ID ANS4B_HUMAN Reviewed; 417 AA. AC Q8N8V4; DT 09-NOV-2004, integrated into UniProtKB/Swiss-Prot. DT 11-JAN-2011, sequence version 2. DT 27-MAR-2024, entry version 160. DE RecName: Full=Ankyrin repeat and SAM domain-containing protein 4B {ECO:0000305}; DE AltName: Full=Harmonin-interacting ankyrin repeat-containing protein {ECO:0000303|PubMed:12588794}; DE Short=Harp {ECO:0000303|PubMed:12588794}; GN Name=ANKS4B {ECO:0000312|HGNC:HGNC:26795}; GN Synonyms=HARP {ECO:0000303|PubMed:12588794}; 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]. RC TISSUE=Liver; 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=15616553; DOI=10.1038/nature03187; RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M., RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., RA Myers R.M., Rubin E.M., Pennacchio L.A.; RT "The sequence and analysis of duplication-rich human chromosome 16."; RL Nature 432:988-994(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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 TISSUE SPECIFICITY. RX PubMed=12588794; DOI=10.1093/hmg/ddg051; RA Weil D., El-Amraoui A., Masmoudi S., Mustapha M., Kikkawa Y., Laine S., RA Delmaghani S., Adato A., Nadifi S., Zina Z.B., Hamel C., Gal A., Ayadi H., RA Yonekawa H., Petit C.; RT "Usher syndrome type I G (USH1G) is caused by mutations in the gene RT encoding SANS, a protein that associates with the USH1C protein, RT harmonin."; RL Hum. Mol. Genet. 12:463-471(2003). RN [5] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-283, AND IDENTIFICATION BY RP 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 [6] RP INTERACTION WITH USH1C. RX PubMed=26812017; DOI=10.1016/j.devcel.2015.12.020; RA Li J., He Y., Lu Q., Zhang M.; RT "Mechanistic basis of organization of the Harmonin/USH1C-mediated brush RT border microvilli tip-link complex."; RL Dev. Cell 36:179-189(2016). RN [7] RP FUNCTION, INTERACTION WITH MYO7B AND USH1C, IDENTIFICATION OF THE IMAC RP COMPLEX, SUBCELLULAR LOCATION, REGION, MOTIF, AND MUTAGENESIS OF LEU-48 AND RP LEU-417. RX PubMed=26812018; DOI=10.1016/j.devcel.2015.12.022; RA Crawley S.W., Weck M.L., Grega-Larson N.E., Shifrin D.A. Jr., Tyska M.J.; RT "ANKS4B is essential for intermicrovillar adhesion complex formation."; RL Dev. Cell 36:190-200(2016). RN [8] RP IDENTIFICATION OF THE IMAC COMPLEX, AND SUBCELLULAR LOCATION. RX PubMed=32209652; DOI=10.1074/jbc.ra120.012820; RA Choi M.S., Graves M.J., Matoo S., Storad Z.A., El Sheikh Idris R.A., RA Weck M.L., Smith Z.B., Tyska M.J., Crawley S.W.; RT "The small EF-hand protein CALML4 functions as a critical myosin light RT chain within the intermicrovillar adhesion complex."; RL J. Biol. Chem. 295:9281-9296(2020). CC -!- FUNCTION: As part of the intermicrovillar adhesion complex/IMAC plays a CC role in epithelial brush border differentiation, controlling microvilli CC organization and length. Plays a role in assembly of the complex CC (PubMed:26812018). May play a role in cellular response to endoplasmic CC reticulum stress (By similarity). {ECO:0000250|UniProtKB:Q8K3X6, CC ECO:0000269|PubMed:26812018}. CC -!- SUBUNIT: Part of the IMAC/intermicrovillar adhesion CC complex/intermicrovillar tip-link complex composed of ANKS4B, MYO7B, CC USH1C, CDHR2 and CDHR5 (PubMed:26812018, PubMed:32209652). Interacts CC with USH1C; the interaction is direct and is required for ANKS4B CC localization to the tip of microvilli (PubMed:26812017, CC PubMed:26812018). Interacts with MYO7B; the interaction is direct CC (PubMed:26812018). May interact with HSPA5 (By similarity). CC {ECO:0000250|UniProtKB:Q8K3X6, ECO:0000269|PubMed:26812017, CC ECO:0000269|PubMed:26812018, ECO:0000269|PubMed:32209652}. CC -!- INTERACTION: CC Q8N8V4; Q5S007: LRRK2; NbExp=2; IntAct=EBI-9658517, EBI-5323863; CC Q8N8V4; Q9Y6N9-4: USH1C; NbExp=5; IntAct=EBI-9658517, EBI-11523636; CC -!- SUBCELLULAR LOCATION: Cell projection, microvillus CC {ECO:0000269|PubMed:26812018, ECO:0000269|PubMed:32209652}. CC Note=Localizes at the tip of microvilli (PubMed:26812018, CC PubMed:32209652). May associate with endoplasmic reticulum membranes CC (By similarity). {ECO:0000250|UniProtKB:Q8K3X6, CC ECO:0000269|PubMed:26812018, ECO:0000269|PubMed:32209652}. CC -!- TISSUE SPECIFICITY: Expressed in kidney and small intestine. CC {ECO:0000269|PubMed:12588794}. CC -!- SEQUENCE CAUTION: CC Sequence=BAC04707.1; Type=Erroneous termination; Note=Extended C-terminus.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AK096138; BAC04707.1; ALT_SEQ; mRNA. DR EMBL; AF001550; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC111784; -; NOT_ANNOTATED_CDS; mRNA. DR CCDS; CCDS42130.1; -. DR RefSeq; NP_665872.2; NM_145865.2. DR AlphaFoldDB; Q8N8V4; -. DR SMR; Q8N8V4; -. DR BioGRID; 129220; 10. DR IntAct; Q8N8V4; 4. DR STRING; 9606.ENSP00000308772; -. DR GlyGen; Q8N8V4; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q8N8V4; -. DR PhosphoSitePlus; Q8N8V4; -. DR BioMuta; ANKS4B; -. DR DMDM; 317373324; -. DR jPOST; Q8N8V4; -. DR MassIVE; Q8N8V4; -. DR MaxQB; Q8N8V4; -. DR PaxDb; 9606-ENSP00000308772; -. DR PeptideAtlas; Q8N8V4; -. DR ProteomicsDB; 72464; -. DR Antibodypedia; 50456; 70 antibodies from 16 providers. DR DNASU; 257629; -. DR Ensembl; ENST00000311620.7; ENSP00000308772.5; ENSG00000175311.7. DR Ensembl; ENST00000639229.2; ENSP00000491748.1; ENSG00000284290.2. DR GeneID; 257629; -. DR KEGG; hsa:257629; -. DR MANE-Select; ENST00000311620.7; ENSP00000308772.5; NM_145865.3; NP_665872.2. DR UCSC; uc010bwp.2; human. DR AGR; HGNC:26795; -. DR CTD; 257629; -. DR DisGeNET; 257629; -. DR GeneCards; ANKS4B; -. DR HGNC; HGNC:26795; ANKS4B. DR HPA; ENSG00000175311; Group enriched (intestine, kidney, liver). DR MIM; 609901; gene. DR neXtProt; NX_Q8N8V4; -. DR OpenTargets; ENSG00000175311; -. DR PharmGKB; PA143485304; -. DR VEuPathDB; HostDB:ENSG00000175311; -. DR eggNOG; KOG0504; Eukaryota. DR GeneTree; ENSGT00390000017548; -. DR HOGENOM; CLU_028071_1_0_1; -. DR InParanoid; Q8N8V4; -. DR OMA; DLQSIHM; -. DR OrthoDB; 5395431at2759; -. DR PhylomeDB; Q8N8V4; -. DR TreeFam; TF324946; -. DR PathwayCommons; Q8N8V4; -. DR SignaLink; Q8N8V4; -. DR SIGNOR; Q8N8V4; -. DR BioGRID-ORCS; 257629; 6 hits in 1138 CRISPR screens. DR GenomeRNAi; 257629; -. DR Pharos; Q8N8V4; Tbio. DR PRO; PR:Q8N8V4; -. DR Proteomes; UP000005640; Chromosome 16. DR RNAct; Q8N8V4; Protein. DR Bgee; ENSG00000175311; Expressed in mucosa of transverse colon and 37 other cell types or tissues. DR GO; GO:0005903; C:brush border; IDA:UniProtKB. DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB. DR GO; GO:0005902; C:microvillus; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IEA:Ensembl. DR GO; GO:1904970; P:brush border assembly; IDA:UniProtKB. DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW. DR GO; GO:1904106; P:protein localization to microvillus; IMP:UniProtKB. DR GO; GO:0065003; P:protein-containing complex assembly; IMP:UniProtKB. DR GO; GO:0034976; P:response to endoplasmic reticulum stress; ISS:UniProtKB. DR CDD; cd21802; CEN_ANKS4B; 1. DR CDD; cd09587; SAM_HARP; 1. DR Gene3D; 1.25.40.20; Ankyrin repeat-containing domain; 1. DR Gene3D; 1.10.150.50; Transcription Factor, Ets-1; 1. DR InterPro; IPR037601; ANKS4B_SAM. DR InterPro; IPR002110; Ankyrin_rpt. DR InterPro; IPR036770; Ankyrin_rpt-contain_sf. DR InterPro; IPR001660; SAM. DR InterPro; IPR013761; SAM/pointed_sf. DR PANTHER; PTHR24161; ANK_REP_REGION DOMAIN-CONTAINING PROTEIN-RELATED; 1. DR PANTHER; PTHR24161:SF20; ANKYRIN REPEAT AND SAM DOMAIN-CONTAINING PROTEIN 4B; 1. DR Pfam; PF12796; Ank_2; 1. DR Pfam; PF00536; SAM_1; 1. DR SMART; SM00248; ANK; 3. DR SMART; SM00454; SAM; 1. DR SUPFAM; SSF48403; Ankyrin repeat; 1. DR SUPFAM; SSF47769; SAM/Pointed domain; 1. DR PROSITE; PS50297; ANK_REP_REGION; 1. DR PROSITE; PS50088; ANK_REPEAT; 2. DR Genevisible; Q8N8V4; HS. PE 1: Evidence at protein level; KW ANK repeat; Cell projection; Coiled coil; Differentiation; Phosphoprotein; KW Reference proteome; Repeat. FT CHAIN 1..417 FT /note="Ankyrin repeat and SAM domain-containing protein 4B" FT /id="PRO_0000066996" FT REPEAT 31..60 FT /note="ANK 1" FT REPEAT 64..93 FT /note="ANK 2" FT REPEAT 97..126 FT /note="ANK 3" FT DOMAIN 351..403 FT /note="SAM" FT REGION 1..252 FT /note="Mediates localization to microvilli" FT /evidence="ECO:0000269|PubMed:26812018" FT REGION 151..195 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 253..346 FT /note="Mediates interaction with MYO7B" FT /evidence="ECO:0000269|PubMed:26812018" FT REGION 305..330 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 130..164 FT /evidence="ECO:0000255" FT MOTIF 415..417 FT /note="PDZ-binding; mediates interaction with USH1C" FT /evidence="ECO:0000269|PubMed:26812018" FT COMPBIAS 165..194 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 313..330 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 283 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MUTAGEN 48 FT /note="L->P: Decreased localization to microvilli." FT /evidence="ECO:0000269|PubMed:26812018" FT MUTAGEN 417 FT /note="L->R: Decreased interaction with USH1C." FT /evidence="ECO:0000269|PubMed:26812018" SQ SEQUENCE 417 AA; 46597 MW; 0B3D8382965DC82E CRC64; MSTRYHQAAS DSYLELLKEA TKRDLNLSDE DGMTPTLLAA YHGNLEALEI ICSRGGDPDR CDIWGNTPLH FAASNGHAHC VSFLVNFGAN IFALDNDLQT PLDAAASREQ NECVALLDKA ATAQNIMNPK KVTRLKEQAQ KNARRQIKEC ERLQEKHQNK MAHTYSKEES GTLSSSKGTF SRSSPSNASA PGTFGSLSKG IKDTFKIKFK KNKDTAEQVG KEGRSGQRNV MEVFREEEED SFSGDFKEKL QLSAEEDGSV HHESILNRPG LGSIVFRRNR ISSPEDISDS KREFGFKLPS ELLQRQGASE ADEGAADEEG EENGLKDDLP WDDDEVEWEE DVVDATPLEV FLLSQHLEEF LPIFKREQID LEALLLCSDE DLQSIQMQLG PRKKVLNAIN RRKQVLQQPG QLVDTSL //