ID FRPD2_HUMAN Reviewed; 1309 AA.
AC Q68DX3; B7WNW0; B7ZML5; Q2VY07; Q6GMQ9; Q6ZN38; Q6ZWI2; Q8N5T9;
DT 02-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 31-MAY-2011, sequence version 3.
DT 01-MAY-2013, entry version 89.
DE RecName: Full=FERM and PDZ domain-containing protein 2;
DE AltName: Full=PDZ domain-containing protein 4;
DE AltName: Full=PDZ domain-containing protein 5C;
GN Name=FRMPD2; Synonyms=PDZD5C, PDZK4, PDZK5C;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5).
RA Xu J., Xie Y., Mao Y.;
RT "Identification of a novel PDZ domain-containing gene.";
RL Submitted (NOV-2003) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3), AND
RP VARIANTS GLU-534 AND LYS-1021.
RC TISSUE=Hippocampus, and Teratocarcinoma;
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT
RP LYS-1021.
RC TISSUE=Retina;
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.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D.,
RA Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L.,
RA Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S.,
RA Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L.,
RA Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J.,
RA Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M.,
RA Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S.,
RA Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M.,
RA Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A.,
RA Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T.,
RA Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I.,
RA Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T.,
RA Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W.,
RA Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H.,
RA Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L.,
RA Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K.,
RA Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T.,
RA Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 4 AND 5).
RC TISSUE=Brain;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP FUNCTION, INTERACTION WITH ARVCF; CTNND2 AND PKP4, MUTAGENESIS OF
RP LYS-955, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=19706687; DOI=10.1242/jcs.046854;
RA Stenzel N., Fetzer C.P., Heumann R., Erdmann K.S.;
RT "PDZ-domain-directed basolateral targeting of the peripheral membrane
RT protein FRMPD2 in epithelial cells.";
RL J. Cell Sci. 122:3374-3384(2009).
RN [7]
RP VARIANT [LARGE SCALE ANALYSIS] TRP-727.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal
RT cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: May play a role in the regulation of tight junction
CC formation. Binds phosphatidylinositol 3,4-bisphosphate
CC (PtdIns(3,4)P2).
CC -!- SUBUNIT: Interacts (via the PDZ 2 domain) with CTNND2 (via the
CC extreme C-terminus). Interacts (via the PDZ 2 domain) with PKP4
CC (via the extreme C-terminus); this interaction directed FRMPD2 to
CC the basolateral membranes. Interacts (via the PDZ 2 domain) with
CC ARVCF (via the extreme C-terminus).
CC -!- SUBCELLULAR LOCATION: Cytoplasm (Potential). Basolateral cell
CC membrane. Cell junction, tight junction. Note=Colocalizes with
CC CTNNB1, CDH1 and PKP4 at the basolateral membrane. Colocalizes
CC with TJP1 at tight junctions. Its recruitment to cell-cell
CC contacts requires CDH1.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=Q68DX3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q68DX3-2; Sequence=VSP_028523, VSP_028524, VSP_028527;
CC Note=No experimental confirmation available;
CC Name=3;
CC IsoId=Q68DX3-3; Sequence=VSP_028525, VSP_028526;
CC Note=No experimental confirmation available;
CC Name=4;
CC IsoId=Q68DX3-4; Sequence=VSP_028522, VSP_028528;
CC Name=5;
CC IsoId=Q68DX3-5; Sequence=VSP_028521;
CC -!- TISSUE SPECIFICITY: Expressed in epithelial cells.
CC -!- DOMAIN: The FERM and PDZ 2 domains are necessary for localization
CC to the basolateral cell membrane. The FERM domain binds to
CC phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) and is
CC sufficient for membrane localization.
CC -!- SIMILARITY: Contains 1 FERM domain.
CC -!- SIMILARITY: Contains 1 KIND domain.
CC -!- SIMILARITY: Contains 3 PDZ (DHR) domains.
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DR EMBL; AY491519; AAS79660.1; -; mRNA.
DR EMBL; AK123038; BAC85520.1; -; mRNA.
DR EMBL; AK131386; BAD18537.1; -; mRNA.
DR EMBL; CR749241; CAH18097.1; -; mRNA.
DR EMBL; AC013284; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC074325; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC031614; AAH31614.1; -; mRNA.
DR EMBL; BC073954; AAH73954.1; -; mRNA.
DR EMBL; BC144635; AAI44636.1; -; mRNA.
DR EMBL; BC144639; AAI44640.1; -; mRNA.
DR IPI; IPI00604498; -.
DR IPI; IPI00604685; -.
DR IPI; IPI00783413; -.
DR IPI; IPI00867584; -.
DR IPI; IPI00939368; -.
DR RefSeq; NP_001018081.3; NM_001018071.3.
DR RefSeq; NP_001035977.2; NM_001042512.2.
DR UniGene; Hs.664786; -.
DR UniGene; Hs.709611; -.
DR HSSP; Q64512; 1GM1.
DR ProteinModelPortal; Q68DX3; -.
DR SMR; Q68DX3; 371-637, 774-857, 917-1166.
DR STRING; 9606.ENSP00000363317; -.
DR PhosphoSite; Q68DX3; -.
DR DMDM; 296434511; -.
DR PaxDb; Q68DX3; -.
DR PRIDE; Q68DX3; -.
DR DNASU; 143162; -.
DR Ensembl; ENST00000305531; ENSP00000307079; ENSG00000170324.
DR Ensembl; ENST00000374201; ENSP00000363317; ENSG00000170324.
DR Ensembl; ENST00000474573; ENSP00000422446; ENSG00000170324.
DR GeneID; 143162; -.
DR KEGG; hsa:143162; -.
DR UCSC; uc001jgf.3; human.
DR UCSC; uc001jgg.3; human.
DR UCSC; uc001jgi.3; human.
DR CTD; 143162; -.
DR GeneCards; GC10M049364; -.
DR H-InvDB; HIX0008804; -.
DR H-InvDB; HIX0035409; -.
DR H-InvDB; HIX0035410; -.
DR HGNC; HGNC:28572; FRMPD2.
DR HPA; HPA018872; -.
DR MIM; 613323; gene.
DR neXtProt; NX_Q68DX3; -.
DR PharmGKB; PA134947461; -.
DR eggNOG; NOG323402; -.
DR HOVERGEN; HBG105760; -.
DR InParanoid; Q68DX3; -.
DR OMA; MIQNSPD; -.
DR OrthoDB; EOG4FFD10; -.
DR GenomeRNAi; 143162; -.
DR NextBio; 84654; -.
DR ArrayExpress; Q68DX3; -.
DR Bgee; Q68DX3; -.
DR CleanEx; HS_FRMPD2; -.
DR Genevestigator; Q68DX3; -.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005856; C:cytoskeleton; IEA:InterPro.
DR GO; GO:0005923; C:tight junction; IDA:UniProtKB.
DR GO; GO:0005545; F:1-phosphatidylinositol binding; IDA:UniProtKB.
DR GO; GO:0070830; P:tight junction assembly; IMP:UniProtKB.
DR Gene3D; 1.20.80.10; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR019749; Band_41_domain.
DR InterPro; IPR019750; Band_41_fam.
DR InterPro; IPR014352; FERM/acyl-CoA-bd_prot_3-hlx.
DR InterPro; IPR019748; FERM_central.
DR InterPro; IPR000299; FERM_domain.
DR InterPro; IPR018979; FERM_N.
DR InterPro; IPR018980; FERM_PH-like_C.
DR InterPro; IPR011019; KIND.
DR InterPro; IPR001478; PDZ.
DR InterPro; IPR011993; PH_like_dom.
DR Pfam; PF09380; FERM_C; 1.
DR Pfam; PF00373; FERM_M; 1.
DR Pfam; PF09379; FERM_N; 1.
DR Pfam; PF00595; PDZ; 3.
DR PRINTS; PR00935; BAND41.
DR SMART; SM00295; B41; 1.
DR SMART; SM00750; KIND; 1.
DR SMART; SM00228; PDZ; 3.
DR SUPFAM; SSF47031; FERM_3-hlx; 1.
DR SUPFAM; SSF50156; PDZ; 3.
DR PROSITE; PS00660; FERM_1; FALSE_NEG.
DR PROSITE; PS00661; FERM_2; FALSE_NEG.
DR PROSITE; PS50057; FERM_3; 1.
DR PROSITE; PS51377; KIND; 1.
DR PROSITE; PS50106; PDZ; 3.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell junction; Cell membrane; Complete proteome;
KW Cytoplasm; Membrane; Polymorphism; Reference proteome; Repeat;
KW Tight junction.
FT CHAIN 1 1309 FERM and PDZ domain-containing protein 2.
FT /FTId=PRO_0000306854.
FT DOMAIN 15 197 KIND.
FT DOMAIN 342 642 FERM.
FT DOMAIN 775 861 PDZ 1.
FT DOMAIN 950 1035 PDZ 2.
FT DOMAIN 1079 1167 PDZ 3.
FT VAR_SEQ 1 1048 Missing (in isoform 5).
FT /FTId=VSP_028521.
FT VAR_SEQ 1 989 Missing (in isoform 4).
FT /FTId=VSP_028522.
FT VAR_SEQ 1 8 MQPLTKDA -> MHVFIV (in isoform 2).
FT /FTId=VSP_028523.
FT VAR_SEQ 103 124 Missing (in isoform 2).
FT /FTId=VSP_028524.
FT VAR_SEQ 391 392 KE -> GE (in isoform 3).
FT /FTId=VSP_028525.
FT VAR_SEQ 393 1309 Missing (in isoform 3).
FT /FTId=VSP_028526.
FT VAR_SEQ 486 486 Missing (in isoform 2).
FT /FTId=VSP_028527.
FT VAR_SEQ 990 996 KEGQILQ -> MTSIPFP (in isoform 4).
FT /FTId=VSP_028528.
FT VARIANT 20 20 A -> T (in dbSNP:rs11101272).
FT /FTId=VAR_055540.
FT VARIANT 239 239 T -> M (in dbSNP:rs55802136).
FT /FTId=VAR_061034.
FT VARIANT 534 534 K -> E (in dbSNP:rs1864345).
FT /FTId=VAR_055541.
FT VARIANT 727 727 R -> W (in a colorectal cancer sample;
FT somatic mutation).
FT /FTId=VAR_035446.
FT VARIANT 1021 1021 T -> K (in dbSNP:rs1898784).
FT /FTId=VAR_065253.
FT MUTAGEN 955 955 K->E: Abolishes the basolateral membrane
FT localization.
FT CONFLICT 601 601 K -> E (in Ref. 3; CAH18097).
FT CONFLICT 624 624 S -> G (in Ref. 3; CAH18097).
FT CONFLICT 826 826 I -> T (in Ref. 3; CAH18097).
FT CONFLICT 874 874 S -> G (in Ref. 2; BAC85520).
FT CONFLICT 895 895 L -> S (in Ref. 2; BAC85520).
FT CONFLICT 969 969 N -> M (in Ref. 5; AAH73954/AAI44636/
FT AAI44640).
FT CONFLICT 1077 1077 K -> N (in Ref. 1; AAS79660).
FT CONFLICT 1174 1174 L -> M (in Ref. 2; BAC85520).
FT CONFLICT 1214 1214 S -> F (in Ref. 1; AAS79660).
SQ SEQUENCE 1309 AA; 144282 MW; 7684E687FA8522B4 CRC64;
MQPLTKDAGM SLSSVTLASA LQVRGEALSE EEIWSLLFLA AEQLLEDLRN DSSDYVVCPW
SALLSAAGSL SFQGRVSHIE AAPFKAPELL QGQSEDEQPD ASQMHVYSLG MTLYWSAGFH
VPPHQPLQLC EPLHSILLTM CEDQPHRRCT LQSVLEACRV HEKEVSVYPA PAGLHIRRLV
GLVLGTISEV EKRVVEESSS VQQNRSYLLR KRLRGTSSES PAAQAPECLH PCRVSERSTE
TQSSPEPHWS TLTHSHCSLL VNRALPGADP QDQQAGRRLS SGSVHSAADS SWPTTPSQRG
FLQRRSKFSR PEFILLAGEA PMTLHLPGSV VTKKGKSYLA LRDLCVVLLN GQHLEVKCDV
ESTVGAVFNA VTSFANLEEL TYFGLAYMKS KEFFFLDSET RLCKIAPEGW REQPQKTSMN
TFTLFLRIKF FVSHYGLLQH SLTRHQFYLQ LRKDILEERL YCNEEILLQL GVLALQAEFG
NYPKEQVESK PYFHVEDYIP ASLIERMTAL RVQVEVSEMH RLSSALWGED AELKFLRVTQ
QLPEYGVLVH QVFSEKRRPE EEMALGICAK GVIVYEVKNN SRIAMLRFQW RETGKISTYQ
KKFTITSSVT GKKHTFVTDS AKTSKYLLDL CSAQHGFNAQ MGSGQPSHVL FDHDKFVQMA
NLSPAHQARS KPLIWIQRLS CSENELFVSR LQGAAGGLLS TSMDNFNVDG SKEAGAEGIG
RSPCTGREQL KSACVIQKPM TWDSLSGPPV QSMHAGSKNN RRKSFIAEPG REIVRVTLKR
DPHRGFGFVI NEGEYSGQAD PGIFISSIIP GGPAEKAKTI KPGGQILALN HISLEGFTFN
MAVRMIQNSP DNIELIISQS KGVGGNNPDE EKNSTANSGV SSTDILSFGY QGSLLSHTQD
QDRNTEELDM AGVQSLVPRL RHQLSFLPLK GAGSSCPPSP PEISAGEIYF VELVKEDGTL
GFSVTGGINT SVPYGGIYVK SIVPGGPAAK EGQILQGDRL LQVDGVILCG LTHKQAVQCL
TGPGQVARLV LERRVPRSTQ QCPSANDSMG DERTAVSLVT ALPGRPSSCV SVTDGPKFEV
KLKKNANGLG FSFVQMEKES CSHLKSDLVR IKRLFPGQPA EENGAIAAGD IILAVNGRST
EGLIFQEVLH LLRGAPQEVT LLLCRPPPGA LPELEQEWQT PELSADKEFT RATCTDSCTS
PILDQEDSWR DSASPDAGEG LGLRPESSQK AIREAQWGQN RERPWASSLT HSPESHPHLC
KLHQERDEST LATSLEKDVR QNCYSVCDIM RLGRYSFSSP LTRLSTDIF
//
