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Protein

Phosphatase and actin regulator 4

Gene

Phactr4

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Regulator of protein phosphatase 1 (PP1) required for neural tube and optic fissure closure, and enteric neural crest cell (ENCCs) migration during development. Acts as an activator of PP1 by interacting with PPP1CA and preventing phosphorylation of PPP1CA at 'Thr-320'. During neural tube closure, localizes to the ventral neural tube and activates PP1, leading to down-regulate cell proliferation within cranial neural tissue and the neural retina. Also acts as a regulator of migration of enteric neural crest cells (ENCCs) by activating PP1, leading to dephosphorylation and subsequent activation of cofilin (COF1 or COF2) and repression of the integrin signaling through the RHO/ROCK pathway.2 Publications

GO - Molecular functioni

  • actin binding Source: UniProtKB
  • protein phosphatase 1 binding Source: UniProtKB
  • protein phosphatase inhibitor activity Source: UniProtKB-KW
  • protein phosphatase type 1 activator activity Source: UniProtKB

GO - Biological processi

  • actin cytoskeleton organization Source: UniProtKB
  • closure of optic fissure Source: UniProtKB
  • enteric nervous system development Source: UniProtKB
  • negative regulation of integrin-mediated signaling pathway Source: UniProtKB
  • neural crest cell migration Source: UniProtKB
  • neural tube closure Source: UniProtKB
  • positive regulation of catalytic activity Source: UniProtKB
  • regulation of cell cycle Source: UniProtKB
  • Rho protein signal transduction Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Protein phosphatase inhibitor

Keywords - Biological processi

Neurogenesis

Keywords - Ligandi

Actin-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Phosphatase and actin regulator 4
Alternative name(s):
Protein Humpty dumpty
Short name:
Humdy
Gene namesi
Name:Phactr4
Synonyms:Kiaa4120
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 4

Organism-specific databases

MGIiMGI:2140327. Phactr4.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB-SubCell
  • intracellular Source: UniProtKB
  • lamellipodium Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell projection, Cytoplasm

Pathology & Biotechi

Disruption phenotypei

Neural tube and eye defects in embryos followed by death. By E9.25, mutant embryos show failure to close the cranial neural tube. About 15% of homozygous mutant embryos exhibit severe exencephaly, along with a wavy spinal neural tube and a shortened anterior/posterior body axis, and die around E10.5. Remaining embryos exhibit complete exencephaly from the forebrain to hindbrain. Most embryos die by E14.5, but a few survive to birth and die shortly thereafter. Embryos also have eye defects: they display overgrowth of the neural retina and retinal pigment epithelium. Embryos also display coloboma at E12.5 and E16.5, due to defects in closure of optic fissure. Defects are due to elevated proliferation and abnormally phosphorylated, inactive PP1, resulting in RB1 hyperphosphorylation, derepression of E2F targets, and abnormal cell-cycle progression. Embryos also show embryonic gastrointestinal defects due to colon hypoganglionosis, which resembles human Hirschsprung disease: ENCCs within the embryonic gut display a collective cell migration defect and show undirected cellular protrusions and disrupted directional and chain migration.2 Publications

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi650 – 6501R → P in humdy; failure to close the neural tube and optic fissure, causing exencephaly and retinal coloboma and common birth defects. Specifically disrupts interaction with PPP1CA while it does not affect interaction with actin. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 694694Phosphatase and actin regulator 4PRO_0000287307Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei116 – 1161PhosphoserineCombined sources
Modified residuei118 – 1181PhosphoserineCombined sources
Modified residuei129 – 1291PhosphoserineBy similarity
Modified residuei145 – 1451PhosphoserineBy similarity
Modified residuei264 – 2641PhosphoserineCombined sources
Modified residuei285 – 2851PhosphoserineCombined sources
Modified residuei335 – 3351PhosphoserineBy similarity
Modified residuei337 – 3371PhosphoserineBy similarity
Modified residuei420 – 4201PhosphoserineCombined sources
Modified residuei425 – 4251PhosphothreonineCombined sources
Modified residuei436 – 4361PhosphoserineCombined sources
Modified residuei446 – 4461PhosphoserineCombined sources
Modified residuei457 – 4571PhosphoserineCombined sources
Modified residuei503 – 5031PhosphoserineCombined sources
Modified residuei505 – 5051PhosphoserineCombined sources
Modified residuei549 – 5491PhosphoserineBy similarity
Modified residuei582 – 5821PhosphoserineBy similarity
Modified residuei620 – 6201PhosphoserineBy similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ501J7.
MaxQBiQ501J7.
PaxDbiQ501J7.
PeptideAtlasiQ501J7.
PRIDEiQ501J7.

PTM databases

iPTMnetiQ501J7.
PhosphoSiteiQ501J7.

Expressioni

Developmental stagei

During embryonic development, most strongly expressed in neural tissue. Expressed in a dynamic pattern during neurulation: from E8.5 to E9.5, the period of cranial neural closure and spatially regulated proliferation, it is expressed strongly in the ventral region of the cranial neural tube. By E10.5, expressed more uniformly along the dorsal and ventral aspects of the cranial neural tube. Also expressed in the neural retina and lens.1 Publication

Gene expression databases

BgeeiENSMUSG00000066043.
CleanExiMM_PHACTR4.
ExpressionAtlasiQ501J7. baseline and differential.
GenevisibleiQ501J7. MM.

Interactioni

Subunit structurei

Binds PPP1CA and actin.

GO - Molecular functioni

  • actin binding Source: UniProtKB
  • protein phosphatase 1 binding Source: UniProtKB

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000099628.

Structurei

3D structure databases

ProteinModelPortaliQ501J7.
SMRiQ501J7. Positions 536-642.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati63 – 8826RPEL 1Add
BLAST
Repeati575 – 60026RPEL 2Add
BLAST
Repeati613 – 63826RPEL 3Add
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi221 – 355135Pro-richAdd
BLAST
Compositional biasi368 – 3714Poly-Ser
Compositional biasi471 – 4744Poly-Glu
Compositional biasi519 – 5235Poly-Asp

Sequence similaritiesi

Contains 3 RPEL repeats.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG4339. Eukaryota.
ENOG4111M01. LUCA.
GeneTreeiENSGT00390000004420.
HOGENOMiHOG000220879.
HOVERGENiHBG108247.
InParanoidiQ501J7.
KOiK17585.
OMAiREKSTCS.
OrthoDBiEOG091G0HBF.
PhylomeDBiQ501J7.
TreeFamiTF316316.

Family and domain databases

InterProiIPR029984. Phactr4.
IPR004018. RPEL_repeat.
[Graphical view]
PANTHERiPTHR12751:SF4. PTHR12751:SF4. 2 hits.
PfamiPF02755. RPEL. 3 hits.
[Graphical view]
SMARTiSM00707. RPEL. 3 hits.
[Graphical view]
PROSITEiPS51073. RPEL. 3 hits.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q501J7-1) [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
MEDPSEEAEQ PSGDPGMGMD SVEAGDTTPP TKRKSKFSAL GKIFKPWKWR
60 70 80 90 100
KKKSSDKFKE TSEVLERKIS MRKPREELVK RGVLLEDPEQ DGEDSGKLSH
110 120 130 140 150
AALKNGHTTP IGSARSSSPV LVEEEPERSL RNLTPEEESK KRLGSTGSQP
160 170 180 190 200
NSEAEPGPEH APKQPLLPPK RPLSSSCEAK EVPAGSTARS VSSTSGSTTV
210 220 230 240 250
TSAATTAATD MTKTVKSFVG PTPAPAPAPR TLPAAPASAN TAATTTAPAK
260 270 280 290 300
QPPIPPPKPA QRNSNPIIAE LSQAMNSGTV LSKPSPPLPP KRGIPSTSIP
310 320 330 340 350
SLEPAASFTT KTANDQREKT VSLCLEPPLI IPPSSPSPPL PTHIPPEPPR
360 370 380 390 400
SPLVPAKTFQ IVPEVEFSSS SDLFQDISQQ EDQKTEVPKK IQDQSFGESH
410 420 430 440 450
IPSRLPPLPL HIRIQQALTS PLPVTPPLEG THRAHSLLFE NSDSFSEDTG
460 470 480 490 500
TLGRTRSLPI TIEMLKVPDD EEEEQTCPFV EDVTSTSATP SLPLCLREEE
510 520 530 540 550
KESDSDSEGP IKYRDEEEDD DDDESHQSAL ANRVKRKDTL AMKLSSRPSE
560 570 580 590 600
PETNLNSWPR KSKEEWNEIR HQIGNTLIRR LSQRPTAEEL EQRNILQPKN
610 620 630 640 650
EADRQAEKRE IKRRLTRKLS QRPTVAELLA RKILRFNEYV EVTDAHDYDR
660 670 680 690
RADKPWTKLT PADKAAIRKE LNEFKSSEME VHVDSKHFTR YHRP
Length:694
Mass (Da):76,632
Last modified:May 15, 2007 - v2
Checksum:i3AEB17E6A390DD29
GO
Isoform 2 (identifier: Q501J7-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     64-90: Missing.

Show »
Length:667
Mass (Da):73,401
Checksum:iC8792813A330F37A
GO
Isoform 3 (identifier: Q501J7-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-5: MEDPS → MGQADVSRPVNPDAV

Show »
Length:704
Mass (Da):77,610
Checksum:i2A63C3E20DBAC762
GO

Sequence cautioni

The sequence BAD90294 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence CAM26520 differs from that shown. Reason: Erroneous gene model prediction. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti212 – 2121T → K in BAC33611 (PubMed:16141072).Curated
Sequence conflicti224 – 2241A → S in AAH96033 (PubMed:19468303).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 55MEDPS → MGQADVSRPVNPDAV in isoform 3. CuratedVSP_025439
Alternative sequencei64 – 9027Missing in isoform 2. 1 PublicationVSP_025440Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK049209 mRNA. Translation: BAC33611.1.
AK220496 mRNA. Translation: BAD90294.1. Different initiation.
AL805897 Genomic DNA. Translation: CAM26521.1.
AL805897 Genomic DNA. Translation: CAM26523.1.
AL805897 Genomic DNA. Translation: CAM26520.1. Sequence problems.
BC075672 mRNA. Translation: AAH75672.1.
BC096033 mRNA. Translation: AAH96033.1.
CCDSiCCDS18724.1. [Q501J7-1]
CCDS51318.1. [Q501J7-2]
RefSeqiNP_001155269.1. NM_001161797.1. [Q501J7-2]
NP_780515.2. NM_175306.4. [Q501J7-1]
XP_006538519.1. XM_006538456.2. [Q501J7-3]
UniGeneiMm.158361.

Genome annotation databases

EnsembliENSMUST00000084170; ENSMUSP00000081185; ENSMUSG00000066043. [Q501J7-2]
ENSMUST00000084249; ENSMUSP00000081270; ENSMUSG00000066043. [Q501J7-3]
ENSMUST00000102568; ENSMUSP00000099628; ENSMUSG00000066043. [Q501J7-1]
GeneIDi100169.
KEGGimmu:100169.
UCSCiuc008vbg.3. mouse. [Q501J7-1]
uc008vbh.3. mouse. [Q501J7-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK049209 mRNA. Translation: BAC33611.1.
AK220496 mRNA. Translation: BAD90294.1. Different initiation.
AL805897 Genomic DNA. Translation: CAM26521.1.
AL805897 Genomic DNA. Translation: CAM26523.1.
AL805897 Genomic DNA. Translation: CAM26520.1. Sequence problems.
BC075672 mRNA. Translation: AAH75672.1.
BC096033 mRNA. Translation: AAH96033.1.
CCDSiCCDS18724.1. [Q501J7-1]
CCDS51318.1. [Q501J7-2]
RefSeqiNP_001155269.1. NM_001161797.1. [Q501J7-2]
NP_780515.2. NM_175306.4. [Q501J7-1]
XP_006538519.1. XM_006538456.2. [Q501J7-3]
UniGeneiMm.158361.

3D structure databases

ProteinModelPortaliQ501J7.
SMRiQ501J7. Positions 536-642.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000099628.

PTM databases

iPTMnetiQ501J7.
PhosphoSiteiQ501J7.

Proteomic databases

EPDiQ501J7.
MaxQBiQ501J7.
PaxDbiQ501J7.
PeptideAtlasiQ501J7.
PRIDEiQ501J7.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000084170; ENSMUSP00000081185; ENSMUSG00000066043. [Q501J7-2]
ENSMUST00000084249; ENSMUSP00000081270; ENSMUSG00000066043. [Q501J7-3]
ENSMUST00000102568; ENSMUSP00000099628; ENSMUSG00000066043. [Q501J7-1]
GeneIDi100169.
KEGGimmu:100169.
UCSCiuc008vbg.3. mouse. [Q501J7-1]
uc008vbh.3. mouse. [Q501J7-2]

Organism-specific databases

CTDi65979.
MGIiMGI:2140327. Phactr4.
RougeiSearch...

Phylogenomic databases

eggNOGiKOG4339. Eukaryota.
ENOG4111M01. LUCA.
GeneTreeiENSGT00390000004420.
HOGENOMiHOG000220879.
HOVERGENiHBG108247.
InParanoidiQ501J7.
KOiK17585.
OMAiREKSTCS.
OrthoDBiEOG091G0HBF.
PhylomeDBiQ501J7.
TreeFamiTF316316.

Miscellaneous databases

PROiQ501J7.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000066043.
CleanExiMM_PHACTR4.
ExpressionAtlasiQ501J7. baseline and differential.
GenevisibleiQ501J7. MM.

Family and domain databases

InterProiIPR029984. Phactr4.
IPR004018. RPEL_repeat.
[Graphical view]
PANTHERiPTHR12751:SF4. PTHR12751:SF4. 2 hits.
PfamiPF02755. RPEL. 3 hits.
[Graphical view]
SMARTiSM00707. RPEL. 3 hits.
[Graphical view]
PROSITEiPS51073. RPEL. 3 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPHAR4_MOUSE
AccessioniPrimary (citable) accession number: Q501J7
Secondary accession number(s): A2ALF7
, A2ALG0, F6QNZ3, Q5DTM4, Q6DI97, Q8C7U9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 15, 2007
Last sequence update: May 15, 2007
Last modified: September 7, 2016
This is version 82 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.