ID   FRMD5_HUMAN             Reviewed;         570 AA.
AC   Q7Z6J6; Q8NBG4;
DT   25-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2003, sequence version 1.
DT   27-MAR-2024, entry version 141.
DE   RecName: Full=FERM domain-containing protein 5;
GN   Name=FRMD5;
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] (ISOFORM 1).
RC   TISSUE=Astrocyte;
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 MRNA] (ISOFORM 2).
RC   TISSUE=Skin;
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   [3]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA   Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA   Elledge S.J., Gygi S.P.;
RT   "A quantitative atlas of mitotic phosphorylation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN   [4]
RP   SUBCELLULAR LOCATION, INTERACTION WITH CTNND1, AND FUNCTION.
RX   PubMed=22846708; DOI=10.1016/j.febslet.2012.07.019;
RA   Wang T., Pei X., Zhan J., Hu J., Yu Y., Zhang H.;
RT   "FERM-containing protein FRMD5 is a p120-catenin interacting protein that
RT   regulates tumor progression.";
RL   FEBS Lett. 586:3044-3050(2012).
RN   [5]
RP   FUNCTION, AND INTERACTION WITH ITGB5 AND ROCK1.
RX   PubMed=25448675; DOI=10.1016/j.febslet.2014.10.012;
RA   Hu J., Niu M., Li X., Lu D., Cui J., Xu W., Li G., Zhan J., Zhang H.;
RT   "FERM domain-containing protein FRMD5 regulates cell motility via binding
RT   to integrin beta5 subunit and ROCK1.";
RL   FEBS Lett. 588:4348-4356(2014).
RN   [6]
RP   VARIANTS NEDEMA LEU-114; ARG-349; ARG-351; GLY-351; ARG-352; PRO-354 AND
RP   CYS-546, AND INVOLVEMENT IN NEDEMA.
RX   PubMed=36206744; DOI=10.1016/j.ajhg.2022.09.005;
RA   Lu S., Ma M., Mao X., Bacino C.A., Jankovic J., Sutton V.R., Bartley J.A.,
RA   Wang X., Rosenfeld J.A., Beleza-Meireles A., Chauhan J., Pan X., Li M.,
RA   Liu P., Prescott K., Amin S., Davies G., Wangler M.F., Dai Y., Bellen H.J.;
RT   "De novo variants in FRMD5 are associated with developmental delay,
RT   intellectual disability, ataxia, and abnormalities of eye movement.";
RL   Am. J. Hum. Genet. 109:1932-1943(2022).
CC   -!- FUNCTION: May be involved in regulation of cell migration
CC       (PubMed:22846708, PubMed:25448675). May regulate cell-matrix
CC       interactions via its interaction with ITGB5 and modifying ITGB5
CC       cytoplasmic tail interactions such as with FERMT2 and TLN1. May
CC       regulate ROCK1 kinase activity possibly involved in regulation of actin
CC       stress fiber formation (PubMed:25448675).
CC   -!- SUBUNIT: Interacts with CTNND1 (PubMed:22846708). Interacts with ITGB5
CC       (via cytoplasmic domain) and ROCK1 (PubMed:25448675).
CC       {ECO:0000269|PubMed:22846708, ECO:0000269|PubMed:25448675}.
CC   -!- INTERACTION:
CC       Q7Z6J6; O60716: CTNND1; NbExp=3; IntAct=EBI-727282, EBI-701927;
CC       Q7Z6J6; P18084: ITGB5; NbExp=3; IntAct=EBI-727282, EBI-1223434;
CC       Q7Z6J6; Q13464: ROCK1; NbExp=4; IntAct=EBI-727282, EBI-876651;
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass membrane
CC       protein {ECO:0000305}. Cell junction, adherens junction
CC       {ECO:0000269|PubMed:22846708}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q7Z6J6-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q7Z6J6-2; Sequence=VSP_019982;
CC   -!- DISEASE: Neurodevelopmental disorder with eye movement abnormalities
CC       and ataxia (NEDEMA) [MIM:620094]: An autosomal dominant disorder
CC       apparent from infancy and characterized by global developmental delay,
CC       intellectual disability, speech difficulties, ataxia, seizures, and
CC       abnormalities of eye movement. {ECO:0000269|PubMed:36206744}. Note=The
CC       disease is caused by variants affecting the gene represented in this
CC       entry.
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DR   EMBL; AK090572; BAC03480.1; -; mRNA.
DR   EMBL; BC053647; AAH53647.1; -; mRNA.
DR   CCDS; CCDS10107.2; -. [Q7Z6J6-1]
DR   RefSeq; NP_116281.2; NM_032892.4. [Q7Z6J6-1]
DR   AlphaFoldDB; Q7Z6J6; -.
DR   SMR; Q7Z6J6; -.
DR   BioGRID; 124407; 90.
DR   IntAct; Q7Z6J6; 28.
DR   MINT; Q7Z6J6; -.
DR   STRING; 9606.ENSP00000403067; -.
DR   iPTMnet; Q7Z6J6; -.
DR   PhosphoSitePlus; Q7Z6J6; -.
DR   BioMuta; FRMD5; -.
DR   DMDM; 74738821; -.
DR   EPD; Q7Z6J6; -.
DR   jPOST; Q7Z6J6; -.
DR   MassIVE; Q7Z6J6; -.
DR   MaxQB; Q7Z6J6; -.
DR   PaxDb; 9606-ENSP00000403067; -.
DR   PeptideAtlas; Q7Z6J6; -.
DR   ProteomicsDB; 69426; -. [Q7Z6J6-1]
DR   ProteomicsDB; 69427; -. [Q7Z6J6-2]
DR   Pumba; Q7Z6J6; -.
DR   Antibodypedia; 2633; 115 antibodies from 17 providers.
DR   DNASU; 84978; -.
DR   Ensembl; ENST00000417257.6; ENSP00000403067.1; ENSG00000171877.21. [Q7Z6J6-1]
DR   GeneID; 84978; -.
DR   KEGG; hsa:84978; -.
DR   MANE-Select; ENST00000417257.6; ENSP00000403067.1; NM_032892.5; NP_116281.2.
DR   UCSC; uc001ztl.5; human. [Q7Z6J6-1]
DR   AGR; HGNC:28214; -.
DR   CTD; 84978; -.
DR   DisGeNET; 84978; -.
DR   GeneCards; FRMD5; -.
DR   HGNC; HGNC:28214; FRMD5.
DR   HPA; ENSG00000171877; Tissue enhanced (brain, heart muscle, retina).
DR   MalaCards; FRMD5; -.
DR   MIM; 616309; gene.
DR   MIM; 620094; phenotype.
DR   neXtProt; NX_Q7Z6J6; -.
DR   OpenTargets; ENSG00000171877; -.
DR   PharmGKB; PA142671751; -.
DR   VEuPathDB; HostDB:ENSG00000171877; -.
DR   eggNOG; KOG3530; Eukaryota.
DR   GeneTree; ENSGT00940000156346; -.
DR   HOGENOM; CLU_003623_1_7_1; -.
DR   InParanoid; Q7Z6J6; -.
DR   OMA; HFLQWNE; -.
DR   OrthoDB; 2912597at2759; -.
DR   PhylomeDB; Q7Z6J6; -.
DR   TreeFam; TF343477; -.
DR   PathwayCommons; Q7Z6J6; -.
DR   SignaLink; Q7Z6J6; -.
DR   BioGRID-ORCS; 84978; 15 hits in 1147 CRISPR screens.
DR   ChiTaRS; FRMD5; human.
DR   GenomeRNAi; 84978; -.
DR   Pharos; Q7Z6J6; Tbio.
DR   PRO; PR:Q7Z6J6; -.
DR   Proteomes; UP000005640; Chromosome 15.
DR   RNAct; Q7Z6J6; Protein.
DR   Bgee; ENSG00000171877; Expressed in cardiac muscle of right atrium and 140 other cell types or tissues.
DR   ExpressionAtlas; Q7Z6J6; baseline and differential.
DR   GO; GO:0005912; C:adherens junction; IDA:UniProtKB.
DR   GO; GO:0005856; C:cytoskeleton; IBA:GO_Central.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0008092; F:cytoskeletal protein binding; IEA:InterPro.
DR   GO; GO:0005178; F:integrin binding; IDA:UniProtKB.
DR   GO; GO:0019901; F:protein kinase binding; IDA:UniProtKB.
DR   GO; GO:0031032; P:actomyosin structure organization; IBA:GO_Central.
DR   GO; GO:2000146; P:negative regulation of cell motility; IMP:UniProtKB.
DR   GO; GO:0045785; P:positive regulation of cell adhesion; IMP:UniProtKB.
DR   GO; GO:0030334; P:regulation of cell migration; IMP:UniProtKB.
DR   CDD; cd14473; FERM_B-lobe; 1.
DR   CDD; cd13192; FERM_C_FRMD3_FRMD5; 1.
DR   CDD; cd17102; FERM_F1_FRMD3; 1.
DR   Gene3D; 1.20.80.10; -; 1.
DR   Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1.
DR   InterPro; IPR019749; Band_41_domain.
DR   InterPro; IPR000798; Ez/rad/moesin-like.
DR   InterPro; IPR014847; FA.
DR   InterPro; IPR014352; FERM/acyl-CoA-bd_prot_sf.
DR   InterPro; IPR035963; FERM_2.
DR   InterPro; IPR019748; FERM_central.
DR   InterPro; IPR019747; FERM_CS.
DR   InterPro; IPR000299; FERM_domain.
DR   InterPro; IPR018979; FERM_N.
DR   InterPro; IPR018980; FERM_PH-like_C.
DR   InterPro; IPR011993; PH-like_dom_sf.
DR   InterPro; IPR029071; Ubiquitin-like_domsf.
DR   PANTHER; PTHR23280; 4.1 G PROTEIN; 1.
DR   PANTHER; PTHR23280:SF5; FERM DOMAIN-CONTAINING PROTEIN 5; 1.
DR   Pfam; PF08736; FA; 1.
DR   Pfam; PF09380; FERM_C; 1.
DR   Pfam; PF00373; FERM_M; 1.
DR   Pfam; PF09379; FERM_N; 1.
DR   PRINTS; PR00935; BAND41.
DR   PRINTS; PR00661; ERMFAMILY.
DR   SMART; SM00295; B41; 1.
DR   SMART; SM01195; FA; 1.
DR   SMART; SM01196; FERM_C; 1.
DR   SUPFAM; SSF50729; PH domain-like; 1.
DR   SUPFAM; SSF47031; Second domain of FERM; 1.
DR   SUPFAM; SSF54236; Ubiquitin-like; 1.
DR   PROSITE; PS00660; FERM_1; 1.
DR   PROSITE; PS50057; FERM_3; 1.
DR   Genevisible; Q7Z6J6; HS.
PE   1: Evidence at protein level;
KW   Alternative splicing; Cell junction; Disease variant;
KW   Intellectual disability; Membrane; Phosphoprotein; Reference proteome;
KW   Transmembrane; Transmembrane helix.
FT   CHAIN           1..570
FT                   /note="FERM domain-containing protein 5"
FT                   /id="PRO_0000247446"
FT   TRANSMEM        504..524
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          17..298
FT                   /note="FERM"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00084"
FT   REGION          308..353
FT                   /note="Interaction with ROCK1"
FT                   /evidence="ECO:0000269|PubMed:25448675"
FT   REGION          344..367
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          385..407
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        387..407
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         375
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q6P5H6"
FT   VAR_SEQ         81..95
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_019982"
FT   VARIANT         114
FT                   /note="F -> L (in NEDEMA; uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:36206744"
FT                   /id="VAR_087746"
FT   VARIANT         349
FT                   /note="S -> R (in NEDEMA; uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:36206744"
FT                   /id="VAR_087747"
FT   VARIANT         351
FT                   /note="S -> G (in NEDEMA)"
FT                   /evidence="ECO:0000269|PubMed:36206744"
FT                   /id="VAR_087748"
FT   VARIANT         351
FT                   /note="S -> R (in NEDEMA)"
FT                   /evidence="ECO:0000269|PubMed:36206744"
FT                   /id="VAR_087749"
FT   VARIANT         352
FT                   /note="C -> R (in NEDEMA)"
FT                   /evidence="ECO:0000269|PubMed:36206744"
FT                   /id="VAR_087750"
FT   VARIANT         354
FT                   /note="S -> P (in NEDEMA; uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:36206744"
FT                   /id="VAR_087751"
FT   VARIANT         546
FT                   /note="Y -> C (in NEDEMA; uncertain significance;
FT                   dbSNP:rs1006096376)"
FT                   /evidence="ECO:0000269|PubMed:36206744"
FT                   /id="VAR_087752"
SQ   SEQUENCE   570 AA;  65065 MW;  8235A774CA2A6DE3 CRC64;
     MLSRLMSGSS RSLEREYSCT VRLLDDSEYT CTIQRDAKGQ YLFDLLCHHL NLLEKDYFGI
     RFVDPDKQRH WLEFTKSVVK QLRSQPPFTM CFRVKFYPAD PAALKEEITR YLVFLQIKRD
     LYHGRLLCKT SDAALLAAYI LQAEIGDYDS GKHPEGYSSK FQFFPKHSEK LERKIAEIHK
     TELSGQTPAT SELNFLRKAQ TLETYGVDPH PCKDVSGNAA FLAFTPFGFV VLQGNKRVHF
     IKWNEVTKLK FEGKTFYLYV SQKEEKKIIL TYFAPTPEAC KHLWKCGIEN QAFYKLEKSS
     QVRTVSSSNL FFKGSRFRYS GRVAKEVMES SAKIKREPPE IHRAGMVPSR SCPSITHGPR
     LSSVPRTRRR AVHISIMEGL ESLRDSAHST PVRSTSHGDT FLPHVRSSRT DSNERVAVIA
     DEAYSPADSV LPTPVAEHSL ELMLLSRQIN GATCSIEEEK ESEASTPTAT EVEALGGELR
     ALCQGHSGPE EEQVNKFVLS VLRLLLVTMG LLFVLLLLLI ILTESDLDIA FFRDIRQTPE
     FEQFHYQYFC PLRRWFACKI RSVVSLLIDT
//