KIF7_MOUSE
ID KIF7_MOUSE Reviewed; 1348 AA.
AC B7ZNG0; B2RUB1;
DT 08-MAR-2011, integrated into UniProtKB/Swiss-Prot.
DT 03-MAR-2009, sequence version 1.
DT 03-AUG-2022, entry version 88.
DE RecName: Full=Kinesin-like protein KIF7;
GN Name=Kif7;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain;
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 [2]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=19592253; DOI=10.1016/j.cub.2009.06.046;
RA Endoh-Yamagami S., Evangelista M., Wilson D., Wen X., Theunissen J.W.,
RA Phamluong K., Davis M., Scales S.J., Solloway M.J., de Sauvage F.J.,
RA Peterson A.S.;
RT "The mammalian Cos2 homolog Kif7 plays an essential role in modulating Hh
RT signal transduction during development.";
RL Curr. Biol. 19:1320-1326(2009).
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP LEU-130.
RX PubMed=19666503; DOI=10.1073/pnas.0906944106;
RA Liem K.F. Jr., He M., Ocbina P.J., Anderson K.V.;
RT "Mouse Kif7/Costal2 is a cilia-associated protein that regulates Sonic
RT hedgehog signaling.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:13377-13382(2009).
RN [4]
RP FUNCTION, DISRUPTION PHENOTYPE, AND INTERACTION WITH GLI2 AND GLI3.
RX PubMed=19549984; DOI=10.1126/scisignal.2000405;
RA Cheung H.O., Zhang X., Ribeiro A., Mo R., Makino S., Puviindran V.,
RA Law K.K., Briscoe J., Hui C.C.;
RT "The kinesin protein Kif7 is a critical regulator of Gli transcription
RT factors in mammalian hedgehog signaling.";
RL Sci. Signal. 2:RA29-RA29(2009).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-903, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Lung;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP FUNCTION IN REGULATION OF IHH SIGNALING AND CHONDROCYTE DEVELOPMENT.
RX PubMed=21795282; DOI=10.1242/dev.069492;
RA Hsu S.H., Zhang X., Yu C., Li Z.J., Wunder J.S., Hui C.C., Alman B.A.;
RT "Kif7 promotes hedgehog signaling in growth plate chondrocytes by
RT restricting the inhibitory function of Sufu.";
RL Development 138:3791-3801(2011).
RN [7]
RP TISSUE SPECIFICITY.
RX PubMed=21633164; DOI=10.1172/jci43639;
RA Dafinger C., Liebau M.C., Elsayed S.M., Hellenbroich Y., Boltshauser E.,
RA Korenke G.C., Fabretti F., Janecke A.R., Ebermann I., Nurnberg G.,
RA Nurnberg P., Zentgraf H., Koerber F., Addicks K., Elsobky E., Benzing T.,
RA Schermer B., Bolz H.J.;
RT "Mutations in KIF7 link Joubert syndrome with Sonic Hedgehog signaling and
RT microtubule dynamics.";
RL J. Clin. Invest. 121:2662-2667(2011).
RN [8]
RP FUNCTION IN REGULATION OF EPIDERMAL DIFFERENTIATION, AND INTERACTION WITH
RP GLI2 AND SUFU.
RX PubMed=23034632; DOI=10.1242/dev.081190;
RA Li Z.J., Nieuwenhuis E., Nien W., Zhang X., Zhang J., Puviindran V.,
RA Wainwright B.J., Kim P.C., Hui C.C.;
RT "Kif7 regulates Gli2 through Sufu-dependent and -independent functions
RT during skin development and tumorigenesis.";
RL Development 139:4152-4161(2012).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, AND INTERACTION WITH MICROTUBULES.
RX PubMed=24952464; DOI=10.1038/ncb2988;
RA He M., Subramanian R., Bangs F., Omelchenko T., Liem K.F. Jr., Kapoor T.M.,
RA Anderson K.V.;
RT "The kinesin-4 protein Kif7 regulates mammalian Hedgehog signalling by
RT organizing the cilium tip compartment.";
RL Nat. Cell Biol. 16:663-672(2014).
RN [10]
RP INTERACTION WITH SMO AND DLG5, AND SUBCELLULAR LOCATION.
RX PubMed=25644602; DOI=10.1101/gad.252676.114;
RA Chong Y.C., Mann R.K., Zhao C., Kato M., Beachy P.A.;
RT "Bifurcating action of Smoothened in Hedgehog signaling is mediated by
RT Dlg5.";
RL Genes Dev. 29:262-276(2015).
RN [11]
RP UBIQUITINATION.
RX PubMed=27195754; DOI=10.1371/journal.pgen.1006054;
RA Li T., Fan J., Blanco-Sanchez B., Giagtzoglou N., Lin G., Yamamoto S.,
RA Jaiswal M., Chen K., Zhang J., Wei W., Lewis M.T., Groves A.K.,
RA Westerfield M., Jia J., Bellen H.J.;
RT "Ubr3, a Novel Modulator of Hh Signaling Affects the Degradation of Costal-
RT 2 and Kif7 through Poly-ubiquitination.";
RL PLoS Genet. 12:E1006054-E1006054(2016).
CC -!- FUNCTION: Essential for hedgehog signaling regulation: acts as both a
CC negative and positive regulator of sonic hedgehog (Shh) and Indian
CC hedgehog (Ihh) pathways, acting downstream of SMO, through both SUFU-
CC dependent and -independent mechanisms. Involved in the regulation of
CC microtubular dynamics. Required for proper organization of the ciliary
CC tip and control of ciliary localization of SUFU-GLI2 complexes.
CC Required for localization of GLI3 to cilia in response to Shh.
CC Negatively regulates Shh signaling by preventing inappropriate
CC activation of the transcriptional activator GLI2 in the absence of
CC ligand. Positively regulates Shh signaling by preventing the processing
CC of the transcription factor GLI3 into its repressor form. In
CC keratinocytes, promotes the dissociation of SUFU-GLI2 complexes, GLI2
CC nuclear translocation and Shh signaling activation. Involved in the
CC regulation of epidermal differentiation and chondrocyte development.
CC {ECO:0000269|PubMed:19549984, ECO:0000269|PubMed:19592253,
CC ECO:0000269|PubMed:19666503, ECO:0000269|PubMed:21795282,
CC ECO:0000269|PubMed:23034632, ECO:0000269|PubMed:24952464}.
CC -!- SUBUNIT: Can form homodimers and interacts with microtubules
CC (PubMed:24952464). Interacts with GLI1 and SMO (By similarity).
CC Interacts with GLI2, GLI3 and SUFU (PubMed:19549984). Interacts with
CC NPHP1 (By similarity). Interacts with SMO and DLG5 (via PDZ4 or
CC guanylate kinase-like domain) (PubMed:25644602).
CC {ECO:0000250|UniProtKB:Q2M1P5, ECO:0000269|PubMed:19549984,
CC ECO:0000269|PubMed:24952464, ECO:0000269|PubMed:25644602}.
CC -!- INTERACTION:
CC B7ZNG0-2; B7ZNG0-2: Kif7; NbExp=2; IntAct=EBI-16110388, EBI-16110388;
CC -!- SUBCELLULAR LOCATION: Cell projection, cilium
CC {ECO:0000269|PubMed:19666503, ECO:0000269|PubMed:24952464,
CC ECO:0000269|PubMed:25644602}. Cytoplasm, cytoskeleton, cilium basal
CC body {ECO:0000269|PubMed:25644602}. Note=Localizes to the cilium tip.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=B7ZNG0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=B7ZNG0-2; Sequence=VSP_040736;
CC -!- TISSUE SPECIFICITY: Expressed in heart, lung, liver, kidney, testis,
CC spleen and cerebellum. {ECO:0000269|PubMed:21633164}.
CC -!- PTM: Polyubiquitinated by UBR3. {ECO:0000269|PubMed:27195754}.
CC -!- DISRUPTION PHENOTYPE: Mutations appear to be the cause of the matariki
CC (maki) phenotype, characterized by expanded motor neuron domain in the
CC 10.5 dpc neural tube. Motor neurons are increased in number and expand
CC dorsally. Mutants die at the end of gestation, when other phenotypes
CC characteristic of elevated Shh signaling are apparent, including
CC preaxial polydactyly. Knockout mice have defects in developmental
CC patterning and die at birth with severe malformations, including
CC exencephaly and polydactyly. {ECO:0000269|PubMed:19549984,
CC ECO:0000269|PubMed:19592253, ECO:0000269|PubMed:19666503}.
CC -!- SIMILARITY: Belongs to the TRAFAC class myosin-kinesin ATPase
CC superfamily. Kinesin family. {ECO:0000255|PROSITE-ProRule:PRU00283}.
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DR EMBL; BC141045; AAI41046.1; -; mRNA.
DR EMBL; BC145222; AAI45223.1; -; mRNA.
DR CCDS; CCDS52278.1; -. [B7ZNG0-2]
DR CCDS; CCDS80739.1; -. [B7ZNG0-1]
DR AlphaFoldDB; B7ZNG0; -.
DR SMR; B7ZNG0; -.
DR CORUM; B7ZNG0; -.
DR DIP; DIP-61761N; -.
DR IntAct; B7ZNG0; 4.
DR STRING; 10090.ENSMUSP00000139359; -.
DR iPTMnet; B7ZNG0; -.
DR PhosphoSitePlus; B7ZNG0; -.
DR EPD; B7ZNG0; -.
DR jPOST; B7ZNG0; -.
DR MaxQB; B7ZNG0; -.
DR PaxDb; B7ZNG0; -.
DR PRIDE; B7ZNG0; -.
DR ProteomicsDB; 269305; -. [B7ZNG0-1]
DR ProteomicsDB; 269306; -. [B7ZNG0-2]
DR MGI; MGI:1098239; Kif7.
DR eggNOG; KOG0244; Eukaryota.
DR InParanoid; B7ZNG0; -.
DR Reactome; R-MMU-5610787; Hedgehog 'off' state.
DR Reactome; R-MMU-5632684; Hedgehog 'on' state.
DR ChiTaRS; Kif7; mouse.
DR PRO; PR:B7ZNG0; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; B7ZNG0; protein.
DR GO; GO:0036064; C:ciliary basal body; IDA:UniProtKB.
DR GO; GO:0097542; C:ciliary tip; IDA:MGI.
DR GO; GO:0005929; C:cilium; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
DR GO; GO:0005871; C:kinesin complex; IBA:GO_Central.
DR GO; GO:0005874; C:microtubule; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0008017; F:microtubule binding; IBA:GO_Central.
DR GO; GO:0003777; F:microtubule motor activity; ISO:MGI.
DR GO; GO:0035904; P:aorta development; IMP:MGI.
DR GO; GO:0003279; P:cardiac septum development; IMP:MGI.
DR GO; GO:0060976; P:coronary vasculature development; IMP:MGI.
DR GO; GO:0007018; P:microtubule-based movement; IBA:GO_Central.
DR GO; GO:0045879; P:negative regulation of smoothened signaling pathway; IMP:UniProtKB.
DR GO; GO:0045880; P:positive regulation of smoothened signaling pathway; IMP:UniProtKB.
DR Gene3D; 3.40.850.10; -; 1.
DR InterPro; IPR019821; Kinesin_motor_CS.
DR InterPro; IPR001752; Kinesin_motor_dom.
DR InterPro; IPR036961; Kinesin_motor_dom_sf.
DR InterPro; IPR027417; P-loop_NTPase.
DR Pfam; PF00225; Kinesin; 1.
DR PRINTS; PR00380; KINESINHEAVY.
DR SMART; SM00129; KISc; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS00411; KINESIN_MOTOR_1; 1.
DR PROSITE; PS50067; KINESIN_MOTOR_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Cell projection; Cilium; Coiled coil;
KW Cytoplasm; Cytoskeleton; Motor protein; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Repressor; Ubl conjugation.
FT CHAIN 1..1348
FT /note="Kinesin-like protein KIF7"
FT /id="PRO_0000405978"
FT DOMAIN 15..349
FT /note="Kinesin motor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00283"
FT REGION 358..1211
FT /note="Interaction with SMO"
FT /evidence="ECO:0000269|PubMed:25644602"
FT REGION 358..479
FT /note="Interaction with DLG5"
FT /evidence="ECO:0000269|PubMed:25644602"
FT REGION 451..486
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 607..674
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1288..1314
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1328..1348
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 480..542
FT /evidence="ECO:0000255"
FT COILED 698..1057
FT /evidence="ECO:0000255"
FT COILED 1109..1211
FT /evidence="ECO:0000255"
FT COMPBIAS 621..636
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 94..101
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00283"
FT MOD_RES 903
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT VAR_SEQ 912
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_040736"
FT MUTAGEN 130
FT /note="L->P: In maki; expanded motor neuron domain in the
FT 10.5 dpc neural tube."
FT /evidence="ECO:0000269|PubMed:19666503"
FT CONFLICT 1226
FT /note="Q -> R (in Ref. 1; AAI41046)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1348 AA; 151624 MW; 76D4B7387965C17C CRC64;
MGLEAQRLPG AEEAPVRVAL RVRPLLPKEL LHGHQSCLRV EPERGRITLG RDRHFGFHVV
LGEDTGQEAV YQACVQPLLE AFFEGFNATV FAYGQTGSGK TYTMGEASVA SLHEDEQGII
PRAMAEAFKL IDENDLLDCL VHVSYLELYK EEFRDLLEVG TASRDIQLRE DDRGNVVLCG
VKEVDVEGLD EVLSLLEMGN AARHTGATHF NRLSSRSHTV FTVTLEQRGR TPSRLPRPAA
GHLLVSKFHF VDLAGSERVL KTGSTGERLK ESIQINSTLL ALGNVISALG DPQRRGSHIP
YRDSKITRIL KDSLGGNAKT VMIACVSPSS SDFDETLNTL NYASRAQNIR NRATVNWHPE
AERVPEEQAA GARGPPRHRS ETRIIHRGRR VPCPAVGSAA VAAGLGAECA RCRARTSAAY
SLLRELQAEP GLPGAAARKV RDWLCAVEGE RSTLSSASGP DSGIESAPAE DQAAQGTSGR
KGDEGTQQLL TLQSQVARLE EENRDFLAAL EDAMEQYKLQ SDRLREQQEE MVELRLRLEL
AQPGWGAPGL LQGLPPGSFV PRPHTAPLGG AHTHMLGMMP STCLPGEEVS SEQQVVSGKE
VKAEVLAQAD KLRSASSTTS EEEGEEEEEE EEEEEEPPRR TLYLRRNGIS NWSQRAGLSP
GSPPDRKGPE VCPEEPAAAI PAPQAVGSGK VPVQTRQAPA AMASEWRLAQ AQQKIRELAI
NIRMKEELIG ELVRTGKAAQ ALNRQHSQRI RELEQEAERV RAELCEGQRQ LRELEGREPQ
DASERSRLQE FRKRVAAAQS QVQVLKEKKQ ATERLVSLSA QSETRLQELE RNVQLMRRQQ
GQLQRRLREE TEQKRRLETE MNKRQHRVKE LELKHEQQQK ILKIKTEEIA AFQRKRRSGS
NGSVVSLEQQ QKIEEQKKWL DQEMEKVLQQ RRALEELGEE LRKREVILAK KEALMQEKTG
LESKRLRSSQ ALNEDIVRVS SRLEHLEKEL SEKSGQLRQG SAQNQQQIRG EIDTLRQEKD
SLLKQRLEID SKLRQGSLLS PEEERTLFQL DEAIEALDAA IEYKNEAITC RQRVLRASAS
LLSQCEMNLM AKLSYLSSSE TRALLCKYFD KVVTLREEQH QQQIAFSELE MQLEEQQRLV
YWLEVALERQ RLEMDRQLTL QQKEHEQNVQ LLLQQGRDHL GEGLADSKRQ YEARIHALEK
ELGRHMWINQ ELKQKLSAGS TAGQSQGCER RSLCLENRQC LGNEDGLHPA APEPLWQSSL
LEGVSRVWDE SRDLVHAPLP LTWKRSSLCS EQGSSEESRV RETTEPPVGR VLPMGEVGLS
WNFGPLPKPR WEPRRTSPGM IDVRKNPL
