WDR81_HUMAN
ID WDR81_HUMAN Reviewed; 1941 AA.
AC Q562E7; B3KW16; B3KXU1; B7Z579; E9PHG7; Q24JP6; Q8N277; Q8N3F3; Q8TEL1;
DT 25-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-SEP-2012, sequence version 2.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=WD repeat-containing protein 81 {ECO:0000312|HGNC:HGNC:26600};
GN Name=WDR81 {ECO:0000312|HGNC:HGNC:26600};
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 [LARGE SCALE MRNA] (ISOFORMS 3 AND 5), NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 873-1941 (ISOFORM 4), AND VARIANT VAL-1535.
RC TISSUE=Mesangial cell, Spleen, Synovium, and Tongue;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 1049-1941 (ISOFORM 3).
RC TISSUE=Lymph;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1033-1941.
RC TISSUE=Melanoma;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [7]
RP FUNCTION, INTERACTION WITH BECN1 AND WDR81, SUBCELLULAR LOCATION, AND
RP TOPOLOGY.
RX PubMed=26783301; DOI=10.1083/jcb.201506081;
RA Liu K., Jian Y., Sun X., Yang C., Gao Z., Zhang Z., Liu X., Li Y., Xu J.,
RA Jing Y., Mitani S., He S., Yang C.;
RT "Negative regulation of phosphatidylinositol 3-phosphate levels in early-
RT to-late endosome conversion.";
RL J. Cell Biol. 212:181-198(2016).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY, AND INTERACTION WITH WDR91.
RX PubMed=27126989; DOI=10.1111/tra.12409;
RA Rapiteanu R., Davis L.J., Williamson J.C., Timms R.T., Paul Luzio J.,
RA Lehner P.J.;
RT "A genetic screen identifies a critical role for the WDR81-WDR91 complex in
RT the trafficking and degradation of tetherin.";
RL Traffic 17:940-958(2016).
RN [9]
RP INVOLVEMENT IN HYC3, AND VARIANTS HYC3 GLU-282 AND 1096-GLN--ALA-1941 DEL.
RX PubMed=28556411; DOI=10.1002/ana.24964;
RA Shaheen R., Sebai M.A., Patel N., Ewida N., Kurdi W., Altweijri I.,
RA Sogaty S., Almardawi E., Seidahmed M.Z., Alnemri A., Madirevula S.,
RA Ibrahim N., Abdulwahab F., Hashem M., Al-Sheddi T., Alomar R., Alobeid E.,
RA Sallout B., AlBaqawi B., AlAali W., Ajaji N., Lesmana H., Hopkin R.J.,
RA Dupuis L., Mendoza-Londono R., Al Rukban H., Yoon G., Faqeih E.,
RA Alkuraya F.S.;
RT "The genetic landscape of familial congenital hydrocephalus.";
RL Ann. Neurol. 81:890-897(2017).
RN [10]
RP FUNCTION, INTERACTION WITH MAP1LC3C AND SQSTM1, SUBCELLULAR LOCATION,
RP REGION, AND MUTAGENESIS OF TRP-544; LEU-547; SER-577; TYR-578 AND VAL-581.
RX PubMed=28404643; DOI=10.1083/jcb.201608039;
RA Liu X., Li Y., Wang X., Xing R., Liu K., Gan Q., Tang C., Gao Z., Jian Y.,
RA Luo S., Guo W., Yang C.;
RT "The BEACH-containing protein WDR81 coordinates p62 and LC3C to promote
RT aggrephagy.";
RL J. Cell Biol. 216:1301-1320(2017).
RN [11]
RP VARIANT CAMRQ2 LEU-856, AND TISSUE SPECIFICITY.
RX PubMed=21885617; DOI=10.1101/gr.126110.111;
RA Gulsuner S., Tekinay A.B., Doerschner K., Boyaci H., Bilguvar K., Unal H.,
RA Ors A., Onat O.E., Atalar E., Basak A.N., Topaloglu H., Kansu T., Tan M.,
RA Tan U., Gunel M., Ozcelik T.;
RT "Homozygosity mapping and targeted genomic sequencing reveal the gene
RT responsible for cerebellar hypoplasia and quadrupedal locomotion in a
RT consanguineous kindred.";
RL Genome Res. 21:1995-2003(2011).
RN [12]
RP VARIANT CAMRQ2 1333-ARG--ALA-1941 DEL.
RX PubMed=26437881; DOI=10.1002/ajmg.a.37421;
RA Komara M., John A., Suleiman J., Ali B.R., Al-Gazali L.;
RT "Clinical and molecular delineation of dysequilibrium syndrome type 2 and
RT profound sensorineural hearing loss in an inbred Arab family.";
RL Am. J. Med. Genet. A 170A:540-543(2016).
CC -!- FUNCTION: Functions as a negative regulator of the PI3 kinase/PI3K
CC activity associated with endosomal membranes via BECN1, a core subunit
CC of the PI3K complex. By modifying the phosphatidylinositol 3-
CC phosphate/PtdInsP3 content of endosomal membranes may regulate endosome
CC fusion, recycling, sorting and early to late endosome transport
CC (PubMed:26783301). It is for instance, required for the delivery of
CC cargos like BST2/tetherin from early to late endosome and thereby
CC participates indirectly to their degradation by the lysosome
CC (PubMed:27126989). May also play a role in aggrephagy, the
CC macroautophagic degradation of ubiquitinated protein aggregates. In
CC this process, may regulate the interaction of SQSTM1 with ubiquitinated
CC proteins and also recruit MAP1LC3C (PubMed:28404643). May also be
CC involved in maintenance of normal mitochondrial structure and
CC organization (By similarity). {ECO:0000250|UniProtKB:Q5ND34,
CC ECO:0000269|PubMed:26783301, ECO:0000269|PubMed:27126989,
CC ECO:0000269|PubMed:28404643}.
CC -!- SUBUNIT: Interacts with WDR91; involved in early to late endosome cargo
CC transport (PubMed:26783301, PubMed:27126989). Interacts with BECN1;
CC negatively regulates the PI3 kinase/PI3K activity associated with
CC endosomal membranes (PubMed:26783301). Interacts with SQSTM1; the
CC interaction is direct and regulates the interaction of SQSTM1 with
CC ubiquitinated proteins (PubMed:28404643). Interacts with MAP1LC3C;
CC recruits MAP1LC3C to ubiquitinated protein aggregates in the aggrephagy
CC process (PubMed:28404643). {ECO:0000269|PubMed:26783301,
CC ECO:0000269|PubMed:27126989, ECO:0000269|PubMed:28404643}.
CC -!- INTERACTION:
CC Q562E7; A4D1P6: WDR91; NbExp=3; IntAct=EBI-5235360, EBI-718046;
CC -!- SUBCELLULAR LOCATION: Early endosome membrane
CC {ECO:0000269|PubMed:26783301, ECO:0000269|PubMed:27126989}; Peripheral
CC membrane protein {ECO:0000269|PubMed:26783301,
CC ECO:0000269|PubMed:27126989}. Late endosome membrane
CC {ECO:0000269|PubMed:26783301, ECO:0000269|PubMed:27126989,
CC ECO:0000269|PubMed:28404643}. Lysosome membrane
CC {ECO:0000269|PubMed:27126989}. Cytoplasmic vesicle, autophagosome
CC membrane {ECO:0000269|PubMed:28404643}. Mitochondrion
CC {ECO:0000269|PubMed:28404643}. Cytoplasm, cytosol
CC {ECO:0000269|PubMed:27126989}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Name=1;
CC IsoId=Q562E7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q562E7-2; Sequence=VSP_044065, VSP_019955;
CC Name=3;
CC IsoId=Q562E7-3; Sequence=VSP_044065;
CC Name=4;
CC IsoId=Q562E7-4; Sequence=VSP_044067;
CC Name=5;
CC IsoId=Q562E7-5; Sequence=VSP_044064, VSP_044066;
CC Name=6;
CC IsoId=Q562E7-6; Sequence=VSP_044063;
CC -!- TISSUE SPECIFICITY: Widely expressed. In the brain, highest levels in
CC cerebellum and corpus callosum. {ECO:0000269|PubMed:21885617}.
CC -!- DISEASE: Cerebellar ataxia, intellectual disability, and dysequilibrium
CC syndrome 2 (CAMRQ2) [MIM:610185]: An autosomal recessive, congenital
CC cerebellar ataxia associated with cerebellar hypoplasia, intellectual
CC disability, and inability to walk bipedally, resulting in quadrupedal
CC locomotion as a functional adaptation. Additional findings include
CC generalized brain atrophy and mild hypoplasia of the corpus callosum.
CC {ECO:0000269|PubMed:21885617, ECO:0000269|PubMed:26437881}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Hydrocephalus, congenital, 3, with brain anomalies (HYC3)
CC [MIM:617967]: A form of congenital hydrocephalus, a disease
CC characterized by onset in utero of enlarged ventricles due to
CC accumulation of ventricular cerebrospinal fluid. HYC3 features include
CC enlarged ventricles, hypoplastic or absent cerebellum,
CC holoprosencephaly and Dandy-Walker malformation. Most patients die in
CC utero or shortly after birth. HYC3 inheritance is autosomal recessive.
CC {ECO:0000269|PubMed:28556411}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the WD repeat WDR81 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAG53978.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK074111; BAB84937.1; -; mRNA.
DR EMBL; AK091136; BAC03593.1; -; mRNA.
DR EMBL; AK123896; BAG53978.1; ALT_INIT; mRNA.
DR EMBL; AK127946; BAG54603.1; -; mRNA.
DR EMBL; AK298567; BAH12815.1; -; mRNA.
DR EMBL; AC130343; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC092513; AAH92513.1; -; mRNA.
DR EMBL; BC114568; AAI14569.1; -; mRNA.
DR EMBL; AL834379; CAD39042.1; -; mRNA.
DR CCDS; CCDS54061.1; -. [Q562E7-5]
DR CCDS; CCDS54062.1; -. [Q562E7-1]
DR CCDS; CCDS54063.1; -. [Q562E7-6]
DR RefSeq; NP_001157145.1; NM_001163673.1. [Q562E7-5]
DR RefSeq; NP_001157281.1; NM_001163809.1. [Q562E7-1]
DR RefSeq; NP_001157283.1; NM_001163811.1. [Q562E7-6]
DR RefSeq; NP_689561.2; NM_152348.3. [Q562E7-3]
DR RefSeq; XP_011521953.1; XM_011523651.2. [Q562E7-3]
DR AlphaFoldDB; Q562E7; -.
DR SMR; Q562E7; -.
DR BioGRID; 125911; 37.
DR IntAct; Q562E7; 13.
DR STRING; 9606.ENSP00000386609; -.
DR iPTMnet; Q562E7; -.
DR PhosphoSitePlus; Q562E7; -.
DR BioMuta; WDR81; -.
DR DMDM; 403314383; -.
DR EPD; Q562E7; -.
DR jPOST; Q562E7; -.
DR MassIVE; Q562E7; -.
DR MaxQB; Q562E7; -.
DR PaxDb; Q562E7; -.
DR PeptideAtlas; Q562E7; -.
DR PRIDE; Q562E7; -.
DR ProteomicsDB; 20529; -.
DR ProteomicsDB; 62557; -. [Q562E7-1]
DR ProteomicsDB; 62558; -. [Q562E7-2]
DR Antibodypedia; 10606; 17 antibodies from 10 providers.
DR DNASU; 124997; -.
DR Ensembl; ENST00000309182.9; ENSP00000312074.5; ENSG00000167716.19. [Q562E7-3]
DR Ensembl; ENST00000409644.6; ENSP00000386609.1; ENSG00000167716.19. [Q562E7-1]
DR Ensembl; ENST00000419248.5; ENSP00000407845.1; ENSG00000167716.19. [Q562E7-6]
DR Ensembl; ENST00000437219.6; ENSP00000391074.2; ENSG00000167716.19. [Q562E7-5]
DR Ensembl; ENST00000611758.2; ENSP00000480442.1; ENSG00000276021.4. [Q562E7-3]
DR Ensembl; ENST00000613381.4; ENSP00000480101.1; ENSG00000276021.4. [Q562E7-6]
DR Ensembl; ENST00000613616.3; ENSP00000477991.1; ENSG00000276021.4. [Q562E7-5]
DR GeneID; 124997; -.
DR KEGG; hsa:124997; -.
DR MANE-Select; ENST00000409644.6; ENSP00000386609.1; NM_001163809.2; NP_001157281.1.
DR UCSC; uc002fth.3; human. [Q562E7-1]
DR CTD; 124997; -.
DR DisGeNET; 124997; -.
DR GeneCards; WDR81; -.
DR HGNC; HGNC:26600; WDR81.
DR HPA; ENSG00000167716; Low tissue specificity.
DR MalaCards; WDR81; -.
DR MIM; 610185; phenotype.
DR MIM; 614218; gene.
DR MIM; 617967; phenotype.
DR neXtProt; NX_Q562E7; -.
DR OpenTargets; ENSG00000167716; -.
DR Orphanet; 1766; Dysequilibrium syndrome.
DR PharmGKB; PA142670584; -.
DR VEuPathDB; HostDB:ENSG00000167716; -.
DR eggNOG; KOG1786; Eukaryota.
DR eggNOG; KOG4190; Eukaryota.
DR GeneTree; ENSGT00930000151039; -.
DR HOGENOM; CLU_011738_0_0_1; -.
DR InParanoid; Q562E7; -.
DR OMA; AYEQFTP; -.
DR PhylomeDB; Q562E7; -.
DR TreeFam; TF323353; -.
DR PathwayCommons; Q562E7; -.
DR Reactome; R-HSA-9013148; CDC42 GTPase cycle.
DR SignaLink; Q562E7; -.
DR BioGRID-ORCS; 124997; 23 hits in 1083 CRISPR screens.
DR ChiTaRS; WDR81; human.
DR GenomeRNAi; 124997; -.
DR Pharos; Q562E7; Tbio.
DR PRO; PR:Q562E7; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q562E7; protein.
DR Bgee; ENSG00000167716; Expressed in granulocyte and 95 other tissues.
DR ExpressionAtlas; Q562E7; baseline and differential.
DR Genevisible; Q562E7; HS.
DR GO; GO:0000421; C:autophagosome membrane; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0031901; C:early endosome membrane; IDA:UniProtKB.
DR GO; GO:0031313; C:extrinsic component of endosome membrane; IDA:UniProtKB.
DR GO; GO:0031902; C:late endosome membrane; IDA:UniProtKB.
DR GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0070530; F:K63-linked polyubiquitin modification-dependent protein binding; IDA:UniProtKB.
DR GO; GO:0035014; F:phosphatidylinositol 3-kinase regulator activity; IMP:UniProtKB.
DR GO; GO:0035973; P:aggrephagy; IMP:UniProtKB.
DR GO; GO:0045022; P:early endosome to late endosome transport; IMP:UniProtKB.
DR GO; GO:0007005; P:mitochondrion organization; ISS:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; IMP:UniProtKB.
DR GO; GO:0043551; P:regulation of phosphatidylinositol 3-kinase activity; IMP:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR CDD; cd06071; Beach; 1.
DR Gene3D; 1.10.1540.10; -; 1.
DR Gene3D; 2.130.10.10; -; 2.
DR InterPro; IPR000409; BEACH_dom.
DR InterPro; IPR036372; BEACH_dom_sf.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR Pfam; PF02138; Beach; 1.
DR Pfam; PF00400; WD40; 1.
DR SMART; SM01026; Beach; 1.
DR SMART; SM00320; WD40; 6.
DR SUPFAM; SSF50978; SSF50978; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR SUPFAM; SSF81837; SSF81837; 1.
DR PROSITE; PS50197; BEACH; 1.
DR PROSITE; PS50082; WD_REPEATS_2; 1.
DR PROSITE; PS50294; WD_REPEATS_REGION; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Cytoplasmic vesicle; Disease variant;
KW Endosome; Intellectual disability; Lysosome; Membrane; Mitochondrion;
KW Reference proteome; Repeat; Transit peptide; WD repeat.
FT CHAIN 1..1941
FT /note="WD repeat-containing protein 81"
FT /id="PRO_0000247244"
FT DOMAIN 337..614
FT /note="BEACH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00026"
FT REPEAT 1639..1677
FT /note="WD 1"
FT REPEAT 1686..1724
FT /note="WD 2"
FT REPEAT 1729..1769
FT /note="WD 3"
FT REPEAT 1777..1815
FT /note="WD 4"
FT REPEAT 1819..1856
FT /note="WD 5"
FT REPEAT 1860..1896
FT /note="WD 6"
FT REPEAT 1902..1941
FT /note="WD 7"
FT REGION 1..650
FT /note="Necessary and sufficient for the interaction with
FT SQSTM1"
FT /evidence="ECO:0000269|PubMed:28404643"
FT REGION 1..27
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 618..637
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 694..718
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1022..1074
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1097..1217
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1523..1556
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1569..1602
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1150..1175
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1177..1191
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..1227
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000305"
FT /id="VSP_044063"
FT VAR_SEQ 1..1203
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044064"
FT VAR_SEQ 1..1051
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_044065"
FT VAR_SEQ 1115..1312
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_019955"
FT VAR_SEQ 1204..1223
FT /note="EEEEALPEQSEGKEQKILLD -> MLVRVVLSLTPSFPEPSALY (in
FT isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044066"
FT VAR_SEQ 1776..1941
FT /note="HEFRLGGGLNPGLVRALAISPSGRSVVAGFSSGFMVLLDTRTGLVLRGWPAH
FT EGDILQIKAVEGSVLVSSSSDHSLTVWKELEQKPTHHYKSASDPIHTFDLYGSEVVTGT
FT VSNKIGVCSLLEPPSQATTKLSSENFRGTLTSLALLPTKRHLLLGSDNGVIRLLA ->
FT VRGVQFPEHSPGSLGTWQGGETPQKQKARMLFWGPS (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044067"
FT VARIANT 282
FT /note="G -> E (in HYC3; unknown pathological significance;
FT dbSNP:rs730882206)"
FT /evidence="ECO:0000269|PubMed:28556411"
FT /id="VAR_081120"
FT VARIANT 856
FT /note="P -> L (in CAMRQ2; dbSNP:rs587776906)"
FT /evidence="ECO:0000269|PubMed:21885617"
FT /id="VAR_068220"
FT VARIANT 1096..1941
FT /note="Missing (in HYC3)"
FT /evidence="ECO:0000269|PubMed:28556411"
FT /id="VAR_081121"
FT VARIANT 1333..1941
FT /note="Missing (in CAMRQ2)"
FT /evidence="ECO:0000269|PubMed:26437881"
FT /id="VAR_079037"
FT VARIANT 1535
FT /note="M -> V (in dbSNP:rs3809870)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_062107"
FT MUTAGEN 544
FT /note="W->A: Loss of interaction with MAP1LC3C; when
FT associated with A-547."
FT /evidence="ECO:0000269|PubMed:28404643"
FT MUTAGEN 547
FT /note="L->A: Loss of interaction with MAP1LC3C; when
FT associated with A-544."
FT /evidence="ECO:0000269|PubMed:28404643"
FT MUTAGEN 577
FT /note="S->A: Loss of interaction with MAP1LC3C; when
FT associated with A-578 and A-581."
FT /evidence="ECO:0000269|PubMed:28404643"
FT MUTAGEN 578
FT /note="Y->A: Loss of interaction with MAP1LC3C; when
FT associated with A-577 and A-581."
FT /evidence="ECO:0000269|PubMed:28404643"
FT MUTAGEN 581
FT /note="V->A: Loss of interaction with MAP1LC3C; when
FT associated with A-577 and A-578."
FT /evidence="ECO:0000269|PubMed:28404643"
FT CONFLICT 1033
FT /note="Missing (in Ref. 1; BAB84937)"
FT /evidence="ECO:0000305"
FT CONFLICT 1051
FT /note="P -> L (in Ref. 4; CAD39042)"
FT /evidence="ECO:0000305"
FT CONFLICT 1298
FT /note="C -> Y (in Ref. 1; BAC03593)"
FT /evidence="ECO:0000305"
FT CONFLICT 1540
FT /note="P -> H (in Ref. 1; BAB84937)"
FT /evidence="ECO:0000305"
FT CONFLICT 1573
FT /note="D -> G (in Ref. 1; BAG53978)"
FT /evidence="ECO:0000305"
FT CONFLICT 1744
FT /note="A -> V (in Ref. 1; BAG54603)"
FT /evidence="ECO:0000305"
FT CONFLICT 1760
FT /note="S -> T (in Ref. 1; BAC03593)"
FT /evidence="ECO:0000305"
FT CONFLICT 1776
FT /note="H -> Y (in Ref. 1; BAC03593)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1941 AA; 211697 MW; F6E62BC07FAAE8DB CRC64;
MAQGSGGREG ALRTPAGGWH SPPSPDMQEL LRSVERDLSI DPRQLAPAPG GTHVVALVPA
RWLASLRDRR LPLGPCPRAE GLGEAEVRTL LQRSVQRLPA GWTRVEVHGL RKRRLSYPLG
GGLPFEDGSC GPETLTRFMQ EVAAQNYRNL WRHAYHTYGQ PYSHSPAPSA VPALDSVRQA
LQRVYGCSFL PVGETTQCPS YAREGPCPPR GSPACPSLLR AEALLESPEM LYVVHPYVQF
SLHDVVTFSP AKLTNSQAKV LFILFRVLRA MDACHRQGLA CGALSLYHIA VDEKLCSELR
LDLSAYERPE EDENEEAPVA RDEAGIVSQE EQGGQPGQPT GQEELRSLVL DWVHGRISNF
HYLMQLNRLA GRRQGDPNYH PVLPWVVDFT TPHGRFRDLR KSKFRLNKGD KQLDFTYEMT
RQAFVAGGAG GGEPPHVPHH ISDVLSDITY YVYKARRTPR SVLCGHVRAQ WEPHEYPASM
ERMQNWTPDE CIPEFYTDPS IFRSIHPDMP DLDVPAWCSS SQEFVAAHRA LLESREVSRD
LHHWIDLTFG YKLQGKEAVK EKNVCLHLVD AHTHLASYGV VQLFDQPHPQ RLAGAPALAP
EPPLIPKLLV QTIQETTGRE DFTENPGQLP NGVGRPVLEA TPCEASWTRD RPVAGEDDLE
QATEALDSIS LAGKAGDQLG SSSQASPGLL SFSVASASRP GRRNKAAGAD PGEGEEGRIL
LPEGFNPMQA LEELEKTGNF LAKGLGGLLE VPEQPRVQPA VPLQCLLHRD MQALGVLLAE
MVFATRVRTL QPDAPLWVRF QAVRGLCTRH PKEVPVSLQP VLDTLLQMSG PEVPMGAERG
KLDQLFEYRP VSQGLPPPCP SQLLSPFSSV VPFPPYFPAL HRFILLYQAR RVEDEAQGRE
LVFALWQQLG AVLKDITPEG LEILLPFVLS LMSEEHTAVY TAWYLFEPVA KALGPKNANK
YLLKPLIGAY ESPCQLHGRF YLYTDCFVAQ LMVRLGLQAF LTHLLPHVLQ VLAGAEASQE
ESKDLAGAAE EEESGLPGAG PGSCAFGEEI PMDGEPPASS GLGLPDYTSG VSFHDQADLP
ETEDFQAGLY VTESPQPQEA EAVSLGRLSD KSSTSETSLG EERAPDEGGA PVDKSSLRSG
DSSQDLKQSE GSEEEEEEED SCVVLEEEEG EQEEVTGASE LTLSDTVLSM ETVVAGGSGG
DGEEEEEALP EQSEGKEQKI LLDTACKMVR WLSAKLGPTV ASRHVARNLL RLLTSCYVGP
TRQQFTVSSG ESPPLSAGNI YQKRPVLGDI VSGPVLSCLL HIARLYGEPV LTYQYLPYIS
YLVAPGSASG PSRLNSRKEA GLLAAVTLTQ KIIVYLSDTT LMDILPRISH EVLLPVLSFL
TSLVTGFPSG AQARTILCVK TISLIALICL RIGQEMVQQH LSEPVATFFQ VFSQLHELRQ
QDLKLDPAGR GEGQLPQVVF SDGQQRPVDP ALLDELQKVF TLEMAYTIYV PFSCLLGDII
RKIIPNHELV GELAALYLES ISPSSRNPAS VEPTMPGTGP EWDPHGGGCP QDDGHSGTFG
SVLVGNRIQI PNDSRPENPG PLGPISGVGG GGLGSGSDDN ALKQELPRSV HGLSGNWLAY
WQYEIGVSQQ DAHFHFHQIR LQSFPGHSGA VKCVAPLSSE DFFLSGSKDR TVRLWPLYNY
GDGTSETAPR LVYTQHRKSV FFVGQLEAPQ HVVSCDGAVH VWDPFTGKTL RTVEPLDSRV
PLTAVAVMPA PHTSITMASS DSTLRFVDCR KPGLQHEFRL GGGLNPGLVR ALAISPSGRS
VVAGFSSGFM VLLDTRTGLV LRGWPAHEGD ILQIKAVEGS VLVSSSSDHS LTVWKELEQK
PTHHYKSASD PIHTFDLYGS EVVTGTVSNK IGVCSLLEPP SQATTKLSSE NFRGTLTSLA
LLPTKRHLLL GSDNGVIRLL A
