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Q86UT5

- NHRF4_HUMAN

UniProt

Q86UT5 - NHRF4_HUMAN

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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

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 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
Complete GO annotation...

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
Complete GO annotation...

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

BgeeiQ86UT5.
CleanExiHS_PDZD3.
ExpressionAtlasiQ86UT5. baseline and differential.
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 – 3336Combined sources
Beta strandi341 – 3477Combined sources
Beta strandi353 – 3608Combined sources
Helixi365 – 3684Combined sources
Beta strandi375 – 3806Combined sources
Helixi390 – 3989Combined sources
Turni399 – 4024Combined sources
Beta strandi403 – 4097Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2V90X-ray2.00A/B/C/D/E/F326-415[»]
ProteinModelPortaliQ86UT5.
SMRiQ86UT5. Positions 113-193, 221-415, 461-550.
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.
GeneTreeiENSGT00530000062999.
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

        10         20         30         40         50
MVTPSPPGNH SLSLEAPRLH TASDLLGNHS LGLPLITALV GSRDRRGRVF
60 70 80 90 100
SPVPVPLPTN PTTQHPTRQK LPSTLSGHRV CQAHGEPVLG LCPLLPLFCC
110 120 130 140 150
PPHPPDPWSL ERPRFCLLSK EEGKSFGFHL QQELGRAGHV VCRVDPGTSA
160 170 180 190 200
QRQGLQEGDR ILAVNNDVVE HEDYAVVVRR IRASSPRVLL TVLARHAHDV
210 220 230 240 250
ARAQLGEDAH LCPTLGPGVR PRLCHIVKDE GGFGFSVTHG NQGPFWLVLS
260 270 280 290 300
TGGAAERAGV PPGARLLEVN GVSVEKFTHN QLTRKLWQSG QQVTLLVAGP
310 320 330 340 350
EVEEQCRQLG LPLAAPLAEG WALPTKPRCL HLEKGPQGFG FLLREEKGLD
360 370 380 390 400
GRPGQFLWEV DPGLPAKKAG MQAGDRLVAV AGESVEGLGH EETVSRIQGQ
410 420 430 440 450
GSCVSLTVVD PEADRFFSMV RLSPLLFLEN TEAPASPRGS SSASLVETED
460 470 480 490 500
PSLEDTSVPS VPLGSRQCFL YPGPGGSYGF RLSCVASGPR LFISQVTPGG
510 520 530 540 550
SAARAGLQVG DVILEVNGYP VGGQNDLERL QQLPEAEPPL CLKLAARSLR
560 570
GLEAWIPPGA AEDWALASDL L
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:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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:
PDBei
RCSB PDBi
PDBji
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, 461-550.
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.
GeneTreei ENSGT00530000062999.
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

Bgeei Q86UT5.
CleanExi HS_PDZD3.
ExpressionAtlasi Q86UT5. baseline and differential.
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

« Hide 'large scale' publications
  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: November 26, 2014
This is version 105 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