FRM4B_HUMAN
ID FRM4B_HUMAN Reviewed; 1034 AA.
AC Q9Y2L6; Q8TAI3;
DT 11-JUL-2001, integrated into UniProtKB/Swiss-Prot.
DT 03-MAY-2011, sequence version 4.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=FERM domain-containing protein 4B;
DE AltName: Full=GRP1-binding protein GRSP1;
GN Name=FRMD4B {ECO:0000312|HGNC:HGNC:24886};
GN Synonyms=GRSP1 {ECO:0000312|HGNC:HGNC:24886}, KIAA1013;
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=Brain;
RX PubMed=10231032; DOI=10.1093/dnares/6.1.63;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 6:63-70(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-222 (ISOFORM 2).
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 780-1034 (ISOFORMS 1/2).
RC TISSUE=Testis;
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 [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-608 AND SER-915, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [7]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-882 AND LYS-1029, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
CC -!- FUNCTION: Member of GRP1 signaling complexes that are acutely recruited
CC to plasma membrane ruffles in response to insulin receptor signaling.
CC May function as a scaffolding protein that regulates epithelial cell
CC polarity by connecting ARF6 activation with the PAR3 complex. Plays a
CC redundant role with FRMD4A in epithelial polarization.
CC {ECO:0000250|UniProtKB:Q920B0}.
CC -!- SUBUNIT: Interacts with CYTH3 (By similarity). Interacts with PARD3 (By
CC similarity). Interacts with CYTH1 (By similarity).
CC {ECO:0000250|UniProtKB:Q920B0}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton
CC {ECO:0000250|UniProtKB:Q920B0}. Cell junction, tight junction
CC {ECO:0000250|UniProtKB:Q920B0}. Cell junction, adherens junction
CC {ECO:0000250|UniProtKB:Q920B0}. Note=Colocalized with PARD3 at adherens
CC junction and tight junction. {ECO:0000250|UniProtKB:Q920B0}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9Y2L6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Y2L6-2; Sequence=VSP_040895;
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA76857.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB023230; BAA76857.1; ALT_INIT; mRNA.
DR EMBL; AC112221; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC135851; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; DA339318; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC028291; AAH28291.1; -; mRNA.
DR CCDS; CCDS46863.1; -. [Q9Y2L6-1]
DR RefSeq; NP_055938.1; NM_015123.2. [Q9Y2L6-1]
DR RefSeq; XP_016861482.1; XM_017005993.1. [Q9Y2L6-2]
DR RefSeq; XP_016861483.1; XM_017005994.1. [Q9Y2L6-2]
DR AlphaFoldDB; Q9Y2L6; -.
DR SMR; Q9Y2L6; -.
DR BioGRID; 116765; 90.
DR IntAct; Q9Y2L6; 9.
DR STRING; 9606.ENSP00000381549; -.
DR iPTMnet; Q9Y2L6; -.
DR PhosphoSitePlus; Q9Y2L6; -.
DR BioMuta; FRMD4B; -.
DR DMDM; 332278248; -.
DR EPD; Q9Y2L6; -.
DR jPOST; Q9Y2L6; -.
DR MassIVE; Q9Y2L6; -.
DR MaxQB; Q9Y2L6; -.
DR PaxDb; Q9Y2L6; -.
DR PeptideAtlas; Q9Y2L6; -.
DR PRIDE; Q9Y2L6; -.
DR ProteomicsDB; 85836; -. [Q9Y2L6-1]
DR ProteomicsDB; 85837; -. [Q9Y2L6-2]
DR Antibodypedia; 2768; 44 antibodies from 9 providers.
DR DNASU; 23150; -.
DR Ensembl; ENST00000398540.8; ENSP00000381549.3; ENSG00000114541.15. [Q9Y2L6-1]
DR GeneID; 23150; -.
DR KEGG; hsa:23150; -.
DR MANE-Select; ENST00000398540.8; ENSP00000381549.3; NM_015123.3; NP_055938.2.
DR UCSC; uc003dnv.3; human. [Q9Y2L6-1]
DR CTD; 23150; -.
DR DisGeNET; 23150; -.
DR GeneCards; FRMD4B; -.
DR HGNC; HGNC:24886; FRMD4B.
DR HPA; ENSG00000114541; Tissue enhanced (brain).
DR MIM; 617467; gene.
DR neXtProt; NX_Q9Y2L6; -.
DR OpenTargets; ENSG00000114541; -.
DR PharmGKB; PA128394605; -.
DR VEuPathDB; HostDB:ENSG00000114541; -.
DR eggNOG; KOG3529; Eukaryota.
DR GeneTree; ENSGT01020000230354; -.
DR HOGENOM; CLU_003623_2_0_1; -.
DR InParanoid; Q9Y2L6; -.
DR OMA; XDENARK; -.
DR OrthoDB; 125121at2759; -.
DR PhylomeDB; Q9Y2L6; -.
DR TreeFam; TF328984; -.
DR PathwayCommons; Q9Y2L6; -.
DR SignaLink; Q9Y2L6; -.
DR BioGRID-ORCS; 23150; 8 hits in 1070 CRISPR screens.
DR ChiTaRS; FRMD4B; human.
DR GenomeRNAi; 23150; -.
DR Pharos; Q9Y2L6; Tbio.
DR PRO; PR:Q9Y2L6; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q9Y2L6; protein.
DR Bgee; ENSG00000114541; Expressed in germinal epithelium of ovary and 191 other tissues.
DR ExpressionAtlas; Q9Y2L6; baseline and differential.
DR Genevisible; Q9Y2L6; HS.
DR GO; GO:0005912; C:adherens junction; IBA:GO_Central.
DR GO; GO:0005923; C:bicellular tight junction; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB.
DR GO; GO:0001726; C:ruffle; IEA:Ensembl.
DR GO; GO:0090162; P:establishment of epithelial cell polarity; IEA:Ensembl.
DR CDD; cd14473; FERM_B-lobe; 1.
DR CDD; cd13191; FERM_C_FRMD4A_FRMD4B; 1.
DR Gene3D; 1.20.80.10; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR019749; Band_41_domain.
DR InterPro; IPR021774; DUF3338.
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; IPR041785; FRMD4A/B_FERM_C.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR Pfam; PF11819; CUPID; 1.
DR Pfam; PF09380; FERM_C; 1.
DR Pfam; PF00373; FERM_M; 1.
DR Pfam; PF09379; FERM_N; 1.
DR PRINTS; PR00935; BAND41.
DR SMART; SM00295; B41; 1.
DR SMART; SM01196; FERM_C; 1.
DR SUPFAM; SSF47031; SSF47031; 1.
DR SUPFAM; SSF54236; SSF54236; 1.
DR PROSITE; PS00661; FERM_2; 1.
DR PROSITE; PS50057; FERM_3; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell junction; Coiled coil; Cytoplasm; Cytoskeleton;
KW Isopeptide bond; Phosphoprotein; Reference proteome; Tight junction;
KW Ubl conjugation.
FT CHAIN 1..1034
FT /note="FERM domain-containing protein 4B"
FT /id="PRO_0000219446"
FT DOMAIN 59..361
FT /note="FERM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00084"
FT REGION 542..971
FT /note="Necessary for adherens junction and tight junction
FT localization"
FT /evidence="ECO:0000250|UniProtKB:Q920B0"
FT REGION 576..614
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 635..698
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 712..735
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 752..786
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 905..925
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1004..1034
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 417..450
FT /evidence="ECO:0000255"
FT COILED 531..561
FT /evidence="ECO:0000255"
FT COMPBIAS 576..609
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 635..652
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 663..698
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 769..786
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 908..925
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 372
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q920B0"
FT MOD_RES 608
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18088087"
FT MOD_RES 697
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q920B0"
FT MOD_RES 915
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18088087"
FT CROSSLNK 882
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 1029
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 1..54
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_040895"
FT CONFLICT 396
FT /note="T -> A (in Ref. 1; BAA76857)"
FT /evidence="ECO:0000305"
FT CONFLICT 947
FT /note="S -> L (in Ref. 1; BAA76857 and 4; AAH28291)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1034 AA; 118047 MW; A825A933DAF56263 CRC64;
MASVFMCGVE DLLFSGSRFV WNLTVSTLRR WYTERLRACH QVLRTWCGLQ DVYQMTEGRH
CQVHLLDDRR LELLVQPKLL ARELLDLVAS HFNLKEKEYF GITFIDDTGQ QNWLQLDHRV
LDHDLPKKPG PTILHFAVRF YIESISFLKD KTTVELFFLN AKACVHKGQI EVESETIFKL
AAFILQEAKG DYTSDENARK DLKTLPAFPT KTLQEHPSLA YCEDRVIEHY LKIKGLTRGQ
AVVQYMKIVE ALPTYGVHYY AVKDKQGLPW WLGISYKGIG QYDIQDKVKP RKLFQWKQLE
NLYFREKKFA VEVHDPRRIS VSRRTFGQSG LFVQTWYANS SLIKSIWVMA ISQHQFYLDR
KQSKAKIPSA RSLDEIAMDL TETGTQRASK LVTLETKSQF IMASNGSLIS SGSQDSEVSE
EQKREKILEL KKKEKLLQEK LLKKVEELKK ICLREAELTG KMPKEYPLNI GEKPPQVRRR
VGTAFKLDDN LLPSEEDPAL QELESNFLIQ QKLVEAAKKL ANEPDLCKTV KKKRKQDYTD
AMKKLQEIEN AINEYRIRCG KKPSQKATVL PEDIIPSESS SLSDTTTYDD PSDAFTFPGQ
RSSSVPHSPR ILPPKSLGIE RIHFRKSSIN EQFVDTRQSR EMLSTHSSPY KTLERRPQGG
RSMPTTPVLT RNAYSSSHLE PESSSQHCRQ RSGSLESQSH LLSEMDSDKP FFSLSKSQRS
SSTEILDDGS SYTSQSSTEY YCVTPVTGPY YTTQTLDTRT RGRRRSKKQN VSTSNSGSMP
NLAQKDSLRN GVYSKSQEPP SSSYYIAGYT PYAECDFYYS GGYVYENDTE GQYSVNPSYR
SSAHYGYERQ RDYSRSFHED EVDRVPHNPY ATLRLPRKAA AKSEHITKNI HKALVAEHLR
GWYQRASGQK DQGHSPQTSF DSDRGSQRCL GFAGLQVPCS PSSRASSYSS VSSTNASGNW
RTQLTIGLSD YETPAHSSYT SCYGNVYNPL PSPSRQYTEI SQLDGTDGNQ LEDNLESSEQ
RLFWHEDSKP GTLV