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   27-MAR-2024, entry version 154.
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; 19.
DR   ComplexPortal; CPX-8103; CRL3 E3 ubiquitin ligase complex, KLHL17 variant.
DR   IntAct; Q6TDP4; 11.
DR   STRING; 9606.ENSP00000343930; -.
DR   GlyGen; Q6TDP4; 1 site, 1 O-linked glycan (1 site).
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; 9606-ENSP00000343930; -.
DR   PeptideAtlas; Q6TDP4; -.
DR   ProteomicsDB; 67385; -.
DR   Antibodypedia; 26039; 30 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   AGR; HGNC:24023; -.
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; ATAECYN; -.
DR   OrthoDB; 5472491at2759; -.
DR   PhylomeDB; Q6TDP4; -.
DR   TreeFam; TF329218; -.
DR   PathwayCommons; Q6TDP4; -.
DR   SignaLink; Q6TDP4; -.
DR   SIGNOR; Q6TDP4; -.
DR   UniPathway; UPA00143; -.
DR   BioGRID-ORCS; 339451; 19 hits in 1193 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 97 other cell types or tissues.
DR   ExpressionAtlas; Q6TDP4; baseline and differential.
DR   GO; GO:0015629; C:actin cytoskeleton; ISS:UniProtKB.
DR   GO; GO:0032839; C:dendrite cytoplasm; IEA:Ensembl.
DR   GO; GO:0005615; C:extracellular space; HDA:UniProtKB.
DR   GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
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; IEA:Ensembl.
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:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
DR   GO; GO:0140252; P:regulation protein catabolic process at postsynapse; IEA:Ensembl.
DR   CDD; cd18456; BACK_KLHL17; 1.
DR   CDD; cd18246; BTB_POZ_KLHL17_actinfilin; 1.
DR   Gene3D; 1.25.40.420; -; 1.
DR   Gene3D; 2.120.10.80; Kelch-type beta propeller; 2.
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; IPR011333; SKP1/BTB/POZ_sf.
DR   PANTHER; PTHR24412:SF498; BTB DOMAIN-CONTAINING PROTEIN; 1.
DR   PANTHER; PTHR24412; KELCH PROTEIN; 1.
DR   Pfam; PF07707; BACK; 1.
DR   Pfam; PF00651; BTB; 1.
DR   Pfam; PF01344; Kelch_1; 5.
DR   PIRSF; PIRSF037037; Kelch-like_protein_gigaxonin; 1.
DR   PRINTS; PR00501; KELCHREPEAT.
DR   SMART; SM00875; BACK; 1.
DR   SMART; SM00225; BTB; 1.
DR   SMART; SM00612; Kelch; 6.
DR   SUPFAM; SSF50965; Galactose oxidase, central domain; 1.
DR   SUPFAM; SSF54695; POZ domain; 1.
DR   PROSITE; PS50097; BTB; 1.
DR   Genevisible; Q6TDP4; HS.
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
//