ANS4B_HUMAN
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 03-AUG-2022, entry version 152.
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).
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). Interacts with USH1C; the
CC interaction is direct and is required for ANKS4B localization to the
CC tip of microvilli (PubMed:26812017, PubMed:26812018). Interacts with
CC MYO7B; the interaction is direct (PubMed:26812018). May interact with
CC HSPA5 (By similarity). {ECO:0000250|UniProtKB:Q8K3X6,
CC ECO:0000269|PubMed:26812017, ECO:0000269|PubMed:26812018}.
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}. Note=Localizes at the tip of microvilli
CC (PubMed:26812018). May associate with endoplasmic reticulum membranes
CC (By similarity). {ECO:0000250|UniProtKB:Q8K3X6,
CC ECO:0000269|PubMed:26812018}.
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};
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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; Q8N8V4; -.
DR PeptideAtlas; Q8N8V4; -.
DR PRIDE; Q8N8V4; -.
DR ProteomicsDB; 72464; -.
DR Antibodypedia; 50456; 66 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 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; EVIWDDE; -.
DR OrthoDB; 1344159at2759; -.
DR PhylomeDB; Q8N8V4; -.
DR TreeFam; TF324946; -.
DR PathwayCommons; Q8N8V4; -.
DR SignaLink; Q8N8V4; -.
DR BioGRID-ORCS; 257629; 4 hits in 1060 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 36 other tissues.
DR Genevisible; Q8N8V4; HS.
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; IMP: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; cd09587; SAM_HARP; 1.
DR Gene3D; 1.10.150.50; -; 1.
DR Gene3D; 1.25.40.20; -; 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 Pfam; PF12796; Ank_2; 1.
DR Pfam; PF00536; SAM_1; 1.
DR SMART; SM00248; ANK; 3.
DR SMART; SM00454; SAM; 1.
DR SUPFAM; SSF47769; SSF47769; 1.
DR SUPFAM; SSF48403; SSF48403; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 2.
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
