KLH17_HUMAN
ID KLH17_HUMAN Reviewed; 642 AA.
AC Q6TDP4; Q5SV94;
DT 27-SEP-2004, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=Kelch-like protein 17;
DE AltName: Full=Actinfilin;
GN Name=KLHL17; Synonyms=AF;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Huang C.Q., Wu S.L., Shan Y.X.;
RL Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
CC -!- FUNCTION: Substrate-recognition component of some cullin-RING-based BCR
CC (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes. The BCR(KLHL17)
CC complex mediates the ubiquitination and subsequent degradation of
CC GLUR6. May play a role in the actin-based neuronal function (By
CC similarity). {ECO:0000250}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with F-actin; the interaction disrupts the F-actin
CC structures and leads to marked changes of neuronal morphology.
CC Component of a complex, composed of PDZK1, SYNGAP1, KLHL17 and NMDA
CC receptors. Interacts directly with PDZK1 (via PDZ1 domain); the
CC interaction is important for integrity of actin cytoskeleton structures
CC in neurons. Interacts with DLG4 and SYNGAP1. Interacts (via kelch
CC repeats) with GRIK2 (via C-terminus); the interaction targets GRIK2 for
CC degradation via ubiquitin-proteasome pathway. Interacts with GRIK1.
CC Interacts with (via BTB domain) CUL3; the interaction regulates surface
CC GRIK2 expression (By similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC Q6TDP4; P54253: ATXN1; NbExp=6; IntAct=EBI-21328926, EBI-930964;
CC Q6TDP4; O60260-5: PRKN; NbExp=3; IntAct=EBI-21328926, EBI-21251460;
CC Q6TDP4; Q13148: TARDBP; NbExp=3; IntAct=EBI-21328926, EBI-372899;
CC Q6TDP4; P40337-2: VHL; NbExp=3; IntAct=EBI-21328926, EBI-12157263;
CC -!- SUBCELLULAR LOCATION: Postsynaptic density
CC {ECO:0000250|UniProtKB:Q8K430}. Synapse {ECO:0000250|UniProtKB:Q8K430}.
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DR EMBL; AY423763; AAR03710.1; -; mRNA.
DR EMBL; AL645608; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS30550.1; -.
DR RefSeq; NP_938073.1; NM_198317.2.
DR PDB; 6HRL; X-ray; 2.60 A; A/B=339-625.
DR PDBsum; 6HRL; -.
DR AlphaFoldDB; Q6TDP4; -.
DR SMR; Q6TDP4; -.
DR BioGRID; 130885; 14.
DR IntAct; Q6TDP4; 8.
DR STRING; 9606.ENSP00000343930; -.
DR iPTMnet; Q6TDP4; -.
DR PhosphoSitePlus; Q6TDP4; -.
DR BioMuta; KLHL17; -.
DR DMDM; 52783052; -.
DR EPD; Q6TDP4; -.
DR jPOST; Q6TDP4; -.
DR MassIVE; Q6TDP4; -.
DR MaxQB; Q6TDP4; -.
DR PaxDb; Q6TDP4; -.
DR PeptideAtlas; Q6TDP4; -.
DR PRIDE; Q6TDP4; -.
DR ProteomicsDB; 67385; -.
DR Antibodypedia; 26039; 19 antibodies from 11 providers.
DR DNASU; 339451; -.
DR Ensembl; ENST00000338591.8; ENSP00000343930.3; ENSG00000187961.15.
DR GeneID; 339451; -.
DR KEGG; hsa:339451; -.
DR MANE-Select; ENST00000338591.8; ENSP00000343930.3; NM_198317.3; NP_938073.1.
DR UCSC; uc001aca.3; human.
DR CTD; 339451; -.
DR DisGeNET; 339451; -.
DR GeneCards; KLHL17; -.
DR HGNC; HGNC:24023; KLHL17.
DR HPA; ENSG00000187961; Low tissue specificity.
DR MIM; 619262; gene.
DR neXtProt; NX_Q6TDP4; -.
DR OpenTargets; ENSG00000187961; -.
DR PharmGKB; PA134887396; -.
DR VEuPathDB; HostDB:ENSG00000187961; -.
DR eggNOG; KOG4441; Eukaryota.
DR GeneTree; ENSGT00940000157635; -.
DR HOGENOM; CLU_004253_14_2_1; -.
DR InParanoid; Q6TDP4; -.
DR OMA; MSCVEAE; -.
DR OrthoDB; 731760at2759; -.
DR PhylomeDB; Q6TDP4; -.
DR TreeFam; TF329218; -.
DR PathwayCommons; Q6TDP4; -.
DR SignaLink; Q6TDP4; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 339451; 17 hits in 1117 CRISPR screens.
DR ChiTaRS; KLHL17; human.
DR GenomeRNAi; 339451; -.
DR Pharos; Q6TDP4; Tdark.
DR PRO; PR:Q6TDP4; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q6TDP4; protein.
DR Bgee; ENSG00000187961; Expressed in lower esophagus mucosa and 95 other tissues.
DR ExpressionAtlas; Q6TDP4; baseline and differential.
DR Genevisible; Q6TDP4; HS.
DR GO; GO:0015629; C:actin cytoskeleton; ISS:UniProtKB.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0032839; C:dendrite cytoplasm; IBA:GO_Central.
DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0014069; C:postsynaptic density; IEA:UniProtKB-SubCell.
DR GO; GO:0051015; F:actin filament binding; IBA:GO_Central.
DR GO; GO:0060090; F:molecular adaptor activity; ISS:UniProtKB.
DR GO; GO:0031208; F:POZ domain binding; IEA:Ensembl.
DR GO; GO:0030036; P:actin cytoskeleton organization; ISS:UniProtKB.
DR GO; GO:0007420; P:brain development; IBA:GO_Central.
DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
DR Gene3D; 2.120.10.80; -; 2.
DR Gene3D; 3.30.710.10; -; 1.
DR InterPro; IPR011705; BACK.
DR InterPro; IPR017096; BTB-kelch_protein.
DR InterPro; IPR000210; BTB/POZ_dom.
DR InterPro; IPR011043; Gal_Oxase/kelch_b-propeller.
DR InterPro; IPR015915; Kelch-typ_b-propeller.
DR InterPro; IPR006652; Kelch_1.
DR InterPro; IPR030594; KLHL17/KLHL20.
DR InterPro; IPR011333; SKP1/BTB/POZ_sf.
DR PANTHER; PTHR24412:SF454; PTHR24412:SF454; 1.
DR Pfam; PF07707; BACK; 1.
DR Pfam; PF00651; BTB; 1.
DR Pfam; PF01344; Kelch_1; 6.
DR PIRSF; PIRSF037037; Kelch-like_protein_gigaxonin; 1.
DR SMART; SM00875; BACK; 1.
DR SMART; SM00225; BTB; 1.
DR SMART; SM00612; Kelch; 6.
DR SUPFAM; SSF50965; SSF50965; 1.
DR SUPFAM; SSF54695; SSF54695; 1.
DR PROSITE; PS50097; BTB; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Actin-binding; Kelch repeat; Reference proteome; Repeat;
KW Synapse; Ubl conjugation pathway.
FT CHAIN 1..642
FT /note="Kelch-like protein 17"
FT /id="PRO_0000119119"
FT DOMAIN 92..159
FT /note="BTB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00037"
FT DOMAIN 194..296
FT /note="BACK"
FT REPEAT 343..389
FT /note="Kelch 1"
FT REPEAT 390..436
FT /note="Kelch 2"
FT REPEAT 438..483
FT /note="Kelch 3"
FT REPEAT 484..530
FT /note="Kelch 4"
FT REPEAT 532..577
FT /note="Kelch 5"
FT REPEAT 578..624
FT /note="Kelch 6"
FT REGION 1..53
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 289..641
FT /note="Interaction with F-actin"
FT /evidence="ECO:0000250"
FT REGION 640..642
FT /note="Interaction with PDZK1"
FT /evidence="ECO:0000250"
FT COMPBIAS 20..39
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT STRAND 341..347
FT /evidence="ECO:0007829|PDB:6HRL"
FT STRAND 359..363
FT /evidence="ECO:0007829|PDB:6HRL"
FT TURN 364..367
FT /evidence="ECO:0007829|PDB:6HRL"
FT STRAND 368..372
FT /evidence="ECO:0007829|PDB:6HRL"
FT STRAND 383..387
FT /evidence="ECO:0007829|PDB:6HRL"
FT STRAND 390..394
FT /evidence="ECO:0007829|PDB:6HRL"
FT STRAND 406..410
FT /evidence="ECO:0007829|PDB:6HRL"
FT TURN 411..414
FT /evidence="ECO:0007829|PDB:6HRL"
FT STRAND 415..419
FT /evidence="ECO:0007829|PDB:6HRL"
FT STRAND 430..434
FT /evidence="ECO:0007829|PDB:6HRL"
FT STRAND 437..441
FT /evidence="ECO:0007829|PDB:6HRL"
FT STRAND 446..449
FT /evidence="ECO:0007829|PDB:6HRL"
FT STRAND 453..457
FT /evidence="ECO:0007829|PDB:6HRL"
FT TURN 458..461
FT /evidence="ECO:0007829|PDB:6HRL"
FT STRAND 462..466
FT /evidence="ECO:0007829|PDB:6HRL"
FT STRAND 477..481
FT /evidence="ECO:0007829|PDB:6HRL"
FT STRAND 484..491
FT /evidence="ECO:0007829|PDB:6HRL"
FT STRAND 496..504
FT /evidence="ECO:0007829|PDB:6HRL"
FT TURN 505..508
FT /evidence="ECO:0007829|PDB:6HRL"
FT STRAND 509..513
FT /evidence="ECO:0007829|PDB:6HRL"
FT STRAND 524..528
FT /evidence="ECO:0007829|PDB:6HRL"
FT STRAND 531..535
FT /evidence="ECO:0007829|PDB:6HRL"
FT STRAND 540..543
FT /evidence="ECO:0007829|PDB:6HRL"
FT STRAND 547..551
FT /evidence="ECO:0007829|PDB:6HRL"
FT TURN 552..555
FT /evidence="ECO:0007829|PDB:6HRL"
FT STRAND 556..560
FT /evidence="ECO:0007829|PDB:6HRL"
FT STRAND 571..575
FT /evidence="ECO:0007829|PDB:6HRL"
FT STRAND 578..582
FT /evidence="ECO:0007829|PDB:6HRL"
FT STRAND 587..590
FT /evidence="ECO:0007829|PDB:6HRL"
FT STRAND 594..598
FT /evidence="ECO:0007829|PDB:6HRL"
FT TURN 599..602
FT /evidence="ECO:0007829|PDB:6HRL"
FT STRAND 603..607
FT /evidence="ECO:0007829|PDB:6HRL"
FT STRAND 618..624
FT /evidence="ECO:0007829|PDB:6HRL"
SQ SEQUENCE 642 AA; 69874 MW; FE37BBCCD32131BF CRC64;
MQPRSERPAG RTQSPEHGSP GPGPEAPPPP PPQPPAPEAE RTRPRQARPA APMEGAVQLL
SREGHSVAHN SKRHYHDAFV AMSRMRQRGL LCDIVLHVAA KEIRAHKVVL ASCSPYFHAM
FTNEMSESRQ THVTLHDIDP QALDQLVQFA YTAEIVVGEG NVQTLLPAAS LLQLNGVRDA
CCKFLLSQLD PSNCLGIRGF ADAHSCSDLL KAAHRYVLQH FVDVAKTEEF MLLPLKQVLE
LVSSDSLNVP SEEEVYRAVL SWVKHDVDAR RQHVPRLMKC VRLPLLSRDF LLGHVDAESL
VRHHPDCKDL LIEALKFHLL PEQRGVLGTS RTRPRRCEGA GPVLFAVGGG SLFAIHGDCE
AYDTRTDRWH VVASMSTRRA RVGVAAVGNR LYAVGGYDGT SDLATVESYD PVTNTWQPEV
SMGTRRSCLG VAALHGLLYS AGGYDGASCL NSAERYDPLT GTWTSVAAMS TRRRYVRVAT
LDGNLYAVGG YDSSSHLATV EKYEPQVNVW SPVASMLSRR SSAGVAVLEG ALYVAGGNDG
TSCLNSVERY SPKAGAWESV APMNIRRSTH DLVAMDGWLY AVGGNDGSSS LNSIEKYNPR
TNKWVAASCM FTRRSSVGVA VLELLNFPPP SSPTLSVSST SL
