromosome 19: entries, gene names and cross-references to MIM