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Q86UT5

- NHRF4_HUMAN

UniProt

Q86UT5 - NHRF4_HUMAN

Protein

Na(+)/H(+) exchange regulatory cofactor NHE-RF4

Gene

PDZD3

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 103 (01 Oct 2014)
      Sequence version 2 (05 Oct 2010)
      Previous versions | rss
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    Functioni

    Acts as a regulatory protein that associates with GUCY2C and negatively modulates its heat-stable enterotoxin-mediated activation. Stimulates SLC9A3 activity in the presence of elevated calcium ions.2 Publications

    GO - Molecular functioni

    1. guanylate cyclase inhibitor activity Source: UniProtKB
    2. ion channel inhibitor activity Source: UniProtKB
    3. protein binding Source: IntAct
    4. protein C-terminus binding Source: UniProtKB

    GO - Biological processi

    1. cGMP-mediated signaling Source: UniProtKB
    2. ion transport Source: UniProtKB
    3. negative regulation of cGMP biosynthetic process Source: UniProtKB
    4. negative regulation of guanylate cyclase activity Source: GOC
    5. receptor guanylyl cyclase signaling pathway Source: UniProtKB
    6. response to toxic substance Source: UniProtKB
    7. water transport Source: UniProtKB

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Na(+)/H(+) exchange regulatory cofactor NHE-RF4
    Short name:
    NHERF-4
    Alternative name(s):
    Intestinal and kidney-enriched PDZ protein
    Natrium-phosphate cotransporter IIa C-terminal-associated protein 2
    Short name:
    Na/Pi cotransporter C-terminal-associated protein 2
    Short name:
    NaPi-Cap2
    PDZ domain-containing protein 2
    PDZ domain-containing protein 3
    Sodium-hydrogen exchanger regulatory factor 4
    Gene namesi
    Name:PDZD3
    Synonyms:IKEPP, NHERF4, PDZK2
    ORF Names:DLNB27
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 11

    Organism-specific databases

    HGNCiHGNC:19891. PDZD3.

    Subcellular locationi

    Cell membrane; Peripheral membrane protein. Cytoplasm
    Note: Preferentially accumulates at the apical surface and ileal brush border of intestinal epithelial cells.

    GO - Cellular componenti

    1. apical part of cell Source: UniProtKB
    2. brush border Source: UniProtKB
    3. cytosol Source: UniProtKB
    4. subapical complex Source: UniProtKB

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Membrane

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA134911718.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 571571Na(+)/H(+) exchange regulatory cofactor NHE-RF4PRO_0000058292Add
    BLAST

    Proteomic databases

    PaxDbiQ86UT5.
    PRIDEiQ86UT5.

    PTM databases

    PhosphoSiteiQ86UT5.

    Expressioni

    Tissue specificityi

    Expressed in kidney and the gastrointestinal tract. Not detected in brain, heart, skeletal muscle or cells of hematopoietic origin.1 Publication

    Gene expression databases

    ArrayExpressiQ86UT5.
    BgeeiQ86UT5.
    CleanExiHS_PDZD3.
    GenevestigatoriQ86UT5.

    Organism-specific databases

    HPAiHPA040482.

    Interactioni

    Subunit structurei

    Interacts with the C-terminal region of GUCY2C. Interacts with the C-terminal region of SLC34A1. Interacts with the C-terminal region SLC9A3 and the interactions decrease in response to elevated calcium ion levels.2 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    GUCY2CP250924EBI-8299496,EBI-2816795

    Protein-protein interaction databases

    BioGridi122940. 4 interactions.
    IntActiQ86UT5. 1 interaction.
    STRINGi9606.ENSP00000327107.

    Structurei

    Secondary structure

    1
    571
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi328 – 3336
    Beta strandi341 – 3477
    Beta strandi353 – 3608
    Helixi365 – 3684
    Beta strandi375 – 3806
    Helixi390 – 3989
    Turni399 – 4024
    Beta strandi403 – 4097

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2V90X-ray2.00A/B/C/D/E/F326-415[»]
    ProteinModelPortaliQ86UT5.
    SMRiQ86UT5. Positions 113-193, 221-415, 464-545.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ86UT5.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini115 – 19682PDZ 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini223 – 30179PDZ 2PROSITE-ProRule annotationAdd
    BLAST
    Domaini329 – 41284PDZ 3PROSITE-ProRule annotationAdd
    BLAST
    Domaini467 – 54882PDZ 4PROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Contains 4 PDZ (DHR) domains.PROSITE-ProRule annotation

    Keywords - Domaini

    Repeat

    Phylogenomic databases

    eggNOGiNOG262468.
    HOGENOMiHOG000048712.
    HOVERGENiHBG080760.
    InParanoidiQ86UT5.
    OMAiGVRPRLC.
    OrthoDBiEOG73V6K7.
    PhylomeDBiQ86UT5.
    TreeFamiTF350449.

    Family and domain databases

    Gene3Di2.30.42.10. 4 hits.
    InterProiIPR001478. PDZ.
    [Graphical view]
    PfamiPF00595. PDZ. 4 hits.
    [Graphical view]
    SMARTiSM00228. PDZ. 4 hits.
    [Graphical view]
    SUPFAMiSSF50156. SSF50156. 4 hits.
    PROSITEiPS50106. PDZ. 4 hits.
    [Graphical view]

    Sequences (5)i

    Sequence statusi: Complete.

    This entry describes 5 isoformsi produced by alternative splicing. Align

    Isoform 11 Publication (identifier: Q86UT5-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MVTPSPPGNH SLSLEAPRLH TASDLLGNHS LGLPLITALV GSRDRRGRVF    50
    SPVPVPLPTN PTTQHPTRQK LPSTLSGHRV CQAHGEPVLG LCPLLPLFCC 100
    PPHPPDPWSL ERPRFCLLSK EEGKSFGFHL QQELGRAGHV VCRVDPGTSA 150
    QRQGLQEGDR ILAVNNDVVE HEDYAVVVRR IRASSPRVLL TVLARHAHDV 200
    ARAQLGEDAH LCPTLGPGVR PRLCHIVKDE GGFGFSVTHG NQGPFWLVLS 250
    TGGAAERAGV PPGARLLEVN GVSVEKFTHN QLTRKLWQSG QQVTLLVAGP 300
    EVEEQCRQLG LPLAAPLAEG WALPTKPRCL HLEKGPQGFG FLLREEKGLD 350
    GRPGQFLWEV DPGLPAKKAG MQAGDRLVAV AGESVEGLGH EETVSRIQGQ 400
    GSCVSLTVVD PEADRFFSMV RLSPLLFLEN TEAPASPRGS SSASLVETED 450
    PSLEDTSVPS VPLGSRQCFL YPGPGGSYGF RLSCVASGPR LFISQVTPGG 500
    SAARAGLQVG DVILEVNGYP VGGQNDLERL QQLPEAEPPL CLKLAARSLR 550
    GLEAWIPPGA AEDWALASDL L 571
    Length:571
    Mass (Da):61,032
    Last modified:October 5, 2010 - v2
    Checksum:iB56CDC91348EE592
    GO
    Isoform 21 Publication (identifier: Q86UT5-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-66: Missing.
         67-105: TRQKLPSTLS...PLFCCPPHPP → MEKAADLQDT...LSLAEDHDPY

    Show »
    Length:505
    Mass (Da):54,217
    Checksum:iACDAE2A896787C5D
    GO
    Isoform 3Curated (identifier: Q86UT5-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-66: Missing.
         67-105: TRQKLPSTLS...PLFCCPPHPP → MEKAADLQDT...LSLAEDHDPY
         272-285: Missing.

    Note: No experimental confirmation available.Curated

    Show »
    Length:491
    Mass (Da):52,548
    Checksum:i46F3C5D292274D56
    GO
    Isoform 4Curated (identifier: Q86UT5-4) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         355-386: QFLWEVDPGLPAKKAGMQAGDRLVAVAGESVE → EWEPWGRWGKVGLGVGTQAYIHLSVHRRGVPV
         387-571: Missing.

    Note: No experimental confirmation available.Curated

    Show »
    Length:386
    Mass (Da):41,888
    Checksum:iBE18E918ECD4009D
    GO
    Isoform 5Curated (identifier: Q86UT5-5) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-66: Missing.
         67-105: TRQKLPSTLS...PLFCCPPHPP → MEKAADLQDT...LSLAEDHDPY
         287-571: Missing.

    Note: No experimental confirmation available.Curated

    Show »
    Length:220
    Mass (Da):24,105
    Checksum:i87EC9259F8262E0A
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti112 – 1121R → P in BAB15474. (PubMed:14702039)Curated
    Sequence conflicti125 – 1251S → G in BAC03780. (PubMed:14702039)Curated
    Sequence conflicti286 – 2861L → V in BAB15474. (PubMed:14702039)Curated
    Sequence conflicti438 – 4381R → Q in BAC76050. 1 PublicationCurated
    Sequence conflicti438 – 4381R → Q in AAH29042. (PubMed:15489334)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 6666Missing in isoform 2, isoform 3 and isoform 5. 3 PublicationsVSP_051786Add
    BLAST
    Alternative sequencei67 – 10539TRQKL…PPHPP → MEKAADLQDTASLTLKFKFN PKLGIDNPVLSLAEDHDPY in isoform 2, isoform 3 and isoform 5. 3 PublicationsVSP_051787Add
    BLAST
    Alternative sequencei272 – 28514Missing in isoform 3. 2 PublicationsVSP_051788Add
    BLAST
    Alternative sequencei287 – 571285Missing in isoform 5. 2 PublicationsVSP_051789Add
    BLAST
    Alternative sequencei355 – 38632QFLWE…GESVE → EWEPWGRWGKVGLGVGTQAY IHLSVHRRGVPV in isoform 4. 2 PublicationsVSP_051790Add
    BLAST
    Alternative sequencei387 – 571185Missing in isoform 4. 2 PublicationsVSP_051791Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY047359 mRNA. Translation: AAL10686.1.
    AB094096 mRNA. Translation: BAC76050.1.
    AK026409 mRNA. Translation: BAB15474.1.
    AK091966 mRNA. Translation: BAC03780.1.
    AP002956 Genomic DNA. No translation available.
    BC029042 mRNA. Translation: AAH29042.1.
    CCDSiCCDS53719.1. [Q86UT5-2]
    CCDS8417.1. [Q86UT5-3]
    RefSeqiNP_001161940.1. NM_001168468.1. [Q86UT5-2]
    NP_079067.3. NM_024791.3. [Q86UT5-3]
    UniGeneiHs.374726.

    Genome annotation databases

    EnsembliENST00000322712; ENSP00000327107; ENSG00000172367. [Q86UT5-3]
    ENST00000355547; ENSP00000347742; ENSG00000172367. [Q86UT5-2]
    ENST00000531114; ENSP00000431164; ENSG00000172367. [Q86UT5-1]
    GeneIDi79849.
    KEGGihsa:79849.
    UCSCiuc001pvz.3. human. [Q86UT5-2]
    uc001pwb.3. human. [Q86UT5-1]

    Polymorphism databases

    DMDMi308153467.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY047359 mRNA. Translation: AAL10686.1 .
    AB094096 mRNA. Translation: BAC76050.1 .
    AK026409 mRNA. Translation: BAB15474.1 .
    AK091966 mRNA. Translation: BAC03780.1 .
    AP002956 Genomic DNA. No translation available.
    BC029042 mRNA. Translation: AAH29042.1 .
    CCDSi CCDS53719.1. [Q86UT5-2 ]
    CCDS8417.1. [Q86UT5-3 ]
    RefSeqi NP_001161940.1. NM_001168468.1. [Q86UT5-2 ]
    NP_079067.3. NM_024791.3. [Q86UT5-3 ]
    UniGenei Hs.374726.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2V90 X-ray 2.00 A/B/C/D/E/F 326-415 [» ]
    ProteinModelPortali Q86UT5.
    SMRi Q86UT5. Positions 113-193, 221-415, 464-545.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 122940. 4 interactions.
    IntActi Q86UT5. 1 interaction.
    STRINGi 9606.ENSP00000327107.

    PTM databases

    PhosphoSitei Q86UT5.

    Polymorphism databases

    DMDMi 308153467.

    Proteomic databases

    PaxDbi Q86UT5.
    PRIDEi Q86UT5.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000322712 ; ENSP00000327107 ; ENSG00000172367 . [Q86UT5-3 ]
    ENST00000355547 ; ENSP00000347742 ; ENSG00000172367 . [Q86UT5-2 ]
    ENST00000531114 ; ENSP00000431164 ; ENSG00000172367 . [Q86UT5-1 ]
    GeneIDi 79849.
    KEGGi hsa:79849.
    UCSCi uc001pvz.3. human. [Q86UT5-2 ]
    uc001pwb.3. human. [Q86UT5-1 ]

    Organism-specific databases

    CTDi 79849.
    GeneCardsi GC11P119056.
    H-InvDB HIX0201614.
    HGNCi HGNC:19891. PDZD3.
    HPAi HPA040482.
    MIMi 607146. gene.
    neXtProti NX_Q86UT5.
    PharmGKBi PA134911718.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG262468.
    HOGENOMi HOG000048712.
    HOVERGENi HBG080760.
    InParanoidi Q86UT5.
    OMAi GVRPRLC.
    OrthoDBi EOG73V6K7.
    PhylomeDBi Q86UT5.
    TreeFami TF350449.

    Miscellaneous databases

    EvolutionaryTracei Q86UT5.
    GenomeRNAii 79849.
    NextBioi 69555.
    PROi Q86UT5.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q86UT5.
    Bgeei Q86UT5.
    CleanExi HS_PDZD3.
    Genevestigatori Q86UT5.

    Family and domain databases

    Gene3Di 2.30.42.10. 4 hits.
    InterProi IPR001478. PDZ.
    [Graphical view ]
    Pfami PF00595. PDZ. 4 hits.
    [Graphical view ]
    SMARTi SM00228. PDZ. 4 hits.
    [Graphical view ]
    SUPFAMi SSF50156. SSF50156. 4 hits.
    PROSITEi PS50106. PDZ. 4 hits.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "A novel PDZ protein regulates the activity of guanylyl cyclase C, the heat-stable enterotoxin receptor."
      Scott R.O., Thelin W.R., Milgram S.L.
      J. Biol. Chem. 277:22934-22941(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, INTERACTION WITH GUCY2C, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
      Tissue: Intestinal epithelium1 Publication.
    2. "Identification of a 500-kb region of common allelic loss in chromosome 11q23 in non-MYCN amplified type of neuroblastoma."
      Kubo T., Arai Y., Ohira M., Gamou T., Maeno G., Sakiyama T., Toyoda A., Hattori M., Sakaki Y., Nakagawara A., Ohki M.
      Submitted (OCT-2002) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    3. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 4 AND 5).
      Tissue: Ileal mucosaImported and KidneyImported.
    4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
    6. "Elevated intracellular calcium stimulates NHE3 activity by an IKEPP (NHERF4) dependent mechanism."
      Zachos N.C., Hodson C., Kovbasnjuk O., Li X., Thelin W.R., Cha B., Milgram S., Donowitz M.
      Cell. Physiol. Biochem. 22:693-704(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH SLC9A3.
    7. "Crystal structure of the 3rd PDZ domain of intestine- and kidney-enriched PDZ domain IKEPP (PDZD3)."
      Structural genomics consortium (SGC)
      Submitted (JUL-2011) to the PDB data bank
      Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 326-415.

    Entry informationi

    Entry nameiNHRF4_HUMAN
    AccessioniPrimary (citable) accession number: Q86UT5
    Secondary accession number(s): Q8N6R4
    , Q8NAW7, Q8NEX7, Q9H5Z3
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 16, 2005
    Last sequence update: October 5, 2010
    Last modified: October 1, 2014
    This is version 103 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 11
      Human chromosome 11: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3