ANKS6_RAT
ID ANKS6_RAT Reviewed; 885 AA.
AC P0C0T2; Q2VWC0; Q5BJL2;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 14-NOV-2006, sequence version 2.
DT 25-MAY-2022, entry version 109.
DE RecName: Full=Ankyrin repeat and SAM domain-containing protein 6;
DE AltName: Full=Polycystic kidney disease protein 1;
DE AltName: Full=SamCystin;
DE AltName: Full=Sterile alpha motif domain-containing protein 6;
DE Short=SAM domain-containing protein 6;
GN Name=Anks6; Synonyms=Pkdr1, Samd6;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, INVOLVEMENT IN
RP CY, AND VARIANT CY TRP-823.
RC STRAIN=Brown Norway; TISSUE=Kidney;
RX PubMed=16207829; DOI=10.1681/asn.2005060601;
RA Brown J.H., Bihoreau M.-T., Hoffmann S., Kranzlin B., Tychinskaya I.,
RA Obermuller N., Podlich D., Boehn S.N., Kaisaki P.J., Megel N., Danoy P.,
RA Copley R.R., Broxholme J., Witzgall R., Lathrop M., Gretz N., Gauguier D.;
RT "Missense mutation in sterile alpha motif of novel protein SamCystin is
RT associated with polycystic kidney disease in (cy/+) rat.";
RL J. Am. Soc. Nephrol. 16:3517-3526(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 864-885.
RC TISSUE=Spleen;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP SUBCELLULAR LOCATION, SUBUNIT, INTERACTION WITH BICC1, AND CHARACTERIZATION
RP OF VARIANT CY TRP-823.
RX PubMed=19324013; DOI=10.1016/j.bbrc.2009.03.113;
RA Stagner E.E., Bouvrette D.J., Cheng J., Bryda E.C.;
RT "The polycystic kidney disease-related proteins Bicc1 and SamCystin
RT interact.";
RL Biochem. Biophys. Res. Commun. 383:16-21(2009).
RN [5]
RP INTERACTION WITH INVS; NEK8 AND NPHP3, DOMAIN ANK REPEATS, HYDROXYLATION AT
RP ASN-129, AND MUTAGENESIS OF ASN-129; ASN-209 AND GLN-433.
RX PubMed=23793029; DOI=10.1038/ng.2681;
RA Hoff S., Halbritter J., Epting D., Frank V., Nguyen T.M., van Reeuwijk J.,
RA Boehlke C., Schell C., Yasunaga T., Helmstadter M., Mergen M., Filhol E.,
RA Boldt K., Horn N., Ueffing M., Otto E.A., Eisenberger T., Elting M.W.,
RA van Wijk J.A., Bockenhauer D., Sebire N.J., Rittig S., Vyberg M., Ring T.,
RA Pohl M., Pape L., Neuhaus T.J., Elshakhs N.A., Koon S.J., Harris P.C.,
RA Grahammer F., Huber T.B., Kuehn E.W., Kramer-Zucker A., Bolz H.J.,
RA Roepman R., Saunier S., Walz G., Hildebrandt F., Bergmann C.,
RA Lienkamp S.S.;
RT "ANKS6 is a central component of a nephronophthisis module linking NEK8 to
RT INVS and NPHP3.";
RL Nat. Genet. 45:951-956(2013).
RN [6]
RP INTERACTION WITH ANKS3.
RX PubMed=26188091; DOI=10.1016/j.bbrc.2015.07.063;
RA Ramachandran H., Engel C., Mueller B., Dengjel J., Walz G., Yakulov T.A.;
RT "Anks3 alters the sub-cellular localization of the Nek7 kinase.";
RL Biochem. Biophys. Res. Commun. 464:901-907(2015).
RN [7]
RP INTERACTION WITH ANKS3.
RX PubMed=25671767; DOI=10.1038/ki.2015.17;
RA Yakulov T.A., Yasunaga T., Ramachandran H., Engel C., Mueller B., Hoff S.,
RA Dengjel J., Lienkamp S.S., Walz G.;
RT "Anks3 interacts with nephronophthisis proteins and is required for normal
RT renal development.";
RL Kidney Int. 87:1191-1200(2015).
RN [8]
RP INTERACTION WITH ANKS3, CHARACTERIZATION OF VARIANT CY TRP-823, AND SITE.
RX PubMed=26327442; DOI=10.1371/journal.pone.0136781;
RA Delestre L., Bakey Z., Prado C., Hoffmann S., Bihoreau M.T., Lelongt B.,
RA Gauguier D.;
RT "ANKS3 Co-Localises with ANKS6 in Mouse Renal Cilia and Is Associated with
RT Vasopressin Signaling and Apoptosis In Vivo in Mice.";
RL PLoS ONE 10:E0136781-E0136781(2015).
CC -!- FUNCTION: Required for renal function. {ECO:0000269|PubMed:16207829}.
CC -!- SUBUNIT: Homooligomer (PubMed:19324013). Central component of a complex
CC containing at least ANKS6, INVS, NEK8 and NPHP3 (PubMed:23793029).
CC ANKS6 may organize complex assembly by linking INVS and NPHP3 to NEK8
CC and INVS may target the complex to the proximal ciliary axoneme
CC (PubMed:23793029). Interacts (via SAM domain) with BICC1 (via KH
CC domains) in an RNA-dependent manner (PubMed:19324013). Interacts (via
CC SAM domain) with ANKS3 (via SAM domain) (PubMed:25671767,
CC PubMed:26327442, PubMed:26188091). {ECO:0000269|PubMed:19324013,
CC ECO:0000269|PubMed:23793029, ECO:0000269|PubMed:25671767,
CC ECO:0000269|PubMed:26188091, ECO:0000269|PubMed:26327442}.
CC -!- SUBCELLULAR LOCATION: Cell projection, cilium
CC {ECO:0000250|UniProtKB:Q6GQX6}. Cytoplasm
CC {ECO:0000269|PubMed:19324013}. Note=Localizes to the proximal region of
CC the primary cilium in the presence of INVS.
CC {ECO:0000250|UniProtKB:Q6GQX6}.
CC -!- TISSUE SPECIFICITY: Widely expressed with moderate level in brain,
CC skeletal muscle and testis. Expressed in renal tubules.
CC {ECO:0000269|PubMed:16207829}.
CC -!- DOMAIN: The ankyrin repeats are necessary and sufficient for NEK8-
CC binding. {ECO:0000269|PubMed:23793029}.
CC -!- PTM: Hydroxylated at Asn-129, most probably by HIF1AN. This
CC hydroxylation results in decreased NEK8-binding.
CC {ECO:0000269|PubMed:23793029}.
CC -!- DISEASE: Note=Defects in Anks6 are the cause of polycystic kidney
CC disease (cy). Heterozygous cy rats are characterized by progressive
CC formation and enlargement of cysts in kidneys.
CC {ECO:0000269|PubMed:16207829, ECO:0000269|PubMed:19324013,
CC ECO:0000269|PubMed:26327442}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH91436.1; Type=Erroneous translation; Note=Wrong choice of frame.; Evidence={ECO:0000305};
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DR EMBL; AY661303; AAT76432.1; -; mRNA.
DR EMBL; AABR03040311; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC091436; AAH91436.1; ALT_SEQ; mRNA.
DR RefSeq; NP_001015028.2; NM_001015028.2.
DR AlphaFoldDB; P0C0T2; -.
DR SMR; P0C0T2; -.
DR CORUM; P0C0T2; -.
DR STRING; 10116.ENSRNOP00000056754; -.
DR PaxDb; P0C0T2; -.
DR GeneID; 362515; -.
DR KEGG; rno:362515; -.
DR UCSC; RGD:3334; rat.
DR CTD; 203286; -.
DR RGD; 3334; Anks6.
DR eggNOG; KOG0504; Eukaryota.
DR eggNOG; KOG4374; Eukaryota.
DR InParanoid; P0C0T2; -.
DR OrthoDB; 1137424at2759; -.
DR PhylomeDB; P0C0T2; -.
DR TreeFam; TF328552; -.
DR PRO; PR:P0C0T2; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0097543; C:ciliary inversin compartment; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0042802; F:identical protein binding; IPI:RGD.
DR GO; GO:0007368; P:determination of left/right symmetry; ISO:RGD.
DR GO; GO:0007507; P:heart development; ISO:RGD.
DR GO; GO:0001701; P:in utero embryonic development; ISO:RGD.
DR GO; GO:0001822; P:kidney development; ISO:RGD.
DR Gene3D; 1.10.150.50; -; 1.
DR Gene3D; 1.25.40.20; -; 3.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR InterPro; IPR001660; SAM.
DR InterPro; IPR013761; SAM/pointed_sf.
DR Pfam; PF00023; Ank; 1.
DR Pfam; PF12796; Ank_2; 3.
DR Pfam; PF00536; SAM_1; 1.
DR PRINTS; PR01415; ANKYRIN.
DR SMART; SM00248; ANK; 10.
DR SMART; SM00454; SAM; 1.
DR SUPFAM; SSF47769; SSF47769; 1.
DR SUPFAM; SSF48403; SSF48403; 2.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 7.
DR PROSITE; PS50105; SAM_DOMAIN; 1.
PE 1: Evidence at protein level;
KW ANK repeat; Cell projection; Cilium; Cytoplasm; Disease variant;
KW Hydroxylation; Phosphoprotein; Reference proteome; Repeat.
FT CHAIN 1..885
FT /note="Ankyrin repeat and SAM domain-containing protein 6"
FT /id="PRO_0000067067"
FT REPEAT 8..37
FT /note="ANK 1"
FT REPEAT 68..97
FT /note="ANK 2"
FT REPEAT 101..130
FT /note="ANK 3"
FT REPEAT 134..163
FT /note="ANK 4"
FT REPEAT 181..210
FT /note="ANK 5"
FT REPEAT 215..244
FT /note="ANK 6"
FT REPEAT 282..312
FT /note="ANK 7"
FT REPEAT 316..345
FT /note="ANK 8"
FT REPEAT 350..379
FT /note="ANK 9"
FT REPEAT 383..414
FT /note="ANK 10"
FT DOMAIN 773..836
FT /note="SAM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00184"
FT REGION 415..439
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 491..522
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 563..775
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 855..885
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 609..636
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 695..775
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 823
FT /note="Essential for ANKS3 interaction"
FT /evidence="ECO:0000269|PubMed:26327442"
FT MOD_RES 129
FT /note="3-hydroxyasparagine"
FT /evidence="ECO:0000269|PubMed:23793029"
FT MOD_RES 650
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q68DC2"
FT MOD_RES 734
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q68DC2"
FT MOD_RES 742
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q68DC2"
FT VARIANT 823
FT /note="R -> W (in cy; loss of ability to self-associate,
FT does not affect interaction with Bicc1; loss of interaction
FT with ANKS3)"
FT /evidence="ECO:0000269|PubMed:16207829,
FT ECO:0000269|PubMed:19324013, ECO:0000269|PubMed:26327442"
FT MUTAGEN 129
FT /note="N->A: Decreased NEK8-binding, but no effect on INVS-
FT binding; when associated with A-209."
FT /evidence="ECO:0000269|PubMed:23793029"
FT MUTAGEN 209
FT /note="N->A: Decreased NEK8-binding, but no effect on INVS-
FT binding; when associated with A-129."
FT /evidence="ECO:0000269|PubMed:23793029"
FT MUTAGEN 433
FT /note="Q->R: No effect on interaction with INVS, NEK8 AND
FT NPHP3, nor on ciliary localization. Unable to rescue ANKS6
FT knockout in a heterologous system."
FT /evidence="ECO:0000269|PubMed:23793029"
FT CONFLICT 870
FT /note="C -> S (in Ref. 1; AAT76432 and 3; AAH91436)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 885 AA; 93809 MW; B4F91C5DFCD2D35E CRC64;
MGEGALAPGL QLLLRACEQG DTDTARRLLE PGGEPVAGSE AGAEPAGPEA ARAVEAGTPV
PVDCSDEAGN SALQLAAAGG HEPLVRFLLR RGASVNSRNH YGWSALMQAA RCGHASVAHL
LLDHGADVNA QNRLGASVLT VASRGGHLGV VKLLLEAGAT VDHRNPSGES TASGGSRDEL
LGITALMAAV QHGHEAVVRL LMEWGADPNH TARTVGWSPL MLAALLGKLS VVQQLVEKGA
NPDHLGVLEK TAFEVALDRK HRDLADYLDP LTTVRPKTDE EKRRPDIFHA LKMGNFQLVK
EIADEDPNHV NLVNGDGATP LMLAAVTGQL PLVQLLVEKH ADMNKQDSVH GWTALMQATY
HGNKEIVKYL LNQGADVTLR AKNGYTAFDL VMLLNDPDTE LVRLLASVCM QVNKDRGGRP
SHRPPLPHSK ARQPWSIPML PDDKGGLKSW WSRMSNRFRK LKLMQTLPRG LAANQPLPFS
DEPELALDST MRAPPQDRTN HLGPPEAAHA AKDSGPGNPR REKDDVLLTT MLRNGAPFPR
LPSDKLKAVI PPFLPPSSFE LWSSDRSRTC PNGKADPMKT VLPPRASRAH PVGCVGTDGA
AGRPVKFPSI SRSPTSPASS GNFNHSPHSS GGASGVGSMS RLGGELHNRS GGSVDSVLSQ
IAAQRKKAAG LCEQKPPCQQ SSPVGPATGS SPPELPASLL GSGSGSSNVT SSSKKLDPGK
RPPSGTSATS KSTSPTLTPS PSPKGHTAES SVSSSSSHRQ SKSSGGSSSG TITDEDELTG
ILKKLSLEKY QPIFEEQEVD MEAFLTLTDG DLQELGIKTD GSRQQILAAI SELNAGKGRE
RQILQETIHN FHSSFESSAS NTRAPGNSPC MAGWVRPEET VSSRR
